Sample records for phytomer2 pap2 encoding

  1. Brassica rapa Has Three Genes That Encode Proteins Associated with Different Neutral Lipids in Plastids of Specific Tissues1

    PubMed Central

    Kim, Hyun Uk; Wu, Sherry S.H.; Ratnayake, Chandra; Huang, Anthony H.C.

    2001-01-01

    Plastid lipid-associated protein (PAP), a predominant structural protein associated with carotenoids and other non-green neutral lipids in plastids, was shown to be encoded by a single nuclear gene in several species. Here we report three PAP genes in the diploid Brassica rapa; the three PAPs are associated with different lipids in specific tissues. Pap1 and Pap2 are more similar to each other (84% amino acid sequence identity) than to Pap3 (46% and 44%, respectively) in the encoded mature proteins. Pap1 transcript was most abundant in the maturing anthers (tapetum) and in lesser amounts in leaves, fruit coats, seeds, and sepals; Pap2 transcript was abundant only in the petals; and Pap3 transcript had a wide distribution, but at minimal levels in numerous organs. Immunoblotting after sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicated that most organs had several nanograms of PAP1 or PAP2 per milligram of total protein, the highest amounts being in the anthers (10.9 μg mg−1 PAP1) and petals (6.6 μg mg−1 PAP2), and that they had much less PAP3 (<0.02 μg mg−1). In these organs PAP was localized in isolated plastid fractions. Plants were subjected to abiotic stresses; drought and ozone reduced the levels of the three Pap transcripts, whereas mechanical wounding and altering the light intensity enhanced their levels. We conclude that the PAP gene family consists of several members whose proteins are associated with different lipids and whose expressions are controlled by distinct mechanisms. Earlier reports of the expression of one Pap gene in various organs in a species need to be re-examined. PMID:11351096

  2. AtPAP2 modulates the import of the small subunit of Rubisco into chloroplasts.

    PubMed

    Zhang, Renshan; Guan, Xiaoqian; Law, Yee-Song; Sun, Feng; Chen, Shuai; Wong, Kam Bo; Lim, Boon Leong

    2016-10-02

    Arabidopsis thaliana purple acid phosphatase 2 (AtPAP2) is the only phosphatase that is dual-targeted to both chloroplasts and mitochondria. Like Toc33/34 of the TOC and Tom 20 of the TOM, AtPAP2 is anchored to the outer membranes of chloroplasts and mitochondria via a hydrophobic C-terminal motif. AtPAP2 on the mitochondria was previously shown to recognize the presequences of several nuclear-encoded mitochondrial proteins and modulate the import of pMORF3 into the mitochondria. Here we show that AtPAP2 binds to the small subunit of Rubisco (pSSU) and that chloroplast import experiments demonstrated that pSSU was imported less efficiently into pap2 chloroplasts than into wild-type chloroplasts. We propose that AtPAP2 is an outer membrane-bound phosphatase receptor that facilitates the import of selected proteins into chloroplasts.

  3. Effects of nitrogen and vapour pressure deficit on phytomer growth and development in a C4 grass.

    PubMed

    Yang, Fang; Gong, Xiao Ying; Liu, Hai Tao; Schäufele, Rudi; Schnyder, Hans

    2016-01-01

    Phytomers are basic morphological units of plants. Knowledge of phytomer development is essential for understanding morphological plasticity, functional-structural modelling of plant growth and the usage of leaf characteristics to indicate growth conditions at the time of production (e.g. stable isotope signals). Yet, systematic analysis on the process of phytomer development is unavailable for wild or perennial C 4 grasses. Also, effects of environmental factors, such as nitrogen nutrition or vapour pressure deficit (VPD), on coordination events of developmental processes of C 4 grasses have not been studied. This study investigates phytomer growth and development in Cleistogenes squarrosa, a predominant C 4 grass in the Eurasian steppe, grown at low (0.63 kPa) or high (1.58 kPa) VPD with low or high nitrogen supply in controlled environments. Elongation of phytomers on marked tillers was measured daily for 13 days. Then lengths of immature and mature phytomer components (blade, sheath and internode) of all phytomers were measured following dissection. Nitrogen nutrition and VPD had no effects on coordination of growth within and between phytomers: phytomer tips emerged when phytomers reached 26 % of their final length, coincident with the acceleration phase of its elongation; blade elongation stopped when phytomers reached ∼75 % of their final length and elongation of the preceding phytomer was confined to the internode. The relationship between fraction of final phytomer length and days after tip emergence for all treatments was well described by a sigmoidal function: y = 1/{1 + exp[(1.82 - x)/1.81]}. C. squarrosa exhibited little morphological plasticity at phytomer-level in response to nitrogen supply and VPD, but a clear increase in tillering under high N supply. Also, the invariant coordination of elongation within and between phytomers was a stable developmental feature, thus the quantitative coordination rules are applicable for predicting morphological development of C. squarrosa under contrasting levels of nitrogen nutrition or VPD. © The Authors 2016. Published by Oxford University Press on behalf of the Annals of Botany Company.

  4. The Barley Phytomer

    PubMed Central

    Forster, Brian P.; Franckowiak, Jerome D.; Lundqvist, Udda; Lyon, Jackie; Pitkethly, Ian; Thomas, William T. B.

    2007-01-01

    Background and Aims Morphological mutants have been useful in elucidating the phytomeric structure of plants. Recently described mutants have shed new light on the ontogeny (development of plant structures) and the phytomeric system of barley (Hordeum vulgare). Since the current model for barley phytomers was not adequate to explain the nature of some mutants, a new model is proposed. Methods New phytomer mutants were detected by visual assessment of mutant families in the Optic barley mutation grid population. This was done at various growth stages using laboratory, glasshouse and field screens. Simple explanations were adopted to account for aberrant phytomer phenotypes and a thesis for a new phytomer model was developed. Key Results and Conclusions A barley phytomer model is presented, in which the origins of vegetative and generative structures can be explained by a single repeating phytomer unit. Organs on the barley plant are divided into two classes, single or paired, depending on their origin. Paired structures are often fused together to create specific organs. The model can be applied to wheat (Triticum aestivum) and related grasses. PMID:17901062

  5. Yeast PAH1-encoded phosphatidate phosphatase controls the expression of CHO1-encoded phosphatidylserine synthase for membrane phospholipid synthesis.

    PubMed

    Han, Gil-Soo; Carman, George M

    2017-08-11

    The PAH1 -encoded phosphatidate phosphatase (PAP), which catalyzes the committed step for the synthesis of triacylglycerol in Saccharomyces cerevisiae , exerts a negative regulatory effect on the level of phosphatidate used for the de novo synthesis of membrane phospholipids. This raises the question whether PAP thereby affects the expression and activity of enzymes involved in phospholipid synthesis. Here, we examined the PAP-mediated regulation of CHO1 -encoded phosphatidylserine synthase (PSS), which catalyzes the committed step for the synthesis of major phospholipids via the CDP-diacylglycerol pathway. The lack of PAP in the pah1 Δ mutant highly elevated PSS activity, exhibiting a growth-dependent up-regulation from the exponential to the stationary phase of growth. Immunoblot analysis showed that the elevation of PSS activity results from an increase in the level of the enzyme encoded by CHO1 Truncation analysis and site-directed mutagenesis of the CHO1 promoter indicated that Cho1 expression in the pah1 Δ mutant is induced through the inositol-sensitive upstream activation sequence (UAS INO ), a cis -acting element for the phosphatidate-controlled Henry (Ino2-Ino4/Opi1) regulatory circuit. The abrogation of Cho1 induction and PSS activity by a CHO1 UAS INO mutation suppressed pah1 Δ effects on lipid synthesis, nuclear/endoplasmic reticulum membrane morphology, and lipid droplet formation, but not on growth at elevated temperature. Loss of the DGK1 -encoded diacylglycerol kinase, which converts diacylglycerol to phosphatidate, partially suppressed the pah1 Δ-mediated induction of Cho1 and PSS activity. Collectively, these data showed that PAP activity controls the expression of PSS for membrane phospholipid synthesis. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. Overexpression of a phosphatidic acid phosphatase type 2 leads to an increase in triacylglycerol production in oleaginous Rhodococcus strains.

    PubMed

    Hernández, Martín A; Comba, Santiago; Arabolaza, Ana; Gramajo, Hugo; Alvarez, Héctor M

    2015-03-01

    Oleaginous Rhodococcus strains are able to accumulate large amounts of triacylglycerol (TAG). Phosphatidic acid phosphatase (PAP) enzyme catalyzes the dephosphorylation of phosphatidic acid (PA) to yield diacylglycerol (DAG), a key precursor for TAG biosynthesis. Studies to establish its role in lipid metabolism have been mainly focused in eukaryotes but not in bacteria. In this work, we identified and characterized a putative PAP type 2 (PAP2) encoded by the ro00075 gene in Rhodococcus jostii RHA1. Heterologous expression of ro00075 in Escherichia coli resulted in a fourfold increase in PAP activity and twofold in DAG content. The conditional deletion of ro00075 in RHA1 led to a decrease in the content of DAG and TAG, whereas its overexpression in both RHA1 and Rhodococcus opacus PD630 promoted an increase up to 10 to 15 % by cellular dry weight in TAG content. On the other hand, expression of ro00075 in the non-oleaginous strain Rhodococcus fascians F7 promoted an increase in total fatty acid content up to 7 % at the expense of free fatty acid (FFA), DAG, and TAG fractions. Moreover, co-expression of ro00075/atf2 genes resulted in a fourfold increase in total fatty acid content by a further increase of the FFA and TAG fractions. The results of this study suggest that ro00075 encodes for a PAP2 enzyme actively involved in TAG biosynthesis. Overexpression of this gene, as single one or with an atf gene, provides an alternative approach to increase the biosynthesis and accumulation of bacterial oils as a potential source of raw material for biofuel production.

  7. Pseudomonas aeruginosa phage PaP1 DNA polymerase is an A-family DNA polymerase demonstrating ssDNA and dsDNA 3'-5' exonuclease activity.

    PubMed

    Liu, Binyan; Gu, Shiling; Liang, Nengsong; Xiong, Mei; Xue, Qizhen; Lu, Shuguang; Hu, Fuquan; Zhang, Huidong

    2016-08-01

    Most phages contain DNA polymerases, which are essential for DNA replication and propagation in infected host bacteria. However, our knowledge on phage-encoded DNA polymerases remains limited. This study investigated the function of a novel DNA polymerase of PaP1, which is the lytic phage of Pseudomonas aeruginosa. PaP1 encodes its sole DNA polymerase called Gp90 that was predicted as an A-family DNA polymerase with polymerase and 3'-5' exonuclease activities. The sequence of Gp90 is homologous but not identical to that of other A-family DNA polymerases, such as T7 DNA polymerases (Pol) and DNA Pol I. The purified Gp90 demonstrated a polymerase activity. The processivity of Gp90 in DNA replication and its efficiency in single-dNTP incorporation are similar to those of T7 Pol with processive thioredoxin (T7 Pol/trx). Gp90 can degrade ssDNA and dsDNA in 3'-5' direction at a similar rate, which is considerably lower than that of T7 Pol/trx. The optimized conditions for polymerization were a temperature of 37 °C and a buffer consisting of 40 mM Tris-HCl (pH 8.0), 30 mM MgCl2, and 200 mM NaCl. These studies on DNA polymerase encoded by PaP1 help advance our knowledge on phage-encoded DNA polymerases and elucidate PaP1 propagation in infected P. aeruginosa.

  8. Peptoid-Substituted Hybrid Antimicrobial Peptide Derived from Papiliocin and Magainin 2 with Enhanced Bacterial Selectivity and Anti-inflammatory Activity.

    PubMed

    Shin, Areum; Lee, Eunjung; Jeon, Dasom; Park, Young-Guen; Bang, Jeong Kyu; Park, Yong-Sun; Shin, Song Yub; Kim, Yangmee

    2015-06-30

    Antimicrobial peptides (AMPs) are important components of the host innate immune system. Papiliocin is a 37-residue AMP purified from larvae of the swallowtail butterfly Papilio xuthus. Magainin 2 is a 23-residue AMP purified from the skin of the African clawed frog Xenopus laevis. We designed an 18-residue hybrid peptide (PapMA) incorporating N-terminal residues 1-8 of papiliocin and N-terminal residues 4-12 of magainin 2, joined by a proline (Pro) hinge. PapMA showed high antimicrobial activity but was cytotoxic to mammalian cells. To decrease PapMA cytotoxicity, we designed a lysine (Lys) peptoid analogue, PapMA-k, which retained high antimicrobial activity but displayed cytotoxicity lower than that of PapMA. Fluorescent dye leakage experiments and confocal microscopy showed that PapMA targeted bacterial cell membranes whereas PapMA-k penetrated bacterial cell membranes. Nuclear magnetic resonance experiments revealed that PapMA contained an N-terminal α-helix from Lys(3) to Lys(7) and a C-terminal α-helix from Lys(10) to Lys(17), with a Pro(9) hinge between them. PapMA-k also had two α-helical structures in the same region connected with a flexible hinge residue at Nlys(9), which existed in a dynamic equilibrium of cis and trans conformers. Using lipopolysaccharide-stimulated RAW264.7 macrophages, the anti-inflammatory activity of PapMA and PapMA-k was confirmed by inhibition of nitric oxide and inflammatory cytokine production. In addition, treatment with PapMA and PapMA-k decreased the level of ultraviolet irradiation-induced expression of genes encoding matrix metalloproteinase-1 (MMP-1), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in human keratinocyte HaCaT cells. Thus, PapMA and PapMA-k are potent peptide antibiotics with antimicrobial and anti-inflammatory activity, with PapMA-k displaying enhanced bacterial selectivity.

  9. The maize (Zea mays ssp. mays var. B73) genome encodes 33 members of the purple acid phosphatase family

    PubMed Central

    González-Muñoz, Eliécer; Avendaño-Vázquez, Aida-Odette; Montes, Ricardo A. Chávez; de Folter, Stefan; Andrés-Hernández, Liliana; Abreu-Goodger, Cei; Sawers, Ruairidh J. H.

    2015-01-01

    Purple acid phosphatases (PAPs) play an important role in plant phosphorus nutrition, both by liberating phosphorus from organic sources in the soil and by modulating distribution within the plant throughout growth and development. Furthermore, members of the PAP protein family have been implicated in a broader role in plant mineral homeostasis, stress responses and development. We have identified 33 candidate PAP encoding gene models in the maize (Zea mays ssp. mays var. B73) reference genome. The maize Pap family includes a clear single-copy ortholog of the Arabidopsis gene AtPAP26, shown previously to encode both major intracellular and secreted acid phosphatase activities. Certain groups of PAPs present in Arabidopsis, however, are absent in maize, while the maize family contains a number of expansions, including a distinct radiation not present in Arabidopsis. Analysis of RNA-sequencing based transcriptome data revealed accumulation of maize Pap transcripts in multiple plant tissues at multiple stages of development, and increased accumulation of specific transcripts under low phosphorus availability. These data suggest the maize PAP family as a whole to have broad significance throughout the plant life cycle, while highlighting potential functional specialization of individual family members. PMID:26042133

  10. Enhancing Flower Color through Simultaneous Expression of the B-peru and mPAP1 Transcription Factors under Control of a Flower-Specific Promoter

    PubMed Central

    Kim, Da-Hye; Park, Sangkyu; Lee, Jong-Yeol; Ha, Sun-Hwa; Lim, Sun-Hyung

    2018-01-01

    Flower color is a main target for flower breeding. A transgenic approach for flower color modification requires a transgene and a flower-specific promoter. Here, we expressed the B-peru gene encoding a basic helix loop helix (bHLH) transcription factor (TF) together with the mPAP1 gene encoding an R2R3 MYB TF to enhance flower color in tobacco (Nicotiana tabacum L.), using the tobacco anthocyanidin synthase (ANS) promoter (PANS) to drive flower-specific expression. The transgenic tobacco plants grew normally and produced either dark pink (PANSBP_DP) or dark red (PANSBP_DR) flowers. Quantitative real time polymerase chain reaction (qPCR) revealed that the expression of five structural genes in the flavonoid biosynthetic pathway increased significantly in both PANSBP_DP and PANSBP_DR lines, compared with the non-transformed (NT) control. Interestingly, the expression of two regulatory genes constituting the active MYB-bHLH-WD40 repeat (WDR) (MBW) complex decreased significantly in the PANSBP_DR plants but not in the PANSBP_DP plants. Total flavonol and anthocyanin abundance correlated with flower color, with an increase of 1.6–43.2 fold in the PANSBP_DP plants and 2.0–124.2 fold in the PANSBP_DR plants. Our results indicate that combinatorial expression of B-peru and mPAP1 genes under control of the ANS promoter can be a useful strategy for intensifying flower color without growth retardation. PMID:29361688

  11. The dual-targeted purple acid phosphatase isozyme AtPAP26 is essential for efficient acclimation of Arabidopsis to nutritional phosphate deprivation.

    PubMed

    Hurley, Brenden A; Tran, Hue T; Marty, Naomi J; Park, Joonho; Snedden, Wayne A; Mullen, Robert T; Plaxton, William C

    2010-07-01

    Induction of intracellular and secreted acid phosphatases (APases) is a widespread response of orthophosphate (Pi)-starved (-Pi) plants. APases catalyze Pi hydrolysis from a broad range of phosphomonoesters at an acidic pH. The largest class of nonspecific plant APases is comprised of the purple APases (PAPs). Although the biochemical properties, subcellular location, and expression of several plant PAPs have been described, their physiological functions have not been fully resolved. Recent biochemical studies indicated that AtPAP26, one of 29 PAPs encoded by the Arabidopsis (Arabidopsis thaliana) genome, is the predominant intracellular APase, as well as a major secreted APase isozyme up-regulated by -Pi Arabidopsis. An atpap26 T-DNA insertion mutant lacking AtPAP26 transcripts and 55-kD immunoreactive AtPAP26 polypeptides exhibited: (1) 9- and 5-fold lower shoot and root APase activity, respectively, which did not change in response to Pi starvation, (2) a 40% decrease in secreted APase activity during Pi deprivation, (3) 35% and 50% reductions in free and total Pi concentration, respectively, as well as 5-fold higher anthocyanin levels in shoots of soil-grown -Pi plants, and (4) impaired shoot and root development when subjected to Pi deficiency. By contrast, no deleterious influence of AtPAP26 loss of function occurred under Pi-replete conditions, or during nitrogen or potassium-limited growth, or oxidative stress. Transient expression of AtPAP26-mCherry in Arabidopsis suspension cells verified that AtPAP26 is targeted to the cell vacuole. Our results confirm that AtPAP26 is a principal contributor to Pi stress-inducible APase activity, and that it plays an important role in the Pi metabolism of -Pi Arabidopsis.

  12. Mycobacterial polyketide-associated proteins are acyltransferases: Proof of principle with Mycobacterium tuberculosis PapA5

    PubMed Central

    Onwueme, Kenolisa C.; Ferreras, Julian A.; Buglino, John; Lima, Christopher D.; Quadri, Luis E. N.

    2004-01-01

    Mycobacterium tuberculosis (Mt) produces complex virulence-enhancing lipids with scaffolds consisting of phthiocerol and phthiodiolone dimycocerosate esters (PDIMs). Sequence analysis suggested that PapA5, a so-called polyketide-associated protein (Pap) encoded in the PDIM synthesis gene cluster, as well as PapA5 homologs found in Mt and other species, are a subfamily of acyltransferases. Studies with recombinant protein confirmed that PapA5 is an acetyltransferase. Deletion analysis in Mt demonstrated that papA5 is required for PDIM synthesis. We propose that PapA5 catalyzes diesterification of phthiocerol and phthiodiolone with mycocerosate. These studies present the functional characterization of a Pap and permit inferences regarding roles of other Paps in the synthesis of complex lipids, including the antibiotic rifamycin. PMID:15070765

  13. A sub-canopy structure for simulating oil palm in the Community Land Model: phenology, allocation and yield

    NASA Astrophysics Data System (ADS)

    Fan, Y.; Roupsard, O.; Bernoux, M.; Le Maire, G.; Panferov, O.; Kotowska, M. M.; Knohl, A.

    2015-06-01

    Land surface modelling has been widely used to characterize the two-way interactions between climate and human activities in terrestrial ecosystems such as deforestation, agricultural expansion, and urbanization. Towards an effort to quantify the effects of forests to oil palm conversion occurring in the tropics on land-atmosphere carbon, water and energy fluxes, we introduce a new perennial crop plant functional type (PFT) for oil palm. Due to the modular and sequential nature of oil palm growth (around 40 stacked phytomers) and yield (fruit bunches axillated on each phytomer), we developed a specific sub-canopy structure for simulating palm's growth and yield within the framework of the Community Land Model (CLM4.5). In this structure each phytomer has its own prognostic leaf growth and fruit yield capacity like a PFT but with shared stem and root components among all phytomers. Phenology and carbon and nitrogen allocation operate on the different phytomers in parallel but at unsynchronized steps, so that multiple fruit yields per annum are enabled in terms of carbon and nitrogen outputs. An important phenological phase is identified for the palm PFT - the storage growth period of bud and "spear" leaves which are photosynthetically inactive before expansion. Agricultural practices such as transplanting, fertilization, and leaf pruning are represented. Parameters introduced for the new PFT were calibrated and validated with field measurements of leaf area index (LAI) and yield from Sumatra, Indonesia. In calibration with a mature oil palm plantation, the cumulative yields from 2005 to 2014 matched perfectly between simulation and observation (mean percentage error = 4 %). Simulated inter-annual dynamics of PFT-level and phytomer-level LAI were both within the range of field measurements. Validation from eight independent oil palm sites shows the ability of the model to adequately predict the average leaf growth and fruit yield across sites but also indicates that seasonal dynamics and site-to-site variability of yield are driven by processes not yet implemented in the model. The new sub-canopy structure and phenology and allocation functions now allow exploring the effects of tropical land use change, from natural ecosystems to oil palm plantations, on carbon, water and energy cycles and regional climate.

  14. Shoot development in grapevine (Vitis vinifera) is affected by the modular branching pattern of the stem and intra- and inter-shoot trophic competition.

    PubMed

    Lebon, Eric; Pellegrino, Anne; Tardieu, Francois; Lecoeur, Jeremie

    2004-03-01

    Shoot architecture variability in grapevine (Vitis vinifera) was analysed using a generic modelling approach based on thermal time developed for annual herbaceous species. The analysis of shoot architecture was based on various levels of shoot organization, including pre-existing and newly formed parts of the stem, and on the modular structure of the stem, which consists of a repeated succession of three phytomers (P0-P1-P2). Four experiments were carried out using the cultivar 'Grenache N': two on potted vines (one of which was carried out in a glasshouse) and two on mature vines in a vineyard. These experiments resulted in a broad diversity of environmental conditions, but none of the plants experienced soil water deficit. Development of the main axis was highly dependent on air temperature, being linearly related to thermal time for all stages of leaf development from budbreak to veraison. The stable progression of developmental stages along the main stem resulted in a thermal-time based programme of leaf development. Leaf expansion rate varied with trophic competition (shoot and cluster loads) and environmental conditions (solar radiation, VPD), accounting for differences in final leaf area. Branching pattern was highly variable. Classification of the branches according to ternary modular structure increased the accuracy of the quantitative analysis of branch development. The rate and duration of leaf production were higher for branches derived from P0 phytomers than for branches derived from P1 or P2 phytomers. Rates of leaf production, expressed as a -function of thermal time, were not stable and depended on trophic competition and environmental conditions such as solar radiation or VPD. The application to grapevine of a generic model developed in annual plants made it possible to identify constants in main stem development and to determine the hierarchical structure of branches with respect to the modular structure of the stem in response to intra- and inter-shoot trophic competition.

  15. Structural isomers of polyfluorinated di- and tri-alkylated phosphate ester surfactants present in industrial blends and in microwave popcorn bags.

    PubMed

    Trier, Xenia; Nielsen, Nikoline Juul; Christensen, Jan H

    2011-09-01

    In this study, we provide strategies for detecting and quantifying the structural isomers of polyfluorinated di- and tri-alkyl surfactants (PFAS) by mass spectrometry (MS). We specifically investigate polyfluorinated dialkylated phosphate ester surfactants (x:2/y:2 diPAPS, (F(CF(2))( x )CH(2)CH(2)O-P(O)(O)(-)-OCH(2)CH(2)(CF(2))( y )F)) and their thioether analogues (x:2/y:2 S-diPAPS, F(CF(2))( x )CH(2)CH(2)SCH(2)-C[CH(2)O)(2)P(O)(O)(-)]-CH(2)SCH(2)CH(2)(CF(2))( y )F), which are used for industrial applications, such as oil- and water-repellent coatings on paper and board. DiPAPS have been found in human blood and are metabolised to the persistent perfluoroalkyl carboxylic acids (PFCA) in rats. A microwave popcorn bag extract was analysed by ultrahigh-pressure liquid chromatography coupled to a negative electrospray ionisation-quadrupole time-of-flight MS. The extract contained S-diPAPS, diPAPS and trialkylated (triPAPS) impurities. TriPAPS were also present in industrial and synthetic diPAPS standards, and were verified with an 8:2/8:2/8:2 triPAPS standard. The eight elemental compositions (m/z's) of diPAPS in the extract represent 19 precursor ion structures, and the six S-diPAPS m/z's represent at least 13 structures. The diPAPS had [M-H](-) precursor ions of m/z 789, 889,…1,489 and the S-diPAPS of m/z 921, 1,021,…1,421, corresponding to fluorinated chains from C(6-18). Each m/z appeared as one to three chromatographic peaks of structural isomers, where, e.g. m/z 1,189 was present as 10:2/10:2, 8:2/12:2 and 6:2/14:2 diPAPS. The isomers formed different products ions, thus only half of the m/z 1,189 diPAPS concentration was measured with one precursor ion > product ion transition. In general, knowledge about structural isomers of poly-alkylated PFAS is needed for the estimation of types and amounts of perfluorinated degradation products, such as PFCA from diPAPS.

  16. Over-expression of AtPAP2 in Camelina sativa leads to faster plant growth and higher seed yield

    PubMed Central

    2012-01-01

    Background Lipids extracted from seeds of Camelina sativa have been successfully used as a reliable source of aviation biofuels. This biofuel is environmentally friendly because the drought resistance, frost tolerance and low fertilizer requirement of Camelina sativa allow it to grow on marginal lands. Improving the species growth and seed yield by genetic engineering is therefore a target for the biofuels industry. In Arabidopsis, overexpression of purple acid phosphatase 2 encoded by Arabidopsis (AtPAP2) promotes plant growth by modulating carbon metabolism. Overexpression lines bolt earlier and produce 50% more seeds per plant than wild type. In this study, we explored the effects of overexpressing AtPAP2 in Camelina sativa. Results Under controlled environmental conditions, overexpression of AtPAP2 in Camelina sativa resulted in longer hypocotyls, earlier flowering, faster growth rate, higher photosynthetic rate and stomatal conductance, increased seed yield and seed size in comparison with the wild-type line and null-lines. Similar to transgenic Arabidopsis, activity of sucrose phosphate synthase in leaves of transgenic Camelina was also significantly up-regulated. Sucrose produced in photosynthetic tissues supplies the building blocks for cellulose, starch and lipids for growth and fuel for anabolic metabolism. Changes in carbon flow and sink/source activities in transgenic lines may affect floral, architectural, and reproductive traits of plants. Conclusions Lipids extracted from the seeds of Camelina sativa have been used as a major constituent of aviation biofuels. The improved growth rate and seed yield of transgenic Camelina under controlled environmental conditions have the potential to boost oil yield on an area basis in field conditions and thus make Camelina-based biofuels more environmentally friendly and economically attractive. PMID:22472516

  17. Nuclear Phosphatidylinositol-Phosphate Type I Kinase α-Coupled Star-PAP Polyadenylation Regulates Cell Invasion.

    PubMed

    A P, Sudheesh; Laishram, Rakesh S

    2018-03-01

    Star-PAP, a nuclear phosphatidylinositol (PI) signal-regulated poly(A) polymerase (PAP), couples with type I PI phosphate kinase α (PIPKIα) and controls gene expression. We show that Star-PAP and PIPKIα together regulate 3'-end processing and expression of pre-mRNAs encoding key anti-invasive factors ( KISS1R , CDH1 , NME1 , CDH13 , FEZ1 , and WIF1 ) in breast cancer. Consistently, the endogenous Star-PAP level is negatively correlated with the cellular invasiveness of breast cancer cells. While silencing Star-PAP or PIPKIα increases cellular invasiveness in low-invasiveness MCF7 cells, Star-PAP overexpression decreases invasiveness in highly invasive MDA-MB-231 cells in a cellular Star-PAP level-dependent manner. However, expression of the PIPKIα-noninteracting Star-PAP mutant or the phosphodeficient Star-PAP (S6A mutant) has no effect on cellular invasiveness. These results strongly indicate that PIPKIα interaction and Star-PAP S6 phosphorylation are required for Star-PAP-mediated regulation of cancer cell invasion and give specificity to target anti-invasive gene expression. Our study establishes Star-PAP-PIPKIα-mediated 3'-end processing as a key anti-invasive mechanism in breast cancer. Copyright © 2018 A.P. and Laishram.

  18. GLD-4-Mediated Translational Activation Regulates the Size of the Proliferative Germ Cell Pool in the Adult C. elegans Germ Line

    PubMed Central

    Millonigg, Sophia; Eckmann, Christian R.

    2014-01-01

    To avoid organ dysfunction as a consequence of tissue diminution or tumorous growth, a tight balance between cell proliferation and differentiation is maintained in metazoans. However, cell-intrinsic gene expression mechanisms controlling adult tissue homeostasis remain poorly understood. By focusing on the adult Caenorhabditis elegans reproductive tissue, we show that translational activation of mRNAs is a fundamental mechanism to maintain tissue homeostasis. Our genetic experiments identified the Trf4/5-type cytoplasmic poly(A) polymerase (cytoPAP) GLD-4 and its enzymatic activator GLS-1 to perform a dual role in regulating the size of the proliferative zone. Consistent with a ubiquitous expression of GLD-4 cytoPAP in proliferative germ cells, its genetic activity is required to maintain a robust proliferative adult germ cell pool, presumably by regulating many mRNA targets encoding proliferation-promoting factors. Based on translational reporters and endogenous protein expression analyses, we found that gld-4 activity promotes GLP-1/Notch receptor expression, an essential factor of continued germ cell proliferation. RNA-protein interaction assays documented also a physical association of the GLD-4/GLS-1 cytoPAP complex with glp-1 mRNA, and ribosomal fractionation studies established that GLD-4 cytoPAP activity facilitates translational efficiency of glp-1 mRNA. Moreover, we found that in proliferative cells the differentiation-promoting factor, GLD-2 cytoPAP, is translationally repressed by the stem cell factor and PUF-type RNA-binding protein, FBF. This suggests that cytoPAP-mediated translational activation of proliferation-promoting factors, paired with PUF-mediated translational repression of differentiation factors, forms a translational control circuit that expands the proliferative germ cell pool. Our additional genetic experiments uncovered that the GLD-4/GLS-1 cytoPAP complex promotes also differentiation, forming a redundant translational circuit with GLD-2 cytoPAP and the translational repressor GLD-1 to restrict proliferation. Together with previous findings, our combined data reveals two interconnected translational activation/repression circuitries of broadly conserved RNA regulators that maintain the balance between adult germ cell proliferation and differentiation. PMID:25254367

  19. Nuclear Phosphatidylinositol-Phosphate Type I Kinase α-Coupled Star-PAP Polyadenylation Regulates Cell Invasion

    PubMed Central

    A.P., Sudheesh

    2017-01-01

    ABSTRACT Star-PAP, a nuclear phosphatidylinositol (PI) signal-regulated poly(A) polymerase (PAP), couples with type I PI phosphate kinase α (PIPKIα) and controls gene expression. We show that Star-PAP and PIPKIα together regulate 3′-end processing and expression of pre-mRNAs encoding key anti-invasive factors (KISS1R, CDH1, NME1, CDH13, FEZ1, and WIF1) in breast cancer. Consistently, the endogenous Star-PAP level is negatively correlated with the cellular invasiveness of breast cancer cells. While silencing Star-PAP or PIPKIα increases cellular invasiveness in low-invasiveness MCF7 cells, Star-PAP overexpression decreases invasiveness in highly invasive MDA-MB-231 cells in a cellular Star-PAP level-dependent manner. However, expression of the PIPKIα-noninteracting Star-PAP mutant or the phosphodeficient Star-PAP (S6A mutant) has no effect on cellular invasiveness. These results strongly indicate that PIPKIα interaction and Star-PAP S6 phosphorylation are required for Star-PAP-mediated regulation of cancer cell invasion and give specificity to target anti-invasive gene expression. Our study establishes Star-PAP–PIPKIα-mediated 3′-end processing as a key anti-invasive mechanism in breast cancer. PMID:29203642

  20. Aerobic biotransformation of polyfluoroalkyl phosphate esters (PAPs) in soil.

    PubMed

    Liu, Chen; Liu, Jinxia

    2016-05-01

    Microbial transformation of polyfluoroalkyl phosphate esters (PAPs) into perfluorocarboxylic acids (PFCAs) has recently been confirmed to occur in activated sludge and soil. However, there lacks quantitative information about the half-lives of the PAPs and their significance as the precursors to PFCAs. In the present study, the biotransformation of 6:2 and 8:2 diPAP in aerobic soil was investigated in semi-dynamics reactors using improved sample preparation methods. To develop an efficient extraction method for PAPs, six different extraction solvents were compared, and the phenomenon of solvent-enhanced hydrolysis was investigated. It was found that adding acetic acid could enhance the recoveries of the diPAPs and inhibit undesirable hydrolysis during solvent extraction of soil. However 6:2 and 8:2 monoPAPs, which are the first breakdown products from diPAPs, were found to be unstable in the six solvents tested and quickly hydrolyzed to form fluorotelomer alcohols. Therefore reliable measurement of the monoPAPs from a live soil was not achievable. The apparent DT50 values of 6:2 diPAP and 8:2 diPAP biotransformation were estimated to be 12 and > 1000 days, respectively, using a double first-order in parallel model. At the end of incubation of day 112, the major degradation products of 6:2 diPAP were 5:3 fluorotelomer carboxylic acid (5:3 acid, 9.3% by mole), perfluoropentanoic acid (PFPeA, 6.4%) and perfluorohexanoic acid (PFHxA, 6.0%). The primary product of 8:2 diPAP was perfluorooctanoic acid (PFOA, 2.1%). The approximately linear relationship between the half-lives of eleven polyfluoroalkyl and perfluoroalkyl substances (PFASs, including 6:2 and 8:2 diPAPs) that biotransform in aerobic soils and their molecular weights suggested that the molecular weight is a good indicator of the general stability of low-molecular-weight PFAS-based compounds in aerobic soils. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. PAH1-encoded Phosphatidate Phosphatase Plays a Role in the Growth Phase- and Inositol-mediated Regulation of Lipid Synthesis in Saccharomyces cerevisiae*

    PubMed Central

    Pascual, Florencia; Soto-Cardalda, Aníbal; Carman, George M.

    2013-01-01

    In the yeast Saccharomyces cerevisiae, the synthesis of phospholipids in the exponential phase of growth occurs at the expense of the storage lipid triacylglycerol. As exponential phase cells progress into the stationary phase, the synthesis of triacylglycerol occurs at the expense of phospholipids. Early work indicates a role of the phosphatidate phosphatase (PAP) in this metabolism; the enzyme produces the diacylglycerol needed for the synthesis of triacylglycerol and simultaneously controls the level of phosphatidate for the synthesis of phospholipids. Four genes (APP1, DPP1, LPP1, and PAH1) encode PAP activity in yeast, and it has been unclear which gene is responsible for the synthesis of triacylglycerol throughout growth. An analysis of lipid synthesis and composition, as well as PAP activity in various PAP mutant strains, showed the essential role of PAH1 in triacylglycerol synthesis throughout growth. Pah1p is a phosphorylated enzyme whose in vivo function is dependent on its dephosphorylation by the Nem1p-Spo7p protein phosphatase complex. nem1Δ mutant cells exhibited defects in triacylglycerol synthesis and lipid metabolism that mirrored those imparted by the pah1Δ mutation, substantiating the importance of Pah1p dephosphorylation throughout growth. An analysis of cells bearing PPAH1-lacZ and PPAH1-DPP1 reporter genes showed that PAH1 expression was induced throughout growth and that the induction in the stationary phase was stimulated by inositol supplementation. A mutant analysis indicated that the Ino2p/Ino4p/Opi1p regulatory circuit and transcription factors Gis1p and Rph1p mediated this regulation. PMID:24196957

  2. Interplay of the modified nucleotide phosphoadenosine 5'-phosphosulfate (PAPS) with global regulatory proteins in Escherichia coli: modulation of cyclic AMP (cAMP)-dependent gene expression and interaction with the HupA regulatory protein.

    PubMed

    Longo, Francesca; Motta, Sara; Mauri, Pierluigi; Landini, Paolo; Rossi, Elio

    2016-11-25

    In the bacterium Escherichia coli, some intermediates of the sulfate assimilation and cysteine biosynthesis pathway can act as signal molecules and modulate gene expression. In addition to sensing and utilization of sulphur sources, these signaling mechanisms also impact more global cell processes, such as resistance to antimicrobial agents and biofilm formation. In a recent work, we have shown that inactivation of the cysH gene, encoding phosphoadenosine-phosphosulfate (PAPS) reductase, and the consequent increase in intracellular PAPS concentration, strongly affect production of several cell surface-associated structures, enhancing surface adhesion and cell aggregation. In order to identify the molecular mechanism relaying intracellular PAPS concentration to regulation of cell surface-associated structures, we looked for mutations able to suppress the effects of cysH inactivation. We found that mutations in the adenylate cyclase-encoding cyaA gene abolished the effects of PAPS accumulation; consistent with this result, cyclic AMP (cAMP)-dependent gene expression appears to be increased in the cysH mutant. Experiments aimed at the direct identification of proteins interacting with either CysC or CysH, i.e. the PAPS-related proteins APS kinase and PAPS reductase, allowed us to identify several regulators, namely, CspC, CspE, HNS and HupA. Protein-protein interaction between HupA and CysH was confirmed by a bacterial two hybrid system, and inactivation of the hupA gene enhanced the effects of the cysH mutation in terms of production of cell surface-associated factors. Our results indicate that PAPS can modulate different regulatory systems, providing evidence that this molecule acts as a global signal molecule in E. coli. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Suppression of DS1 Phosphatidic Acid Phosphatase Confirms Resistance to Ralstonia solanacearum in Nicotiana benthamiana

    PubMed Central

    Nakano, Masahito; Nishihara, Masahiro; Yoshioka, Hirofumi; Takahashi, Hirotaka; Sawasaki, Tatsuya; Ohnishi, Kouhei; Hikichi, Yasufumi; Kiba, Akinori

    2013-01-01

    Nicotiana benthamiana is susceptible to Ralstonia solanacearum. To analyze molecular mechanisms for disease susceptibility, we screened a gene-silenced plant showing resistance to R. solanacearum, designated as DS1 (Disease suppression 1). The deduced amino acid sequence of DS1 cDNA encoded a phosphatidic acid phosphatase (PAP) 2. DS1 expression was induced by infection with a virulent strain of R. solanacearum in an hrp-gene-dependent manner. DS1 rescued growth defects of the temperature-sensitive ∆lpp1∆dpp1∆pah1 mutant yeast. Recombinant DS1 protein showed Mg2+-independent PAP activity. DS1 plants showed reduced PAP activity and increased phosphatidic acid (PA) content. After inoculation with R. solanacearum, DS1 plants showed accelerated cell death, over-accumulation of reactive oxygen species (ROS), and hyper-induction of PR-4 expression. In contrast, DS1-overexpressing tobacco plants showed reduced PA content, greater susceptibility to R. solanacearum, and reduced ROS production and PR-4 expression. The DS1 phenotype was partially compromised in the plants in which both DS1 and NbCoi1 or DS1 and NbrbohB were silenced. These results show that DS1 PAP may affect plant immune responses related to ROS and JA cascades via regulation of PA levels. Suppression of DS1 function or DS1 expression could rapidly activate plant defenses to achieve effective resistance against Ralstonia solanacearum. PMID:24073238

  4. Genetics of digalactoside-binding adhesin from a uropathogenic Escherichia coli strain.

    PubMed Central

    Normark, S; Lark, D; Hull, R; Norgren, M; Båga, M; O'Hanley, P; Schoolnik, G; Falkow, S

    1983-01-01

    The uropathogenic strain Escherichia coli J96 mediates mannose-resistant hemagglutination owing to production of a digalactoside-binding adhesin. A cosmid clone from this strain has been isolated that, when harbored in E. coli K-12, expressed Pap pili and this adhesin (R. Hull et al., Infect. Immun. 33:933-938, 1981). By transposon mutagenesis and by the construction of a number of hybrid plasmid derivatives, we have demonstrated that about 8.5 kilobases of DNA is required to generate a mannose-resistant hemagglutination-positive phenotype in E. coli K-12 strain P678-54. The structural gene for the Pap pili monomer, papA, has been identified and mapped close to the promotor-proximal end of the Pap operon. Although strain P678-54 that harbored a Tn5 insertion within papA showed a mannose-resistant hemagglutination-positive phenotype, it was negative in a competitive enzyme-linked immunosorbent assay with anti-Pap pilus serum. This could mean that a Pap adhesin is encoded by a region on the Pap operon that is distinct from papA. Images PMID:6136465

  5. Involvement of phosphatidate phosphatase in the biosynthesis of triacylglycerols in Chlamydomonas reinhardtii * #

    PubMed Central

    Deng, Xiao-dong; Cai, Jia-jia; Fei, Xiao-wen

    2013-01-01

    Lipid biosynthesis is essential for eukaryotic cells, but the mechanisms of the process in microalgae remain poorly understood. Phosphatidic acid phosphohydrolase or 3-sn-phosphatidate phosphohydrolase (PAP) catalyzes the dephosphorylation of phosphatidic acid to form diacylglycerols and inorganic orthophosphates. This reaction is integral in the synthesis of triacylglycerols. In this study, the mRNA level of the PAP isoform CrPAP2 in a species of Chlamydomonas was found to increase in nitrogen-free conditions. Silencing of the CrPAP2 gene using RNA interference resulted in the decline of lipid content by 2.4%–17.4%. By contrast, over-expression of the CrPAP2 gene resulted in an increase in lipid content by 7.5%–21.8%. These observations indicate that regulation of the CrPAP2 gene can control the lipid content of the algal cells. In vitro CrPAP2 enzyme activity assay indicated that the cloned CrPAP2 gene exhibited biological activities. PMID:24302712

  6. Performance of a New HPV Cervi-Collect Collection and Transportation Kit

    PubMed Central

    Chernesky, M.; Huang, S.; Jang, D.; Erickson, B.; Salituro, J.; Engel, H.; Gilchrist, J.; Neuscheler, P.; Mak, W. B.; Abravaya, K.

    2012-01-01

    Background. Liquid-based Pap (L-Pap) media are used for Pap and human papillomavirus (HPV) testing. Objectives. To compare RealTime High Risk (HR) HPV testing of a new collection kit (Cervi-Collect) and PreservCyt L-Pap specimens. To determine ease of use and safety of Cervi-Collect. Methods. L-Pap samples (n = 203) were tested with HC2 and RealTime HR HPV and Cervi-Collect with RealTime HR HPV. Discordant samples were genotyped. Results. L-Pap and Cervi-Collect specimens tested by RealTime HR HPV showed 93.1% agreement (Kappa 0.86). RealTime HR HPV and HC2 on L-Pap had 90.3% agreement (Kappa 0.80). RealTime HR HPV on Cervi-Collect and HC2 on L-Pap showed 88.2% agreement (Kappa 0.76). Sixteen of 21 samples which were HC2 negative and RealTime HR HPV positive on L-Pap or Cervi-Collect contained HR HPV genotypes. Eleven healthcare collectors were in strong agreement on a usability and safety questionnaire. Conclusion. Cervi-Collect samples were easy to collect and showed strong agreement with L-Pap samples tested with RealTime HR HPV or HC2. PMID:22174716

  7. Exploring Indirect Sources of Human Exposure to Perfluoroalkyl Carboxylates (PFCAs): Evaluating Uptake, Elimination, and Biotransformation of Polyfluoroalkyl Phosphate Esters (PAPs) in the Rat

    PubMed Central

    D’eon, Jessica C.; Mabury, Scott A.

    2011-01-01

    Background Perfluorinated carboxylic acids (PFCAs) are ubiquitous in human sera worldwide. Biotransformation of the polyfluoroalkyl phosphate esters (PAPs) is a possible source of PFCA exposure, because PAPs are used in food-contact paper packaging and have been observed in human sera. Objectives We determined pharmacokinetic parameters for the PAP monoesters (monoPAPs) and PAP diesters (diPAPs), as well as biotransformation yields to the PFCAs, using a rat model. Methods The animals were dosed intravenously or by oral gavage with a mixture of 4:2, 6:2, 8:2, and 10:2 monoPAP or diPAP chain lengths. Concentrations of the PAPs and PFCAs, as well as metabolic intermediates and phase II metabolites, were monitored over time in blood, urine, and feces. Results The diPAPs were bioavailable, with bioavailability decreasing as the chain length increased from 4 to 10 perfluorinated carbons. The monoPAPs were not absorbed from the gut; however, we found evidence to suggest phosphate-ester cleavage within the gut contents. We observed biotransformation to the PFCAs for both monoPAP and diPAP congeners. Conclusions Using experimentally derived biotransformation yields, perfluorooctanoic acid (PFOA) sera concentrations were predicted from the biotransformation of 8:2 diPAP at concentrations observed in human serum. Because of the long human serum half-life of PFOA, biotransformation of diPAP even with low-level exposure could over time result in significant exposure to PFOA. Although humans are exposed directly to PFCAs in food and dust, the pharmacokinetic parameters determined here suggest that PAP exposure should be considered a significant indirect source of human PFCA contamination. PMID:21059488

  8. Engineering of the PapMV vaccine platform with a shortened M2e peptide leads to an effective one dose influenza vaccine.

    PubMed

    Carignan, Damien; Thérien, Ariane; Rioux, Gervais; Paquet, Geneviève; Gagné, Marie-Ève Laliberté; Bolduc, Marilène; Savard, Pierre; Leclerc, Denis

    2015-12-16

    The emergence of highly virulent influenza strains and the risks of pandemics as well as the limited efficiency of the current seasonal vaccines are important public health concerns. There is a major need for new influenza vaccines that would be broadly cross-protective. The ectodomain of matrix protein 2 (M2e) is highly conserved amongst different influenza strains and could be used as a broad spectrum antigen. To overcome its low immunogenicity we have fused a short peptide epitope derived from the human consensus sequence of M2e (amino acids 6-14, EVETPIRNE) to the N-terminus of papaya mosaic virus coat protein. The fusion harboring coat proteins were assembled around a single stranded RNA into virus-like particles (PapMV-sM2e). The resulting PapMV-sM2e rod-shaped particle was stable and indistinguishable from regular PapMV particles. A single intramuscular immunization with PapMV-sM2e was sufficient to mount appreciable levels of CD4 dependent M2e specific total IgG and IgG2a antibody in mice sera. PapMV-sM2e proved to be self-adjuvanting since the addition of PapMV as an exogenous adjuvant did not result in significantly improved antibody titers. In addition, we confirmed the adjuvant property of PapMV-sM2e using the trivalent inactivated flu vaccine as antigen and demonstrated that the newly engineered nanoparticles areas efficacious as an adjuvant than the original PapMV nanoparticles. Upon infection with a sub-lethal dose of influenza, PapMV-sM2e vaccinated animals were completely protected from virus induced morbidity and mortality. Mice immunized with decreasing amounts of PapMV-sM2e and challenged with a more stringent dose of influenza virus displayed dose-dependent levels of protection. Seventy percent of the mice immunized once with the highest dose of PapMV-sM2e survived the challenged. The survival of the mice correlated mainly with the levels of anti-M2e IgG2a antibodies obtained before the infection. These results demonstrate that PapMV-sM2e can be an important component of a broadly cross-reactive influenza vaccine. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Patient-Reported Usability of Positive Airway Pressure Equipment Is Associated With Adherence in Older Adults

    PubMed Central

    Martin, Jennifer L.; Hays, Ron D.; Patterson, Emily S.; Aysola, Ravi; Col, Nananda; Mitchell, Michael N.; Truong, Cindy; Dzierzewski, Joseph M.; Jouldjian, Stella; Song, Yeonsu; Rodriguez, Juan Carlos; Josephson, Karen; Alessi, Cathy

    2017-01-01

    Abstract Study objectives: To examine the usability of positive airway pressure (PAP) devices and its association with PAP adherence among older adults with sleep-disordered breathing. Methods: We mailed questionnaires to patients aged ≥65 years prescribed PAP therapy during the prior 36 months from two large healthcare systems. Survey participants completed the Usability of Sleep Apnea Equipment-Positive Airway Pressure (USE-PAP) questionnaire, which assessed the usability of their PAP device. Other questionnaire items included demographics and self-rated health. We also abstracted adherence data (mean nightly hours of PAP use available from one site) and interface type from the electronic health record. Results: Five hundred sixty-four patients completed the survey (response rate = 33%). The mean USE-PAP score (0 = best to 100 = worst) was 20 (SD ± 20). Mean duration of PAP use (available in 189 respondents) was 5.2 hours per night (SD ± 2.0). In a nested regression model predicting nightly hours of PAP use, a 10-point (0.5 SD) increase in USE-PAP score corresponded to a 0.37 hour/night reduction in PAP use. The model including the USE-PAP score explained a significant proportion (R2 = 15%) of the variation in nightly hours of PAP use above and beyond demographics, self-reported health, and interface type (∆R2 = 12%). Conclusions: Our results demonstrate that PAP usability varies among older patients and is associated with PAP adherence, above and beyond other predictors of adherence. These results support measuring and improving PAP usability to further improve PAP adherence for older patients. PMID:28364429

  10. Auto-trilevel versus bilevel positive airway pressure ventilation for hypercapnic overlap syndrome patients.

    PubMed

    Su, Mei; Huai, De; Cao, Juan; Ning, Ding; Xue, Rong; Xu, Meijie; Huang, Mao; Zhang, Xilong

    2018-03-01

    Although bilevel positive airway pressure (Bilevel PAP) therapy is usually used for overlap syndrome (OS), there is still a portion of OS patients in whom Bilevel PAP therapy could not simultaneously eliminate residual apnea events and hypercapnia. The current study was expected to explore whether auto-trilevel positive airway pressure (auto-trilevel PAP) therapy with auto-adjusting end expiratory positive airway pressure (EEPAP) can serve as a better alternative for these patients. From January of 2014 to June of 2016, 32 hypercapnic OS patients with stable chronic obstructive pulmonary diseases (COPD) and moderate-to-severe obstructive sleep apnea syndrome (OSAS) were recruited. Three variable modes of positive airway pressure (PAP) from the ventilator (Prisma25ST, Weinmann Inc., Germany) were applicated for 8 h per night. We performed the design of each mode at each night with an interval of two nights with no PAP treatment as a washout period among different modes. In Bilevel-1 mode (Bilevel-1), the expiratory positive airway pressure (EPAP) delivered from Bilevel PAP was always set as the lowest PAP for abolishment of snoring. For each patient, the inspiratory positive airway pressure (IPAP) was constantly set the same as the minimal pressure for keeping end-tidal CO 2 (ETCO 2 ) ≤45 mmHg for all three modes. However, the EPAP issued by Bilevel PAP in Bilevel-2 mode (Bilevel-2) was kept 3 cmH 2 O higher than that in Bilevel-1. In auto-trilevel mode (auto-trilevel) with auto-trilevel PAP, the initial part of EPAP was fixed at the same PAP as that in Bilevel-1 while the EEPAP was automatically regulated to rise at a range of ≤4 cmH 2 O based on nasal airflow wave changes. Comparisons were made for parameters before and during or following treatment as well as among different PAP therapy modes. The following parameters were compared such as nocturnal apnea hypopnea index (AHI), minimal SpO 2 (minSpO 2 ), arousal index, sleep structure and efficiency, morning PaCO 2 , and daytime Epworth Sleepiness Scale (ESS). Compared with the parameters before PAP therapies, during each mode of PAP treatment, significant reduction was detected in nocturnal AHI, arousal index, morning PaCO 2 , and daytime ESS while significant elevation was revealed in nocturnal minSpO 2 and sleep efficiency (all P < 0.01). Comparison among three PAP modes indicated that under the same IPAP, the auto-trilevel PAP mode could result in the lowest arousal index, daytime ESS, and the highest sleep efficiency. Compared with Bilevel-1, it was detected that (a) AHI was lower but minSpO 2 was higher in both Bilevel-2 and auto-trilevel (all P < 0.05) and (b) morning PaCO 2 showed no statistical difference from that in auto-trilevel but displayed higher in Bilevel-2 (P < 0.05). Compared with Bilevel-2, in auto-trilevel, both AHI and minSpO 2 showed no obvious changes (all P > 0.05) except with a lower morning PaCO 2 (P < 0.05). Auto-trilevel PAP therapy was superior over conventional Bilevel PAP therapy for hypercapnic OS patients with their OSAS moderate to severe, since auto-trilevel PAP was more efficacious in synchronous elimination of residual obstructive apnea events and CO 2 retention as well as in obtaining a better sleep quality and milder daytime drowsiness.

  11. Patient-Reported Usability of Positive Airway Pressure Equipment Is Associated With Adherence in Older Adults.

    PubMed

    Fung, Constance H; Martin, Jennifer L; Hays, Ron D; Patterson, Emily S; Aysola, Ravi; Col, Nananda; Mitchell, Michael N; Truong, Cindy; Dzierzewski, Joseph M; Jouldjian, Stella; Song, Yeonsu; Rodriguez, Juan Carlos; Josephson, Karen; Alessi, Cathy

    2017-03-01

    To examine the usability of positive airway pressure (PAP) devices and its association with PAP adherence among older adults with sleep-disordered breathing. We mailed questionnaires to patients aged ≥65 years prescribed PAP therapy during the prior 36 months from two large healthcare systems. Survey participants completed the Usability of Sleep Apnea Equipment-Positive Airway Pressure (USE-PAP) questionnaire, which assessed the usability of their PAP device. Other questionnaire items included demographics and self-rated health. We also abstracted adherence data (mean nightly hours of PAP use available from one site) and interface type from the electronic health record. Five hundred sixty-four patients completed the survey (response rate = 33%). The mean USE-PAP score (0 = best to 100 = worst) was 20 (SD ± 20). Mean duration of PAP use (available in 189 respondents) was 5.2 hours per night (SD ± 2.0). In a nested regression model predicting nightly hours of PAP use, a 10-point (0.5 SD) increase in USE-PAP score corresponded to a 0.37 hour/night reduction in PAP use. The model including the USE-PAP score explained a significant proportion (R2 = 15%) of the variation in nightly hours of PAP use above and beyond demographics, self-reported health, and interface type (∆R2 = 12%). Our results demonstrate that PAP usability varies among older patients and is associated with PAP adherence, above and beyond other predictors of adherence. These results support measuring and improving PAP usability to further improve PAP adherence for older patients. Published by Oxford University Press on behalf of Sleep Research Society (SRS) 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  12. Characterization of recombinant prolyl aminopeptidase from Aspergillus oryzae.

    PubMed

    Matsushita-Morita, M; Furukawa, I; Suzuki, S; Yamagata, Y; Koide, Y; Ishida, H; Takeuchi, M; Kashiwagi, Y; Kusumoto, K-I

    2010-07-01

    Prolyl aminopeptidase (PAP) degrades only amino-terminal proline from peptides. The food-grade fungus Aspergillus oryzae produces this enzyme only in small amounts. In this paper, we present efficient production of recombinant PAP with an overexpression system of A. oryzae and characterization of its biochemical properties. The gene encoding PAP was overexpressed as a His-tag fusion protein under a taka-amylase gene (amyB) promoter with a limited expressing condition in A. oryzae. The PAP activity in the mycelia grown in rich medium containing glucose (repressing condition) was twice that in starch (inducing condition). The enzyme prepared as cell-free extract was partially purified through two-step column chromatography. The PAP was estimated to be a hexameric protein and exhibited salt tolerance against NaCl of up to 4 mol l(-1). Aspergillus oryzae PAP was produced under the repressing condition of amyB promoter in a PAP-overexpressing strain and purified 1800-folds. Overproduction of PAP under promoter-inducing conditions led to an increase in inactive PAP, possibly because of irregular folding. PAP with a high specific activity and salt tolerance may be used effectively in the manufacturing processes of fermented foods. Journal compilation © 2009 The Society for Applied Microbiology. No claim to Japanese Government works.

  13. Metabolism of para-aminophenol by rat hepatocytes.

    PubMed

    Yan, Z; Nikelly, J G; Killmer, L; Tarloff, J B

    2000-08-01

    Autoxidation of para-aminophenol (PAP) has been proposed to account for the selective nephrotoxicity of this compound. However, other studies suggest that hepatic metabolites of PAP rather than the parent compound may be responsible for renal damage. These studies were designed to investigate PAP metabolism in isolated hepatocytes. We synthesized several proposed metabolites for analysis by HPLC/mass spectrometry and compared those results with HPLC/mass spectrometric analyses of metabolites found after incubating hepatocytes with PAP. Hepatocytes prepared from male Sprague-Dawley rats were incubated in Krebs-Henseleit buffer at 37 degrees C for 5 h with 2.3 mM PAP under an atmosphere of 5% CO2/95% O2. Aliquots were withdrawn at 0.1 h of incubation and then hourly through 5 h of incubation. Reactions were terminated by the addition of acetonitrile. Hepatocyte viability was unaltered with PAP present in the incubation medium. We found that hepatocytes converted PAP to two major metabolites (PAP-GSH conjugates and PAP-N-acetylcysteine conjugates) and several minor metabolites [PAP-O-glucuronide, acetaminophen (APAP), APAP-O-glucuronide, APAP-GSH conjugates, and 4-hydroxyformanilide]. Preincubating hepatoyctes with 1-aminobenzotriazole, an inhibitor of cytochromes P450, did not alter the pattern of PAP metabolism. In conclusion, we found that PAP was metabolized in hepatocytes predominantly to PAP-GSH conjugates and PAP-N-acetylcysteine conjugates in sufficient quantities to account for the nephrotoxicity of PAP.

  14. Occurrence of pathogenicity island I(APEC-O1) genes among Escherichia coli implicated in avian colibacillosis.

    PubMed

    Kariyawasam, Subhashinie; Johnson, Timothy J; Debroy, Chitrita; Nolan, Lisa K

    2006-09-01

    Colibacillosis caused by avian pathogenic Escherichia coli (APEC) is a leading cause of economic loss to the poultry industry worldwide. The ability of APEC to cause disease is determined by certain virulence markers, some of which are located on pathogenicity islands (PAls). We recently described one such PAI in an APEC O1:K1 strain (APEC-O1). This PAI, termed PAI I(APEC-O1), carries the genes of the pap operon, a region similar to the tia invasion determinant of enterotoxigenic E coli; ireA, a gene that encodes an iron-responsive element; and a novel 1.5-kb region, ORF 54. Here, the occurrence of six selected loci of PAI I(APEC-O1) (papA, papC, papG, ireA, tia, and ORF 54) among APEC and fecal E. coli strains from apparently healthy chickens (avian commensal E. coli) was determined using polymerase chain reaction (PCR) techniques. None of the commensal E. coli was positive for all six traits, whereas 7.2% of the APEC isolates were positive for all the traits. Although there was no significant difference in the occurrence of ORF 54 among APEC and commensal E. coli, tia, ireA, papC, and papG genes were predominantly present in APEC rather than in avian commensal E. coli. papA was detected in only 6.3% of APEC, perhaps because of the presence of allelic variants of the gene. Additionally, the presence of all six traits was tested with PCR in APEC isolates collected in the 1980s, and these results were compared with those obtained with the APEC isolated in the 1990s. There was no significant difference in the occurrence of tia, ireA, papC, papG, and ORF 54 between APEC isolates collected during the different decades. However, papA was more frequently present in APEC from the 1980s than it was in APEC from the 1990s. Phylogenetic group of an isolate did not correlate with pathogenicity or the presence of PAI traits, except that more APEC of the low-pathogenicity group belonged to the phylogenetic group B1. However, PAI traits occurred more frequently in isolates belonging to the intermediate- and high-pathogenicity groups than in isolates of low pathogenicity.

  15. Characterization of a soluble phosphatidic acid phosphatase in bitter melon (Momordica charantia).

    PubMed

    Cao, Heping; Sethumadhavan, Kandan; Grimm, Casey C; Ullah, Abul H J

    2014-01-01

    Momordica charantia is often called bitter melon, bitter gourd or bitter squash because its fruit has a bitter taste. The fruit has been widely used as vegetable and herbal medicine. Alpha-eleostearic acid is the major fatty acid in the seeds, but little is known about its biosynthesis. As an initial step towards understanding the biochemical mechanism of fatty acid accumulation in bitter melon seeds, this study focused on a soluble phosphatidic acid phosphatase (PAP, 3-sn-phosphatidate phosphohydrolase, EC 3.1.3.4) that hydrolyzes the phosphomonoester bond in phosphatidate yielding diacylglycerol and P(i). PAPs are typically categorized into two subfamilies: Mg(2+)-dependent soluble PAP and Mg(2+)-independent membrane-associated PAP. We report here the partial purification and characterization of an Mg(2+)-independent PAP activity from developing cotyledons of bitter melon. PAP protein was partially purified by successive centrifugation and UNOsphere Q and S columns from the soluble extract. PAP activity was optimized at pH 6.5 and 53-60 °C and unaffected by up to 0.3 mM MgCl2. The K(m) and Vmax values for dioleoyl-phosphatidic acid were 595.4 µM and 104.9 ηkat/mg of protein, respectively. PAP activity was inhibited by NaF, Na(3)VO(4), Triton X-100, FeSO4 and CuSO4, but stimulated by MnSO4, ZnSO4 and Co(NO3)2. In-gel activity assay and mass spectrometry showed that PAP activity was copurified with a number of other proteins. This study suggests that PAP protein is probably associated with other proteins in bitter melon seeds and that a new class of PAP exists as a soluble and Mg(2+)-independent enzyme in plants.

  16. Star-PAP Control of BIK Expression and Apoptosis Is Regulated by Nuclear PIPKIα and PKCδ Signaling

    PubMed Central

    Li, Weimin; Laishram, Rakesh S.; Ji, Zhe; Barlow, Christy A.; Tian, Bin; Anderson, Richard A.

    2012-01-01

    SUMMARY BIK protein is an initiator of mitochondrial apoptosis and BIK expression is induced by pro-apoptotic signals including DNA damage. Here we demonstrate that 3′-end processing and expression of BIK mRNA are controlled by the nuclear PI4,5P2-regulated poly(A) polymerase Star-PAP downstream of DNA damage. Nuclear PKCδ is a key mediator of apoptosis and DNA damage stimulates PKCδ association with the Star-PAP complex where PKCδ is required for Star-PAP-dependent BIK expression. PKCδ binds the PI4,5P2-generating enzyme PIPKIα, which is essential for PKCδ interaction with the Star-PAP complex and PKCδ activity is directly stimulated by PI4,5P2. Features in the BIK 3′-UTR uniquely define Star-PAP specificity and may block canonical PAP activity toward BIK mRNA. This reveals a nuclear phosphoinositide signaling nexus where PIPKIα, PI4,5P2 and PKCδ regulate Star-PAP control of BIK expression and induction of apoptosis. This pathway is distinct from the Star-PAP-mediated oxidative stress pathway indicating signal-specific regulation of mRNA 3′-end processing. PMID:22244330

  17. Polyfluoroalkyl phosphate esters and perfluoroalkyl carboxylic acids in target food samples and packaging--method development and screening.

    PubMed

    Gebbink, Wouter A; Ullah, Shahid; Sandblom, Oskar; Berger, Urs

    2013-11-01

    Polyfluoroalkyl phosphate mono-, di-, and tri-esters (mono-, di-, and triPAPs) are used to water- and grease-proof food packaging materials, and these chemicals are known precursors to perfluoroalkyl carboxylic acids (PFCAs). Existing analytical methods for PAPs lack sample clean-up steps in the sample preparation. In the present study, a method based on ultra performance liquid chromatography coupled to tandem mass spectrometry (UPLC/MS/MS) was developed and optimized for the analysis of mono-, di-, and triPAPs, including a clean-up step for the raw extracts. The method was applied to food samples and their PAP-containing packaging materials. The optimized UPLC/MS/MS method enabled the separation and identification of a total of 4 monoPAPs, 16 diPAPs, and 7 triPAPs in the technical mixture Zonyl®-RP. For sample clean-up, weak anion exchange solid phase extraction columns were tested. PAPs standard solutions spiked onto the columns were separated into a fraction containing neutral compounds (triPAPs) and a fraction with ionic compounds (mono- and diPAPs) with recoveries between 72-110%. Method limits of quantification for food samples were in the sub to low picogram per gram range. For quantitative analysis of PAPs, compound-specific labeled internal standards showed to be essential as sorption and matrix effects were observed. Mono-, di-, and/or triPAPs were detected in all food packaging materials obtained from the Swedish market. Up to nine diPAPs were detected in the food samples, with the 6:2/6:2 and 6:2/8:2 diPAPs as the dominant compounds. DiPAP concentrations in the food samples ranged from 0.9 to 36 pg/g, which was comparable to individual PFCA concentrations in the same samples. Consumption of food packed in PAP-containing materials could be an indirect source of human exposure to PFCAs.

  18. Determinants of exercise-induced pulmonary arterial hypertension in systemic sclerosis.

    PubMed

    Voilliot, Damien; Magne, Julien; Dulgheru, Raluca; Kou, Seisyou; Henri, Christine; Laaraibi, Saloua; Sprynger, Muriel; Andre, Béatrice; Pierard, Luc A; Lancellotti, Patrizio

    2014-05-15

    Exercise-induced pulmonary arterial hypertension (EIPH) in systemic sclerosis (SSc) has already been observed but its determinants remain unclear. The aim of this study was to determine the incidence and the determinants of EIPH in SSc. We prospectively enrolled 63 patients with SSc (age 54±3years, 76% female) followed in CHU Sart-Tilman in Liège. All patients underwent graded semi-supine exercise echocardiography. Systolic pulmonary arterial pressure (sPAP) was derived from the peak velocity of the tricuspid regurgitation jet and adding the estimation of right atrial pressure, both at rest and during exercise. Resting pulmonary arterial hypertension (PH) was defined as sPAP > 35 mmHg and EIPH as sPAP > 50 mmHg during exercise. The following formulas were used: mean PAP (mPAP) = 0.61 × sPAP + 2, left atrial pressure (LAP)=1.9+1.24 × left ventricular (LV) E/e' and pulmonary vascular resistance (PVR)=(mPAP-LAP)/LV cardiac output (CO) and slope of mPAP-LVCO relationship=changes in mPAP/changes in LVCO. Resting PH was present in 3 patients (7%) and 21 patients developed EIPH (47%). Patients with EIPH had higher resting LAP (10.3 ± 2.2 versus 8.8 ± 2.3 mmHg; p = 0.03), resting PVR (2.6 ± 0.8 vs. 1.4 ± 1.1 Woods units; p=0.004), exercise LAP (13.3 ± 2.3 vs. 9 ± 1.7 mmHg; p < 0.0001), exercise PVR (3.6 ± 0.7 vs. 2.1 ± 0.9 Woods units; p = 0.02) and slope of mPAP-LVCO (5.8 ± 2.4 vs. 2.9 ± 2.1 mmHg/L/min; p < 0.0001). After adjustment for age and gender, exercise LAP (β=3.1 ± 0.8; p=0.001) and exercise PVR (β=7.9 ± 1.7; p=0.0001) were independent determinants of exercise sPAP. EIPH is frequent in SSc patients and is mainly related to both increased exercise LV filling pressure and exercise PVR. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  19. CKI isoforms α and ε regulate Star–PAP target messages by controlling Star–PAP poly(A) polymerase activity and phosphoinositide stimulation

    PubMed Central

    Laishram, Rakesh S.; Barlow, Christy A.; Anderson, Richard A.

    2011-01-01

    Star–PAP is a non-canonical, nuclear poly(A) polymerase (PAP) that is regulated by the lipid signaling molecule phosphatidylinositol 4,5 bisphosphate (PI4,5P2), and is required for the expression of a select set of mRNAs. It was previously reported that a PI4,5P2 sensitive CKI isoform, CKIα associates with and phosphorylates Star–PAP in its catalytic domain. Here, we show that the oxidative stress-induced by tBHQ treatment stimulates the CKI mediated phosphorylation of Star–PAP, which is critical for both its polyadenylation activity and stimulation by PI4,5P2. CKI activity was required for the expression and efficient 3′-end processing of its target mRNAs in vivo as well as the polyadenylation activity of Star–PAP in vitro. Specific CKI activity inhibitors (IC261 and CKI7) block in vivo Star–PAP activity, but the knockdown of CKIα did not equivalently inhibit the expression of Star–PAP targets. We show that in addition to CKIα, Star–PAP associates with another CKI isoform, CKIε in the Star–PAP complex that phosphorylates Star–PAP and complements the loss of CKIα. Knockdown of both CKI isoforms (α and ε) resulted in the loss of expression and the 3′-end processing of Star–PAP targets similar to the CKI activity inhibitors. Our results demonstrate that CKI isoforms α and ε modulate Star–PAP activity and regulates Star–PAP target messages. PMID:21729869

  20. Characterization of a cryptic plasmid from an alpha-proteobacterial endosymbiont of Amoeba proteus.

    PubMed

    Park, Miey; Kim, Min-Soo; Lee, Kyung-Min; Hwang, Sue-Yun; Ahn, Tae In

    2009-01-01

    A new cryptic plasmid pAP3.9 was discovered in symbiotic alpha-proteobacteria present in the cytoplasm of Amoeba proteus. The plasmid is 3869bp with a GC content of 34.66% and contains replication origins for both double-strand (dso) and single-strand (sso). It has three putative ORFs encoding Mob, Rep and phosphoglycolate phosphatase (PGPase). The pAP3.9 plasmid appears to propagate by the conjugative rolling-circle replication (RCR), since it contains all required factors such as Rep, sso and dso. Mob and Rep showed highest similarities to those of the cryptic plasmid pBMYdx in Bacillus mycoides. The PGPase was homologous to that of Bacillus cereus and formed a clade with those of Bacillus sp. in molecular phylogeny. These results imply that the pAP3.9 plasmid evolved by the passage through Bacillus species. We hypothesize that the plasmid-encoded PGPase may have contributed to the establishment of bacterial symbiosis within the hostile environment of amoeba cytoplasm.

  1. Mutagenicity of p-aminophenol in E. coli WP2uvrA/pKM101 and its relevance to oxidative DNA damage.

    PubMed

    Yoshida, R; Oikawa, S; Ogawa, Y; Miyakoshi, Y; Ooida, M; Asanuma, K; Shimizu, H

    1998-07-08

    It was recently reported that p-aminophenol (p-AP) induces DNA cleavage in mouse lymphoma cells, CHO cells and human lymphoblastoid cells. The mutagenicity of p-AP has not, however, been detected by reverse mutation assays. The purpose of this study was to assess the mutagenicity of p-AP by reverse mutation assay using Escherichia coli WP2uvrA/pKM101, which has a spectrum for detecting mutations different from those of other strains in the family with an AT base pair at the mutation site and has higher sensitivity to certain oxidative mutagens as compared to other strains. We found that p-AP was mutagenic to E. coli WP2uvrA/pKM101. The mutagenic activity of this compound was suppressed with the addition of dimethylsulfoxide or catalase, suggesting the involvement of active oxygen species in the mutagenic process induced by p-AP. To further elucidate the underlying mechanism, we used isolated DNA for the following experiments. It was revealed, by gel electrophoretic analysis, that p-AP induced DNA cleavage in the presence of Fe(III). However, p-AP alone did not induce this cleavage. Formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine by p-AP in calf thymus DNA was also detected in the presence of Fe(III) by HPLC with an electrochemical detector. ESR-spin trapping experiments using DMPO detected the production of hydroxyl radical (.OH) in the solution of p-AP with Fe(III). Both p-AP mediated DNA damages and .OH production by p-AP in the presence of Fe(III) were completely inhibited by .OH scavengers (ethanol, mannitol, sodium formate, dimethylsulfoxide) and catalase. These results suggest that .OH derived from the reaction between H2O2 and Fe(III) (Fenton reaction) participates in the oxidative DNA damage. Accordingly, the same mechanism might be working in E. coli WP2uvrA/pKM101 during induction of the mutation by p-AP.

  2. Manduca sexta proprophenoloxidase activating proteinase-3 (PAP3) stimulates melanization by activating proPAP3, proSPHs, and proPOs

    PubMed Central

    Wang, Yang; Lu, Zhiqiang; Jiang, Haobo

    2014-01-01

    Melanization participates in various insect physiological processes including antimicrobial immune responses. Phenoloxidase (PO), a critical component of the enzyme system catalyzing melanin formation, is produced as an inactive precursor prophenoloxidase (proPO) and becomes active via specific proteolytic cleavage by proPO activating proteinase (PAP). In Manduca sexta, three PAPs can activate proPOs in the presence of two serine proteinase homologs (SPH1 and SPH2). While the hemolymph proteinases (HPs) that generate the active PAPs are known, it is unclear how the proSPHs (especially proSPH1) are activated. In this study, we isolated from plasma of bar-stage M. sexta larvae an Ile-Glu-Ala-Arg-p-nitroanilide hydrolyzing enzyme that cleaved the proSPHs. This proteinase, PAP3, generated active SPH1 and SPH2, which function as cofactors for PAP3 in proPO activation. Cleavage of the purified recombinant proSPHs by PAP3 yielded 38 kDa bands similar in mobility to the SPHs formed in vivo. Surprisingly, PAP3 also can activate proPAP3 to stimulate melanization in a direct positive feedback loop. The enhanced proPO activation concurred with the cleavage activation of proHP6, proHP8, proPAP1, proPAP3, proSPH1, proSPH2, proPOs, but not proHP14 or proHP21. These results indicate that PAP3, like PAP1, is a key factor of the self-reinforcing mechanism in the proPO activation system, which is linked to other immune responses in M. sexta. PMID:24768974

  3. Mutations in MARS identified in a specific type of pulmonary alveolar proteinosis alter methionyl-tRNA synthetase activity.

    PubMed

    Comisso, Martine; Hadchouel, Alice; de Blic, Jacques; Mirande, Marc

    2018-05-18

    Biallelic missense mutations in MARS are responsible for rare but severe cases of pulmonary alveolar proteinosis (PAP) prevalent on the island of La Réunion. MARS encodes cytosolic methionyl-tRNA synthetase (MetRS), an essential translation factor. The multisystemic effects observed in patients with this form of PAP are consistent with a loss-of-function defect in an ubiquitously expressed enzyme. The pathophysiological mechanisms involved in MARS-related PAP are currently unknown. In this work, we analyzed the effect of the PAP-related mutations in MARS on the thermal stability and on the catalytic parameters of the MetRS mutants, relative to wild-type. The effect of these mutations on the structural integrity of the enzyme as a member of the cytosolic multisynthetase complex was also investigated. Our results establish that the PAP-related substitutions in MetRS impact the tRNA Met -aminoacylation reaction especially at the level of methionine recognition, and suggest a direct link between the loss of activity of the enzyme and the pathological disorders in PAP. © 2018 Federation of European Biochemical Societies.

  4. Covalent attachment of phospholipid analogous polymers to modify a polymeric membrane surface: a novel approach.

    PubMed

    Xu, Zhi-Kang; Dai, Qing-Wen; Wu, Jian; Huang, Xiao-Jun; Yang, Qian

    2004-02-17

    A novel method for the surface modification of a microporous polypropylene membrane by tethering phospholipid analogous polymers (PAPs) is given, which includes the photoinduced graft polymerization of N,N-dimethylaminoethyl methacrylate (DMAEMA) and the ring-opening reaction of grafted poly-(DMAEMA) with 2-alkyloxy-2-oxo-1,3,2-dioxaphospholanes. Five 2-alkyloxy-2-oxo-1,3,2-dioxaphospholanes, containing octyloxy, dodecyloxy, tetradecyloxy, hexadecyloxy, and octadecyloxy groups in the molecular structure, were used to fabricate the PAP-modified polypropylene membranes. The attenuated total reflectance FT-IR spectra of the original, poly(DMAEMA)-grafted, and PAP-modified membranes confirmed the chemical changes on the membrane surface. Scanning electron microscope pictures showed that, compared with the original membrane, the surface porosities ofpoly(DMAEMA)-grafted and PAP-modified membranes were somewhat reduced. Water contact angles measured by the sessile drop method on PAP-modified membranes were slightly lower than that on the original polypropylene membrane, but higher than those on poly(DMAEMA)-grafted membranes with the exception of octyloxy-containing PAP-modified membranes. However, BSA adsorption experiments indicated that the five PAP-modified membranes had a much better protein-resistant property than the original polypropylene membrane and the poly(DMAEMA)-grafted membranes. For hexadecyloxy- and octadecyloxy-containing PAP-modified membranes, almost no protein adsorption was observed when the grafting degree was above 6 wt %. It was also found that the platelet adhesion was remarkably suppressed on the PAP-modified membranes. All these results demonstrate that the described approach is an effective way to improve the surface biocompatibility for polymeric membranes.

  5. The Novel Poly(A) Polymerase Star-PAP is a Signal-Regulated Switch at the 3′-end of mRNAs

    PubMed Central

    Li, Weimin; Laishram, Rakesh S.; Anderson, Richard A.

    2013-01-01

    The mRNA 3′-untranslated region (3′-UTR) modulates message stability, transport, intracellular location and translation. We have discovered a novel nuclear poly(A) polymerase termed Star-PAP (nuclear speckle targeted PIPKIα regulated-poly(A) polymerase) that couples with the transcriptional machinery and is regulated by the phosphoinositide lipid messenger phosphatidylinositol-4,5-bisphosphate (PI4,5P2), the central lipid in phosphoinositide signaling. PI4,5P2 is generated primarily by type I phosphatidylinositol phosphate kinases (PIPKI). Phosphoinositides are present in the nucleus including at nuclear speckles compartments separate from known membrane structures. PIPKs regulate cellular functions by interacting with PI4,5P2 effectors where PIPKs generate PI4,5P2 that then modulates the activity of the associated effectors. Nuclear PIPKIα interacts with and regulates Star-PAP, and PI4,5P2 specifically activates Star-PAP in a gene- and signaling-dependent manner. Importantly, other select signaling molecules integrated into the Star-PAP complex seem to regulate Star-PAP activities and processivities toward RNA substrates, and unique sequence elements around the Star-PAP binding sites within the 3′-UTR of target genes contribute to Star-PAP specificity for processing. Therefore, Star-PAP and its regulatory molecules form a signaling nexus at the 3′-end of target mRNAs to control the expression of select group of genes including the ones involved in stress responses. PMID:23306079

  6. Lipin-1 Phosphatidic Phosphatase Activity Modulates Phosphatidate Levels to Promote Peroxisome Proliferator-activated Receptor γ (PPARγ) Gene Expression during Adipogenesis*

    PubMed Central

    Zhang, Peixiang; Takeuchi, Kazuharu; Csaki, Lauren S.; Reue, Karen

    2012-01-01

    Adipose tissue plays a key role in metabolic homeostasis. Disruption of the Lpin1 gene encoding lipin-1 causes impaired adipose tissue development and function in rodents. Lipin-1 functions as a phosphatidate phosphatase (PAP) enzyme in the glycerol 3-phosphate pathway for triglyceride storage and as a transcriptional coactivator/corepressor for metabolic nuclear receptors. Previous studies established that lipin-1 is required at an early step in adipocyte differentiation for induction of the adipogenic gene transcription program, including the key regulator peroxisome proliferator-activated receptor γ (PPARγ). Here, we investigate the requirement of lipin-1 PAP versus coactivator function in the establishment of Pparg expression during adipocyte differentiation. We demonstrate that PAP activity supplied by lipin-1, lipin-2, or lipin-3, but not lipin-1 coactivator activity, can rescue Pparg gene expression and lipogenesis during adipogenesis in lipin-1-deficient preadipocytes. In adipose tissue from lipin-1-deficient mice, there is an accumulation of phosphatidate species containing a range of medium chain fatty acids and an activation of the MAPK/extracellular signal-related kinase (ERK) signaling pathway. Phosphatidate inhibits differentiation of cultured adipocytes, and this can be rescued by the expression of lipin-1 PAP activity or by inhibition of ERK signaling. These results emphasize the importance of lipid intermediates as choreographers of gene regulation during adipogenesis, and the results highlight a specific role for lipins as determinants of levels of a phosphatidic acid pool that influences Pparg expression. PMID:22157014

  7. Estimating right ventricular stroke work and the pulsatile work fraction in pulmonary hypertension.

    PubMed

    Chemla, Denis; Castelain, Vincent; Zhu, Kaixian; Papelier, Yves; Creuzé, Nicolas; Hoette, Susana; Parent, Florence; Simonneau, Gérald; Humbert, Marc; Herve, Philippe

    2013-05-01

    The mean pulmonary artery pressure (mPAP) replaces mean systolic ejection pressure (msePAP) in the classic formula of right ventricular stroke work (RVSW) = (mPAP - RAP) × stroke volume, where RAP is mean right atrial pressure. Only the steady work is thus taken into account, not the pulsatile work, whereas pulmonary circulation is highly pulsatile. Our retrospective, high-fidelity pressure study tested the hypothesis that msePAP was proportional to mPAP, and looked at the implications for RVSW. Eleven patients with severe, precapillary pulmonary hypertension (PH) (six patients with idiopathic pulmonary arterial hypertension and five with chronic thromboembolic PH; mPAP = 57 ± 10 mm Hg) were studied at rest and during mild to moderate exercise. Eight non-PH control subjects were also studied at rest (mPAP = 16 ± 2 mm Hg). The msePAP was averaged from end diastole to dicrotic notch. In the full data set (53 pressure-flow points), mPAP ranged from 14 to 99.5 mm Hg, cardiac output from 2.38 to 11.1 L/min, and heart rate from 53 to 163 beats/min. There was a linear relationship between msePAP and mPAP (r² = 0.99). The msePAP matched 1.25 mPAP (bias, -0.5 ± 2.6 mm Hg). Results were similar in the resting non-PH group and in resting and the exercising PH group. This implies that the classic formula markedly underestimates RVSW and that the pulsatile work may be a variable 20% to 55% fraction of RVSW, depending on RAP and mPAP. At rest, RVSW in patients with PH was twice as high as that of the non-PH group (P < .05), but pulsatile work fraction was similar between the two groups (26 ± 4% vs 24 ± 1%) because of the counterbalancing effects of high RAP (11 ± 5 mm Hg vs 4 ± 2 mm Hg), which increases the fraction, and high mPAP, which decreases the fraction. Our study favored the use of an improved formula that takes into account the variable pulsatile work fraction: RVSW = (1.25 mPAP - RAP) × stroke volume. Increased RAP and increased mPAP have opposite effects on the pulsatile work fraction.

  8. Insulin-like growth factor II mRNA-binding protein 3 (IMP3) is a marker that predicts presence of invasion in papillary biliary tumors.

    PubMed

    Sasaki, Motoko; Sato, Yasunori

    2017-04-01

    Biliary tumors showing intraductal papillary growth (Pap-BTs) include intraductal papillary neoplasm of the bile duct (IPNB) and papillary cholangiocarcinoma (CC). A differential diagnosis between IPNB and papillary CC currently remains challenging. The aim of the present study is to identify histological features and immunohistochemical markers of malignant potential such as tumor invasion in Pap-BTs. Subjects comprised 37 patients with Pap-BT (intrahepatic and perihilar [proximal], 27: 17 noninvasive and 10 invasive; distal, 10: all invasive). We examined histological features and the expression of p53, enhancer of zeste homolog 2, insulin-like growth factor II mRNA-binding protein 3 (IMP3), and DNA methyltransferase-1 in the intraductal area in Pap-BTs. Noninvasive Pap-BT was characterized by the presence of a low-grade dysplastic area, edematous stroma, and the absence of necrosis. The expression of p53, enhancer of zeste homolog 2, IMP3, and DNA methyltransferase-1 was significantly weaker in noninvasive Pap-BTs than in invasive Pap-BTs (P<.01). Diffuse cytoplasmic IMP3 expression was absent in noninvasive Pap-BTs. IMP3 showed the greatest specificity to predict a presence of invasion. A heatmap demonstrated that proximal noninvasive Pap-BTs and distal Pap-BTs may be completely different. In bile duct biopsies, the expression of IMP3 was the most precise predictor of invasion in Pap-BTs. In conclusion, Pap-BTs may be separated into 3 subgroups: (1) proximal noninvasive Pap-BT, corresponding to IPNB; (2) distal invasive Pap-BT, corresponding to papillary CC; and (3) the remaining Pap-BT including IPNB with associated adenocarcinomas, based on histological and immunohistochemical features. IMP3 may be a useful marker for predicting invasion in Pap-BT. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Relationship Between Pelvic Organ Prolapse and Non-Human Papillomavirus Pap Smear Abnormalities.

    PubMed

    Menhaji, Kimia; Harvie, Heidi S; Cheston, Emily; Levin, Pamela J; Arya, Lily A; Andy, Uduak U

    2017-07-13

    The aim of this study was to determine the association between pelvic organ prolapse (POP) and non-human papillomavirus (HPV) Papanicolaou (Pap) smear abnormalities. This was a retrospective cohort study of women aged 40 to 70 years who presented for consultation at our institution between 2010 and 2015 and had results of a Pap smear and HPV test available within 5 years of their visit. We extracted demographic information, medical and social history, Pap smear, and HPV results from the electronic medical record. Associations between the presence of POP and non-HPV Pap smear abnormalities were estimated using univariable and multivariable analyses. We reviewed 1590 charts and excluded 980 women, leaving 610 women in the study: 183 with POP and 427 without POP. Women with POP were significantly older (58.2 ± 7.2 vs 55.6 ± 6.6, P < 0.01) and more likely to have a remote (>10 year) history of abnormal Pap smear (24.0% vs 14.8%, P < 0.01). The rate of non-HPV-associated abnormal Pap smears was higher in the POP group than in the non-POP group (12/183 [6.6%] vs 12/427 [2.8%], P = 0.029). In the POP group, the rate of non-HPV Pap smear abnormality was significantly associated with increasing prolapse stage (stage 1: 0/16 [0%], stage 2: 5/77 [6.5%], stage 3: 3/73 [4.1%], stage 4: 4/17 [23.5%]; P = 0.02). After controlling for age and remote history of abnormal Pap smear, the odds ratio for non-HPV Pap smear abnormalities in the POP group remained significant (2.49; 95% confidence interval, 1.08-5.79). Human papillomavirus-negative Pap smear abnormalities may be related to POP. Our findings have important implications for surgeons seeking to leave the cervix in situ in women with POP.

  10. Novel Type of Fimbriae Encoded by the Large Plasmid of Sorbitol-Fermenting Enterohemorrhagic Escherichia coli O157:H−

    PubMed Central

    Brunder, Werner; Khan, A. Salam; Hacker, Jörg; Karch, Helge

    2001-01-01

    Sorbitol-fermenting (SF) enterohemorrhagic Escherichia coli (EHEC) O157:H− have emerged as important causes of diarrheal diseases and the hemolytic-uremic syndrome in Germany. In this study, we characterized a 32-kb fragment of the plasmid of SF EHEC O157:H−, pSFO157, which differs markedly from plasmid pO157 of classical non-sorbitol-fermenting EHEC O157:H7. We found a cluster of six genes, termed sfpA, sfpH, sfpC, sfpD, sfpJ, and sfpG, which mediate mannose-resistant hemagglutination and the expression of fimbriae. sfp genes are similar to the pap genes, encoding P-fimbriae of uropathogenic E. coli, but the sfp cluster lacks homologues of genes encoding subunits of a tip fibrillum as well as regulatory genes. The major pilin, SfpA, despite its similarity to PapA, does not cluster together with known PapA alleles in a phylogenetic tree but is structurally related to the PmpA pilin of Proteus mirabilis. The putative adhesin gene sfpG, responsible for the hemagglutination phenotype, shows significant homology neither to papG nor to other known sequences. Sfp fimbriae are 3 to 5 nm in diameter, in contrast to P-fimbriae, which are 7 nm in diameter. PCR analyses showed that the sfp gene cluster is a characteristic of SF EHEC O157:H− strains and is not present in other EHEC isolates, diarrheagenic E. coli, or other Enterobacteriaceae. The sfp gene cluster is flanked by two blocks of insertion sequences and an origin of plasmid replication, indicating that horizontal gene transfer may have contributed to the presence of Sfp fimbriae in SF EHEC O157:H−. PMID:11401985

  11. Fluorochemicals used in food packaging inhibit male sex hormone synthesis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rosenmai, A.K., E-mail: akjro@food.dtu.dk; Nielsen, F.K.; Pedersen, M.

    Polyfluoroalkyl phosphate surfactants (PAPS) are widely used in food contact materials (FCMs) of paper and board and have recently been detected in 57% of investigated materials. Human exposure occurs as PAPS have been measured in blood; however knowledge is lacking on the toxicology of PAPS. The aim of this study was to elucidate the effects of six fluorochemicals on sex hormone synthesis and androgen receptor (AR) activation in vitro. Four PAPS and two metabolites, perfluorooctanoic acid (PFOA) and 8:2 fluorotelomer alcohol (8:2 FTOH) were tested. Hormone profiles, including eight steroid hormones, generally showed that 8:2 diPAPS, 8:2 monoPAPS and 8:2more » FTOH led to decreases in androgens (testosterone, dehydroepiandrosterone, and androstenedione) in the H295R steroidogenesis assay. Decreases were observed for progesterone and 17-OH-progesterone as well. These observations indicated that a step prior to progestagen and androgen synthesis had been affected. Gene expression analysis of StAR, Bzrp, CYP11A, CYP17, CYP21 and CYP19 mRNA showed a decrease in Bzrp mRNA levels for 8:2 monoPAPS and 8:2 FTOH indicating interference with cholesterol transport to the inner mitochondria. Cortisol, estrone and 17β-estradiol levels were in several cases increased with exposure. In accordance with these data CYP19 gene expression increased with 8:2 diPAPS, 8:2 monoPAPS and 8:2 FTOH exposures indicating that this is a contributing factor to the decreased androgen and the increased estrogen levels. Overall, these results demonstrate that fluorochemicals present in food packaging materials and their metabolites can affect steroidogenesis through decreased Bzrp and increased CYP19 gene expression leading to lower androgen and higher estrogen levels. -- Highlights: ► Fluorochemicals found in 57% of paper and board food packaging were tested. ► Collectively six fluorochemicals were tested for antiandrogenic potential in vitro. ► Three out of six tested fluorochemicals inhibited synthesis of male sex hormones. ► Generally, levels of estrogens and cortisol stayed unaffected or increased. ► The effect on steroid synthesis was specific on gene expression of Bzrp and CYP19.« less

  12. The role of compliance with PAP use on blood pressure in patients with obstructive sleep apnea: is longer use a key-factor?

    PubMed

    Bouloukaki, I; Mermigkis, C; Tzanakis, N; Giannadaki, K; Mauroudi, E; Moniaki, V; Kallergis, E M; Schiza, S E

    2017-02-01

    Scientific data about the effects of positive airway pressure (PAP) treatment on blood pressure (BP) control are continuously increasing; however, they are controversial. We aimed to determine the long-term effects of compliance with PAP therapy on BP in both hypertensive and normotensive patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). One thousand one hundred sixty eight consecutive patients with newly diagnosed OSAHS, who had been recommended PAP therapy, were followed up for a minimum of 2 years. Patients with previous cardiovascular disease were excluded. BP was measured at baseline and after 2 years of PAP treatment. In addition, the correlation between the changes in BP with different levels of PAP compliance was assessed. At the end of the follow-up period, in the hypertensive group of patients (n=586), a significant decrease was shown in systolic (-11.2 mm Hg, P<0.001) and diastolic BP (-4.2 mm Hg, P<0.001). Furthermore, in the patients without hypertension (n=528), a significant decrease was noted both in systolic and diastolic BP (-3.6, P<0.001 and -2.4, P<0.001, respectively). A correlation between the magnitude of change in systolic and diastolic BP and hours of use of PAP (r=0.14, P=0.002 and r=0.1, P=0.025, respectively) was observed in all patients. Long-term use of PAP treatment, as well as increased hours of PAP in patients with OSAHS use showed significant reductions in BP not only in patients with hypertension, but also in normotensive patients. Therefore a significant potential reduction in cardiovascular mortality and morbidity should be expected in these patients.

  13. Production of a pokeweed antiviral protein (PAP)-containing immunotoxin, B43-PAP, directed against the CD19 human B lineage lymphoid differentiation antigen in highly purified form for human clinical trials.

    PubMed

    Myers, D E; Irvin, J D; Smith, R S; Kuebelbeck, V M; Uckun, F M

    1991-02-15

    We describe a standardized method for the preparation and purification of a potent immunotoxin against B-lineage leukemia/lymphoma cells, constructed with the ribosome inhibitory single chain plant toxin pokeweed antiviral protein (PAP) and a murine IgG1 monoclonal antibody (MoAb) specific for the human B lineage differentiation antigen CD19 for human clinical trials. PAP was prepared from spring leaves of Phytolacca americana plants by ammonium sulfate precipitation and purified to homogeneity by successive steps of ion exchange chromatography. B43 MoAb was produced in vitro by hollow fiber technology and purified to homogeneity by affinity chromatography. PAP toxin and B43 MoAb were modified via their free amino groups prior to their intermolecular conjugation. 2-iminothiolane was used to introduce reactive sulfhydryl groups into PAP and N-succinimidyl 3-(2-pyridyldithio) propionate was used to introduce 2-pyridyl disulfide bonds into B43 MoAb. Modified PAP was reacted with modified B43 MoAb resulting in a sulfhydryl-disulfide exchange reaction and yielding disulfide linked PAP-B43 MoAb conjugates, which we refer to as B43-PAP immunotoxin. B43-PAP immunotoxin was subjected to preparative gel filtration chromatography and cation exchange chromatography to obtain a highly purified, sterile, and pyrogen-free immunotoxin preparation with less than 5% free antibody contamination and less than 0.5% free PAP contamination. The final product displayed a high affinity for and a very potent anti-leukemic activity against B lineage leukemia cells. With slight modifications, the procedures detailed in this report should be generally applicable to preparation of other PAP-MoAb conjugates for treatment of cancer or AIDS.

  14. Characterization of phosphatidic acid phosphatase activity in the oleaginous yeast Yarrowia lipolytica and its role in lipid biosynthesis.

    PubMed

    Hardman, Derell; McFalls, Daniel; Fakas, Stylianos

    2017-02-01

    Phosphatidic acid phosphatase (PAP) catalyses the committed step of triacylglycerol (TAG) biosynthesis and thus regulates the amounts of TAG produced by the cell. TAG is the target of biotechnological processes developed for the production of food lipids or biofuels. These processes are using oleaginous microorganisms like the yeast Yarrowia lipolytica as the TAG producers. Thus manipulating key enzymatic activities like PAP in Y. lipolytica could drive lipid biosynthesis towards TAG production and increase TAG yields. In this study, PAP activity in Y. lipolytica was characterized in detail and its role in lipid biosynthesis was addressed. PAP activity increased 2.5-fold with the addition of Mg 2+ (1 mm) in the assay mixture, which means that most of the PAP activity was due to Mg 2+ -dependent PAP enzymes (e.g. Pah1, App1). In contrast, N-ethylmaleimide (NEM) potently inhibited PAP activity, indicating the presence of NEM-sensitive PAP enzymes (e.g. App1, Lpp1). Localization studies revealed that the majority of PAP activity resides in the membrane fraction, while the cytosolic fraction harbours only a small amount of activity. PAP activity was regulated in a growth-dependent manner, being induced at the early exponential phase and declining thereafter. PAP activity did not correlate with TAG synthesis, which increased as cells progressed from the exponential phase to the early stationary phase. In stationary phase, TAG was mobilized with the concomitant synthesis of sterols and sterol esters. These results provide the first insights into the role of PAP in lipid biosynthesis by Y. lipolytica. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  15. Phosphorylation regulates the Star-PAP-PIPKIα interaction and directs specificity toward mRNA targets

    PubMed Central

    Mohan, Nimmy; AP, Sudheesh; Francis, Nimmy; Anderson, Richard; Laishram, Rakesh S.

    2015-01-01

    Star-PAP is a nuclear non-canonical poly(A) polymerase (PAP) that shows specificity toward mRNA targets. Star-PAP activity is stimulated by lipid messenger phosphatidyl inositol 4,5 bisphoshate (PI4,5P2) and is regulated by the associated Type I phosphatidylinositol-4-phosphate 5-kinase that synthesizes PI4,5P2 as well as protein kinases. These associated kinases act as coactivators of Star-PAP that regulates its activity and specificity toward mRNAs, yet the mechanism of control of these interactions are not defined. We identified a phosphorylated residue (serine 6, S6) on Star-PAP in the zinc finger region, the domain required for PIPKIα interaction. We show that S6 is phosphorylated by CKIα within the nucleus which is required for Star-PAP nuclear retention and interaction with PIPKIα. Unlike the CKIα mediated phosphorylation at the catalytic domain, Star-PAP S6 phosphorylation is insensitive to oxidative stress suggesting a signal mediated regulation of CKIα activity. S6 phosphorylation together with coactivator PIPKIα controlled select subset of Star-PAP target messages by regulating Star-PAP-mRNA association. Our results establish a novel role for phosphorylation in determining Star-PAP target mRNA specificity and regulation of 3′-end processing. PMID:26138484

  16. Novel Immune-Modulating Cellular Vaccine for Prostate Cancer Immunotherapy

    DTIC Science & Technology

    2015-10-01

    the 3-month timeline and details provided in year 1 report. Anti-murine CTLA4 RNA Murine PAP Murine PSMA Murine PAP no signal sequence (mPAP-SS...Murine PSMA no signal sequence (mPSMA-SS) Year 2 (current) report: In addition to what we proposed to do, we wanted to determine if other...PAP, PSCA, PSMA and STEAP in the prostate cell lines TRAMP-C1 and TRAMP-C2. Both are cell lines that have been generated by in vitro propagation of

  17. Counteracting Fusarium proliferatum toxicity in broiler chicks by supplementing drinking water with Poultry Aid Plus.

    PubMed

    Wu, W

    1997-03-01

    To test whether Poultry Aid Plus (PAP, a commercial product for drinking water application) could reduce the stress on broiler chicks caused by Fusarium proliferatum contamination of feed, water (with or without PAP application, according to the manufacturer's instructions), and feed (experimentally infected with F. proliferatum fermented and dried corn culture material, CM) were provided to broiler chicks for 3 wk. Eight treatments consisting of a 2 (with or without PAP in water) x 4 (0, 1, 2, and 4% CM in feed) factorial design were tested in four replicate cages of six chicks each. The diet with 2% CM reduced weight gain by 23%; this reduction was preventable by PAP water application. The diet with 4% CM caused a cumulative mortality of 87.5%, which was reduced by PAP water application to 50%. The population half-life of the chicks on the diet with 4% CM was 6.5 d; this half-life was prolonged to at least 21 d by PAP water application. The PAP application also reduced the relative weight of the small intestine and promoted Lactobacillus colonization of the large intestine regardless of the level of CM in feed. Therefore, water application of PAP can be a prophylactic measure for F. proliferatum toxicity in poultry production.

  18. Phosphorylation regulates the Star-PAP-PIPKIα interaction and directs specificity toward mRNA targets.

    PubMed

    Mohan, Nimmy; Sudheesh, A P; Francis, Nimmy; Anderson, Richard; Laishram, Rakesh S

    2015-08-18

    Star-PAP is a nuclear non-canonical poly(A) polymerase (PAP) that shows specificity toward mRNA targets. Star-PAP activity is stimulated by lipid messenger phosphatidyl inositol 4,5 bisphoshate (PI4,5P2) and is regulated by the associated Type I phosphatidylinositol-4-phosphate 5-kinase that synthesizes PI4,5P2 as well as protein kinases. These associated kinases act as coactivators of Star-PAP that regulates its activity and specificity toward mRNAs, yet the mechanism of control of these interactions are not defined. We identified a phosphorylated residue (serine 6, S6) on Star-PAP in the zinc finger region, the domain required for PIPKIα interaction. We show that S6 is phosphorylated by CKIα within the nucleus which is required for Star-PAP nuclear retention and interaction with PIPKIα. Unlike the CKIα mediated phosphorylation at the catalytic domain, Star-PAP S6 phosphorylation is insensitive to oxidative stress suggesting a signal mediated regulation of CKIα activity. S6 phosphorylation together with coactivator PIPKIα controlled select subset of Star-PAP target messages by regulating Star-PAP-mRNA association. Our results establish a novel role for phosphorylation in determining Star-PAP target mRNA specificity and regulation of 3'-end processing. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  19. Identification of phase-I metabolites and chronic toxicity study of the Kv1.3 blocker PAP-1 (5-(4-phenoxybutoxy)psoralen) in the rat.

    PubMed

    Hao, B; Chen, Z-W; Zhou, X-J; Zimin, P I; Miljanich, G P; Wulff, H; Wang, Y-X

    2011-03-01

    1. PAP-1 (5-(4-phenoxybutoxy)psoralen), a potent small-molecule blocker of the voltage-gated potassium Kv1.3 channel, is currently in preclinical development for psoriasis. This study was undertaken to identify the major phase I metabolites of PAP-1 in Sprague-Dawley (SD) rats. 2. Five phase I metabolites, that is 5-(oxybutyric-acid)psoralen (M1), 5-[4-(4-hydroxybutoxy)]psoralen (M2), 5-[4-(4-hydroxyphenoxy)butoxy]psoralen (M3), 5-[4-(3-hydroxyphenoxy)butoxy]psoralen (M4), and 8-hydroxyl-5-(4-phenoxybutoxy)psoralen (M5), were isolated from the bile of rats and identified by mass spectrometry and NMR spectroscopy. The last four metabolites are new compounds. 3. Incubation of PAP-1 with SD rat liver microsomes rendered the same five major metabolites in a nicotinamide adenine dinucleotide phosphate (NADPH)-dependent manner suggesting that cytochrome P450 (CYP) enzymes are involved in PAP-1 metabolism. Inhibitors of rat CYP1A1/2 (alpha-naphthoflavone) and CYP3A (ketoconazole) but not CYP2D6 (quinidine), CYP2E (diethyldithiocarbamate), or CYP2C9 (sulphaphenazole) blocked the metabolism of PAP-1 in rat microsomes. 4. Of the five metabolites M3, M4, and M5 were found to inhibit Kv1.3 currents with nanomolar IC50s, while M1 and M2 were inactive. Our results identified the Kv1.3-inactive M1 as the major phase I metabolite, and suggest that hydroxylation and O-dealkylation are the major pathways of PAP-1 metabolism. 5. We further conducted a 6-month repeat-dose toxicity study with PAP-1 at 50 mg/kg in both male and female Lewis rats and did not observe any toxic effects.

  20. [Preparation and activity validation of PP7 bacteriophage-like particles displaying PAP114-128 peptide].

    PubMed

    Sun, Yanli; Sun, Yanhua

    2016-10-01

    Objective To obtain the PP7 bacteriophage-like particles carrying the peptide of prostatic acid phosphatase PAP 114-128 , and prove that they retain the original biological activity. Methods First, the plasmid pETDuet-2PP7 was constructed as follows: the gene of PP7 coat protein dimer was amplified by gene mutation combined with overlapping PCR technology, and inserted into the vector pETDuet-1. Following that, the plasmid pETDuet-2PP7-PAP 114-128 was constructed as follows: the PP7 coat protein gene carrying the coding gene of PAP 114-128 peptide was amplified using PCR, and then inserted into the vector pETDuet-2PP7. Both pETDuet-2PP7 and pETDuet-2PP7-PAP 114-128 were transformed into E.coli and expressed. The expression product was verified by SDS-PAGE, double immunodiffusion assay and ELISA. Results The gene fragment of PP7 coat protein dimer was obtained by overlapping PCR using Ex Taq DNA polymerase, and the antigenicity of its expression product was the same as that of the coat protein of wild-type PP7 bacteriophage. Moreover, the PAP 114-128 peptide epitope that was displayed on the surface of PP7 bacteriophage was identical with the corresponding epitope of natural human PAP, and it was able to induce high levels of antibodies. Conclusion The gene of PP7 coat protein dimer with repeated sequences can be prepared by gene mutation combined with overlapping PCR. Based on this, PP7 bacteriophage-like particles carrying PAP peptide can be prepared, which not only solves the problem of the instability of the peptides, but also lays a foundation for the study on their delivery and function.

  1. Depression May Reduce Adherence during CPAP Titration Trial

    PubMed Central

    Law, Mandy; Naughton, Matthew; Ho, Sally; Roebuck, Teanau; Dabscheck, Eli

    2014-01-01

    Study Objectives: Depression is a risk factor for medication non-compliance. We aimed to identify if depression is associated with poorer adherence during home-based autotitrating continuous positive airway pressure (autoPAP) titration. Design: Mixed retrospective-observational study. Setting: Academic center. Participants: Two-hundred forty continuous positive airway pressure-naïve obstructive sleep apnea (OSA) patients. Measurements: Patients underwent approximately 1 week of home-based autoPAP titration with adherence data downloaded from the device. Electronic hospital records were reviewed in a consecutive manner for inclusion. Three areas of potential predictors were examined: (i) demographics and clinical factors, (ii) disease severity, and (iii) device-related variables. Depression and anxiety were assessed using the Hospital Anxiety and Depression Scale (HADS). Scores on the subscales were categorized as normal or clinical diagnoses of depression (≥ 8) and anxiety (≥ 11). The primary outcome variable was the mean hours of autoPAP used per night. Results: Patients were diagnosed with OSA by either attended polysomnography (n = 73, AHI 25.5[15.1-41.5]) or unattended home oximetry (n = 167, ODI3 34.0[22.4-57.4]) and had home-based autoPAP titration over 6.2 ± 1.2 nights. Mean autoPAP use was 4.5 ± 2.4 hours per night. Multiple linear regression analysis revealed that depression and lower 95th percentile pressures significantly predicted lesser hours of autoPAP use (R2 = 0.19, p < 0.001). Significantly milder OSA in those requiring lower pressures may have confounded the relationship between 95th percentile pressure and autoPAP use. Conclusion: Depression was independently associated with poorer adherence during home-based autoPAP titration. Depression may be a potential target for clinicians and future research aimed at enhancing adherence to autoPAP therapy. Citation: Law M; Naughton M; Ho S; Roebuck T; Dabscheck E. Depression may reduce adherence during CPAP titration trial. J Clin Sleep Med 2014;10(2):163-169. PMID:24532999

  2. ABO blood group in primary antiphospholipid syndrome: influence in the site of thrombosis?

    PubMed

    Nascimento, Natália Mastantuono; Bydlowski, Sergio Paulo; Soares, Rosangela Paula Silva; de Andrade, Danieli Castro Oliveira; Bonfá, Eloísa; Seguro, Luciana Parente Costa; Borba, Eduardo Ferreira

    2015-10-01

    Antiphospholipid syndrome (APS) is characterized by vascular thrombosis and/or obstetric complications associated with presence of antiphospholipid antibodies (aPL) but additional factors would also induce thrombosis. ABO (H) blood groups are known to be closely related to thrombosis, especially non-O blood type with venous events. The aim of this study was to investigate possible role of ABO (H) blood types in the thrombotic events in primary APS (PAPS). Seventy PAPS patients were selected for the study and were divided according to ABO blood group in: O PAPS (n = 26) and non-O PAPS (n = 44). ABO blood group phenotyping was performed by indirect technique. aPL anticardiolipin (aCL) and anti-βeta2 glycoprotein-1 (aβ2GPI) and the concentrations and activities of von Willebrand factor (VWF) were measured with ELISA. Lupus anticoagulant (LA) was detected by coagulation assays. A significant higher frequency of venous events was observed in non-O PAPS group (72.7 vs. 46.2 %, p = 0.040). In contrast, the frequency of arterial events was significantly higher in the O PAPS compared to the non-O PAPS group (69.2 vs. 36.4 %, respectively; p = 0.013). Frequencies of aCL, LA, aβ2GPI and triple aPL positivity were similar in both groups (p > 0.05). VWF antigen (75.54 ± 8.68 vs. 79.51 ± 7.07 IU/dl, p = 0.041) and activity (70.23 ± 11.96 vs. 77.92 ± 13.67 %, p = 0.020) were decreased in O PAPS compared to non-O blood group. VWF:CB/VWF:Ag ratio was similar among groups (p > 0.05). This is the first report that confirms the role of ABO blood system in thrombosis of PAPS and suggests that non-O blood group was related with venous events and O blood group with arterial thrombosis.

  3. Identification of Biomarkers of Exposure to FTOHs and PAPs in Humans Using a Targeted and Nontargeted Analysis Approach.

    PubMed

    Dagnino, Sonia; Strynar, Mark J; McMahen, Rebecca L; Lau, Christopher S; Ball, Carol; Garantziotis, Stavros; Webster, Thomas F; McClean, Michael D; Lindstrom, Andrew B

    2016-09-20

    Although historic perfluorinated compounds are currently under scrutiny and growing regulatory control in the world, little is known about human exposure to other polyfluorinated compounds presently in use. Fluorotelomer alcohols (FTOHs) and polyfluoroalkyl phosphate esters (PAPs) are known to degrade to terminal perfluorinated acids and toxic reactive intermediates through metabolic pathways. Therefore, it is important to characterize their human exposure by the identification of unique biomarkers. With the use of liquid chromatography-mass spectrometry-time-of-flight analysis (LC-MS-TOF), we developed a workflow for the identification of metabolites for the 8:2 FTOH and 8:2 diPAP. Analysis of serum and urine of dosed rats indicated the 8:2 FTOH-sulfate and the 8:2 diPAP as potential biomarkers. These compounds, as well as 25 other fluorinated compounds and metabolites, were analyzed in human serum and urine samples from the general population (n = 100) and office workers (n = 30). The 8:2 FTOH-sulfate was measured for the first time in human samples in 5 to 10% of the serum samples, ranging from 50 to 80 pg/mL. The 8:2 diPAP was measured in 58% of the samples, ranging from 100 to 800 pg/mL. This study indicates the FTOH-sulfate conjugate as a biomarker of exposure to FTOHs and PAPs in humans.

  4. Structural characteristics of pineapple pulp polysaccharides and their antitumor cell proliferation activities.

    PubMed

    Wang, Ling; Tang, De-Qiang; Kuang, Yu; Lin, Feng-Jiao; Su, Yu

    2015-09-01

    Pineapple has a delicious taste and good health benefits. Bioactive polysaccharides are important components of pineapple that might contribute to its health benefits. Since little structural information on these polysaccharides is currently available, the aim of this study was to investigate their structural characteristics and bioactivities. The polysaccharides of pineapple pulp were fractionated into three fractions (PAPs 1-3) by anion exchange chromatography. Their structural characteristics were first identified, including molecular weights and glycosidic linkages. The monosaccharide compositions were revealed as PAP 1 (Ara, Xyl, Man, Glc and Gal), PAP 2 (Rha, Ara, Xyl, Man, Glc and Gal) and PAP 3 (Rha, Ara, Xyl, Man and Gal). Nuclear magnetic resonance (NMR) spectra suggested that PAP 2 had a backbone of → 4)-α-d-Manp-(1 → 2,4)-α-d-Manp-(1 → with branches attached to O-4 of Manp. The NMR data of α-l-Araf-(1→, →3)-α-l-Araf-(1→, →4)-β-d-Galp-(1 → and → 4)-α-d-GalpAMe-(1 → were assigned. PAPs 1 and 2 showed significant antitumor cell proliferation activities against breast carcinoma cell line and strong antioxidant activities. The above findings indicated that PAPs 1-3 contributed much to the health benefits of pineapple. They could be used as health-beneficial food additives in functional foods. © 2015 Society of Chemical Industry.

  5. Human DHEA sulfation requires direct interaction between PAPS synthase 2 and DHEA sulfotransferase SULT2A1.

    PubMed

    Mueller, Jonathan W; Idkowiak, Jan; Gesteira, Tarsis F; Vallet, Cecilia; Hardman, Rebecca; van den Boom, Johannes; Dhir, Vivek; Knauer, Shirley K; Rosta, Edina; Arlt, Wiebke

    2018-06-22

    The high-energy sulfate donor 3'-phosphoadenosine-5'-phosphosulfate (PAPS), generated by human PAPS synthase isoforms PAPSS1 and PAPSS2, is required for all human sulfation pathways. Sulfotransferase SULT2A1 uses PAPS for sulfation of the androgen precursor dehydroepiandrosterone (DHEA), thereby reducing downstream activation of DHEA to active androgens. Human PAPSS2 mutations manifest with undetectable DHEA sulfate, androgen excess, and metabolic disease, suggesting that ubiquitous PAPSS1 cannot compensate for deficient PAPSS2 in supporting DHEA sulfation. In knockdown studies in human adrenocortical NCI-H295R1 cells, we found that PAPSS2, but not PAPSS1, is required for efficient DHEA sulfation. Specific APS kinase activity, the rate-limiting step in PAPS biosynthesis, did not differ between PAPSS1 and PAPSS2. Co-expression of cytoplasmic SULT2A1 with a cytoplasmic PAPSS2 variant supported DHEA sulfation more efficiently than co-expression with nuclear PAPSS2 or nuclear/cytosolic PAPSS1. Proximity ligation assays revealed protein-protein interactions between SULT2A1 and PAPSS2 and, to a lesser extent, PAPSS1. Molecular docking studies showed a putative binding site for SULT2A1 within the PAPSS2 APS kinase domain. Energy-dependent scoring of docking solutions identified the interaction as specific for the PAPSS2 and SULT2A1 isoforms. These findings elucidate the mechanistic basis for the selective requirement for PAPSS2 in human DHEA sulfation. © 2018 Mueller et al.

  6. Phosphate or phosphite addition promotes the proteolytic turnover of phosphate-starvation inducible tomato purple acid phosphatase isozymes.

    PubMed

    Bozzo, Gale G; Singh, Vinay K; Plaxton, William C

    2004-08-27

    Within 48 h of the addition of 2.5 mM phosphate (HPO42-, Pi) or phosphite (H2PO3-, Phi) to 8-day-old Pi-starved (-Pi) tomato suspension cells: (i) secreted and intracellular purple acid phosphatase (PAP) activities decreased by about 12- and 6-fold, respectively and (ii) immunoreactive PAP polypeptides either disappeared (secreted PAPs) or were substantially reduced (intracellular PAP). The degradation of both secreted PAP isozymes was correlated with the de novo synthesis of two extracellular serine proteases having M(r)s of 137 and 121 kDa. In vitro proteolysis of purified secreted tomato PAP isozymes occurred following their 24 h incubation with culture filtrate from Pi-resupplied cells. The results indicate that Pi or Phi addition to -Pi tomato cells induces serine proteases that degrade Pi-starvation inducible extracellular proteins.

  7. Evaluation of Papanicolaou stain for studying micronuclei in buccal cells under field conditions.

    PubMed

    Ayyad, Sohair B A; Israel, Ebenezer; El-Setouhy, Maged; Nasr, Ghada Radwan; Mohamed, Mostafa K; Loffredo, Christopher A

    2006-01-01

    To compare Papanicolaou (Pap) and May-Grünwald Giemsa (MGG) stain as 2 techniques for staining for buccal mucosal cells to detect micronuclei (MN) infield studies. Eighty cytologic smears (2 per individual) were taken from the buccal mucosa of 40 cigarette smokers recruited at a rural village in Egypt. Forty smears were stained with Pap stain and 40 with MGG stain. All were assessed for cellularity and scored for MN. Pap stain was faster and easier to process and transport in the field study than was MGG stain. Regarding MGG smears, bacteria and cell debris masked the MN as compared to Pap smears, in which the fixative destroyed the bacteria and made the cell boundaries clearly demarcated. Using Pap stain, MN were seen easily in transparent cytoplasm. Pap stain is the preferred method infield studies for scoring and detecting MN in cells of buccal mucosa.

  8. Women's knowledge and attitudes toward anal Pap testing.

    PubMed

    Ferris, Daron; Lambert, Rebecca; Waller, Jennifer; Dickens, Porscha; Kabaria, Reena; Han, Chi-Son; Steelman, Charlotte; Fawole, Fiyinfoluwa

    2013-10-01

    The objectives of this study were to determine women's knowledge of human papillomavirus (HPV) and anal cancer and knowledge and attitudes toward the anal Pap test. A convenience sample of 370 women from the general population 21 years or older completed a 48-question preintervention survey; read an informational pamphlet about anal cancer, HPV, and anal Pap tests; and then completed a 21-question postintervention survey in Augusta, Atlanta, and Savannah, GA. The survey assessed their knowledge about anal cancer, HPV, and the anal Pap test and determined their attitudes toward the anal Pap test. Only preintervention results were considered in this article. Descriptive statistics were determined for all variables. Only 17.6% of women had previously heard of anal Pap tests, and the majority knew nothing (48.9%) or only a little (38.5%) about anal cancer. Yet, most women (78.6%) knew that anal Pap tests help to prevent anal cancer, and 86.2% knew that anal Pap tests are not only for people who have anal sex. Only a minority of women recognized known risk factors for anal cancer. Lack of knowledge about anal Pap tests (43.8%), pain or discomfort (41.3%), cost (24.0%), and embarrassment (21.2%) were the main reasons cited for not wanting an anal Pap test. Although most women had limited knowledge about anal cancer and anal Pap tests and few recognized known risk factors for anal cancer, women were receptive to screening. Further implementation of anal Pap testing for women may be improved by understanding women's limited knowledge and concerns.

  9. A sub-canopy structure for simulating oil palm in the Community Land Model (CLM-Palm): phenology, allocation and yield

    NASA Astrophysics Data System (ADS)

    Fan, Y.; Roupsard, O.; Bernoux, M.; Le Maire, G.; Panferov, O.; Kotowska, M. M.; Knohl, A.

    2015-11-01

    In order to quantify the effects of forests to oil palm conversion occurring in the tropics on land-atmosphere carbon, water and energy fluxes, we develop a new perennial crop sub-model CLM-Palm for simulating a palm plant functional type (PFT) within the framework of the Community Land Model (CLM4.5). CLM-Palm is tested here on oil palm only but is meant of generic interest for other palm crops (e.g., coconut). The oil palm has monopodial morphology and sequential phenology of around 40 stacked phytomers, each carrying a large leaf and a fruit bunch, forming a multilayer canopy. A sub-canopy phenological and physiological parameterization is thus introduced so that each phytomer has its own prognostic leaf growth and fruit yield capacity but with shared stem and root components. Phenology and carbon and nitrogen allocation operate on the different phytomers in parallel but at unsynchronized steps, separated by a thermal period. An important phenological phase is identified for the oil palm - the storage growth period of bud and "spear" leaves which are photosynthetically inactive before expansion. Agricultural practices such as transplanting, fertilization and leaf pruning are represented. Parameters introduced for the oil palm were calibrated and validated with field measurements of leaf area index (LAI), yield and net primary production (NPP) from Sumatra, Indonesia. In calibration with a mature oil palm plantation, the cumulative yields from 2005 to 2014 matched notably well between simulation and observation (mean percentage error = 3 %). Simulated inter-annual dynamics of PFT-level and phytomer-level LAI were both within the range of field measurements. Validation from eight independent oil palm sites shows the ability of the model to adequately predict the average leaf growth and fruit yield across sites and sufficiently represent the significant nitrogen- and age-related site-to-site variability in NPP and yield. Results also indicate that seasonal dynamics of yield and remaining small-scale site-to-site variability of NPP are driven by processes not yet implemented in the model or reflected in the input data. The new sub-canopy structure and phenology and allocation functions in CLM-Palm allow exploring the effects of tropical land-use change, from natural ecosystems to oil palm plantations, on carbon, water and energy cycles and regional climate.

  10. Symptoms of insomnia among patients with obstructive sleep apnea before and after two years of positive airway pressure treatment.

    PubMed

    Björnsdóttir, Erla; Janson, Christer; Sigurdsson, Jón F; Gehrman, Philip; Perlis, Michael; Juliusson, Sigurdur; Arnardottir, Erna S; Kuna, Samuel T; Pack, Allan I; Gislason, Thorarinn; Benediktsdóttir, Bryndis

    2013-12-01

    To assess the changes of insomnia symptoms among patients with obstructive sleep apnea (OSA) from starting treatment with positive airway pressure (PAP) to a 2-y follow-up. Longitudinal cohort study. Landspitali--The National University Hospital of Iceland. There were 705 adults with OSA who were assessed prior to and 2 y after starting PAP treatment. PAP treatment for OSA. All patients underwent a medical examination along with a type 3 sleep study and answered questionnaires on health and sleep before and 2 y after starting PAP treatment. The change in prevalence of insomnia symptoms by subtype was assessed by questionnaire and compared between individuals who were using or not using PAP at follow-up. Symptoms of middle insomnia were most common at baseline and improved significantly among patients using PAP (from 59.4% to 30.7%, P < 0.001). Symptoms of initial insomnia tended to persist regardless of PAP treatment, and symptoms of late insomnia were more likely to improve among patients not using PAP. Patients with symptoms of initial and late insomnia at baseline were less likely to adhere to PAP (odds ratio [OR] 0.56, P = 0.007, and OR 0.53, P < 0.001, respectively). Positive airway pressure treatment significantly reduced symptoms of middle insomnia. Symptoms of initial and late insomnia, however, tended to persist regardless of positive airway pressure treatment and had a negative effect on adherence. Targeted treatment for insomnia may be beneficial for patients with obstructive sleep apnea comorbid with insomnia and has the potential to positively affect adherence to positive airway pressure.

  11. Domain activities of PapC usher reveal the mechanism of action of an Escherichia coli molecular machine.

    PubMed

    Volkan, Ender; Ford, Bradley A; Pinkner, Jerome S; Dodson, Karen W; Henderson, Nadine S; Thanassi, David G; Waksman, Gabriel; Hultgren, Scott J

    2012-06-12

    P pili are prototypical chaperone-usher pathway-assembled pili used by Gram-negative bacteria to adhere to host tissues. The PapC usher contains five functional domains: a transmembrane β-barrel, a β-sandwich Plug, an N-terminal (periplasmic) domain (NTD), and two C-terminal (periplasmic) domains, CTD1 and CTD2. Here, we delineated usher domain interactions between themselves and with chaperone-subunit complexes and showed that overexpression of individual usher domains inhibits pilus assembly. Prior work revealed that the Plug domain occludes the pore of the transmembrane domain of a solitary usher, but the chaperone-adhesin-bound usher has its Plug displaced from the pore, adjacent to the NTD. We demonstrate an interaction between the NTD and Plug domains that suggests a biophysical basis for usher gating. Furthermore, we found that the NTD exhibits high-affinity binding to the chaperone-adhesin (PapDG) complex and low-affinity binding to the major tip subunit PapE (PapDE). We also demonstrate that CTD2 binds with lower affinity to all tested chaperone-subunit complexes except for the chaperone-terminator subunit (PapDH) and has a catalytic role in dissociating the NTD-PapDG complex, suggesting an interplay between recruitment to the NTD and transfer to CTD2 during pilus initiation. The Plug domain and the NTD-Plug complex bound all of the chaperone-subunit complexes tested including PapDH, suggesting that the Plug actively recruits chaperone-subunit complexes to the usher and is the sole recruiter of PapDH. Overall, our studies reveal the cooperative, active roles played by periplasmic domains of the usher to initiate, grow, and terminate a prototypical chaperone-usher pathway pilus.

  12. Compliance with Papanicolaou smear screening following tubal ligation in women with cervical cancer.

    PubMed

    Winkler, H A; Anderson, P S; Fields, A L; Runowicz, C D; DeVictoria, C; Goldberg, G L

    1999-01-01

    To evaluate patient compliance with Papanicolaou (Pap) smear screening after tubal ligation compared with other methods of birth control in patients who develop cervical cancer, a retrospective review of 262 women with cervical cancer diagnosed at age < or = 70 years was undertaken at the Albert Einstein College of Medicine from January 1987 to December 1995. Demographic data, stage of the disease, histologic type, history of smoking, history of sexually transmitted disease (STD), and birth control use were recorded. The Pap screening history was obtained from all the patients. Women who had a bilateral tubal ligation (BTL) were compared with those who did not have this form of birth control. The date and result of their last Pap test prior to their diagnosis of cervical cancer was noted. Two hundred fourteen women with cervical cancer were evaluable. The clinical stage, mean age, history of smoking, and history of STD were similar for both groups. Gravidity among the BTL group was higher than in the non-BTL group (p < 0.01). Forty-eight (22.4%) women had a previous BTL. Twenty-seven of these 48 patients (56.3%) did not have a Pap smear within 3 years prior to the diagnosis of cervical cancer. Of the 166 patients, 61 (36.7%) did not have a Pap test within 3 years (p < 0.05). Fourteen women (29.2%) in the tubal ligation group never returned for a Pap test following the BTL. An average of 6.2+/-5.9 years elapsed since the last Pap test in the BTL group, with 4.0+/-5.1 years in the nontubal ligation group (p < 0.05). There was a correlation between the number of years since BTL (14.2+/-7.7) to the number of years since the last Pap test (6.2+/-5.9) (p < 0.05). Women who have had a BTL should be considered high risk because of poor screening compliance. A Pap test every 3 years is not adequate in this high-risk population group. We advocate improved counseling regarding the importance of continued annual Pap screening for women who are considering tubal ligation.

  13. Clinical significance of cigarette smoking and dust exposure in pulmonary alveolar proteinosis: a Korean national survey.

    PubMed

    Hwang, Ji An; Song, Joo Han; Kim, Jung Hoon; Chung, Man Pyo; Kim, Dong Soon; Song, Jin Woo; Kim, Young Whan; Choi, Sun Mi; Cha, Seung Ick; Uh, Soo Taek; Park, Choon-Sik; Jeong, Sung Hwan; Park, Yong Bum; Lee, Hong Lyeol; Shin, Jong Wook; Lee, Eun Joo; Jegal, Yangjin; Lee, Hyun Kyung; Park, Jong Sun; Park, Moo Suk

    2017-11-21

    This study aimed to investigate clinical characteristics of Korean PAP patients and to examine the potential risk factors of PAP. We retrospectively reviewed medical records of 78 Korean PAP patients diagnosed between 1993 and 2014. Patients were classified into two groups according to the presence/absence of treatment (lavage). Clinical and laboratory features were compared between the two groups. Of the total 78 PAP patients, 60% were male and median age at diagnosis was 47.5 years. Fifty three percent were ever smokers (median 22 pack-years) and 48% had a history of dust exposure (metal 26.5%, stone or sand 20.6%, chemical or paint 17.7%, farming dust 14.7%, diesel 14.7%, textile 2.9%, and wood 2.9%). A history of cigarette smoking or dust exposure was present in 70.5% of the total PAP patients, with 23% having both of them. Patients who underwent lavage (n = 38) presented symptoms more frequently (38/38 [100%] vs. 24/40 [60%], P < 0.001) and had significantly lower PaO 2 and DL CO with higher D(A-a)O 2 at the onset of disease than those without lavage (n = 40) (P = 0.006, P < 0.001, and P = 0.036, respectively). Correspondingly, the distribution of disease severity score (DSS) differed significantly between the two groups (P = 0.001). Based on these, when the total patients were categorized according to DSS (low DSS [DSS 1-2] vs. high DSS [DSS 3-5]), smoking status differed significantly between the two groups with the proportion of current smokers significantly higher in the high DSS group (11/22 [50%] vs. 7/39 [17.9%], P = 0.008). Furthermore, current smokers had meaningfully higher DSS and serum CEA levels than non-current smokers (P = 0.011 and P = 0.031), whereas no difference was found between smokers and non-smokers. Regarding type of exposed dust, farming dust was significantly associated with more severe form of PAP (P = 0.004). A considerable proportion of PAP patients had a history of cigarette smoking and/or dust exposure, suggestive of their possible roles in the development of PAP. Active cigarette smoking at the onset of PAP is associated with the severity of PAP.

  14. [Virulence factors and pathophysiology of extraintestinal pathogenic Escherichia coli].

    PubMed

    Bidet, P; Bonarcorsi, S; Bingen, E

    2012-11-01

    Extraintestinal pathogenic Escherichia coli (ExPEC) causing urinary tract infections, bacteraemia or meningitis are characterized by a particular genetic background (phylogenetic group B2 and D) and the presence, within genetic pathogenicity islands (PAI) or plasmids, of genes encoding virulence factors involved in adhesion to epithelia, crossing of the body barriers (digestive, kidney, bloodbrain), iron uptake and resistance to the immune system. Among the many virulence factors described, two are particularly linked with a pathophysiological process: type P pili PapGII adhesin is linked with acute pyelonephritis, in the absence of abnormal flow of urine, and the K1 capsule is linked with neonatal meningitis. However, if the adhesin PapGII appears as the key factor of pyelonephritis, such that its absence in strain causing the infection is predictive of malformation or a vesico-ureteral reflux, the meningeal virulence of E. coli can not be reduced to a single virulence factor, but results from a combination of factors unique to each clone, and an imbalance between the immune defenses of the host and bacterial virulence. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  15. Screening and Characterization of a Novel RNA Aptamer That Specifically Binds to Human Prostatic Acid Phosphatase and Human Prostate Cancer Cells

    PubMed Central

    Kong, Hoon Young; Byun, Jonghoe

    2015-01-01

    Prostatic acid phosphatase (PAP) expression increases proportionally with prostate cancer progression, making it useful in prognosticating intermediate to high-risk prostate cancers. A novel ligand that can specifically bind to PAP would be very helpful for guiding prostate cancer therapy. RNA aptamers bind to target molecules with high specificity and have key advantages such as low immunogenicity and easy synthesis. Here, human PAP-specific aptamers were screened from a 2′-fluoropyrimidine (FY)-modified RNA library by SELEX. The candidate aptamer families were identified within six rounds followed by analysis of their sequences and PAP-specific binding. A gel shift assay was used to identify PAP binding aptamers and the 6N aptamer specifically bound to PAP with a Kd value of 118 nM. RT-PCR and fluorescence labeling analyses revealed that the 6N aptamer bound to PAP-positive mammalian cells, such as PC-3 and LNCaP. IMR-90 negative control cells did not bind the 6N aptamer. Systematic minimization analyses revealed that 50 nucleotide sequences and their two hairpin structures in the 6N 2′-FY RNA aptamer were equally important for PAP binding. Renewed interest in PAP combined with the versatility of RNA aptamers, including conjugation of anti-cancer drugs and nano-imaging probes, could open up a new route for early theragnosis of prostate cancer. PMID:25591398

  16. Perfluoroalkyl acids and their precursors in Swedish food: The relative importance of direct and indirect dietary exposure.

    PubMed

    Gebbink, Wouter A; Glynn, Anders; Darnerud, Per Ola; Berger, Urs

    2015-03-01

    We analyzed food market basket samples obtained in Sweden from 1999, 2005, and 2010 for perfluoroalkyl acids (PFAAs) and a range of precursor compounds. Perfluorooctane sulfonic acid (PFOS) precursors were detected in all food year pools with the highest concentrations in 1999. Six polyfluoroalkyl phosphate diesters (diPAPs, 4:2/6:2, 6:2/6:2, 6:2/8:2, 8:2/8:2, 6:2/10:2, and 10:2/10:2) were detected in the year pools with the highest ∑diPAP concentrations in 1999 and 2005. All precursors were predominantly found in meat, fish, and/or eggs based on analysis of individual food groups from 1999. Based on year pools, PFOS precursors contributed between 4 and 1% as an indirect source to total dietary PFOS intakes between 1999 and 2010. Perfluorohexanoic acid (PFHxA) exposure originated entirely from diPAPs, whereas for perfluorooctanoic acid (PFOA) and perfluorodecanoic acid (PFDA), diPAPs contributed between 1 and 19% to total exposure. The lowest precursor contributions were generally seen in food samples from 2010. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. Star-PAP, a poly(A) polymerase, functions as a tumor suppressor in an orthotopic human breast cancer model.

    PubMed

    Yu, C; Gong, Y; Zhou, H; Wang, M; Kong, L; Liu, J; An, T; Zhu, H; Li, Y

    2017-02-02

    Star-PAP is a noncanonical poly(A) polymerase and required for the expression of a select set of mRNAs. However, the pathological role of Star-PAP in cancer largely remains unknown. In this study, we observed decreased expression of Star-PAP in breast cancer cell lines and tissues. Ectopic Star-PAP expression inhibited proliferation as well as colony-forming ability of breast cancer cells. In breast cancer patients, high levels of Star-PAP correlated with an improved prognosis. Moreover, by regulating the expression of BIK (BCL2-interacting killer), Star-PAP induced apoptosis of breast cancer cells through the mitochondrial pathway. The growth of breast cancer xenografts in NOD/SCID mice was also inhibited by the doxycycline-induced Star-PAP overexpression. Furthermore, Star-PAP sensitized breast cancer cells to chemotherapy drugs both in vitro and in vivo. In mammary epithelial cells, Star-PAP knockdown partially transformed these cells and induced them to undergo epithelial-mesenchymal transition (EMT). These findings suggested that Star-PAP possesses tumor-suppressing activity and can be a valuable target for developing new cancer therapeutic strategies.

  18. HPV test results and histological follow-up results of patients with LSIL Cervical Cytology from the Largest CAP-certified laboratory in China.

    PubMed

    Zheng, Baowen; Yang, Huaitao; Li, Zaibo; Wei, Guijian; You, Jia; Liang, Xiaoman; Zhao, Chengquan

    2017-01-01

    Age-adjusted evaluations have explored the possible utility of (HPV test results in women with LSIL Pap. We investigated HPV test results and histopathologic follow-up results of LSIL patients from China's largest CAP-certified laboratory. Patients with LSIL between 2011 and 2015 from the Guangzhou Kingmed Diagnostics were retrospectively retrieved and their hrHPV test results and histological follow-up results were collected and analyzed. LSIL result was identified in 37,895 cases from 2,206,588 Pap tests (1.7%) including 1,513,265 liquid-based cytology and 693,323 conventional Pap tests. The average of these women was 38.4 years (15-88). The LSIL reporting rate in women <30 years was significantly higher than that in women > 30 years (2.1% vs 1.7%). The age specific reporting LSIL rates declined with increased age. 8,014 of 37,895 (21.2%) women with LSIL cytology also had HC2 HPV test results. 75.8% of women with LSIL Pap tests were hrHPV+ and the HPV+ rates declined with increased age except in patients older than 60 years. Overall histopathologic diagnoses within 6 months after LSIL were identified in 5,987 of 37,895 patients at Guangzhou Kingmed Diagnostics. CIN2/3 was identified in 15.2% patients, CIN1 in 66.9%, negative in 14.9% patients. No invasive carcinoma was found in all patients. Of 8014 patients with LSIL Pap test and HPV testing results, 1727 patients had histological follow-up within 6 months after Pap cytology test and HPV testing. The detection rate of CIN2/3 was significantly higher in patients with positive HPV testing result than that in patients with negative HPV testing result (17.8% vs. 8.1%). Among patients with LSIL/HPV negative tests, CIN2/3 was detected in 1 of 30 (3.3%) women aged 50 years and above, appearing lower than those in women less than 50 years (8.0%, 28/351, P=0.357). This is the largest histological follow-up study in women with LSIL Pap from China and the data are helpful in establishing a baseline for better understanding the status of cervical screening in China. The 85.1% positive predict value of LSIL Pap cytology for follow-up CIN lesion was within currently recognized benchmark ranges.

  19. [Lactic acid inhibits the formation of semen-derived amyloid fibrils].

    PubMed

    Li, Jin-Qing; Song, Ya-Li; Xun, Tian-Rong; Tan, Sui-Yi; Liu, Shu-Wen

    2017-07-20

    To investigate the inhibitory effect of lactic acid on semen-derived amyloid (SEVI) fibril formation. PAP248-286 (2 mg/mL) was incubated with 4.0, 2.0, 1.0, 0.5, 0.25, and 0.125 mg/mL of lactic acid. After incubation for different times, aliquots were drawn from each sample for Thioflavin T (ThT) and Congo red staining to monitor semen-derived amyloid fibril formation. The β sheet structure formation of PAP248-286 was measured by circular dichroism spectrum, and the morphology of amyloid fibrils incubated with or without lactic acid was observed with transmission electron microscopy (TEM). The enhancing effect of amyloid fibril incubated with lactic acid at different time points was determined using virus infection assay. PAP248-286 (2 mg/mL) was incubated with dilutions of vaginal secretion from healthy women, and amyloid fibril formation was detected with ThT and Congo red staining. Lactic acid inhibited SEVI fibril formation in a dose-dependent manner in vitro. Lactic acid at 0.5 mg/mL completely inhibited 2 mg/mL SEVI fibril formation within 48 h. After incubation for 48 h, lactic acid at 1 mg/mL inhibited the formation of β-sheet structure of SEVI (2 mg/mL) and completely inhibited 2 mg/mL PAP248-286 aggregation as observed with TEM. In the presence of lactic acid, PAP248-286 lost the ability to enhance virus infection. Vaginal secretion inhibited SEVI fibril formation in a dose-dependent manner, and virtually no SEVI fibril occurred after incubation of 2 mg/mL PAP248-286 with 67% vaginal secretion. Lactic acid inhibits SEVI fibril formation in vitro.

  20. Confusion about Pap smears: lack of knowledge among high-risk women.

    PubMed

    Daley, Ellen; Perrin, Kay; Vamos, Cheryl; Hernandez, Natalie; Anstey, Erica; Baker, Elizabeth; Kolar, Stephanie; Ebbert, Judith

    2013-01-01

    The impact of the Papanicolaou (Pap) smear on the prevention of cervical cancer is one of the greatest public health success stories. However, it is not clear if women understand the purpose of the Pap smear despite recent advancements and national attention over cervical cancer prevention. The purpose of this study was to examine Pap smear knowledge among three high-risk populations at different points in time. Women from three separate human papillomavirus (HPV) psychosocial studies completed surveys assessing Pap smear knowledge: (1) HPV-positive women (prevaccine population in 2005-2006, n=154, mean age 23.5), (2) college women (postvaccine population in 2008, n=276, mean age 18.9), and (3) minority college women (postvaccine population in 2011, n=711, mean age 23.3). Frequencies and logistic regression were employed to examine associations between demographic factors and accurate knowledge of Pap smear testing within each study. Approximately one quarter of participants across all three samples did not know that the Pap smear is a test for cervical cancer. Participants also incorrectly believed that the Pap smear tests for HPV (82%-91%), vaginal infections (76%-92%), yeast infections (65%-86%), gonorrhea (55%-81%), herpes (53%-80%), HIV/AIDS (22%-59%), and pregnancy (17%-38%). Among all three studies, older age was the only factor significant with higher Pap knowledge. Higher HPV knowledge scores were significantly associated with higher Pap knowledge in studies 2 and 3 only. Knowledge about the purpose of the Pap smear remains low. Findings underscore the significant need for clear and consistent messages among high-risk women regarding the prevention of cervical cancer and other reproductive health conditions.

  1. A Novel Therapy for Chronic Sleep-Onset Insomnia: A Retrospective, Nonrandomized Controlled Study of Auto-Adjusting, Dual-Level, Positive Airway Pressure Technology.

    PubMed

    Krakow, Barry; Ulibarri, Victor A; McIver, Natalia D; Nadorff, Michael R

    2016-09-29

    Evidence indicates that behavioral or drug therapy may not target underlying pathophysiologic mechanisms for chronic insomnia, possibly due to previously unrecognized high rates (30%-90%) of sleep apnea in chronic insomnia patients. Although treatment studies with positive airway pressure (PAP) demonstrate decreased severity of chronic sleep maintenance insomnia in patients with co-occurring sleep apnea, sleep-onset insomnia has not shown similar results. We hypothesized advanced PAP technology would be associated with decreased sleep-onset insomnia severity in a sample of predominantly psychiatric patients with comorbid sleep apnea. We reviewed charts of 74 severe sleep-onset insomnia patients seen from March 2011 to August 2015, all meeting American Academy of Sleep Medicine Work Group criteria for a chronic insomnia disorder and all affirming behavioral and psychological origins for insomnia (averaging 10 of 18 indicators/patient), as well as averaging 2 or more psychiatric symptoms or conditions: depression (65.2%), anxiety (41.9%), traumatic exposure (35.1%), claustrophobia (29.7%), panic attacks (28.4%), and posttraumatic stress disorder (20.3%). All patients failed continuous or bilevel PAP and were manually titrated with auto-adjusting PAP modes (auto-bilevel and adaptive-servo ventilation). At 1-year follow-up, patients were compared through nonrandom assignment on the basis of a PAP compliance metric of > 20 h/wk (56 PAP users) versus < 20 h/wk (18 partial PAP users). PAP users showed significantly greater decreases in global insomnia severity (Hedges' g = 1.72) and sleep-onset insomnia (g = 2.07) compared to partial users (g = 1.04 and 0.91, respectively). Both global and sleep-onset insomnia severity decreased below moderate levels in PAP users compared to partial users whose outcomes persisted at moderately severe levels. In a nonrandomized controlled retrospective study, advanced PAP technology (both auto-bilevel and adaptive servo-ventilation) were associated with large decreases in insomnia severity for sleep-onset insomnia patients who strongly believed psychological factors caused their sleeplessness. PAP treatment of sleep-onset insomnia merits further investigation. © Copyright 2016 Physicians Postgraduate Press, Inc.

  2. Highly permeable artificial water channels that can self-assemble into two-dimensional arrays

    PubMed Central

    Shen, Yue-xiao; Si, Wen; Erbakan, Mustafa; Decker, Karl; De Zorzi, Rita; Saboe, Patrick O.; Kang, You Jung; Majd, Sheereen; Butler, Peter J.; Walz, Thomas; Aksimentiev, Aleksei; Hou, Jun-li; Kumar, Manish

    2015-01-01

    Bioinspired artificial water channels aim to combine the high permeability and selectivity of biological aquaporin (AQP) water channels with chemical stability. Here, we carefully characterized a class of artificial water channels, peptide-appended pillar[5]arenes (PAPs). The average single-channel osmotic water permeability for PAPs is 1.0(±0.3) × 10−14 cm3/s or 3.5(±1.0) × 108 water molecules per s, which is in the range of AQPs (3.4∼40.3 × 108 water molecules per s) and their current synthetic analogs, carbon nanotubes (CNTs, 9.0 × 108 water molecules per s). This permeability is an order of magnitude higher than first-generation artificial water channels (20 to ∼107 water molecules per s). Furthermore, within lipid bilayers, PAP channels can self-assemble into 2D arrays. Relevant to permeable membrane design, the pore density of PAP channel arrays (∼2.6 × 105 pores per μm2) is two orders of magnitude higher than that of CNT membranes (0.1∼2.5 × 103 pores per μm2). PAP channels thus combine the advantages of biological channels and CNTs and improve upon them through their relatively simple synthesis, chemical stability, and propensity to form arrays. PMID:26216964

  3. Influence of hormonal contraceptive use and health beliefs on sexual orientation disparities in Papanicolaou test use.

    PubMed

    Charlton, Brittany M; Corliss, Heather L; Missmer, Stacey A; Frazier, A Lindsay; Rosario, Margaret; Kahn, Jessica A; Austin, S Bryn

    2014-02-01

    Reproductive health screenings are a necessary part of quality health care. However, sexual minorities underutilize Papanicolaou (Pap) tests more than heterosexuals do, and the reasons are not known. Our objective was to examine if less hormonal contraceptive use or less positive health beliefs about Pap tests explain sexual orientation disparities in Pap test intention and utilization. We used multivariable regression with prospective data gathered from 3821 females aged 18 to 25 years in the Growing Up Today Study (GUTS). Among lesbians, less hormonal contraceptive use explained 8.6% of the disparities in Pap test intention and 36.1% of the disparities in Pap test utilization. Less positive health beliefs associated with Pap testing explained 19.1% of the disparities in Pap test intention. Together, less hormonal contraceptive use and less positive health beliefs explained 29.3% of the disparities in Pap test intention and 42.2% of the disparities in Pap test utilization. Hormonal contraceptive use and health beliefs, to a lesser extent, help to explain sexual orientation disparities in intention and receipt of a Pap test, especially among lesbians.

  4. Estimation of pulmonary artery pressure in patients with primary pulmonary hypertension by quantitative analysis of magnetic resonance images.

    PubMed

    Murray, T I; Boxt, L M; Katz, J; Reagan, K; Barst, R J

    1994-01-01

    The use of magnetic resonance (MR) images for estimating mean pulmonary artery pressure (PAP) was tested by comparing main pulmonary artery (MPA) and middescending thoracic aorta (AO) caliber in 12 patients with primary pulmonary hypertension (PPH) with measurements made in eight other patients who were observed for diseases other than heart disease (controls). The ratio MPA/AO and the ratios of vessel caliber normalized to body surface area (MPAI and AOI, respectively) were computed. The PAP was obtained in all PPH patients and compared with caliber measurements. The PPH MPA (3.6 +/- 0.8 cm) was significantly larger than the control MPA (2.9 +/- 0.3 cm, p = 0.02); the PPH MPAI (2.8 +/- 0.7 cm/M2) was significantly greater than the control MPA (1.7 +/- 0.2 cm/M2, p < 0.0001). Control AO (2.2 +/- 0.3 cm) was significantly greater than PPH AO (1.6 +/- 0.4 cm, p < 0.0001); there was no significant difference between control AOI (1.3 +/- 0.2 cm/M2) and PPH AOI (1.2 +/- 0.2 cm/M2, p = 0.25). The PPH MPA/AO (2.3 +/- 0.6) was significantly greater than the control MPA/AO (1.3 +/- 0.1, p < 0.0001); overlap between MPA in the two groups was eliminated by indexing values to AO caliber (MPA/AO). Among PPH patients there was strong correlation between PAP and MPA/AO (PAP = 24 x MPA/AO + 3.7, r = 0.7, p < 0.01). Increased MPA/AO denotes the presence of pulmonary hypertension and may be used to estimate PAP.

  5. On the generation and outcome of 3-(N-phenylamino)propane-1,2-diol derivatives in deodorized model oils related to toxic oil syndrome.

    PubMed

    Morató, Anna; Escabrós, Jordi; Manich, Albert; Reig, Natàlia; Castaño, Yolanda; Abián, Joaquín; Messeguer, Angel

    2005-04-01

    Toxic Oil Syndrome (TOS) was a massive food-born intoxication that occurred in Spain in 1981 and affected more than 20,000 people. TOS was attributed to the ingestion of rapeseed oil that had been adulterated with aniline, illegally refined, and delivered for human consumption. Two chemical species derived from aniline have been identified in oil batches: fatty acid anilides, qualified as biomarkers of the adulterated oil, and fatty acid esters of 3-(N-phenylamino)propane-1,2-diol (PAP), considered toxic oil biomarkers. These esters were generated by chemical processes during oil refining, specifically in the deodorization step, which involves treatment of the oil at high temperatures under vacuum to remove volatile contaminants. Since PAP derivatives are strongly associated with TOS, their formation and putative interconversion in a toxic oil model has been studied. The main results obtained are (i) only triglycerides and aniline are required to produce PAP esters, thus eliminating the possibility that unknown activators present in the deodorization tank were required for toxification of the oil; (ii) PAP and PAP mono- and diesters are chemically interrelated, as are anilides and PAP esters to an even higher degree. In addition to the reaction of aniline with triglycerides, anilides can be also formed via attack of PAP esters by aniline. However, the most important source of anilides during deodorization seems to be the thermal decomposition of PAP esters. Overall, these results suggest that the generation and outcome of PAP derivatives during deodorization is a complex scenario whereby PAP esters are not only generated from different reactions but decompose to produce anilides, among other compounds. In addition to providing a rapeseed oil model that reproduces the composition of case oils with respect to anilides and PAP derivatives, the results presented herein further support the hypothesis imputing PAP diesters or their metabolites for the intoxication episode.

  6. 1,5-Diamido-9,10-anthraquinone, a Centrosymmetric Redox-Active Bridge with Two Coupled β-Ketiminato Chelate Functions: Symmetric and Asymmetric Diruthenium Complexes.

    PubMed

    Ansari, Mohd Asif; Mandal, Abhishek; Paretzki, Alexa; Beyer, Katharina; Fiedler, Jan; Kaim, Wolfgang; Lahiri, Goutam Kumar

    2016-06-06

    The dinuclear complexes {(μ-H2L)[Ru(bpy)2]2}(ClO4)2 ([3](ClO4)2), {(μ-H2L)[Ru(pap)2]2}(ClO4)2 ([4](ClO4)2), and the asymmetric [(bpy)2Ru(μ-H2L)Ru(pap)2](ClO4)2 ([5](ClO4)2) were synthesized via the mononuclear species [Ru(H3L)(bpy)2]ClO4 ([1]ClO4) and [Ru(H3L)(pap)2]ClO4 ([2]ClO4), where H4L is the centrosymmetric 1,5-diamino-9,10-anthraquinone, bpy is 2,2'-bipyridine, and pap is 2-phenylazopyridine. Electrochemistry of the structurally characterized [1]ClO4, [2]ClO4, [3](ClO4)2, [4](ClO4)2, and [5](ClO4)2 reveals multistep oxidation and reduction processes, which were analyzed by electron paramagnetic resonance (EPR) of paramagnetic intermediates and by UV-vis-NIR spectro-electrochemistry. With support by time-dependent density functional theory (DFT) calculations the redox processes could be assigned. Significant results include the dimetal/bridging ligand mixed spin distribution in 3(3+) versus largely bridge-centered spin in 4(3+)-a result of the presence of Ru(II)-stabilizig pap coligands. In addition to the metal/ligand alternative for electron transfer and spin location, the dinuclear systems allow for the observation of ligand/ligand and metal/metal site differentiation within the multistep redox series. DFT-supported EPR and NIR absorption spectroscopy of the latter case revealed class II mixed-valence behavior of the oxidized asymmetric system 5(3+) with about equal contributions from a radical bridge formulation. In comparison to the analogues with the deprotonated 1,4-diaminoanthraquinone isomer the centrosymmetric H2L(2-) bridge shows anodically shifted redox potentials and weaker electronic coupling between the chelate sites.

  7. Metabolism of (R)- and (S)-3-(phenylamino)propane-1,2-diol in C57BL/6- and A/J-strain mice. Identification of new metabolites with potential toxicological significance to the toxic oil syndrome.

    PubMed

    Bujons, J; Ladona, M G; Messeguer, A; Morató, A; Ampurdanés, C

    2001-08-01

    The Toxic Oil Syndrome was a massive food-borne intoxication that occurred in Spain in 1981. Epidemiological studies point to 3-(phenylamino)propane-1,2-diol (PAP) derivatives as the putative toxic agents. We report further identification of metabolites cleared in urine of A/J and C57BL/6 mice in which (R)- and (S)-3-(phenylamino)propane-1,2-diol were administered intraperitoneally. This investigation is an extension of previous studies carried out with the racemic compound [Ladona, M. G., Bujons, J., Messeguer, A., Ampurdanés, C., Morató, A., and Corbella, J. (1999) Chem. Res. Toxicol. 12, 1127-1137]. Both PAP enantiomers were extensively metabolized, and several metabolites were eliminated in urine. The HPLC profiles of the urine samples of both mouse strains treated with each enantiomer were qualitatively similar, but differences were found in a relatively higher proportion of several detected metabolites in mice treated with (R)-PAP compared with those treated with (S)-PAP. The main urine metabolite continues to be 2-hydroxy-3-(phenylamino)propanoic acid (1), which confirms our previous results obtained with rac-PAP. In addition to the detection of other metabolites already reported in our previous paper, interesting evidence is provided on the presence of 4-aminophenol and paracetamol conjugates in the urine samples from both mouse strains. The detection of these metabolites suggests the in vivo formation of quinoneimine PAP derivatives. Indeed, some quinoneimine species (11 and 12), as well as other PAP metabolites (13) that bear modifications in the alkyl chain, have been tentatively identified in mouse urine. These metabolic findings might imply a potential toxicological significance for the Toxic Oil Syndrome.

  8. Cervical and Breast Cancer Screening After CARES: A Community Program for Immigrant and Marginalized Women.

    PubMed

    Dunn, Sheila F; Lofters, Aisha K; Ginsburg, Ophira M; Meaney, Christopher A; Ahmad, Farah; Moravac, M Catherine; Nguyen, Cam Tu Janet; Arisz, Angela M

    2017-05-01

    Marginalized populations such as immigrants and refugees are less likely to receive cancer screening. Cancer Awareness: Ready for Education and Screening (CARES), a multifaceted community-based program in Toronto, Canada, aimed to improve breast and cervical screening among marginalized women. This matched cohort study assessed the impact of CARES on cervical and mammography screening among under-screened/never screened (UNS) attendees. Provincial administrative data collected from 1998 to 2014 and provided in 2015 were used to match CARES participants who were age eligible for screening to three controls matched for age, geography, and pre-education screening status. Dates of post-education Pap and mammography screening up to June 30, 2014 were determined. Analysis in 2016 compared screening uptake and time to screening for UNS participants and controls. From May 15, 2012 to October 31, 2013, a total of 1,993 women attended 145 educational sessions provided in 20 languages. Thirty-five percent (118/331) and 48% (99/206) of CARES participants who were age eligible for Pap and mammography, respectively, were UNS on the education date. Subsequently, 26% and 36% had Pap and mammography, respectively, versus 9% and 14% of UNS controls. ORs for screening within 8 months of follow-up among UNS CARES participants versus their matched controls were 5.1 (95% CI=2.4, 10.9) for Pap and 4.2 (95%=CI 2.3, 7.8) for mammography. Hazard ratios for Pap and mammography were 3.6 (95% CI=2.1, 6.1) and 3.2 (95% CI=2.0, 5.3), respectively. CARES' multifaceted intervention was successful in increasing Pap and mammography screening in this multiethnic under-screened population. Copyright © 2017 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  9. Star-PAP, a poly(A) polymerase, functions as a tumor suppressor in an orthotopic human breast cancer model

    PubMed Central

    Yu, C; Gong, Y; Zhou, H; Wang, M; Kong, L; Liu, J; An, T; Zhu, H; Li, Y

    2017-01-01

    Star-PAP is a noncanonical poly(A) polymerase and required for the expression of a select set of mRNAs. However, the pathological role of Star-PAP in cancer largely remains unknown. In this study, we observed decreased expression of Star-PAP in breast cancer cell lines and tissues. Ectopic Star-PAP expression inhibited proliferation as well as colony-forming ability of breast cancer cells. In breast cancer patients, high levels of Star-PAP correlated with an improved prognosis. Moreover, by regulating the expression of BIK (BCL2-interacting killer), Star-PAP induced apoptosis of breast cancer cells through the mitochondrial pathway. The growth of breast cancer xenografts in NOD/SCID mice was also inhibited by the doxycycline-induced Star-PAP overexpression. Furthermore, Star-PAP sensitized breast cancer cells to chemotherapy drugs both in vitro and in vivo. In mammary epithelial cells, Star-PAP knockdown partially transformed these cells and induced them to undergo epithelial–mesenchymal transition (EMT). These findings suggested that Star-PAP possesses tumor-suppressing activity and can be a valuable target for developing new cancer therapeutic strategies. PMID:28151486

  10. Association between sexual behavior and cervical cancer screening.

    PubMed

    Smith, Anthony M A; Heywood, Wendy; Ryall, Richard; Shelley, Julia M; Pitts, Marian K; Richters, Juliet; Simpson, Judy M; Patrick, Kent

    2011-07-01

    Not much is known about whether women who follow Pap testing recommendations report the same pattern of sexual behavior as women who do not. Data come from part of a larger population-based computer-assisted telephone survey of 8656 Australians aged 16-64 years resident in Australian households with a fixed telephone line (Australian Longitudinal Study of Health and Relationships [ALSHR]). The main outcome measure in the current study was having had a Pap test in the past 2 years. Data on a weighted sample of 4052 women who reported sexual experience (ever had vaginal intercourse) were analyzed. Overall, 73% of women in the sample reported having a Pap test in the past 2 years. Variables individually associated with Pap testing behavior included age, education, occupation, cohabitation status, residential location, tobacco and alcohol use, body mass index (BMI), lifetime and recent number of opposite sex partners, sexually transmitted infection (STI) history, and condom reliance for contraception. In adjusted analyses, women in their 30s, those who lived with their partner, and nonsmokers were more likely to have had a recent Pap test. Those who drank alcohol at least weekly were more likely to have had a recent test than irregular drinkers or nondrinkers. Women with no sexual partners in the last year were less likely to have had a Pap test, and women who reported a previous STI diagnosis were more likely to have had a Pap test in the past 2 years. There are differences in Pap testing behavior among Australian women related to factors that may affect their risk of developing cervical abnormalities. Younger women and regular smokers were less likely to report a recent test. Screening programs should consider the need to focus recruitment strategies for these women.

  11. Benchmarking CIN3+ risk as the basis for incorporating HPV and Pap cotesting into cervical screening and management guidelines

    PubMed Central

    Katki, Hormuzd A.; Schiffman, Mark; Castle, Philip E.; Fetterman, Barbara; Poitras, Nancy E.; Lorey, Thomas; Cheung, Li C.; Raine-Bennett, Tina R.; Gage, Julia C.; Kinney, Walter K.

    2013-01-01

    Objective In 2012, the United States Preventive Services Task Force (USPSTF) and a consensus of 25 organizations endorsed concurrent cytology and HPV testing (“cotesting”) for cervical cancer screening. Past screening and management guidelines were implicitly based on risks defined by Pap-alone, without consideration of HPV test results. To promote management that is consistent with accepted practice, new guidelines incorporating cotesting should aim to achieve equal management of women at equal risk of cervical intraepithelial neoplasia grade 3 and cancer (CIN3+). Methods We estimated cumulative 5-year risks of CIN3+ for 965,360 women aged 30–64 undergoing cotesting at Kaiser Permanente Northern California 2003–2010. We calculated the implicit risk thresholds for Pap-alone and applied them for new management guidance on HPV and Pap cotesting, citing 2 examples: HPV-positive/ASC-US and HPV-negative/Pap-negative. We call this guidance process “benchmarking”. Results LSIL, for which immediate colposcopy is prescribed, carries 5-year CIN3+ risk of 5.2%, suggesting that test results with similar risks should be managed with colposcopy. Similarly, ASC-US (2.6% risk) is managed with 6–12 month follow-up and Pap-negative (0.26% risk) is managed with 3-year follow-up. The 5-year CIN3+ risk for women with HPV-positive/ASC-US was 6.8% (95%CI 6.2% to 7.6%). This is greater than the 5.2% risk implicitly leading to referral to colposcopy, consistent with current management recommendations that HPV-positive/ASC-US should be referred for immediate colposcopy. The 5-year CIN3+ risk for women with HPV-negative/Pap-negative was 0.08% (95%CI 0.07% to 0.09%), far below the 0.26% implicitly required for a 3-year return and justifying a longer (e.g., 5-year) return. Conclusions Using the principle of “equal management of equal risks,” benchmarking to implicit risk thresholds based on Pap-alone can be used to achieve safe and consistent incorporation of cotesting. PMID:23519302

  12. Application of ATC/DDD methodology to evaluate perioperative antimicrobial prophylaxis.

    PubMed

    Akalin, Serife; Kutlu, Selda Sayin; Cirak, Bayram; Eskiçorapcı, Saadettin Yilmaz; Bagdatli, Dilek; Akkaya, Semih

    2012-02-01

    To evaluate quality of perioperative antibiotic prophylaxis (PAP) and to calculate the cost per procedure in a Turkish university hospital. A 352-bed teaching hospital in Denizli, Turkey. An prospective audit was performed between July and October 2010. All clean, clean-contaminated and contaminated elective surgical procedures in ten surgical wards were recorded. Antimicrobial use was calculated per procedure using the ATC-DDD system. The appropriateness of antibiotic use for each procedure was evaluated according to international guidelines on PAP. In addition, the cost per procedure was calculated. Overall, in 577 of the 625 (92.3%) of the studied procedures, PAP was used. PAP was indicated in 12.5% of the group where it was not used, and not indicated in 7.1% of the group where it was used. Unnecessarily prolonged antimicrobial prophylaxis was observed in 56.9% of the procedures, mean duration was 2.6 ± 2.7 days. The most frequently used antimicrobials were cefazolin (117.9 DDD/100-operation) and sulbactam/ampicillin (102.2 DDD/100-operation). The timing of the starting dose was appropriate in 545 procedures (94.5%). In the group that received PAP, only 80 (13.7%) of the procedures were found to be fully appropriate and correct. The density of antimicrobial use per operation was 2.8 DDD. The mean cost of the use of prophylactic antimicrobials 18.6 per procedure. The density of antimicrobial use in PAP was found to be very high in our hospital. Antibiotic overuse extended into the postoperative period.

  13. Cellular immune response to β2-glycoprotein-I valine/leucine247 phenotypes in Mexican patients with primary antiphospholipid syndrome.

    PubMed

    Núñez-Álvarez, Carlos A; Hernández-Ramírez, Diego F; Martinez-Castillo, Araceli; Pascual Ramos, Virginia; Cabiedes, Javier; Ortega, Alicia; Cabral, Antonio R

    2017-02-01

    Homozygote genotype V 247 of the β 2 -glycoprotein-I (β 2 GP-I) gene has been associated with anti-β 2 GP-I and thrombosis in patients with primary anti-phospholipid syndrome APS (PAPS). However, the cellular immune response to β 2 GP-I 247 has been little studied. To evaluate the immune cellular proliferation in response to native and non-native β 2 GP-I 247 valine/leucine phenotype from Mexican patients with PAPS. We studied 10 patients with PAPS and 10 healthy control subjects (HC). The polymorphism at position 247 of the β 2 GP-I gene was determined by PCR-RFLP and the corresponding β 2 GP-I protein was subsequently purified from normal human plasma by affinity chromatography. PBMC purified from patients and controls were stimulated with β 2 GP-I under native and in non native (reduced) conditions. We also determined the anti-β 2 GP-I production in vitro by B cell clones (EBV) generated in cocultures experiments. Differential Scanning Calorimetry (DSC) was studied to determine the structural differences between the β 2 GP-I 247 valine/leucine isoforms. Cytokine profile (IL-2, IL-4, IL-6, TNFα, INFγ) was evaluated in culture supernatants. PAPS and healthy control PBMCs had a higher proliferative response when stimulated with β 2 GP-I under reduced cultures conditions compared to non-denatured conditions. PBMCs response from PAPS patients was higher. We observed more cell proliferation in response to β 2 GP-I 247 valine/leucine or valine isoforms in non-native conditions. In contrast, this response was not significant against β 2 GP-I 247 leucine. These findings were T CD4 + -dependent. Similar results were obtained with B cell clones derived from PAPS patients, which showed more pronounced proliferation in non native conditions and higher against β 2 GP-I 247 valine. No differences were found in anti-β 2 GP-I production, but high levels of IL-6 in vitro were identified. The structural analysis of both β 2 GP-I 247 isoforms by DSC showed a major conformational change due to a single mutation in the β 2 GP-I variants. PAPS PBMCs had a higher cellular response against β 2 GP-I 247 in non-native culture conditions preferentially to the β 2 GP-I 247 valine phenotype. This effect is T CD4 + dependent and appears to be driven by tertiary structural changes adopted by β 2 GP-I 247 polymorphism. Copyright © 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

  14. Atypical Findings on Cervicovaginal Smears Correlate with Cervical Involvement by Malignant Mixed Müllerian Tumors of the Uterus.

    PubMed

    Hanley, Krisztina Z; Oprea-Ilies, Gabriela; Ormenisan, Claudia; Seydafkan, Shabnam; Mosunjac, Marina B

    2015-01-01

    A malignant mixed müllerian tumor (MMMT) is a high-grade neoplasm commonly arising from the uterus. Patients present with bleeding and a mass protruding from the cervix. This study was designed to correlate Papanicolaou (Pap) smear findings with histological findings in women diagnosed with MMMT. Women diagnosed with MMMT were identified. Preoperative Pap tests were correlated with histological findings. Statistical analysis was performed to assess associations between abnormal Pap tests and histological findings. Forty patients with MMMT were included in the study. Age ranged from 37-85 years and tumor size ranged from 1.2 to 21 cm. In presurgical Pap tests (4 conventional and 36 liquid based), 11 smears (27.5%) were diagnosed as negative, 5 (12.5%) as atypical squamous cells of undetermined significance, 6 (15%) as atypical glandular cells, 16 (40%) as malignant and 2 (5%) as high-grade squamous intraepithelial lesion. Malignant cells detected on Pap smears showed a strong correlation with endocervical involvement by MMMT (p = 0.002). Larger tumors were more likely to involve the cervix (p = 0.0115). The Pap test can predict cervical involvement by MMMT. On Pap smears, MMMT cells showed no correlation with other adverse histological features (lymphovascular invasion, myoinvasion or adnexal involvement). © 2015 S. Karger AG, Basel.

  15. Influence of Hormonal Contraceptive Use and Health Beliefs on Sexual Orientation Disparities in Papanicolaou Test Use

    PubMed Central

    Corliss, Heather L.; Missmer, Stacey A.; Frazier, A. Lindsay; Rosario, Margaret; Kahn, Jessica A.; Austin, S. Bryn

    2014-01-01

    Objectives. Reproductive health screenings are a necessary part of quality health care. However, sexual minorities underutilize Papanicolaou (Pap) tests more than heterosexuals do, and the reasons are not known. Our objective was to examine if less hormonal contraceptive use or less positive health beliefs about Pap tests explain sexual orientation disparities in Pap test intention and utilization. Methods. We used multivariable regression with prospective data gathered from 3821 females aged 18 to 25 years in the Growing Up Today Study (GUTS). Results. Among lesbians, less hormonal contraceptive use explained 8.6% of the disparities in Pap test intention and 36.1% of the disparities in Pap test utilization. Less positive health beliefs associated with Pap testing explained 19.1% of the disparities in Pap test intention. Together, less hormonal contraceptive use and less positive health beliefs explained 29.3% of the disparities in Pap test intention and 42.2% of the disparities in Pap test utilization. Conclusions. Hormonal contraceptive use and health beliefs, to a lesser extent, help to explain sexual orientation disparities in intention and receipt of a Pap test, especially among lesbians. PMID:23763393

  16. Evaluation of a nurse-designed mobile health education application to enhance knowledge of Pap testing.

    PubMed

    Christensen, Stacy

    2014-01-01

    An experimental study was conducted using a 2-group randomized control pretest/ posttest design to determine if knowledge about Pap testing could be increased through use of a nurse-designed mobile smartphone app developed to educate individuals about the Pap test. A 14-item pretest survey of knowledge about Pap tests was distributed to women attending a university in New England. Participants in the intervention group were provided with an Android device on which a digital health education application on Pap testing had been downloaded. The control group was given a standard pamphlet on Pap testing., Paired t test results demonstrated that knowledge scores on the posttest increased significantly in both groups, but were significantly higher in the intervention group. User satisfaction with the app was high. The results of this study may enhance nursing care by informing nurses about a unique way of learning about Pap testing to recommend to patients.

  17. Induced sputum deposition improves diagnostic yields of pulmonary alveolar proteinosis: A clinicopathological and methodological study of 17 cases.

    PubMed

    Huang, Ziling; Yi, Xianghua; Luo, Benfang; Zhu, Jian; Wu, Yunjin; Jiang, Wenxia; Chu, Haiqing; Yang, Zhongmin; Li, Shuai; Zhu, Hailong; Zhang, Suxia; Zhang, Lanjing; Zeng, Yu

    2016-01-01

    Pulmonary alveolar proteinosis (PAP) is a rare diffuse lung disease characterized by the accumulation of intra-alveolar lipoprotein-like surfactants. Lung core biopsy and bronchoalveolar lavage (BAL) fluid are currently the two major sources of sampling for diagnosis. In the present study, we assessed the value of induced sputum in diagnosing PAP by transmission electron microscopy and examined the PAP 2-year death rate in Asians. Transmission electron microscopy was performed on the samples from 17 patients with PAP, 13 patients with inflammatory lung diseases, and 13 healthy adults. The PAP patients were followed up for 3-156 months, and inflammatory lung diseases patients or healthy adults for 12-36 months. The ultrastructural features including diagnostic lamellar bodies of induced sputum deposition (ISD) samples were similar to that of the BAL fluid sediment. However, the rates of lamellar bodies were 73.7% in the ISD group, significantly higher than the spontaneous sputum deposition (SSD) group (42.1%, P < .0487) and similar to the BAL sediment (76.2%) and the lung biopsy (54.5%) groups. The overall 2-year death rate of our PAP patients was 17.6% (3/17), not statistically different from the healthy adults and patients with inflammatory diseases (0/13, P = .237 for both). ISD may be the preferred non-invasive sampling method for diagnosing PAP by electronic microscopy because of the higher diagnostic yield than SSD. The diagnostic yields of this noninvasive method were similar to that of lung core biopsy and BAL.

  18. Social and Structural Determinants of Cervical Health among Women Engaged in HIV Care

    PubMed Central

    Bynum, Shalanda A.; Wigfall, Lisa T.; Brandt, Heather M.; Julious, Carmen Hampton; Glover, Saundra H.; Hébert, James R.

    2016-01-01

    Cervical cancer prevention/control efforts among women living with HIV/AIDS (WLH) are socially and structurally challenging. Healthcare access and perceived HIV stigma and discrimination are factors that may challenge risk reduction efforts. This study examined socio-structural determinants of cervical cancer screening among women engaged in HIV care. One hundred forty-five WLH seeking health/social services from AIDS Service Organizations in the southeastern US completed a questionnaire assessing factors related to cervical cancer prevention/control. Ninety percent were African American, mean age 46.15 ± 10.65 years. Eighty-one percent had a Pap test <1 year ago. Low healthcare access was positively associated with having a Pap test <1 year ago, (Odds ratio [OR] 3.80; 95 % Confidence interval [CI] 1.34–10.78). About 36 % reported ≥2 Pap tests during the first year after HIV diagnosis. Lower educational attainment was positively associated with having ≥2 Pap tests, OR 3.22; CI 1.08–9.62. Thirty-five percent reported more frequent Pap tests after diagnosis. Lower income was moderately associated with more frequent Pap tests post-diagnosis, OR 2.47; CI .98–6.23. Findings highlight the successes of HIV initiatives targeting socio-economically disadvantaged women and provide evidence that health policy aimed at providing and expanding healthcare access for vulnerable WLH has beneficial health implications. PMID:26955821

  19. Inflammation and nerve injury induce expression of pancreatitis-associated protein-II in primary sensory neurons.

    PubMed

    He, Shao-Qiu; Yao, Jun-Ru; Zhang, Fang-Xiong; Wang, Qiong; Bao, Lan; Zhang, Xu

    2010-04-26

    Pancreatitis-associated protein (PAP)-I and -II, lectin-related secretory proteins, are members of the regenerating gene (Reg) family. Although expression of PAP-I was found in the dorsal root ganglion (DRG) neurons following peripheral nerve injury and cystitis, whether PAP-II could be expressed in DRG neurons in chronic pain models remains unclear. The present study shows an inflammation- and nerve injury-triggered expression of PAP-II in rat DRG neurons. In situ hybridization showed that only a few DRG neurons normally contained PAP-I and -II mRNAs. After peripheral inflammation, PAP-I and -II mRNAs were present in over half of small DRG neurons. Such an elevated expression of PAP-I and -II reached the peak level on the second day. Immunostaining showed that the expression of PAP-II was mostly increased in the isolectin B4-positive subset of small DRG neurons after inflammation. Furthermore, the expression of PAP-II was also induced in DRG neurons after peripheral nerve injury. Interestingly, PAP-II expression was shifted from small neurons on day 2 to large DRG neurons that expressed neuropeptide Y during the later post-injury days. These results suggest that PAP-II may play potential roles in the modulation of spinal sensory pathways in pathological pain states.

  20. INACTIVATION OF LACTATE DEHYDROGENASE BY SEVERAL CHEMICALS: IMPLICATIONS FOR IN VITRO TOXICOLOGY STUDIES

    PubMed Central

    Kendig, Derek M.; Tarloff, Joan B.

    2007-01-01

    Lactate dehydrogenase (LDH) release is frequently used as an end-point for cytotoxicity studies. We have been unable to measure LDH release during studies using para-aminophenol (PAP) in LLC-PK1 cells. When LLC-PK1 cells were incubated with either PAP (0–10 mM) or menadione (0–1000 μM), viability was markedly reduced when assessed by alamar Blue or total LDH activity but not by release of LDH into the incubation medium. In addition, we incubated cells with PAP or menadione and compared LDH activity using two different assays. Both assays confirmed our observation of decreased LDH activity in cell lysates without corresponding increases in LDH activity in incubation media. Using purified LDH and 10 mM PAP, we that PAP produced loss of LDH activity that was inversely proportional to the amount of LDH initially added. In additional experiments, we incubated 0.5 units of LDH for 1 h with varying concentrations of PAP, menadione, hydrogen peroxide (H2O2) or cisplatin. All four chemicals produced concentration-dependent decreases in LDH activity. In previous experiments, inclusion of antioxidants such as reduced glutathione (GSH) and ascorbate protected cells from PAP toxicity. GSH (1 mM) preserved LDH activity in the presence of toxicants while ascorbate (1 mM) only prevented LDH loss induced by PAP. These studies suggest that LDH that is released into the incubation medium is susceptible to degradation when reactive chemicals are present. PMID:17079110

  1. Overexpression of the PAP1 Transcription Factor Reveals a Complex Regulation of Flavonoid and Phenylpropanoid Metabolism in Nicotiana tabacum Plants Attacked by Spodoptera litura

    PubMed Central

    Mitsunami, Tomoko; Nishihara, Masahiro; Galis, Ivan; Alamgir, Kabir Md; Hojo, Yuko; Fujita, Kohei; Sasaki, Nobuhiro; Nemoto, Keichiro; Sawasaki, Tatsuya; Arimura, Gen-ichiro

    2014-01-01

    Anthocyanin pigments and associated flavonoids have demonstrated antioxidant properties and benefits for human health. Consequently, current plant bioengineers have focused on how to modify flavonoid metabolism in plants. Most of that research, however, does not consider the role of natural biotic stresses (e.g., herbivore attack). To understand the influence of herbivore attack on the metabolic engineering of flavonoids, we examined tobacco plants overexpressing the Arabidopsis PAP1 gene (encoding an MYB transcription factor), which accumulated anthocyanin pigments and other flavonoids/phenylpropanoids. In comparison to wild-type and control plants, transgenic plants exhibited greater resistance to Spodoptera litura. Moreover, herbivory suppressed the PAP1-induced increase of transcripts of flavonoid/phenylpropanoid biosynthetic genes (e.g., F3H) and the subsequent accumulation of these genes' metabolites, despite the unaltered PAP1 mRNA levels after herbivory. The instances of down-regulation were independent of the signaling pathways mediated by defense-related jasmonates but were relevant to the levels of PAP1-induced and herbivory-suppressed transcription factors, An1a and An1b. Although initially F3H transcripts were suppressed by herbivory, after the S. litura feeding was interrupted, F3H transcripts increased. We hypothesize that in transgenic plants responding to herbivory, there is a complex mechanism regulating enriched flavonoid/phenylpropanoid compounds, via biotic stress signals. PMID:25268129

  2. Coagulation and fibrinolysis in inflammatory bowel disease and in giant cell arteritis.

    PubMed

    Vrij, Anton A; Rijken, Joop; van Wersch, Jan W J; Stockbrügger, Reinhold W

    2003-01-01

    In inflammatory bowel disease (IBD), gut microvascular thrombosis as well as thromboembolic complications have repeatedly been observed. We examined the long-term course of markers of coagulation and fibrinolysis in relation to clinical disease activity. In a prospective study, prothrombin fragment 1 and 2 (F1.2), thrombin-antithrombin complex (TAT), antithrombin, D-dimer, plasmin-alpha(2)-antiplasmin complex (PAP) and plasminogen activator inhibitor-1 (PAI-1) were measured in 20 patients with Crohn's disease (CD), 18 with ulcerative colitis (UC), and 19 with giant cell arteritis during active and inactive disease, as well as in 51 controls without inflammation. Levels of F1.2, TAT, D-dimer, PAP and PAI-1 were significantly higher in active versus inactive CD and UC. However, even after 12 months of follow-up, in CD and UC the mean levels of F1.2, D-dimer and PAP were significantly higher than the levels of the controls. Levels of F1.2, D-dimer and PAP were markedly raised for a long time in clinically inactive IBD, underlining a chronic state of hypercoagulation and enhanced fibrinolysis. Copyright 2003 S. Karger AG, Basel

  3. Increasing Pap Smear Utilization Among Samoan Women: Results from a Community Based Participatory Randomized Trial

    PubMed Central

    Mishra, Shiraz I.; Luce, Pat H.; Baquet, Claudia R.

    2013-01-01

    Background We tested the effectiveness of a theory-guided, culturally tailored cervical cancer education program designed to increase Pap smear use among Samoan women residing in the U.S. Territory of American Samoa. Methods We used a two-group, pretest-posttest design. The sample comprised 398 Samoan women age 20 and older who we recruited from Samoan churches. Women in the intervention group received a culturally tailored cervical cancer education program in three weekly sessions. The primary outcome was self-reported receipt of a Pap smear. Results Overall, there was a significant intervention effect, with intervention compared with control group women twice (adjusted odds ratio = 2.0, 95% confidence interval = 1.3–3.2, p<.01) as likely to self-report Pap smear use at the posttest. Conclusions The findings support the efficacy of the multifaceted, theory-guided, culturally tailored community-based participatory cervical cancer education program for Samoan women in effecting positive changes in Pap smear use and cervical cancer related knowledge and attitudes. PMID:19711495

  4. A heterodimer of human 3'-phospho-adenosine-5'-phosphosulphate (PAPS) synthases is a new sulphate activating complex

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Grum, Daniel, E-mail: daniel.grum@uni-due.de; Boom, Johannes van den, E-mail: johannes.van-den-boom@stud.uni-due.de; Neumann, Daniel, E-mail: dneuman@gwdg.de

    2010-05-07

    3'-Phospho-adenosine-5'-phosphosulphate (PAPS) synthases are fundamental to mammalian sulphate metabolism. These enzymes have recently been linked to a rising number of human diseases. Despite many studies, it is not yet understood how the mammalian PAPS synthases 1 and 2 interact with each other. We provide first evidence for heterodimerisation of these two enzymes by pull-down assays and Foerster resonance energy transfer (FRET) measurements. Kinetics of dimer dissociation/association indicates that these heterodimers form as soon as PAPSS1 and -S2 encounter each other in solution. Affinity of the homo- and heterodimers were found to be in the low nanomolar range using anisotropy measurementsmore » employing proteins labelled with the fluorescent dye IAEDANS that - in spite of its low quantum yield - is well suited for anisotropy due to its large Stokes shift. Within its kinase domain, the PAPS synthase heterodimer displays similar substrate inhibition by adenosine-5'-phosphosulphate (APS) as the homodimers. Due to divergent catalytic efficacies of PAPSS1 and -S2, the heterodimer might be a way of regulating PAPS synthase function within mammalian cells.« less

  5. Systolic pulmonary artery pressure assessed during routine exercise Doppler echocardiography: insights of a real-world setting in patients with elevated pulmonary pressures.

    PubMed

    Korff, Susanne; Enders-Gier, Patricia; Uhlmann, Lorenz; Aurich, Matthias; Greiner, Sebastian; Hirschberg, Kristof; Katus, Hugo A; Mereles, Derliz

    2018-03-19

    Pulmonary hypertension is a marker of disease severity. Exercise Doppler echocardiography (EDE) has proven to be feasible and reliable to assess pulmonary pressure. Increase in systolic pulmonary artery pressure (sPAP) has diagnostic and prognostic value in controlled studies. However, its value when assessed during routine examination in patients with cardiopulmonary diseases and resting sPAP > 35 mmHg is not clearly defined. Clinical documentation and offline reevaluation of digitally stored EDE examinations of patients with appropriate clinical indications for EDE were analyzed. N = 278 patients with sPAP at rest > 35 mmHg met inclusion criteria. One patient was lost to follow-up. Mean age of patients was 72 ± 10 years, 178 (64%) of the study population were men. There were no relevant differences among survivors and non-survivors concerning comorbidities. Exercise performance (3.6 ± 1.2 vs. 4.9 ± 1.4 MET, p < 0.001) was lower, whereas sPAP during exercise was higher (67.3 ± 14.7 vs. 62.1 ± 13.2 mmHg, p = 0.027) in non-survivors. Univariate predictors of all-cause mortality were NYHA functional class III (HR = 2.56, p < 0.001), ≥ 2-vessels coronary artery disease (CAD) (HR = 1.93, p = 0.04), left atrial diameter > 45 mm (HR = 2.58, p < 0.001), rest sPAP > 42 mmHg (HR = 1.94, p = 0.010) and ΔsPAP increase ≥ 0.23 mmHg/Watt (HF = 1.92, p = 0.010). After multivariate analysis, NYHA functional class III (HR = 2.35, p < 0.001), LA diameter (HR = 2.28, p = 0.003) and sPAP increase ≥ 0.23 mmHg/Watt (HF = 2.19, p = 0.002) remained significant predictors of mortality, whereas a double product (HR = 0.42, p = 0.005) was associated with better prognosis. sPAP assessment during routine EDE provides relevant prognostic information comparable to findings in studies in selected populations. A higher sPAP increase at lower exercise performance shows significant association with increased of mortality.

  6. Portal Annular Pancreas

    PubMed Central

    Harnoss, Jonathan M.; Harnoss, Julian C.; Diener, Markus K.; Contin, Pietro; Ulrich, Alexis B.; Büchler, Markus W.; Schmitz-Winnenthal, Friedrich H.

    2014-01-01

    Abstract Portal annular pancreas (PAP) is an asymptomatic congenital pancreas anomaly, in which portal and/or mesenteric veins are encased by pancreas tissue. The aim of the study was to determine the role of PAP in pancreatic surgery as well as its management and potential complication, specifically, postoperative pancreatic fistula (POPF). On the basis of a case report, the MEDLINE and ISI Web of Science databases were systematically reviewed up to September 2012. All articles describing a case of PAP were considered. In summary, 21 studies with 59 cases were included. The overall prevalence of PAP was 2.4% and the patients' mean (SD) age was 55.9 (16.2) years. The POPF rate in patients with PAP (12 pancreaticoduodenectomies and 3 distal pancreatectomies) was 46.7% (in accordance with the definition of the International Study Group of Pancreatic Surgery). Portal annular pancreas is a quite unattended pancreatic variant with high prevalence and therefore still remains a clinical challenge to avoid postoperative complications. To decrease the risk for POPF, attentive preoperative diagnostics should also focus on PAP. In pancreaticoduodenectomy, a shift of the resection plane to the pancreas tail should be considered; in extensive pancreatectomy, coverage of the pancreatic remnant by the falciform ligament could be a treatment option. PMID:25207658

  7. The glycolytic metabolite methylglyoxal activates Pap1 and Sty1 stress responses in Schizosaccharomyces pombe.

    PubMed

    Zuin, Alice; Vivancos, Ana P; Sansó, Miriam; Takatsume, Yoshifumi; Ayté, José; Inoue, Yoshiharu; Hidalgo, Elena

    2005-11-04

    Methylglyoxal, a toxic metabolite synthesized in vivo during glycolysis, inhibits cell growth. One of the mechanisms protecting eukaryotic cells against its toxicity is the glyoxalase system, composed of glyoxalase I and II (glo1 and glo2), which converts methylglyoxal into d-lactic acid in the presence of glutathione. Here we have shown that the two principal oxidative stress response pathways of Schizosaccharomyces pombe, Sty1 and Pap1, are involved in the response to methylglyoxal toxicity. The mitogen-activated protein kinase Sty1 is phosphorylated and accumulates in the nucleus following methylglyoxal treatment. Moreover, glo2 expression is induced by methylglyoxal and environmental stresses in a Sty1-dependent manner. The transcription factor Pap1 also accumulates in the nucleus, activating the expression of its target genes following methylglyoxal treatment. Our studies showed that the C-terminal cysteine-rich domain of Pap1 is sufficient for methylglyoxal sensing. Furthermore, the redox status of Pap1 is not changed by methylglyoxal. We propose that methylglyoxal treatment triggers Pap1 and Sty1 nuclear accumulation, and we describe the molecular basis of such activation mechanisms. In addition, we discuss the potential physiological significance of these responses to a natural toxic metabolite.

  8. Pulmonary Vascular Response Patterns During Exercise in Left Ventricular Systolic Dysfunction Predict Exercise Capacity and Outcomes

    PubMed Central

    Lewis, Gregory D.; Murphy, Ryan M.; Shah, Ravi V.; Pappagianopoulos, Paul P.; Malhotra, Rajeev; Bloch, Kenneth D.; Systrom, David M.; Semigran, Marc J.

    2012-01-01

    Background Elevated resting pulmonary arterial pressure (PAP) in patients with left ventricular systolic dysfunction (LVSD) purports a poor prognosis. However, PAP response patterns to exercise in LVSD and their relationship to functional capacity and outcomes have not been characterized. Methods and Results Sixty consecutive patients with LVSD (age 60±12 years, LV ejection fraction 0.31±0.07, mean±SD) and 19 controls underwent maximum incremental cardiopulmonary exercise testing with simultaneous hemodynamic monitoring. During low-level exercise (30 Watts), LVSD subjects compared to controls, had greater augmentation in mean PAPs (15±1 vs. 5±1 mmHg), transpulmonary gradients (5±1 vs. 1±1 mmHg), and effective PA elastance (0.05±0.02 vs. −0.03±0.01 mmHg/ml, p<0.0001 for all). A linear increment in PAP relative to work (0.28±0.12 mmHg/watt) was observed in 65% of LVSD patients, which exceeded that observed in controls (0.07±0.02 mmHg/watt, P<0.0001). Exercise capacity and survival was worse in patients with a PAP/watt slope above the median than in patients with a lower slope. In the remaining 35% of LVSD patients, exercise induced a steep initial increment in PAP (0.41±0.16 mmHg/watt) followed by a plateau. The plateau pattern, compared to a linear pattern, was associated with reduced peak VO2 (10.6±2.6 vs. 13.1±4.0 ml/kg/min, P=0.005), lower right ventricular stroke work index augmentation with exercise (5.7±3.8 vs. 9.7±5.0 g/m2, P=0.002), and increased mortality (HR 8.1, 95% CI 2.7-23.8, P<0.001). Conclusions A steep increment in PAP during exercise and failure to augment PAP throughout exercise are associated with decreased exercise capacity and survival in patients with LVSD, and may therefore represent therapeutic targets. Clinical Trial Information URL: http://www.clinicaltrials.gov. Unique Identifier: NCT00309790) PMID:21292991

  9. An audit of the cervical cancer screening histories of 246 women with carcinoma.

    PubMed

    Duggan, Máire A; Nation, Jill

    2012-07-01

    Women with cervical carcinoma and residing in the Calgary Health Region between 1996 and 2001 were audited to characterize factors in the opportunistic cervical cancer screening pathway contributing to screening failures. The cohort consisted of 246 women. Information on their Pap tests and colposcopic/gynecologic examinations was obtained from the files of Calgary Laboratory Services and their colposcopic/cancer center treatment charts. Screening failure factors were defined, and frequencies were calculated. Screening failure factors were as follows: (1) 41 (16.7%) were not screened, that is, no Pap test screening; (2) 29 (11.8%) were underscreened, that is, no Pap test within 12 months of diagnosis; (3) 28 (13.7%) were undersampled, that is, the Pap test result was negative; (4) 34 (13.8%) had no referral for a colposcopy/gynecology examination, and/or it was delayed for more than 3 months; (5) 18 (13.2%) had delayed referral for examination of an atypical glandular cell-high-grade squamous intraepithelial lesion and higher Pap test for more than 3 months; and (6) 73 (55.3%) were underdiagnosed, that is, the diagnosis in colposcopy examination was less than malignant. Underreported Pap tests and delayed Pap test reporting could not be fully investigated, but limited evidence suggested that underreporting contributed to some failures. Factors other than recruitment to cytological screening need targeted improvement if the region's cervical cancer prevention program is to be more effective.

  10. TALEN-mediated functional correction of human iPSC-derived macrophages in context of hereditary pulmonary alveolar proteinosis.

    PubMed

    Kuhn, Alexandra; Ackermann, Mania; Mussolino, Claudio; Cathomen, Toni; Lachmann, Nico; Moritz, Thomas

    2017-11-09

    Hereditary pulmonary alveolar proteinosis (herPAP) constitutes a rare, life threatening lung disease characterized by the inability of alveolar macrophages to clear the alveolar airspaces from surfactant phospholipids. On a molecular level, the disorder is defined by a defect in the CSF2RA gene coding for the GM-CSF receptor alpha-chain (CD116). As therapeutic options are limited, we currently pursue a cell and gene therapy approach aiming for the intrapulmonary transplantation of gene-corrected macrophages derived from herPAP-specific induced pluripotent stem cells (herPAP-iPSC) employing transcriptional activator-like effector nucleases (TALENs). Targeted insertion of a codon-optimized CSF2RA-cDNA driven by the hybrid cytomegalovirus (CMV) early enhancer/chicken beta actin (CAG) promoter into the AAVS1 locus resulted in robust expression of the CSF2RA gene in gene-edited herPAP-iPSCs as well as thereof derived macrophages. These macrophages displayed typical morphology, surface phenotype, phagocytic and secretory activity, as well as functional CSF2RA expression verified by STAT5 phosphorylation and GM-CSF uptake studies. Thus, our study provides a proof-of-concept, that TALEN-mediated integration of the CSF2RA gene into the AAVS1 safe harbor locus in patient-specific iPSCs represents an efficient strategy to generate functionally corrected monocytes/macrophages, which in the future may serve as a source for an autologous cell-based gene therapy for the treatment of herPAP.

  11. p-Aminophenol-induced hepatotoxicity in hamsters: role of glutathione.

    PubMed

    Fu, Xin; Chen, Theresa S; Ray, Mukunda B; Nagasawa, Herbert T; Williams, Walter M

    2004-01-01

    p-Aminophenol (PAP) is a widely used industrial chemical and a known nephrotoxin. Recently, it was found to also cause hepatotoxicity and glutathione (GSH) depletion in mice. The exact mechanism of liver toxicity is not known. The aims of this study were to determine whether PAP can cause acute hepatotoxicity in hamsters and to further investigate the role of GSH in PAP-induced toxicity. PAP was administered ip to hamsters in doses of 200-800 mg/kg. Liver damage at 24 h after PAP administration was assessed by elevations in plasma enzyme activities and histopathologic examination. GSH and cysteine (Cys) levels in liver at 4 h were determined by HPLC. PAP decreased hepatic GSH concentration to 8% and Cys to 30% of vehicle control values. It increased plasma glutamic pyruvic transaminase (GPT) activity by 47-fold and sorbitol dehydrogenase (SDH) activity by 113-fold. PAP also caused severe centrilobular hepatocellular necrosis. 2(RS)-n-Propylthiazolidine-4(R)-carboxylic acid (PTCA), a Cys precursor, attenuated the PAP-induced decreases in hepatic sulfhydryl levels; GSH and Cys were 39% and 78% of vehicle controls, respectively. PTCA also attenuated the PAP-induced elevations in plasma enzyme activities and hepatic necrosis. It was concluded that PAP hepatotoxicity is associated with depletion of hepatic GSH and can be prevented by PTCA. Copyright 2004 Wiley Periodicals, Inc.

  12. Depression score changes in response to sleep disordered breathing treatment with positive airway pressure in a large clinic-based cohort.

    PubMed

    Relia, Sachin; Thompson, Nicolas R; Mehra, Reena; Moul, Douglas; Katzan, Irene; Foldvary-Schaefer, Nancy; Walia, Harneet K

    2018-03-01

    The clinical-population impact of positive airway pressure (PAP) on depressive symptoms in sleep disordered breathing (SDB) awaits clear documentation. We hypothesized that depressive symptoms improve in response to PAP treatment in a large clinical setting, and that lower socio-economic status poses barriers to full therapeutic response. We performed a retrospective cohort study of SDB patients attending a tertiary ambulatory sleep center between January 1, 2010 and December 31, 2015. Data extracted from electronic health records included Patient Health Questionnaire-9 (PHQ-9) scores, demographic characteristics, PAP adherence, and medical history. Paired- and two-sample t tests were utilized to assess changes in PHQ-9 score according to PAP adherence. Linear regression models were constructed to evaluate the association of socioeconomic status (SES) and other clinical variables on PHQ-9 scores. The cohort consisted of 1981 SDB patients (56.4 ± 13.3 years; 45.7% female; 76.2% Caucasian). Regardless of adherence, PAP therapy improved PHQ-9 scores (- 2.4 ± 4.6, p < 0.0001), with more robust responses in patients with baseline PHQ-9 scores > 10 (- 4.8 ± 5.7; p < 0.0001). Adherent patients had significantly greater improvement (- 2.8 ± 4.4 vs. 1.6 + 4.2, p < 0.0001), and even greater benefit if baseline PHQ-9 was > 10 (-6.0 ± 5.3 vs. - 3.8 ± 4.9, p < 0.001). Patients from lower socioeconomic status and greater depressive symptom had worse post-PAP PHQ-9 scores. PAP therapy and adherence were associated with improvement in depressive symptom severity in this clinical cohort. Patients with lower socioeconomic status derived less therapeutic benefit, suggesting that they faced additional barriers to treatment effectiveness.

  13. Understanding the role of violence in incarcerated women's cervical cancer screening and history.

    PubMed

    Ramaswamy, Megha; Kelly, Patricia J; Koblitz, Amber; Kimminau, Kim S; Engelman, Kimberly K

    2011-07-22

    In this exploratory study the authors investigated characteristics, including reported experiences of violence, related to incarcerated women's self-report of cervical cancer screening and cancer history and treatment. During a four month period in 2010, 204 women in Kansas City jails were surveyed. Multiple logistic regression models were used to examine the relations of socio-demographic and community characteristics and history of violence among the women to their cervical cancer screening, diagnosis, and treatment histories. Forty percent of the women in the current sample reported abnormal Pap histories, though only 6% of all Pap smears done in the U.S. are abnormal. Women who reported abuse histories in this study were found to be more likely to report having ever had an abnormal Pap smear (for physical abuse Odds Ratio [OR] = 6.05; CI 2.36, 15.54 and for past year intimate partner violence OR = 2.41; CI 1.09, 5.31). Participants who did not fear neighborhood violence were less likely to report an abnormal Pap history (OR = 0.57; CI 0.34, 0.96) and more likely to visit a family doctor for their Pap screenings (OR = 1.91; CI 1.01, 3.60). Women who perceived greater neighborhood violence had increased odds of reporting that they received Pap screenings in a hospital setting (OR = 1.47; CI 1.08, 2.00). Frequency of Pap screening did not differ in women who did and did not have fear of neighborhood violence. This study highlights the heightened cervical cancer risk experienced by women with criminal justice histories and suggests that violence at several levels has implications for cervical cancer prevention for these women.

  14. The cell wall-targeted purple acid phosphatase AtPAP25 is critical for acclimation of Arabidopsis thaliana to nutritional phosphorus deprivation.

    PubMed

    Del Vecchio, Hernan A; Ying, Sheng; Park, Joonho; Knowles, Vicki L; Kanno, Satomi; Tanoi, Keitaro; She, Yi-Min; Plaxton, William C

    2014-11-01

    Plant purple acid phosphatases (PAPs) belong to a relatively large gene family whose individual functions are poorly understood. Three PAP isozymes that are up-regulated in the cell walls of phosphate (Pi)-starved (-Pi) Arabidopsis thaliana suspension cells were purified and identified by MS as AtPAP12 (At2g27190), AtPAP25 (At4g36350) and AtPAP26 (At5g34850). AtPAP12 and AtPAP26 were previously isolated from the culture medium of -Pi cell cultures, and shown to be secreted by roots of Arabidopsis seedlings to facilitate Pi scavenging from soil-localized organophosphates. AtPAP25 exists as a 55 kDa monomer containing complex NX(S/T) glycosylation motifs at Asn172, Asn367 and Asn424. Transcript profiling and immunoblotting with anti-AtPAP25 immune serum indicated that AtPAP25 is exclusively synthesized under -Pi conditions. Coupled with potent mixed-type inhibition of AtPAP25 by Pi (I50 = 50 μm), this indicates a tight feedback control by Pi that prevents AtPAP25 from being synthesized or functioning as a phosphatase except when Pi levels are quite low. Promoter-GUS reporter assays revealed AtPAP25 expression in shoot vascular tissue of -Pi plants. Development of an atpap25 T-DNA insertion mutant was arrested during cultivation on soil lacking soluble Pi, but rescued upon Pi fertilization or complementation with AtPAP25. Transcript profiling by quantitative RT-PCR indicated that Pi starvation signaling was attenuated in the atpap25 mutant. AtPAP25 exhibited near-optimal phosphatase activity with several phosphoproteins and phosphoamino acids as substrates. We hypothesize that AtPAP25 plays a key signaling role during Pi deprivation by functioning as a phosphoprotein phosphatase rather than as a non-specific scavenger of Pi from extracellular P-monoesters. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.

  15. Correlation of echocardiographic and hemodynamic parameters in pulmonary hypertension assessment prior to heart transplantation.

    PubMed

    Mogollón Jiménez, M V; Escoresca Ortega, A M; Cabeza Letrán, M L; Hinojosa Pérez, R; Lage Gallé, E; Sobrino Márquez, J M; Herruzo Avilés, A; Romero Rodríguez, N; Frutos López, M; Pérez de la Yglesia, R; Martínez Martínez, A

    2008-11-01

    Invasive assessment of pulmonary artery pressure (PAP), via right heart catheterization, is part of the usual protocol prior to heart transplantation. Echocardiography is considered a valuable technique to evaluate PAP. We sought to determine the reliability of measurements of PAP via a noninvasive technique, echocardiography, in relation to the estimated PAP via right catheterization. We also determined its safety when invasive procedures are restricted to just patients with pulmonary hypertension (PHT) according to echocardiographic parameters. We performed a retrospective study of 67 right catheterizations performed in our hospital, within the heart transplant study protocol, from January 2000 to December 2006. PAP parameters were estimated by echocardiography and right catheterization. Hemodynamically, 57.1% of the patients had severe PHT (more than 45 mm Hg mean PAP); 13.2% moderate PHT (between 35 and 45 mm Hg mean PAP); 12.1% had mild PHT (between 25 and 35 mm Hg mean PAP); and 17.6% of patients showed no PHT. Pearson correlation index with systolic PAP (estimated via echocardiography) and mean PAP (calculated via invasive method) was 0.69 (P < .001). PHT was considered significant when systolic PAP estimated via echocardiography reached more than 40 mm Hg and mean PAP estimated via right catheterization reached more than 35 mm Hg, the value from which the vasodilator test was carried out. According to these parameters, echocardiography showed a sensitivity of 89% to diagnose significant PHT and 46% specificity, with positive and negative predictive values of 70% and 76%, respectively.

  16. Symptoms of Insomnia among Patients with Obstructive Sleep Apnea Before and After Two Years of Positive Airway Pressure Treatment

    PubMed Central

    Björnsdóttir, Erla; Janson, Christer; Sigurdsson, Jón F.; Gehrman, Philip; Perlis, Michael; Juliusson, Sigurdur; Arnardottir, Erna S.; Kuna, Samuel T.; Pack, Allan I.; Gislason, Thorarinn; Benediktsdóttir, Bryndis

    2013-01-01

    Study Objectives: To assess the changes of insomnia symptoms among patients with obstructive sleep apnea (OSA) from starting treatment with positive airway pressure (PAP) to a 2-y follow-up. Design: Longitudinal cohort study. Setting: Landspitali—The National University Hospital of Iceland. Participants: There were 705 adults with OSA who were assessed prior to and 2 y after starting PAP treatment. Intervention: PAP treatment for OSA. Measurements and Results: All patients underwent a medical examination along with a type 3 sleep study and answered questionnaires on health and sleep before and 2 y after starting PAP treatment. The change in prevalence of insomnia symptoms by subtype was assessed by questionnaire and compared between individuals who were using or not using PAP at follow-up. Symptoms of middle insomnia were most common at baseline and improved significantly among patients using PAP (from 59.4% to 30.7%, P < 0.001). Symptoms of initial insomnia tended to persist regardless of PAP treatment, and symptoms of late insomnia were more likely to improve among patients not using PAP. Patients with symptoms of initial and late insomnia at baseline were less likely to adhere to PAP (odds ratio [OR] 0.56, P = 0.007, and OR 0.53, P < 0.001, respectively). Conclusion: Positive airway pressure treatment significantly reduced symptoms of middle insomnia. Symptoms of initial and late insomnia, however, tended to persist regardless of positive airway pressure treatment and had a negative effect on adherence. Targeted treatment for insomnia may be beneficial for patients with obstructive sleep apnea comorbid with insomnia and has the potential to positively affect adherence to positive airway pressure. Citation: Björnsdóttir E; Janson C; Sigurdsson JF; Gehrman P; Perlis M; Juliusson S; Arnardottir ES; Kuna ST; Pack AI; Gislason T; Benediktsdóttir B. Symptoms of insomnia among patients with obstructive sleep apnea before and after two years of positive airway pressure treatment. SLEEP 2013;36(12):1901-1909. PMID:24293765

  17. Get Tested for Cervical Cancer

    MedlinePlus

    ... cervical cancer can help find abnormal (changed) cervical cells before they turn into cervical cancer. There are 2 kinds of screening tests that can find abnormal cervical cells: Pap tests, also called Pap smears HPV (human ...

  18. Arabidopsis floral phytomer development: auxin response relative to biphasic modes of organ initiation

    PubMed Central

    Chandler, J. W.; Werr, W.

    2014-01-01

    In the Arabidopsis inflorescence meristem (IM), auxin is considered a prepatterning signal for floral primordia, whereas a centripetal mode of positional information for floral organ identity is inherent to the ABCE model. However, spatio-temporal patterns of organ initiation in each whorl at the earliest initiation stages are largely unknown. Evidence suggests that initial flower development occurs along an abaxial/adaxial axis and conforms to phytomer theory. Use of the founder cell marker DORNRÖSCHEN-LIKE (DRNL) as a tool in leafy, puchi, and apetala 1 cauliflower mutant backgrounds suggests that bract founder cells are marked at the IM periphery. The DRNL transcription domain in the wild-type IM is spatially discrete from DR5 expression, suggesting that bract initiation is independent of canonical auxin response. When bracts develop in lfy and puchi mutant floral primordia the initiation of lateral sepals precedes the specification of medial sepals compared with wild type, showing an interplay between bract and abaxial sepal founder cell recruitment. In the perianthia (pan) mutant background, DRNL expression indicates that a radial outer whorl arrangement derives from splitting of sepal founder cell populations at abaxial and adaxial positions. This splitting of incipient sepal primordia is partially dependent on PRESSED FLOWER (PRS) activity and implies that sepal specification is independent of WUSCHEL and CLAVATA3 expression, as both marker genes only regain activity in stage-2 flowers, when patterning of inner floral organs switches to a centripetal mode. The transition from an initially abaxial/adaxial into a centripetal patterning programme, and its timing represent an adaptive trait that possibly contributes to variation in floral morphology, especially unidirectional organ initiation. PMID:24744428

  19. Arabidopsis floral phytomer development: auxin response relative to biphasic modes of organ initiation.

    PubMed

    Chandler, J W; Werr, W

    2014-07-01

    In the Arabidopsis inflorescence meristem (IM), auxin is considered a prepatterning signal for floral primordia, whereas a centripetal mode of positional information for floral organ identity is inherent to the ABCE model. However, spatio-temporal patterns of organ initiation in each whorl at the earliest initiation stages are largely unknown. Evidence suggests that initial flower development occurs along an abaxial/adaxial axis and conforms to phytomer theory. Use of the founder cell marker DORNRÖSCHEN-LIKE (DRNL) as a tool in leafy, puchi, and apetala 1 cauliflower mutant backgrounds suggests that bract founder cells are marked at the IM periphery. The DRNL transcription domain in the wild-type IM is spatially discrete from DR5 expression, suggesting that bract initiation is independent of canonical auxin response. When bracts develop in lfy and puchi mutant floral primordia the initiation of lateral sepals precedes the specification of medial sepals compared with wild type, showing an interplay between bract and abaxial sepal founder cell recruitment. In the perianthia (pan) mutant background, DRNL expression indicates that a radial outer whorl arrangement derives from splitting of sepal founder cell populations at abaxial and adaxial positions. This splitting of incipient sepal primordia is partially dependent on PRESSED FLOWER (PRS) activity and implies that sepal specification is independent of WUSCHEL and CLAVATA3 expression, as both marker genes only regain activity in stage-2 flowers, when patterning of inner floral organs switches to a centripetal mode. The transition from an initially abaxial/adaxial into a centripetal patterning programme, and its timing represent an adaptive trait that possibly contributes to variation in floral morphology, especially unidirectional organ initiation. © The Author 2014. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  20. Stochastic modelling of tree architecture and biomass allocation: application to teak (Tectona grandis L. f.), a tree species with polycyclic growth and leaf neoformation.

    PubMed

    Tondjo, Kodjo; Brancheriau, Loïc; Sabatier, Sylvie; Kokutse, Adzo Dzifa; Kokou, Kouami; Jaeger, Marc; de Reffye, Philippe; Fourcaud, Thierry

    2018-06-08

    For a given genotype, the observed variability of tree forms results from the stochasticity of meristem functioning and from changing and heterogeneous environmental factors affecting biomass formation and allocation. In response to climate change, trees adapt their architecture by adjusting growth processes such as pre- and neoformation, as well as polycyclic growth. This is the case for the teak tree. The aim of this work was to adapt the plant model, GreenLab, in order to take into consideration both these processes using existing data on this tree species. This work adopted GreenLab formalism based on source-sink relationships at organ level that drive biomass production and partitioning within the whole plant over time. The stochastic aspect of phytomer production can be modelled by a Bernoulli process. The teak model was designed, parameterized and analysed using the architectural data from 2- to 5-year-old teak trees in open field stands. Growth and development parameters were identified, fitting the observed compound organic series with the theoretical series, using generalized least squares methods. Phytomer distributions of growth units and branching pattern varied depending on their axis category, i.e. their physiological age. These emerging properties were in accordance with the observed growth patterns and biomass allocation dynamics during a growing season marked by a short dry season. Annual growth patterns observed on teak, including shoot pre- and neoformation and polycyclism, were reproduced by the new version of the GreenLab model. However, further updating is discussed in order to ensure better consideration of radial variation in basic specific gravity of wood. Such upgrading of the model will enable teak ideotypes to be defined for improving wood production in terms of both volume and quality.

  1. Acute physical exercise is safe in patients with primary antiphospholipid syndrome with exclusive venous thrombosis and under oral anticoagulation with warfarin.

    PubMed

    Garcia, Carolina Borges; Seguro, Luciana Parente Costa; Perandini, Luiz Augusto; de Sá Pinto, Ana Lúcia; Lima, Fernanda Rodrigues; Negrão, Carlos Eduardo; Bonfa, Eloisa; Borba, Eduardo Ferreira

    2014-12-01

    The purpose of present study was to evaluate the effects of maximal acute physical exercise on prothrombin time/international normalized ratio (PT/INR) in patients with primary antiphospholipid syndrome (PAPS) under oral anticoagulation with warfarin and the safety of acute exercise in regard to thrombosis and bleeding risk. Eighteen physically inactive women with PAPS (Sydney criteria) with exclusive venous events and without thrombocytopenia were included. All patients were under stable warfarin therapy (PT/INR target: 2.0-3.0). Eighteen age-matched healthy sedentary women without thrombosis/bleeding disorders were selected as controls. All subjects performed a maximal exercise test, and capillary blood samples were obtained pre-, post- and at 1-h post-exercise (recovery time) for PT/INR analysis using a portable CoaguCheck. PAPS patients and controls had similar mean age (31.50 ± 8.06 vs. 29.61 ± 7.05 years, p = 0.46) and body mass index (24.16 ± 3.67 vs. 24.66 ± 2.71 kg/m(2), p = 0.65). PAPS had a mild but significant increase in PT/INR value at 1-h post-exercise (recovery) compared with pre- (2.33 ± 0.34 vs. 2.26 ± 0.29, p = 0.001) and post-exercise (2.33 ± 0.34 vs. 2.26 ± 0.32, p = 0.001) that was observed in 61.11 % of these patients. None of the subjects had thrombotic or bleeding complications related to the acute exercise. Acute exercise in patients with PAPS with exclusive venous thrombosis was safe with a minor increase in PT/INR. This is an important step to introduce regular exercise training as a therapeutic tool in the management of these patients.

  2. CIR, a corepressor of CBF1, binds to PAP-1 and effects alternative splicing

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Maita, Hiroshi; CREST, Japan Science and Technology Corporation, Saitama 332-0012; Kitaura, Hirotake

    2005-02-15

    We have reported that PAP-1, a product of a causative gene for autosomal retinitis pigmentosa, plays a role in splicing. In this study, CIR, a protein originally identified as a CBF1-interacting protein and reported to act as a transcriptional corepressor, was identified as a PAP-1 binding protein and its function as a splicing factor was investigated. In addition to a basic lysine and acidic serine-rich (BA) domain and a zinc knuckle-like motif, CIR has an arginine/serine dipeptide repeat (RS) domain in its C terminal region. The RS domain has been reported to be present in the superfamily of SR proteins,more » which are involved in splicing reactions. We generated CIR mutants with deletions of each BA and RS domain and studied their subcellular localizations and interactions with PAP-1 and other SR proteins, including SC35, SF2/ASF, and U2AF{sup 35}. CIR was found to interact with U2AF{sup 35} through the BA domain, with SC35 and SF2/ASF through the RS domain, and with PAP-1 outside the BA domain in vivo and in vitro. CIR was found to be colocalized with SC35 and PAP-1 in nuclear speckles. Then the effect of CIR on splicing was investigated using the E1a minigene as a reporter in HeLa cells. Ectopic expression of CIR with the E1a minigene changed the ratio of spliced isoforms of E1a that were produced by alternative selection of 5'-splice sites. These results indicate that CIR is a member of the family of SR-related proteins and that CIR plays a role in splicing regulation.« less

  3. Pulmonary vascular function and exercise capacity in black sub-Saharan Africans.

    PubMed

    Simaga, Bamodi; Vicenzi, Marco; Faoro, Vitalie; Caravita, Sergio; Di Marco, Giovanni; Forton, Kevin; Deboeck, Gael; Lalande, Sophie; Naeije, Robert

    2015-09-01

    Sex and age affect the pulmonary circulation. Whether there may be racial differences in pulmonary vascular function is unknown. Thirty white European Caucasian subjects (15 women) and age and body-size matched 30 black sub-Saharan African subjects (15 women) underwent a cardiopulmonary exercise test and exercise stress echocardiography with measurements of pulmonary artery pressure (PAP) and cardiac output (CO). A pulmonary vascular distensibility coefficient α was mathematically determined from the natural curvilinearity of multipoint mean PAP (mPAP)-CO plots. Maximum oxygen uptake (V̇o2max) and workload were higher in the whites, while maximum respiratory exchange ratio and ventilatory equivalents for CO2 were the same. Pulmonary hemodynamics were not different at rest. Exercise was associated with a higher maximum total pulmonary vascular resistance, steeper mPAP-CO relationships, and lower α-coefficients in the blacks. These differences were entirely driven by higher slopes of mPAP-CO relationships (2.5 ± 0.7 vs. 1.4 ± 0.7 mmHg·l(-1)·min; P < 0.001) and lower α-coefficients (0.85 ± 0.33 vs. 1.35 ± 0.51%/mmHg; P < 0.01) in black men compared with white men. There were no differences in any of the hemodynamic variables between black and white women. In men only, the slopes of mPAP-CO relationships were inversely correlated to V̇o2max (P < 0.01). Thus the pulmonary circulation is intrinsically less distensible in black sub-Saharan African men compared with white Caucasian Europeans men, and this is associated with a lower exercise capacity. This study did not identify racial differences in pulmonary vascular function in women. Copyright © 2015 the American Physiological Society.

  4. A chloroplast retrograde signal, 3'-phosphoadenosine 5'-phosphate, acts as a secondary messenger in abscisic acid signaling in stomatal closure and germination.

    PubMed

    Pornsiriwong, Wannarat; Estavillo, Gonzalo M; Chan, Kai Xun; Tee, Estee E; Ganguly, Diep; Crisp, Peter A; Phua, Su Yin; Zhao, Chenchen; Qiu, Jiaen; Park, Jiyoung; Yong, Miing Tiem; Nisar, Nazia; Yadav, Arun Kumar; Schwessinger, Benjamin; Rathjen, John; Cazzonelli, Christopher I; Wilson, Philippa B; Gilliham, Matthew; Chen, Zhong-Hua; Pogson, Barry J

    2017-03-21

    Organelle-nuclear retrograde signaling regulates gene expression, but its roles in specialized cells and integration with hormonal signaling remain enigmatic. Here we show that the SAL1-PAP (3'-phosphoadenosine 5'- phosphate) retrograde pathway interacts with abscisic acid (ABA) signaling to regulate stomatal closure and seed germination in Arabidopsis . Genetically or exogenously manipulating PAP bypasses the canonical signaling components ABA Insensitive 1 (ABI1) and Open Stomata 1 (OST1); priming an alternative pathway that restores ABA-responsive gene expression, ROS bursts, ion channel function, stomatal closure and drought tolerance in ost1 -2. PAP also inhibits wild type and abi1 -1 seed germination by enhancing ABA sensitivity. PAP-XRN signaling interacts with ABA, ROS and Ca 2+ ; up-regulating multiple ABA signaling components, including lowly-expressed Calcium Dependent Protein Kinases (CDPKs) capable of activating the anion channel SLAC1. Thus, PAP exhibits many secondary messenger attributes and exemplifies how retrograde signals can have broader roles in hormone signaling, allowing chloroplasts to fine-tune physiological responses.

  5. Portal annular pancreas: a systematic review of a clinical challenge.

    PubMed

    Harnoss, Jonathan M; Harnoss, Julian C; Diener, Markus K; Contin, Pietro; Ulrich, Alexis B; Büchler, Markus W; Schmitz-Winnenthal, Friedrich H

    2014-10-01

    Portal annular pancreas (PAP) is an asymptomatic congenital pancreas anomaly, in which portal and/or mesenteric veins are encased by pancreas tissue. The aim of the study was to determine the role of PAP in pancreatic surgery as well as its management and potential complication, specifically, postoperative pancreatic fistula (POPF).On the basis of a case report, the MEDLINE and ISI Web of Science databases were systematically reviewed up to September 2012. All articles describing a case of PAP were considered.In summary, 21 studies with 59 cases were included. The overall prevalence of PAP was 2.4% and the patients' mean (SD) age was 55.9 (16.2) years. The POPF rate in patients with PAP (12 pancreaticoduodenectomies and 3 distal pancreatectomies) was 46.7% (in accordance with the definition of the International Study Group of Pancreatic Surgery).Portal annular pancreas is a quite unattended pancreatic variant with high prevalence and therefore still remains a clinical challenge to avoid postoperative complications. To decrease the risk for POPF, attentive preoperative diagnostics should also focus on PAP. In pancreaticoduodenectomy, a shift of the resection plane to the pancreas tail should be considered; in extensive pancreatectomy, coverage of the pancreatic remnant by the falciform ligament could be a treatment option.

  6. Pap Screening Goals and Perceptions of Pain among Black, Latina, and Arab Women: Steps toward Breaking down Psychological Barriers

    PubMed Central

    Gauss, Julie W.; Mabiso, Athur; Williams, Karen Patricia

    2013-01-01

    BACKGROUND Understanding women’s psychological barriers to getting Papanicolaou (Pap) screening has potential to impact cancer disparities. This study examined pain perceptions of Pap testing among Black, Latina and Arab women and goal setting to receive Pap tests. METHODS Data on 420 women, a longitudinal study, were analyzed using Chi-square tests of differences and generalized linear mixed models. RESULTS At baseline, 30.3% of Black and 35.5% of Latina women perceived Pap tests to be very painful compared to 24.2% of Arab women. Perceptions of pain influenced goal settings, such as scheduling a first ever Pap test (Odds ratio = 0.58, 95% Confidence interval: 0.14-0.94). Immediately following the intervention, women’s perception that Pap tests are very painful significantly declined (P-value<0.001) with Arab and Black women registering the greatest improvements (20.3 and 17.3 percent reduction, respectively compared to 8.4 percent for Latina). CONCLUSIONS Having the perception that the Pap test is very painful significantly reduces the likelihood of Black, Latina and Arab women setting the goal to schedule their first ever Pap test. Latina women are the least likely to improve their perception that the Pap test is very painful, though national statistics show they have the highest rates of morbidity and mortality from cervical cancer. These findings are instructive for designing tailored interventions to break down psychological barriers to Pap screening among underserved women. PMID:23288606

  7. Correlation between pulmonary artery pressure and thoracic impedance: Insights from daily monitoring through an implanted device in chronic heart failure.

    PubMed

    Perego, Giovanni Battista; Oldani, Matteo; Pellegrini, Dario; Brasca, Francesco Maria Angelo; Malfatto, Gabriella; Villani, Alessandra; Brambilla, Roberto; Rella, Valeria; Parati, Gianfranco

    2017-10-15

    Thoracic impedance (TI) decrease and pulmonary artery pressure (PAP) elevation precede acute decompensation in congestive heart failure (HF). However, the relationship between TI and PAP has been studied only in the context of acute decompensation. This prospective, observational study enrolled subjects with reduced ejection fraction HF, previously implanted with an ICD capable of measuring TI. Patients underwent implantation of a sensor for direct measurement of PAP (CardioMEMs™). Both TI and PAP were remotely monitored daily during follow up. Investigators were blinded to PAP values during the first three months, then PAP was used as a guide to therapy. Ten patients were followed up for 405±141days (3720 patient-days). During hemodynamic guided therapy, diastolic PAP (dPAP) decreased from 27.8±10.2mmHg to 24.0±8.0mmHg (p<0.001); non-significant variations of TI were observed. A significant negative correlation was found between the variations of TI and PAP vs. baseline (p<0.001). Episodes of sustained increase of PAP preceded subsequent periods of TI decrease by 5.6±3.9days, but the former were poor predictors of the latter (sensitivity 0.37). Our study confirms the strict correlation that exists between left ventricular filling pressures and lung water content, estimated by dPAP and TI, respectively. However, dPAP acute variation analysis showed a limited value in predicting subsequent episodes of TI decrease. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Evidence for a SAL1-PAP chloroplast retrograde pathway that functions in drought and high light signaling in Arabidopsis.

    PubMed

    Estavillo, Gonzalo M; Crisp, Peter A; Pornsiriwong, Wannarat; Wirtz, Markus; Collinge, Derek; Carrie, Chris; Giraud, Estelle; Whelan, James; David, Pascale; Javot, Hélène; Brearley, Charles; Hell, Rüdiger; Marin, Elena; Pogson, Barry J

    2011-11-01

    Compartmentation of the eukaryotic cell requires a complex set of subcellular messages, including multiple retrograde signals from the chloroplast and mitochondria to the nucleus, to regulate gene expression. Here, we propose that one such signal is a phosphonucleotide (3'-phosphoadenosine 5'-phosphate [PAP]), which accumulates in Arabidopsis thaliana in response to drought and high light (HL) stress and that the enzyme SAL1 regulates its levels by dephosphorylating PAP to AMP. SAL1 accumulates in chloroplasts and mitochondria but not in the cytosol. sal1 mutants accumulate 20-fold more PAP without a marked change in inositol phosphate levels, demonstrating that PAP is a primary in vivo substrate. Significantly, transgenic targeting of SAL1 to either the nucleus or chloroplast of sal1 mutants lowers the total PAP levels and expression of the HL-inducible ASCORBATE PEROXIDASE2 gene. This indicates that PAP must be able to move between cellular compartments. The mode of action for PAP could be inhibition of 5' to 3' exoribonucleases (XRNs), as SAL1 and the nuclear XRNs modulate the expression of a similar subset of HL and drought-inducible genes, sal1 mutants accumulate XRN substrates, and PAP can inhibit yeast (Saccharomyces cerevisiae) XRNs. We propose a SAL1-PAP retrograde pathway that can alter nuclear gene expression during HL and drought stress.

  9. Evidence for a SAL1-PAP Chloroplast Retrograde Pathway That Functions in Drought and High Light Signaling in Arabidopsis[C][W][OA

    PubMed Central

    Estavillo, Gonzalo M.; Crisp, Peter A.; Pornsiriwong, Wannarat; Wirtz, Markus; Collinge, Derek; Carrie, Chris; Giraud, Estelle; Whelan, James; David, Pascale; Javot, Hélène; Brearley, Charles; Hell, Rüdiger; Marin, Elena; Pogson, Barry J.

    2011-01-01

    Compartmentation of the eukaryotic cell requires a complex set of subcellular messages, including multiple retrograde signals from the chloroplast and mitochondria to the nucleus, to regulate gene expression. Here, we propose that one such signal is a phosphonucleotide (3′-phosphoadenosine 5′-phosphate [PAP]), which accumulates in Arabidopsis thaliana in response to drought and high light (HL) stress and that the enzyme SAL1 regulates its levels by dephosphorylating PAP to AMP. SAL1 accumulates in chloroplasts and mitochondria but not in the cytosol. sal1 mutants accumulate 20-fold more PAP without a marked change in inositol phosphate levels, demonstrating that PAP is a primary in vivo substrate. Significantly, transgenic targeting of SAL1 to either the nucleus or chloroplast of sal1 mutants lowers the total PAP levels and expression of the HL-inducible ASCORBATE PEROXIDASE2 gene. This indicates that PAP must be able to move between cellular compartments. The mode of action for PAP could be inhibition of 5′ to 3′ exoribonucleases (XRNs), as SAL1 and the nuclear XRNs modulate the expression of a similar subset of HL and drought-inducible genes, sal1 mutants accumulate XRN substrates, and PAP can inhibit yeast (Saccharomyces cerevisiae) XRNs. We propose a SAL1-PAP retrograde pathway that can alter nuclear gene expression during HL and drought stress. PMID:22128124

  10. p-Aminophenol degradation by ozonation combined with sonolysis: operating conditions influence and mechanism.

    PubMed

    He, Zhiqiao; Song, Shuang; Ying, Haiping; Xu, Lejin; Chen, Jianmeng

    2007-07-01

    The degradation of p-aminophenol (PAP) in aqueous solution by sonolysis, by ozonation, and by a combination of both was investigated in laboratory-scale experiments. Operation parameters such as pH, temperature, ultrasonic energy density and ozone dose were optimized with regard to the efficiency of PAP removal. The concentration of PAP during the reaction was detected by high-pressure liquid chromatography. The concentrations of ammonium ions and nitrate ions were monitored during the degradation. Intermediate products such as 4-iminocyclohexa-2,5-dien-1-one, phenol, but-2-enedioic acid, and acetic acid were detected by gas chromatography coupled with mass spectrometry. The degradation rate of PAP was higher in the combined system than in the linear combination of separate experiments. The degradation efficiency was decreased rapidly when n-butanol was added to the combined reaction system, which showed that some radical reaction might proceed during the laboratory experiments.

  11. Pharmacogenetics of human 3'-phosphoadenosine 5'-phosphosulfate synthetase 1 (PAPSS1): gene resequencing, sequence variation, and functional genomics.

    PubMed

    Xu, Zhen-Hua; Thomae, Bianca A; Eckloff, Bruce W; Wieben, Eric D; Weinshilboum, Richard M

    2003-06-01

    3'-Phosphoadenosine 5'-phosphosulfate (PAPS) is the high-energy "sulfate donor" for reactions catalyzed by sulfotransferase (SULT) enzymes. The strict requirement of SULTs for PAPS suggests that PAPS synthesis might influence the rate of sulfate conjugation. In humans, PAPS is synthesized from ATP and SO(4)(2-) by two isoforms of PAPS synthetase (PAPSS): PAPSS1 and PAPSS2. As a step toward pharmacogenetic studies, we have resequenced the entire coding sequence of the human PAPSS1 gene, including exon-intron splice junctions, using DNA samples from 60 Caucasian-American and 58 African-American subjects. Twenty-one genetic polymorphisms were observed-1 insertion-deletion event and 20 single nucleotide polymorphisms (SNPs)-including two non-synonymous coding SNPs (cSNPs) that altered the following amino acids: Arg333Cys and Glu531Gln. Twelve pairs of these polymorphisms were tightly linked, and a total of twelve unequivocal haplotypes could be identified-two that were common to both ethnic groups and ten that were ethnic-specific. The Arg333Cys polymorphism, with an allele frequency of 2.5%, was observed only in DNA samples from Caucasian subjects. The Glu531Gln polymorphism was rare, with only a single copy of that allele in a DNA sample from an African-American subject. Transient expression in mammalian cells showed that neither of the non-synonymous cSNPs resulted in a change in the basal level of enzyme activity measured under optimal assay conditions. However, the Glu531Gln polymorphism altered the substrate kinetic properties of the enzyme. The Gln531 variant allozyme had a 5-fold higher K(m) value for SO(4)(2-) than did the wild-type allozyme and displayed monophasic kinetics for Na(2)SO(4). The wild-type allozyme (Glu531) showed biphasic kinetics for that substrate. These observations represent a step toward testing the hypothesis that genetic variation in PAPS synthesis catalyzed by PAPSS1 might alter in vivo sulfate conjugation.

  12. Identification and physiological characterization of phosphatidic acid phosphatase enzymes involved in triacylglycerol biosynthesis in Streptomyces coelicolor

    PubMed Central

    2013-01-01

    Background Phosphatidic acid phosphatase (PAP, EC 3.1.3.4) catalyzes the dephosphorylation of phosphatidate yielding diacylglycerol (DAG), the lipid precursor for triacylglycerol (TAG) biosynthesis. Despite the importance of PAP activity in TAG producing bacteria, studies to establish its role in lipid metabolism have been so far restricted only to eukaryotes. Considering the increasing interest of bacterial TAG as a potential source of raw material for biofuel production, we have focused our studies on the identification and physiological characterization of the putative PAP present in the TAG producing bacterium Streptomyces coelicolor. Results We have identified two S. coelicolor genes, named lppα (SCO1102) and lppβ (SCO1753), encoding for functional PAP proteins. Both enzymes mediate, at least in part, the formation of DAG for neutral lipid biosynthesis. Heterologous expression of lppα and lppβ genes in E. coli resulted in enhanced PAP activity in the membrane fractions of the recombinant strains and concomitantly in higher levels of DAG. In addition, the expression of these genes in yeast complemented the temperature-sensitive growth phenotype of the PAP deficient strain GHY58 (dpp1lpp1pah1). In S. coelicolor, disruption of either lppα or lppβ had no effect on TAG accumulation; however, the simultaneous mutation of both genes provoked a drastic reduction in de novo TAG biosynthesis as well as in total TAG content. Consistently, overexpression of Lppα and Lppβ in the wild type strain of S. coelicolor led to a significant increase in TAG production. Conclusions The present study describes the identification of PAP enzymes in bacteria and provides further insights on the genetic basis for prokaryotic oiliness. Furthermore, this finding completes the whole set of enzymes required for de novo TAG biosynthesis pathway in S. coelicolor. Remarkably, the overexpression of these PAPs in Streptomyces bacteria contributes to a higher productivity of this single cell oil. Altogether, these results provide new elements and tools for future cell engineering for next-generation biofuels production. PMID:23356794

  13. Dietary exposure to brominated flame retardants and abnormal Pap test results.

    PubMed

    Jamieson, Denise J; Terrell, Metrecia L; Aguocha, Nnenna N; Small, Chanley M; Cameron, Lorraine L; Marcus, Michele

    2011-09-01

    This study examined a possible association of dietary exposure to polybrominated biphenyls (PBBs), a brominated flame retardant, and self-reported abnormal Pap test results and cervical dysplasia as a precursor to cervical cancer. Women in Michigan who ingested contaminated poultry, beef, and dairy products in the early 1970s were enrolled in a population-based cohort study in Michigan. Serum PBB and serum polychlorinated biphenyl (PCB) concentrations were measured. Reproductive history and health information, including Pap test results, were self-reported by participants. Of the women, 23% (223 of 956) reported an abnormal Pap test. In unadjusted analyses, self-reporting an abnormal Pap test was associated with younger age, current smoking (hazard ratio [HR] 1.61, 95% confidence interval [CI] 1.19-2.17), and longer duration of lifetime use of oral contraceptives (≥10 years; HR 1.92, 95% CI 1.21-3.06). When adjusting for PCB exposure, age at the interview, and smoking history, there was a slightly elevated risk of self-reporting an abnormal Pap test among the highly exposed women compared to women with nondetectable PBB concentrations (PBB≥13 μg/L, HR 1.23, 95% CI 0.74-2.06); however, the CI was imprecise. When breastfeeding duration after the initial PBB measurement was taken into account, there was a reduced risk of self-reporting an abnormal Pap test among the highly exposed women who breastfed for ≥12 months (HR 0.41, 95% CI 0.06-3.03; referent group: women with nondetectable PBB concentrations who did not breastfeed). It remains important to evaluate the potential reproductive health consequences of this class of chemicals as well as other potential predictors of abnormal Pap tests.

  14. Dietary Exposure to Brominated Flame Retardants and Abnormal Pap Test Results

    PubMed Central

    Jamieson, Denise J.; Terrell, Metrecia L.; Aguocha, Nnenna N.; Small, Chanley M.; Cameron, Lorraine L.

    2011-01-01

    Abstract Objective This study examined a possible association of dietary exposure to polybrominated biphenyls (PBBs), a brominated flame retardant, and self-reported abnormal Pap test results and cervical dysplasia as a precursor to cervical cancer. Methods Women in Michigan who ingested contaminated poultry, beef, and dairy products in the early 1970s were enrolled in a population-based cohort study in Michigan. Serum PBB and serum polychlorinated biphenyl (PCB) concentrations were measured. Reproductive history and health information, including Pap test results, were self-reported by participants. Results Of the women, 23% (223 of 956) reported an abnormal Pap test. In unadjusted analyses, self-reporting an abnormal Pap test was associated with younger age, current smoking (hazard ratio [HR] 1.61, 95% confidence interval [CI] 1.19-2.17), and longer duration of lifetime use of oral contraceptives (≥10 years; HR 1.92, 95% CI 1.21-3.06). When adjusting for PCB exposure, age at the interview, and smoking history, there was a slightly elevated risk of self-reporting an abnormal Pap test among the highly exposed women compared to women with nondetectable PBB concentrations (PBB≥13 μg/L, HR 1.23, 95% CI 0.74-2.06); however, the CI was imprecise. When breastfeeding duration after the initial PBB measurement was taken into account, there was a reduced risk of self-reporting an abnormal Pap test among the highly exposed women who breastfed for ≥12 months (HR 0.41, 95% CI 0.06-3.03; referent group: women with nondetectable PBB concentrations who did not breastfeed). Conclusions It remains important to evaluate the potential reproductive health consequences of this class of chemicals as well as other potential predictors of abnormal Pap tests. PMID:21797757

  15. Progression and regression of cervical pap test lesions in an urban AIDS clinic in the combined antiretroviral therapy era: a longitudinal, retrospective study.

    PubMed

    Lofgren, Sarah M; Tadros, Talaat; Herring-Bailey, Gina; Birdsong, George; Mosunjac, Marina; Flowers, Lisa; Nguyen, Minh Ly

    2015-05-01

    Our objective was to evaluate the progression and regression of cervical dysplasia in human immunodeficiency virus (HIV)-positive women during the late antiretroviral era. Risk factors as well as outcomes after treatment of cancerous or precancerous lesions were examined. This is a longitudinal retrospective review of cervical Pap tests performed on HIV-infected women with an intact cervix between 2004 and 2011. Subjects needed over two Pap tests for at least 2 years of follow-up. Progression was defined as those who developed a squamous intraepithelial lesion (SIL), atypical glandular cells (AGC), had low-grade SIL (LSIL) followed by atypical squamous cells-cannot exclude high-grade SIL (ASC-H) or high-grade SIL (HSIL), or cancer. Regression was defined as an initial SIL with two or more subsequent normal Pap tests. Persistence was defined as having an SIL without progression or regression. High-risk human papillomavirus (HPV) testing started in 2006 on atypical squamous cells of undetermined significance (ASCUS) Pap tests. AGC at enrollment were excluded from progression analysis. Of 1,445 screened, 383 patients had over two Pap tests for a 2-year period. Of those, 309 had an intact cervix. The median age was 40 years and CD4+ cell count was 277 cells/mL. Four had AGC at enrollment. A quarter had persistently normal Pap tests, 64 (31%) regressed, and 50 (24%) progressed. Four developed cancer. The only risk factor associated with progression was CD4 count. In those with treated lesions, 24 (59%) had negative Pap tests at the end of follow-up. More studies are needed to evaluate follow-up strategies of LSIL patients, potentially combined with HPV testing. Guidelines for HIV-seropositive women who are in care, have improved CD4, and have persistently negative Pap tests could likely lengthen the follow-up interval.

  16. Effects of Age and Acute Moderate Alcohol Administration on Electrophysiological Correlates of Working Memory Maintenance

    PubMed Central

    Boissoneault, Jeff; Frazier, Ian; Lewis, Ben; Nixon, Sara Jo

    2016-01-01

    Background Previous studies suggest older adults may be differentially susceptible to the acute neurobehavioral effects of moderate alcohol intake. To our knowledge, no studies have addressed acute moderate alcohol effects on the electrophysiological correlates of working memory in younger and older social drinkers. This study characterized alcohol-related effects on frontal theta (FTP) and posterior alpha power (PAP) associated with maintenance of visual information during a working memory task. Methods Older (55–70 years of age; n = 51, 29 women) and younger (25–35 years of age; n = 70, 39 women) community-dwelling moderate drinkers were recruited for this study. Participants were given either placebo or an active dose targeting breath alcohol concentrations (BrACs) of 0.04 or 0.065 g/dL. Following absorption, participants completed a visual working memory task assessing cue recognition following a 9s delay. FTP and PAP were determined via Fourier transformation and subjected to 2 (age group) X 3 (dose) X 2 (repeated: working memory task condition) mixed models analysis. Results In addition to expected age-related reductions in PAP, a significant age group X dose interaction was detected for PAP such that 0.04 g/dL dose level was associated with greater PAP in younger adults but lower PAP in their older counterparts. PAP was lower in older vs younger adults at both active doses. Further mixed models revealed a significant negative association between PAP and working memory efficiency for older adults. No effects of age, dose, or their interaction were noted for FTP. Conclusions Results bolster the small but growing body of evidence that older adults exhibit differential sensitivity to the neurobehavioral effects of moderate alcohol use. Given the theoretical role of PAP in attentional and working memory function, these findings shed light on the attentional mechanisms underlying effects of acute moderate alcohol on working memory efficiency in older adults. PMID:27419803

  17. Progression and Regression of Cervical Pap Test Lesions in an Urban AIDS Clinic in the Combined Antiretroviral Therapy Era: A Longitudinal, Retrospective Study

    PubMed Central

    Tadros, Talaat; Herring-Bailey, Gina; Birdsong, George; Mosunjac, Marina; Flowers, Lisa; Nguyen, Minh Ly

    2015-01-01

    Abstract Our objective was to evaluate the progression and regression of cervical dysplasia in human immunodeficiency virus (HIV)-positive women during the late antiretroviral era. Risk factors as well as outcomes after treatment of cancerous or precancerous lesions were examined. This is a longitudinal retrospective review of cervical Pap tests performed on HIV-infected women with an intact cervix between 2004 and 2011. Subjects needed over two Pap tests for at least 2 years of follow-up. Progression was defined as those who developed a squamous intraepithelial lesion (SIL), atypical glandular cells (AGC), had low-grade SIL (LSIL) followed by atypical squamous cells-cannot exclude high-grade SIL (ASC-H) or high-grade SIL (HSIL), or cancer. Regression was defined as an initial SIL with two or more subsequent normal Pap tests. Persistence was defined as having an SIL without progression or regression. High-risk human papillomavirus (HPV) testing started in 2006 on atypical squamous cells of undetermined significance (ASCUS) Pap tests. AGC at enrollment were excluded from progression analysis. Of 1,445 screened, 383 patients had over two Pap tests for a 2-year period. Of those, 309 had an intact cervix. The median age was 40 years and CD4+ cell count was 277 cells/mL. Four had AGC at enrollment. A quarter had persistently normal Pap tests, 64 (31%) regressed, and 50 (24%) progressed. Four developed cancer. The only risk factor associated with progression was CD4 count. In those with treated lesions, 24 (59%) had negative Pap tests at the end of follow-up. More studies are needed to evaluate follow-up strategies of LSIL patients, potentially combined with HPV testing. Guidelines for HIV-seropositive women who are in care, have improved CD4, and have persistently negative Pap tests could likely lengthen the follow-up interval. PMID:25693769

  18. Pulmonary hemodynamics responses to hypoxia and/or CO2 inhalation during moderate exercise in humans.

    PubMed

    Doutreleau, Stéphane; Enache, Irina; Pistea, Cristina; Geny, Bernard; Charloux, Anne

    2018-03-03

    In this study, we hypothesized that adding CO 2 to an inhaled hypoxic gas mixture will limit the rise of pulmonary artery pressure (PAP) induced by a moderate exercise. Eight 20-year-old males performed four constant-load exercise tests on cycle at 40% of maximal oxygen consumption in four conditions: ambient air, normobaric hypoxia (12.5% O 2 ), inhaled CO 2 (4.5% CO 2 ), and combination of hypoxia and inhaled CO 2 . Doppler echocardiography was used to measure systolic (s)PAP, cardiac output (CO). Total pulmonary resistance (TPR) was calculated. Arterialized blood pH was 7.40 at exercise in ambient and hypoxia conditions, whereas CO 2 inhalation and combined conditions showed acidosis. sPAP increases from rest in ambient air to exercise ranged as follows: ambient + 110%, CO 2 inhalation + 135%, combined + 184%, hypoxia + 217% (p < 0.001). CO was higher when inhaling O 2 -poor gas mixtures with or without CO 2 (~ 17 L min -1 ) than in the other conditions (~ 14 L min -1 , p < 0.001). Exercise induced a significant decrease in TPR in the four conditions (p < 0.05) but less marked in hypoxia (- 19% of the resting value in ambient air) than in ambient (- 33%) and in both CO 2 inhalation and combined condition (- 29%). We conclude that (1) acute CO 2 inhalation did not significantly modify pulmonary hemodynamics during moderate exercise. (2) CO 2 adjunction to hypoxic gas mixture did not modify CO, despite a higher CaO 2 in combined condition than in hypoxia. (3) TPR was lower in combined than in hypoxia condition, limiting sPAP increase in combined condition.

  19. How much does a reminder letter increase cervical screening among under-screened women in NSW?

    PubMed

    Morrell, Stephen; Taylor, Richard; Zeckendorf, Sue; Niciak, Amanda; Wain, Gerard; Ross, Jayne

    2005-02-01

    To evaluate a direct mail-out campaign to increase Pap screening rates in women who have not had a test in 48 months. Ninety thousand under-screened women were randomised to be mailed a 48-month reminder letter to have a Pap test (n=60,000), or not to be mailed a letter (n=30,000). Differences in Pap test rates were assessed by Kaplan-Meier survival analysis, by chi2 tests of significance between Pap test rates in letter versus no-letter groups, and by proportional hazards regression modelling of predictors of a Pap test with letter versus no-letter as the main study variable. T-tests were conducted on mean time to Pap test to assess whether time to Pap test was significantly different between the intervention and control groups. After 90 days following each mail-out, Pap test rates in the letter group were significantly higher than in the non-letter group, by approximately two percentage points. After controlling for potential confounders, the hazard ratio of a Pap test within 90 days of a mail-out in the letter group was 1.5 compared with 1.0 in the no-letter group. Hazard ratios of having a Pap test within 90 days decreased significantly with time since last Pap test (p<0.0001); were significantly higher than 1.0 for most non-metropolitan areas of NSW compared with metropolitan areas; and increased significantly with age (p<0.0001). Pap test hazard ratios were not associated with socio-economic status of area of residence, but the hazard ratio was significantly higher than 1.0 if the reminder letter was sent after the Christmas/New Year break. No significant differences in mean time to Pap test were found between the letter and no-letter groups. Being sent a reminder letter is associated with higher Pap testing rates in under-screened women.

  20. Associations of an abnormal Pap test result with attitudes and beliefs relevant to cervical cancer: a study of rural Appalachian women.

    PubMed

    Crosby, Richard A; Vanderpool, Robin; Jones, Cissi

    2016-07-01

    To compare women who recall being informed of an abnormal Pap to those not having this experience relative to attitudes and beliefs pertaining to screening for cervical cancer. Four hundred women were recruited from eight rural Appalachian counties, in 2013 and 2014. Women completed a paper-and-pencil survey after providing written informed consent. Bivariate associations and age-adjusted associations were calculated between the self-reported experience of being told of an abnormal Pap test result and eight attitudes/beliefs relative to the prevention of cervical cancer. Data analyses were performed in 2014. The mean age was 40.2 years (range 30-64 years). Eighteen women chose not to answer the question asking about ever having an abnormal Pap test result, leaving n = 382. Of the 382 women who did answer, 122 (30.6 %) indicated having an abnormal Pap test result and the remaining 260 (65.2 %) indicated never having this experience. With the exception of one item assessing knowledge that HPV is the cause of cervical cancer, between-group differences in attitudes, beliefs, and intent to have a Pap test the next time one is due were not observed. Although we hypothesized that women ever having an abnormal Pap test may have actively sought to learn more about cervical cancer and its prevention, findings suggest that this is not the case. Informing women of an abnormal result could be coupled with a high-intensity counseling designed to improve attitudes and beliefs relative to women's role in protecting themselves from cervical cancer.

  1. A Study of Pap Smear in HIV-Positive Females.

    PubMed

    Madan, Apeksha; Patil, Sunita; Nakate, Leena

    2016-12-01

    HIV-positive females are more likely to have abnormal Pap smears than HIV-negative women. These abnormal Pap smears are usually associated with low CD4 cell counts and human papilloma virus infection. This was a prospective hospital-based study from April 2013 till March 2014. A total of 250 (both symptomatic and asymptomatic) HIV-positive females were examined in Gynaecology OPD at R.C.S.M. G.M.C and C.P.R. Hospital, Kolhapur, and their cervical smears were taken. They were categorized as per modified Bethesda system 2001. The findings in HIV-positive women were correlated with risk factors (age, disease duration, CD4 count and ART use). To study the spectrum of cytological abnormalities on Pap smear in HIV-positive females and classify precancerous and cancerous lesions in HIV-positive females according to Bethesda system 2001 and to be familiar with terminology and morphological criteria of Bethesda system 2001. To study the association of Pap smears abnormalities among HIV-positive women with their immune status (CD4 count). NILM is the commonest finding (83.2 %) which is subdivided into non-inflammatory, non-specific and specific inflammatory and atrophic smears. Candida vaginitis was the commonest cause of specific inflammatory condition accounted for (2.52 %) of all inflammatory smears. The percentage of squamous cell abnormalities was 12 %: ASCUS + ASC-H-6.22 %, LSIL-2.10 %, HSIL-3.4 % and SCC-0.8 %. The highest incidence of intraepithelial lesions in HIV-positive females was in the age group 31-40 years. There is no association of Pap smear abnormalities among HIV-positive women with their immune status (CD4 count) and duration of ART. Periodic, regular gynaecologic and Pap smear examination would help in early detection of intraepithelial lesions and their treatment so as to prevent invasive malignancy and mortality.

  2. A chloroplast retrograde signal, 3’-phosphoadenosine 5’-phosphate, acts as a secondary messenger in abscisic acid signaling in stomatal closure and germination

    PubMed Central

    Pornsiriwong, Wannarat; Estavillo, Gonzalo M; Chan, Kai Xun; Tee, Estee E; Ganguly, Diep; Crisp, Peter A; Phua, Su Yin; Zhao, Chenchen; Qiu, Jiaen; Park, Jiyoung; Yong, Miing Tiem; Nisar, Nazia; Yadav, Arun Kumar; Schwessinger, Benjamin; Rathjen, John; Cazzonelli, Christopher I; Wilson, Philippa B; Gilliham, Matthew; Chen, Zhong-Hua; Pogson, Barry J

    2017-01-01

    Organelle-nuclear retrograde signaling regulates gene expression, but its roles in specialized cells and integration with hormonal signaling remain enigmatic. Here we show that the SAL1-PAP (3′-phosphoadenosine 5′- phosphate) retrograde pathway interacts with abscisic acid (ABA) signaling to regulate stomatal closure and seed germination in Arabidopsis. Genetically or exogenously manipulating PAP bypasses the canonical signaling components ABA Insensitive 1 (ABI1) and Open Stomata 1 (OST1); priming an alternative pathway that restores ABA-responsive gene expression, ROS bursts, ion channel function, stomatal closure and drought tolerance in ost1-2. PAP also inhibits wild type and abi1-1 seed germination by enhancing ABA sensitivity. PAP-XRN signaling interacts with ABA, ROS and Ca2+; up-regulating multiple ABA signaling components, including lowly-expressed Calcium Dependent Protein Kinases (CDPKs) capable of activating the anion channel SLAC1. Thus, PAP exhibits many secondary messenger attributes and exemplifies how retrograde signals can have broader roles in hormone signaling, allowing chloroplasts to fine-tune physiological responses. DOI: http://dx.doi.org/10.7554/eLife.23361.001 PMID:28323614

  3. Gene expression polymorphisms and ESTs associated with gravitropic response of subterranean branch meristems and growth habit in Leymus wildryes

    Treesearch

    Parminder Kaur; Ivan W. Mott; Steven R. Larson; B. Shaun Bushman; Alvaro G. Hernandez; W. Ryan Kim; Lei Liu; Mark A. Mikel

    2008-01-01

    Negatively orthogeotropic (NOGT) tiller and diageotropic (DGT) rhizome meristems develop from the same type of lateral axillary meristems and phytomer structure. Although subterranean NOGT and DGT buds appear similar, they display different responses to gravity and perhaps other cues governing branch angle and overall growth habit (GH). Leymus wildryes show remarkable...

  4. Efficacy of positive airway pressure on brain natriuretic peptide in patients with heart failure and sleep-disorder breathing: a meta-analysis of randomized controlled trials.

    PubMed

    Zhang, Xiao-Bin; Yuan, Ya-Ting; Du, Yan-Ping; Jiang, Xing-Tang; Zeng, Hui-Qing

    2015-04-01

    Positive airway pressure (PAP) has been recognized as an effective therapeutic option for sleep-disordered breathing (SDB) in patients with heart failure (HF), and it can improve left ventricular function. Whether PAP can ameliorate serum brain natriuretic peptide (BNP) levels, a biomarker of HF, is controversial. The purpose of the present study was to quantitatively assess the efficacy of PAP on BNP in patients with HF and SDB. A systematic search of PubMed, Embase, Web of Science and Cochrane library identified six randomized controlled trials (RCTs), in which PAP was compared with medical therapy, subtherapeutic PAP or different types of PAP. The data of BNP were extracted and pooled into meta-analysis using STATA 12.0. Totally 6 RCT studies (7 cohorts) with 222 patients were enrolled into analysis. The quality of each study was high and the heterogeneity (I(2) = 58.1%) was noted between studies. A significant reduction of BNP was observed after PAP treatment in patients with HF and SDB (SMD -0.517, 95% CI -0.764 to -0.270, z = 4.11, p = 0.000). Our meta-analysis of RCTs demonstrated that PAP elicits significant reduction of BNP in patients with HF and SDB.

  5. The impact of patient assistance programs and the 340B Drug Pricing Program on medication cost.

    PubMed

    Castellon, Yelba M; Bazargan-Hejazi, Shahrzad; Masatsugu, Miles; Contreras, Roberto

    2014-02-01

    Patient assistance programs and the 340B Drug Pricing Program promise to improve the financial stability, better serve vulnerable patients, and decrease the burden of cost for uninsured patients. Our objective is to examine the financial impact that PAPs and the 340B Program have on improving medication cost. Retrospective analysis of medication dispensary data. Dispensary data for uninsured patients obtaining medications at 2 community health centers were collected from February 1 to February 29, 2012. Uninsured patients were divided into 2 samples: (1) patients receiving PAP medications and (2) patients receiving 340B medications. The main outcome measured was the patient's cost savings. Cost savings were calculated based on the amount a medication would have cost had it been purchased by patients at prices found on Epocrates software (drugstore.com). A paired sample t test model using continuous variables was utilized to calculate confidence intervals. A total of 1420 PAP and 2772 340B individual medications were dispensed to uninsured patients in February 2012. For patients receiving PAP medications the mean ± standard deviation (SD) for age = 52 ± 10. Average cost was $0.11 (95% CI, $0.04-$0.17) and average savings was $617.36 (95% Cl, $581.32-$653.40). For patients receiving 340B medications the mean ±SD for age = 50 ± 14. Average cost was $11.50 (95% CI, $10.55-$12.45). Average saving was $62.31 (95% CI, $57.99-$66.63). PAPs and 340B provide significant medication savings for uninsured patient. More research is needed to establish "best practices" for the successful integration of PAPs.

  6. The association of social support and education with breast and cervical cancer screening.

    PubMed

    Documet, Patricia; Bear, Todd M; Flatt, Jason D; Macia, Laura; Trauth, Jeanette; Ricci, Edmund M

    2015-02-01

    Disparities in breast and cervical cancer screening by socioeconomic status persist in the United States. It has been suggested that social support may facilitate screening, especially among women of low socioeconomic status. However, at present, it is unclear whether social support enables mammogram and Pap test compliance. This study examines the association between social support and compliance with mammogram and Pap test screening guidelines, and whether social support provides added value for women of low education. Data were from a countywide 2009-2010 population-based survey, which included records of 2,588 women 40 years and older (mammogram) and 2,123 women 21 to 65 years old (Pap test). Compliance was determined using the guidelines in effect at the time of data collection. Social support was significantly related to mammogram (adjusted odds ratio = 1.43; 95% confidence interval [1.16, 1.77]) and Pap test (adjusted odds ratio = 1.71; 95% confidence interval [1.27, 2.29]) compliance after controlling for age, race, having a regular health care provider, and insurance status. The interaction between social support and education had a significant effect on Pap test compliance only among women younger than 40; the effect was not significant for mammogram compliance. Social support is associated with breast and cervical cancer screening compliance. The association between education and cancer screening behavior may be moderated by social support; however, results hold only for Pap tests among younger women. Practitioners and researchers should focus on interventions that activate social support networks as they may help increase both breast and cervical cancer screening compliance among women with low educational attainment. © 2014 Society for Public Health Education.

  7. Effects of body position on exercise capacity and pulmonary vascular pressure-flow relationships.

    PubMed

    Forton, Kevin; Motoji, Yoshiki; Deboeck, Gael; Faoro, Vitalie; Naeije, Robert

    2016-11-01

    There has been revival of interest in exercise testing of the pulmonary circulation for the diagnosis of pulmonary vascular disease, but there still is uncertainty about body position and the most relevant measurements. Doppler echocardiography pulmonary hemodynamic measurements were performed at progressively increased workloads in 26 healthy adult volunteers in supine, semirecumbent, and upright positions that were randomly assigned at 24-h intervals. Mean pulmonary artery pressure (mPAP) was estimated from the maximum tricuspid regurgitation jet velocity. Cardiac output was calculated from the left ventricular outflow velocity-time integral. Pulmonary vascular distensibility α-index, the percent change of vessel diameter per millimeter mercury of mPAP, was calculated from multipoint mPAP-cardiac output plots. Body position did not affect maximum oxygen uptake (Vo 2max ), maximum respiratory exchange ratio, ventilatory equivalent for carbon dioxide, or slope of mPAP-cardiac output relationships, which was on average of 1.5 ± 0.4 mmHg·l -1 ·min -1 Maximum mPAP, cardiac output, and total pulmonary vascular resistance were, respectively, 34 ± 4 mmHg, 18 ± 3 l/min, and 1.9 ± 0.3 Wood units. However, the semirecumbent position was associated with a 10% decrease in maximum workload. Furthermore, cardiac output-workload or cardiac output-Vo 2 relationships were nonlinear and variable. These results suggest that body position does not affect maximum exercise testing of the pulmonary circulation when results are expressed as mPAP-cardiac output or maximum total pulmonary vascular resistance. Maximum workload is decreased in semirecumbent compared with upright exercise. Workload or Vo 2 cannot reliably be used as surrogates for cardiac output. Copyright © 2016 the American Physiological Society.

  8. Comparison of Pap smear screening results between Akha hill tribe and urban women in Chiang Rai province, Thailand.

    PubMed

    Kritpetcharat, Onanong; Wutichouy, Wiwat; Sirijaichingkul, Suchat; Kritpetcharat, Panutas

    2012-01-01

    Cervical cancer is an important woman's health problems worldwide, especially in low socio-economic countries. The aim of this study was to compare the Pap smear screening results between Akha hill tribe and urban women who live in Chiang Rai province, Thailand. Screening was conducted for 1,100 Akha women and 1,100 urban women who came to have the Pap smear at Chiangrai Prachanukroh Hospital and 1 private cytology laboratory from January to June 2008. The demographic characteristics and factors related to abnormal Pap smears of these women were gathered using closed model questionnaires. Abnormal Rap smears were defined according to the Bethesda 2001 system. The results showed that the prevalence of abnormal Pap smears was 12.2% in Akha women and 4.5% in urban women. The highest prevalence of Pap abnormalities was found in the 41-50 years age group in both populations (4.5% in Akha and 1.7% in urban women). In both populations, abnormal Pap smears were found in <21 years age groups. From the questionnaires, the possible risk factors related to the higher prevalence of abnormal Pap smears in Akha women were early age at marriage (≤17 years), high frequency pregnacies and high parity and no/low education level. In conclusion, cervical cancer control by education and early detection by Pap smear screening is necessary for hill tribe women. More Pap smear screening service units should be set to improve the coverage for the risk group women who got married in young age, especial in ethnic groups.

  9. An experimental study: quantitatively evaluating the change of the content of collagen fibres in penis with two-dimensional ShearWave™ Elastography.

    PubMed

    Qiao, X-H; Zhang, J-J; Gao, F; Li, F; Bai, M; Du, L-F; Xing, J-F

    2017-06-01

    The purpose of this study was to explore the value of two-dimensional ShearWave ™ Elastography (2D-SWE) on quantitatively evaluating the change of the content of collagen fibres in penis. Twenty male Sprague Dawley rats were divided into the pre-sexual maturity group (Group 1) and the sexual decline group (Group 2) according to age. The ultrafast ultrasound device Aixplorer ® (SuperSonic Imagine, Aix-en-Provence, France) was used for 2D-SWE imaging of penis, and the measurement index was shear wave stiffness (SWS). The immunohistochemistry was used to analyse the content of collagen fibres in penis, and the measurement index was positive area percentage (PAP). The differences of SWS between the two groups and PAP between the two groups were analysed. SWS of Group 1 and Group 2 was 10.18 ± 1.09 and 8.02 ± 1.34 kPa, and SWS of Group 2 was significantly lower than Group 1 (p < .01). PAP of Group 1 and Group 2 was 4.83 ± 3.61% and 16.41 ± 10.02%, and PAP of Group 2 was significantly higher than Group 1 (p < .01). Our results indicate that when the content of collagen fibres changes, SWS of penis measured with 2D-SWE would change significantly as well. Two-dimensional SWE can be used to quantitatively evaluate the change of the content of collagen fibres in penis. © 2016 Blackwell Verlag GmbH.

  10. Cervical Cancer Screening in the US–Mexico Border Region: A Binational Analysis

    PubMed Central

    Schiefelbein, Emily L.; Smith, Ruben; Rojas, Rosalba; Mirchandani, Gita G.; McDonald, Jill A.

    2015-01-01

    Cervical cancer mortality is high along the US–Mexico border. We describe the prevalence of a recent Papanicolaou screening test (Pap) among US and Mexican border women. We analyzed 2006 cross-sectional data from Mexico’s National Survey of Health and Nutrition and the US Behavioral Risk Factor Surveillance System. Women aged 20–77 years in 44 US border counties (n = 1,724) and 80 Mexican border municipios (n = 1,454) were studied. We computed weighted proportions for a Pap within the past year by age, education, employment, marital status, health insurance, health status, risk behaviors, and ethnicity and adjusted prevalence ratios (APR) for the US, Mexico, and the region overall. Sixty-five percent (95 %CI 60.3–68.6) of US women and 32 % (95 %CI 28.7–35.2) of Mexican women had a recent Pap. US residence (APR = 2.01, 95 %CI 1.74–2.33), marriage (APR = 1.31, 95 %CI 1.17–1.47) and insurance (APR = 1.38, 95 %CI 1.22–1.56) were positively associated with a Pap test. Among US women, insurance and marriage were associated (APR = 1.21, 95 %CI 1.05–1.38 and 1.33, 95 %CI 1.10–1.61, respectively), and women aged 20–34 years were about 25 % more likely to have received a test than older women. Insurance and marriage were also positively associated with Pap testing among Mexican women (APR = 1.39, 95 %CI 1.17–1.64 and 1.50; 95 %CI 1.23–1.82, respectively), as were lower levels of education (≤8th grade or 9th–12th grade versus some college) (APR = 1.74; 95 %CI 1.21–2.52 and 1.60; 95 %CI 1.03–2.49, respectively). Marriage and insurance were associated with a recent Pap test on both sides of the border. Binational insurance coverage increases and/or cost reductions might bolster testing among unmarried and uninsured women, leading to earlier cervical cancer diagnosis and potentially lower mortality. PMID:22965734

  11. Cervical cancer screening in the US-Mexico border region: a binational analysis.

    PubMed

    Herrera, Dyanne G; Schiefelbein, Emily L; Smith, Ruben; Rojas, Rosalba; Mirchandani, Gita G; McDonald, Jill A

    2012-12-01

    Cervical cancer mortality is high along the US-Mexico border. We describe the prevalence of a recent Papanicolaou screening test (Pap) among US and Mexican border women. We analyzed 2006 cross-sectional data from Mexico's National Survey of Health and Nutrition and the US Behavioral Risk Factor Surveillance System. Women aged 20-77 years in 44 US border counties (n = 1,724) and 80 Mexican border municipios (n = 1,454) were studied. We computed weighted proportions for a Pap within the past year by age, education, employment, marital status, health insurance, health status, risk behaviors, and ethnicity and adjusted prevalence ratios (APR) for the US, Mexico, and the region overall. Sixty-five percent (95 %CI 60.3-68.6) of US women and 32 % (95 %CI 28.7-35.2) of Mexican women had a recent Pap. US residence (APR = 2.01, 95 %CI 1.74-2.33), marriage (APR = 1.31, 95 %CI 1.17-1.47) and insurance (APR = 1.38, 95 %CI 1.22-1.56) were positively associated with a Pap test. Among US women, insurance and marriage were associated (APR = 1.21, 95 %CI 1.05-1.38 and 1.33, 95 %CI 1.10-1.61, respectively), and women aged 20-34 years were about 25 % more likely to have received a test than older women. Insurance and marriage were also positively associated with Pap testing among Mexican women (APR = 1.39, 95 %CI 1.17-1.64 and 1.50; 95 %CI 1.23-1.82, respectively), as were lower levels of education (≤8th grade or 9th-12th grade versus some college) (APR = 1.74; 95 %CI 1.21-2.52 and 1.60; 95 %CI 1.03-2.49, respectively). Marriage and insurance were associated with a recent Pap test on both sides of the border. Binational insurance coverage increases and/or cost reductions might bolster testing among unmarried and uninsured women, leading to earlier cervical cancer diagnosis and potentially lower mortality.

  12. Abnormal pap tests among women living in a Hispanic migrant farmworker community: A narrative of health literacy.

    PubMed

    Vamos, Cheryl A; Lockhart, Elizabeth; Vázquez-Otero, Coralia; Thompson, Erika L; Proctor, Sara; Wells, Kristen J; Daley, Ellen M

    2016-08-01

    This study explored narrative responses following abnormal Pap tests among Hispanic migrant farmworkers ( N = 18; ages 22-50 years) via in-depth interviews in Florida. Qualitative analyses utilized health literacy domains (obtain/process/understand/communicate) as a conceptual framework. Participants described how they (1) obtained information about getting a Pap test, (2) processed positive and negative reactions following results, (3) understood results and recommended health-promoting behaviors, and (4) communicated and received social support. Women had disparate reactions and understanding following an abnormal Pap result. Health literacy was a meaningful conceptual framework to understand assets and gaps among women receiving an abnormal Pap test result. Future interventions should incorporate health literacy domains and facilitate patient-provider communications and social support to assist women in decision-making and health-promoting behaviors, ultimately decreasing cancer disparities.

  13. Increased concentrations of soluble CD40 ligand platelet in patients with primary antiphospholipidic syndrome.

    PubMed

    Galicia López, Aida; Olguín Ortega, Lourdes; Saavedra, Miguel A; Méndez Cruz, René; Jimenez Flores, Rafael; García de la Peña, Maximiliano

    2013-01-01

    To determine the concentrations of sCD40L in patients with PAPS, and establish its association with the number of thrombosis. We included patients with PAPS and healthy controls of the same age and sex. For analysis, patients with PAPS were divided into 2 groups: 1) patients with 1 thrombosis, and 2) patients with >1 thrombosis. Soluble CD40L concentrations were determined by ELISA method. sCD40L concentrations were significantly higher in patients with PAPS compared with the controls (9.72 ng ± 11.23 ng/ml vs. 4.69 ± 4.04 ng/ml) (P=.04) There was no association between serum levels of sCD40L and the number of thrombosis (1 thrombosis: 9.81 ± 9.87 ng/ml vs 9.63 ± 12.75 ng/ml in ≥ 1thrombosis (P=.13). In women with pregnancy and abortions, (13 patients) concentrations of sCD40L were higher than in those patients without a history of abortion (26 patients) but without statically significant difference (12.11 ± 16.46 ng/ml vs. 8.80 ± 8.61 ng/ml) (P=.33). There was no correlation between levels of sCD40L and the total number of thrombosis. Patients with PAPS have higher concentrations of sCD40L compared with healthy subjects, although this is not associated with a greater number of thrombosis. Among patients with PAPS, there is a tendency to higher concentrations of sCD40L in women with pregnancy and history of abortion. Since the platelet is the main cellular source of sCD40L, is possible that this pathway plays a pathogenic role in patients with PAPS. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  14. Effects of Different Post-Activation Potentiation Warm-Ups on Repeated Sprint Ability in Soccer Players from Different Competitive Levels.

    PubMed

    Sanchez-Sanchez, Javier; Rodriguez, Alejandro; Petisco, Cristina; Ramirez-Campillo, Rodrigo; Martínez, Cristian; Nakamura, Fábio Y

    2018-03-01

    This study aimed to compare the effects of a traditional warm-up with two post-activation potentiation (PAP) warm-up strategies on the repeated sprint ability (RSA) of soccer players from national (NL) and regional (RL) competitive levels. Sixteen young players (NL, n = 8, age = 20.7 ± 1.4 y, body mass = 68.5 ± 7.0 kg, body height = 177.4 ± 5.2 cm; RL, n = 8, age = 20.8 ± 1.0 y, body mass = 68.7 ± 4.0 kg, body height = 176.6 ± 5.6 cm) were recruited to complete a traditional warm-up (CONTROL), a PAP warm-up incorporating squats with a load (~60% 1RM) that allowed a high speed (1 m/s) of movement and a high number of repetitions (PAP-1), and a PAP warm-up with a load (~90% 1RM) that allowed a moderate speed (0.5 m/s) of movement and a reduced number of repetitions (PAP-0.5). A RSA test (six 20-m sprints with 20 s of recovery) was performed 5 min after the PAP warm-up to assess the effects of the different protocols on the fastest sprint (RSAb) and the mean time of all sprints (RSAm). A meaningful improvement of RSA performance was observed with PAP-0.5, attaining a large effect on NL (RSAb, ES = -1.5; RSAm, ES = -1.3) and only a small effect on RL athletes (RSAb and RSAm, ES = -0.2). Moreover, when each RSA sprint performance was compared between NL and RL players, after PAP-0.5 greater performance for all sprints was observed in the NL players. Therefore, adding a heavy strength-based conditioning exercise during the warm-up prior to a RSA test may induce significant performance improvements in NL, but only small effects in RL players.

  15. Effects of Different Post-Activation Potentiation Warm-Ups on Repeated Sprint Ability in Soccer Players from Different Competitive Levels

    PubMed Central

    Sanchez-Sanchez, Javier; Rodriguez, Alejandro; Petisco, Cristina; Ramirez-Campillo, Rodrigo; Martínez, Cristian; Nakamura, Fábio Y.

    2018-01-01

    Abstract This study aimed to compare the effects of a traditional warm-up with two post-activation potentiation (PAP) warm-up strategies on the repeated sprint ability (RSA) of soccer players from national (NL) and regional (RL) competitive levels. Sixteen young players (NL, n = 8, age = 20.7 ± 1.4 y, body mass = 68.5 ± 7.0 kg, body height = 177.4 ± 5.2 cm; RL, n = 8, age = 20.8 ± 1.0 y, body mass = 68.7 ± 4.0 kg, body height = 176.6 ± 5.6 cm) were recruited to complete a traditional warm-up (CONTROL), a PAP warm-up incorporating squats with a load (~60% 1RM) that allowed a high speed (1 m/s) of movement and a high number of repetitions (PAP-1), and a PAP warm-up with a load (~90% 1RM) that allowed a moderate speed (0.5 m/s) of movement and a reduced number of repetitions (PAP-0.5). A RSA test (six 20-m sprints with 20 s of recovery) was performed 5 min after the PAP warm-up to assess the effects of the different protocols on the fastest sprint (RSAb) and the mean time of all sprints (RSAm). A meaningful improvement of RSA performance was observed with PAP-0.5, attaining a large effect on NL (RSAb, ES = -1.5; RSAm, ES = -1.3) and only a small effect on RL athletes (RSAb and RSAm, ES = -0.2). Moreover, when each RSA sprint performance was compared between NL and RL players, after PAP-0.5 greater performance for all sprints was observed in the NL players. Therefore, adding a heavy strength-based conditioning exercise during the warm-up prior to a RSA test may induce significant performance improvements in NL, but only small effects in RL players. PMID:29599871

  16. Oral health in patients treated by positive airway pressure for obstructive sleep apnea: a population-based case-control study.

    PubMed

    Carra, M C; Thomas, F; Schmitt, A; Pannier, B; Danchin, N; Bouchard, Ph

    2016-03-01

    Recent epidemiological evidence suggests that patients with obstructive sleep apnea (OSA) have an increased risk of periodontal disease. Little is known about the oral health of OSA patients treated by continuous or bi-level positive airway pressure (CPAP/BiPAP). The aim of this population-based case-control study was to compare oral health variables (amount of plaque, calculus, gingival inflammation, and masticatory function) between CPAP/BiPAP users and control subjects. The study population was retrieved from a French cohort examined between 2012 and 2013 at the Centre d'Investigations Préventives et Cliniques of Paris. Cases were selected if they reported to be treated by CPAP/BiPAP; controls were age-, gender-, and BMI-matched based on a 1:2 ratio. Univariate and logistic regression analyses were performed for group comparisons. Over a total of 20,436 subjects, 287 CPAP/BiPAP users (mean age (SD) 57.6 years (11.5); 76.3 % males) who underwent medical and dental examinations were compared with 574 matched controls (no OSA, no CPAP/BiPAP). CPAP/BiPAP users reported significantly higher prevalence of diabetes (15.6 vs. 10.3 %; p = 0.012; odds ratio (OR) 1.68), history of hypertension (36.5 vs. 26.1 %; p = 0.003; OR 1.62), cardiovascular diseases (14.1 vs. 8.8 %; p = 0.029; OR 1.69), and sleep complaints (59 vs. 34.4 %; p = 0.0001; OR 2.75). CPAP/BiPAP users also showed higher levels of depression and stress compared to controls. However, no group difference was observed for the amount of dental plaque, calculus, gingival inflammation, and masticatory function. Oral health of OSA patients treated by CPAP/BiPAP is comparable to that of matched controls in terms of amount of plaque, gingival inflammation, and masticatory function.

  17. A community-based randomized trial of a faith-placed intervention to reduce cervical cancer burden in Appalachia.

    PubMed

    Studts, Christina R; Tarasenko, Yelena N; Schoenberg, Nancy E; Shelton, Brent J; Hatcher-Keller, Jennifer; Dignan, Mark B

    2012-06-01

    Faith Moves Mountains assessed the effectiveness of a faith-placed lay health advisor (LHA) intervention to increase Papanicolaou (Pap) test use among middle-aged and older women in a region disproportionately affected by cervical cancer and low screening rates (regionally, only 68% screened in prior 3 years). This community-based RCT was conducted in four Appalachian Kentucky counties (December 2005-June 2008). Women aged 40-64 and overdue for screening were recruited from churches and individually randomized to treatment (n=176) or wait-list control (n=169). The intervention provided LHA home visits and newsletters addressing barriers to screening. Self-reported Pap test receipt was the primary outcome. Intention-to-treat analyses revealed that treatment group participants (17.6% screened) had over twice the odds of wait-list controls (11.2% screened) of reporting Pap test receipt post-intervention, OR=2.56, 95% CI: 1.03-6.38, p=0.04. Independent of group, recently screened participants (last Pap >1 but <5 years ago) had significantly higher odds of obtaining screening during the study than rarely or never screened participants (last Pap ≥5 years ago), OR=2.50, 95% CI: 1.48-4.25, p=0.001. The intervention was associated with increased cervical cancer screening. The faith-placed LHA addressing barriers comprises a novel approach to reducing cervical cancer disparities among Appalachian women. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. A community-based randomized trial of a faith-placed intervention to reduce cervical cancer burden in Appalachia

    PubMed Central

    Studts, Christina R.; Tarasenko, Yelena N.; Schoenberg, Nancy E.; Shelton, Brent J.; Hatcher-Keller, Jennifer; Dignan, Mark B.

    2012-01-01

    Objective Faith Moves Mountains assessed the effectiveness of a faith-placed lay health advisor (LHA) intervention to increase Papanicolaou (Pap) test use among middle-aged and older women in a region disproportionately affected by cervical cancer and low screening rates (regionally, only 68% screened in prior 3 years). Method This community-based RCT was conducted in four Appalachian Kentucky counties (December 2005 – June 2008). Women aged 40–64 and overdue for screening were recruited from churches and individually randomized to treatment (n=176) or wait-list control (n=169). The intervention provided LHA home visits and newsletters addressing barriers to screening. Self-reported Pap test receipt was the primary outcome. Results Intention-to-treat analyses revealed that treatment group participants (17.6% screened) had over twice the odds of wait-list controls (11.2% screened) of reporting Pap test receipt post-intervention, OR=2.56, 95%CI: 1.03–6.38, p=0.04. Independent of group, recently screened participants (last Pap >1 but <5 years ago) had significantly higher odds of obtaining screening during the study than rarely or never screened participants (last Pap ≥5 years ago), OR=2.50, 95%CI: 1.48–4.25, p=0.001. Conclusions The intervention was associated with increased cervical cancer screening. The faith-placed LHA addressing barriers comprises a novel approach to reducing cervical cancer disparities among Appalachian women. PMID:22498022

  19. ThinPrep Pap-smear and cervical intraepithelial neoplasia in reproductive-aged Thai women.

    PubMed

    Rugpao, S; Koonlertkit, S; Ruengkrist, T; Lamlertkittikul, S; Pinjaroen, S; Limtrakul, A; Werawatakul, Y; Sinchai, W

    2009-06-01

    To estimate the incidence of abnormal cervical cytology by ThinPrep Pap-tests and cervical intraepithelial neoplasia (CIN) in young adult reproductive-aged Thai women. A total of 1254 women distributed in all regions of Thailand were monitored from 2002 through 2004. Women were screened for abnormal cervical cytology using the ThinPrep method every 6 months. Interpretation of cervical cytology was based on the Bethesda system, version 2001. Women who had the ThinPrep Pap results as atypical squamous cells of undetermined significance or worse underwent colposcopic examination. The ThinPrep and all cervical tissue samples obtained from diagnostic or therapeutic procedures were analyzed and reviewed by Covance Central Laboratory Service, Inc., Indianapolis, USA. The cumulative incidence of abnormal ThinPrep Pap-tests was as follows: 15.3 per 100 woman years (WY) (95% confidence interval [CI] 12.3, 18.9) at 6 months; 12.3 per 100 WY (95% CI 10.3, 14.6) at 12 months; and 11.6 per 100 WY (95% CI 10.0, 13.5) at 18 months. Of 1448.6 woman years of follow up, the incidence of CIN1 was 4.1 per 100 WY (95% CI 3.2, 5.3); CIN2 0.8 per 100 WY (95% CI 0.4, 1.4); and CIN3 0.6 per 100 WY (95% CI 0.3, 1.2). The incidence of abnormal ThinPrep Pap-test and CIN in young adult Thai women had been reported. No comparable data is available.

  20. The comparative and cost-effectiveness of HPV-based cervical cancer screening algorithms in El Salvador.

    PubMed

    Campos, Nicole G; Maza, Mauricio; Alfaro, Karla; Gage, Julia C; Castle, Philip E; Felix, Juan C; Cremer, Miriam L; Kim, Jane J

    2015-08-15

    Cervical cancer is the leading cause of cancer death among women in El Salvador. Utilizing data from the Cervical Cancer Prevention in El Salvador (CAPE) demonstration project, we assessed the health and economic impact of HPV-based screening and two different algorithms for the management of women who test HPV-positive, relative to existing Pap-based screening. We calibrated a mathematical model of cervical cancer to epidemiologic data from El Salvador and compared three screening algorithms for women aged 30-65 years: (i) HPV screening every 5 years followed by referral to colposcopy for HPV-positive women (Colposcopy Management [CM]); (ii) HPV screening every 5 years followed by treatment with cryotherapy for eligible HPV-positive women (Screen and Treat [ST]); and (iii) Pap screening every 2 years followed by referral to colposcopy for Pap-positive women (Pap). Potential harms and complications associated with overtreatment were not assessed. Under base case assumptions of 65% screening coverage, HPV-based screening was more effective than Pap, reducing cancer risk by ∼ 60% (Pap: 50%). ST was the least costly strategy, and cost $2,040 per year of life saved. ST remained the most attractive strategy as visit compliance, costs, coverage, and test performance were varied. We conclude that a screen-and-treat algorithm within an HPV-based screening program is very cost-effective in El Salvador, with a cost-effectiveness ratio below per capita GDP. © 2015 UICC.

  1. Papanicolaou Testing by Physicians in Manitoba: Who Does Them?

    PubMed Central

    Cohen, Marsha M.; Hammarstrand, Karen M.

    1989-01-01

    Pap testing is one of the few effective preventive health practices available to primary care physicians. Yet we know little about how well this procedure is being done. Using data from the province of Manitoba's universal health insurance plan for the years 1976, 1978 and 1982, we determined the proportion of all Pap tests of women over 25 years of age performed by the various physician specialties; the percentage of physicians in each specialty who performed tests; and the mean number of tests per specialty group. We also determined the mean number of tests by age and training of the physician. The number of physicians performing Pap tests increased from 749 in 1976 to 780 in 1982. About 2% of Pap tests performed in the province were done by internists, 5% by general surgeons, about 33% by obstetrician/gynecologists, 40% by urban general practitioners, and 22% by rural general practitioners. Other physicians accounted for less than 0.2% of all tests. The mean number of Pap tests performed increased with increasing physician age up to age 60 and declined thereafter. Manitoba-trained physicians performed the highest rate of Pap testing, and this pattern was maintained over time. In 1982, only 22% of internists, 29% of general surgeons, and 78% of family physicians/general practitioners were performing tests. These results raise the question of why a significant number of physicians are not carrying out this effective preventive health practice. PMID:21248879

  2. Effects of Age and Acute Moderate Alcohol Administration on Electrophysiological Correlates of Working Memory Maintenance.

    PubMed

    Boissoneault, Jeff; Frazier, Ian; Lewis, Ben; Nixon, Sara Jo

    2016-09-01

    Previous studies suggest older adults may be differentially susceptible to the acute neurobehavioral effects of moderate alcohol intake. To our knowledge, no studies have addressed acute moderate alcohol effects on the electrophysiological correlates of working memory in younger and older social drinkers. This study characterized alcohol-related effects on frontal theta (FTP) and posterior alpha power (PAP) associated with maintenance of visual information during a working memory task. Older (55 to 70 years of age; n = 51, 29 women) and younger (25 to 35 years of age; n = 70, 39 women) community-dwelling moderate drinkers were recruited for this study. Participants were given either placebo or an active dose targeting breath alcohol concentrations (BrACs) of 0.04 or 0.065 g/dl. Following absorption, participants completed a visual working memory task assessing cue recognition following a 9-s delay. FTP and PAP were determined via Fourier transformation and subjected to 2 (age group) × 3 (dose) × 2 (repeated: working memory task condition) mixed models analysis. In addition to expected age-related reductions in PAP, a significant age group × dose interaction was detected for PAP such that 0.04 g/dl dose level was associated with greater PAP in younger adults but lower PAP in their older counterparts. PAP was lower in older versus younger adults at both active doses. Further mixed models revealed a significant negative association between PAP and working memory efficiency for older adults. No effects of age, dose, or their interaction were noted for FTP. Results bolster the small but growing body of evidence that older adults exhibit differential sensitivity to the neurobehavioral effects of moderate alcohol use. Given the theoretical role of PAP in attentional and working memory function, these findings shed light on the attentional mechanisms underlying effects of acute moderate alcohol on working memory efficiency in older adults. Copyright © 2016 by the Research Society on Alcoholism.

  3. Cost-effectiveness of HPV-based cervical cancer screening in the public health system in Nicaragua.

    PubMed

    Campos, Nicole G; Mvundura, Mercy; Jeronimo, Jose; Holme, Francesca; Vodicka, Elisabeth; Kim, Jane J

    2017-06-15

    To evaluate the cost-effectiveness of human papillomavirus (HPV) DNA testing (versus Papanicolaou (Pap)-based screening) for cervical cancer screening in Nicaragua. A previously developed Monte Carlo simulation model of the natural history of HPV infection and cervical cancer was calibrated to epidemiological data from Nicaragua. Cost data inputs were derived using a micro-costing approach in Carazo, Chontales and Chinandega departments; test performance data were from a demonstration project in Masaya department. Nicaragua's public health sector facilities. Women aged 30-59 years. Screening strategies included (1) Pap testing every 3 years, with referral to colposcopy for women with an atypical squamous cells of undetermined significance or worse result ('Pap'); (2) HPV testing every 5 years, with referral to cryotherapy for HPV-positive eligible women (HPV cryotherapy or 'HPV-Cryo'); (3) HPV testing every 5 years, with referral to triage with visual inspection with acetic acid (VIA) for HPV-positive women ('HPV-VIA'); and (4) HPV testing every 5 years, with referral to Pap testing for HPV-positive women ('HPV-Pap'). Reduction in lifetime risk of cancer and incremental cost-effectiveness ratios (ICER; 2015 US$ per year of life saved (YLS)). HPV-based screening strategies were more effective than Pap testing. HPV-Cryo was the least costly and most effective strategy, reducing lifetime cancer risk by 29.5% and outperforming HPV-VIA, HPV-Pap and Pap only, which reduced cancer risk by 19.4%, 12.2% and 10.8%, respectively. With an ICER of US$320/YLS, HPV-Cryo every 5 years would be very cost-effective using a threshold based on Nicaragua's per capita gross domestic product of US$2090. Findings were robust across sensitivity analyses on test performance, coverage, compliance and cost parameters. HPV testing is very cost-effective compared with Pap testing in Nicaragua, due to higher test sensitivity and the relatively lower number of visits required. Increasing compliance with recommended follow-up will further improve the health benefits and value for public health dollars. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  4. High-Flow Nasal Oxygen vs Noninvasive Positive Airway Pressure in Hypoxemic Patients After Cardiothoracic Surgery: A Randomized Clinical Trial.

    PubMed

    Stéphan, François; Barrucand, Benoit; Petit, Pascal; Rézaiguia-Delclaux, Saida; Médard, Anne; Delannoy, Bertrand; Cosserant, Bernard; Flicoteaux, Guillaume; Imbert, Audrey; Pilorge, Catherine; Bérard, Laurence

    2015-06-16

    Noninvasive ventilation delivered as bilevel positive airway pressure (BiPAP) is often used to avoid reintubation and improve outcomes of patients with hypoxemia after cardiothoracic surgery. High-flow nasal oxygen therapy is increasingly used to improve oxygenation because of its ease of implementation, tolerance, and clinical effectiveness. To determine whether high-flow nasal oxygen therapy was not inferior to BiPAP for preventing or resolving acute respiratory failure after cardiothoracic surgery. Multicenter, randomized, noninferiority trial (BiPOP Study) conducted between June 15, 2011, and January 15, 2014, at 6 French intensive care units. A total of 830 patients who had undergone cardiothoracic surgery, of which coronary artery bypass, valvular repair, and pulmonary thromboendarterectomy were the most common, were included when they developed acute respiratory failure (failure of a spontaneous breathing trial or successful breathing trial but failed extubation) or were deemed at risk for respiratory failure after extubation due to preexisting risk factors. Patients were randomly assigned to receive high-flow nasal oxygen therapy delivered continuously through a nasal cannula (flow, 50 L/min; fraction of inspired oxygen [FiO2], 50%) (n = 414) or BiPAP delivered with a full-face mask for at least 4 hours per day (pressure support level, 8 cm H2O; positive end-expiratory pressure, 4 cm H2O; FiO2, 50%) (n = 416). The primary outcome was treatment failure, defined as reintubation, switch to the other study treatment, or premature treatment discontinuation (patient request or adverse effects, including gastric distention). Noninferiority of high-flow nasal oxygen therapy would be demonstrated if the lower boundary of the 95% CI were less than 9%. Secondary outcomes included mortality during intensive care unit stay, changes in respiratory variables, and respiratory complications. High-flow nasal oxygen therapy was not inferior to BiPAP: the treatment failed in 87 of 414 patients with high-flow nasal oxygen therapy (21.0%) and 91 of 416 patients with BiPAP (21.9%) (absolute difference, 0.9%; 95% CI, -4.9% to 6.6%; P = .003). No significant differences were found for intensive care unit mortality (23 patients with BiPAP [5.5%] and 28 with high-flow nasal oxygen therapy [6.8%]; P = .66) (absolute difference, 1.2% [95% CI, -2.3% to 4.8%]. Skin breakdown was significantly more common with BiPAP after 24 hours (10% vs 3%; 95% CI, 7.3%-13.4% vs 1.8%-5.6%; P < .001). Among cardiothoracic surgery patients with or at risk for respiratory failure, the use of high-flow nasal oxygen therapy compared with intermittent BiPAP did not result in a worse rate of treatment failure. The findings support the use of high-flow nasal oxygen therapy in similar patients. clinicaltrials.gov Identifier: NCT01458444.

  5. Repurposing Hsp104 to antagonize seminal amyloid and counter HIV infection

    PubMed Central

    Castellano, Laura M.; Bart, Stephen M.; Holmes, Veronica M.; Weissman, Drew; Shorter, James

    2015-01-01

    Naturally occurring proteolytic fragments of prostatic acid phosphatase (PAP248-286 and PAP85-120) and semenogelins (SEM1 and 2) form amyloid fibrils in seminal fluid, which capture HIV virions and promote infection. For example, PAP248-286 fibrils, termed SEVI (Semen derived Enhancer of Viral Infection), can potentiate HIV infection by several orders of magnitude. Here, we design three disruptive technologies to rapidly antagonize seminal amyloid by repurposing Hsp104, an amyloid-remodeling nanomachine from yeast. First, Hsp104 and an enhanced engineered variant, Hsp104A503V, directly remodel SEVI and PAP85-120 fibrils into non-amyloid forms. Second, we elucidate catalytically inactive Hsp104 scaffolds that do not remodel amyloid structure, but cluster SEVI, PAP85-120, and SEM1(45-107) fibrils into larger assemblies. Third, we modify Hsp104 to interact with the chambered protease ClpP, which enables coupled remodeling and degradation to irreversibly clear SEVI and PAP85-120 fibrils. Each strategy diminished the ability of seminal amyloid to promote HIV infection and could have therapeutic utility. PMID:26256479

  6. Repurposing Hsp104 to Antagonize Seminal Amyloid and Counter HIV Infection.

    PubMed

    Castellano, Laura M; Bart, Stephen M; Holmes, Veronica M; Weissman, Drew; Shorter, James

    2015-08-20

    Naturally occurring proteolytic fragments of prostatic acid phosphatase (PAP248-286 and PAP85-120) and semenogelins (SEM1 and SEM2) form amyloid fibrils in seminal fluid, which capture HIV virions and promote infection. For example, PAP248-286 fibrils, termed SEVI (semen-derived enhancer of viral infection), can potentiate HIV infection by several orders of magnitude. Here, we design three disruptive technologies to rapidly antagonize seminal amyloid by repurposing Hsp104, an amyloid-remodeling nanomachine from yeast. First, Hsp104 and an enhanced engineered variant, Hsp104(A503V), directly remodel SEVI and PAP85-120 fibrils into non-amyloid forms. Second, we elucidate catalytically inactive Hsp104 scaffolds that do not remodel amyloid structure, but cluster SEVI, PAP85-120, and SEM1(45-107) fibrils into larger assemblies. Third, we modify Hsp104 to interact with the chambered protease ClpP, which enables coupled remodeling and degradation to irreversibly clear SEVI and PAP85-120 fibrils. Each strategy diminished the ability of seminal amyloid to promote HIV infection, and could have therapeutic utility. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. [EzPAP® therapy of postoperative hypoxemia in the recovery room : experiences with the new compact system of end-expiratory positive airway pressure].

    PubMed

    Rieg, A D; Stoppe, C; Rossaint, R; Coburn, M; Hein, M; Schälte, G

    2012-10-01

    Postoperative hypoxemia is a common complication in the anesthesia recovery room (ARR), which is predominantly based on the development of atelectasis, excessive intraoperative fluid shift and insufficient ventilation. The goal of this prospective observational study was to compare the effect of standard oxygen administration via a face mask with oxygen administration using the EzPAP® system, a device which additionally provides a positive end-expiratory pressure (PEEP). This study included 210 patients with postoperative hypoxemia (S(p)O(2) < 93%) subdivided into the control group (105 patients) and the EzPAP group (105 patients). Postoperative residual paralysis was excluded using relaxometry and a train of four (TOF) ratio of 0.9 was assumed to ensure sufficient recovery of respiratory function from neuromuscular blockade. Patients who received a reversal of neuromuscular blockade were excluded. In cases of hypoxemia (S(p)O(2) < 93%) control patients were treated with oxygen (6 l/min) using a face mask, whereas the EzPAP group received oxygen using the EzPAP® system. In order to adjust the PEEP in the EzPAP group, the O(2) flow was verified and measured by a manometer. After 1 h of oxygen therapy, the oxygen supply was stopped. In cases of reoccurring hypoxemia (S(p)O(2) < 93%, persistence > 5 min), the oxygen therapy was restarted in both groups via a facemask. Both groups were compared using repeat measurement analysis of variance (ANOVA), the unpaired t-test, the Mann-Whitney U-test, Fisher's exact test and the χ(2)-test. The correlation of O(2) flow and PEEP was evaluated by regression analysis and p < 0.05 was considered to be statistically significant. Apart from this a subgroup analysis was performed depending on body-mass index (BMI), American Society of Anesthesiologists (ASA) classification, intraoperative airway management, the use of neuromuscular blocking agents and co-existing disorders, e.g. chronic obstructive lung disease (COLD), obesity and chronic heart failure. All patients were equally distributed between both groups with respect to demographic data, ASA classification, BMI, co-existing disorders and surgical procedures. The S(p)O(2) values did not differ between the EzPAP patients and the control group, except for 0.5 min after initiation of oxygen therapy: EzPAP group 96 ± 3.7% (mean ± standard deviation) versus the control group 93.8 ± 4.4% (p < 0.001). However, restarting oxygen therapy was less common in the EzPAP group (EzPAP group 25 versus control group 41, p = 0.03), as well as the occurrence of postoperative complications (EzPAP group 13 versus control group 25, p = 0.02), e.g. nosocomial pneumonia (0 versus 4) and wound infections (2 versus 3). Furthermore, patients with obesity and pulmonary disorders, such as COLD had a benefit from oxygen administration using the EzPAP device and showed higher postoperative than preoperative S(p)O(2) values. In contrast, the subgroup analysis of patients with heart failure did not reveal any differences between both groups and both groups did not differ in terms of time spent in the recovery room (EzPAP group 113 min versus control group 174.8 min, p = 0.2). In this observational study oxygen supply using the EzPAP® system appeared to be at least equally as effective in the therapy of postoperative hypoxemia compared to standard oxygen supply using a face mask. In patients with a high risk of postoperative hypoxemia, such as patients with obesity and/or pulmonary disorders, oxygen administration using the EzPAP® system possibly improves pulmonary oxygenation more effectively and is longer lasting compared to standard oxygen supply via a face mask. Hence, the EzPAP® system represents a well-tolerated, effective, cost-effective and easily operated tool to improve postoperative oxygenation. In order to investigate the possibilities of this promising tool more intensively, randomized clinical trials are warranted.

  8. Short term evaluation of respiratory effort by premature infants supported with bubble nasal continuous airway pressure using Seattle-PAP and a standard bubble device

    PubMed Central

    Welty, Stephen E.; Rusin, Craig G.; Stanberry, Larissa I.; Mandy, George T.; Gest, Alfred L.; Ford, Jeremy M.; Backes, Carl H.; Richardson, C. Peter; Howard, Christopher R.; Hansen, Thomas N.

    2018-01-01

    Background Almost one million prematurely born infants die annually from respiratory insufficiency, predominantly in countries with limited access to respiratory support for neonates. The primary hypothesis tested in the present study was that a modified device for bubble nasal continuous positive airway pressure (Bn-CPAP) would provide lower work of spontaneous breathing, estimated by esophageal pressure-rate products. Methods Infants born <32 weeks gestation and stable on Bn-CPAP with FiO2 <0.30 were studied within 72 h following delivery. Esophageal pressures during spontaneous breathing were measured during 2 h on standard Bn-CPAP, then 2 h with Bn-CPAP using a modified bubble device presently termed Seattle-PAP, which produces a different pattern of pressure fluctuations and which provided greater respiratory support in preclinical studies, then 2 h on standard Bn-CPAP. Results All 40 infants enrolled completed the study and follow-up through 36 wks post menstrual age or hospital discharge, whichever came first. No infants were on supplemental oxygen at completion of follow-up. No infants developed pneumothoraces or nasal trauma, and no adverse events attributed to the study were observed. Pressure-rate products on the two devices were not different, but effort of breathing, assessed by areas under esophageal pressure-time curves, was lower with Seattle-PAP than with standard Bn-CPAP. Conclusion Use of Seattle-PAP to implement Bn-CPAP lowers the effort of breathing exerted even by relatively healthy spontaneously breathing premature neonates. Whether the lower effort of breathing observed with Seattle-PAP translates to improvements in neonatal mortality or morbidity will need to be determined by studies in appropriate patient populations. PMID:29590143

  9. Optimized expression of prolyl aminopeptidase in Pichia pastoris and its characteristics after glycosylation.

    PubMed

    Yang, Hongyu; Zhu, Qiang; Zhou, Nandi; Tian, Yaping

    2016-11-01

    Prolyl aminopeptidases are specific exopeptidases that catalyze the hydrolysis of the N-terminus proline residue of peptides and proteins. In the present study, the prolyl aminopeptidase gene (pap) from Aspergillus oryzae JN-412 was optimized through the codon usage of Pichia pastoris. Both the native and optimized pap genes were inserted into the expression vector pPIC9 K and were successfully expressed in P. pastoris. Additionally, the activity of the intracellular enzyme expressed by the recombinant optimized pap gene reached 61.26 U mL(-1), an activity that is 2.1-fold higher than that of the native gene. The recombinant enzyme was purified by one-step elution through Ni-affinity chromatography. The optimal temperature and pH of the purified PAP were 60 °C and 7.5, respectively. Additionally, the recombinant PAP was recovered at a yield greater than 65 % at an extremely broad range of pH values from 6 to 10 after treatment at 50 °C for 6 h. The molecular weight of the recombinant PAP decreased from 50 kDa to 48 kDa after treatment with a deglycosylation enzyme, indicating that the recombinant PAP was completely glycosylated. The glycosylated PAP exhibited high thermo-stability. Half of the activity remained after incubation at 50 °C for 50 h, whereas the remaining activity of PAP expressed in E. coli was only 10 % after incubation at 50 °C for 1 h. PAP could be activated by the appropriate salt concentration and exhibited salt tolerance against NaCl at a concentration up to 5 mol L(-1).

  10. Costs to physician offices of providing medications to medically indigent patients via pharmaceutical manufacturer prescription assistance programs.

    PubMed

    Clay, Patrick; Vaught, Eric; Glaros, Alan; Mangum, Stacy; Hansen, Daniel; Lindsey, Cameron

    2007-01-01

    Prescription assistance programs (PAPs) are offered by pharmaceutical manufacturers to provide medications at no out-of-pocket cost to various categories of medically indigent patients. some PAPs require only 1 application whereas others require as many as 4 applications per year per drug per patient, depending on the manufacturer's requirements. to measure the costs incurred by a medical clinic that provides chronic prescription medications via PAPs. this project was conducted in a free-standing, inner-city, Midwestern health clinic on the PAP application process for 1 representative drug for 32 pharmaceutical manufacturers that offered PAPs for drugs taken on a long-term basis for chronic conditions. time and motion studies were conducted using a medical assistant with the greatest amount of PAP experience. Assessment of time-to-access and time-to-complete forms was performed outside of normal clinic business hours to avoid interruptions. Personnel time costs also included receipt and delivery of drug to the patient (drug distribution time), which were assessed during normal business hours for actual medications received for 10 patients and included the time required to notify the patient of the arrival of the drug and to dispense the medication to the patient. supply costs for this PAP service included printing and copying costs. submission costs associated with mailing or faxing the documents were determined and calculated using the price of materials only. total application cost was calculated by adding the personnel time cost, supply cost, and submission cost. Annual PAP time was the time spent completing PAPs for 1 medication for 1 patient for 1 year. the time and resources required and the associated costs were aggregated separately for the pharmaceutical manufacturers that required 1, 2, or 4 applications per drug per patient per year. The total average application cost for all 32 companies was $25.18 [SD, $17.23]. Personnel time costs accounted for half or more of the total application cost, regardless of submission mode. the time to complete the form for any PAP was 0:06:20 [SD, 0:05:03] minutes with a range from 0:03:01 to 0:34:22 minutes. Printing costs were $0.20 [SD, $0.10] and copying costs were $1.96 [SD, $0.21]. Average supply costs were $2.16 [SD, $0.23]. Faxing versus mailing PAPs saved $17.90 per application. total annual clinic cost to assist patients in obtaining drugs through a PAP ranged from $10.42 per patient for a drug that requires 1 application per year (15 manufacturers, 47%) to $46.30 per patient for a drug in a PAP that requires 4 (re)applications per year (12 manufacturers, 38%). PAPs transmitted by mail required 0:49:18 [SD, 0:32:18] minutes, approximately 0:25:00 [SD, 0:21:00] minutes more than by fax (0:24:13 [SD, 0:11:32] minutes) or by Internet submissions (0:28:20 minutes), respectively. The number of PAP applications required per patient per medication annually has the greatest impact on clinic time and financial resources. Application submission method also influences the overall costs of providing this service in the clinical setting. Medical clinics should base their decision to provide a PAP application service to patients on the time and costs associated over the course of 1 year and not on the 1-time application cost.

  11. Exercise during cardiac catheterization distinguishes between pulmonary and left ventricular causes of dyspnea in systemic sclerosis patients.

    PubMed

    Hager, W David; Collins, Irina; Tate, Janet P; Azrin, Michael; Foley, Raymond; Lakshminarayanan, Santha; Rothfield, Naomi F

    2013-07-01

    The cause for shortness of breath among systemic sclerosis (SSc) patients is often lacking. We sought to characterize the hemodynamics of these patients by using simple isotonic arm exercise during cardiac catheterization. Catheterization was performed in 173 SSc patients when resting echocardiographic pulmonary systolic pressures were <40 but >40 mmHg post stress. Patients with resting mean pulmonary arterial pressures (mPAP) ≤ 25 and pulmonary arterial wedge pressures (PAWP) ≤ 15 mmHg exercised with 1-pound hand weights. Normal exercise was defined as a change in mPAP divided by the change in cardiac output (CO) (ΔmPAP/ΔCO) ratio ≤ 2 for patients <50 years (≤3 for >50). An abnormal ΔmPAP/ΔCO ratio, an exercise transpulmonary gradient (TPG) ≥ 15, a PAWP < 20, a ΔTPG > ΔPAWP and a pulmonary vascular resistance (PVR) which increased defined exercise-induced pulmonary arterial hypertension (EIPAH). An abnormal ΔmPAP/ΔCO ratio, an exercise TPG < 15, a PAWP ≥ 20, a ΔTPG < ΔPAWP and a drop in PVR defined left ventricular diastolic dysfunction (DD). Twelve patients without SSc served as controls. Pulmonary pressures increased with exercise in 53 patients. Six had EIPAH and 47 had DD. With exercise, mPAP and PAWP were 20 ± 4 and 13 ± 2 in controls, 36 ± 3 and 12 ± 4 in EIPAH and 34 ± 6 and 26 ± 4 in DD. Control ΔmPAP/ΔCO was 0.8 ± 0.7, 7.5 ± 3.9 in EIPAH and 9.1 ± 7.2 in DD. Rest and exercise TPG was normal for control and DD patients but increased (12 ± 4 to 23 ± 4) in EIPAH (P < 0.0001). PVR decreased in DD but increased in EIPAH with exercise. Exercise during catheterization elucidates the pathophysiology of dyspnea and distinguishes EIPAH from the more common DD in SSc patients. © 2012 John Wiley & Sons Ltd.

  12. Glandular Lesions of the Cervix in Clinical Practice: A Cytology, Histology, and Human Papillomavirus Correlation Study From 2 Institutions.

    PubMed

    Miller, Ross A; Mody, Dina R; Tams, Kimberlee C; Thrall, Michael J

    2015-11-01

    The Papanicolaou (Pap) test has indisputably decreased cervical cancer mortality, as rates have declined by up to 80% in the United States since its implementation. However, the Pap test is considered less sensitive for detecting glandular lesions than for detecting those of squamous origin. Some studies have even suggested an increasing incidence of cervical adenocarcinoma, which may be a consequence of a relatively reduced ability to detect glandular lesions with cervical cancer screening techniques. To evaluate the detection rate of glandular lesions with screening techniques currently used for cervical cancer screening and to provide insight as to which techniques are most efficacious in our study population. We retrospectively reviewed any available cytology, human papillomavirus (HPV), and histologic malignancy data in patients diagnosed with adenocarcinoma in situ and adenocarcinoma from 2 geographically and socioeconomically disparate hospital systems. Identified patients having had a negative/unsatisfactory Pap test within 5 years of adenocarcinoma in situ or adenocarcinoma tissue diagnosis were considered Pap test screening failures. Patients with negative HPV tests on cytology samples were considered HPV screening failures. One hundred thirty cases were identified (age range, 22-93 years); 39 (30%) had no Pap history in our files. Eight of 91 remaining cases (8.8%) were screening failures. The detected sensitivity for identifying adenocarcinoma in situ/adenocarcinoma in this study was 91.2% by cytology alone and 92.3% when incorporating HPV testing. The most common cytologic diagnosis was atypical glandular cells (25 cases), and those diagnosed with adenocarcinoma were 7.4 years older than those diagnosed with adenocarcinoma in situ (50.3 versus 42.9 years). Nine of 24 HPV-tested cases (37.5%) were called atypical squamous cell of undetermined significance on cytology. Our results highlight the importance of combined Pap and HPV cotesting. Although the number of cases identified is relatively small, our data suggest screening for squamous lesions facilitates the recognition of glandular lesions in the cervix. Additionally, increased use of combined Pap and HPV cotesting may decrease detection failure rates with regard to glandular lesions.

  13. Breast and cervical cancer screening: impact of health insurance status, ethnicity, and nativity of Latinas.

    PubMed

    Rodríguez, Michael A; Ward, Lisa M; Pérez-Stable, Eliseo J

    2005-01-01

    Although rates of cancer screening for Latinas are lower than for non-Latina whites, little is known about how insurance status, ethnicity, and nativity interact to influence these disparities. Using a large statewide database, our study examined the relationship between breast and cervical cancer screening rates and socioeconomic and health insurance status among foreign-born Latinas, US-born Latinas, and non-Latina whites in California. Data from the1998 California Women's Health Survey (CWHS) were analyzed (n = 3,340) using multiple logistic regression models. Utilization rates of mammography, clinical breast examinations, and Papanicolaou (Pap) smear screening among foreign-born Latinas, US-born Latinas, and non-Latina whites were the outcome measures. Foreign-born Latinas had the highest rates of never receiving mammography, clinical breast examinations, and Pap smears (21%, 24%, 9%, respectively) compared with US-born Latinas (12%, 11%, 7%, respectively) and non-Latina whites (9%, 5%, 2%, respectively). After controlling for socioeconomic factors, foreign-born Latinas were more likely to report mammography use in the previous 2 years and Pap smear in the previous 3 years than non-Latina whites. Lack of health insurance coverage was the strongest independent predictor of low utilization rates for mammography (odds ratio [OR] = 2.05; 95% confidence interval [CI], 1.53-2.76), clinical breast examinations (OR = 2.29; 95% CI, 1.80-2.90) and Pap smears (OR = 2.89; 95% CI, 2.17-3.85.) Breast and cervical cancer screening rates vary by ethnicity and nativity, with foreign-born Latinas experiencing the highest rates of never being screened. After accounting for socioeconomic factors, differences by ethnicity and nativity are reversed or eliminated. Lack of health insurance coverage remains the strongest predictor of cancer screening underutilization.

  14. Transgenic Arabidopsis thaliana containing increased levels of ATP and sucrose is more susceptible to Pseudomonas syringae

    PubMed Central

    Zhang, Renshan; Qi, Hua; Sun, Yuzhe; Xiao, Shi

    2017-01-01

    Disease resistance exerts a fitness cost on plants, presumably due to the extra consumption of energy and carbon. In this study, we examined whether transgenic Arabidopsis thaliana with increased levels of ATP and sucrose is more resistant or susceptible to pathogen infection. Lines of A. thaliana over-expressing purple acid phosphatase 2 (AtPAP2) (OE lines) contain increased levels of ATP and sucrose, with improved growth rate and seed production. Compared to wild type (WT) and pap2 lines, the OE lines were more susceptible to several Pseudomonas syringae pv. tomato (Pst) strains carrying AvrRpm1, AvrRpt2 AvrRps4, AvrPtoB, HrcC and WT strain DC3000. The increased susceptibility of the OE lines to Pst strains cannot solely be attributed to the suppressed expression of R-genes but must also be attributed to the suppression of downstream signaling components, such as MOS2, EDS1 and EDS5. Before infection, the levels of salicylic acid (SA) and jasmonic acid (JA) precursor OPDA were similar in the leaves of OE, pap2 and WT plants, whereas the levels of JA and its derivative JA-Ile were significantly lower in the leaves of OE lines and higher in the pap2 line. The expression of JA marker defense gene PDF1.2 was up-regulated in the OE lines compared to the WT prior to Pst DC3000 infection, but its expression was lower in the OE lines after infection. In summary, high fitness Arabidopsis thaliana exhibited altered JA metabolism and broad suppression of R-genes and downstream genes as well as a higher susceptibility to Pst infections. PMID:28152090

  15. Cervical cancer screening after 50: near extinction?

    PubMed

    Abdullah, Nik N; Daud, Suzanna; Al-Kubaisy, Waqar; Saari, Izni S; Saad, Siti R

    2016-11-01

    The objectives of this study were to determine the prevalence and predictors of Pap smear screening among women aged 50 years and older. This cross-sectional study was conducted at two large urban health centres in Selangor. A total of 515 women aged 50 and older were recruited. The mean age of the respondents was 58.83±7.05, with a range of 50- 83 years. The prevalence of Pap smear screening was 39.22% (n=202). From the multivariate analysis, Pap smear screening was significantly associated with health care provider advice (adjusted odds ratio (AOR)=18.75; 95% CI=8.30, 42.37); tertiary (AOR=11.26; 95% CI=1.50, 84.68) and secondary education level (AOR=9.47; 95% CI=1.43, 62.84); use of contraception (AOR=2.90; 95% CI=1.48, 5.69); heart disease (AOR=0.22; 95% CI=0.05, 0.97); and worry about Pap smear results (AOR=0.20; 95% CI=0.09, 0.42). The prevalence of Pap smear screening in the older women is unsatisfactory. Health care provider advice, education level, use of contraception, heart disease and worry about Pap smear results were predictors of undergoing Pap smear screening in this study population. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. A Novel fry1 Allele Reveals the Existence of a Mutant Phenotype Unrelated to 5′->3′ Exoribonuclease (XRN) Activities in Arabidopsis thaliana Roots

    PubMed Central

    Hirsch, Judith; Estavillo, Gonzalo M.; Javot, Hélène; Chiarenza, Serge; Mallory, Allison C.; Maizel, Alexis; Declerck, Marie; Pogson, Barry J.; Vaucheret, Hervé; Crespi, Martin; Desnos, Thierry; Thibaud, Marie-Christine; Nussaume, Laurent; Marin, Elena

    2011-01-01

    Background Mutations in the FRY1/SAL1 Arabidopsis locus are highly pleiotropic, affecting drought tolerance, leaf shape and root growth. FRY1 encodes a nucleotide phosphatase that in vitro has inositol polyphosphate 1-phosphatase and 3′,(2′),5′-bisphosphate nucleotide phosphatase activities. It is not clear which activity mediates each of the diverse biological functions of FRY1 in planta. Principal Findings A fry1 mutant was identified in a genetic screen for Arabidopsis mutants deregulated in the expression of Pi High affinity Transporter 1;4 (PHT1;4). Histological analysis revealed that, in roots, FRY1 expression was restricted to the stele and meristems. The fry1 mutant displayed an altered root architecture phenotype and an increased drought tolerance. All of the phenotypes analyzed were complemented with the AHL gene encoding a protein that converts 3′-polyadenosine 5′-phosphate (PAP) into AMP and Pi. PAP is known to inhibit exoribonucleases (XRN) in vitro. Accordingly, an xrn triple mutant with mutations in all three XRNs shared the fry1 drought tolerance and root architecture phenotypes. Interestingly these two traits were also complemented by grafting, revealing that drought tolerance was primarily conferred by the rosette and that the root architecture can be complemented by long-distance regulation derived from leaves. By contrast, PHT1 expression was not altered in xrn mutants or in grafting experiments. Thus, PHT1 up-regulation probably resulted from a local depletion of Pi in the fry1 stele. This hypothesis is supported by the identification of other genes modulated by Pi deficiency in the stele, which are found induced in a fry1 background. Conclusions/Significance Our results indicate that the 3′,(2′),5′-bisphosphate nucleotide phosphatase activity of FRY1 is involved in long-distance as well as local regulatory activities in roots. The local up-regulation of PHT1 genes transcription in roots likely results from local depletion of Pi and is independent of the XRNs. PMID:21304819

  17. Cervical Cancer Screening among HIV-Positive Women in Nigeria: An Assessment of Use and Willingness to Pay in the Absence of Donor Support.

    PubMed

    Dim, Cyril C; Onyedum, Cajetan C; Dim, Ngozi R; Chukwuka, Judith C

    2015-01-01

    The sustainability of donor-supported cervical cancer screening for HIV-positive women in underresourced setting is a concern. The authors aimed to determine the willingness of HIV-positive women for out-of-pocket payment for the cancer screening, if necessary. Questionnaires were administered to 400 HIV-positive women at the Adult HIV clinic, University of Nigeria Teaching Hospital (UNTH), Enugu, Nigeria. In all 11 (2.8%) respondents were aware of Pap smear, but only 1 (9.1%) of them had used it. After cervical cancer screening counseling, 378 (94.5%) respondents were willing to pay for Pap smear, irrespective of the cost. This willingness showed no trend across marital or educational groups. Younger age of respondents was not associated with willingness to pay for Pap smear (odds ratio = 1.24; confidence interval 95%: 0.52, 2.94). Willingness to pay for Pap smear by HIV-positive women in Enugu, Nigeria, is high. This has implication for the program sustainability. © The Author(s) 2013.

  18. Status and awareness of cervical, breast, and colon cancer screening in a Turkish city.

    PubMed

    Zafer, E; Tanrιkulu, P; Atakul, T; Ömürlü, I K; Yüksel, H

    2017-01-01

    Mortality and morbidity rates of cervical, breast, and colorectal cancers (CRC) can be decreased via effective screening strategies. Developing countries are to be expected to establish and implement their own programs. To evaluate regional awareness and status of cervical, breast, and CRC screening, a questionnaire-based study was conducted in 500 volunteers from a Turkish community hospital. Awareness rates were 57.4% for Pap smear, 61.2% for mammography, and 25.4% for CRC. Implementation rates were 19.2%, 23.9%, and 12%, respectively. Positive family history for gynecologic cancer and past cervical ablative procedure parameters were related to higher Pap smear rates. Educational level, breast self-exam, and positive Pap smear history parameters were related to higher mammography rates. Factors related to higher colorectal cancer screening rates were nulliparity and positive Pap smear history. Cancer screening rates for this Turkish city are still below the expected levels despite recently revitalized national screening program. For success, it is essential not only to educate rural populations but also to train negligent healthcare providers regularly.

  19. Predictors of Iranian women's intention to first papanicolaou test practice: An application of protection motivation theory.

    PubMed

    Dehdari, T; Hassani, L; Shojaeizadeh, D; Hajizadeh, E; Nedjat, S; Abedini, M

    2016-01-01

    Given the importance of papanicolaou (Pap) test in the early detection and timely treatment of cervical cancer, present study was designed to determine predictors of a sample of Iranian women's intention to first Pap test practice based on the protection motivation theory (PMT) variables. In this cross-sectional study, a total of 240 women referral to the 30 primary health care clinics were selected. They completed a developed scale based on PMT variables including intention, perceived vulnerability and severity, fear, response costs, response efficacy and self-efficacy. Path analysis was used to determine the association between predictive factors and intention. The results showed that PMT had goodness of fit with a χ2/df = 2.37, df = 28, P= 0.001 and RMSEA = 0.076. PMT explained 42% of the variance in women's intention to get first Pap smear test. Self-efficacy (b = 0.55, P< 0.001) and response efficacy (b = 0.19, P< 0.001) were found to be the predictors of intention. These findings may be used to develop tailored, theory-based educational interventions associated with Pap testing among women.

  20. Immunohistochemical staining of precursor forms of prostate-specific antigen (proPSA) in metastatic prostate cancer.

    PubMed

    Parwani, Anil V; Marlow, Cameron; Demarzo, Angelo M; Mikolajczyk, Stephen D; Rittenhouse, Harry G; Veltri, Robert W; Chan, Theresa Y

    2006-10-01

    Precursors of prostate-specific antigen (proPSA) have been previously shown to be more concentrated in prostate cancer tissue. This study characterizes the immunohistochemical staining (IHS) of proPSA forms in metastatic prostate cancer compared with prostate specific antigen (PSA) and prostatic acid phosphatase (PAP). A tissue microarray, consisting of 74 cases of metastatic prostate carcinoma and control tissues, was used. IHS, using monoclonal antibodies against proPSA with a truncated proleader peptide containing 2 amino acids ([-2]pPSA), native ([-5/-7]pPSA), PSA, and PAP, was analyzed. The monoclonal antibodies were specific for both benign and malignant prostatic glandular tissue. IHS with [-5/-7]pPSA showed the least number of cases with negative staining (3%), and the most number of cases with moderate or strong staining (76%). In the 60 cases where all 4 stains could be evaluated, none of them were negative for proPSA and positive for PSA or PAP, and all 7 cases that were negative for both PSA and PAP showed IHS to proPSA. [-5/-7]pPSA (native proPSA) may be a better marker than PSA and PAP in characterizing metastatic prostate adenocarcinoma, with most of the cases showing positivity for the marker. Even cases that were negative for PSA and PAP, were reactive for proPSA. Such enhanced detection is particularly important in poorly differentiated carcinomas involving metastatic sites where prostate carcinoma is a consideration. A panel of markers, including proPSA, should be performed when metastatic prostate carcinoma is in the differential diagnosis.

  1. Evaluating the Efficacy of Lay Health Advisors for Increasing Risk-appropriate Pap Test Screening: A randomized controlled trial among Ohio Appalachian women

    PubMed Central

    Paskett, Electra D.; McLaughlin, John M.; Lehman, Amy M.; Katz, Mira L.; Tatum, Cathy M.; Oliveri, Jill M.

    2011-01-01

    Background Cervical cancer is a significant health disparity among women in Ohio Appalachia. The goal of this study was to evaluate the efficacy of a lay health advisor (LHA) intervention for improving Pap testing rates, to reduce cervical cancer, among women in need of screening. Methods Women from 14 Ohio Appalachian clinics in need of a Pap test were randomized to receive either usual care or an LHA intervention over a ten-month period. The intervention consisted of two in-person visits with an LHA, two phone calls, and four post cards. Both self-report and medical record review (MRR) data (primary outcome) were analyzed. Results Of the 286 women, 145 and 141 were randomized to intervention and usual care arms, respectively. According to MRR, more women in the LHA arm had a Pap test by the end of the study compared to those randomized to usual care (51.1% vs. 42.0%; OR=1.44, 95%CI: 0.89, 2.33; p=0.135). Results of self-report were more pronounced (71.3% vs. 54.2%; OR=2.10, 95%CI: 1.22, 3.61; p=0.008). Conclusions An LHA intervention showed some improvement in the receipt of Pap tests among Ohio Appalachian women in need of screening. While biases inherent in using self-reports of screening are well known, this study also identified biases in using MRR data in clinics located in underserved areas. Impact LHA interventions show promise for improving screening behaviors among non-adherent women from underserved populations. PMID:21430302

  2. Responsiveness of the Countermovement Jump and Handgrip Strength to an Incremental Running Test in Endurance Athletes: Influence of Sex

    PubMed Central

    García-Pinillos, Felipe; Delgado-Floody, Pedro; Martínez-Salazar, Cristian; Latorre-Román, Pedro Á.

    2018-01-01

    Abstract The present study analyzed the acute effects of an incremental running test on countermovement jump (CMJ) and handgrip strength performance in endurance athletes, considering the effect of post-exercise recovery time and sex. Thirty-three recreationally trained long-distance runners, 20 men and 13 women, participated voluntarily in this study. The participants performed the Léger test, moreover, the CMJ and handgrip strength tests were carried out before and after the running test and during different stages of recovery (at the 1st min of recovery (posttest1), 5th min of recovery (posttest2), and 10th min of recovery (posttest3)). Two-way analysis of variance revealed a significant improvement in the CMJ (pre-posttest1, p = 0.001) and handgrip strength (pre-posttest2, p = 0.017) during recovery time. The Pearson’s Chi-2 test showed no significant relationship (p ≥ 0.05) between sex and post-activation potentiation (PAP). A linear regression analysis pointed to heart rate recovery as a predictive factor of CMJ improvement (PAP). In conclusion, despite significant fatigue reached during the Léger test, the long-distance runners did not experience an impaired CMJ and handgrip strength performance, either men or women, achieving an improvement (PAP) in posttest conditions. The results obtained showed no significant relationship between sex and PAP. Moreover, significant effect of recovery after running at high intensity on CMJ performance and handgrip strength was found. Finally, the data suggest that PAP condition can be predicted by heart rate recovery in endurance runners. PMID:29599872

  3. Papanicolaou smear findings in solid-organ transplant recipients compared with normal subjects according to the Bethesda 2001 system.

    PubMed

    Ok Atılgan, Alev; Tepeoğlu, Merih; Haberal, A Nihan; Durukan, Elif; Kuşcu, Esra; Haberal, Mehmet

    2015-04-01

    Solid-organ transplant recipients are at increased risk of developing cancer including cervical cancer compared with woman in the general population, mostly due to long-term immunosuppressive therapy. The Papanicolaou smear remains the primary method of screening cervical pathology including preinvasive and invasive lesions. The objective of this study was to evaluate Pap smear findings in solid-organ transplant recipients, determine the prevalence of abnormal smears, and compare these patients with the general population. We retrospectively examined 111 women patients who received liver or kidney transplant between January 1990 to December 2012 at Başkent University Ankara Hospital. Pap smear findings were compared with normal control patients matched for same age and technical procedure of cervical cytology. To selection of control patients, propensity score matching program was performed. All Pap smears were re-examined according to Bethesda 2001 criteria. In 111 transplant patients, 2 patients (1.8%) had atypical squamous cells of undetermined significance, 8 patients (7.2%) had low-grade squamous intraepithelial lesion, 15 patients (13.5%) had Candida infection, 2 patients (1.8%) had Trichomonas vaginalis, 1 patient (0.9%) had herpes simplex infection, 13 patients (11.7%) had bacterial vaginosis, 15 patients (13.5%) had reactive changes due to inflammation, and 18 patients (16.2%) had atrophy. When we compared our results with the control group, there were statistically significant differences (P ≤ .05) between the 2 groups in epithelial cell abnormalities (low-grade squamous intraepithelial lesion), Candida infection, bacterial vaginosis, and atrophy. Pap smear screening potentially may help recognize cervical preinvasive and invasive lesions. The risk of developing cervical intraepithelial neoplasia is greater in transplant recipients because of immunosuppressive therapy. The incidence of low-grade squamous intraepithelial lesion was significantly greater in transplant recipients than the general population. Intensive follow-up with Pap smear in transplant recipients is important in the early detection of these lesions.

  4. Time to clinical investigation for Indigenous and non-Indigenous Queensland women after a high grade abnormal Pap smear, 2000-2009.

    PubMed

    Whop, Lisa J; Baade, Peter D; Brotherton, Julia Ml; Canfell, Karen; Cunningham, Joan; Gertig, Dorota; Lokuge, Kamalini; Garvey, Gail; Moore, Suzanne P; Diaz, Abbey; O'Connell, Dianne L; Valery, Patricia; Roder, David M; Condon, John R

    2017-02-06

    To investigate time to follow-up (clinical investigation) for Indigenous and non-Indigenous women in Queensland after a high grade abnormality (HGA) being detected by Pap smear. Population-based retrospective cohort analysis of linked data from the Queensland Pap Smear Register (PSR), the Queensland Hospital Admitted Patient Data Collection, and the Queensland Cancer Registry. 34 980 women aged 20-68 years (including 1592 Indigenous women) with their first HGA Pap smear result recorded on the PSR (index smear) during 2000-2009 were included and followed to the end of 2010. Time from the index smear to clinical investigation (histology test or cancer diagnosis date), censored at 12 months. The proportion of women who had a clinical investigation within 2 months of a HGA finding was lower for Indigenous (34.1%; 95% CI, 31.8-36.4%) than for non-Indigenous women (46.5%; 95% CI, 46.0-47.0%; unadjusted incidence rate ratio [IRR], 0.65; 95% CI, 0.60-0.71). This difference remained after adjusting for place of residence, area-level disadvantage, and age group (adjusted IRR, 0.74; 95% CI, 0.68-0.81). However, Indigenous women who had not been followed up within 2 months were subsequently more likely to have a clinical investigation than non-Indigenous women (adjusted IRR for 2-4 month interval, 1.21; 95% CI, 1.08-1.36); by 6 months, a similar proportion of Indigenous (62.2%; 95% CI, 59.8-64.6%) and non-Indigenous women (62.8%; 95% CI, 62.2-63.3%) had been followed up. Prompt follow-up after a HGA Pap smear finding needs to improve for Indigenous women. Nevertheless, slow follow-up is a smaller contributor to their higher cervical cancer incidence and mortality than their lower participation in cervical screening.

  5. A subclinical high tricuspid regurgitation pressure gradient independent of the mean pulmonary artery pressure is a risk factor for the survival after living donor liver transplantation.

    PubMed

    Saragai, Yosuke; Takaki, Akinobu; Umeda, Yuzo; Matsusaki, Takashi; Yasunaka, Tetsuya; Oyama, Atsushi; Kaku, Ryuji; Nakamura, Kazufumi; Yoshida, Ryuichi; Nobuoka, Daisuke; Kuise, Takashi; Takagi, Kosei; Adachi, Takuya; Wada, Nozomu; Takeuchi, Yasuto; Koike, Kazuko; Ikeda, Fusao; Onishi, Hideki; Shiraha, Hidenori; Nakamura, Shinichiro; Morimatsu, Hiroshi; Ito, Hiroshi; Fujiwara, Toshiyoshi; Yagi, Takahito; Okada, Hiroyuki

    2018-05-15

    Portopulmonary hypertension (POPH) is characterized by pulmonary vasoconstriction, while hepatopulmonary syndrome (HPS) is characterized by vasodilation. Definite POPH is a risk factor for the survival after orthotopic liver transplantation (OLT), as the congestive pressure affects the grafted liver, while subclinical pulmonary hypertension (PH) has been acknowledged as a non-risk factor for deceased donor OLT. Given that PH measurement requires cardiac catheterization, the tricuspid regurgitation pressure gradient (TRPG) measured by echocardiography is used to screen for PH and congestive pressure to the liver. We investigated the impact of a subclinical high TRPG on the survival of small grafted living donor liver transplantation (LDLT). We retrospectively analyzed 84 LDLT candidates. Patients exhibiting a TRPG ≥25 mmHg on echocardiography were categorized as potentially having liver congestion (subclinical high TRPG; n = 34). The mean pulmonary artery pressure (mPAP) measured after general anesthesia with FIO 2 0.6 (mPAP-FIO 2 0.6) was also assessed. Patients exhibiting pO 2  < 80 mmHg and an alveolar-arterial oxygen gradient (AaDO 2 ) ≥ 15 mmHg were categorized as potentially having HPS (subclinical HPS; n = 29). The clinical course after LDLT was investigated according to subclinical high TRPG. A subclinical high TRPG (p = 0.012) and older donor age (p = 0.008) were correlated with a poor 40-month survival. Although a higher mPAP-FIO 2 0.6 was expected to correlate with a worse survival, a high mPAP-FIO 2 0.6 with a low TRPG was associated with high frequency complicating subclinical HPS and a good survival, suggesting a reduction in the PH pressure via pulmonary shunt. In cirrhosis patients, mPAP-FIO 2 0.6 may not accurately reflect the congestive pressure to the liver, as the pressure might escape via pulmonary shunt. A subclinical high TRPG is an important marker for predicting a worse survival after LDLT, possibly reflecting congestive pressure to the grafted small liver.

  6. Effects of 2 Types of Activation Protocols Based on Postactivation Potentiation on 50-m Freestyle Performance.

    PubMed

    Cuenca-Fernández, Francisco; Ruiz-Teba, Ana; López-Contreras, Gracia; Arellano, Raúl

    2018-06-14

    Cuenca-Fernández, F, Ruiz-Teba, A, López-Contreras, G, and Arellano, R. Effects of 2 types of activation protocols based on postactivation potentiation on 50-m freestyle performance. J Strength Cond Res XX(X): 000-000, 2018-Postactivation potentiation (PAP) is a phenomenon which improves muscle contractility, strength, and speed in sporting performances through previously applied maximal or submaximal loads on the muscle system. This study aimed to assess the effects of 2 types of activation protocols based on PAP, on sprint swimming performance. A repeated-measures design was used to compare 3 different scenarios before a 50-m race. First, all of the participants performed a standard warm-up (SWU), consisting of a 400-m swim followed by dynamic stretching. This protocol acted as the control. Subsequently, the swimmers were randomly assigned into 2 groups: the swimmers in the first group performed the SWU followed by a PAP one-repetition maximum warm-up (RMWU), consisting of 3 "lunge" and 3 "arm stroke" repetitions, both at 85% of the one-repetition maximum. The swimmers in the second group performed the SWU followed by a PAP eccentric flywheel warm-up (EWU), consisting of one set of 4 repetitions of exercises of both the lower and upper limbs on an adapted eccentric flywheel at the maximal voluntary contraction. The time required for the swimmers to swim 5 and 10 m was shorter with the PAP protocols. The swimming velocity of the swimmers who underwent the EWU and RMWU protocols was faster at 5 and 10 m. The best total swimming time was not influenced by any of the protocols. When isolating swimming (excluding start performance and turn), best time was achieved with the SWU and RMWU compared with EWU (SWU: 20.86 ± 0.95 seconds; EWU: 21.25 ± 1.12 seconds; RMWU: 20.97 ± 1.22 seconds). In conclusion, a warm-up based on PAP protocols might exert an influence on performance in the first meters of a 50-m race. Nevertheless, other factors, such as fatigue, could modify swimming patterns and yield results contradictory to those of the desired task.

  7. Role of p16 testing in cervical cancer screening among HIV-infected women.

    PubMed

    McGrath, Christine J; Garcia, Rochelle; Trinh, Trong T; Richardson, Barbra A; John-Stewart, Grace C; Nyongesa-Malava, Evans; Mugo, Nelly R; Glynn, Emily H; Sakr, Samah R; De Vuyst, Hugo; Chung, Michael H

    2017-01-01

    p16 immunohistochemistry is used to evaluate for HPV-associated cervical intraepithelial neoplasia. The diagnostic performance of p16 in HIV infection is unclear. Between June-December 2009, HIV-infected women underwent Papanicolaou (Pap) smear, human papillomavirus (HPV) testing, visual inspection with acetic acid (VIA), and colposcopy-directed biopsy as the disease gold standard at a HIV clinic in Kenya. Pap smears were evaluated for p16 expression. Sensitivity, specificity, positive predictive value (PPV), and area under the receiver operating characteristic curve (AUC) of p16 to detect CIN2/3 on histology and the impact of immunosuppression and ART was assessed. Of 331 cervical samples with p16 expression, p16 sensitivity and specificity to detect CIN2/3 was 54.1% and 72.4% respectively, which was lower than Pap and HPV in sensitivity, but higher in specificity than Pap, HPV, and VIA. Combining tests and p16 reduced sensitivity and increased specificity of Pap from 90.5% to 48.7% and 51.4% to 81.7%; of VIA from 59.5% to 37.8% and 67.6% to 89.9%; and of HPV from 82.4% to 50.0% and 55.3% to 84.8%. Combination p16 increased the PPV of Pap from 34.9% to 43.4%; of HPV from 34.7% to 48.7%; and VIA from 34.9% to 51.9%. Adjunctive p16 did not change AUC (P>0.05). P16 performance was not altered by immunosuppression or ART use. Combining p16 with HPV and VIA reduced the variation in HPV and VIA performance associated with CD4 and ART. As an adjunctive test in HIV-infected women, p16 immunohistochemistry increased specificity and PPV of HPV and VIA for CIN2/3, and was not altered in performance by immunosuppression, ART, or age.

  8. Tropical plant supplementation effects on the performance and parasite burden of goats

    PubMed Central

    2018-01-01

    Objective Examine the effects of supplementing bahiagrass hay (BG) with potentially anthelmintic quantities of hays of perennial peanut (PEA) or sericea lespedeza (LES) or seeds of velvet bean (Mucuna pruriens L.; MUC) or papaya (PAP) on the intake and nutritive value (Experiment 1), and the performance and parasite burden (Experiment 2) of goats. Methods In Experiment 1, 38 male goats (27.4±5.7 kg body weight) were randomly assigned to each of 5 treatments: i) BG alone and BG plus; ii) PEA; iii) LES; iv) MUC; and v) PAP. Goats were fed for ad libitum consumption and adapted to the diets for 14 d followed by 7 d of measurement. The PEA, LES, MUC (50%, 50%, and 10% of the diet dry matter [DM], respectively), and PAP (forced-fed at 10 g/d) were fed at rates that would elicit anthelmintic effects. In Experiment 2, goats remained in the same treatments but were allocated to 15 pens (3 pens per treatment) from d 22 to 63. All goats were infected with parasites by grazing an infected bahiagrass pasture from 0800 to 1500 h daily and then returned to the pens. Results Dry matter intake tended to be greater in goats fed PEA and LES than those fed BG (757 and 745 vs 612 g/d, respectively). Digestibility of DM (59.5% vs 54.9%) and organic matter (60.8% vs 56.0%) were greater in goats fed MUC vs BG, respectively. In Experiment 2, feeding PAP, LES, and PEA to goats reduced nematode fecal egg counts by 72%, 52%, and 32%, reduced abomasal adult worm counts by 78%, 52%, and 42%, and decreased plasma haptoglobin concentrations by 42%, 40%, and 45% relative to feeding BG alone, respectively. Conclusion Supplementation with PEA, LES, and PAP decreased the parasite burden of goats but did not increase their performance. PAP was the most effective anthelmintic supplement. PMID:28728358

  9. Tropical plant supplementation effects on the performance and parasite burden of goats.

    PubMed

    Romero, Juan J; Zarate, Miguel A; Ogunade, Ibukun M; Arriola, Kathy G; Adesogan, Adegbola T

    2018-02-01

    Examine the effects of supplementing bahiagrass hay (BG) with potentially anthelmintic quantities of hays of perennial peanut (PEA) or sericea lespedeza (LES) or seeds of velvet bean ( Mucuna pruriens L.; MUC) or papaya (PAP) on the intake and nutritive value (Experiment 1), and the performance and parasite burden (Experiment 2) of goats. In Experiment 1, 38 male goats (27.4±5.7 kg body weight) were randomly assigned to each of 5 treatments: i) BG alone and BG plus; ii) PEA; iii) LES; iv) MUC; and v) PAP. Goats were fed for ad libitum consumption and adapted to the diets for 14 d followed by 7 d of measurement. The PEA, LES, MUC (50%, 50%, and 10% of the diet dry matter [DM], respectively), and PAP (forced-fed at 10 g/d) were fed at rates that would elicit anthelmintic effects. In Experiment 2, goats remained in the same treatments but were allocated to 15 pens (3 pens per treatment) from d 22 to 63. All goats were infected with parasites by grazing an infected bahiagrass pasture from 0800 to 1500 h daily and then returned to the pens. Dry matter intake tended to be greater in goats fed PEA and LES than those fed BG (757 and 745 vs 612 g/d, respectively). Digestibility of DM (59.5% vs 54.9%) and organic matter (60.8% vs 56.0%) were greater in goats fed MUC vs BG, respectively. In Experiment 2, feeding PAP, LES, and PEA to goats reduced nematode fecal egg counts by 72%, 52%, and 32%, reduced abomasal adult worm counts by 78%, 52%, and 42%, and decreased plasma haptoglobin concentrations by 42%, 40%, and 45% relative to feeding BG alone, respectively. Supplementation with PEA, LES, and PAP decreased the parasite burden of goats but did not increase their performance. PAP was the most effective anthelmintic supplement.

  10. Arterial-to-end-tidal carbon dioxide tension difference in children with congenital heart disease.

    PubMed

    Choudhury, Minati; Kiran, Usha; Choudhary, Shiv Kumar; Airan, Balram

    2006-04-01

    This study estimated the arterial-to-end-tidal carbon dioxide tension difference (deltaPaCO2-PE'CO2) in children with congenital heart disease; evaluated whether hyperventilation can reduce this difference; and analyzed the relationship between the difference and the oxygen saturation (SaO2) and hemoglobin level. Prospective clinical study. Tertiary health care center. One hundred patients scheduled for correction of their underlying cardiac defect with either right-to-left or left-to-right intracardiac shunts were divided into 4 groups (n = 25 each): (1) N1, cyanotic with severe pulmonary artery hypertension; (2) N2, cyanotic with normal or decreased pulmonary artery pressure (PAP); (3) N3, acyanotic with normal or mild increases in PAP and severe increases in pulmonary blood flow (PBF); and (4) N4, acyanotic with normal PAP and normal or mild increase in PBF. All the patients received the same anesthetic regimen. The initial settings for tidal volume, respiratory rate, and inspiratory-to-expiratory (I:E) ratio were 10 mL/kg, 15 to 30 breath/min, and inspired time 40% of the total respiratory period with a 10% end-inspiratory pause. After the measurement of oxygen saturation, PO2, Hb, and deltaPaCO2-PE'CO2, all the children were hyperventilated (tidal volume: 14-15 mL/kg, respiratory rate: 5-6 breaths/min more than the initial rate, I:E ratio: same) to observe its effects on the deltaPaCO2-PE'CO2. The deltaPaCO2-PE'CO2, when predicted from the oxygen saturation, hemoglobin concentration, and PaO2, was found to be greater than the observed value in the first 3 groups (p < 0.001); whereas in group N4 these 2 values were comparable. It was also found that the gradient was higher when there was a decrease in SaO2 and an increase in the hemoglobin level. After hyperventilation, in groups N1 and N3, deltaPaCO2-PE'CO2 was decreased when compared with their baseline values; this reduction was not as much as predicted (p = 0.363 and 0.236, respectively). However, in groups N2 and N4 posthyperventilation, the deltaPaCO2-PE'27 CO2 was decreased significantly below their baseline measurements. These decreases were as much predicted. The deltaPaCO2-end-tidal carbon dioxide (PE'CO2) can be increased both in cyanotic and acyanotic children. Increased PAP is as important as increased PBF or right-to-left shunting in producing disorders in carbon dioxide homeostasis. Hyperventilation is of little use in reducing deltaPaCO2-PE'CO2 in children with high PAPs and pulmonary hyperperfusion.

  11. Perfluoroalkyl Acids (PFAAs) and Selected Precursors in the Baltic Sea Environment: Do Precursors Play a Role in Food Web Accumulation of PFAAs?

    PubMed

    Gebbink, Wouter A; Bignert, Anders; Berger, Urs

    2016-06-21

    The present study examined the presence of perfluoroalkyl acids (PFAAs) and selected precursors in the Baltic Sea abiotic environment and guillemot food web, and investigated the relative importance of precursors in food web accumulation of PFAAs. Sediment, water, zooplankton, herring, sprat, and guillemot eggs were analyzed for perfluoroalkane sulfonic acids (PFSAs; C4,6,8,10) and perfluoroalkyl carboxylic acids (PFCAs; C6-15) along with six perfluoro-octane sulfonic acid (PFOS) precursors and 11 polyfluoroalkyl phosphoric acid diesters (diPAPs). FOSA, FOSAA and its methyl and ethyl derivatives (Me- and EtFOSAA), and 6:2/6:2 diPAP were detected in sediment and water. While FOSA and the three FOSAAs were detected in all biota, a total of nine diPAPs were only detected in zooplankton. Concentrations of PFOS precursors and diPAPs exceeded PFOS and PFCA concentrations, respectively, in zooplankton, but not in fish and guillemot eggs. Although PFOS precursors were present at all trophic levels, they appear to play a minor role in food web accumulation of PFOS based on PFOS precursor/PFOS ratios and PFOS and FOSA isomer patterns. The PFCA pattern in fish could not be explained by the intake pattern based on PFCAs and analyzed precursors, that is, diPAPs. Exposure to additional precursors might therefore be a dominant exposure pathway compared to direct PFCA exposure for fish.

  12. High throughput virtual screening and in silico ADMET analysis for rapid and efficient identification of potential PAP248-286 aggregation inhibitors as anti-HIV agents

    NASA Astrophysics Data System (ADS)

    Malik, Ruchi; Bunkar, Devendra; Choudhary, Bhanwar Singh; Srivastava, Shubham; Mehta, Pakhuri; Sharma, Manish

    2016-10-01

    Human semen is principal vehicle for transmission of HIV-1 and other enveloped viruses. Several endogenous peptides present in semen, including a 39-amino acid fragments of prostatic acid phosphatase (PAP248-286) assemble into amyloid fibrils named as semen-derived enhancer of viral infection (SEVI) that promote virion attachment to target cells which dramatically enhance HIV virus infection by up to 105-fold. Epigallocatechin-3-gallate (EGCG), a polyphenolic compound, is the major catechin found in green tea which disaggregates existing SEVI fibers, and inhibits the formation of SEVI fibers. The aim of this study was to screen a number of relevant polyphenols to develop a rational approach for designing PAP248-286 aggregation inhibitors as potential anti-HIV agents. The molecular docking based virtual screening results showed that polyphenolic compounds 2-6 possessed good docking score and interacted well with the active site residues of PAP248-286. Amino acid residues of binding site namely; Lys255, Ser256, Leu258 and Asn265 are involved in binding of these compounds. In silico ADMET prediction studies on these hits were also found to be promising. Polyphenolic compounds 2-6 identified as hits may act as novel leads for inhibiting aggregation of PAP248-286 into SEVI.

  13. Phenazopyridine-phthalimide nano-cocrystal: Release rate and oral bioavailability enhancement.

    PubMed

    Huang, Yu; Li, Jin-Mei; Lai, Zhi-Hui; Wu, Jun; Lu, Tong-Bu; Chen, Jia-Mei

    2017-11-15

    Both cocrystal and nanocrystal technologies have been widely used in the pharmaceutical development for poorly soluble drugs. However, the synergistic effects due to the integration of these two technologies have not been well investigated. The aim of this study is to develop a nano-sized cocrystal of phenazopyridine (PAP) with phthalimide (PI) to enhance the release rate and oral bioavailability of PAP. A PAP-PI nano-cocrystal with particle diameter of 21.4±0.1nm was successfully prepared via a sonochemical approach and characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and dynamic light scattering (DLS) analysis. An in vitro release study revealed a significant release rate enhancement for PAP-PI nano-cocrystal as compared to PAP-PI cocrystal and PAP hydrochloride salt. Further, a comparative oral bioavailability study in rats indicated significant improvement in C max and oral bioavailability (AUC 0-∞ ) by 1.39- and 2.44-fold, respectively. This study demonstrated that this novel nano-cocrystal technology can be a new promising option to improve release rate and absorption of poorly soluble compounds in the pharmaceutical industry. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. Attitudes and factors affecting acceptability of self-administered cervicovaginal sampling for human papillomavirus (HPV) genotyping as an alternative to Pap testing among multiethnic Malaysian women

    PubMed Central

    Ma'som, Mahirah; Bhoo-Pathy, Nirmala; Nasir, Nazrila Hairizan; Bellinson, Jerome; Subramaniam, Shridevi; Ma, Yuntong; Yap, Siew-Hwei; Goh, Pik-Pin; Gravitt, Patti; Woo, Yin Ling

    2016-01-01

    Objective The objective of this study was to determine the attitudes and acceptability of self-administered cervicovaginal sampling compared with conventional physician-acquired Papanicolaou (Pap) smear among multiethnic Malaysian women. Method A cross-sectional study was carried out via interviewer-administered surveys from August 2013 through August 2015 at five government-run, urban health clinics in the state of Selangor. Subjects were participants from an ongoing community-based human papillomavirus (HPV) prevalence study who answered a standard questionnaire before and after self-sampling. The cervicovaginal self-sampling for HPV genotyping was performed using a simple brush (‘Just for Me’; Preventive Oncology International, Hong Kong). Detailed data on sociodemographics, previous Pap smear experience, and attitudes towards self-administered cervicovaginal sampling were collected and analysed. Acceptability was inferred using a five-item Likert scale that included six different subjective descriptives: experience, difficulty, convenience, embarrassment, discomfort or pain, and confidence in collecting one's own sample. Results Of the 839 participants, 47.9% were Malays, followed by 30.8% Indians, 18.8% Chinese and 2.5% from other ethnicities. The median age of the participants was 38 years (IQR 30–48). Some 68.2% of participants indicated a preference for self-sampling over the Pap test, with 95% indicating willingness to follow-up a positive result at the hospital. Age, ethnicity and previous Pap test experience were significant independent factors associated with preference for self-sampling. The older the individual, the less likely they were to prefer self-sampling (adjusted OR 0.94, 95% CI 0.90 to 0.98). The Chinese were less likely to prefer self-sampling (72.6%) than the Malays (85.1%) (adjusted OR 0.57, 95% CI 0.33 to 0.98, p=0.004). Participants who had never undergone a Pap smear were also more likely to prefer self-sampling (88.5%) than women who had undergone a previous Pap (80.9%) (adjusted OR 0.06, 95% CI 0.35 to 0.87). Conclusions Overall, urban Malaysian women from multiethnic backgrounds found self-sampling to be an acceptable alternative to Pap smear. PMID:27491667

  15. Cervical cancer risk levels in Turkey and compliance to the national cervical cancer screening standard.

    PubMed

    Açikgöz, Ayla; Ergör, Gül

    2011-01-01

    Cervical cancer screening with Pap smear test is a cost-effective method. The Ministry of Health in Turkey recommends that it be performed once every five years after age 35. The purpose of this study was to determine the cervical cancer risk levels of women between 35 and 69, and the intervals they have the Pap smear test, and to investigate the relation between the two. This study was performed on 227 women aged between 35 and 69 living in Balçova District of İzmir province. Using the cervical cancer risk index program of Harvard School of Public Health, the cervical cancer risk level of 70% of the women was found below average, 22.1% average, and 7.9% above average. Only 52% of the women have had Pap smear test at least once in their lives. The percentage screening regularly in conformity with the national screening standard was 39.2%. Women in the 40-49 age group, were married, conformed significantly more (p<0.05) to the national screening standard. Compliance also increased with the level of education and decreased with the cervical cancer risk level (p<0.05). A logistic regression model was constructed including age, education level, menstruation state of the women and the economic level of the family. Not having the Pap smear test in conformity with the national cervical cancer screening standard in 35-39 age group was 2.52 times more than 40-49 age group, while it was 3.26 times more in 60-69 age group (p< 0.05). Not having Pap smear test in 35-39 age group more than other groups might result from lack of information on the cervical cancer national screening standard and the necessity of having Pap smear test. As for 60-69 age group, the low education level might cause not having Pap smear test. Under these circumstances, the cervical cancer risk levels should be determined and the individuals should be informed. Providing Pap smear test screening service to individuals in the target group of national screening standard, as a public service may resolve the inequalities due to age and educational differences.

  16. Detection and localisation of protein-protein interactions in Saccharomyces cerevisiae using a split-GFP method.

    PubMed

    Barnard, Emma; McFerran, Neil V; Trudgett, Alan; Nelson, John; Timson, David J

    2008-05-01

    An alternative method for monitoring protein-protein interactions in Saccharomyces cerevisiae has been developed. It relies on the ability of two fragments of enhanced green fluorescent protein (EGFP) to reassemble and fluoresce when fused to interacting proteins. Since this fluorescence can be detected in living cells, simultaneous detection and localisation of interacting pairs is possible. DNA sequences encoding N- and C-terminal EGFP fragments flanked by sequences from the genes of interest were transformed into S. cerevisiae JPY5 cells and homologous recombination into the genome verified by PCR. The system was evaluated by testing known interacting proteins: labelling of the phosphofructokinase subunits, Pfk1p and Pfk2p, with N- and C-terminal EGFP fragments, respectively, resulted in green fluorescence in the cytoplasm. The system works in other cellular compartments: labelling of Idh1p and Idh2p (mitochondrial matrix), Sdh3p and Sdh4p (mitochondrial membrane) and Pap2p and Mtr4p (nucleus) all resulted in fluorescence in the appropriate cellular compartment.

  17. Prostate Secretory Protein of 94 Amino Acids (PSP94) Binds to Prostatic Acid Phosphatase (PAP) in Human Seminal Plasma

    PubMed Central

    Anklesaria, Jenifer H.; Jagtap, Dhanashree D.; Pathak, Bhakti R.; Kadam, Kaushiki M.; Joseph, Shaini; Mahale, Smita D.

    2013-01-01

    Prostate Secretory Protein of 94 amino acids (PSP94) is one of the major proteins present in the human seminal plasma. Though several functions have been predicted for this protein, its exact role either in sperm function or in prostate pathophysiology has not been clearly defined. Attempts to understand the mechanism of action of PSP94 has led to the search for its probable binding partners. This has resulted in the identification of PSP94 binding proteins in plasma and seminal plasma from human. During the chromatographic separation step of proteins from human seminal plasma by reversed phase HPLC, we had observed that in addition to the main fraction of PSP94, other fractions containing higher molecular weight proteins also showed the presence of detectable amounts of PSP94. This prompted us to hypothesize that PSP94 could be present in the seminal plasma complexed with other protein/s of higher molecular weight. One such fraction containing a major protein of ∼47 kDa, on characterization by mass spectrometric analysis, was identified to be Prostatic Acid Phosphatase (PAP). The ability of PAP present in this fraction to bind to PSP94 was demonstrated by affinity chromatography. Co-immunoprecipitation experiments confirmed the presence of PSP94-PAP complex both in the fraction studied and in the fresh seminal plasma. In silico molecular modeling of the PSP94-PAP complex suggests that β-strands 1 and 6 of PSP94 appear to interact with domain 2 of PAP, while β-strands 7 and 10 with domain 1 of PAP. This is the first report which suggests that PSP94 can bind to PAP and the PAP-bound PSP94 is present in human seminal plasma. PMID:23469287

  18. Pandemic influenza immunization in primary antiphospholipid syndrome (PAPS): a trigger to thrombosis and autoantibody production?

    PubMed

    de Medeiros, D Martins; Silva, C A; Bueno, C; Ribeiro, A C Medeiros; Viana, V dos Santos T; Carvalho, J Freire; Bonfa, E

    2014-11-01

    The objective of this report is to conduct short- and long-term evaluation of a large panel of antiphospholipid (aPL) autoantibodies following pandemic influenza A/H1N1 non-adjuvant vaccine in primary antiphospholipid syndrome (PAPS) patients and healthy controls. Forty-five PAPS and 33 healthy controls were immunized with H1N1 vaccine. They were prospectively assessed at pre-vaccination, and three weeks and six months after vaccination. aPL autoantibodies were determined by an enzyme-linked immunosorbent assay (ELISA) and included IgG/IgM: anticardiolipin (aCL), anti-beta2glycoprotein I (anti-β2GPI); anti-annexin V, anti-phosphatidyl serine and anti-prothrombin antibodies. Anti-Sm was determined by ELISA and anti-double-stranded DNA (anti-dsDNA) by indirect immunofluorescence. Arterial and venous thrombosis were also clinically assessed. Pre-vaccination frequency of at least one aPL antibody was significantly higher in PAPS patients versus controls (58% vs. 24%, p = 0.0052). The overall frequencies of aPL antibody at pre-vaccination, and three weeks and six months after immunization remained unchanged in patients (p = 0.89) and controls (p = 0.83). The frequency of each antibody specificity for patients and controls remained stable in the three evaluated periods (p > 0.05). At three weeks, two PAPS patients developed a new but transient aPL antibody (aCL IgG and IgM), whereas at six months new aPL antibodies were observed in six PAPS patients and none had high titer. Anti-Sm and anti-dsDNA autoantibodies were uniformly negative and no new arterial or venous thrombosis were observed throughout the study. This is the first study to demonstrate that pandemic influenza vaccine in PAPS patients does not trigger short- and long-term thrombosis or a significant production of aPL-related antibodies (ClinicalTrials.gov, #NCT01151644). © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  19. Impact of Pharmacist Involvement in Early Identification and Enrollment in Patient Assistance Programs on CMV Outcomes in Transplantation.

    PubMed

    Byrns, Jennifer S; Pilch, Nicole W; Taber, David J

    2016-04-01

    No data exist evaluating the utilization of patient assistance programs (PAPs) on cytomegalovirus (CMV)-related outcomes. To determine whether early identification and enrollment in PAPs can prevent CMV-related events. Retrospective analysis of patients at risk of CMV reactivation who received kidney and/or pancreas transplants. Two groups were evaluated with patients receiving oral valganciclovir for CMV prophylaxis through enrollment in PAPs or oral acyclovir with preemptive CMV monitoring. Primary outcomes include the incidence of CMV infection. Secondary outcomes include a cost benefit analysis, incidence of rejection, patient/graft survival, and time to CMV infection. There were 97 patients identified; valganciclovir through PAPs (n = 39) and preemptive CMV quantitative nucleic acid testing monitoring (n = 58). The incidence of CMV viremia was lower in the PAP group (12.8% vs 36.2%, respectively; P = .021). There were no significant differences in CMV syndrome/disease, acute rejection, graft loss, or death between the groups. The time to CMV infection was shorter in the preemptive group. Cost benefit analysis found that hiring a full time pharmacy employee for enrolling patients in PAPs was cost beneficial for the institution/health care system. Early identification and enrollment of patients in PAPs reduces the incidence of CMV viremia. Pharmacists play a crucial role in this process. © The Author(s) 2014.

  20. Cervical Cancer Screening and Sexual Risky Behaviors among a Population of Hispanic Origin.

    PubMed

    González, Daisy; Suárez, Erick L; Ortiz, Ana Patricia

    2015-01-01

    To assess the prevalence of cervical cancer screening through Papanicolaou (Pap) test utilization and its association with sexual behaviors among a population-based sample of Hispanic women in Puerto Rico (PR). This study was a secondary data analysis of the database of a cross-sectional study of HPV infection in PR (2010-2013; n = 554 women). Pap test utilization (past 3 years) was self-reported and sexual risky behavior was defined as an index that considered the following sexual behaviors: early age of sexual debut (≤16 years), 11 or more lifetime sexual partners, and 2 or more sexual partners in the last year. Multivariable logistic regression was used to estimate the magnitude of the association between sexual risk behavior and Pap test utilization, after adjusting for socioeconomic and lifestyles characteristics. The overall prevalence of Pap test utilization was 78.0%. Pap test screening varied with sexual behavior, with women with none or one risky sexual behavior having higher odds of Pap test utilization in the past 3 years (odds ratio [OR], 1.74; 95% CI, 1.03-2.93) compared with those with two or three risky sexual behaviors. This difference remained marginally significant (p < .10) after adjusting for age, educational attainment, smoking status and STI history (OR, 1.72; 95% CI, 0.96-3.08). The prevalence of cervical cancer screening in this population (78%) is still below Healthy People 2020 recommendations (93%). Also, women with risky sexual behaviors are less likely to have been screened. Efforts to promote cervical screening programs should focus on these high-risk women as a method for cervical cancer prevention and control. Copyright © 2015 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

  1. Self-sampling for cervical screening: could it overcome some of the barriers to the Pap test?

    PubMed

    Mullins, Robyn; Scalzo, Katherine; Sultana, Farhana

    2014-12-01

    To determine which groups of women would be most likely to take part in self-sampling for cervical screening, and what they perceive as the key barriers and benefits to self-sampling. A random sample of 3000 women aged 18-69 in Victoria, Australia, were asked questions about "taking their own Pap test" in a telephone survey about cervical screening; 2526 answered the questions about self-sampling. The terminology "Pap test" was used in questions, due to the very low understanding of HPV and its link to cervical cancer. One-third of women (34.0%) indicated they would prefer to self-sample, 57.2% would not and 8.7% were unsure. Preference for self-sampling was significantly stronger among women who had not had a Pap test for more than three years (64.8%, p < .001) or who had never had one (62.1%, p < .001), compared with those up-to-date (27.0%). Convenience was a key benefit (37.8%), as was less embarrassment (31.5%). For those who did not want to self-sample or were unsure, key factors included professionals being more skilled (53.4% and 28.2% respectively), and doubts about being able to do it properly (28.9% and 23.6%). Self-sampling was most popular among women who needed to have a Pap test, and could potentially reach some women who are not participating appropriately in cervical screening. Key barriers to participation could be addressed by providing information about the test being for HPV, and being easier to do properly than a Pap test. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  2. Cervical Cancer Screening (Pap Testing) Behaviours and Acceptability of Human Papillomavirus Self-Testing among Lesbian and Bisexual Women Aged 21–26 Years in the USA

    PubMed Central

    Reiter, Paul L.; McRee, Annie-Laurie

    2017-01-01

    Objective Lesbian and bisexual women are at risk for human papillomavirus (HPV) infection and cervical disease. We examined Pap testing among these women and their acceptability of HPV self-testing at home, a potential cervical cancer screening strategy. Methods We analyzed data from a national sample of lesbian and bisexual women ages 21–26 who completed our online survey during Fall 2013 (n=418). Logistic regression identified correlates of: 1) receipt of a Pap test in the last three years; and 2) willingness to use an HPV self-test at home. Results About 70% of women had received a Pap test in the last three years. Pap testing was more common among women who had disclosed their sexual orientation to their healthcare provider (OR=2.01, 95% CI: 1.02–3.95) and less common among women who self-identified as lesbian (OR=0.48, 95% CI: 0.25–0.93). Just over half of women (51%) were willing to use an HPV self-test at home. Women were more willing to use an HPV self-test at home if they were older (OR=1.16, 95% CI: 1.03–1.30) or reported higher levels of worry about getting an HPV-related disease (OR=1.28, 95% CI: 1.01–1.63). The most common concerns about HPV self-testing at home were using the test incorrectly (70%) and test accuracy (64%). Conclusions Many young lesbian and bisexual women have not received a recent Pap test. HPV self-testing at home may be a promising future strategy for reaching and screening these women. Findings highlight beliefs and concerns that could be addressed by self-test programs. PMID:25385868

  3. GA-DELLA pathway is involved in regulation of nitrogen deficiency-induced anthocyanin accumulation.

    PubMed

    Zhang, Yongqiang; Liu, Zhongjuan; Liu, Jianping; Lin, Sheng; Wang, Jianfeng; Lin, Wenxiong; Xu, Weifeng

    2017-04-01

    DELLA proteins positively regulate nitrogen deficiency-induced anthocyanin accumulation through directly interaction with PAP1 to enhance its transcriptional activity on anthocyanin biosynthetic gene expressions. Plants can survive a limiting nitrogen supply by undergoing adaptive responses, including induction of anthocyanin production. However, the detailed mechanism is still unclear. In this study, we found that this process was impaired and enhanced, respectively, by exogenous GA 3 (an active form of GAs) and paclobutrazol (PAC, a specific GA biosynthesis inhibitor) in Arabidopsis seedlings. Consistently, the nitrogen deficiency-induced transcript levels of several key genes involved in anthocyanin biosynthesis, including F3'H, DFR, LDOX, and UF3GT, were decreased and enhanced by exogenous GA 3 and PAC, respectively. Moreover, the nitrogen deficiency-induced anthocyanin accumulation and biosynthesis gene expressions were impaired in the loss-of-function mutant gai-t6/rga-t2/rgl1-1/rgl2-1/rgl3-1 (della) but enhanced in the GA-insensitive mutant gai, suggesting that DELLA proteins, known as repressors of GA signaling, are necessary for fully induction of nitrogen deficiency-driven anthocyanin biosynthesis. Using yeast two-hybrid (Y2H) assay, pull-down assay, and luciferase complementation assay, it was found that RGA, a DELLA of Arabidopsis, could strongly interact with PAP1, a known regulatory transcription factor positively involved in anthocyanin biosynthesis. Furthermore, transient expression assays indicated that RGA and GAI could enhance the transcriptional activities of PAP1 on its downstream genes, including F3'H and DFR. Taken together, this study suggests that DELLAs are necessary regulators for nitrogen deficiency-induced anthocyanin accumulation through interaction with PAP1 and enhancement of PAP1's transcriptional activity on its target genes. GA-DELLA-involved anthocyanin accumulation is important for plant adaptation to nitrogen deficiency.

  4. Protease-functionalized mucus penetrating microparticles: In-vivo evidence for their potential.

    PubMed

    Mahmood, Arshad; Laffleur, Flavia; Leonaviciute, Gintare; Bernkop-Schnürch, Andreas

    2017-10-30

    The focus of the current study was to explore whether immobilization of proteases to microparticles could result in their enhanced penetration into mucus. The proteases papain (PAP) and bromelain (BROM) were covalently attached to a polyacrylate (PAA; Carbopol 971P) via amide bond formation based on carbodiimide reaction. Microparticles containing these conjugates were generated via ionic gelation with calcium chloride and were characterized regarding size, surface charge, enzymatic activity and fluorescein diacetate (FDA) loading efficiency. Furthermore, mucus penetration potential of these microparticles was evaluated in-vitro on freshly collected porcine intestinal mucus, on intact intestinal mucosa and in-vivo in Sprague-Dawley rats. Results showed mean diameter of microparticles ranging between 2-3μm and surface charge between -8 to -18mV. The addition of PAA-microparticles to porcine intestinal mucus led to a 1.39-fold increase in dynamic viscosity whereas a 3.10- and 2.12-fold decrease was observed in case of PAA-PAP and PAA-BROM microparticles, respectively. Mucus penetration studies showed a 4.27- and 2.21- fold higher permeation of FDA loaded PAA-PAP and PAA-BROM microparticles as compared to PAA microparticles, respectively. Extent of mucus diffusion determined via silicon tube assay illustrated 3.96- fold higher penetration for PAA-PAP microparticles and 1.99- fold for PAA-BROM microparticles. An in-vitro analysis on porcine intestinal mucosa described up to 16- and 7.35-fold higher degree of retention and furthermore, during in-vivo evaluation in Sprague-Dawley rats a 3.35- and 2.07-fold higher penetration behavior was observed in small intestine for PAA-PAP and PAA-BROM microparticles as compared to PAA microparticles, respectively. According to these results, evidence for microparticles decorated with proteases in order to overcome the mucus barrier and to reach the absorption lining has been provided that offers wide ranging applications in mucosal drug delivery. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. The effects of acute oral antioxidants on diving-induced alterations in human cardiovascular function

    PubMed Central

    Obad, Ante; Palada, Ivan; Valic, Zoran; Ivančev, Vladimir; Baković, Darija; Wisløff, Ulrik; Brubakk, Alf O; Dujić, Željko

    2007-01-01

    Diving-induced acute alterations in cardiovascular function such as arterial endothelial dysfunction, increased pulmonary artery pressure (PAP) and reduced heart function have been recently reported. We tested the effects of acute antioxidants on arterial endothelial function, PAP and heart function before and after a field dive. Vitamins C (2 g) and E (400 IU) were given to subjects 2 h before a second dive (protocol 1) and in a placebo-controlled crossover study design (protocol 2). Seven experienced divers performed open sea dives to 30 msw with standard decompression in a non-randomized protocol, and six of them participated in a randomized trial. Before and after the dives ventricular volumes and function and pulmonary and brachial artery function were assessed by ultrasound. The control dive resulted in a significant reduction in flow-mediated dilatation (FMD) and heart function with increased mean PAP. Twenty-four hours after the control dive FMD was still reduced 37% below baseline (8.1 versus 5.1%, P = 0.005), while right ventricle ejection fraction (RV-EF), left ventricle EF and endocardial fractional shortening were reduced much less (∼2–3%). At the same time RV end-systolic volume was increased by 9% and mean PAP by 5%. Acute antioxidants significantly attenuated only the reduction in FMD post-dive (P < 0.001), while changes in pulmonary artery and heart function were unaffected by antioxidant ingestion. These findings were confirmed by repeating the experiments in a randomized study design. FMD returned to baseline values 72 h after the dive with pre-dive placebo, whereas for most cardiovascular parameters this occurred earlier (24–48 h). Right ventricular dysfunction and increased PAP lasted longer. Acute antioxidants attenuated arterial endothelial dysfunction after diving, while reduction in heart and pulmonary artery function were unchanged. Cardiovascular changes after diving are not fully reversed up to 3 days after a dive, suggesting longer lasting negative effects. PMID:17110413

  6. [Study on clinical management of HPV(+)/Pap(-) during cervical cancer screening].

    PubMed

    Huang, A J; Zhao, Y; Zou, X L; Yan, J; Zhao, C; Cui, S H; Li, Y Y; Ren, L H; Li, J R; Li, M Z; Wang, Y; Wang, J L; Wei, L H

    2017-11-25

    Objective: To study the clinical management way for HPV(+)/papanicolaou (Pap)(-) during cervical cancer screening. Methods: To analyze retrospectively the data from the patients who had loop electrical excision procedure (LEEP) for biopsy confirmed cervical intraepithelial neoplasia (CIN) Ⅱ in Peking University People's Hospital from Jan. 2010 to Dec. 2014. Results: (1) For biopsy confirmed CIN Ⅱ, HPV positive rate was 98.5% (135/137), Pap test positive [≥atypical squamous cell of undetermined significance (ASCUS)] rate was 69.3% (95/137), there was significant difference between them (χ(2)=43.32, P< 0.01). (2) For the 42 patients with HPV(+)/Pap(-), whose cytology slides were reviewed again. Among them, the interpretations of there were 16 cases confirmed as the same before, while 26 cases were changed to abnormal (≥ASCUS). Cytology be misdiagnosed was 19.0% (26/137) at the first review. Among the 26 cases, 13 (50.0%) cases were missed for the little amount of abnormal cells, 8 (30.8%) cases for mild atypical morphology changed; the other 5 (19.2%) cases missed for stain problems. (3) For the cervical LEEP samples, 37 cases of the pathology diagnosis were upgrade to CIN Ⅲ(+), among them, 2 cases of microinvasive cervical carcinoma, 1 case of invasive cancer, 34 cases of CIN Ⅲ; 37 cases were CINⅠ or no lesion found; 63 cases were still CIN Ⅱ. Four to six months later after LEEP, the cytology abnormal rate was 11.7% (16/137), and the HR-HPV positive rate was 34.3% (47/137). Conclusions: Compared with cytology alone, cytology combined with HPV testing increase the sensitivity of cervical high grade lesion. For the cases of HPV(+)/Pap(-) cases, the cytology slides should be reviewed. The quality control of cervical exfoliate sample collection and interpretation should be strengthened. LEEP procedure is not only a treatment method, but also it could provide samples to confirm the diagnosis.

  7. The Prevalence of Vancomycin-Intermediate Staphylococcus aureus and Heterogeneous VISA Among Methicillin-Resistant Strains Isolated from Pediatric Population in a Turkish University Hospital.

    PubMed

    Mirza, Hasan Cenk; Sancak, Banu; Gür, Deniz

    2015-10-01

    There are limited data regarding the prevalence of vancomycin-intermediate Staphylococcus aureus (VISA)/heterogeneous VISA (hVISA) among pediatric population. Our objective was to determine the distribution of vancomycin and daptomycin minimum inhibitory concentrations (MICs) and explore the phenomenon of vancomycin MIC creep and the VISA/hVISA prevalence among the methicillin-resistant Staphylococcus aureus (MRSA) strains belonging to pediatric population by population analysis profile-area under the curve (PAP-AUC) and Etest macromethod. Vancomycin and daptomycin susceptibilities of 94 pediatric isolates of MRSA were tested by broth microdilution (BMD) and Etest methods. To determine the prevalence of VISA/hVISA, Etest macromethod and PAP-AUC was performed on all isolates. All isolates were susceptible to vancomycin and daptomycin by both BMD and Etest methods. Twenty-eight (29.8%) isolates had vancomycin MICs of 2 μg/ml by BMD. No increase in vancomycin MICs was observed over time. There were no VISA among 94 MRSA tested but 20 (21.3%) hVISA isolates were identified by PAP-AUC. Results of Etest macromethod were compared to PAP-AUC. Etest macromethod was 60.0% sensitive and 90.5% specific. The hVISA isolates represented 53.6% of isolates with vancomycin MICs of 2 μg/ml. Also, 75% of hVISA isolates had vancomycin MICs of 2 μg/ml. To our knowledge, this is the first study investigating the prevalence of VISA/hVISA among MRSA isolated from pediatric patients by PAP-AUC method. Based on our findings, MRSA isolates, which have vancomycin MIC of 2 μg/ml can be investigated for the presence of hVISA. In this study, daptomycin showed potent activity against all isolates and may represent a therapeutic option for MRSA infections.

  8. Clinical significance of atypical glandular cells in Pap tests: An analysis of more than 3000 cases at a large academic women's center.

    PubMed

    Pradhan, Dinesh; Li, Zaibo; Ocque, Rebecca; Patadji, Stell; Zhao, Chengquan

    2016-08-01

    The interpretation of atypical glandular cells (AGC) in Papanicolaou (Pap) tests and screening for glandular neoplasia remain challenging. Pap tests with an AGC interpretation from January 2008 to December 2013 were retrieved from a pathology database, and cases with histologic follow-up within 1 year were included in the study. There were 589,830 Pap tests during the study period, and 3709 cases (0.6%) were reported as AGC, which included the following: AGC, not otherwise specified (52.0%); atypical endocervical cells (28.0%); and other categories. There were 3007 cases (81.1%) with histologic follow-up results within 1 year. Cervical intraepithelial neoplasia 2/3 (CIN2/3), cervical adenocarcinoma in situ (AIS)/adenocarcinoma, and endometrial carcinoma were identified in 5.6%, 1.9%, and 5.5% of cases, respectively. Glandular neoplasia was more likely to be identified in cases with pure AGC subcategories than cases with AGC and squamous abnormalities. Endometrial neoplasia was more likely to be identified in cases with atypical endometrial cells than other categories. Overall, the most common severe abnormality on histologic follow-up was CIN2/3. Although CIN2/3 was the most common severe lesion in patients younger than 30 years (10.0%) and in patients aged 30 to 49 years (6.4%), endometrial carcinoma was the most common lesion in women who were 50 years old or older (13.7%). Endocervical glandular lesions (AIS and adenocarcinoma) occurred in only 1.9% of women. AGC subtypes and ages significantly affect histological follow-up results; 90.5% of cases with carcinoma on histologic follow-up were either endometrial or metastatic carcinoma. This study supports the recommendation that women with AGC Pap test results should be followed up with both endocervical and endometrial sampling. Cancer Cytopathol 2016;124:589-95. © 2016 American Cancer Society. © 2016 American Cancer Society.

  9. The effects of acute oral antioxidants on diving-induced alterations in human cardiovascular function.

    PubMed

    Obad, Ante; Palada, Ivan; Valic, Zoran; Ivancev, Vladimir; Baković, Darija; Wisløff, Ulrik; Brubakk, Alf O; Dujić, Zeljko

    2007-02-01

    Diving-induced acute alterations in cardiovascular function such as arterial endothelial dysfunction, increased pulmonary artery pressure (PAP) and reduced heart function have been recently reported. We tested the effects of acute antioxidants on arterial endothelial function, PAP and heart function before and after a field dive. Vitamins C (2 g) and E (400 IU) were given to subjects 2 h before a second dive (protocol 1) and in a placebo-controlled crossover study design (protocol 2). Seven experienced divers performed open sea dives to 30 msw with standard decompression in a non-randomized protocol, and six of them participated in a randomized trial. Before and after the dives ventricular volumes and function and pulmonary and brachial artery function were assessed by ultrasound. The control dive resulted in a significant reduction in flow-mediated dilatation (FMD) and heart function with increased mean PAP. Twenty-four hours after the control dive FMD was still reduced 37% below baseline (8.1 versus 5.1%, P = 0.005), while right ventricle ejection fraction (RV-EF), left ventricle EF and endocardial fractional shortening were reduced much less (approximately 2-3%). At the same time RV end-systolic volume was increased by 9% and mean PAP by 5%. Acute antioxidants significantly attenuated only the reduction in FMD post-dive (P < 0.001), while changes in pulmonary artery and heart function were unaffected by antioxidant ingestion. These findings were confirmed by repeating the experiments in a randomized study design. FMD returned to baseline values 72 h after the dive with pre-dive placebo, whereas for most cardiovascular parameters this occurred earlier (24-48 h). Right ventricular dysfunction and increased PAP lasted longer. Acute antioxidants attenuated arterial endothelial dysfunction after diving, while reduction in heart and pulmonary artery function were unchanged. Cardiovascular changes after diving are not fully reversed up to 3 days after a dive, suggesting longer lasting negative effects.

  10. Use of Prescription Assistance Programs After the Affordable Health Care Act.

    PubMed

    Khan, Ghazala; Karabon, Patrick; Lerchenfeldt, Sarah

    2018-03-01

    Insurance coverage in the United States seems to be in a state of unrest. The 2010 passage of the Patient Protection and Affordable Health Care Act (ACA) extended health insurance coverage to roughly 32 million people. An increase in the number of people with health insurance benefits raised the question of whether prescription assistance programs (PAPs) would still be used after ACA implementation. To evaluate the use of PAPs following the implementation of the ACA insurance mandate. Health insurance was not required by the ACA until January 2014, so we retrospectively examined the use of drug company-sponsored PAPs before and after the ACA implementation. Since each PAP had its own qualifying criteria, any person who used a PAP through the assistance of NeedyMeds and its PAPTracker between the years of 2011 and 2016 were included for analysis. Data were pulled by NeedyMeds from the PAPTracker software, which produces completed PAP applications from drug manufacturer forms for PAPs. The number of PAP orders, number of unique patient orders, and annual patient prescription savings were assessed. Between 2011 and 2013, there was an average of 4.2 annual PAP orders per patient; however, annual PAP orders decreased to 3.1 per patient between 2014 and 2016 (P < 0.001). PAP orders declined by an average of 3.0% per month between 2014 and 2016 (P < 0.001), and average prescription savings per order increased from $870.40 before the ACA to $1,086.40 after ACA implementation (P = 0.0024). Patients saved an average of over $3,000 on prescriptions annually with the use of PAPs after the ACA mandate. Although health care reform is inevitable, our study showed that PAPs remain important to help cover prescription drug costs for eligible patients, even with invariable changes to health insurance, including a health insurance requirement. While the ACA may have been an important step forward in extending health insurance coverage to millions, PAPs are still used to help U.S. patients obtain their medications at no cost or very low cost. These programs will most likely remain relevant until other approaches are taken to help alleviate the effects of increasing drug prices in the United States. No outside funding supported this research. The authors have no relevant financial or nonfinancial relationships to disclose. Study concept and design were contributed by Khan, Lerchenfeldt, and Karabon. Khan collected the data, and all authors participated in data analysis. The manuscript was primarily written by Lerchenfeldt, along with Khan and Karabon, and revised by Lerchenfeldt, along with Karabon and Khan.

  11. Efficacy of nasal bi-level positive airway pressure in congestive heart failure patients with cheyne-stokes respiration and central sleep apnea.

    PubMed

    Kasai, Takatoshi; Narui, Koji; Dohi, Tomotaka; Ishiwata, Sugao; Yoshimura, Kunihiko; Nishiyama, Shin-Ichiro; Yamaguchi, Tetsu; Momomura, Shin-Ichi

    2005-08-01

    Cheyne - Stokes respiration with central sleep apnea (CSR-CSA) contributes to the poor prognosis in patients with congestive heart failure (CHF). Bi-level positive airway pressure (bi-level PAP) may be an effective alternative for treating CSR-CSA and CHF. Fourteen patients with CSR-CSA were divided into 2 groups, a control group that included 7 patients who decided to receive only conventional medications and a group of 7 patients that received bi-level PAP. Left ventricular ejection fraction (LVEF), mitral regurgitation (MR) area, plasma brain natriuretic peptide (BNP) concentration and the New York Heart Association (NYHA) functional class were evaluated initially (baseline) and 3 months later. In the control group, there were no significant changes in cardiac function during the study period. In contrast, in the group that received bi-level PAP, there were significant improvements in LVEF (from 36.3+/-2.9% to 46.0+/-4.0%, p = 0.02), MR area (from 30.4+/-7.6% to 20.0+/-5.1%, p = 0.02), BNP (from 993.6+/-332.0 pg/ml to 474.0+/-257.6 pg/ml, p = 0.02) and NYHA functional class (from 3.1+/-0.1 to 2.1+/-0.1, p = 0.03). Treatment with bi-level PAP improved cardiac functions in CHF patients with CSR-CSA.

  12. The utilization and barriers of Pap smear among women with visual impairment.

    PubMed

    Fang, Wen-Hui; Yen, Chia-Feng; Hu, Jung; Lin, Jin-Ding; Loh, Ching-Hui

    2016-04-12

    Many evidences illustrate that the Pap smear screening successfully reduces if the cervical cancer could be detected and treated sufficiently early. People with disability were higher comorbidity prevalence, and less likely to use preventive health care and health promotion activities. There were also to demonstrate that people with visual impairment has less access to appropriate healthcare services and is less likely to receive screening examinations. In Taiwan, there was no study to explore utilization of Pap smear, associated factors and use barriers about Pap smear screening test among women with visual impairment. The purpose is to explore the utilization and barriers of using Pap smear for women with visual impairment in Taiwan. To identify the barriers of women with visual from process of receiving Pap smear screening test. The cross-sectional study was conducted and the totally 316 participators were selected by stratified proportional and random sampling from 15 to 64 year old women with visual impairment who lived in Taipei County during December 2009 to January 2010. The data was been collected by phone interview and the interviewers were well trained before interview. The mean age was 47.1 years old and the highest percentage of disabled severity was mile (40.2 %). Totally, 66.5 % of participators were ever using Pap smear and 38.9 % used it during pass 1 year. Their first time to accept Pap smear was 38.8 year old. There was near 50 % of them not to be explained by professionals before accepting the Pap smear. For non-using cases, the top two percentage of barriers were "feel still younger" (22.3 %), the second was "there's no sexual experience" (21.4 %). We found the gynecology experiences was key factor for women with visual impairment to use Pap smear, especially the experiences was during 1 year (OR = 4). Associated factors and barriers to receive Pap smear screening test for women with visual impairment can be addressed through interventions aimed at improving on cognitions and attitudes for cervical cancer risk factors. Our study would be as a reference resource for erasing the barriers and inequality among the visually disabled women.

  13. Assessment of perioperative antimicrobial prophylaxis using ATC/DDD methodology.

    PubMed

    Bozkurt, Fatma; Kaya, Safak; Gulsun, Serda; Tekin, Recep; Deveci, Özcan; Dayan, Saim; Hoşoglu, Salih

    2013-12-01

    In the light of international experience and guidelines and in order to improve the quality of perioperative antimicrobial prophylaxis (PAP), various hospitals have set up their own multidisciplinary healthcare teams and have evaluated the density of PAP through close supervision and interventions. The aim of the present study was to compare the density, quality, and cost of PAP before and after an intervention implemented at our hospital in order to increase the quality of PAP. PAP was monitored using a form prepared in line with the international guidelines, which was completed by the infection control nurse under the supervision of the infectious diseases specialist. In order to reduce the frequent errors in our PAP procedures, an intervention was implemented, and the period before this intervention (January-April 2011) was compared with the post-intervention period 1 year later (January-April 2012). The density of PAP was calculated according to the Anatomical Therapeutic Chemical classification/defined daily dose (ATC/DDD) methodology. A total of 2398 patients received PAP during this period. The most frequently used antibiotic before and after the intervention was cefazolin. Its use further increased after the intervention (p<0.001). After the intervention, the ratio of the correct timing of the first antibiotic dose increased from 91.7% to 99.0% (p<0.001), while the excessively long administration of PAP was reduced from 77.0% to 44.7% (p<0.001). The ratio of full compliance with the guidelines increased from 15.5% to 40.2% (p<0.001) and the rate of surgical site infections dropped from 18.5% to 12.0%. The density of antibiotic use dropped from 305.7 DDD/100 procedures=3.1 DDD/procedure to 162.1 DDD/100 procedures=1.6 DDD/procedure. The quality of PAP may be improved through better compliance with healthcare guidelines, close supervision, and training activities. Also, surgical site infections and the cost of PAP may be reduced through more appropriate antibiotic use, thus contributing to the national healthcare budget. Copyright © 2013 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  14. Evaluation of end-tidal CO2 pressure at the anaerobic threshold for detecting and assessing pulmonary hypertension.

    PubMed

    Higashi, Akifumi; Dohi, Yoshihiro; Yamabe, Sayuri; Kinoshita, Hiroki; Sada, Yoshiharu; Kitagawa, Toshiro; Hidaka, Takayuki; Kurisu, Satoshi; Yamamoto, Hideya; Yasunobu, Yuji; Kihara, Yasuki

    2017-11-01

    Cardiopulmonary exercise testing (CPET) is useful for the evaluation of patients with suspected or confirmed pulmonary hypertension (PH). End-tidal carbon dioxide pressure (PETCO 2 ) during exercise is reduced with elevated pulmonary artery pressure. However, the utility of ventilatory parameters such as CPET for detecting PH remains unclear. We conducted a review in 155 patients who underwent right heart catheterization and CPET. Fifty-nine patients had PH [mean pulmonary arterial pressure (mPAP) ≥25 mmHg]. There was an inverse correlation between PETCO 2 at the anaerobic threshold (AT) and mPAP (r = -0.66; P < 0.01). Multiple regression analysis showed that PETCO 2 at the AT was independently associated with an elevated mPAP (P = 0.04). The sensitivity and specificity of CPET for PH were 80 and 86%, respectively, when the cut-off value identified by receiver operating characteristic curve analysis for PETCO 2 at the AT was ≤34.7 mmHg. A combination of echocardiography and CPET improved the sensitivity in detecting PH without markedly reducing specificity (sensitivity 87%, specificity 85%). Evaluation of PETCO 2 at the AT is useful for estimating pulmonary pressure. A combination of CPET and previous screening algorithms for PH may enhance the diagnostic ability of PH.

  15. Impact of Pulmonary Artery Pressure on Exercise Function in Severe COPD

    PubMed Central

    Sims, Michael W.; Margolis, David J.; Localio, A. Russell; Panettieri, Reynold A.; Kawut, Steven M.; Christie, Jason D.

    2009-01-01

    Background: Although pulmonary hypertension commonly complicates COPD, the functional consequences of increased pulmonary artery pressures in patients with this condition remain poorly defined. Methods: We conducted a cross-sectional analysis of a cohort of 362 patients with severe COPD who were evaluated for lung transplantation. Patients with pulmonary hemodynamics measured by cardiac catheterization and available 6-min walk test results were included. The association of mean pulmonary artery pressure (mPAP) with pulmonary function, echocardiographic variables, and 6-min walk distance was assessed. Results: The prevalence of pulmonary hypertension (mPAP, > 25 mm Hg; pulmonary artery occlusion pressure [PAOP], < 16 mm Hg) was 23% (95% confidence interval, 19 to 27%). In bivariate analysis, higher mPAP was associated with lower FVC and FEV1, higher Pco2 and lower Po2 in arterial blood, and more right heart dysfunction. Multivariate analysis demonstrated that higher mPAP was associated with shorter distance walked in 6 min, even after adjustment for age, gender, race, height, weight, FEV1, and PAOP (−11 m for every 5 mm Hg rise in mPAP; 95% confidence interval, −21 to −0.7; p = 0.04). Conclusions: Higher pulmonary artery pressures are associated with reduced exercise function in patients with severe COPD, even after controlling for demographics, anthropomorphics, severity of airflow obstruction, and PAOP. Whether treatments aimed at lowering pulmonary artery pressures may improve clinical outcomes in COPD, however, remains unknown. PMID:19318664

  16. Cost-effectiveness of liquid-based cytology with or without hybrid-capture II HPV test compared with conventional Pap smears: a study by the French Society of Clinical Cytology.

    PubMed

    Cochand-Priollet, Béatrix; Cartier, Isabelle; de Cremoux, Patricia; Le Galès, Catherine; Ziol, Marianne; Molinié, Vincent; Petitjean, Alain; Dosda, Anne; Merea, Estelle; Biaggi, Annonciade; Gouget, Isabelle; Arkwright, Sylviane; Vacher-Lavenu, Marie-Cécile; Vielh, Philippe; Coste, Joël

    2005-11-01

    Many articles concerning conventional Pap smears, ThinPrep liquid-based cytology (LBC) and Hybrid-Capture II HPV test (HC II) have been published. This study, carried out by the French Society of Clinical Cytology, may be conspicuous for several reasons: it was financially independent; it compared the efficiency of the conventional Pap smear and LBC, of the conventional Pap smear and HC II, and included an economic study based on real costs; for all the women, a "gold standard" reference method, colposcopy, was available and biopsies were performed whenever a lesion was detected; The conventional Pap smear, the LBC (split-sample technique), the colposcopy, and the biopsies were done at the same time. This study included 2,585 women shared into two groups: a group A of a high-risk population, a group B of a screening population. The statistical analysis of the results showed that conventional Pap smears consistently had superior or equivalent sensitivity and specificity than LBC for the lesions at threshold CIN-I (Cervical Intraepithelial Neoplasia) or CIN-II or higher. It underlined the low specificity of the HC II. Finally, the LBC mean cost was never covered by the Social Security tariff.

  17. Cancer preventive screening: A cross-border comparison of United States and Canadian Chinese women

    PubMed Central

    Tu, Shin-Ping; Jackson, Sara L.; Yasui, Yutaka; Deschamps, Michéle; Hislop, T. Gregory; Taylor, Vicky M.

    2006-01-01

    Objective To compare screening mammography and Pap testing among Chinese women in Seattle, Washington to Vancouver, and British Columbia. Methods Using community-based sampling methods, trilingual female interviewers surveyed Chinese women in Seattle and Vancouver. Multiple preventive health behaviors and health care access variables were assessed. Mammography analysis included 409 women aged 50–74 years. Pap testing analysis included 973 women aged 20–69 years. Main outcome measures were ever use and use in the last 2 years of screening mammography and Pap testing. Results Chinese women in Vancouver were younger, more educated and fluent in English. Unadjusted rates of mammography and Pap testing were similar between the two cities. Provider type was consistently associated with screening in both cities; female providers had the highest rates and Chinese male providers the lowest. Adjusted logistic regression analysis demonstrated similar mammography use in the two cities. However, for Pap testing, women in Seattle had higher odds of screening compared to Vancouver. Conclusion Despite universal health care coverage and baseline characteristics typically associated with greater utilization of preventive screening services, Chinese women in Vancouver did not have higher rates of screening mammography and Pap testing compared to Chinese women in Seattle. PMID:15916991

  18. Prostate-specific acid phosphatase versus acid phosphatase in monitoring patients with prostate cancer.

    PubMed

    Killian, C S; Vargas, F P; Slack, N H; Murphy, G P; Chu, T M

    1982-01-01

    Serial levels of PAP and AcP activity were compared for their relative values in monitoring 57 early and 33 advanced prostate cancer patients. Several findings regarding the patients' disease status and the enzyme levels have been observed that may be beneficial to therapeutic management of these patients. They are: [1] an elevated PAP activity in disease recurrence and disease progression generally precedes an elevated AcP activity, and thus represents a more sensitive index for patients with early and advanced disease; [2] serial mean levels of PAP activity greater than the mean + 3 SD are more predictive for disease recurrence and progression than are those of AcP activity in both groups of patients; [3] PAP activity is a more sensitive monitor for changes in objective treatment response than is AcP activity; and [4] PAP is more specific than AcP for prostate, thus offering a more reliable marker to identify metastasis of unknown origin, or to confirm metastasis derived from a primary prostate tumor that may have been suggested by other non-prostate-specific marker[s]. In addition, data suggest a favorable prognosis for patients receiving therapy as inferred by a serial mean of PAP activity that is less than mean + 3 SD.

  19. HPV testing for cervical cancer screening appears more cost-effective than Papanicolau cytology in Mexico.

    PubMed

    Flores, Yvonne N; Bishai, David M; Lorincz, Attila; Shah, Keerti V; Lazcano-Ponce, Eduardo; Hernández, Mauricio; Granados-García, Víctor; Pérez, Ruth; Salmerón, Jorge

    2011-02-01

    To determine the incremental costs and effects of different HPV testing strategies, when compared to Papanicolau cytology (Pap), for cervical cancer screening in Mexico. A cost-effectiveness analysis (CEA) examined the specific costs and health outcomes associated with (1) no screening; (2) only the Pap test; (3) only self-administered HPV; (4) only clinician administered HPV; and (5) clinician administered HPV plus the Pap test. The costs of self- and clinician-HPV testing, as well as with the Pap test, were identified and quantified. Costs were reported in 2008 US dollars. The health outcome associated with these screening strategies was defined as the number of high-grade cervical intraepithelial neoplasia or cervical cancer cases detected. This CEA was performed using the perspective of the Mexican Institute of Social Security (IMSS) in Morelos, Mexico. Screening women between the ages of 30-80 for cervical cancer using clinical-HPV testing or the combination of clinical-HPV testing, and the Pap is always more cost-effective than using the Pap test alone. This CEA indicates that HPV testing could be a cost-effective screening alternative for a large health delivery organization such as IMSS. These results may help policy-makers implement HPV testing as part of the IMSS cervical cancer screening program.

  20. HPV testing for cervical cancer screening appears more cost-effective than Papanicolau cytology in Mexico

    PubMed Central

    Bishai, David M.; Lőrincz, Attila; Shah, Keerti V.; Lazcano-Ponce, Eduardo; Hernández, Mauricio; Granados-García, Víctor; Pérez, Ruth; Salmerón, Jorge

    2010-01-01

    Objective To determine the incremental costs and effects of different HPV testing strategies, when compared to Papanicolau cytology (Pap), for cervical cancer screening in Mexico. Methods A cost-effectiveness analysis (CEA) examined the specific costs and health outcomes associated with (1) no screening; (2) only the Pap test; (3) only self-administered HPV; (4) only clinician administered HPV; and (5) clinician administered HPV plus the Pap test. The costs of self- and clinician-HPV testing, as well as with the Pap test, were identified and quantified. Costs were reported in 2008 US dollars. The health outcome associated with these screening strategies was defined as the number of high-grade cervical intraepithelial neoplasia or cervical cancer cases detected. This CEA was performed using the perspective of the Mexican Institute of Social Security (IMSS) in Morelos, Mexico. Results Screening women between the ages of 30–80 for cervical cancer using clinical-HPV testing or the combination of clinical-HPV testing, and the Pap is always more cost-effective than using the Pap test alone. Conclusions This CEA indicates that HPV testing could be a cost-effective screening alternative for a large health delivery organization such as IMSS. These results may help policy-makers implement HPV testing as part of the IMSS cervical cancer screening program. PMID:21170578

  1. Trade-offs between seed and leaf size (seed-phytomer-leaf theory): functional glue linking regenerative with life history strategies … and taxonomy with ecology?

    PubMed

    Hodgson, John G; Santini, Bianca A; Montserrat Marti, Gabriel; Royo Pla, Ferran; Jones, Glynis; Bogaard, Amy; Charles, Mike; Font, Xavier; Ater, Mohammed; Taleb, Abdelkader; Poschlod, Peter; Hmimsa, Younes; Palmer, Carol; Wilson, Peter J; Band, Stuart R; Styring, Amy; Diffey, Charlotte; Green, Laura; Nitsch, Erika; Stroud, Elizabeth; Romo-Díez, Angel; de Torres Espuny, Lluis; Warham, Gemma

    2017-11-10

    While the 'worldwide leaf economics spectrum' (Wright IJ, Reich PB, Westoby M, et al. 2004. The worldwide leaf economics spectrum. Nature : 821-827) defines mineral nutrient relationships in plants, no unifying functional consensus links size attributes. Here, the focus is upon leaf size, a much-studied plant trait that scales positively with habitat quality and components of plant size. The objective is to show that this wide range of relationships is explicable in terms of a seed-phytomer-leaf (SPL) theoretical model defining leaf size in terms of trade-offs involving the size, growth rate and number of the building blocks (phytomers) of which the young shoot is constructed. Functional data for 2400+ species and English and Spanish vegetation surveys were used to explore interrelationships between leaf area, leaf width, canopy height, seed mass and leaf dry matter content (LDMC). Leaf area was a consistent function of canopy height, LDMC and seed mass. Additionally, size traits are partially uncoupled. First, broad laminas help confer competitive exclusion while morphologically large leaves can, through dissection, be functionally small. Secondly, leaf size scales positively with plant size but many of the largest-leaved species are of medium height with basally supported leaves. Thirdly, photosynthetic stems may represent a functionally viable alternative to 'small seeds + large leaves' in disturbed, fertile habitats and 'large seeds + small leaves' in infertile ones. Although key elements defining the juvenile growth phase remain unmeasured, our results broadly support SPL theory in that phytometer and leaf size are a product of the size of the initial shoot meristem (≅ seed mass) and the duration and quality of juvenile growth. These allometrically constrained traits combine to confer ecological specialization on individual species. Equally, they appear conservatively expressed within major taxa. Thus, 'evolutionary canalization' sensu Stebbins (Stebbins GL. 1974. Flowering plants: evolution above the species level . Cambridge, MA: Belknap Press) is perhaps associated with both seed and leaf development, and major taxa appear routinely specialized with respect to ecologically important size-related traits. © The Author 2017. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com

  2. Impact of HPV testing, HPV vaccine development, and changing screening frequency on national Pap test volume: projections from the National Health Interview Survey (NHIS).

    PubMed

    Eltoum, Isam A; Roberson, Janie

    2007-02-25

    The frequently cited number of 50 million annual Papanicolaou cervical screening (Pap) tests performed in the US was based on the National Health Interview Survey (NHIS) of the 1980s. Since then, monumental changes have occurred. More change will soon follow when primary human papilloma virus (HPV) testing and/or HPV vaccine delivery are fully accepted and implemented. The objectives of this study were 1) to estimate the total annual Pap tests performed in the US based on recent NHIS surveys, and 2) to estimate the potential change in the total annual Pap volume produced by changing demographics, reduced screening frequency, HPV testing, and the HPV vaccine. In the NHIS 2000 and NHIS 2005, women were asked to report the frequency of their Pap tests for the 6 years prior to the interview and to report whether they had abnormal findings. The authors analyzed the survey respondents answers to these questions by using SAS Survey Procedures (SAS Institute, NC). The results were stratified by age, and the total national volume was then extrapolated from a similarly stratified 2000 US census. The projected increase of total Pap tests for the next 25 years was determined by using the projected census data. Potential reductions of Pap tests performed secondarily to HPV testing of women >30 years old and of HPV vaccination were also determined. Based on NHIS 2000 and NHIS 2005, 66 million (95% CI, 65-68) and 65 million (95% CI, 64-67) Pap tests were performed in the US, respectively. Had HPV testing been performed in women older than 30 years who had both negative HPV and negative 3-year Pap tests, then 30% (95% CI, 29-32%) of Pap tests would not have been performed. If both HPV testing and vaccination are performed, the total number of Pap tests performed annually is predicted to be reduced by 43% (95% CI, 35-38%). Therefore, despite an expected increase in the population of women eligible for Pap tests, the total number will likely decrease substantially in the future. This, in turn, will decrease the demand for a traditionally trained cytotechnology workforce. (c) 2007 American Cancer Society.

  3. Arabidopsis thaliana G2-LIKE FLAVONOID REGULATOR and BRASSINOSTEROID ENHANCED EXPRESSION1 are low-temperature regulators of flavonoid accumulation.

    PubMed

    Petridis, Antonios; Döll, Stefanie; Nichelmann, Lars; Bilger, Wolfgang; Mock, Hans-Peter

    2016-08-01

    Flavonoid synthesis is predominantly regulated at the transcriptional level through the MYB-basic helix-loop-helix (bHLH)-WD40 (MBW) (MYB: transcription factor of the myeloblastosis protein family, WD40: tanscription factor with a short structural motif of 40 amino acids which terminates in an aspartic acid-tryptophan dipeptide) complex, and responds to both environmental and developmental stimuli. Although the developmental regulation of flavonoid accumulation in Arabidopsis thaliana has been examined in great detail, the response of the flavonoid synthesis pathway to abiotic stress (particularly low temperature) remains unclear. A screen of a Dissociation element (Ds) transposon-induced mutation collection identified two lines which exhibited an altered profile of phenylpropanoid accumulation following exposure to low-temperature stress. One of the mutated genes (BRASSINOSTEROID ENHANCED EXPRESSION1 (BEE1)) encoded a brassinosteroid enhanced expression transcription factor, while the other (G2-LIKE FLAVONOID REGULATOR (GFR)) encoded a G2-like flavonoid regulator. Phenylpropanoid-targeted analysis was performed using high-performance LC-MS, and gene expression analysis using quantitative reverse transcription-PCR. In both mutants, the accumulation of quercetins and scopolin was reduced under low-temperature growing conditions, whereas that of anthocyanin was increased. BEE1 and GFR were both shown to negatively regulate anthocyanin accumulation by inhibiting anthocyanin synthesis genes via the suppression of the bHLH (TRANSPARENT TESTA8 (TT8) and GLABROUS3 (GL3)) and/or the MYB (PRODUCTION OF ANTHOCYANIN PIGMENTS2 (PAP2)) components of the MBW complex. Our results provide new insight into the regulatory control of phenylpropanoid metabolism at low temperatures, and reveal that BEE1 and GFR act as important components of the signal transduction chain. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

  4. Association of Borderline Pulmonary Hypertension With Mortality and Hospitalization in a Large Patient Cohort: Insights From the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program.

    PubMed

    Maron, Bradley A; Hess, Edward; Maddox, Thomas M; Opotowsky, Alexander R; Tedford, Ryan J; Lahm, Tim; Joynt, Karen E; Kass, Daniel J; Stephens, Thomas; Stanislawski, Maggie A; Swenson, Erik R; Goldstein, Ronald H; Leopold, Jane A; Zamanian, Roham T; Elwing, Jean M; Plomondon, Mary E; Grunwald, Gary K; Barón, Anna E; Rumsfeld, John S; Choudhary, Gaurav

    2016-03-29

    Pulmonary hypertension (PH) is associated with increased morbidity across the cardiopulmonary disease spectrum. Based primarily on expert consensus opinion, PH is defined by a mean pulmonary artery pressure (mPAP) ≥25 mm Hg. Although mPAP levels below this threshold are common among populations at risk for PH, the relevance of mPAP <25 mm Hg to clinical outcome is unknown. We analyzed retrospectively all US veterans undergoing right heart catheterization (2007-2012) in the Veterans Affairs healthcare system (n=21,727; 908-day median follow-up). Cox proportional hazards models were used to evaluate the association between mPAP and outcomes of all-cause mortality and hospitalization, adjusted for clinical covariates. When treating mPAP as a continuous variable, the mortality hazard increased beginning at 19 mm Hg (hazard ratio [HR]=1.183; 95% confidence interval [CI], 1.004-1.393) relative to 10 mm Hg. Therefore, patients were stratified into 3 groups: (1) referent (≤18 mm Hg; n=4,207); (2) borderline PH (19-24 mm Hg; n=5,030); and (3) PH (≥25 mm Hg; n=12,490). The adjusted mortality hazard was increased for borderline PH (HR=1.23; 95% CI, 1.12-1.36; P<0.0001) and PH (HR=2.16; 95% CI, 1.96-2.38; P<0.0001) compared with the referent group. The adjusted hazard for hospitalization was also increased in borderline PH (HR=1.07; 95% CI, 1.01-1.12; P=0.0149) and PH (HR=1.15; 95% CI, 1.09-1.22; P<0.0001). The borderline PH cohort remained at increased risk for mortality after excluding the following high-risk subgroups: (1) patients with pulmonary artery wedge pressure >15 mm Hg; (2) pulmonary vascular resistance ≥3.0 Wood units; or (3) inpatient status at the time of right heart catheterization. These data illustrate a continuum of risk according to mPAP level and that borderline PH is associated with increased mortality and hospitalization. Future investigations are needed to test the generalizability of our findings to other populations and study the effect of treatment on outcome in borderline PH. © 2016 American Heart Association, Inc.

  5. From guidelines to practice: a pharmacist-driven prospective audit and feedback improvement model for peri-operative antibiotic prophylaxis in 34 South African hospitals.

    PubMed

    Brink, Adrian J; Messina, Angeliki P; Feldman, Charles; Richards, Guy A; van den Bergh, Dena

    2017-04-01

    Few data exist on the implementation of process measures to facilitate adherence to peri-operative antibiotic prophylaxis (PAP) guidelines in Africa. To implement an improvement model for PAP utilizing existing resources, in order to achieve a reduction in surgical site infections (SSIs) across a heterogeneous group of 34 urban and rural South African hospitals. A pharmacist-driven, prospective audit and feedback strategy involving change management and improvement principles was utilized. This 2.5 year intervention involved a pre-implementation phase to test a PAP guideline and a 'toolkit' at pilot sites. Following antimicrobial stewardship committee and clinician endorsement, the model was introduced in all institutions and a survey of baseline SSI and compliance rates with four process measures (antibiotic choice, dose, administration time and duration) was performed. The post-implementation phase involved audit, intervention and monthly feedback to facilitate improvements in compliance. For 70 weeks of standardized measurements and feedback, 24 206 surgical cases were reviewed. There was a significant improvement in compliance with all process measures (composite compliance) from 66.8% (95% CI 64.8-68.7) to 83.3% (95% CI 80.8-85.8), representing a 24.7% increase ( P  <   0.0001). The SSI rate decreased by 19.7% from a mean group rate of 2.46 (95% CI 2.18-2.73) pre-intervention to 1.97 post-intervention (95% CI 1.79-2.15) ( P  =   0.0029). The implementation of process improvement initiatives and principles targeted to institutional needs utilizing pharmacists can effectively improve PAP guideline compliance and sustainable patient outcomes. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  6. Endometrial cancer surveillance adherence reduces utilization and subsequent costs.

    PubMed

    Schwartz, Zachary P; Frey, Melissa K; Philips, Sarah; Curtin, John P

    2017-09-01

    In June 2011, the SGO recommended that physical exam and symptoms be the primary surveillance methods in patients with endometrial cancer. We sought to evaluate adherence to these guidelines by comparing the use of CT scans, paps and serum CA125 ordered for endometrial cancer surveillance before and after publication of these guidelines. A retrospective review was performed for all patients undergoing surveillance for endometrial cancer at a single institution between June 2009 and June 2013. We assessed the number of patients without symptoms or abnormal physical exam findings who underwent surveillance CT scans, paps and/or CA125 during the 2years pre- and 2years post-SGO guidelines. 92 patients (n=48 pre-6/2011, n=44 post-6/2011) were identified. Mean patient age was 58years. No significant difference in age, ethnicity, body mass index, or disease grade or stage was noted. There was a significant decline in surveillance CT scans (n=13, 27% vs. n=4, 9%, p=0.03), CA125 (n=14, 29% vs. 5, 11%, p=0.035) and paps (n=34, 71% vs. n=8 vs. 18%, p<0.001). There was no significant difference in disease status at the last follow-up. Institutional cost of surveillance also declined ($14,102.46 2years pre-guidelines, $3,054.99 2years post-guidelines). In a single urban academic public hospital, after only 2years, clinical adherence to the 2011 SGO endometrial cancer surveillance guidelines resulted in a significant decline in the use of CT scans, CA125 and paps. This reduction does not appear to affect patient outcomes and led to an appreciable decrease in surveillance costs. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. Two IIIf Clade-bHLHs from Freesia hybrida Play Divergent Roles in Flavonoid Biosynthesis and Trichome Formation when Ectopically Expressed in Arabidopsis

    PubMed Central

    Li, Yueqing; Shan, Xiaotong; Gao, Ruifang; Yang, Song; Wang, Shucai; Gao, Xiang; Wang, Li

    2016-01-01

    The MBW complex, comprised by R2R3-MYB, basic helix-loop-helix (bHLH) and WD40, is a single regulatory protein complex that drives the evolution of multiple traits such as flavonoid biosynthesis and epidermal cell differentiation in plants. In this study, two IIIf Clade-bHLH regulator genes, FhGL3L and FhTT8L, were isolated and functionally characterized from Freesia hybrida. Different spatio-temporal transcription patterns were observed showing diverse correlation with anthocyanin and proanthocyanidin accumulation. When overexpressed in Arabidopsis, FhGL3L could enhance the anthocyanin accumulation through up-regulating endogenous regulators and late structural genes. Unexpectedly, trichome formation was inhibited associating with the down-regulation of AtGL2. Comparably, only the accumulation of anthocyanins and proanthocyanidins was strengthened in FhTT8L transgenic lines. Furthermore, transient expression assays demonstrated that FhGL3L interacted with AtPAP1, AtTT2 and AtGL1, while FhTT8L only showed interaction with AtPAP1 and AtTT2. In addition, similar activation of the AtDFR promoter was found between AtPAP1-FhGL3L/FhTT8L and AtPAP1- AtGL3/AtTT8 combinations. When FhGL3L was fused with a strong activation domain VP16, it could activate the AtGL2 promoter when co-transfected with AtGL1. Therefore, it can be concluded that the functionality of bHLH factors may have diverged, and a sophisticated interaction and hierarchical network might exist in the regulation of flavonoid biosynthesis and trichome formation. PMID:27465838

  8. Two IIIf Clade-bHLHs from Freesia hybrida Play Divergent Roles in Flavonoid Biosynthesis and Trichome Formation when Ectopically Expressed in Arabidopsis.

    PubMed

    Li, Yueqing; Shan, Xiaotong; Gao, Ruifang; Yang, Song; Wang, Shucai; Gao, Xiang; Wang, Li

    2016-07-28

    The MBW complex, comprised by R2R3-MYB, basic helix-loop-helix (bHLH) and WD40, is a single regulatory protein complex that drives the evolution of multiple traits such as flavonoid biosynthesis and epidermal cell differentiation in plants. In this study, two IIIf Clade-bHLH regulator genes, FhGL3L and FhTT8L, were isolated and functionally characterized from Freesia hybrida. Different spatio-temporal transcription patterns were observed showing diverse correlation with anthocyanin and proanthocyanidin accumulation. When overexpressed in Arabidopsis, FhGL3L could enhance the anthocyanin accumulation through up-regulating endogenous regulators and late structural genes. Unexpectedly, trichome formation was inhibited associating with the down-regulation of AtGL2. Comparably, only the accumulation of anthocyanins and proanthocyanidins was strengthened in FhTT8L transgenic lines. Furthermore, transient expression assays demonstrated that FhGL3L interacted with AtPAP1, AtTT2 and AtGL1, while FhTT8L only showed interaction with AtPAP1 and AtTT2. In addition, similar activation of the AtDFR promoter was found between AtPAP1-FhGL3L/FhTT8L and AtPAP1- AtGL3/AtTT8 combinations. When FhGL3L was fused with a strong activation domain VP16, it could activate the AtGL2 promoter when co-transfected with AtGL1. Therefore, it can be concluded that the functionality of bHLH factors may have diverged, and a sophisticated interaction and hierarchical network might exist in the regulation of flavonoid biosynthesis and trichome formation.

  9. Glomerular filtration rate estimation from plasma creatinine after inhibition of tubular secretion: relevance of the creatinine assay.

    PubMed

    Kemperman, F A; Silberbusch, J; Slaats, E H; van Zanten, A P; Weber, J A; Krediet, R T; Arisz, L

    1999-05-01

    Estimation of glomerular filtration rate (GFR) from plasma creatinine concentration after inhibition of tubular creatinine secretion with cimetidine provides a good assessment in patients with various nephropathies and with non-insulin-dependent diabetes mellitus (NIDDM). The aim of this study was to compare cimetidine-aided GFR estimations using various creatinine assays. In 30 outpatients with NIDDM GFR was measured as the urinary clearance of continuously infused [125I]iothalamate. Plasma creatinine concentration was analysed after oral cimetidine with an alkaline picrate (AP) method, with an enzymatic (PAP) assay and with HPLC. GFR estimations were calculated with the Cockcroft Gault formula (CG). AP creatinine concentrations were significantly higher than PAP or HPLC values. GFR estimations by AP (CG(AP) 66 +/- 19 ml/min/1.73 m2, mean SD) were significantly lower than GFR (89 +/- 30), whereas CG(PAP) (85 +/- 30) and CG(HPLC) (84 +/- 34 ml/min/1.73 m2) were not. Bland and Altman analysis showed a difference between CG(AP) and GFR of -22.4 +/- 17.7 ml/min/1.73 m2; this difference becomes larger when the GFR increases. The difference between CG and GFR was only -3.8 +/- 14.8 ml/min/1.73 m2 for PAP and -4.4 +/- 17.5 ml/min/1.73 m2 for HPLC, without any systematic difference. A good assessment of the GFR from plasma creatinine after cimetidine administration is possible when creatinine is measured with an enzymatic assay or with the less convenient HPLC method. The more widespread and cheaper alkaline picrate assay is not suitable for GFR-estimation.

  10. Do health care providers have a lower prevalence of abnormal pap smears than the general public?

    PubMed

    Suwannarurk, Komsun; Bhamarapravatana, Konkarn; Kheolamai, Pakpoom; Thaweekul, Yuttadej; Mairaing, Karicha; Poomtavorn, Yenrudee; Pattaraarchachai, Junya

    2010-12-01

    Most Thai people believe that health care providers have a lower risk of any disease than their patients. This belief may lull Thai health care providers into accepting the false belief that they are at a lower risk of having the precancerous conditions that lead to cervical cancer. This study compares the prevalence of abnormal Pap smears from health care providers (HC) and non health care providers (NHC) by using the standard liquid-based Pap smear processing at Thammasat University Hospital's pathology department, Thailand. Both health care providers (HC) and non health care providers (NHC) were patients at the outpatient clinic, Thammasat University Hospital. They were screened for cervical cancer by using liquid-based Pap smear (LBP). Cytological diagnoses and specimen adequacy were classified using the Bethesda system 2001. All subjects who had abnormal cytology more than atypical squamous cells or atypical glandular cells were counseled to have performed a colposcopic directed biopsy for confirmation of pathology. A total of 250 liquid-base Pap smears were processed and evaluated at the Gynecology clinic, Thammasat University Hospital from April 2008 to May 2008. The groups of HC and NHC consisted of 122 and 128 women, respectively. In general, both the HC and NHC groups were similar in their age, religion, income and education level distributions. The range of ages was between 16 and 75 years, with the mean age equal to 40.2 +/- 10.5 years. Prevalence of abnormal Pap smears was 9.8% in HC and 9.4% in NHC (p-value = 0.90). HC showed atypical change (ASC, AGC), low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL) at 0.8%, 1.6% and 7.4%, respectively. NHC had an incidence of atypical change, LSIL and HSIL at 0.8%, 0.8% and 7.8%. HC had an equal incidence of abnormal Pap smears prevalence to NHC. Further, the percentage of HC and NHC groups with histological confirmed cervical intraepithelial neoplasia (CIN) 1 were not significantly different (4.92% vs. 6.25%, p-value = 0.70), likewise CIN 2/3 (1.64% vs. 1.56%, p-value = 1.00). According to our study the rate of abnormal Pap smears observed in both health care providers and clients was essentially the same. The prevalence of abnormal Pap smears in health care providers was statistically equivalent to that in their clients.

  11. Rates of initial acceptance of PAP masks and outcomes of mask switching.

    PubMed

    Bachour, Adel; Vitikainen, Pirjo; Maasilta, Paula

    2016-05-01

    Recently, we noticed a considerable development in alleviating problems related to positive airway pressure (PAP) masks. In this study, we report on the initial PAP mask acceptance rates and the effects of mask switching on mask-related symptoms. We prospectively collected all cases of mask switching in our sleep unit for a period of 14 months. At the time of the study, we used ResMed™ CPAP devices and masks. Mask switching was defined as replacing a mask used for at least 1 day with another type of mask. Changing to a different size but keeping the same type of mask did not count as mask switching. Switching outcomes were considered failed if the initial problem persisted or reappeared during the year that followed switching. Our patient pool was 2768. We recorded 343 cases of mask switching among 267 patients. Of the 566 patients who began new PAP therapy, 108 (39 women) had switched masks, yielding an initial mask acceptance rate of 81 %. The reason for switching was poor-fit/uncomfortable mask in 39 %, leak-related in 30 %, outdated model in 25 %, and nasal stuffiness in 6 % of cases; mask switching resolved these problems in 61 %. Mask switching occurred significantly (p = 0.037) more often in women and in new PAP users. The odds ratio for abandoning PAP therapy within 1 year after mask switching was 7.2 times higher (interval 4.7-11.1) than not switching masks. The initial PAP mask acceptance rate was high. Patients who switched their masks are at greater risk for abandoning PAP therapy.

  12. Associations Between Religion-Related Factors and Cervical Cancer Screening Among Muslims in Greater Chicago

    PubMed Central

    Padela, Aasim I.; Peek, Monica; Johnson-Agbakwu, Crista E.; Hosseinian, Zahra; Curlin, Farr

    2015-01-01

    Objective This study aimed to assess rates of Papanicolaou (Pap) testing and associations between religion-related factors and these rates among a racially and ethnically diverse sample of American Muslim women. Materials and Methods A community-based participatory research design was used in partnering with the Council of Islamic Organizations of Greater Chicago to recruit Muslim women attending mosque and community events. These participants self-administered surveys incorporating measures of fatalism, religiosity, perceived discrimination, Islamic modesty, and a marker of Pap test use. Results A total of 254 survey respondents were collected with nearly equal numbers of Arabs, South Asians, and African American respondents. Of these respondents, 84% had obtained a Pap test in their lifetime, with individuals who interpret disease as a manifestation of God’s punishment having a lower odds of having had Pap testing after controlling for sociodemographic factors (odds ratio [OR] = 0.87, 95% CI = 0.77–1.0). In multivariate models, living in the United States for more than 20 years (OR = 4.7, 95% CI = 1.4–16) and having a primary care physician (OR = 7.7, 95% CI = 2.5–23.4) were positive predictors of having had a Pap test. Ethnicity, fatalistic beliefs, perceived discrimination, and modesty levels were not significantly associated with Pap testing rates. Conclusions To our knowledge, this is the first study to assess Pap testing behaviors among a diverse sample of American Muslim women and to observe that negative religious coping (e.g., viewing health problems as a punishment from God) is associated with a lower odds of obtaining a Pap test. The relationship between religious coping and cancer screening behaviors deserves further study so that religious values can be appropriately addressed through cancer screening programs. PMID:24914883

  13. A model to evaluate the costs and clinical effectiveness of human papilloma virus screening compared with annual papanicolaou cytology in Germany.

    PubMed

    Petry, Karl Ulrich; Barth, Cordula; Wasem, Jürgen; Neumann, Anja

    2017-05-01

    We modelled human papilloma virus (HPV) primary screening scenarios compared with Pap cytology to evaluate clinical effectiveness and projected annual costs in Germany. A Markov cohort model was built to compare the budget impact of annual Pap cytology with different 5-yearly HPV screening scenarios: (1) a positive HPV test followed by Pap cytology; (2) a positive HPV test followed by p16/Ki-67 dual-stained cytology; (3) a positive HPV test followed by colposcopy if HPV-16/18-positive or p16/Ki-67 dual-stained cytology if positive for other subtypes; (4) co-testing with HPV and Pap. Screening scenarios were based on a 10-year horizon. All HPV screening scenarios in the model were associated with fewer deaths from missed diagnosis of cervical cancer compared with Pap screening; 10-year totals n=172-344 (1.5-3 per 100,000) versus n=477 (4.1 per 100,000), respectively. Total annual costs were lower with HPV screening than Pap cytology. The projected average annual cost for HPV screening ranged from €117 million to €136 million compared with €177 million for Pap screening, representing annual savings of €41-60 million. The greatest clinical impact was achieved with primary HPV screening (with genotyping) followed by colposcopy for HPV 16/18-positive women or p16/Ki-67 dual-stained cytology for women positive for other HPV subtypes. Screening strategies including primary HPV testing for high-risk subtypes (HPV-16/18) in conjunction with p16/Ki-67 dual-stained cytology can improve the detection of cervical cancer at a lower total annual cost than conventional Pap cytology screening. Copyright © 2017. Published by Elsevier B.V.

  14. Community-Based Screening for Cervical Cancer: A Feasibility Study of Rural Appalachian Women

    PubMed Central

    Crosby, Richard A.; Hagensee, Michael E.; Vanderpool, Robin; Nelson, Nia; Parrish, Adam; Collins, Tom; Jones, Nebraska

    2015-01-01

    Objectives To describe women’s comfort levels and perceptions about their experience self-collecting cervico-vaginal swabs for HPV testing; to determine whether nurse-guided patient navigation increases the odds of women receiving a traditional Pap test after HPV screening; and to test the hypothesis that women testing positive for oncogenic HPV would be more likely to have a subsequent Pap test than those testing negative. Methods 400 women were recruited from eight rural Appalachian counties, in 2013 and 2014. After completing a survey, women were provided instructions for self-collecting a cervico-vaginal swab. Specimens were tested for 13 oncogenic HPV types. Simultaneously, women were notified of their test results and offered initial navigation for Pap testing. Chart-verified Pap testing within the next six months served as the endpoint. Results Comfort levels with self-collection were high: 89.2% indicated they would be more likely to self-collect a specimen for testing, on a regular basis, compared to Pap testing. Thirty women (7.5%) had a follow-up Pap test. Women receiving added nurse-guided navigation efforts were significantly less likely to have a subsequent test (P = .01). Women testing positive for oncogenic HPV were no more likely than those testing negative to have a subsequent Pap test (P = .27). Data were analyzed in 2014. Conclusions Rural Appalachian women are comfortable self-collecting cervico-vaginal swabs for HPV testing. Further, efforts to re-contact women who have received an oncogenic HPV test result and an initial navigation contact may not be useful. Finally, testing positive for oncogenic HPV may not be a motivational factor for subsequent Pap testing. PMID:26462184

  15. Clinical Human Papillomavirus Detection Forecasts Cervical Cancer Risk in Women Over 18 Years of Follow-Up

    PubMed Central

    Castle, Philip E.; Glass, Andrew G.; Rush, Brenda B.; Scott, David R.; Wentzensen, Nicolas; Gage, Julia C.; Buckland, Julie; Rydzak, Greg; Lorincz, Attila T.; Wacholder, Sholom

    2012-01-01

    Purpose To describe the long-term (≥ 10 years) benefits of clinical human papillomavirus (HPV) DNA testing for cervical precancer and cancer risk prediction. Methods Cervicovaginal lavages collected from 19,512 women attending a health maintenance program were retrospectively tested for HPV using a clinical test. HPV positives were tested for HPV16 and HPV18 individually using a research test. A Papanicolaou (Pap) result classified as atypical squamous cells of undetermined significance (ASC-US) or more severe was considered abnormal. Women underwent follow-up prospectively with routine annual Pap testing up to 18 years. Cumulative incidence rates (CIRs) of ≥ grade 3 cervical intraepithelial neoplasia (CIN3+) or cancer for enrollment test results were calculated. Results A baseline negative HPV test provided greater reassurance against CIN3+ over the 18-year follow-up than a normal Pap (CIR, 0.90% v 1.27%). Although both baseline Pap and HPV tests predicted who would develop CIN3+ within the first 2 years of follow-up, only HPV testing predicted who would develop CIN3+ 10 to 18 years later (P = .004). HPV16- and HPV18-positive women with normal Pap were at elevated risk of CIN3+ compared with other HPV-positive women with normal Pap and were at similar risk of CIN3+ compared with women with a low-grade squamous intraepithelial Pap. Conclusion HPV testing to rule out cervical disease followed by Pap testing and possibly combined with the detection of HPV16 and HPV18 among HPV positives to identify those at immediate risk of CIN3+ would be an efficient algorithm for cervical cancer screening, especially in women age 30 years or older. PMID:22851570

  16. A hand-made supplementary food for malnourished children.

    PubMed

    Vanelli, Maurizio; Virdis, Raffaele; Contini, Sandro; Corradi, Mara; Cremonini, Giulia; Marchesi, Maddalena; Mele, Alessandra; Monti, Francesca; Pagano, Blandina; Proietti, Ilaria; Savina, Francesca; Verna, Marta; Vitale, Rosa; Zanzucchi, Matteo; Brighenti, Furio; Vittadini, Elena; Del Rio, Daniele; Scazzina, Francesca; Porcu, Andrea

    2014-12-17

    We tested the possibility to prepare a hyperproteic and hyperenergetic supplementary food for malnutrition rehabilitation in children starting from available ingredients in popular markets in Sierra Leone. Twelve residents in Paediatrics from University of Parma, Italy, prepared in a hospital near the capital Freetown with modest technology a mixture of peanut flour, palm oil, milk powder, sugar and vitamins to which they gave the name of "Parma pap". Three hundred and thirty-two malnourished children (mean age 14±6.3 months) who were receiving Feeding Program Supplementations (FPS), were enrolled in the study: 177 participants received randomly FSP portions only (Group 1), and 159 participants were treated with FSP regimen plus a supplement of "Parma pap" (Group 2). Outcomes of the study were computed as WHZ-score increment (Δ value) by subtracting the discharge WHZ-score from the admission WHZ-score. The best Δ-WHZ-scores (>+4) were recorded among participants of Group 2 (64%) rather than in Group 1 (21%; p=0.040). The children receiving FSP portions plus "Parma pap" recovered faster (5.54 week on average) than those treated with FSP regimen only (8.16 on average). The percentage of children who did not recover was higher in Group 1 (25.3%) than in Group 2 (; 13%; p=0.05). A slight positive correlation has been found between WHZ-scores at admission and at the end of the study (r=0.19; p=0.045). During the experience in Sierra Leone we have had the chance to give "Parma pap" to twenty one malnourished children admitted to Xaverian Mission in Makeni, northern Sierra Leone, not taking other supplementary food. Sixteen of these children recovered in 4.9 week on average and five in 6 to 8 weeks. Mean Δ-WHZ-scores ranged between + 1 and + 5. The data from the present study suggest that "Parma pap" could be an effective additional food to FPS regimen in malnutrition recovering. Further researches are needed on the contrary to prove if "Parma pap" could be defined as a veritable ready to use therapeutic food, although this characteristic seems already to result from the experience in Makeni Mission.

  17. Incidence of High Grade Squamous Intraepithelial Lesions in Patients with Atypical Squamous Cells of Undetermined Significance Papanicolaou Smears at Naresuan University Hospital.

    PubMed

    Heng, Suttichai; Sirichaisutdhikorn, Daranee

    2016-01-01

    To determine the incidence of high-grade cervical intraepithelial neoplasia (CIN2-3) among patients with atypical squamous cells of undetermined significance (ASC-US) Papanicolaou (Pap) smears. One-hundred and eighty-seven patients with ASC-US Pap smears who underwent colposcopy with histological study were enrolled between September 2007 and August 2015. Patient factors (including age, parity, current pills used, HIV status, age at first sexual intercourse and number of sexual partners) were obtained. Logistic regression analysis was used to evaluate clinical factors associated with CIN2-3. CIN was diagnosed in 92 of 187 women (49.2%). Sixty-one of these (32.6%) had CIN1 and 31 (16.6%) had CIN2-3. There was no woman who had invasive cancer. There was no correlation of high-grade CIN with factors in this study including age, parity, current pills used, HIV status, age at first sexual intercourse and number of sexual partners. Data from this study showed no invasive cervical cancer was found in patients with ASC-US. There was no patient factor associated with high grade intraepithelial neoplasia in patients with ASC-US Pap smears.

  18. Attitudes and factors affecting acceptability of self-administered cervicovaginal sampling for human papillomavirus (HPV) genotyping as an alternative to Pap testing among multiethnic Malaysian women.

    PubMed

    Ma'som, Mahirah; Bhoo-Pathy, Nirmala; Nasir, Nazrila Hairizan; Bellinson, Jerome; Subramaniam, Shridevi; Ma, Yuntong; Yap, Siew-Hwei; Goh, Pik-Pin; Gravitt, Patti; Woo, Yin Ling

    2016-08-04

    The objective of this study was to determine the attitudes and acceptability of self-administered cervicovaginal sampling compared with conventional physician-acquired Papanicolaou (Pap) smear among multiethnic Malaysian women. A cross-sectional study was carried out via interviewer-administered surveys from August 2013 through August 2015 at five government-run, urban health clinics in the state of Selangor. Subjects were participants from an ongoing community-based human papillomavirus (HPV) prevalence study who answered a standard questionnaire before and after self-sampling. The cervicovaginal self-sampling for HPV genotyping was performed using a simple brush ('Just for Me'; Preventive Oncology International, Hong Kong). Detailed data on sociodemographics, previous Pap smear experience, and attitudes towards self-administered cervicovaginal sampling were collected and analysed. Acceptability was inferred using a five-item Likert scale that included six different subjective descriptives: experience, difficulty, convenience, embarrassment, discomfort or pain, and confidence in collecting one's own sample. Of the 839 participants, 47.9% were Malays, followed by 30.8% Indians, 18.8% Chinese and 2.5% from other ethnicities. The median age of the participants was 38 years (IQR 30-48). Some 68.2% of participants indicated a preference for self-sampling over the Pap test, with 95% indicating willingness to follow-up a positive result at the hospital. Age, ethnicity and previous Pap test experience were significant independent factors associated with preference for self-sampling. The older the individual, the less likely they were to prefer self-sampling (adjusted OR 0.94, 95% CI 0.90 to 0.98). The Chinese were less likely to prefer self-sampling (72.6%) than the Malays (85.1%) (adjusted OR 0.57, 95% CI 0.33 to 0.98, p=0.004). Participants who had never undergone a Pap smear were also more likely to prefer self-sampling (88.5%) than women who had undergone a previous Pap (80.9%) (adjusted OR 0.06, 95% CI 0.35 to 0.87). Overall, urban Malaysian women from multiethnic backgrounds found self-sampling to be an acceptable alternative to Pap smear. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  19. The role of severity of obstructive sleep apnea measured by apnea-hypopnea index in predicting compliance with pressure therapy, a meta-analysis.

    PubMed

    Madbouly, Essam M; Nadeem, Rashid; Nida, Mahwish; Molnar, Janos; Aggarwal, Saurabh; Loomba, Rohit

    2014-01-01

    Obstructive sleep apnea (OSA) is associated with diabetes, hypertension, stroke, coronary artery disease, and premature death. Positive airway pressure (PAP) is the mainstay of therapy. Despite its effective treatment with PAP therapy, noncompliance remains high. Many factors determine compliance. The role of severity of OSA measured by the apnea-hypopnea index (AHI) remains controversial. Meta-analysis of studies examining this role of AHI was performed. A systematic review of the medical literature was conducted using PubMed and Cochrane library by utilizing different combinations of key words: sleep apnea, AHI, compliance, and nonadherence. Inclusion criteria were English articles; Studies with adult population; with 2 groups of patients (compliant and noncompliant); Studies utilizing objective definition of compliance (PAP usage of >4 hours per night for 70% of days or usage >5 d/wk and for >4 hours per night). Studies were analyzed by standard methods of meta-analysis. The studies were heterogeneous for AHI; therefore, the random effect model was used. Six hundred forty-one manuscripts were found. Of these, 230 were found to be appropriate for full text evaluation. Thirty-one met inclusion criteria. Twelve of these studies used objective criteria for PAP compliance and were hence included in meta-analysis. All the subjects had OSA determined by polysomnography, for whom PAP was employed. Compliance to PAP therapy was evaluated after a period of time ranging from 4 weeks to 8 years. There were 1438 subjects included in the meta-analysis; 886 subjects were PAP compliant, whereas 552 subjects were noncompliant. A greater AHI was found in PAP compliant patients. The mean difference between compliant and noncompliant groups was 5.9 (95% confidence interval: 0.19-11.67, P < 0.05). Patients with mild OSA are less likely to be compliant with PAP therapy. These patients should receive aggressive management particularly at the start of therapy with close follow-up to increase compliance.

  20. Cost-effectiveness of HPV-based cervical cancer screening in the public health system in Nicaragua

    PubMed Central

    Mvundura, Mercy; Jeronimo, Jose; Holme, Francesca; Vodicka, Elisabeth; Kim, Jane J

    2017-01-01

    Objectives To evaluate the cost-effectiveness of human papillomavirus (HPV) DNA testing (versus Papanicolaou (Pap)-based screening) for cervical cancer screening in Nicaragua. Design A previously developed Monte Carlo simulation model of the natural history of HPV infection and cervical cancer was calibrated to epidemiological data from Nicaragua. Cost data inputs were derived using a micro-costing approach in Carazo, Chontales and Chinandega departments; test performance data were from a demonstration project in Masaya department. Setting Nicaragua’s public health sector facilities. Participants Women aged 30–59 years. Interventions Screening strategies included (1) Pap testing every 3 years, with referral to colposcopy for women with an atypical squamous cells of undetermined significance or worse result (‘Pap’); (2) HPV testing every 5 years, with referral to cryotherapy for HPV-positive eligible women (HPV cryotherapy or ‘HPV-Cryo’); (3) HPV testing every 5 years, with referral to triage with visual inspection with acetic acid (VIA) for HPV-positive women (‘HPV-VIA’); and (4) HPV testing every 5 years, with referral to Pap testing for HPV-positive women (‘HPV-Pap’). Outcome measures Reduction in lifetime risk of cancer and incremental cost-effectiveness ratios (ICER; 2015 US$ per year of life saved (YLS)). Results HPV-based screening strategies were more effective than Pap testing. HPV-Cryo was the least costly and most effective strategy, reducing lifetime cancer risk by 29.5% and outperforming HPV-VIA, HPV-Pap and Pap only, which reduced cancer risk by 19.4%, 12.2% and 10.8%, respectively. With an ICER of US$320/YLS, HPV-Cryo every 5 years would be very cost-effective using a threshold based on Nicaragua’s per capita gross domestic product of US$2090. Findings were robust across sensitivity analyses on test performance, coverage, compliance and cost parameters. Conclusions HPV testing is very cost-effective compared with Pap testing in Nicaragua, due to higher test sensitivity and the relatively lower number of visits required. Increasing compliance with recommended follow-up will further improve the health benefits and value for public health dollars. PMID:28619772

  1. Effect of four processed animal proteins in the diet on digestibility and performance in laying hens.

    PubMed

    van Krimpen, M M; Veldkamp, T; Binnendijk, G P; de Veer, R

    2010-12-01

    An experiment was performed to investigate the effect of animal vs. vegetable protein sources in the diet of laying hens on the development of hen performance. A diet containing protein sources of only vegetable origin was compared with 4 diets, each containing 1 of 4 processed animal proteins (PAP). Two PAP (Daka-58 and Sonac-60) were classified as meat meals, and the remaining 2 (Daka-40 and Sonac-50) were classified as meat and bone meals. First, fecal digestibility of nutrients in the PAP was determined in Lohmann Brown layers. Hens (n = 132) were housed in 22 cages (6 hens/cage) and allotted to 5 dietary treatments. In the PAP diets (4 replicates/treatment), 100 g/kg of CP of animal origin was added, replacing soybean meal and corn (Zea mays) in the basal diet (6 replicates/treatment). The PAP sources differed largely in chemical composition and digestibility coefficients. Energy content (AME(n)) varied from 1,817 (Daka-40) to 3,107 kcal/kg (Sonac-60), and digestible lysine varied from 15.4 (Daka-40) to 28.3 g/kg (Sonac-50). Subsequently, the effect of a control diet (without PAP) vs. 4 PAP diets (50 g/kg of CP of animal origin from the same batches as used in the digestibility study) on performance was determined. All diets were isocaloric (AME(n) = 2,825 kcal/kg) and isonitrogenous (digestible lysine = 6.8 g/kg). Hens were housed in 40 floor pens (12 hens/pen, 8 pens/treatment) from 20 to 40 wk of age. Feed intake levels of the hens fed the meat and bone meal diets were reduced compared with those of hens fed the meat meal diets, whereas the feed intake level of hens fed the control diet was intermediate. Laying hen performance differed between treatments, being was most favorable for the Sonac-50 treatment and most adverse for the Daka-40 treatment. Differences in laying hen performance seemed to be related partly to differences in feed intake and corresponding amino acid intake.

  2. Effects of feeding a spray-dried multivalent polyclonal antibody preparation on feedlot performance, feeding behavior, carcass characteristics, rumenitis, and blood gas profile of Brangus and Nellore yearling bulls.

    PubMed

    Millen, D D; Pacheco, R D L; DiLorenzo, N; Martins, C L; Marino, C T; Bastos, J P S T; Mariani, T M; Barducci, R S; Sarti, L M N; DiCostanzo, A; Rodrigues, P H M; Arrigoni, M D B

    2015-09-01

    The objective of this study was to evaluate the effects of replacing monensin (MON) with a spray-dried multivalent polyclonal antibody preparation (PAP) against several ruminal microorganisms on feedlot performance, carcass characteristics, feeding behavior, blood gas profile, and the rumenitis incidence of Brangus and Nellore yearling bulls. The study was designed as a completely randomized design with a 2 × 2 factorial arrangement, replicated 6 times (4 bulls per pen and a total of 24 pens), in which bulls ( = 48) of each biotype were fed diets containing either MON fed at 300 mg/d or PAP fed at 3 g/d. No significant feed additive main effects were observed for ADG ( = 0.27), G:F ( = 0.28), HCW ( = 0.99), or dressing percentage ( = 0.80). However, bulls receiving PAP had greater DMI ( = 0.02) and larger ( = 0.02) final LM area as well as greater ( < 0.01) blood concentrations of bicarbonate and base excess in the extracellular fluid than bulls receiving MON. Brangus bulls had greater ( < 0.01) ADG and DMI expressed in kilograms, final BW, heavier HCW, and larger initial and final LM area than Nellore bulls. However, Nellore bulls had greater daily DMI fluctuation ( < 0.01), expressed as a percentage, and greater incidence of rumenitis ( = 0.05) than Brangus bulls. In addition, Brangus bulls had greater ( < 0.01) DMI per meal and also presented lower ( < 0.01) DM and NDF rumination rates when compared with Nellore bulls. Significant interactions ( < 0.05) between biotype and feed additive were observed for SFA, unsaturated fatty acids (UFA), MUFA, and PUFA concentrations in adipose tissues. When Nellore bulls were fed PAP, fat had greater ( < 0.05) SFA and PUFA contents but less ( < 0.01) UFA and MUFA than Nellore bulls receiving MON. For Brangus bulls, MON led to greater ( < 0.05) SFA and PUFA and less ( < 0.05) UFA and MUFA than Brangus bulls fed PAP. Feeding a spray-dried PAP led to similar feedlot performance compared with that when feeding MON. Spray-dried PAP might provide a new technology alternative to ionophores.

  3. Effect of positive airway pressure therapy on seizure control in patients with epilepsy and obstructive sleep apnea.

    PubMed

    Pornsriniyom, Darakul; Kim, Hu won; Bena, James; Andrews, Noah D; Moul, Douglas; Foldvary-Schaefer, Nancy

    2014-08-01

    Previous studies suggest that treatment for obstructive sleep apnea (OSA) in patients with epilepsy can improve seizure control. We investigated the effect of positive airway pressure (PAP) therapy on seizures in adults with epilepsy referred to the Cleveland Clinic for polysomnography (PSG) from 1997 to 2010. Seizure outcome at baseline and 1 year later was compared in patients with no OSA (apnea-hypopnea index [AHI] <5), patients with PAP-treated OSA, and patients with untreated OSA. One hundred thirty-two subjects (age: 40.2±13 (18-76) years, 65.4% female) were included. Seventy-six (57.6%) subjects had OSA; of these, 43 (56.6%) were on PAP therapy, and 33 (43.4%) were not on PAP therapy (either PAP-intolerant or refused therapy). Of the group with PAP-treated OSA, 83.7% were adherent (use ≥4 h/night at least 5 nights/week). The percentage of subjects with ≥50% seizure reduction and the mean percentage of seizure reduction were significantly greater in the group with PAP-treated OSA (73.9%; 58.5%) than in subjects with untreated OSA (14.3%; 17.0%). There were significantly more subjects with successful outcomes (with ≥50% seizure reduction or seizure-free at both baseline and follow-up) in the group with PAP-treated OSA (83.7%) than in the groups with no OSA (53.6%) and untreated OSA (39.4%). After adjusting for age, gender, body mass index, AHI, and epilepsy duration, we found that the odds of successful outcomes in subjects in the group with PAP-treated OSA were 9.9 and 3.91 times those of the groups with untreated OSA and no OSA, respectively. The group with PAP-treated OSA had 32.3 times the odds of having a ≥50% seizure reduction compared with the group with untreated OSA and 6.13 times compared with the group with no OSA. Positive airway pressure therapy appears to produce beneficial effects on seizures in adult patients with epilepsy and OSA. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. Comparative Assessment of Conventional Papanicolaou and Modified Ultrafast Papanicolaou Stains in Fine Needle Aspiration Samples and Body Fluids.

    PubMed

    Arul, P; Eniya, S; Pushparaj, Magesh; Masilamani, Suresh; Kanmani, P; Lingasamy, C

    2018-01-01

    Conventional Papanicolaou (Pap) stain has undergone many modifications; of these, ultrafast Pap stain is the most popular as it shortens the turnaround time of reporting. Application of modified ultrafast Pap (MUFP) stain in the evaluation of fine needle aspiration (FNA) samples and body fluids are scanty. To evaluate the utility of MUFP stain in various FNA samples and body fluids and compare the findings with those of conventional Pap stain. In this cross-sectional study, two wet-fixed and two airdried smears from each sample [301 samples (255 FNA samples and 46 body fluids)] were prepared and stained by the conventional Pap and MUFP stains, respectively. Concordant and discordant rate was calculated. Quality index (QI) of MUFP stain was assessed by background, overall staining, cell morphology, and nuclear characteristics. MUFP-stained smears were also categorized into excellent, good, and fair. The concordance rate for MUFP stain was 100%. QI of MUFP stain for breast, thyroid, lymph node, soft tissue, salivary gland, and body fluids was 0.9, 0.93, 0.95, 1, 0.94, and 1, respectively. Excellent quality of stain was noted in 53.2% and good in 24.6% of the cases allowing easy diagnosis. In 22.2% of fair cases, diagnosis was possible with some difficulties. Our study concluded that MUFP stain could be considered as a rapid and reliable diagnostic tool and can be applied on a regular basis in FNA samples and body fluids to offer immediate diagnosis. However, caution should be taken while reporting certain MUFP-stained smears to avoid over/under diagnosis.

  5. Disparities in cervical cancer screening between Asian American and Non-Hispanic white women.

    PubMed

    Wang, Judy H; Sheppard, Vanessa B; Schwartz, Marc D; Liang, Wenchi; Mandelblatt, Jeanne S

    2008-08-01

    Asian American women have higher cervical cancer mortality rates than non-Hispanic White women, yet have lower Pap screening rates than their White counterparts. This study examined whether ethnic differences in the use of Pap screening were associated with differences in cultural views, controlling for demographic and access factors. Cross-sectional survey data from the Commonwealth 2001 Health Care Quality Survey were used. Non-Hispanic White (n = 2,146) and Asian American women (including Chinese, Vietnamese, Korean, Filipino, and Japanese; n = 259) were included in this study. Eastern cultural views were measured by beliefs in the role of self-care and luck. Access factors (having health insurance, regular providers, and communication with providers) and demographics of patients and providers were measured. The outcome was receipt of a Pap test in the past 2 years. Asian American women had a lower rate of obtaining a recent Pap test (70%) than non-Hispanic White women (81%; P = 0.001). More Asians believed in the role of luck and self-care and experienced access barriers than Whites (P < 0.0001). Women with less Eastern cultural views are more likely to be recently screened than women with more (odds ratio, 1.08; 95% confidence interval, 1.00-1.16; P < 0.05). All access factors and provider gender types predicted the outcome. Within the Asian subgroups, Vietnamese women had lower screening rates (55%) and greater Eastern cultural views than their Asian counterparts. More research is needed to understand cultural and other barriers to Pap screening in high-risk Asian women, and attention should be paid to within-group differences.

  6. Simultaneous detection of papaya ringspot virus, papaya leaf distortion mosaic virus, and papaya mosaic virus by multiplex real-time reverse transcription PCR.

    PubMed

    Huo, P; Shen, W T; Yan, P; Tuo, D C; Li, X Y; Zhou, P

    2015-12-01

    Both the single infection of papaya ringspot virus (PRSV), papaya leaf distortion mosaic virus (PLDMV) or papaya mosaic virus (PapMV) and double infection of PRSV and PLDMV or PapMV which cause indistinguishable symptoms, threaten the papaya industry in Hainan Island, China. In this study, a multiplex real-time reverse transcription PCR (RT-PCR) was developed to detect simultaneously the three viruses based on their distinctive melting temperatures (Tms): 81.0±0.8°C for PRSV, 84.7±0.6°C for PLDMV, and 88.7±0.4°C for PapMV. The multiplex real-time RT-PCR method was specific and sensitive in detecting the three viruses, with a detection limit of 1.0×10(1), 1.0×10(2), and 1.0×10(2) copies for PRSV, PLDMV, and PapMV, respectively. Indeed, the reaction was 100 times more sensitive than the multiplex RT-PCR for PRSV, and 10 times more sensitive than multiplex RT-PCR for PLDMV. Field application of the multiplex real-time RT-PCR demonstrated that some non-symptomatic samples were positive for PLDMV by multiplex real-time RT-PCR but negative by multiplex RT-PCR, whereas some samples were positive for both PRSV and PLDMV by multiplex real-time RT-PCR assay but only positive for PLDMV by multiplex RT-PCR. Therefore, this multiplex real-time RT-PCR assay provides a more rapid, sensitive and reliable method for simultaneous detection of PRSV, PLDMV, PapMV and their mixed infections in papaya.

  7. Preventive health pamphlets in the emergency department.

    PubMed

    Berger, P; Luskin, M; Krishel, S

    1998-01-01

    We conducted a prospective clinical trial to determine the effectiveness of an emergency department informational pamphlet in improving patients' compliance with recommendations that they receive Pap smears, mammograms, and a pneumococcal vaccination. Informational pamphlets were distributed to 1,000 consecutive patients who presented to a university-affiliated emergency department (ED). The pamphlet contained information stating the indications for obtaining routine Pap smears, mammograms, and a pneumococcal vaccination. Target individuals were women 18 years and older and men 65 years and older. Target patients were called approximately 2 months after their ED visits to obtain follow-up data. There were 464 target patients obtained from the 1,000 pamphlets distributed (409 female/55 male), and 68% (316) of the 464 were contacted by telephone for follow-up data. Significantly more women than men had read the pamphlet (62% vs. 8%). Of the women contacted (279), 31.9% (89) were not up to date (UTD) with Pap smears, and 11.2% (10) stated that they had scheduled an appointment for a Pap smear; 14.5% (11) of the women were not UTD with mammograms, and none had scheduled an appointment to receive care. Of the patients over age 65, 67% were not UTD with a pneumococcal vaccination, and no appointments were scheduled to obtain one. We conclude that a significant number of patients who present to this ED are in need of preventive health care. Emergency department informational pamphlets may have a role in improving Pap smear compliance. Women may be more likely then men to read informational pamphlets distributed in the ED.

  8. Impact of severe tricuspid regurgitation on accuracy of systolic pulmonary arterial pressure measured by Doppler echocardiography: Analysis in an unselected patient population.

    PubMed

    Fei, Beini; Fan, Ting; Zhao, Ling; Pei, Xiaoli; Shu, Xianhong; Fang, Xiaoyan; Cheng, Leilei

    2017-07-01

    Pulmonary arterial pressure is an important index in cardiovascular disorders, especially for pulmonary hypertension (PH). Doppler echocardiography (DE) is widely used as a noninvasive method to assess pulmonary arterial pressure. However, recent studies have found several hemodynamic factors that affect its accuracy in estimating systolic pulmonary arterial pressure (sPAP). But the effect of tricuspid regurgitation (TR) has not been investigated. Therefore, our study is aimed to determine whether the severity of TR will affect the accuracy of sPAP measured by DE in an unselected patient population. We retrospectively studied 177 patients who underwent DE and right heart catheterization (RHC) examinations. Patients were categorized into 3 groups according to the severity of TR (mild, moderate, and severe). The discrepancy in sPAP measured by DE and RHC was calculated and compared in each group. Determinants of discordant results between two methods were also evaluated. Age, gender, interval between DE and RHC, sequence of DE and RHC were similar among groups (all P>.05). Differences in sPAP, RAP, and tricuspid regurgitation pressure gradient (TR-PG) were similar in group 1 and 2 (all P>.05), while all significantly higher in group 3 (all P<.05). The difference in sPAP between DE and RHC was affected independently by severe TR and severe PH (both P<.05). Severe TR and severe PH affect the accuracy of sPAP measured by DE. Modification of echocardiographic sPAP measurements by taking into consideration of these factors may lead to reduced systemic errors. © 2017, Wiley Periodicals, Inc.

  9. Kinetic intermediates of unfolding of dimeric prostatic phosphatase.

    PubMed

    Kuciel, Radosława; Mazurkiewicz, Aleksandra; Dudzik, Paulina

    2007-01-01

    Kinetics of guanidine hydrochloride (GdnHCl)-induced unfolding of human prostatic acid phosphatase (hPAP), a homodimer of 50 kDa subunit molecular mass was investigated with enzyme activity measurements, capacity for binding an external hydrophobic probe, 1-anilinonaphtalene-8-sulfonate (ANS), accessibility of thiols to reaction with 5,5'-dithiobis(2-nitrobenzoic acid) (DTNB) and 2-(4'-maleimidylanilino)naphthalene-6-sulfonate (MIANS) and ability to bind Congo red dye. Kinetic analysis was performed to describe a possible mechanism of hPAP unfolding and dissociation that leads to generation of an inactive monomeric intermediate that resembles, in solution of 1.25 M GdnHCl pH 7.5, at 20 degrees C, in equilibrium, a molten globule state. The reaction of hPAP inactivation in 1.25 M GdnHCl followed first order kinetics with the reaction rate constant 0.0715 +/- 0.0024 min(-1) . The rate constants of similar range were found for the pseudo-first-order reactions of ANS and Congo red binding: 0.0366 +/- 0.0018 min(-1) and 0.0409 +/- 0.0052 min(-1), respectively. Free thiol groups, inaccessible in the native protein, were gradually becoming, with the progress of unfolding, exposed for the reactions with DTNB and MIANS, with the pseudo-first-order reaction rate constants 0.327 +/- 0.014 min(-1) and 0.216 +/- 0.010 min(-1), respectively. The data indicated that in the course of hPAP denaturation exposure of thiol groups to reagents took place faster than the enzyme inactivation and exposure of the protein hydrophobic surface. This suggested the existence of a catalytically active, partially unfolded, but probably dimeric kinetic intermediate in the process of hPAP unfolding. On the other hand, the protein inactivation was accompanied by exposure of a hydrophobic, ANS-binding surface, and with an increased capacity to bind Congo red. Together with previous studies these results suggest that the stability of the catalytically active conformation of the enzyme depends mainly on the dimeric structure of the native hPAP.

  10. Treatment of OSA with CPAP Is Associated with Improvement in PTSD Symptoms among Veterans

    PubMed Central

    Orr, Jeremy E.; Smales, Carolina; Alexander, Thomas H.; Stepnowsky, Carl; Pillar, Giora; Malhotra, Atul; Sarmiento, Kathleen F.

    2017-01-01

    Study Objectives: Posttraumatic stress disorder (PTSD) is common among veterans of the military, with sleep disturbance as a hallmark manifestation. A growing body of research has suggested a link between obstructive sleep apnea and PTSD, potentially due to obstructive sleep apnea (OSA) related sleep disruption, or via other mechanisms. We examined the hypothesis that treatment of OSA with positive airway pressure would reduce PTSD symptoms over 6 months. Methods: A prospective study of Veterans with confirmed PTSD and new diagnosis of OSA not yet using PAP therapy were recruited from a Veteran's Affairs sleep medicine clinic. All subjects were instructed to use PAP each night. Assessments were performed at 3 and 6 months. The primary outcome was a reduction in PTSD symptoms at 6 months. Results: Fifty-nine subjects were enrolled; 32 remained in the study at 6 months. A significant reduction in PTSD symptoms, measured by PCL-S score was observed over the course of the study (60.6 ± 2.7 versus 52.3 ± 3.2 points; p < 0.001). Improvement was also seen in measures of sleepiness, sleep quality, and daytime functioning, as well as depression and quality of life. Percentage of nights in which PAP was used, but not mean hours used per night, was predictive of improvement. Conclusions: Treatment of OSA with PAP therapy is associated with improvement in PTSD symptoms, although the mechanism is unclear. Nonetheless, PAP should be considered an important component of PTSD treatment for those with concurrent OSA. Improving PAP compliance is a challenge in this patient population warranting further investigation. Clinical Trial Registration: ClinicalTrials.gov, ID: NCT02019914. Commentary: A commentary on this article appears in this issue on page 5. Citation: Orr JE, Smales C, Alexander TH, Stepnowsky C, Pillar G, Malhotra A, Sarmiento KF. Treatment of OSA with CPAP is associated with improvement in PTSD symptoms among veterans. J Clin Sleep Med. 2017;13(1):57–63. PMID:27707436

  11. Cervical cancer screening in the National Breast and Cervical Cancer Early Detection Program (NBCCEDP) in four US-Affiliated Pacific Islands between 2007 and 2015.

    PubMed

    Senkomago, Virginia; Royalty, Janet; Miller, Jacqueline W; Buenconsejo-Lum, Lee E; Benard, Vicki B; Saraiya, Mona

    2017-10-01

    Cervical cancer incidence in the US-Affiliated Pacific Islands (USAPIs) is double that of the US mainland. American Samoa, Commonwealth of Northern Mariana Islands (CNMI), Guam and the Republic of Palau receive funding from the Centers for Disease Control (CDC) National Breast and Cervical Cancer Early Detection Program (NBCCEDP) to implement cervical cancer screening to low-income, uninsured or under insured women. The USAPI grantees report data on screening and follow-up activities to the CDC. We examined cervical cancer screening and follow-up data from the NBCCEDP programs in the four USAPIs from 2007 to 2015. We summarized screening done by Papanicolaou (Pap) and oncogenic human papillomavirus (HPV) tests, follow-up and diagnostic tests provided, and histology results observed. A total of 22,249 Pap tests were conducted in 14,206 women in the four USAPIs programs from 2007-2015. The overall percentages of abnormal Pap results (low-grade squamous intraepithelial lesions or worse) was 2.4% for first program screens and 1.8% for subsequent program screens. Histology results showed a high proportion of cervical intraepithelial neoplasia grade 2 or worse (57%) among women with precancers and cancers. Roughly one-third (32%) of Pap test results warranting follow-up had no data recorded on diagnostic tests or follow-up done. This is the first report of cervical cancer screening and outcomes of women served in the USAPI through the NBCCEDP with similar results for abnormal Pap tests, but higher proportion of precancers and cancers, when compared to national NBCCEDP data. The USAPI face significant challenges in implementing cervical cancer screening, particularly in providing and recording data on diagnostic tests and follow-up. The screening programs in the USAPI should further examine specific barriers to follow-up of women with abnormal Pap results and possible solutions to address them. Published by Elsevier Ltd.

  12. Cardiovascular risk in pulmonary alveolar proteinosis.

    PubMed

    Manali, Effrosyni D; Papadaki, Georgia; Konstantonis, Dimitrios; Tsangaris, Iraklis; Papaioannou, Andriana I; Kolilekas, Likurgos; Schams, Andrea; Kagouridis, Konstantinos; Karakatsani, Anna; Orfanos, Stylianos; Griese, Matthias; Papiris, Spyros A

    2016-02-01

    We hypothesized that cardiovascular events and/or indices of cardiac dysfunction may be increased in pulmonary alveolar proteinosis (PAP). Systemic and pulmonary arterial hypertension, arrhythmias, pulmonary embolism, stroke and ischemic heart attack were reported. Patients underwent serum anti-GM-CSF antibodies, disease severity score (DSS), Doppler transthoracic echocardiograph, glucose, thyroid hormones, lipids, troponin and pro-Brain natriuretic peptide (BNP) examination. Thirteen patients (8 female) were studied, median age of 47. Pro-BNP inversely related to DLCO% and TLC%; troponin directly related to DSS, age, P(A-a)O2, left atrium-, left ventricle-end-diastole diameter and BMI. On multiple regression analysis DSS was the only parameter significantly and strongly related with troponin (R(2) = 0.776, p = 0.007). No cardiovascular event was reported during follow-up. In PAP cardiovascular risk indices relate to lung disease severity. Therefore, PAP patients could be at increased risk for cardiovascular events. Quantitation of its magnitude and potential links to lungs' physiologic derangement will be addressed in future studies.

  13. Acute Hemodynamic Effects of Riociguat in Patients With Pulmonary Hypertension Associated With Diastolic Heart Failure (DILATE-1)

    PubMed Central

    Pretsch, Ingrid; Steringer-Mascherbauer, Regina; Jansa, Pavel; Rosenkranz, Stephan; Tufaro, Caroline; Bojic, Andja; Lam, Carolyn S. P.; Frey, Reiner; Ochan Kilama, Michael; Unger, Sigrun; Roessig, Lothar; Lang, Irene M.

    2014-01-01

    BACKGROUND: Deficient nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate signaling results from endothelial dysfunction and may underlie impaired cardiac relaxation in patients with heart failure with preserved left ventricular ejection fraction (HFpEF) and pulmonary hypertension (PH). The acute hemodynamic effects of riociguat, a novel soluble guanylate cyclase stimulator, were characterized in patients with PH and HFpEF. METHODS: Clinically stable patients receiving standard HF therapy with a left ventricular ejection fraction > 50%, mean pulmonary artery pressure (mPAP) ≥ 25 mm Hg, and pulmonary arterial wedge pressure (PAWP) > 15 mm Hg at rest were randomized to single oral doses of placebo or riociguat (0.5, 1, or 2 mg). The primary efficacy variable was the peak decrease in mPAP from baseline up to 6 h. Secondary outcomes included hemodynamic and echocardiographic parameters, safety, and pharmacokinetics. RESULTS: There was no significant change in peak decrease in mPAP with riociguat 2 mg (n = 10) vs placebo (n = 11, P = .6). However, riociguat 2 mg significantly increased stroke volume (+9 mL [95% CI, 0.4-17]; P = .04) and decreased systolic BP (−12 mm Hg [95% CI, −22 to −1]; P = .03) and right ventricular end-diastolic area (−5.6 cm2 [95% CI, −11 to −0.3]; P = .04), without significantly changing heart rate, PAWP, transpulmonary pressure gradient, or pulmonary vascular resistance. Riociguat was well tolerated. CONCLUSIONS: In patients with HFpEF and PH, riociguat was well tolerated, had no significant effect on mPAP, and improved exploratory hemodynamic and echocardiographic parameters. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT01172756; URL: www.clinicaltrials.gov PMID:24991733

  14. Redundant roles of the phosphatidate phosphatase family in triacylglycerol synthesis in human adipocytes.

    PubMed

    Temprano, Ana; Sembongi, Hiroshi; Han, Gil-Soo; Sebastián, David; Capellades, Jordi; Moreno, Cristóbal; Guardiola, Juan; Wabitsch, Martin; Richart, Cristóbal; Yanes, Oscar; Zorzano, Antonio; Carman, George M; Siniossoglou, Symeon; Miranda, Merce

    2016-09-01

    In mammals, the evolutionary conserved family of Mg(2+)-dependent phosphatidate phosphatases (PAP1), involved in phospholipid and triacylglycerol synthesis, consists of lipin-1, lipin-2 and lipin-3. While mutations in the murine Lpin1 gene cause lipodystrophy and its knockdown in mouse 3T3-L1 cells impairs adipogenesis, deleterious mutations of human LPIN1 do not affect adipose tissue distribution. However, reduced LPIN1 and PAP1 activity has been described in participants with type 2 diabetes. We aimed to characterise the roles of all lipin family members in human adipose tissue and adipogenesis. The expression of the lipin family was analysed in adipose tissue in a cross-sectional study. Moreover, the effects of lipin small interfering RNA (siRNA)-mediated depletion on in vitro human adipogenesis were assessed. Adipose tissue gene expression of the lipin family is altered in type 2 diabetes. Depletion of every lipin family member in a human Simpson-Golabi-Behmel syndrome (SGBS) pre-adipocyte cell line, alters expression levels of adipogenic transcription factors and lipid biosynthesis genes in early stages of differentiation. Lipin-1 knockdown alone causes a 95% depletion of PAP1 activity. Despite the reduced PAP1 activity and alterations in early adipogenesis, lipin-silenced cells differentiate and accumulate neutral lipids. Even combinatorial knockdown of lipins shows mild effects on triacylglycerol accumulation in mature adipocytes. Overall, our data support the hypothesis of alternative pathways for triacylglycerol synthesis in human adipocytes under conditions of repressed lipin expression. We propose that induction of alternative lipid phosphate phosphatases, along with the inhibition of lipid hydrolysis, contributes to the maintenance of triacylglycerol content to near normal levels.

  15. Ultrasound-guided fine-needle aspiration of a posterior neck dedifferentiated liposarcoma with MDM2 fluorescence in situ hybridization performed on a Pap-stained smear.

    PubMed

    Zreik, Riyam; Soyalp, Krystal; Ruiz, Steve; Ward, Russell; Dobin, Sheila; Chen, Xiangbai; Liu, Lina; Rao, Arundhati

    2015-04-01

    Head and neck liposarcomas, while rare, tend to be subcutaneous and well-differentiated. Dedifferentiated liposarcomas of the head and neck are exceedingly rare in the literature. We present a case of a dedifferentiated liposarcoma arising in the soft tissue of the posterior neck of an 86-year-old man and diagnosed by fine-needle aspiration. Aspirate smears showed a dual population of atypical lipomatous and spindled cells. MDM2 (murine double minute 2) amplification was demonstrated on a Pap-stained smear using fluorescence in situ hybridization (FISH). To the best of our knowledge, this is the first report of MDM2 FISH amplification in a liposarcoma performed on an aspirate smear. © 2014 Wiley Periodicals, Inc.

  16. Bacterial vaginosis, aerobic vaginitis, vaginal inflammation and major Pap smear abnormalities.

    PubMed

    Vieira-Baptista, P; Lima-Silva, J; Pinto, C; Saldanha, C; Beires, J; Martinez-de-Oliveira, J; Donders, G

    2016-04-01

    The purpose of this investigation was to evaluate the impact of the vaginal milieu on the presence of abnormal Pap smears and a positive human papilloma virus (HPV) test. A cross-sectional study was conducted between June 2014 and May 2015, evaluating the vaginal discharge by fresh wet mount microscopy and comparing these data with Pap smear findings. Wet mount slides were scored for bacterial vaginosis (BV), aerobic vaginitis (AV), presence of Candida and Trichomonas vaginalis. Cytologic evaluation was done on all Pap smears according to the Bethesda criteria. The cobas© HPV Test (Roche) was performed for HPV detection. A total of 622 cases were evaluated. The mean age of the patients was 41.6 ± 10.65 years (range 21-75). Eighty-three women (13.3 %) had a cytology result worse than low-grade squamous intraepithelial lesion (LSIL). When comparing this group with the one with normal or minor [atypical squamous cells of undetermined significance (ASC-US) or LSIL] Pap smear abnormalities, there were no differences in the presence of Candida (32.5 % vs. 33.2 %, p = 1.0), absence of lactobacilli (38.6 % vs. 32.5 %, p = 0.32) or BV (20.5 % vs. 13.2 %, p = 0.09). On the other hand, moderate or severe inflammation (msI) (41.0 % vs. 28.8 %, p = 0,04), moderate or severe AV (msAV) (16.9 % vs. 7.2 %, p = 0.009) and msAV/BV (37.3 % vs. 20.0 %, p = 0.001) were more common in women with such major cervical abnormalities. No significant association was found between deviations of the vaginal milieu and high-risk HPV infection. The presence of msI or msAV, but not BV, is independently associated with an increased risk of major cervical cytological abnormalities, but not with HPV infection.

  17. Racial/Ethnic Differences Affecting Adherence to Cancer Screening Guidelines Among Women.

    PubMed

    Hirth, Jacqueline M; Laz, Tabassum Haque; Rahman, Mahbubur; Berenson, Abbey B

    2016-04-01

    Race/ethnicity has been shown to modify the effects between obesity and cancer screening among women. The purpose of this article is to update the literature with recent data to examine how the association between different characteristics, including body mass index (BMI), and cancer screening compliance varies by race/ethnicity in a national sample of women. Three cycles of the Health Information National Trends Survey (HINTS) were combined for this cross-sectional study. Weighted descriptive statistics were evaluated using chi-square tests. Multivariable logistic regression evaluated associations between women with underweight or normal (<25), overweight (25-29.9), and obese (>30) BMIs and cancer screening concordant with guidelines (Papanicolaou [Pap] testing ≤3 years, ages 21+ years; mammography ≤2 years, ages 40+ years) in analyses stratified by race/ethnicity. We also assessed variance between racial/ethnic groups in how age, income, and insurance status were associated with cancer screening compliance. This study included 4992 women who were evaluated for Pap testing and 3773 for mammography. In analyses stratified by race/ethnicity, whites with a higher household income were more likely to report having a Pap test (adjusted prevalence ratio [aPR] 2.16, 95% confidence interval [95% CI] 1.38-3.40) and a mammogram (aPR 1.63, 95% CI 1.04-2.55) compared to lower income white women. Black women with BMIs between 25 and 30 were less likely to receive a Pap test (aPR 0.38, 95% CI 0.19-0.76) than black women with BMIs <25, while no association was observed among the other groups. Insurance was associated with increased likelihood of Pap testing among white and black women. Insurance coverage was positively associated with mammography only among white and Hispanic women. We found variations in adherence to cancer screening guidelines by age, insurance coverage, and income between racial/ethnic groups. Little evidence was observed for variations in screening by BMI.

  18. Lipin 2 binds phosphatidic acid by the electrostatic hydrogen bond switch mechanism independent of phosphorylation.

    PubMed

    Eaton, James M; Takkellapati, Sankeerth; Lawrence, Robert T; McQueeney, Kelley E; Boroda, Salome; Mullins, Garrett R; Sherwood, Samantha G; Finck, Brian N; Villén, Judit; Harris, Thurl E

    2014-06-27

    Lipin 2 is a phosphatidic acid phosphatase (PAP) responsible for the penultimate step of triglyceride synthesis and dephosphorylation of phosphatidic acid (PA) to generate diacylglycerol. The lipin family of PA phosphatases is composed of lipins 1-3, which are members of the conserved haloacid dehalogenase superfamily. Although genetic alteration of LPIN2 in humans is known to cause Majeed syndrome, little is known about the biochemical regulation of its PAP activity. Here, in an attempt to gain a better general understanding of the biochemical nature of lipin 2, we have performed kinetic and phosphorylation analyses. We provide evidence that lipin 2, like lipin 1, binds PA via the electrostatic hydrogen bond switch mechanism but has a lower rate of catalysis. Like lipin 1, lipin 2 is highly phosphorylated, and we identified 15 phosphosites. However, unlike lipin 1, the phosphorylation of lipin 2 is not induced by insulin signaling nor is it sensitive to inhibition of the mammalian target of rapamycin. Importantly, phosphorylation of lipin 2 does not negatively regulate either membrane binding or PAP activity. This suggests that lipin 2 functions as a constitutively active PA phosphatase in stark contrast to the high degree of phosphorylation-mediated regulation of lipin 1. This knowledge of lipin 2 regulation is important for a deeper understanding of how the lipin family functions with respect to lipid synthesis and, more generally, as an example of how the membrane environment around PA can influence its effector proteins. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Effectiveness of rapid prescreening and 10% rescreening in liquid-based Papanicolaou testing.

    PubMed

    Currens, Heather S; Nejkauf, Katharine; Wagner, Lynn; Raab, Stephen S

    2012-01-01

    Although rapid prescreening (RPS) has been shown to be an effective quality control procedure for detecting false-negative conventional Papanicolaou (Pap) tests, RPS has not been widely implemented in the United States. In our laboratory, cytotechnologists performed RPS in 3,567 liquid-based Pap tests: 1,911 SurePath (BD Diagnostics-TriPath, Burlington, NC) preparations that were manually screened and 1,656 ThinPrep Pap tests (Hologic, Bedford, MA) that were imaged using the ThinPrep Imaging System (Hologic). We compared the sensitivity of RPS, 10% rescreening (R-10%), and routine screening (RS). In contrast with previously published findings, we found that RS + RPS did not improve screening sensitivity compared with RS + R-10%. These results support the following hypotheses: (1) Higher baseline RS sensitivity as a result of Pap test diagnoses standardization implemented for quality improvement purposes decreases the performance impact of RPS. (2) R-10% and RPS quality assurance methods detect diagnostic failures caused by different types of cognitive errors.

  20. Peptidomic Approach to Developing ELISAs for the Determination of Bovine and Porcine Processed Animal Proteins in Feed for Farmed Animals.

    PubMed

    Huet, Anne-Catherine; Charlier, Caroline; Deckers, Elise; Marbaix, Hélène; Raes, Martine; Mauro, Sergio; Delahaut, Philippe; Gillard, Nathalie

    2016-11-30

    The European Commission (EC) wants to reintroduce nonruminant processed animal proteins (PAPs) safely into the feed chain. This would involve replacing the current ban in feed with a species-to-species ban which, in the case of nonruminants, would only prohibit feeding them with proteins from the same species. To enforce such a provision, there is an urgent need for species-specific methods for detecting PAPs from several species in animal feed and in PAPs from other species. Currently, optical microscopy and the polymerase chain reaction are the officially accepted methods, but they have limitations, and alternative methods are needed. We have developed immunoassays using antibodies raised against targets which are not influenced by high temperature and pressure. These targets were identified in a previous study based on an experimental approach. One optimized competitive ELISA detects bovine PAPs at 2% in plant-derived feed. The detection capability demonstrated on blind samples shows a good correlation with mass spectrometry results.

  1. Honouring Stories: Mi'kmaq Women's Experiences with Pap Screening in Eastern Canada.

    PubMed

    MacDonald, Catherine; Martin-Misener, Ruth; Steenbeek, Audrey; Browne, Annette

    2015-03-01

    Mi'kmaq women are reported to have lower rates of Papanicolaou (Pap) screening and higher rates of cervical cancer than non-Aboriginal women. This qualitative participatory study used postcolonial feminist perspectives and Indigenous principles to explore Mi'kmaq women's experiences with Pap screening within the contexts that shaped their experiences. Community facilitators assisted with the research process. Talking circles and individual in-depth interviews were conducted with 16 Mi'kmaq women. Also, health-care providers were interviewed in 2 Mi'kmaq communities. The findings indicate that historical and social contexts are shaping Mi'kmaq women's screening experiences and that these experiences are diverse, as are their understandings about screening. Some women were accessing regular screening despite challenging personal circumstances. The results highlight the need for nurses and other health-care providers to understand the uniqueness of each woman's experiences with Pap screening. Improvements in screening rates depend on multifaceted nursing approaches developed in partnership with Mi'kmaq women. Copyright© by Ingram School of Nursing, McGill University.

  2. ISP Descriptions of Four Military Computer Architectures

    DTIC Science & Technology

    1978-04-01

    9 1? LOAD "AGNITLII II Ill FO El 2 *> lorto0c VS * Lga ?i LOAD B AmU I 22 5LXt.At*Cf S Set 1 23 STORE 1 $A[ I 24 STORE A 5xg9 I 2S STORE a r-W I WE...HOOP: 79 3 0051E WLEVINt A Os’tx I 70 i opE!’ I 70 6 DPEI: 70 5 GPO !’ 70’ 7 HOP. I ?21 120 4 LOGCALSU He: 1 72 2 SLIM HANi I 72 2 OIMPENtCI I44OR2 I7...34. 15111 ’IflCfNI.CIJI no0 ,3 F4 ’l1’ 11. W hVI tWtJ-W J p O5-2 VS PAP I I 1 3.), \\F) PrI30("I I. \\c PAP141 dtitt-r(17󈧤>i \\D P0PISI -d.11wC27,32): \\U

  3. Combination of cephalosporins with vancomycin or teicoplanin enhances antibacterial effect of glycopeptides against heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) and VISA.

    PubMed

    Lai, Chih-Cheng; Chen, Chi-Chung; Chuang, Yin-Ching; Tang, Hung-Jen

    2017-01-31

    Eight heterogeneous vancomycin-intermediate S. aureus (h-VISA) and seven VISA clinical isolates confirmed by the population analysis profile/area under the curve ratio (PAP/AUC) were collected. We further performed the PAP/AUC, time-killing methods and MIC tests using vancomycin/teicoplanin alone or combination with susceptible breakpoint concentrations of cefazolin, cefmetazole, cefotaxime, and cefepime for these isolates. The PAP/AUC MIC curve shifted left after addition of cephalosporins with vancomycin or teicoplanin for both h-VISA and VISA isolates. With the combination of different cephalosporins with vancomycin or teicoplanin, the AUC/Mu3 AUC ratio decreased to <0.9 for the standard Mu3 isolate which are compatible with the definition of vancomycin susceptible S. aureus. These decreases ranged between 1.81-2.02 and 2.37-2.85-fold for h-VISA treated with cephalosporins and vancomycin or teicoplanin, and 2.05-4.59, and 2.93-4,89-fold for VISA treated with cephalosporins with vancomycin or teicoplanin. As measured by time-killing assays, the combinations of different cephalosporins with vancomycin concentrations at 1/2 and 1/4 MIC, exhibited a bactericidal and bacteriostatic effect in VISA. The mean fold of MIC decline for vancomycin base combinations ranged from 1.81-3.83 and 2.71-9.33 for h-VISA and VISA, respectively. Overall, this study demonstrated the enhanced antibacterial activity of vancomycin/teicoplanin after adding cephalosporins against clinical h-VISA/VISA isolates.

  4. A specific PFT and sub-canopy structure for simulating oil palm in the Community Land Model

    NASA Astrophysics Data System (ADS)

    Fan, Y.; Knohl, A.; Roupsard, O.; Bernoux, M.; LE Maire, G.; Panferov, O.; Kotowska, M.; Meijide, A.

    2015-12-01

    Towards an effort to quantify the effects of rainforests to oil palm conversion on land-atmosphere carbon, water and energy fluxes, a specific plant functional type (PFT) and sub-canopy structure are developed for simulating oil palm within the Community Land Model (CLM4.5). Current global land surface models only simulate annual crops beside natural vegetation. In this study, a multilayer oil palm subroutine is developed in CLM4.5 for simulating oil palm's phenology and carbon and nitrogen allocation. The oil palm has monopodial morphology and sequential phenology of around 40 stacked phytomers, each carrying a large leaf and a fruit bunch, forming a natural multilayer canopy. A sub-canopy phenological and physiological parameterization is thus introduced, so that multiple phytomer components develop simultaneously but according to their different phenological steps (growth, yield and senescence) at different canopy layers. This specific multilayer structure was proved useful for simulating canopy development in terms of leaf area index (LAI) and fruit yield in terms of carbon and nitrogen outputs in Jambi, Sumatra (Fan et al. 2015). The study supports that species-specific traits, such as palm's monopodial morphology and sequential phenology, are necessary representations in terrestrial biosphere models in order to accurately simulate vegetation dynamics and feedbacks to climate. Further, oil palm's multilayer structure allows adding all canopy-level calculations of radiation, photosynthesis, stomatal conductance and respiration, beside phenology, also to the sub-canopy level, so as to eliminate scale mismatch problem among different processes. A series of adaptations are made to the CLM model. Initial results show that the adapted multilayer radiative transfer scheme and the explicit represention of oil palm's canopy structure improve on simulating photosynthesis-light response curve. The explicit photosynthesis and dynamic leaf nitrogen calculations per canopy layer also enhance simulated CO2 flux when compared to eddy covariance flux data. More investigations on energy and water fluxes and nitrogen balance are being conducted. These new schemes would hopefully promote the understanding of climatic effects of the tropical land use transformation system.

  5. HPV DNA testing with cytology triage in cervical cancer screening: Influence of revealing HPV infection status.

    PubMed

    Richardson, Lyndsay Ann; El-Zein, Mariam; Ramanakumar, Agnihotram V; Ratnam, Samuel; Sangwa-Lugoma, Ghislain; Longatto-Filho, Adhemar; Cardoso, Marly Augusto; Coutlée, Francois; Franco, Eduardo L

    2015-12-01

    Knowledge of cervical human papillomavirus (HPV) status might influence a cytotechnician's assessment of cellular abnormalities. The authors compared original cytotechnicians' Papanicolaou (Pap) readings for which HPV status was concealed with Pap rereads for which HPV status was revealed separately for 3 screening populations. Previously collected cervical Pap smears and clinical data were obtained from the Canadian Cervical Cancer Screening Trial (study A), the Democratic Republic of Congo Community-Based Screening Study (study B), and the Brazilian Investigation into Nutrition and Cervical Cancer Prevention (study C). Smears were reread with knowledge of HPV status for all HPV-positive women as well as a sample of HPV-negative women. Diagnostic performance of Pap cytology was compared between original readings and rereads. A total of 1767 Pap tests were reread. Among 915 rereads for HPV-positive women, the contrast between "revealed" and "concealed" Pap readings demonstrated revisions from negative to positive results for 109 women (cutoff was atypical squamous cells of undetermined significance or worse) and 124 women (cutoff was low-grade squamous intraepithelial lesions [LSIL] or worse). For a disease threshold of cervical intraepithelial neoplasia of grade 2 or worse, specificity significantly declined at the atypical squamous cells of undetermined significance cutoff for studies A (86.6% to 75.3%) and C (42.5% to 15.5%), and at the LSIL cutoff for study C (61.9% to 37.6%). Sensitivity remained nearly unchanged between readings, except in study C, in which reread performance was superior (91.3% vs 71.9% for the LSIL cutoff). A reduction in the diagnostic accuracy of Pap cytology was observed when revealing patients' cervical HPV status, possibly due to a heightened awareness of potential abnormalities, which led to more false-positive results. © 2015 American Cancer Society.

  6. Bovine brain pyroglutamyl aminopeptidase (type-1): purification and characterisation of a neuropeptide-inactivating peptidase.

    PubMed

    Cummins, P M; O'Connor, B

    1996-08-01

    Pyroglutamyl aminopeptidase type-1 (PAP-I) is reported to be a soluble, broad specificity aminopeptidase, capable of removing the pyroglutamic acid (pGlu) residue from the amino terminus of pGlu-peptides (e.g. TRH, LHRH, neurotensin and bombesin). The central aim of this study was to undertake, for the first time, the complete purification and characterisation of a PAP activity observed within the cytosolic fraction of bovine whole brain and to compare the properties of the enzyme with previous findings. A series of chromatographic steps (DEAE-Sepharose, Sephacryl S-200 and Activated Thiol Sepharose 4B) generated a soluble PAP activity purified to near homogeneity with a total active yield of 6.6% The enzyme displayed a native molecular mass of approximately 23,700 Da, which compares well with that value obtained under denaturing conditions via SDS-PAGE (24,000 Da), suggesting that the enzyme exists as a monomer. The expression of PAP activity displayed an absolute requirement for the presence of a disulphide bond-reducing agent such as DTT, whilst optimum activity was observed at pH 8.5. strong inhibition of PAP activity was observed with a number of different agents, including transition metal ions, sulphydryl-blocking agents and 2-pyrrolidone (a pGlu analog). A broad pyroglutamyl substrate specificity, which excludes substrates commencing with the pGlu-Pro bond, was also demonstrated for the bovine brain enzyme. Based on a comparison of these findings with those reported for PAP-I in other mammalian tissues, the soluble PAP activity observed in bovine whole brain can tentatively be classified as a pyroglutamyl aminopeptidase type-1 (EC 3.4.19.3).

  7. Provider management of equivocal cervical cancer screening results among underserved women, 2009–2011: follow-up of atypical squamous cells of undetermined significance

    PubMed Central

    Watson, Meg; Benard, Vicki; Lin, Lavinia; Rockwell, Tanner; Royalty, Janet

    2015-01-01

    Purpose Reflex human papillomavirus (HPV) testing is the preferred triage option for most women diagnosed with atypical squamous cells of undetermined significance (ASC-US). This study was conducted to describe follow-up results of women with ASC-US Pap test results in the National Breast and Cervical Cancer Early Detection Program (NBCCEDP), focusing on HPV test use. Methods We examined the follow-up of 45,049 women in the NBCCEDP with ASC-US Pap tests during 2009–2011. Data on demographic characteristics, diagnostic procedures, and clinical outcomes were analyzed. Results NBCCEDP providers diagnosed 45,049 women (4.5 % of all Pap tests) with an ASC-US result. Of those, 28,271 (62.8 %) were followed with an HPV test, 3,883 (8.6 %) with a repeat Pap test, 6,592 (14.6 %) with colposcopy, and 6,303 were lost to follow-up (14.0 %). Women aged 40 and older were followed more often with an HPV test. White, black, and Asian/Pacific Islander women were followed more often with an HPV test after an ASC-US Pap compared to Hispanic and American Indian/Alaska Native (AI/AN) women. Among women with a positive HPV test on follow-up, almost 90 % continued with colposcopy as recommended. AI/AN women had the highest rates of HPV positivity (55.2 %) and of no follow-up (25.0 %). Conclusion This is the first analysis describing follow-up of ASC-US Pap test results in the NBCCEDP, providing a window into current management of ASC-US results. Findings raise concerns about persistent disparities among AI/AN women. During 2009–2011, nearly two-thirds of women with an ASC-US Pap test result were followed with an HPV reflex test. PMID:25794897

  8. Prevalence and predicting factors for anxiety in thai women with abnormal cervical cytology undergoing colposcopy.

    PubMed

    Jerachotechueantaveechai, Tanut; Charoenkwan, Kittipat; Wongpakaran, Nahathai

    2015-01-01

    To compare prevalence of anxiety in women with abnormal cervical cytology (Pap) undergoing colposcopy to that of women attending the outpatient clinic for check-up and to examine predicting factors. In this cross-sectional analytical study, 100 women with abnormal cervical cytology (abnormal Pap group) and 100 women who attended our outpatient clinic for check-up (control group) were recruited from June 2013 to January 2014. The Hospital Anxiety and Depression Scale (HADS) was employed to determine anxiety in the participants with the score of ≥ 11 suggestive of clinically significant anxiety. The prevalence of anxiety and the mean HADS scores for anxiety were compared between the groups. For those with abnormal Pap, association between clinical factors and anxiety was assessed. A p-value of < 0.05 was considered significant. Median age was different between the groups, 44.0 years in the abnormal Pap group and 50.0 years in the control group (p=0.01). The proportion of participants who had more than one sexual partner was higher in the abnormal Pap group, 39.2% vs. 24.7% (p=0.03) and the prevalence of anxiety was significantly higher 14/100 (14.0%) vs. 3/100 (3.0%) (p < 0.01). The prevalence of depression was comparable between the groups. The mean HADS scores for anxiety and depression subscales were significantly higher in the abnormal Pap group, 6.6 vs. 4.8 (P < 0.01) and 3.9 vs. 3.1 (p=0.05), respectively. For the abnormal Pap group, no definite association between clinical factors and anxiety was demonstrated. The prevalence of anxiety in women with abnormal Pap awaiting colposcopy was significantly higher than that of normal controls. Special attention including thorough counselling, with use of information leaflets and psychological support, should be directed to these women.

  9. Percutaneous device closure of patent ductus arteriosus with pulmonary artery hypertension: long-term results.

    PubMed

    Vijayalakshmi, Ishwarappa Balekundri; Setty, Natraj; Narasimhan, Chitra; Singla, Vivek; Manjunath, Cholenahalli Nanjappa

    2014-12-01

    Device closure of patent ductus arteriosus (PDA) is treatment of choice. But device closure in presence of pulmonary artery hypertension (PAH) remains a challenge. Data on patient selection, technical considerations, and complications are limited. To know the challenges and efficacy of device closure of PDA with PAH. Out of 1,325 cases of device closure of PDA, 246 (18.6%) with PAH formed the study material. To test the feasibility, chosen device is used to occlude PDA for ten minutes without oxygen inhalation. The device is released only if PAH reduced. PAH decreased in all except in 1 patient after closure with muscular ventricular septal occluder (MVSDO), pulmonary artery pressure (PAP) transiently increased (became supra-systemic), without significant reduction in aortic pressure. Device embolized in 8 patients (3.3%). Percutaneous retrieval was done in 4 (by snare in 2 and by fixing the cable to device in 2) and replaced with bigger devices. The surgical removal of the embolized MVSDO and ligation was done in 4 cases. All patients were on oral sildenafil and bosentan until PAP regressed to normal. Follow up was from 6 months to 9 years. No residual shunt in any patient on follow-up. The PAP regressed to normal in all except 5 cases (2.03%) of Down's syndrome with systemic PAP. Device closure of PDA with PAH is feasible, safe in all age groups. Temporary PDA occlusion with device is effective and time saving for evaluating pulmonary vascular reactivity. Device embolization in aorta is higher with severe PAH. Novel method of retrieval is effective. © 2014, Wiley Periodicals, Inc.

  10. Pap test

    MedlinePlus

    ... Pap; Low-grade Pap; High-grade Pap; Carcinoma in situ - Pap; CIS - Pap; ASCUS - Pap; Atypical glandular cells - ... to cervical cancer is greater with HSIL. CARCINOMA IN SITU (CIS): This result most often means the abnormal ...

  11. Physical activity on prescription (PAP): self-reported physical activity and quality of life in a Swedish primary care population, 2-year follow-up.

    PubMed

    Rödjer, Lars; H Jonsdottir, Ingibjörg; Börjesson, Mats

    2016-12-01

    To study the self-reported level of physical activity (PA) and quality of life (QOL) in patients receiving physical activity on prescription (PAP) for up to 24 months. Observational study conducted in a regular healthcare setting. A primary care population in Sweden receiving physical activity on prescription as part of regular care was studied alongside a reference group. The group comprised 146 patients receiving PAP at two different primary care locations (n = 96 and 50, respectively). The reference group comprised 58 patients recruited from two different primary care centres in the same region. We used two self-report questionnaires - the four-level Saltin-Grimby Physical Activity Level Scale (SGPALS) to assess physical activity, and SF-36 to assess QOL. A significant increase in the PA level was found at six and 12 months following PAP, with an ongoing non-significant trend at 24 months (p = .09). A clear improvement in QOL was seen during the period. At 24 months, significant and clinically relevant improvements in QOL persisted in four out of eight sub-scale scores (Physical Role Limitation, Bodily Pain, General Health,Vitality) and in one out of two summary scores (Physical Component Summary). Patients receiving PAP showed an increased level of self-reported PA at six and 12 months and improved QOL for up to 24 months in several domains. The Swedish PAP method seems to be a feasible method for bringing about changes in physical activity in different patient populations in regular primary healthcare. While increased physical activity (PA) is shown to improve health, the implementation of methods designed to increase activity is still being developed. Key points The present study confirms that the Swedish physical activity on prescription (PAP) method increases the self-reported level of PA in the primary care setting at six and 12 months. Furthermore, this study shows that PAP recipients report a clinically relevant long-term improvement in quality of life, persisting for two years post-prescription, thus extending earlier findings. These findings have clinical implications for the implementation of PAP in healthcare.

  12. Evaluation of a low-cost liquid-based Pap test in rural El Salvador: a split-sample study.

    PubMed

    Guo, Jin; Cremer, Miriam; Maza, Mauricio; Alfaro, Karla; Felix, Juan C

    2014-04-01

    We sought to test the diagnostic efficacy of a low-cost, liquid-based cervical cytology that could be implemented in low-resource settings. A prospective, split-sample Pap study was performed in 595 women attending a cervical cancer screening clinic in rural El Salvador. Collected cervical samples were used to make a conventional Pap (cell sample directly to glass slide), whereas residual material was used to make the liquid-based sample using the ClearPrep method. Selected samples were tested from the residual sample of the liquid-based collection for the presence of high-risk Human papillomaviruses. Of 595 patients, 570 were interpreted with the same diagnosis between the 2 methods (95.8% agreement). There were comparable numbers of unsatisfactory cases; however, ClearPrep significantly increased detection of low-grade squamous intraepithelial lesions and decreased the diagnoses of atypical squamous cells of undetermined significance. ClearPrep identified an equivalent number of high-grade squamous intraepithelial lesion cases as the conventional Pap. High-risk human papillomavirus was identified in all cases of high-grade squamous intraepithelial lesion, adenocarcinoma in situ, and cancer as well as in 78% of low-grade squamous intraepithelial lesions out of the residual fluid of the ClearPrep vials. The low-cost ClearPrep Pap test demonstrated equivalent detection of squamous intraepithelial lesions when compared with the conventional Pap smear and demonstrated the potential for ancillary molecular testing. The test seems a viable option for implementation in low-resource settings.

  13. Pulmonary blood volume (PRV) in rats with chronic mountain sickness

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ou, L.C.; Sardella, G.L.; Hill, N.S.

    1986-03-05

    Upon chronic exposure to severe hypoxia, Hilltop (H) strain of Sprague-Dawley rats develops excessive polycythemia, severe hypervolemia and marked elevation in pulmonary arterial pressure (PAP), whereas Madison (M) strain develops only moderate responses. Hypervolemia is expected to increase the PBV which might contribute to the development of severe pulmonary hypertension. Two groups of 6 animals each of the H and M strains were exposed to sea level (SL) and a simulated altitude of 18,000 ft for 14 days. At the end of exposure each animal was measured for RBC volume (RBCV), total blood volume (TBV), PBV and PAP under normoxiamore » for control and under hypoxia (10% O/sub 2/) for the hypoxic groups. RBCV was determined by /sup 51/Cr-RBC dilution and PBV was trapped by tightening an implanted loose ligature around the ascending aorta and PA. There were not strain differences in all parameters studied at SL. RBCV, TBV and PAP increased with hypoxia in both strains but significantly more so in H than M. PBV per g lung WT decreased in both strains despite elevated TBV and PAP, but more so in M than H. There were good correlations between the PBV and TBV, and between PAP and PBV in the hypoxic H and M rats. The data suggest that chronic hypoxia reduced the distensibility and perhaps the vascular capacity of the lungs such that small relative increase in PBV could significantly contribute to the rise in PAP.« less

  14. Applying the Transtheoretical Model to evaluate the effect of a call-recall program in enhancing Pap smear practice: a cluster randomized trial.

    PubMed

    Abdullah, Fauziah; Su, Tin Tin

    2013-01-01

    The objective of this study was to evaluate the effect of a call-recall approach in enhancing Pap smear practice by changes of motivation stage among non-compliant women. A cluster randomized controlled trial with parallel and un-blinded design was conducted between January and November 2010 in 40 public secondary schools in Malaysia among 403 female teachers who never or infrequently attended for a Pap test. A cluster randomization was applied in assigning schools to both groups. An intervention group received an invitation and reminder (call-recall program) for a Pap test (20 schools with 201 participants), while the control group received usual care from the existing cervical screening program (20 schools with 202 participants). Multivariate logistic regression was performed to determine the effect of the intervention program on the action stage (Pap smear uptake) at 24 weeks. In both groups, pre-contemplation stage was found as the highest proportion of changes in stages. At 24 weeks, an intervention group showed two times more in the action stage than control group (adjusted odds ratio 2.44, 95% CI 1.29-4.62). The positive effect of a call-recall approach in motivating women to change the behavior of screening practice should be appreciated by policy makers and health care providers in developing countries as an intervention to enhance Pap smear uptake. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Cervical cancer screening among university students in South Africa: a theory based study.

    PubMed

    Hoque, Muhammad Ehsanu; Ghuman, Shanaz; Coopoosmay, Roger; Van Hal, Guido

    2014-01-01

    Cervical cancer is a serious public health problem in South Africa. Even though the screening is free in health facilities in South Africa, the Pap smear uptake is very low. The objective of the study is to investigate the knowledge and beliefs of female university students in South Africa. A cross sectional study was conducted among university women in South Africa to elicit information about knowledge and beliefs, and screening history. A total of 440 students completed the questionnaire. The average age of the participants was 20.39 years (SD  = 1.71 years). Regarding cervical cancer, 55.2% (n = 243) had ever heard about it. Results indicated that only 15% (22/147) of the students who had ever had sex and had heard about cervical cancer had taken a Pap test. Pearson correlation analysis showed that cervical cancer knowledge had a significantly negative relationship with barriers to cervical cancer screening. Susceptibility and seriousness score were significantly moderately correlated with benefit and motivation score as well as barrier score. Self-efficacy score also had a moderate correlation with benefit and motivation score. Students who had had a Pap test showed a significantly lower score in barriers to being screened compared to students who had not had a Pap test. This study showed that educated women in South Africa lack complete information on cervical cancer. Students who had had a Pap test had significantly lower barriers to cervical cancer screening than those students who had not had a Pap test.

  16. Correction of intermittent hypoxia reduces inflammation in obese subjects with obstructive sleep apnea

    PubMed Central

    Perrini, Sebastio; Quaranta, Vitaliano Nicola; Falcone, Vito Antonio; Kounaki, Stella; Ciavarella, Alessandro; Ficarella, Romina; Barbaro, Maria; Nigro, Pasquale; Carratù, Pierluigi; Natalicchio, Annalisa; Laviola, Luigi; Resta, Onofrio

    2017-01-01

    BACKGROUND. In obese subjects with obstructive sleep apnea (OSA), chronic intermittent hypoxia (CIH) may be linked to systemic and adipose tissue inflammation. METHODS. We obtained abdominal subcutaneous adipose tissue biopsies from OSA and non-OSA obese (BMI > 35) subjects at baseline and after 24 weeks (T1) of weight-loss intervention plus continuous positive airway pressure (c-PAP) or weight-loss intervention alone, respectively. OSA subjects were grouped according to good (therapeutic) or poor (subtherapeutic) adherence to c-PAP. RESULTS. At baseline, anthropometric and metabolic parameters, serum cytokines, and adipose tissue mRNA levels of obesity-associated chemokines and inflammatory markers were not different in OSA and non-OSA subjects. At T1, body weight was significantly reduced in all groups. Serum concentrations of IL-2, IL-4, IL-6, MCP-1, PDGFβ, and VEGFα were reduced by therapeutic c-PAP in OSA subjects and remained unaltered in non-OSA and subtherapeutic c-PAP groups. Similarly, adipose tissue mRNA levels of macrophage-specific (CD68, CD36) and ER stress (ATF4, CHOP, ERO-1) gene markers, as well as of IL-6, PDGFβ, and VEGFα, were decreased only in the therapeutic c-PAP group. CONCLUSION. CIH does not represent an additional factor increasing systemic and adipose tissue inflammation in morbid obesity. However, in subjects with OSA, an effective c-PAP therapy improves systemic and obesity-associated inflammatory markers. FUNDING. Ministero dell’Università e della Ricerca and Progetti di Rilevante Interesse Nazionale. PMID:28878129

  17. Bacterial Community and Spoilage Profiles Shift in Response to Packaging in Yellow-Feather Broiler, a Highly Popular Meat in Asia

    PubMed Central

    Wang, Huhu; Zhang, Xinxiao; Wang, Guangyu; Jia, Kun; Xu, Xinglian; Zhou, Guanghong

    2017-01-01

    The consumption of yellow-feathered broiler has been advocated for purchasing with chilled meat rather than live broilers in Asia due to the outbreaks of animal influenza. Here, the microbial community of chilled yellow-feathered broiler response to modified-air packaging (MAP, 80% CO2/20% N2) and penetrated-air packaging (PAP, air-filling) during storage was revealed by a combination of whole-metagenome shotgun sequencing and traditional isolation methods, and the volatile organic compounds and proteolytic activity of representative dominant isolates were also accessed. The results revealed that MAP prolonged shelf life from 4 to 8 days compared to PAP, when the numbers of total viable counts and lactic acid bacteria reached more than 7 log CFU/g. Aeromonas, Acinetobacter, Escherichia, and Streptococcus occupied the bacteria communities in initial broiler carcasses. MAP dramatically increased the bacteria diversity during storage compared to PAP. Clear shifts of the dominant bacteria species were obviously observed, with the top genera of Aeromonas, Lactococcus, Serratia, and Shewanella in MAP, whereas the microbial communities in PAP were largely dominated by Pseudomonas. The isolates of Pseudomonas from PAP carcasses and Aeromonas from MAP carcasses displayed strong proteolytic activities. Meanwhile, the principal component analysis based on the volatile organic compounds indicated that the metabolic profiles greatly varied between each treatment, and no link between the natural odor of spoilage meat in situ and the volatile odor of the dominant isolates incubated in standard culture was found. These data could lead to new insights into the bacteria communities of yellow-feathered broiler meat during storage and would benefit the development of novel preservative approaches. PMID:29312261

  18. Development of an HPV Educational Protocol for Adolescents

    PubMed Central

    Wetzel, Caitlin; Tissot, Abbigail; Kollar, Linda M.; Hillard, Paula A.; Stone, Rachel; Kahn, Jessica A.

    2007-01-01

    Study Objectives To develop an educational protocol about HPV and Pap tests for adolescents, to evaluate the protocol for understandability and clarity, and to evaluate the protocol for its effectiveness in increasing knowledge about HPV. Design In phase 1, investigators and adolescents developed the protocol. In phase 2, adolescents evaluated the protocol qualitatively, investigators evaluated its effectiveness in increasing HPV knowledge in a sample of adolescents, and the protocol was revised. In phase 3, investigators evaluated the effectiveness of the revised protocol in an additional adolescent sample. Setting Urban, hospital-based teen health center. Participants A total of 252 adolescent girls and boys in the three study phases. Main Outcome Measures Pre- and post-protocol knowledge about HPV, measured using a 10- or 11-item scale. Results Scores on the HPV knowledge scale increased significantly (p<.0001) among adolescents who participated in phases 2 and 3 after they received the protocol. Initial differences in scores based on race, insurance type and condom use were not noted post-protocol. Conclusion The protocol significantly increased knowledge scores about HPV in this population, regardless of sociodemographic characteristics and risk behaviors. Effective, developmentally appropriate educational protocols about HPV and Pap tests are particularly important in clinical settings as cervical cancer screening guidelines evolve, HPV DNA testing is integrated into screening protocols, and HPV vaccines become available. In-depth, one-on-one education about HPV may also prevent adverse psychosocial responses and promote healthy sexual and Pap screening behaviors in adolescents with abnormal HPV or Pap test results. Synopsis The investigators developed an educational protocol about HPV and Pap tests and evaluated its effectiveness in increasing knowledge about HPV among adolescents. PMID:17868894

  19. Clinical Implications of the Cervical Papanicolaou Test Results in the Management of Anal Warts in HIV-Infected Women

    PubMed Central

    Luu, Hung N.; Amirian, E. Susan; Piller, Linda; Chan, Wenyaw; Scheurer, Michael E.

    2013-01-01

    The Papanicolaou test (or Pap test) has long been used as a screening tool to detect cervical precancerous/cancerous lesions. However, studies on the use of this test to predict both the presence and change in size of genital warts are limited. We examined whether cervical Papanicolaou test results are associated with the size of the largest anal wart over time in HIV-infected women in an on-going cohort study in the US. A sample of 976 HIV-infected women included in a public dataset obtained from the Women’s Interagency HIV Study (WIHS) was selected for analysis. A linear mixed model was performed to determine the relationship between the size of anal warts and cervical Pap test results. About 32% of participants had abnormal cervical Pap test results at baseline. In the adjusted model, a woman with a result of Atypia Squamous Cell Undetermined Significance/Low-grade Squamous Intraepithelial Lesion (ASCUS/LSIL) had an anal wart, on average, 12.81 mm2 larger than a woman with normal cervical cytology. The growth rate of the largest anal wart after each visit in a woman with ASCUS/LSIL was 1.56 mm2 slower than that of a woman with normal cervical results. However, they were not significant (P = 0.54 and P = 0.82, respectively). This is the first study to examine the relationship between cervical Pap test results and anal wart development in HIV-infected women. Even though no association between the size of anal wart and cervical Pap test results was found, a screening program using anal cytology testing in HIV-infected women should be considered. Further studies in cost-effectiveness and efficacy of an anal cytology test screening program are warranted. PMID:24312348

  20. Adherence to Positive Airway Therapy After Switching From CPAP to ASV: A Big Data Analysis.

    PubMed

    Pépin, Jean-Louis D; Woehrle, Holger; Liu, Dongquan; Shao, Shiyun; Armitstead, Jeff P; Cistulli, Peter A; Benjafield, Adam V; Malhotra, Atul

    2018-01-15

    There is a lack of data regarding adherence trajectories when switching from continuous positive airway pressure (CPAP) to adaptive servoventilation (ASV) in the context of persistent or treatment-emergent central sleep apnea (CSA). This study investigated 90-day adherence rates in patients with sleep apnea based on the type of positive airway pressure (PAP) device used and any switching of PAP modality over time. Telemonitoring data were obtained from a United States PAP database. Eligible patients were a 30% random sample who started PAP, plus all who started ASV, from January 1, 2015 to October 2, 2015. All received PAP and had at least one session with usage of 1 hour or more. Adherence and device usage were determined in three groups: started on CPAP and stayed on CPAP (CPAP only); started on ASV and stayed on ASV (ASV only); started on CPAP, switched to ASV (Switch). The United States Medicare definition of adherence was used. The study included 198,890 patients; 189,724 (CPAP only), 8,957 (ASV only) and 209 (Switch). In the Switch group, average apnea-hypopnea index decreased significantly on ASV versus CPAP. At 90 days, adherence rates were 73.8% and 73.2% in the CPAP only and ASV only groups. In the Switch group, CPAP adherence was 62.7%, improving to 76.6% after the switch to ASV. Mean device usage at 90 days was 5.27, 5.31, and 5.73 h/d in the CPAP only, ASV only, and Switch groups, respectively. Treatment-emergent or persistent CSA during CPAP reduced therapy adherence, but adherence improved early after switching from CPAP to ASV. © 2018 American Academy of Sleep Medicine

  1. Potentiation of Paclitaxel-Induced Pain Syndrome in Mice by Angiotensin I Converting Enzyme Inhibition and Involvement of Kinins.

    PubMed

    Brusco, Indiara; Silva, Cássia Regina; Trevisan, Gabriela; de Campos Velho Gewehr, Camila; Rigo, Flávia Karine; La Rocca Tamiozzo, Lidia; Rossato, Mateus Fortes; Tonello, Raquel; Dalmolin, Gerusa Duarte; de Almeida Cabrini, Daniela; Gomez, Marcus Vinícius; Ferreira, Juliano; Oliveira, Sara Marchesan

    2017-12-01

    Paclitaxel is a chemotherapeutic agent used to treat solid tumours. However, it causes an acute and neuropathic pain syndrome that limits its use. Among the mechanisms involved in neuropathic pain caused by paclitaxel is activation of kinin receptors. Angiotensin converting enzyme (ACE) inhibitors can enhance kinin receptor signalling. The goal of this study was to evaluate the role of kinins on paclitaxel-associated acute pain syndromes (P-APS) and the effect of ACE inhibition on P-APS and paclitaxel-associated chronic peripheral neuropathy (P-CPN) in mice. Herein, we show that paclitaxel caused mechanical allodynia and spontaneous nociceptive behaviour that was reduced by antagonists of kinin receptors B 1 (DALBk and SSR240612) and B 2 (Hoe140 and FR173657). Moreover, enalapril (an ACE inhibitor) enhanced the mechanical allodynia induced by a low dose of paclitaxel. Likewise, paclitaxel injection inhibited ACE activity and increased the expressions of B 1 and B 2 receptors and bradykinin-related peptides levels in peripheral tissue. Together, our data support the involvement of kinin receptors in the P-APS and suggest kinin receptor antagonists to treat this syndrome. Because hypertension is the most frequent comorbidity affecting cancer patients, treatment of hypertension with ACE inhibitors in patients undergoing paclitaxel chemotherapy should be reviewed, since this could enhance the P-APS and P-CPN.

  2. Awareness of cervical cancer and Pap smear among nursing staff at a rural tertiary care hospital in Central India.

    PubMed

    Jain, S M; Bagde, M N; Bagde, N D

    2016-01-01

    Cancer cervix is the leading cause of cancer deaths in females in developing countries and one in five women suffering from cervical cancer lives in India. The aim of this study is to determine the awareness about cervical cancer and Pap smear among nurses working in a tertiary care institute. Study Setting and Design: Cross-sectional survey in a tertiary care institute. Nurses working at our institute excluding those who have worked or working in the Obstetrics and Gynecology department were provided with a pre-designed questionnaire testing their knowledge about cervical cancer. Approximately, 86% were aware about cancer cervix and 69% were aware of a pre-cancerous stage. 42.3% were not aware of any risk factor and 27.6% were not aware of any symptom of cancer cervix. 86.2% were aware about Pap smear, but only 58.6% were aware that facilities of Pap smear were available at our hospital. Knowledge about cervical cancer and awareness of Pap smear as screening test was inadequate in nursing staff. Awareness programs about cervical cancer and screening are needed to increase awareness for this preventable condition. There is a need to arrange reorientation programs to sensitize nurses and establish cytology clinics to offer facilities for easily accessible and affordable screening.

  3. Pain predicts non-adherence to pap smear screening among middle-aged African American women.

    PubMed

    Hoyo, Cathrine; Yarnall, Kimberly S H; Skinner, Celette Sugg; Moorman, Patricia G; Sellers, Denethia; Reid, LaVerne

    2005-08-01

    Middle-aged African American women have the highest incidence and mortality of invasive cervical cancer in the United States and the lowest adherence to pap smear screening. In 2001, we identified factors associated with non-adherence to screening recommendations using three focus group interviews and subsequently developed a questionnaire administered to 144 African American women aged 45 to 65 years. The perception that the Pap test was painful was associated with non-adherence to screening recommendations (OR = 4.78; 95%CI: 1.67-13.7). Difficulty to pay for the office visit coupled with perceived pain was associated with a nearly sixfold increase in risk of non-adherence (OR = 5.8; 95%CI: 2.8-15.5). Previously identified barriers to screening including lower education and socioeconomic status, poor access to care, knowledge of and exposure to known risk factors of invasive cervical cancer, cancer fatalism, and perceived racism were not independently associated with non-adherence. These data suggest that, among middle-aged African American women, future interventions addressing pain during a Pap test will likely increase acceptability of and adherence to cervical cancer screening. Pain could be addressed either by providing information during the pap test and/or using smaller lubricated speculums.

  4. Nature of immobilization surface affects antibody specificity to placental alkaline phosphatase.

    PubMed

    Kumar, Mukesh; Khan, Imran; Sinha, Subrata

    2015-01-01

    Retention of native conformation of immobilized protein is essential for various applications including selection and detection of specific recombinant antibodies (scFvs). Placental alkaline phosphatase (PAP), an onco-fetal antigen expressed on the surface of several tumors, was immobilized on supermagnetic particles for selection of recombinant antibodies from a human phage display antibody library. The isolated antibodies were found to be cross-reactive to either of the isozymes of alkaline phosphatase, i.e., bone alkaline phosphatase (BAP) or intestinal alkaline phosphatase (IAP) and could not be used for tumor targeting. A specific anti-PAP monoclonal antibody H17E2 was tested for retention of specificity under these conditions. Binding of the antibody to magnetic beads conjugated IAP and BAP along with PAP and the ability of the two isozymes to inhibit its binding to PAP depicted the loss of isozyme specificity of the antibody. However, the antibody retained its specificity to PAP immobilized on polyvinyl chloride (PVC) surface. Enzyme activity was observed on both surfaces. This demonstrates that nature of immobilization may affect antigen-antibody binding in subtle ways, resulting in alteration of conformation of the epitopes. This may have consequences for determining the specificity of antibody binding for proteins that share a high degree of homology.

  5. Molecular features determining different partitioning patterns of papain and bromelain in aqueous two-phase systems.

    PubMed

    Rocha, Maria Victoria; Nerli, Bibiana Beatriz

    2013-10-01

    The partitioning patterns of papain (PAP) and bromelain (BR), two well-known cysteine-proteases, in polyethyleneglycol/sodium citrate aqueous two-phase systems (ATPSs) were determined. Polyethyleneglycols of different molecular weight (600, 1000, 2000, 4600 and 8000) were assayed. Thermodynamic characterization of partitioning process, spectroscopy measurements and computational calculations of protein surface properties were also carried out in order to explain their differential partitioning behavior. PAP was observed to be displaced to the salt-enriched phase in all the assayed systems with partition coefficients (KpPAP) values between 0.2 and 0.9, while BR exhibited a high affinity for the polymer phase in systems formed by PEGs of low molecular weight (600 and 1000) with partition coefficients (KpBR) values close to 3. KpBR values resulted higher than KpPAP in all the cases. This difference could be assigned neither to the charge nor to the size of the partitioned biomolecules since PAP and BR possess similar molecular weight (23,000) and isoelectric point (9.60). The presence of highly exposed tryptophans and positively charged residues (Lys, Arg and His) in BR molecule would be responsible for a charge transfer interaction between PEG and the protein and, therefore, the uneven distribution of BR in these systems. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Genotyping for Human Papillomavirus (HPV) 16/18/52/58 Has a Higher Performance than HPV16/18 Genotyping in Triaging Women with Positive High-risk HPV Test in Northern Thailand

    PubMed Central

    Khunamornpong, Surapan; Settakorn, Jongkolnee; Sukpan, Kornkanok; Suprasert, Prapaporn; Srisomboon, Jatupol; Intaraphet, Suthida; Siriaunkgul, Sumalee

    2016-01-01

    Background Testing for high-risk human papillomavirus DNA (HPV test) has gained increasing acceptance as an alternative method to cytology in cervical cancer screening. Compared to cytology, HPV test has a higher sensitivity for the detection of histologic high-grade squamous intraepithelial lesion or worse (HSIL+), but this could lead to a large colposcopy burden. Genotyping for HPV16/18 has been recommended in triaging HPV-positive women. This study was aimed to evaluate the screening performance of HPV testing and the role of genotyping triage in Northern Thailand. Methods A population-based cervical screening program was performed in Chiang Mai (Northern Thailand) using cytology (conventional Pap test) and HPV test (Hybrid Capture 2). Women who had abnormal cytology or were HPV-positive were referred for colposcopy. Cervical samples from these women were genotyped using the Linear Array assay. Results Of 5,456 women, 2.0% had abnormal Pap test results and 6.5% tested positive with Hybrid Capture 2. Of 5,433 women eligible for analysis, 355 with any positive test had histologic confirmation and 57 of these had histologic HSIL+. The sensitivity for histologic HSIL+ detection was 64.9% for Pap test and 100% for Hybrid Capture 2, but the ratio of colposcopy per detection of each HSIL+ was more than two-fold higher with Hybrid Capture 2 than Pap test (5.9 versus 2.8). Genotyping results were available in 316 samples. HPV52, HPV16, and HPV58 were the three most common genotypes among women with histologic HSIL+. Performance of genotyping triage using HPV16/18/52/58 was superior to that of HPV16/18, with a higher sensitivity (85.7% versus 28.6%) and negative predictive value (94.2% versus 83.9%). Conclusions In Northern Thailand, HPV testing with genotyping triage shows better screening performance than cervical cytology alone. In this region, the addition of genotyping for HPV52/58 to HPV16/18 is deemed necessary in triaging women with positive HPV test. PMID:27336913

  7. Tuberculosis in Pap samples with emphasis on LBC: Caught only when thought.

    PubMed

    Bharani, Vani; Gupta, Nalini; Suri, Vanita; Rajwanshi, Arvind

    2018-05-01

    Despite being a commonly encountered infection, the clinical diagnosis of tuberculosis of the uterine cervix is elusive. Though a straightforward diagnosis on tissue sections, identification of typical features of tubercular infection on cervical Pap samples is challenging. In our experience, the infrequent pale staining collections of epithelioid cells are difficult to pick up on Pap stained smears, particularly LBC samples. In this series, 2 of the three samples were reported as atypical squamous cells of undetermined significance while 1 was reported as inflammatory at the initial diagnosis. Scattered Langhans' type giant cells may be seen as a subtle clue which should prompt the search for epithelioid cell granulomas. These cases may have a mass lesion clinically while no obvious signs of malignancy on the cervical samples. © 2017 Wiley Periodicals, Inc.

  8. Combination of cephalosporins with vancomycin or teicoplanin enhances antibacterial effect of glycopeptides against heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) and VISA

    PubMed Central

    Lai, Chih-Cheng; Chen, Chi-Chung; Chuang, Yin-Ching; Tang, Hung-Jen

    2017-01-01

    Eight heterogeneous vancomycin-intermediate S. aureus (h-VISA) and seven VISA clinical isolates confirmed by the population analysis profile/area under the curve ratio (PAP/AUC) were collected. We further performed the PAP/AUC, time-killing methods and MIC tests using vancomycin/teicoplanin alone or combination with susceptible breakpoint concentrations of cefazolin, cefmetazole, cefotaxime, and cefepime for these isolates. The PAP/AUC MIC curve shifted left after addition of cephalosporins with vancomycin or teicoplanin for both h-VISA and VISA isolates. With the combination of different cephalosporins with vancomycin or teicoplanin, the AUC/Mu3 AUC ratio decreased to <0.9 for the standard Mu3 isolate which are compatible with the definition of vancomycin susceptible S. aureus. These decreases ranged between 1.81–2.02 and 2.37–2.85-fold for h-VISA treated with cephalosporins and vancomycin or teicoplanin, and 2.05–4.59, and 2.93–4,89-fold for VISA treated with cephalosporins with vancomycin or teicoplanin. As measured by time-killing assays, the combinations of different cephalosporins with vancomycin concentrations at 1/2 and 1/4 MIC, exhibited a bactericidal and bacteriostatic effect in VISA. The mean fold of MIC decline for vancomycin base combinations ranged from 1.81–3.83 and 2.71–9.33 for h-VISA and VISA, respectively. Overall, this study demonstrated the enhanced antibacterial activity of vancomycin/teicoplanin after adding cephalosporins against clinical h-VISA/VISA isolates. PMID:28139739

  9. Inhibition of Voltage-Gated K+ Channel Kv1.5 by Antiarrhythmic Drugs.

    PubMed

    Chen, Rong; Chung, Shin-Ho

    2018-05-08

    Molecular dynamics simulations are employed to determine the inhibitory mechanisms of three drugs, 5-(4-phenoxybutoxy)psoralen (PAP-1), vernakalant, and flecainide, on the voltage-gated K + channel Kv1.5, a target for the treatment of cardiac arrhythmia. At neutral pH, PAP-1 is neutral, whereas the other two molecules carry one positive charge. We show that PAP-1 forms stable dimers in water, primarily through hydrophobic interactions between aromatic rings. All three molecules bind to the cavity between the Ile508 and Val512 residues from the four subunits of the channel. Once bound, the drug molecules are flexible, with the average root-mean-square fluctuation being between 2 and 3 Å, which is larger than the radius of gyration of a bulky amino acid. The presence of a monomeric PAP-1 causes the permeating K + ion to dehydrate, thereby creating a significant energy barrier. In contrast, vernakalant blocks the ion permeation primarily via an electrostatic mechanism and, therefore, must be in the protonated and charged form to be effective.

  10. Downregulation of adenosine and adenosine 1 receptor contributes to neuropathic pain in resiniferatoxin neuropathy.

    PubMed

    Kan, Hung-Wei; Chang, Chin-Hong; Lin, Chih-Lung; Lee, Yi-Chen; Hsieh, Sung-Tsang; Hsieh, Yu-Lin

    2018-04-16

    The neurochemical effects of adenosine signaling in small-fiber neuropathy leading to neuropathic pain are yet to be explored in a direct manner. This study examined this system at the level of ligand (via the ectonucleotidase activity of prostatic acid phosphatase, PAP) and adenosine A1 receptors (A1Rs) in resiniferatoxin (RTX) neuropathy, a peripheral neurodegenerative disorder which specifically affects nociceptive nerves expressing transient receptor potential vanilloid type 1 (TRPV1). We conducted immunohistochemistry on dorsal root ganglion neurons (DRG), high-performance liquid chromatography (HPLC) for functional assays, and pharmacological interventions to alter PAP and A1Rs in mice with RTX neuropathy. In DRG of RTX neuropathy, PAP(+) neurons were reduced compared with vehicle-treated mice (P = 0.002) . Functionally, PAP ectonucleotidase activity was consequently reduced (i.e., the content of adenosine in DRG, P = 0.012). PAP(+) neuronal density was correlated with the degree of mechanical allodynia, which was reversed by intrathecal lumbar puncture (i.t.) injection of recombinant PAP with a dose-dependent effect. Furthermore, A1Rs were downregulated (P = 0.002), and this downregulation was colocalized with the TRPV1 receptor (31.0% ± 2.8%). Mechanical allodynia was attenuated in a dose-dependent response by i.t. injection of the A1R ligand, adenosine; however, no analgesia was evident when an exogenous adenosine was blocked by A1R antagonist. This study demonstrated dual mechanisms of neuropathic pain in TRPV1-induced neuropathy, involving a reduced adenosine system at both the ligand (adenosine) and receptor (A1Rs) levels.

  11. Assessment of pulmonary arterial compliance evaluated using harmonic oscillator kinematics

    PubMed Central

    Hayabuchi, Yasunobu; Ono, Akemi; Homma, Yukako; Kagami, Shoji

    2017-01-01

    We hypothesized that KPA, a harmonic oscillator kinematics-derived spring constant parameter of the pulmonary artery pressure (PAP) profile, reflects PA compliance in pediatric patients. In this prospective study of 33 children (age range = 0.5–20 years) with various cardiac diseases, we assessed the novel parameter designated as KPA calculated using the pressure phase plane and the equation KPA = (dP/dt_max)2/([Pmax – Pmin])/2)2, where dP/dt_max is the peak derivative of PAP, and Pmax – Pmin is the difference between the minimum and maximum PAP. PA compliance was also calculated using two conventional methods: systolic PA compliance (sPAC) was expressed as the stroke volume/Pmax – Pmin; and diastolic PA compliance (dPAC) was determined according to a two-element Windkessel model of PA diastolic pressure decay. In addition, data were recorded during abdominal compression to determine the influence of preload on KPA. A significant correlation was observed between KPA and sPAC (r = 0.52, P = 0.0018), but not dPAC. Significant correlations were also seen with the time constant (τ) of diastolic PAP (r = −0.51, P = 0.0026) and the pulmonary vascular resistance index (r = −0.39, P = 0.0242). No significant difference in KPA was seen between before and after abdominal compression. KPA had a higher intraclass correlation coefficient than other compliance and resistance parameters for both intra-observer and inter-observer variability (0.998 and 0.997, respectively). These results suggest that KPA can provide insight into the underlying mechanisms and facilitate the quantification of PA compliance. PMID:28621582

  12. Assessment of pulmonary arterial compliance evaluated using harmonic oscillator kinematics.

    PubMed

    Hayabuchi, Yasunobu; Ono, Akemi; Homma, Yukako; Kagami, Shoji

    2017-01-01

    We hypothesized that K PA , a harmonic oscillator kinematics-derived spring constant parameter of the pulmonary artery pressure (PAP) profile, reflects PA compliance in pediatric patients. In this prospective study of 33 children (age range = 0.5-20 years) with various cardiac diseases, we assessed the novel parameter designated as K PA calculated using the pressure phase plane and the equation K PA  = (dP/dt_max) 2 /([Pmax - Pmin])/2) 2 , where dP/dt_max is the peak derivative of PAP, and Pmax - Pmin is the difference between the minimum and maximum PAP. PA compliance was also calculated using two conventional methods: systolic PA compliance (sPAC) was expressed as the stroke volume/Pmax - Pmin; and diastolic PA compliance (dPAC) was determined according to a two-element Windkessel model of PA diastolic pressure decay. In addition, data were recorded during abdominal compression to determine the influence of preload on K PA . A significant correlation was observed between K PA and sPAC (r = 0.52, P = 0.0018), but not dPAC. Significant correlations were also seen with the time constant (τ) of diastolic PAP (r = -0.51, P = 0.0026) and the pulmonary vascular resistance index (r = -0.39, P = 0.0242). No significant difference in K PA was seen between before and after abdominal compression. K PA had a higher intraclass correlation coefficient than other compliance and resistance parameters for both intra-observer and inter-observer variability (0.998 and 0.997, respectively). These results suggest that K PA can provide insight into the underlying mechanisms and facilitate the quantification of PA compliance.

  13. Diversity in Expression of Phosphorus (P) Responsive Genes in Cucumis melo L

    PubMed Central

    Fita, Ana; Bowen, Helen C.; Hayden, Rory M.; Nuez, Fernando; Picó, Belén; Hammond, John P.

    2012-01-01

    Background Phosphorus (P) is a major limiting nutrient for plant growth in many soils. Studies in model species have identified genes involved in plant adaptations to low soil P availability. However, little information is available on the genetic bases of these adaptations in vegetable crops. In this respect, sequence data for melon now makes it possible to identify melon orthologues of candidate P responsive genes, and the expression of these genes can be used to explain the diversity in the root system adaptation to low P availability, recently observed in this species. Methodology and Findings Transcriptional responses to P starvation were studied in nine diverse melon accessions by comparing the expression of eight candidate genes (Cm-PAP10.1, Cm-PAP10.2, Cm-RNS1, Cm-PPCK1, Cm-transferase, Cm-SQD1, Cm-DGD1 and Cm-SPX2) under P replete and P starved conditions. Differences among melon accessions were observed in response to P starvation, including differences in plant morphology, P uptake, P use efficiency (PUE) and gene expression. All studied genes were up regulated under P starvation conditions. Differences in the expression of genes involved in P mobilization and remobilization (Cm-PAP10.1, Cm-PAP10.2 and Cm-RNS1) under P starvation conditions explained part of the differences in P uptake and PUE among melon accessions. The levels of expression of the other studied genes were diverse among melon accessions, but contributed less to the phenotypical response of the accessions. Conclusions This is the first time that these genes have been described in the context of P starvation responses in melon. There exists significant diversity in gene expression levels and P use efficiency among melon accessions as well as significant correlations between gene expression levels and phenotypical measurements. PMID:22536378

  14. The effect of low molecular weight dextran on haemodynamics and respiratory function during endotoxin-induced shock.

    PubMed Central

    Christenson, J T; al-Sarraf, A; Abu-Saleh, R

    1992-01-01

    The effects of low molecular weight dextran (LMWD) infusion, on gas exchange and haemodynamics were evaluated in sheep during endotoxin shock. The infusion of LMWD was started after signs of shock and lung injury were evident. After a stabilization period 10 micrograms kg-1 E. Coli endotoxin was infused i.v.. Endotoxin infusion resulted in an marked increase in pulmonary artery pressure (PAP) and decrease in mean arterial pressure (MAP), respiratory compliance, arterial oxygen tension (PaO2) and oxygen delivery index (DO2l). After 3 h MAP, PaO2, DO2l and compliance improved significantly in LMWD treated animals. The PAP had also decreased significantly in the LMWD-treated animals, but remained high in the controls (P less than 0.01). It was concluded that LMWD infusion improves haemodynamics and gas-exchange in sheep during endotoxin shock. PMID:1373624

  15. Using probabilistic record linkage methods to identify Australian Indigenous women on the Queensland Pap Smear Register: the National Indigenous Cervical Screening Project

    PubMed Central

    Diaz, Abbey; Baade, Peter; Garvey, Gail; Cunningham, Joan; Brotherton, Julia M L; Canfell, Karen; Valery, Patricia C; O'Connell, Dianne L; Taylor, Catherine; Moore, Suzanne P; Condon, John R

    2016-01-01

    Objective To evaluate the feasibility and reliability of record linkage of existing population-based data sets to determine Indigenous status among women receiving Pap smears. This method may allow for the first ever population measure of Australian Indigenous women's cervical screening participation rates. Setting/participants A linked data set of women aged 20–69 in the Queensland Pap Smear Register (PSR; 1999–2011) and Queensland Cancer Registry (QCR; 1997–2010) formed the Initial Study Cohort. Two extracts (1995–2011) were taken from Queensland public hospitals data (Queensland Hospital Admitted Patient Data Collection, QHAPDC) for women, aged 20–69, who had ever been identified as Indigenous (extract 1) and had a diagnosis or procedure code relating to cervical cancer (extract 2). The Initial Study Cohort was linked to extract 1, and women with cervical cancer in the initial cohort were linked to extract 2. Outcome measures The proportion of women in the Initial Cohort who linked with the extracts (true -pairs) is reported, as well as the proportion of potential pairs that required clerical review. After assigning Indigenous status from QHAPDC to the PSR, the proportion of women identified as Indigenous was calculated using 4 algorithms, and compared. Results There were 28 872 women (2.1%) from the Initial Study Cohort who matched to an ever Indigenous record in extract 1 (n=76 831). Women with cervical cancer in the Initial Study Cohort linked to 1385 (71%) records in extract 2. The proportion of Indigenous women ranged from 2.00% to 2.08% when using different algorithms to define Indigenous status. The Final Study Cohort included 1 372 823 women (PSR n=1 374 401; QCR n=1955), and 5 062 118 records. Conclusions Indigenous status in Queensland cervical screening data was successfully ascertained through record linkage, allowing for the crucial assessment of the current cervical screening programme for Indigenous women. Our study highlights the need to include Indigenous status on Pap smear request and report forms in any renewed and redesigned cervical screening programme in Australia. PMID:26873047

  16. Comparison of HFNC, bubble CPAP and SiPAP on aerosol delivery in neonates: An in-vitro study.

    PubMed

    Sunbul, Fatemah S; Fink, James B; Harwood, Robert; Sheard, Meryl M; Zimmerman, Ralph D; Ari, Arzu

    2015-11-01

    Aerosol drug delivery via high flow nasal cannula (HFNC), bubble continuous positive airway pressure (CPAP), and synchronized inspiratory positive airway pressure (SiPAP) has not been quantified in spontaneously breathing premature infants. The purpose of this study was to compare aerosol delivery via HFNC, bubble CPAP, and SiPAP in a model of a simulated spontaneously breathing preterm infant. The types of CPAP systems and nebulizer positions used during aerosol therapy will impact aerosol deposition in simulated spontaneously breathing infants. Quantitative, comparative, in-vitro study. A breath simulator was set to preterm infant settings (VT : 9 ml, RR: 50 bpm and Ti: 0.5 sec) and connected to the trachea of an anatomical upper airway model of a preterm infant via collecting filter distal to the trachea. The HFNC (Optiflow; Fisher & Paykel), Bubble CPAP (Fisher & Paykel), and SiPAP (Carefusion) were attached to the nares of the model via each device's proprietary nasal cannula and set to deliver a baseline of 5 cm H2 O pressure. Albuterol sulfate (2.5 mg/0.5 ml) was aerosolized with a mesh nebulizer (Aeroneb Solo) positioned(1) proximal to the patient and(2) prior to the humidifier (n = 5). The drug was eluted from the filter with 0.1 N HCl and analyzed via spectrophotometry (276 nm). Data were analyzed using descriptive statistics, t-tests, and one-way analysis of variance (ANOVA), with P < 0.05 significant. At position 1, the trend of lower deposition (mean ± SD%) across devices was not significant (0.90 ± 0.26, 0.70 ± 0.16 and 0.59 ± 0.19, respectively; P = 0.098); however, in position 2, drug delivery with SiPAP (0.79 ± 0.11) was lower compared to both HFNC (1.30 ± 0.17; P = 0.003) and bubble CPAP (1.24 ± 0.24; p = 0.008). Placement of the nebulizer prior to the humidifier increased deposition with all devices (P < 0.05). Aerosol can be delivered via all three devices used in this study. Device selection and nebulizer position impacted aerosol delivery in this simulated model of a spontaneously breathing preterm infant. © 2014 Wiley Periodicals, Inc.

  17. Serologic response to Epstein-Barr virus antigens in patients with systemic lupus erythematosus: a controlled study.

    PubMed

    Esen, Bahar Artım; Yılmaz, Gülden; Uzun, Sami; Ozdamar, Melda; Aksözek, Alper; Kamalı, Sevil; Türkoğlu, Salih; Gül, Ahmet; Ocal, Lale; Aral, Orhan; Inanç, Murat

    2012-01-01

    Previous studies showed a link between systemic lupus erythematosus (SLE) and Epstein-Barr virus (EBV) infection. We sought to determine the features of serologic response to EBV in SLE patients and whether this response differs from those of systemic sclerosis (SSc) and primary antiphospholipid syndrome (PAPS) patients as well as healthy individuals. Sera from 198 consecutive SLE patients have been tested to detect IgG antibodies to EA/D, EBNA-1, VCA P18 and for comparison, cytomegalovirus (CMV) using commercially available ELISA kits (Trinity Biotech, USA). Forty-six SSc patients and 38 PAPS patients were enrolled as diseased control groups and sixty-five individuals as healthy controls. Significantly more SLE (54%, P = 0.001, OR 5.77, 95% CI 2.8-11.6), SSc (41.3%, P = 0.005, OR 3.4, 95% CI 1.4-8.2) and PAPS sera (36.8%, P = 0.023, OR 2.86, 95% CI 1.14-7.22) reacted against EA/D than healthy controls (16.9%). The mean age of anti-EA/D-positive SLE patients was significantly higher, and their disease duration was longer compared to anti-EA/D-negative SLE patients (41 ± 14 vs. 33.8 ± 10.8 years, P < 0.001 and 100 ± 73 vs. 71 ± 62 months, P = 0.003). In SLE patients, EA/D reactivity was associated with Raynaud's phenomenon and the presence of any anti-ENA antibodies. Although it did not reach a statistical significance, anti-EBNA-1 reactivity was slightly lower in patients with SLE. The frequency of anti-CMV Ig G positivity was found significantly higher in SLE patients (100%) when compared to patients with SSc (95.7%), PAPS (94.7%) and healthy controls (95.4%) (P = 0.035, P = 0.025 and P = 0.015 respectively). Our results support the proposed link between EBV and SLE. The finding that SSc and PAPS patients also have increased frequency of anti-EA/D response has revealed that this immune interaction may not be unique to patients with SLE, and there may be a common mechanism involving EBV in these autoimmune diseases.

  18. Genetic Predisposition to Persistent Apical Periodontitis

    PubMed Central

    Morsani, Jussara M.; Aminoshariae, Anita; Han, Yiping Weng; Montagnese, Thomas A.; Mickel, Andre

    2013-01-01

    Introduction The proinflammatory cytokine interleukin (IL)-1 is a key regulator of host responses to microbial infection and a major modulator of extracellular matrix catabolism and bone resorption. Allele2 of IL-1b is associated with a four-fold increase in IL-1β production. The aim of this case-control study was to evaluate the gene polymorphism of IL-1β in the pathogenesis of endodontic failure. We hypothesized that the gene polymorphism (allele2 of IL-1β) would influence host response and enhance inflammatory reactions predisposing to persistent apical periodontitis (PAP). Materials and Methods Subjects with at least 1 year of follow-up after root canal therapy (RCT) were recalled. Inclusion and exclusion criteria were applied, and 34 subjects with signs/symptoms of PAP with otherwise acceptable RCT were included. Sixty-one controls showed healing with acceptable RCT. Genomic DNA from buccal mucosa was amplified by polymerase chain reaction followed by restriction fragment length polymorphism to distinguish the alleles of IL-1β gene polymorphism. Results A significant difference in the distribution of the polymorphic genotype among cases (70.6%) and controls (24.6%) (P < .001, Pearson χ2) was shown. Conclusions These findings suggest that specific genetic markers associated with increased IL-1β production may contribute to increased susceptibility to PAP. PMID:21419289

  19. Inuit women's attitudes and experiences towards cervical cancer and prevention strategies in Nunavik, Quebec.

    PubMed

    Cerigo, Helen; Macdonald, Mary Ellen; Franco, Eduardo L; Brassard, Paul

    2012-03-19

    To describe the attitudes about and experiences with cervical cancer, Pap smear screenings and the HPV vaccine among a sample of Inuit women from Nunavik, Quebec, Canada. We also evaluated demographic and social predictors of maternal interest in HPV vaccination. A mixed method design was used with a cross-sectional survey and focus group interviews. Women were recruited through convenience sampling at 2 recruitment sites in Nunavik from March 2008 to June 2009. Differences in women's responses by age, education, and marital status were assessed. Unconditional logistic regression was used to determine predictors of women's interest in HPV vaccination for their children. Questionnaires were completed by 175 women aged 18-63, and of these women a total of 6 women aged 31-55 participated in 2 focus groups. Almost half the survey participants had heard of cervical cancer. Women often reported feelings of embarrassment and pain during the Pap smear and older women were more likely to feel embarrassed than younger women. Only 27% of women had heard of the HPV vaccine, and 72% of these women were interested in vaccinating their child for HPV. No statistically significant predictors of maternal interest in HPV vaccination were found. Our findings indicate that health service planners and providers in Nunavik should be aware of potential barriers to Pap smear attendance, especially in the older age groups. Given the low awareness of cervical cancer, the Pap smear and the HPV vaccine, education on cervical cancer and prevention strategies may be beneficial.

  20. Comparative Assessment of a Self-sampling Device and Gynecologist Sampling for Cytology and HPV DNA Detection in a Rural and Low Resource Setting: Malaysian Experience.

    PubMed

    Latiff, Latiffah A; Ibrahim, Zaidah; Pei, Chong Pei; Rahman, Sabariah Abdul; Akhtari-Zavare, Mehrnoosh

    2015-01-01

    This study was conducted to assess the agreement and differences between cervical self-sampling with a Kato device (KSSD) and gynecologist sampling for Pap cytology and human papillomavirus DNA (HPV DNA) detection. Women underwent self-sampling followed by gynecologist sampling during screening at two primary health clinics. Pap cytology of cervical specimens was evaluated for specimen adequacy, presence of endocervical cells or transformation zone cells and cytological interpretation for cells abnormalities. Cervical specimens were also extracted and tested for HPV DNA detection. Positive HPV smears underwent gene sequencing and HPV genotyping by referring to the online NCBI gene bank. Results were compared between samplings by Kappa agreement and McNemar test. For Pap specimen adequacy, KSSD showed 100% agreement with gynecologist sampling but had only 32.3% agreement for presence of endocervical cells. Both sampling showed 100% agreement with only 1 case detected HSIL favouring CIN2 for cytology result. HPV DNA detection showed 86.2%agreement (K=0.64, 95% CI 0.524-0.756, p=0.001) between samplings. KSSD and gynaecologist sampling identified high risk HPV in 17.3% and 23.9% respectively (p= 0.014). The self-sampling using Kato device can serve as a tool in Pap cytology and HPV DNA detection in low resource settings in Malaysia. Self-sampling devices such as KSSD can be used as an alternative technique to gynaecologist sampling for cervical cancer screening among rural populations in Malaysia.

  1. Elevated arterial blood pressure after superior cavo-pulmonary anastomosis is associated with elevated pulmonary artery pressure and cerebrovascular dysautoregulation.

    PubMed

    Cabrera, Antonio G; Kibler, Kathleen K; Blaine Easley, R; Goldsworthy, Michelle; Shekerdemian, Lara S; Andropoulos, Dean B; Heinle, Jeffrey; Gottlieb, Erin A; Vu, Eric; Brady, Ken M

    2018-04-18

    BackgroundElevated arterial blood pressure (ABP) is common after superior bidirectional cavopulmonary anastomosis (BCPA). The effects of elevated ABP after BCPA on cerebrovascular hemodynamics are unknown. We sought to determine the relationship between elevated ABP and cerebrovascular autoregulation after BCPA.MethodsProspective, observational study on infants with single-ventricle physiology after BCPA surgery. Continuous recordings of mean ABP, mean cavopulmonary artery pressure (PAP), near-infrared spectroscopy measures of cerebral oximetry (regional cerebral oxygen saturation (rSO 2 )), and relative cerebral blood volume index were obtained from admission to extubation. Autoregulation was measured as hemoglobin volume index (HVx). Physiologic variables, including the HVx, were tested for variance across ABP.ResultsSixteen subjects were included in the study. Elevated ABP post-BCPA was associated with both, elevated PAP (P<0.0001) and positive HVx (dysautoregulation; P<0.0001). No association was observed between ABP and alterations in rSO 2 . Using piecewise regression, the relationship of PAP to ABP demonstrated a breakpoint at 68 mm Hg (interquartile range (IQR) 62-70 mm Hg). Curve fit of HVx as a function of ABP identified optimal ABP supporting robust autoregulation at a median ABP of 55 mm Hg (IQR 51-64 mm Hg).ConclusionsElevated ABP post-BCPA is associated with cerebrovascular dysautoregulation, and elevated PAP. The effects, of prolonged dysautoregulation within this population, require further study.Pediatric Research advance online publication, 18 April 2018; doi:10.1038/pr.2018.31.

  2. Physical activity on prescription (PAP): self-reported physical activity and quality of life in a Swedish primary care population, 2-year follow-up

    PubMed Central

    Rödjer, Lars; H. Jonsdottir, Ingibjörg; Börjesson, Mats

    2016-01-01

    Objective To study the self-reported level of physical activity (PA) and quality of life (QOL) in patients receiving physical activity on prescription (PAP) for up to 24 months. Design Observational study conducted in a regular healthcare setting. Setting A primary care population in Sweden receiving physical activity on prescription as part of regular care was studied alongside a reference group. Subjects The group comprised 146 patients receiving PAP at two different primary care locations (n = 96 and 50, respectively). The reference group comprised 58 patients recruited from two different primary care centres in the same region. Main outcome measurements We used two self-report questionnaires – the four-level Saltin-Grimby Physical Activity Level Scale (SGPALS) to assess physical activity, and SF-36 to assess QOL. Results A significant increase in the PA level was found at six and 12 months following PAP, with an ongoing non-significant trend at 24 months (p = .09). A clear improvement in QOL was seen during the period. At 24 months, significant and clinically relevant improvements in QOL persisted in four out of eight sub-scale scores (Physical Role Limitation, Bodily Pain, General Health,Vitality) and in one out of two summary scores (Physical Component Summary). Conclusion Patients receiving PAP showed an increased level of self-reported PA at six and 12 months and improved QOL for up to 24 months in several domains. The Swedish PAP method seems to be a feasible method for bringing about changes in physical activity in different patient populations in regular primary healthcare. While increased physical activity (PA) is shown to improve health, the implementation of methods designed to increase activity is still being developed. Key points The present study confirms that the Swedish physical activity on prescription (PAP) method increases the self-reported level of PA in the primary care setting at six and 12 months. Furthermore, this study shows that PAP recipients report a clinically relevant long-term improvement in quality of life, persisting for two years post-prescription, thus extending earlier findings. These findings have clinical implications for the implementation of PAP in healthcare. PMID:27978781

  3. An N-terminal fragment of yeast ribosomal protein L3 inhibits the cytotoxicity of pokeweed antiviral protein in Saccharomyces cerevisiae.

    PubMed

    Di, Rong; Tumer, Nilgun E

    2014-04-11

    We have previously shown that ribosomal protein L3 is required for pokeweed antiviral protein (PAP), a type I ribosome inactivating protein, to bind to ribosomes and depurinate the α-sarcin/ricin loop (SRL) in yeast. Co-expression of the N-terminal 99 amino acids of yeast L3 (L3Δ99) with PAP in transgenic tobacco plants completely abolished the toxicity of PAP. In this study, we investigated the interaction between PAP and L3Δ99 in Saccharomyces cerevisiae. Yeast cells co-transformed with PAP and L3Δ99 showed markedly reduced growth inhibition and reduced rRNA depurination by PAP, compared to cells transformed with PAP alone. Co-transformation of yeast with PAP and L3Δ21 corresponding to the highly conserved N-terminal 21 amino acids of L3Δ99, reduced the cytotoxicity of PAP. PAP mRNA and protein levels were elevated and L3Δ99 or L3Δ21 mRNA and protein levels were reduced in yeast co-transformed with PAP and L3Δ99 or with PAP and L3Δ21, respectively. PAP interacted with L3Δ21 in yeast cells in vivo and by Biacore analysis in vitro, suggesting that the interaction between L3Δ21 and PAP may inhibit PAP-mediated depurination of the SRL, leading to a reduction in the cytotoxicity of PAP.

  4. Physical Activity on Prescription (PAP), in patients with metabolic risk factors. A 6-month follow-up study in primary health care.

    PubMed

    Lundqvist, Stefan; Börjesson, Mats; Larsson, Maria E H; Hagberg, Lars; Cider, Åsa

    2017-01-01

    There is strong evidence that inadequate physical activity (PA) leads to an increased risk of lifestyle-related diseases and premature mortality. Physical activity on prescription (PAP) is a method to increase the level of PA of patients in primary care, but needs further evaluation. The aim of this observational study was to explore the association between PAP-treatment and the PA level of patients with metabolic risk factors and the relationship between changes in the PA level and health outcomes at the 6 month follow-up. This study included 444 patients in primary care, aged 27-85 years (56% females), who were physically inactive with at least one component of metabolic syndrome. The PAP-treatment model included: individualized dialogue concerning PA, prescribed PA, and a structured follow-up. A total of 368 patients (83%) completed the 6 months of follow-up. Of these patients, 73% increased their PA level and 42% moved from an inadequate PA level to sufficient, according to public health recommendations. There were significant improvements (p≤ 0.05) in the following metabolic risk factors: body mass index, waist circumference, systolic blood pressure, fasting plasma glucose, cholesterol, and low density lipoprotein. There were also significant improvements regarding health-related quality of life, assessed by the Short Form 36, in: general health, vitality, social function, mental health, role limitation-physical/emotional, mental component summary, and physical component summary. Regression analysis showed a significant association between changes in the PA level and health outcomes. During the first 6-month period, the caregiver provided PAP support 1-2 times. This study indicates that an individual-based model of PAP-treatment has the potential to change people's PA behavior with improved metabolic risk factors and self-reported quality of life at the 6 month follow-up. Thus, PAP seems to be feasible in a clinical primary care practice, with minimum effort from healthcare professionals.

  5. Association between aerobic vaginitis, bacterial vaginosis and squamous intraepithelial lesion of low grade.

    PubMed

    Jahic, Mahira; Mulavdic, Mirsada; Hadzimehmedovic, Azra; Jahic, Elmir

    2013-01-01

    To determine frequency of HPV infection, aerobic vaginitis and bacterial vaginosis in respondents with squamous intraepithelial lesion of lower grade comparing to respondents with normal PAP test results. Prospective research of 100 respondents has been conducted at University-Clinic Center Tuzla and Gynecology and Obstetrics Department at Primary Health Care Center Tuzla in period from May 2011 untill January 2012. Examination program included: anamnesis, clinical gynecological examination, HPV typization, microbiological examination of vaginal and cervical smear and PAP test. High risk HPV group has been found more frequently among the respondents with LG SIL 46% (23) than in those with normal PAP result 14% (7) p < 0.05. Aerobic vaginitis has been found in the respondents with LG SIL in 28% (14) and there is statistically significant difference of this vaginitis comparing to the respondents with normal PAP result (p < 0.05). Bacterial vaginosis has been found in 12% (6) of the respondents with LG SIL and in 4% (2) of those with normal PAP result which is not statistically significant. In women with LG SIL and aerobic vaginitis in 9 cases E. coli has been isolated, in 4 E. faecalis and in 1 Staphylococcus aureus, while in women with normal PAP test results 3 cases of E.coli have been isolated. Examining changes in pH value of vaginal environment, higher measured values have been found in the respondents with LG SIL- 5.26 while in the respondents with normal PAP test result was 4.94 (p < 0.05). There is also statistically significant increase in the number of leukocytes in the respondents with LG SIL in relation to those with normal result. In women with LG SIL aerobic vaginitis is very common but is not an indicator of HPV infection. An adequate treatment of aerobic vaginitis would decrease the frequency of LG SIL and number of precancerous lesions which may

  6. Physical Activity on Prescription (PAP), in patients with metabolic risk factors. A 6-month follow-up study in primary health care

    PubMed Central

    Börjesson, Mats; Larsson, Maria E. H.; Hagberg, Lars; Cider, Åsa

    2017-01-01

    There is strong evidence that inadequate physical activity (PA) leads to an increased risk of lifestyle-related diseases and premature mortality. Physical activity on prescription (PAP) is a method to increase the level of PA of patients in primary care, but needs further evaluation. The aim of this observational study was to explore the association between PAP-treatment and the PA level of patients with metabolic risk factors and the relationship between changes in the PA level and health outcomes at the 6 month follow-up. This study included 444 patients in primary care, aged 27–85 years (56% females), who were physically inactive with at least one component of metabolic syndrome. The PAP-treatment model included: individualized dialogue concerning PA, prescribed PA, and a structured follow-up. A total of 368 patients (83%) completed the 6 months of follow-up. Of these patients, 73% increased their PA level and 42% moved from an inadequate PA level to sufficient, according to public health recommendations. There were significant improvements (p≤ 0.05) in the following metabolic risk factors: body mass index, waist circumference, systolic blood pressure, fasting plasma glucose, cholesterol, and low density lipoprotein. There were also significant improvements regarding health-related quality of life, assessed by the Short Form 36, in: general health, vitality, social function, mental health, role limitation-physical/emotional, mental component summary, and physical component summary. Regression analysis showed a significant association between changes in the PA level and health outcomes. During the first 6-month period, the caregiver provided PAP support 1–2 times. This study indicates that an individual-based model of PAP-treatment has the potential to change people’s PA behavior with improved metabolic risk factors and self-reported quality of life at the 6 month follow-up. Thus, PAP seems to be feasible in a clinical primary care practice, with minimum effort from healthcare professionals. PMID:28403151

  7. CstF-64 and 3'-UTR cis-element determine Star-PAP specificity for target mRNA selection by excluding PAPα.

    PubMed

    Kandala, Divya T; Mohan, Nimmy; A, Vivekanand; A P, Sudheesh; G, Reshmi; Laishram, Rakesh S

    2016-01-29

    Almost all eukaryotic mRNAs have a poly (A) tail at the 3'-end. Canonical PAPs (PAPα/γ) polyadenylate nuclear pre-mRNAs. The recent identification of the non-canonical Star-PAP revealed specificity of nuclear PAPs for pre-mRNAs, yet the mechanism how Star-PAP selects mRNA targets is still elusive. Moreover, how Star-PAP target mRNAs having canonical AAUAAA signal are not regulated by PAPα is unclear. We investigate specificity mechanisms of Star-PAP that selects pre-mRNA targets for polyadenylation. Star-PAP assembles distinct 3'-end processing complex and controls pre-mRNAs independent of PAPα. We identified a Star-PAP recognition nucleotide motif and showed that suboptimal DSE on Star-PAP target pre-mRNA 3'-UTRs inhibit CstF-64 binding, thus preventing PAPα recruitment onto it. Altering 3'-UTR cis-elements on a Star-PAP target pre-mRNA can switch the regulatory PAP from Star-PAP to PAPα. Our results suggest a mechanism of poly (A) site selection that has potential implication on the regulation of alternative polyadenylation. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  8. CstF-64 and 3′-UTR cis-element determine Star-PAP specificity for target mRNA selection by excluding PAPα

    PubMed Central

    Kandala, Divya T.; Mohan, Nimmy; A, Vivekanand; AP, Sudheesh; G, Reshmi; Laishram, Rakesh S.

    2016-01-01

    Almost all eukaryotic mRNAs have a poly (A) tail at the 3′-end. Canonical PAPs (PAPα/γ) polyadenylate nuclear pre-mRNAs. The recent identification of the non-canonical Star-PAP revealed specificity of nuclear PAPs for pre-mRNAs, yet the mechanism how Star-PAP selects mRNA targets is still elusive. Moreover, how Star-PAP target mRNAs having canonical AAUAAA signal are not regulated by PAPα is unclear. We investigate specificity mechanisms of Star-PAP that selects pre-mRNA targets for polyadenylation. Star-PAP assembles distinct 3′-end processing complex and controls pre-mRNAs independent of PAPα. We identified a Star-PAP recognition nucleotide motif and showed that suboptimal DSE on Star-PAP target pre-mRNA 3′-UTRs inhibit CstF-64 binding, thus preventing PAPα recruitment onto it. Altering 3′-UTR cis-elements on a Star-PAP target pre-mRNA can switch the regulatory PAP from Star-PAP to PAPα. Our results suggest a mechanism of poly (A) site selection that has potential implication on the regulation of alternative polyadenylation. PMID:26496945

  9. PAP and NT5E inhibit nociceptive neurotransmission by rapidly hydrolyzing nucleotides to adenosine

    PubMed Central

    2011-01-01

    Background Prostatic acid phosphatase (PAP) and ecto-5'-nucleotidase (NT5E, CD73) produce extracellular adenosine from the nucleotide AMP in spinal nociceptive (pain-sensing) circuits; however, it is currently unknown if these are the main ectonucleotidases that generate adenosine or how rapidly they generate adenosine. Results We found that AMP hydrolysis, when measured histochemically, was nearly abolished in dorsal root ganglia (DRG) neurons and lamina II of spinal cord from Pap/Nt5e double knockout (dKO) mice. Likewise, the antinociceptive effects of AMP, when combined with nucleoside transport inhibitors (dipyridamole or 5-iodotubericidin), were reduced by 80-100% in dKO mice. In addition, we used fast scan cyclic voltammetry (FSCV) to measure adenosine production at subsecond resolution within lamina II. Adenosine was maximally produced within seconds from AMP in wild-type (WT) mice but production was reduced >50% in dKO mice, indicating PAP and NT5E rapidly generate adenosine in lamina II. Unexpectedly, we also detected spontaneous low frequency adenosine transients in lamina II with FSCV. Adenosine transients were of short duration (<2 s) and were reduced (>60%) in frequency in Pap-/-, Nt5e-/- and dKO mice, suggesting these ectonucleotidases rapidly hydrolyze endogenously released nucleotides to adenosine. Field potential recordings in lamina II and behavioral studies indicate that adenosine made by these enzymes acts through the adenosine A1 receptor to inhibit excitatory neurotransmission and nociception. Conclusions Collectively, our experiments indicate that PAP and NT5E are the main ectonucleotidases that generate adenosine in nociceptive circuits and indicate these enzymes transform pulsatile or sustained nucleotide release into an inhibitory adenosinergic signal. PMID:22011440

  10. Phosphate forms an unusual tripodal complex with the Fe–Mn center of sweet potato purple acid phosphatase

    PubMed Central

    Schenk, Gerhard; Gahan, Lawrence R.; Carrington, Lyle E.; Mitić, Nataša; Valizadeh, Mohsen; Hamilton, Susan E.; de Jersey, John; Guddat, Luke W.

    2005-01-01

    Purple acid phosphatases (PAPs) are a family of binuclear metalloenzymes that catalyze the hydrolysis of phosphoric acid esters and anhydrides. A PAP in sweet potato has a unique, strongly antiferromagnetically coupled Fe(III)–Mn(II) center and is distinguished from other PAPs by its increased catalytic efficiency for a range of activated and unactivated phosphate esters, its strict requirement for Mn(II), and the presence of a μ-oxo bridge at pH 4.90. This enzyme displays maximum catalytic efficiency (kcat/Km) at pH 4.5, whereas its catalytic rate constant (kcat) is maximal at near-neutral pH, and, in contrast to other PAPs, its catalytic parameters are not dependent on the pKa of the leaving group. The crystal structure of the phosphate-bound Fe(III)–Mn(II) PAP has been determined to 2.5-Å resolution (final Rfree value of 0.256). Structural comparisons of the active site of sweet potato, red kidney bean, and mammalian PAPs show several amino acid substitutions in the sweet potato enzyme that can account for its increased catalytic efficiency. The phosphate molecule binds in an unusual tripodal mode to the two metal ions, with two of the phosphate oxygen atoms binding to Fe(III) and Mn(II), a third oxygen atom bridging the two metal ions, and the fourth oxygen pointing toward the substrate binding pocket. This binding mode is unique among the known structures in this family but is reminiscent of phosphate binding to urease and of sulfate binding to λ protein phosphatase. The structure and kinetics support the hypothesis that the bridging oxygen atom initiates hydrolysis. PMID:15625111

  11. Dynamic properties of bacterial pili measured by optical tweezers

    NASA Astrophysics Data System (ADS)

    Fallman, Erik G.; Andersson, Magnus J.; Schedin, Staffan S.; Jass, Jana; Uhlin, Bernt Eric; Axner, Ove

    2004-10-01

    The ability of uropathogenic Escherichia coli (UPEC) to cause urinary tract infections is dependent on their ability to colonize the uroepithelium. Infecting bacteria ascend the urethra to the bladder and then kidneys by attaching to the uroepithelial cells via the differential expression of adhesins. P pili are associated with pyelonephritis, the more severe infection of the kidneys. In order to find means to treat pyelonephritis, it is therefore of interest to investigate the properties P pili. The mechanical behavior of individual P pili of uropathogenic Escherichia coli has recently been investigated using optical tweezers. P pili, whose main part constitutes the PapA rod, composed of ~1000 PapA subunits in a helical arrangement, are distributed over the bacterial surface and mediate adhesion to host cells. We have earlier studied P pili regarding its stretching/elongation properties where we have found and characterized three different elongation regions, of which one constitute an unfolding of the quaternary (helical) structure of the PapA rod. It was shown that this unfolding takes place at an elongation independent force of 27 +/- 2 pN. We have also recently performed studies on its folding properties and shown that the unfolding/folding of the PapA rod is completely reversible. Here we present a study of the dynamical properties of the PapA rod. We show, among other things, that the unfolding force increases and that the folding force decreases with the speed of unfolding and folding respectively. Moreover, the PapA rod can be folded-unfolded a significant number of times without loosing its characteristics, a phenomenon that is believed to be important for the bacterium to keep close contact to the host tissue and consequently helps the bacterium to colonize the host tissue.

  12. Rate of Opportunistic Pap Smear Screening and Patterns of Epithelial Cell Abnormalities in Pap Smears in Ajman, United Arab Emirates

    PubMed Central

    Al Eyd, Ghaith J.; Shaik, Rizwana B.

    2012-01-01

    Objectives: The aim of this study was to estimate the proportion of women undergoing Papanicolaou (Pap) smear examinations, and the frequency of epithelial cell abnormalities in a teaching hospital in one emirate of the United Arab Emirates (UAE) during a three-year period. Methods: A retrospective study of 602 patient records from July 2007 to July 2010 was done in a teaching hospital in Ajman, UAE. The variables studied were age, ethnicity, menopausal status, and abnormalities in the Pap smear. Data were analysed using the Statistical Package for the Social Sciences and presented mainly as percentages; to assess associations, the chi-square test was used. Results: The total number of outpatients who attended the Obstetrics & Gynaecology Department from July 2007 to July 2010 was 150,111 patients, of which 602 (0.4% of the total) had a Pap smear test. The sample was 50.1% Arabs and 49.9% other nationalities. While 73% of the outpatients had specific complaints, 27% came for a routine screening. Epithelial cell abnormalities were seen in 3.3% of the sample, with atypical squamous cells of undetermined significance (ASCUS) found in 1.8%, low-grade squamous intraepithelial lesions (LSILs) found in 1.2%, and high-grade squamous intraepithelial lesions (HSILs) found in 0.3%. There were no cases of squamous cell carcinoma. Conclusion: Voluntary routine Pap smear screening was remarkably low in the study group. ASCUS was the most common epithelial cell abnormality. Community health education and opportunistic screening for cervical cancer are recommended for both national and expatriate women in the region. PMID:23275844

  13. The acute effect of a plyometric stimulus on jump performance in professional rugby players.

    PubMed

    Tobin, Daniel P; Delahunt, Eamonn

    2014-02-01

    Post-activation potentiation (PAP) is the elevation of motor performance to a higher level in response to a conditioning stimulus. Extensive research exists examining the PAP effect after a heavy resistance exercise. However, there is limited research examining the PAP effect after a plyometric stimulus. This study was designed to examine whether a plyometric stimulus could produce a PAP effect comparable to that typically reported with a heavy resistance protocol. Importantly, it was hypothesized that the PAP effect would exist without the same levels of acute fatigue resulting from a heavy stimulus, thus allowing improvement in performance within a short rest interval range. Twenty professional rugby players were recruited for the study. Subjects performed 2 countermovement jumps (CMJs) at baseline and at 1, 3, and 5 minutes after a plyometric stimulus consisting of 40 jumps. Two separate 1-way repeated-measures analyses of variance were conducted to compare the dependent variables CMJ height and peak force at the 4 time points. Results of the Bonferroni adjusted pairwise comparisons indicated that jump height and peak force before plyometric exercises were significantly lower than all other time points (p < 0.01). The main finding of this study indicates that a series of plyometric exercises causes a significant acute enhancement in CMJ height (p < 0.01) and peak force (p < 0.01) throughout the rest interval range of 1-5 minutes. The plyometric series induced an improvement in CMJ height comparable to that reported elsewhere after a heavy lifting stimulus but without the need for a prolonged rest interval. Performing repeated series of plyometric jumps appears to be an efficient method of taking advantage of the PAP phenomenon, thus possibly eliminating the need for a complex training protocol.

  14. Factors Infuencing Women in Pap Smear Uptake

    NASA Astrophysics Data System (ADS)

    Wijayanti, K. E.; Alam, I. G.

    2017-03-01

    Objective: Pap smear has proven can decrease death caused by cervical cancer. However, in Indonesia, only few woman who already did pap smear. The aim of this study was to investigate women’s knowledge about pap smear cervical cancer, and to investigate factors influence women to do pap smear test. Methods: Quantitative data colected through questionairre towards 31 women who did pap smear and 55 women who did not do pap smear. Questionairre was made using Health Belief model as a guideline to examine percieved susceptibility, perceived serioussnes, perceived benefits and perceived barriers. Chi square and multiple logistic regresion were used to investigate difference in knowledge and what the most factor that influence women to take pap smear test. Results: There’s significance knowledge difference betweeen women who did and did not do pap smear. But furthermore, by using Multiple Logistic Regression test, appearantly knowledge was not a strong predictor factor for women to take pap smear test (koefisiensi β = -0,164) Conclusion: Perceived barriers were factors that affected pap smear uptake in women in Indonesia. Few respondents get the wrong informations about pap smear, cevical cancer and its symptoms

  15. Right Ventricular Structure and Function in Idiopathic Pulmonary Fibrosis with or without Pulmonary Hypertension.

    PubMed

    D'Andrea, Antonello; Stanziola, Anna; Di Palma, Enza; Martino, Maria; D'Alto, Michele; Dellegrottaglie, Santo; Cocchia, Rosangela; Riegler, Lucia; Betancourt Cordido, Meredyth Vanessa; Lanza, Maurizia; Maglione, Marco; Diana, Veronica; Calabrò, Raffaele; Russo, Maria Giovanna; Vannan, Mani; Bossone, Eduardo

    2016-01-01

    To elucidate right ventricular (RV) function in patients with idiopathic pulmonary fibrosis (IPF) with and without pulmonary hypertension (PH) and its relation to other features of the disease. Clinical evaluation, standard Doppler echo, Doppler myocardial imaging (DMI), and 2D strain echocardiography (STE) of RV septal and lateral walls were performed in 52 IPF patients (66.5 ± 8.5 years; 27 males) and in 45 age- and sex-comparable controls using a commercial US system (MyLab Alpha, Esaote). Pulmonary artery mean pressure (mPAP) was estimated by standard echo Doppler. RV global longitudinal strain (RV GLS) was calculated by averaging RV local strains. The IPF patients were divided into 2 groups by noninvasive assessment of PH: no PH (mPAP<25 mmHg; 36 pts) and PH (mPAP ≥25 mmHg; 16 pts). Left ventricular diameters and ejection fraction were comparable between controls and IPF, while GLS was impaired in IPF (P < 0.01). RV end-diastolic diameters, wall thickness andmPAP were increased in IPF patients with PH. In addition, pulsed DMI detected in PH IPF impaired myocardial RV early diastolic (Em) peak velocity. Also peak systolic RV strain was reduced in basal and middle RV lateral free walls in IPF, as well as RV GLS (P < 0.0001). The impairment in RV wall strain was more evident when comparing controls with the no PH group than comparing the no PH group with the PH group. By multivariate analysis, independent association of RV strain with both six-minute walking test distance (P < 0.001), mPAP (P < 0.0001), as well as with forced vital capacity (FVC) % (P < 0.005) in IPF patients were observed. Impaired RV diastolic and systolic myocardial function were present even in IPF patients without PH, which indicates an early impact on RV function and structure in patients with IPF. © 2015, Wiley Periodicals, Inc.

  16. A Randomized Controlled Trial of a Cervical Cancer Education Intervention for Latinas Delivered Through Interactive, Multimedia Kiosks.

    PubMed

    Valdez, Armando; Napoles, Anna M; Stewart, Susan L; Garza, Alvaro

    2018-02-01

    US Latina women experience disproportionately high cervical cancer incidence and mortality rates. These health disparities are largely preventable with routine pap tests and human papillomavirus (HPV) screening. This study tested the efficacy of a cervical cancer education intervention to improve risk factor knowledge, attitudes, self-efficacy, and self-reported behavior related to cervical cancer screening among low-income Latinas who had not been screened in the past 2 years, compared to a usual care control group. Low-income Latinas who had not had a pap test in the prior 2 years were recruited from three Federally Qualified Health Centers and randomly assigned to intervention and control groups, with in-person assessment at baseline and 6-month follow-up. Women in the intervention group received a one-time low-literacy cervical cancer education program through an interactive, multimedia kiosk in either English or Spanish based on their language preference. Compared to the control group, the intervention group demonstrated greater knowledge (p < 0.0001) and more favorable attitudes at follow-up; fewer intervention group women never thought of getting a pap test (46 vs. 54 %, p = 0.050) or agreed that it is fate whether a woman gets cervical cancer or not (24 vs. 31 %, p = 0.043). The groups did not differ significantly on the proportion who had obtained or made an appointment for a pap test at follow-up (51 vs. 48 %, p = 0.35). Both groups reported high levels of self-efficacy regarding pap screening at post-intervention. A one-time interactive, multimedia educational intervention improved cervical cancer knowledge and attitudes among low-income Latinas but had no effect on cervical cancer-screening behavior. Exposure of the control group to the pre-test conducted on the multimedia kiosk may have influenced their screening behavior.

  17. Difference Between Cryotherapy and Follow Up Low Grade Squamous Lesion of Cervix Uteri.

    PubMed

    Jahic, Mahira; Jahic, Elmir; Mulavdic, Mirsada; Hadzimehmedovic, Azra

    2017-08-01

    Cervical cancer can be successfully prevented by effective treatment. Analyse of success of cryotherapy in LSIL and ASCUS. In retrospective study between January 2016 to March 2017, 3244 PAP test were analysed. 257 patients who had been diagnosed with LSIL and ASCUS from PAP smear were divided in two groups: women who had HPV positive, colposcopic positive and cytologic finding of LSIL or ASCUS treathed with cryotherapy and women with LSIL, ASCUS and negative colposcopy. χ 2 test was used for statistical analysis of data. Analysis of 3244 PAP smears showed negative for intraepithelial lesion or malignancy (NILM) in 90,10% (N-2923), and abnormal in 9,8% (N-321) of women. ASCUS was found in 4,8% (N-156) and ASC-H in 0,2% (N-6), LSIL in 3,1% (N-101), HSIL in 0,64% (N-21). The average age of patients with ASCUS lesion was 41 ± 12 years. After cryotherapy, HSIL had progression in 1,5% (N-1), persistence in 6,3% (N-4) and regression in 91,7% (N-58). Progression occured in 10,5% (N-4) of HSIL, persistence in 52,6% (N-20) and regression in 36,7% (N-14) in 38 women with LSIL lesion after repeated PAP test. Progression occured in 8% (N-10) of LSIL and 4% HSIL (N-5), persistence in 58% (N-72) and regression in 29,8% (N-37) in 124 women with ASCUS lesion after treatment and repeated PAP test. Difference in progression lesions in HSIL between women with cryotherapy (1,5%) and follow-up (10,5%) after LSIL is not significant, but progression to CIN II occured after cryotherapy. CIN III or cervical cancer was not found. Cryotherapy prevents progression of LSIL in HSIL and in cervical cancer. Because of that cryotherapy is successful method in prevention of cervical cancer.

  18. Difference Between Cryotherapy and Follow Up Low Grade Squamous Lesion of Cervix Uteri

    PubMed Central

    Jahic, Mahira; Jahic, Elmir; Mulavdic, Mirsada; Hadzimehmedovic, Azra

    2017-01-01

    Introduction: Cervical cancer can be successfully prevented by effective treatment. Aim: Analyse of success of cryotherapy in LSIL and ASCUS. Materials et methods: In retrospective study between January 2016 to March 2017, 3244 PAP test were analysed. 257 patients who had been diagnosed with LSIL and ASCUS from PAP smear were divided in two groups: women who had HPV positive, colposcopic positive and cytologic finding of LSIL or ASCUS treathed with cryotherapy and women with LSIL, ASCUS and negative colposcopy. χ2 test was used for statistical analysis of data. Results: Analysis of 3244 PAP smears showed negative for intraepithelial lesion or malignancy (NILM) in 90,10% (N-2923), and abnormal in 9,8% (N-321) of women. ASCUS was found in 4,8% (N-156) and ASC-H in 0,2% (N-6), LSIL in 3,1% (N-101), HSIL in 0,64% (N-21). The average age of patients with ASCUS lesion was 41 ± 12 years. After cryotherapy, HSIL had progression in 1,5% (N-1), persistence in 6,3% (N-4) and regression in 91,7% (N-58). Progression occured in 10,5% (N-4) of HSIL, persistence in 52,6% (N-20) and regression in 36,7% (N-14) in 38 women with LSIL lesion after repeated PAP test. Progression occured in 8% (N-10) of LSIL and 4% HSIL (N-5), persistence in 58% (N-72) and regression in 29,8% (N-37) in 124 women with ASCUS lesion after treatment and repeated PAP test. Difference in progression lesions in HSIL between women with cryotherapy (1,5%) and follow-up (10,5%) after LSIL is not significant, but progression to CIN II occured after cryotherapy. CIN III or cervical cancer was not found. Conclusion: Cryotherapy prevents progression of LSIL in HSIL and in cervical cancer. Because of that cryotherapy is successful method in prevention of cervical cancer. PMID:28974850

  19. Prevalence of high-risk human papillomavirus and abnormal pap smears in female sex workers compared to the general population in Antwerp, Belgium.

    PubMed

    Vorsters, Alex; Cornelissen, Tine; Leuridan, Elke; Bogers, Johannes; Vanden Broeck, Davy; Benoy, Ina; Goossens, Herman; Hens, Niel; Van Damme, Pierre

    2016-06-07

    Although female sex workers (FSWs) are a well-known high-risk group for Human Papillomavirus (HPV) infections, few tailored intervention programmes for HPV have been established worldwide. The lack of reliable data on the prevalence of HPV and related cervical lesions hampers the establishment of evidence-based intervention programmes. The objectives of this study were to describe the prevalence of high-risk Human Papillomavirus (hrHPV) infections and abnormal pap smears in FSWs compared to a control group in Antwerp, Belgium. HPV genotyping and cytology data were analysed from routine Pap smear tests that were collected from both FSWs and the general population (1334 samples for each group) between June 2006 and June 2010. Within the laboratory database, all FSWs were matched 1:1 for age and testing date to determine the ORs of hrHPV genotypes, DNA and cytology outcome. The prevalence of hrHPV DNA in FSWs was 41.7 % compared to 19.8 % in the age-matched controls with an overall OR of 2.8 (95 % CI: 2.3-3.4). Significant differences were observed in all age groups, and the most significant differences were observed in the cohort under 21 years of age (prevalence of 64.4 % in FSWs versus 14.8 % in controls; OR 10.3 (95 % CI: 5.0-21.2). Significantly more cervical lesions were observed in FSWs, particularly in the 17- to 21-year old age group (OR for LSIL or HSIL: 10.3 (95 % CI: 3.2-33.8). In both groups, HPV 16 was the most prevalent at 12.1 and 6.6 % in the FSW and control groups, respectively. HPV 18 was the 8(th) and 7(th) most frequent genotype at 5.0 and 2.5 % in the FSW and control groups, respectively. FSWs have a significantly higher prevalence of hrHPV and more abnormal Pap smears than does the general population in Antwerp, Belgium. The hrHPV prevalence in FSWs is similar to that reported in the literature. The need for tailored intervention programmes should be investigated further.

  20. [Aerosolized iloprost therapy for pulmonary hypertensive crisis in 4 patients with idiopathic pulmonary arterial hypertension].

    PubMed

    Deng, Ke-wu; Zhou, Yu-jie; Xu, Xi-qi; Wu, Ming-ying; Wang, Guo-hong; Bian, Hong; Chen, Bo; Wang, Chun-bo

    2012-10-01

    To summary the efficacy and safety of aerosolized iloprost in patients with pulmonary hypertensive crisis. On the basis of conventional therapy, aerosolized iloprost (10 µg per time for 10 - 15 min in 2 hours interval, 8 times per day) was administered to four patients with idiopathic pulmonary arterial hypertension and pulmonary hypertensive crisis. Blood pressure, heart rate, systemic artery oxygen saturation, systolic pulmonary arterial pressure (sPAP) measured by echocardiography and the adverse events were analyzed. After aerosolized iloprost therapy, sPAP was significantly decreased and systemic artery oxygen saturation was improved. Adverse events (nausea, vomiting, diarrhea, dry cough) were observed in two patients, and the iloprost use was stopped in one patient due to severe vomiting and diarrhea. Aerosolized iloprost could significantly reduce the sPAP and improve the systemic artery oxygen saturation in patients with pulmonary hypertension crisis.

  1. Investigation of pharmaceuticals in processed animal by-products by liquid chromatography coupled to high-resolution mass spectrometry.

    PubMed

    Nácher-Mestre, Jaime; Ibáñez, María; Serrano, Roque; Boix, Clara; Bijlsma, Lubertus; Lunestad, Bjørn Tore; Hannisdal, Rita; Alm, Martin; Hernández, Félix; Berntssen, Marc H G

    2016-07-01

    There is an on-going trend for developing more sustainable salmon feed in which traditionally applied marine feed ingredients are replaced with alternatives. Processed animal products (PAPs) have been re-authorized as novel high quality protein ingredients in 2013. These PAPs may harbor undesirable substances such as pharmaceuticals and metabolites which are not previously associated with salmon farming, but might cause a potential risk for feed and food safety. To control these contaminants, an analytical strategy based on a generic extraction followed by ultra-high performance liquid chromatography coupled to high resolution mass spectrometry (UHPLC-HRMS) using quadrupole time-of-flight mass analyzer (QTOF MS) was applied for wide scope screening. Quality control samples, consisting of PAP commodities spiked at 0.02, 0.1 and 0.2 mg/kg with 150 analytes, were injected in every sample batch to verify the overall method performance. The methodology was applied to 19 commercially available PAP samples from six different types of matrices from the EU animal rendering industry. This strategy allows assessing possible emergent risk exposition of the salmon farming industry to 1005 undesirables, including pharmaceuticals, several dyes and relevant metabolites. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. [Growth inhibition effection of perlecan anti-sense cDNA on human laryngeal carcinoma xnograft in nude mice].

    PubMed

    Chen, Guangli; Gong, Shusheng; Chen, Pei; Luo, Linghui

    2014-09-01

    To observe growth inhibition effect of perlecan anti-sense cDNA (pAP) on human laryngeal carcinoma xnografted in nude mice. To vertify its antitumor effect and mechanism in vivo, and it may be useful as a biomarker in carcinoma of larynx cancer. Created the model of human laryngeal carcinoma xnograft in nude mice. To observe growth of those xnografts in nude mice and draw growth curve of xnografted. The expression of perlecan mRNA and portein in xnografts were examined by RT-PCR and immunohistochemistry. Volume of xnografts in the group transfected by the plasmids of pAP were significant small as compared with other two groups made by the wild type cells and phpApr-neol cells (P < 0.05). It was showed that the expression of perlecan mRNA and protein were significantly reduced in the tumor of pAP transfected Hep-2 cells as compared with the tumors transfected by the wild type cells and phβApr-neol cells (P < 0.01). These data raise the possibility that pAP many play key roles in the growth of those xnografts in nude mice.

  3. Structural analysis of a type 1 ribosome inactivating protein reveals multiple L-asparagine-N-acetyl-D-glucosamine monosaccharide modifications: Implications for cytotoxicity

    PubMed Central

    HOGG, TANIS; MENDEL, JAMESON T.; LAVEZO, JONATHAN L.

    2015-01-01

    Pokeweed antiviral protein (PAP) belongs to the family of type I ribosome-inactivating proteins (RIPs): Ribotoxins, which function by depurinating the sarcin-ricin loop of ribosomal RNA. In addition to its antibacterial and antifungal properties, PAP has shown promise in antiviral and targeted tumor therapy owing to its ability to depurinate viral RNA and eukaryotic rRNA. Several PAP genes are differentially expressed across pokeweed tissues, with natively isolated seed forms of PAP exhibiting the greatest cytotoxicity. To help elucidate the molecular basis of increased cytotoxicity of PAP isoenzymes from seeds, the present study used protein sequencing, mass spectroscopy and X-ray crystallography to determine the complete covalent structure and 1.7 Å X-ray crystal structure of PAP-S1aci isolated from seeds of Asian pokeweed (Phytolacca acinosa). PAP-S1aci shares ~95% sequence identity with PAP-S1 from P. americana and contains the signature catalytic residues of the RIP superfamily, corresponding to Tyr72, Tyr122, Glu175 and Arg178 in PAP-S1aci. A rare proline substitution (Pro174) was identified in the active site of PAP-S1aci, which has no effect on catalytic Glu175 positioning or overall active-site topology, yet appears to come at the expense of strained main-chain geometry at the pre-proline residue Val173. Notably, a rare type of N-glycosylation was detected consisting of N-acetyl-D-glucosamine monosaccharide residues linked to Asn10, Asn44 and Asn255 of PAP-S1aci. Of note, our modeling studies suggested that the ribosome depurination activity of seed PAPs would be adversely affected by the N-glycosylation of Asn44 and Asn255 with larger and more typical oligosaccharide chains, as they would shield the rRNA-binding sites on the protein. These results, coupled with evidence gathered from the literature, suggest that this type of minimal N-glycosylation in seed PAPs and other type I seed RIPs may serve to enhance cytotoxicity by exploiting receptor-mediated uptake pathways of seed predators while preserving ribosome affinity and rRNA recognition. PMID:26238506

  4. Enhancement of oxidative and drought tolerance in Arabidopsis by overaccumulation of antioxidant flavonoids

    PubMed Central

    Nakabayashi, Ryo; Yonekura-Sakakibara, Keiko; Urano, Kaoru; Suzuki, Makoto; Yamada, Yutaka; Nishizawa, Tomoko; Matsuda, Fumio; Kojima, Mikiko; Sakakibara, Hitoshi; Shinozaki, Kazuo; Michael, Anthony J; Tohge, Takayuki; Yamazaki, Mami; Saito, Kazuki

    2014-01-01

    The notion that plants use specialized metabolism to protect against environmental stresses needs to be experimentally proven by addressing the question of whether stress tolerance by specialized metabolism is directly due to metabolites such as flavonoids. We report that flavonoids with radical scavenging activity mitigate against oxidative and drought stress in Arabidopsis thaliana. Metabolome and transcriptome profiling and experiments with oxidative and drought stress in wild-type, single overexpressors of MYB12/PFG1 (PRODUCTION OF FLAVONOL GLYCOSIDES1) or MYB75/PAP1 (PRODUCTION OF ANTHOCYANIN PIGMENT1), double overexpressors of MYB12 and PAP1, transparent testa4 (tt4) as a flavonoid-deficient mutant, and flavonoid-deficient MYB12 or PAP1 overexpressing lines (obtained by crossing tt4 and the individual MYB overexpressor) demonstrated that flavonoid overaccumulation was key to enhanced tolerance to such stresses. Antioxidative activity assays using 2,2-diphenyl-1-picrylhydrazyl, methyl viologen, and 3,3′-diaminobenzidine clearly showed that anthocyanin overaccumulation with strong in vitro antioxidative activity mitigated the accumulation of reactive oxygen species in vivo under oxidative and drought stress. These data confirm the usefulness of flavonoids for enhancing both biotic and abiotic stress tolerance in crops. PMID:24274116

  5. The Impact of Achievement Goals on Cardiorespiratory Fitness: Does Self-Efficacy Make a Difference?

    ERIC Educational Resources Information Center

    Gao, Zan; Xiang, Ping; Lochbaum, Marc; Guan, Jianmin

    2013-01-01

    Purpose: The relationships among students' self-efficacy, 2 × 2 achievement goals (mastery-approach [MAp], mastery-avoidance [MAv], performance-approach [PAp], and performance-avoidance goals), and achievement performance remain largely unanswered. We tested a model of the mediating role of self-efficacy on the relationship between 2 × 2…

  6. Factors Modulating Post-Activation Potentiation of Jump, Sprint, Throw, and Upper-Body Ballistic Performances: A Systematic Review with Meta-Analysis.

    PubMed

    Seitz, Laurent B; Haff, G Gregory

    2016-02-01

    Although post-activation potentiation (PAP) has been extensively examined following the completion of a conditioning activity (CA), the precise effects on subsequent jump, sprint, throw, and upper-body ballistic performances and the factors modulating these effects have yet to be determined. Moreover, weaker and stronger individuals seem to exhibit different PAP responses; however, how they respond to the different components of a strength-power-potentiation complex remains to be elucidated. This meta-analysis determined (1) the effect of performing a CA on subsequent jump, sprint, throw, and upper-body ballistic performances; (2) the influence of different types of CA, squat depths during the CA, rest intervals, volumes of CA, and loads during the CA on PAP; and (3) how individuals of different strength levels respond to these various strength-power-potentiation complex components. A computerized search was conducted in ADONIS, ERIC, SPORTDiscus, EBSCOhost, Google Scholar, MEDLINE, and PubMed databases up to March 2015. The analysis comprised 47 studies and 135 groups of participants for a total of 1954 participants. The PAP effect is small for jump (effect size [ES] = 0.29), throw (ES = 0.26), and upper-body ballistic (ES = 0.23) performance activities, and moderate for sprint (ES = 0.51) performance activity. A larger PAP effect is observed among stronger individuals and those with more experience in resistance training. Plyometric (ES = 0.47) CAs induce a slightly larger PAP effect than traditional high-intensity (ES = 0.41), traditional moderate-intensity (ES = 0.19), and maximal isometric (ES = -0.09) CAs, and a greater effect after shallower (ES = 0.58) versus deeper (ES = 0.25) squat CAs, longer (ES = 0.44 and 0.49) versus shorter (ES = 0.17) recovery intervals, multiple- (ES = 0.69) versus single- (ES = 0.24) set CAs, and repetition maximum (RM) (ES = 0.51) versus sub-maximal (ES = 0.34) loads during the CA. It is noteworthy that a greater PAP effect can be realized earlier after a plyometric CA than with traditional high- and moderate-intensity CAs. Additionally, shorter recovery intervals, single-set CAs, and RM CAs are more effective at inducing PAP in stronger individuals, while weaker individuals respond better to longer recovery intervals, multiple-set CAs, and sub-maximal CAs. Finally, both weaker and stronger individuals express greater PAP after shallower squat CAs. Performing a CA elicits small PAP effects for jump, throw, and upper-body ballistic performance activities, and a moderate effect for sprint performance activity. The level of potentiation is dependent on the individual's level of strength and resistance training experience, the type of CA, the depth of the squat when this exercise is employed to elicit PAP, the rest period between the CA and subsequent performance, the number of set(s) of the CA, and the type of load used during the CA. Finally, some components of the strength-power-potentiation complex modulate the PAP response of weaker and stronger individuals in a different way.

  7. Extended-spectrum beta-lactamase-producing Escherichia coli infections in children: are community-acquired strains different from nosocomial strains?

    PubMed

    Morgand, Marjolaine; Vimont, Sophie; Bleibtreu, Alexandre; Boyd, Anders; Thien, Hoang Vu; Zahar, Jean-Ralph; Denamur, Erick; Arlet, Guillaume

    2014-11-01

    Infections caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli are an important cause of morbidity and mortality, especially in children. We compared 58 epidemiologically unrelated ESBL-producing E. coli strains that caused infections. They were isolated between 2008 and 2012 in two Parisian pediatric hospitals and grouped according to their origin into either community-acquired (CA) (n=37) or nosocomially acquired (NA) (n=21) strains. Molecular characteristics of the ESBLs, phylogenetic traits of the strains including their belonging to clone O25b-ST131, prevalence of associated virulence genes, growth capacities in different media, metabolic phenotype and biofilm formation abilities were studied. ESBL type, associated resistance and distribution of phylogenetic groups were similar in the CA and NA groups. More than 60% of the B2 phylogroup strains in both groups belonged to the ST131 clone. Interestingly, CA strains possessed more genes encoding virulence factors and the distribution of these genes differed significantly between the two groups: fyuA, hlyC, papC and papGII were more frequent in the CA group, whereas iroN was more frequent in the NA group. CA strains also showed enhanced growth capacities in Luria Bertani rich medium. They tended to produce more biofilm but the difference was not significant. This study confirms the wide spread of clone ST131 among infected children, regardless of whether their infections were community- or nosocomially acquired. It highlights genotypic and phenotypic differences according to the origin of the strains that could indicate adaptability of these multi-resistant bacteria to specific environmental and host factors. Copyright © 2014 Elsevier GmbH. All rights reserved.

  8. Concurrent, but not sequential, PD-1 blockade with a DNA vaccine elicits anti-tumor responses in patients with metastatic, castration-resistant prostate cancer.

    PubMed

    McNeel, Douglas G; Eickhoff, Jens C; Wargowski, Ellen; Zahm, Christopher; Staab, Mary Jane; Straus, Jane; Liu, Glenn

    2018-05-22

    T-cell checkpoint inhibitors have demonstrated dramatic clinical activity against multiple cancer types, however little activity in patients with prostate cancer. Conversely, an anti-tumor vaccine was approved for the treatment of prostate cancer, having demonstrated an improvement in overall survival, despite few objective disease responses. In murine studies, we found that PD-1 expression on CD8+ T cells increased following anti-tumor vaccination, and that PD-1/PD-L1 blockade at the time of immunization elicited greater anti-tumor responses. Based on these data we initiated a pilot trial evaluating the immunological and clinical efficacy of a DNA encoding prostatic acid phosphatase (PAP) when delivered in combination with pembrolizumab. 26 patients were treated for 12 weeks with vaccine and received pembrolizumab either during this time or during the subsequent 12 weeks. Adverse events included grade 2 and 3 fatigue, diarrhea, thyroid dysfunction, and hepatitis. Median time to radiographic progression was not different between study arms. 8/13 (62%) of patients treated concurrently, and 1/12 (8%, p=0.01) of patients treated sequentially, experienced PSA declines from baseline. Of these, two were over 50% and one was a complete PSA response. No confirmed CR or PR were observed, however 4/5 patients treated concurrently had measurable decreases in tumor volume at 12 weeks. PSA declines were associated with the development of PAP-specific Th1-biased T cell immunity and CD8+ T cell infiltration in metastatic tumor biopsy specimens. These data are the first report of a clinical trial demonstrating that the efficacy of an anti-tumor vaccine can be augmented by concurrent PD-1 blockade.

  9. Mechanical versus humoral determinants of brain death-induced lung injury

    PubMed Central

    Dewachter, Laurence; Rorive, Sandrine; Remmelink, Myriam; Weynand, Birgit; Melot, Christian; Hupkens, Emeline; Dewachter, Céline; Creteur, Jacques; Mc Entee, Kathleen; Naeije, Robert; Rondelet, Benoît

    2017-01-01

    Background The mechanisms of brain death (BD)-induced lung injury remain incompletely understood, as uncertainties persist about time-course and relative importance of mechanical and humoral perturbations. Methods Brain death was induced by slow intracranial blood infusion in anesthetized pigs after randomization to placebo (n = 11) or to methylprednisolone (n = 8) to inhibit the expression of pro-inflammatory mediators. Pulmonary artery pressure (PAP), wedged PAP (PAWP), pulmonary vascular resistance (PVR) and effective pulmonary capillary pressure (PCP) were measured 1 and 5 hours after Cushing reflex. Lung tissue was sampled to determine gene expressions of cytokines and oxidative stress molecules, and pathologically score lung injury. Results Intracranial hypertension caused a transient increase in blood pressure followed, after brain death was diagnosed, by persistent increases in PAP, PCP and the venous component of PVR, while PAWP did not change. Arterial PO2/fraction of inspired O2 (PaO2/FiO2) decreased. Brain death was associated with an accumulation of neutrophils and an increased apoptotic rate in lung tissue together with increased pro-inflammatory interleukin (IL)-6/IL-10 ratio and increased heme oxygenase(HO)-1 and hypoxia inducible factor(HIF)-1 alpha expression. Blood expressions of IL-6 and IL-1β were also increased. Methylprednisolone pre-treatment was associated with a blunting of increased PCP and PVR venous component, which returned to baseline 5 hours after BD, and partially corrected lung tissue biological perturbations. PaO2/FiO2 was inversely correlated to PCP and lung injury score. Conclusions Brain death-induced lung injury may be best explained by an initial excessive increase in pulmonary capillary pressure with increased pulmonary venous resistance, and was associated with lung activation of inflammatory apoptotic processes which were partially prevented by methylprednisolone. PMID:28753621

  10. Women’s Experiences of Abnormal Cervical Cytology: Illness Representations, Care Processes, and Outcomes

    PubMed Central

    Karasz, Alison; McKee, M. Diane; Roybal, Krista

    2003-01-01

    BACKGROUND We wanted to explore the conceptual representations of illness and experiences with care among women who have learned of an abnormal Papanicolaou (Pap) smear result. METHODS The study took place in 2 primary care, family practice clinics serving low-income, multiethnic patients in the Bronx, New York City. We conducted qualitative, semistructured telephone interviews with 17 patients who had recently learned of abnormal findings on a Pap smear. After a preliminary coding phase, the investigators identified 2 important outcomes: distress and dissatisfaction with care, and factors affecting these outcomes. A model was developed on a subset of the data, which was then tested on each transcript with an explicit search for disconfirming cases. A revised coding scheme conforming to the dimensions of the model was used to recode transcripts. RESULTS Women reported complex, syncretic models of illness that included both biomedical and folk elements. Many concerns, especially nonbiomedical concerns, were not addressed in interactions with physicians. An important source of both distress and dissatisfaction with care was the women’s lack of understanding of the inherent ambiguity of Pap smear results. When perceived care needs, which included emotional support as well as information, were not met, distress and dissatisfaction were greatly increased. CONCLUSION In this study, patients’ illness models and expectations of care were not routinely addressed in their conversations with physicians about abnormal Pap smear results. When physicians can take the time to review patients’ illness models carefully, distress and dissatisfaction with care can be reduced considerably. PMID:15055408

  11. Impact of pap test compliance and cervical cancer screening intervals on human papillomavirus vaccine acceptance.

    PubMed

    Ferris, Daron G; Waller, Jennifer; Dickinson, Ashley; McCracken, Courtney; Goebel, Angela

    2012-01-01

    The objective of this study was to determine the impact of Pap test compliance and cervical cancer screening intervals on human papillomavirus (HPV) vaccination acceptance. A convenience sample of 499 women 21 to 65 years old completed a 37-question survey in Augusta and Savannah, GA. The survey assessed their knowledge about HPV, cervical cancer, and the HPV vaccine. The questionnaire also determined their Pap test compliance and how longer Pap test intervals would influence their willingness to receive the HPV vaccine. Differences between categorical variables and knowledge scores were examined using χ test and unequal-variance t tests, respectively. Pap test-noncompliant women were more likely to get the HPV vaccine if they only needed a Pap test every 10 years compared with Pap test-compliant women (27.6% vs 14.6%, p = .02). A greater number (83.5%) of Pap test-noncompliant women preferred the HPV vaccine plus every 10-year Pap test option compared with Pap test-compliant women (31.3%, p < .0001). Most women (87%) responded that they would likely get the HPV vaccine if it would safely reduce the frequency of Pap testing. Women are receptive to getting the HPV vaccine in exchange for longer cervical cancer screening intervals. Moreover, Pap test-noncompliant women are more likely to get the HPV vaccine if Pap testing was needed less frequently. Increasing the Pap testing interval may be an excellent method to improving HPV vaccine acceptance in women at highest risk for cervical cancer.

  12. Screening with Papanicolaou tests in Alberta

    PubMed Central

    Symonds, Christopher J.; Chen, Wenxin; Rose, Marianne Sarah; Cooke, Lara J.

    2018-01-01

    Abstract Objective To describe the prevalence and geographic distribution of cervical cancer screening, as well as the age groups of those undergoing screening, in Alberta, and to determine if screening practices conform to current guidelines and follow Choosing Wisely Canada recommendations. Design Descriptive study using data from the Alberta Ministry of Health Analytics and Performance Reporting Branch. Setting Alberta. Participants Women who had 1 or more Papanicolaou tests between 2011 and 2013. Main outcome measures Number of women aged 15 to 20 and those aged 70 and older who had 1 or more Pap tests in a 3-year period; year-to-year trends in screening rates for women in these 2 age groups; trends in screening rates in various geographic regions (ie, cities and zones) in Alberta; and the discipline of clinicians who ordered the Pap tests. Results Between 2011 and 2013, 805 632 women in the province of Alberta had 1 or more Pap tests for cervical cancer screening. Overall, 25 511 (17.5%) women aged 15 to 20 and 16 818 (10.3%) aged 70 and older were screened contrary to most existing guidelines. Screening rates varied markedly in different geographic regions of the province. Most Pap tests were ordered by family physicians or general practitioners. Conclusion Within the geographic regions of Alberta, provincial, national, and international guidelines for screening with Pap tests are inconsistently followed. This strongly echoes the need for clinicians and patients to consider the Choosing Wisely Canada recommendations and current guidelines for cervical cancer screening. PMID:29358254

  13. Indium Lung Disease

    PubMed Central

    Nakano, Makiko; Omae, Kazuyuki; Takeuchi, Koichiro; Chonan, Tatsuya; Xiao, Yong-long; Harley, Russell A.; Roggli, Victor L.; Hebisawa, Akira; Tallaksen, Robert J.; Trapnell, Bruce C.; Day, Gregory A.; Saito, Rena; Stanton, Marcia L.; Suarthana, Eva; Kreiss, Kathleen

    2012-01-01

    Background: Reports of pulmonary fibrosis, emphysema, and, more recently, pulmonary alveolar proteinosis (PAP) in indium workers suggested that workplace exposure to indium compounds caused several different lung diseases. Methods: To better understand the pathogenesis and natural history of indium lung disease, a detailed, systematic, multidisciplinary analysis of clinical, histopathologic, radiologic, and epidemiologic data for all reported cases and workplaces was undertaken. Results: Ten men (median age, 35 years) who produced, used, or reclaimed indium compounds were diagnosed with interstitial lung disease 4-13 years after first exposure (n = 7) or PAP 1-2 years after first exposure (n = 3). Common pulmonary histopathologic features in these patients included intraalveolar exudate typical of alveolar proteinosis (n = 9), cholesterol clefts and granulomas (n = 10), and fibrosis (n = 9). Two patients with interstitial lung disease had pneumothoraces. Lung disease progressed following cessation of exposure in most patients and was fatal in two. Radiographic data revealed that two patients with PAP subsequently developed fibrosis and one also developed emphysematous changes. Epidemiologic investigations demonstrated the potential for exposure to respirable particles and an excess of lung abnormalities among coworkers. Conclusions: Occupational exposure to indium compounds was associated with PAP, cholesterol ester crystals and granulomas, pulmonary fibrosis, emphysema, and pneumothoraces. The available evidence suggests exposure to indium compounds causes a novel lung disease that may begin with PAP and progress to include fibrosis and emphysema, and, in some cases, premature death. Prospective studies are needed to better define the natural history and prognosis of this emerging lung disease and identify effective prevention strategies. PMID:22207675

  14. Negative regulation of prophenoloxidase (proPO) activation by a clip-domain serine proteinase homolog (SPH) from endoparasitoid venom.

    PubMed

    Zhang, Guangmei; Lu, Zhi-Qiang; Jiang, Haobo; Asgari, Sassan

    2004-05-01

    Most parasitic wasps inject maternal factors into the host hemocoel to suppress the host immune system and ensure successful development of their progeny. Melanization is one of the insect defence mechanisms against intruding pathogens or parasites. We previously isolated from the venom of Cotesia rubecula a 50 kDa protein that blocked melanization in the hemolymph of its host, Pieris rapae [Insect Biochem. Mol. Biol. 33 (2003) 1017]. This protein, designated Vn50, is a serine proteinase homolog (SPH) containing an amino-terminal clip domain. In this work, we demonstrated that recombinant Vn50 bound P. rapae hemolymph components that were recognized by antisera to Tenebrio molitor prophenoloxidase (proPO) and Manduca sexta proPO-activating proteinase (PAP). Vn50 is stable in the host hemolymph-it remained intact for at least 72 h after parasitization. Using M. sexta as a model system, we found that Vn50 efficiently down-regulated proPO activation mediated by M. sexta PAP-1, SPH-1, and SPH-2. Vn50 did not inhibit active phenoloxidase (PO) or PAP-1, but it significantly reduced the proteolysis of proPO. If recombinant Vn50 binds P. rapae proPO and PAP (as suggested by the antibody reactions), it is likely that the molecular interactions among M. sexta proPO, PAP-1, and SPHs were impaired by this venom protein. A similar strategy might be employed by C. rubecula to negatively impact the proPO activation reaction in its natural host.

  15. Characterization of the regulatory network of BoMYB2 in controlling anthocyanin biosynthesis in purple cauliflower

    USDA-ARS?s Scientific Manuscript database

    Purple cauliflower (Brassica oleracea L. var. botrytis) Graffiti represents a unique mutant in conferring ectopic anthocyanin biosynthesis, which is caused by the tissue specific activation of BoMYB2, an ortholog of Arabidopsis PAP2 or MYB113. To gain a better understanding of the regulatory network...

  16. Management of ASCUS findings in Papanicolaou smears. A retrospective study.

    PubMed

    Iavazzo, C; Boutas, I; Grigoriadis, C; Vrachnis, N; Salakos, N

    2012-01-01

    Atypical squamous cells of undetermined significance (ASCUS) are a cervical cytologic finding category suggestive but not definitive of squamous intraepithelial lesions. ASCUS remains an incompletely described entity and accounts for even 5%-10% of reported Papanicolaou (Pap) smears. The management of women with such cytologic findings remains controversial. The aim of this study was to evaluate the cytology laboratory findings with regards to ASCUS diagnosis, using cervical Pap smears, and colposcopic biopsies, as well as their management. This is a retrospective study of patients with ASCUS Pap smears taken during the period January 2010 - December 2010 in the Second Department of Obstetrics and Gynecology, Aretaieion Hospital. During the study period, 657 Pap smears were examined at the Aretaieion Hospital; moreover, seven patients, whose Pap smears were cytologically diagnosed with ASCUS, were referred from other clinics, providing a total of 42 cases with a descriptive diagnosis of ASCUS for review. Of the 42 cases, eight were not studied because they were either lost in follow-up or they did not have available data. The remaining 34/42 patients were evaluated by colposcopic examination and directed biopsies where necessary. The ratio of ASCUS to low-grade squamous intraepithelial lesion (LGSIL), high-grade squamous cell intraepithelial lesion (HGSIL) or squamous cell carcinoma (SCC) was 5/34, 1/34, and 0/34, respectively. In the 34 ASCUS cases evaluated by colposcopy, the age distribution varied from 22 to 54 years. Eight of 34 cases did not have a child, 7/34 were primigravida, 18/34 were secondi-gravida, and 1/34 had four children. Four out of 34 cases were postmenopausal, 3/34 referred no history of abnormal bleeding, 21/34 were smokers, 6/34 used oral contraceptives, 2/34 used intrauterine devices, 1/34 took replacement of hormones, 4/34 had prior abnormal Pap smears human papillomavirus (HPV), or 1/34 had previous cancer (breast cancer). Colposcopy was inconclusive in 4/34 patients, while 8/34 cases were negative for Schiller and acetic acid tests and also had normal colposcopy. Infectious organisms were found in 8/34 patients with ASCUS, including actinomyces (1/8), trichomonas (5/8), and candida albicans (2/8). Histologic tests revealed 16/34 koilocytosis cases, 5/34 LGSIL, 1/34 HGSIL, and 0/34 SCC. The dilemma in the management of patients with an ASCUS diagnosis still exists as a significant problem for clinicians.

  17. Biochemical characterization of the triticale TsPAP1, a new type of plant prolyl aminopeptidase, and its impact on proline content and flowering time in transgenic Arabidopsis plants.

    PubMed

    Zdunek-Zastocka, Edyta; Grabowska, Agnieszka; Branicki, Tomasz; Michniewska, Beata

    2017-07-01

    Proline aminopeptidase (PAP, EC 3.4.11.5) is the only enzyme that effectively releases proline from the N-termini of peptides. The amino acid sequence of the PAP from Triticosecale, TsPAP1, comprises conserved regions, characteristic of the monomeric forms of PAP found in bacteria but not yet identified in plants. Therefore, we aimed to obtain and biochemically characterize the TsPAP1 protein. The recombinant TsPAP1 protein was received through heterologous expression of the TsPAP1 coding sequence in a bacterial expression system and purified with affinity chromatography. Gel filtration chromatography and SDS electrophoresis revealed that TsPAP1 is a monomer with a molecular mass of 37.5 kDa. TsPAP1 prefers substrates with proline at the N-terminus but is also capable of hydrolyzing β-naphthylamides of hydroxyproline and alanine. Among the peptides tested, the most preferred were di- and tripeptides, especially those with glycine in the Y position. The use of diagnostic inhibitors indicated that TsPAP1 is a serine peptidase; however, further characterization revealed that the SH residues are also important for maintaining its activity. To examine the role of TsPAP1 under physiological conditions, we developed transgenic Arabidopsis plants overexpressing TsPAP1. Compared with wild-type plants, the transgenic lines accumulated more proline, flowered an average of 3.5 days earlier, and developed more siliques than did untransformed controls. Our paper is the first to describe the biochemical properties of a novel monomeric plant PAP and contributes to the functional characterization of PAP proteins in plants. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  18. Awareness of Pap testing and factors associated with intent to undergo Pap testing by level of sexual experience in unmarried university students in Korea: results from an online survey

    PubMed Central

    2014-01-01

    Background Young and unmarried women have not been a target group for cervical cancer prevention in Korea. No previous studies have investigated the awareness of Pap testing, the intention to undergo Pap testing, or the factors associated with that intention, in this group of women. This information would be useful for an expansion in the focus of primary cervical cancer prevention. This study aimed to compare the awareness of Pap testing between groups of unmarried university students in Korea, and to investigate the factors associated with the intention to undergo Pap testing, by level of sexual experience. Methods A total of 475 unmarried university students who had never undergone a Pap test completed a web-based survey. Differences in awareness of the importance of the Pap test, confidence in Pap testing, intention to undergo the test, attitudes, subjective norms, perceived control, stigma, and shame by level of sexual experience were analysed using independent t-tests. Associations between measurement variables and intention to undergo Pap testing were analysed using correlation analysis. Variables yielding significant associations (p < 0.05) were included in a stepwise multiple regression model of intention to undergo Pap testing. Results Most participants perceived that the need for regular Pap testing was less important (score, 77.76) than other methods of cervical cancer prevention. They were not confident that is was an effective method of cervical cancer prevention for themselves (score, 59.56). There were differences in confidence in Pap testing and in the factors associated with intention to undergo Pap testing between sexually experienced and sexually inexperienced students. Regardless of level of sexual experience, the subjective norm was the most important predictor of intention to undergo Pap testing. Conclusions There was a low level of Pap screening awareness among the students. The factors associated with intention to undergo Pap testing differed by level of sexual experience. Social influence was an important factor that could be used to increase the intention to receive a Pap test in the university student population. Strategies to increase the intention to undergo Pap screening should be introduced and should be adapted to the level of sexual experience. PMID:25163938

  19. Clinical progress of human papillomavirus genotypes and their persistent infection in subjects with atypical squamous cells of undetermined significance cytology: Statistical and latent Dirichlet allocation analysis

    PubMed Central

    Kim, Yee Suk; Lee, Sungin; Zong, Nansu; Kahng, Jimin

    2017-01-01

    The present study aimed to investigate differences in prognosis based on human papillomavirus (HPV) infection, persistent infection and genotype variations for patients exhibiting atypical squamous cells of undetermined significance (ASCUS) in their initial Papanicolaou (PAP) test results. A latent Dirichlet allocation (LDA)-based tool was developed that may offer a facilitated means of communication to be employed during patient-doctor consultations. The present study assessed 491 patients (139 HPV-positive and 352 HPV-negative cases) with a PAP test result of ASCUS with a follow-up period ≥2 years. Patients underwent PAP and HPV DNA chip tests between January 2006 and January 2009. The HPV-positive subjects were followed up with at least 2 instances of PAP and HPV DNA chip tests. The most common genotypes observed were HPV-16 (25.9%, 36/139), HPV-52 (14.4%, 20/139), HPV-58 (13.7%, 19/139), HPV-56 (11.5%, 16/139), HPV-51 (9.4%, 13/139) and HPV-18 (8.6%, 12/139). A total of 33.3% (12/36) patients positive for HPV-16 had cervical intraepithelial neoplasia (CIN)2 or a worse result, which was significantly higher than the prevalence of CIN2 of 1.8% (8/455) in patients negative for HPV-16 (P<0.001), while no significant association was identified for other genotypes in terms of genotype and clinical progress. There was a significant association between clearance and good prognosis (P<0.001). Persistent infection was higher in patients aged ≥51 years (38.7%) than in those aged ≤50 years (20.4%; P=0.036). Progression from persistent infection to CIN2 or worse (19/34, 55.9%) was higher than clearance (0/105, 0.0%; P<0.001). In the LDA analysis, using symmetric Dirichlet priors α=0.1 and β=0.01, and clusters (k)=5 or 10 provided the most meaningful groupings. Statistical and LDA analyses produced consistent results regarding the association between persistent infection of HPV-16, old age and long infection period with a clinical progression of CIN2 or worse. Therefore, LDA results may be presented as explanatory evidence during time-constrained patient-doctor consultations in order to deliver information regarding the patient's status. PMID:28587376

  20. Using probabilistic record linkage methods to identify Australian Indigenous women on the Queensland Pap Smear Register: the National Indigenous Cervical Screening Project.

    PubMed

    Whop, Lisa J; Diaz, Abbey; Baade, Peter; Garvey, Gail; Cunningham, Joan; Brotherton, Julia M L; Canfell, Karen; Valery, Patricia C; O'Connell, Dianne L; Taylor, Catherine; Moore, Suzanne P; Condon, John R

    2016-02-12

    To evaluate the feasibility and reliability of record linkage of existing population-based data sets to determine Indigenous status among women receiving Pap smears. This method may allow for the first ever population measure of Australian Indigenous women's cervical screening participation rates. A linked data set of women aged 20-69 in the Queensland Pap Smear Register (PSR; 1999-2011) and Queensland Cancer Registry (QCR; 1997-2010) formed the Initial Study Cohort. Two extracts (1995-2011) were taken from Queensland public hospitals data (Queensland Hospital Admitted Patient Data Collection, QHAPDC) for women, aged 20-69, who had ever been identified as Indigenous (extract 1) and had a diagnosis or procedure code relating to cervical cancer (extract 2). The Initial Study Cohort was linked to extract 1, and women with cervical cancer in the initial cohort were linked to extract 2. The proportion of women in the Initial Cohort who linked with the extracts (true -pairs) is reported, as well as the proportion of potential pairs that required clerical review. After assigning Indigenous status from QHAPDC to the PSR, the proportion of women identified as Indigenous was calculated using 4 algorithms, and compared. There were 28,872 women (2.1%) from the Initial Study Cohort who matched to an ever Indigenous record in extract 1 (n=76,831). Women with cervical cancer in the Initial Study Cohort linked to 1385 (71%) records in extract 2. The proportion of Indigenous women ranged from 2.00% to 2.08% when using different algorithms to define Indigenous status. The Final Study Cohort included 1,372,823 women (PSR n=1,374,401; QCR n=1955), and 5,062,118 records. Indigenous status in Queensland cervical screening data was successfully ascertained through record linkage, allowing for the crucial assessment of the current cervical screening programme for Indigenous women. Our study highlights the need to include Indigenous status on Pap smear request and report forms in any renewed and redesigned cervical screening programme in Australia. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  1. Physical Activity on Prescription with Counsellor Support: A 4-Year Registry-Based Study in Routine Health Care in Sweden.

    PubMed

    Andersen, Pia; Holmberg, Sara; Lendahls, Lena; Nilsen, Per; Kristenson, Margareta

    2018-04-16

    Background : Public health gains from physical activity on prescription (PAP) depend on uptake in routine care. We performed an evaluation of the implementation, in a Swedish county council, of counsellors who give personalized support to PAP recipients aimed at facilitating PAP delivery. The aim was to compare characteristics between PAP recipients and the health care population as well as between PAP recipients who used and did not use counsellor support. We also investigated professional belonging and health care setting of health care professionals who prescribed PAP. Methods: All patients’ ≥18 years who received PAP during 2009–2012 in primary and secondary care in the County Council of Kronoberg were included ( n = 4879). Data were retrieved from electronic medical records. Main outcome measures were patient and professional characteristics. Results: A third of the PAP recipients had diseases in ≥5 diagnostic groups and more than half had ≥11 office visits the year before receiving PAP. Counsellor support was used by one-third and PAP recipients who used counsellor support had more multiple diagnoses and office visits compared with non-users. Physicians issued 44% of prescriptions and primary care was the predominant setting. The amount of PAP did not change over time, but the proportion of physicians’ prescriptions decreased while the proportion of nurses’ prescriptions increased. Conclusions: PAP recipients had high morbidity and were frequent health care attenders, indicating that PAP was predominantly used for secondary or tertiary prevention. PAP rates did not increase as intended after the implementation of counsellor support.

  2. Three-year risk of high-grade CIN for women aged 30 years or older who undergo baseline Pap cytology and HPV co-screening.

    PubMed

    Guo, Ming; Khanna, Abha; Wang, Jianping; Dawlett, Marilyn A; Kologinczak, Teresa L; Lyons, Genevieve R; Bassett, Roland L; Sneige, Nour; Gong, Yun; Bevers, Therese B

    2017-08-01

    Papanicolaou (Pap) cytology and high-risk human papillomavirus (HPV) DNA cotesting for women aged ≥30 years are recommended for the prevention of cervical cancer. The objective of the current study was to evaluate the efficacy of this cotesting for predicting the risk of high-grade cervical intraepithelial neoplasia 3 (CIN3) during a 3-year follow-up period. A retrospective database search identified women aged ≥30 years who had baseline HPV and Pap cytology cotesting results in 2007 or 2008 and for whom 3-year follow-up results were available. The cumulative 3-year risks of developing CIN-3 were calculated. The 3-year follow-up data after baseline Pap/HPV cotesting were available for 1986 women (mean age, 53 years). Of the 1668 women who had a baseline Pap-negative (Pap-)/HPV- cotesting result, 1561 (93.6%) had a follow-up Pap cytology result that was negative for intraepithelial lesions or malignancy. Of the 1530 women who had follow-up Pap/HPV cotesting, 1504 (98.3%) had a Pap-/HPV- result. The 3-year cumulative risk of developing CIN-3 was found to be highest for women with a baseline Pap-positive (Pap+)/HPV+ cotesting result (12.5%); the risk of CIN-3 was lower in those with a Pap-/HPV+ result (1.5%; P = .0032) or a Pap-/HPV- result (0.06%; P<.0001). The 3-year cumulative risk of CIN-3 was found to be significantly greater for women with an HPV+ result (4.8%) compared with those with an HPV- result (0.06%; P<.0001). Pap cytology and HPV cotesting are valuable for stratifying CIN-3 risk. Pap cytology and HPV co-screening at a 3-year screening interval appears to carry a low risk of CIN-3 for women who have a baseline Pap-/HPV- cotesting result. Cancer Cytopathol 2017;125:644-51. © 2017 American Cancer Society. © 2017 American Cancer Society.

  3. Decision making for Pap testing among Pacific Islander women.

    PubMed

    Weiss, Jie W; Mouttapa, Michele; Sablan-Santos, Lola; DeGuzman Lacsamana, Jasmine; Quitugua, Lourdes; Park Tanjasiri, Sora

    2016-12-01

    This study employed a Multi-Attribute Utility (MAU) model to examine the Pap test decision-making process among Pacific Islanders (PI) residing in Southern California. A total of 585 PI women were recruited through social networks from Samoan and Tongan churches, and Chamorro family clans. A questionnaire assessed Pap test knowledge, beliefs and past behaviour. The three MAU parameters of subjective value, subjective probability and momentary salience were measured for eight anticipated consequences of having a Pap test (e.g., feeling embarrassed, spending money). Logistic regression indicated that women who had a Pap test (Pap women) had higher total MAU utility scores compared to women who had not had a Pap test within the past three years (No Pap women) (adjusted Odds Ratio = 1.10). In particular, Pap women had higher utilities for the positive consequences 'Detecting cervical cancer early, Peace of mind, and Protecting my family', compared to No Pap women. It is concluded that the connection between utility and behaviour offers a promising pathway toward a better understanding of the decision to undergo Pap testing. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  4. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Konishi, Hiroyuki, E-mail: konishi@med.osaka-cu.ac.jp; The 21st Century COE Program 'Base to Overcome Fatigue', Osaka City University Graduate School of Medicine, Osaka; Department of Anatomy and Neuroscience, Nagoya University, Graduate School of Medicine, Nagoya

    Research highlights: {yields} We focused on the rat pituitary intermediate lobe (IL) under continuous stress (CS). {yields} CS induced PAP-I and PAP-II expression in melanotrophs of the IL. {yields} This gene induction was triggered by CS-related dopamine dysregulation. {yields} PAP-I and PAP-II may sustain homeostasis of the IL under CS. -- Abstract: Under continuous stress (CS) in rats, melanotrophs, the predominant cell-type in the intermediate lobe (IL) of the pituitary, are hyperactivated to secrete {alpha}-melanocyte-stimulating hormone and thereafter degenerate. Although these phenomena are drastic, the molecular mechanisms underlying the cellular changes are mostly unknown. In this study, we focused onmore » the pancreatitis-associated protein (PAP) family members of the secretory lectins and characterized their expression in the IL of CS model rats because we had identified two members of this family as up-regulated genes in our previous microarray analysis. RT-PCR and histological studies demonstrated that prominent PAP-I and PAP-II expression was induced in melanotrophs in the early stages of CS, while another family member, PAP-III, was not expressed. We further examined the regulatory mechanisms of PAP-I and PAP-II expression and revealed that both were induced by the decreased dopamine levels in the IL under CS. Because the PAP family members are implicated in cell survival and proliferation, PAP-I and PAP-II secreted from melanotrophs may function to sustain homeostasis of the IL under CS conditions in an autocrine or a paracrine manner.« less

  5. Accuracy of Doppler echocardiographic estimates of pulmonary artery pressures in a canine model of pulmonary hypertension

    PubMed Central

    Soydan, Lydia C.; Kellihan, Heidi B.; Bates, Melissa L.; Stepien, Rebecca L.; Consigny, Daniel W.; Bellofiore, Alessandro; Francois, Christopher J.; Chesler, Naomi C.

    2015-01-01

    Objectives To compare noninvasive estimates of pulmonary artery pressure (PAP) obtained via echocardiography (ECHO) to invasive measurements of PAP obtained during right heart catheterization (RHC) across a wide range of PAP, to examine the accuracy of estimating right atrial pressure via ECHO (RAPECHO) compared to RAP measured by catheterization (RAPRHC), and to determine if adding RAPECHO improves the accuracy of noninvasive PAP estimations. Animals Fourteen healthy female beagle dogs. Methods ECHO and RHC performed at various data collection points, both at normal PAP and increased PAP (generated by microbead embolization). Results Noninvasive estimates of PAP were moderately but significantly correlated with invasive measurements of PAP. A high degree of variance was noted for all estimations, with increased variance at higher PAP. The addition of RAPECHO improved correlation and bias in all cases. RAPRHC was significantly correlated with RAPECHO and with subjectively assessed right atrial size (RA sizesubj). Conclusions Spectral Doppler assessments of tricuspid and pulmonic regurgitation are imperfect methods for predicting PAP as measured by catheterization despite an overall moderate correlation between invasive and noninvasive values. Noninvasive measurements may be better utilized as part of a comprehensive assessment of PAP in canine patients. RAPRHC appears best estimated based on subjective assessment of RA size. Including estimated RAPECHO in estimates of PAP improves the correlation and relatedness between noninvasive and invasive measures of PAP, but notable variability in accuracy of estimations persists. PMID:25601540

  6. Identifying priorities to improve paediatric in-hospital antimicrobial use by cross-sectional evaluation of prevalence and appropriateness of prescription.

    PubMed

    Goycochea-Valdivia, Walter Alfredo; Moreno-Ramos, Francisco; Paño-Pardo, José Ramón; Aracil-Santos, Francisco Javier; Baquero-Artigao, Fernando; Del Rosal-Rabes, Teresa; Mellado-Peña, María José; Escosa-García, Luis

    2017-11-01

    Information about paediatric in-hospital antimicrobial usage and prescribing patterns to guide improvement strategies is scant. We aim to use an evaluation of the prevalence and appropriateness of antimicrobial prescription to identify antimicrobial stewardship priorities in children. A cross-sectional point study was performed on hospitalised paediatric patients in a Spanish tertiary hospital, assessing the prevalence of antimicrobial prescription (PAP) and appropriateness of antimicrobial prescription (AAP). AAP was defined as a correct indication plus an appropriate prescribing pattern (dose, spectrum and interval). Evaluation was performed using established antimicrobial guidelines. Other factors that may have a bearing on antimicrobial prescription were also analysed. A total of 171 patients were included. PAP was 49.7% (85/171) and AAP was 60.9% (91/161). The most common indications for antimicrobial use were antimicrobial prophylaxis (28.3%, 32/113) and pneumonia (8.2%, 8/113). Overall, 161 antimicrobials were prescribed (1.9 antimicrobials per patient): 55.3% (89/161) were empiric, 16.1% (26/161) were targeted and 28.6% (46/161) were prophylactic. Amoxicillin/clavulanate (8.2%, 14/171) and sulfamethoxazole/trimethoprim (8.2%, 14/171) were the most prescribed antimicrobials. The prescription of antifungals (11.7%, 20/171) and antivirals (1.8%, 3/171) was analysed. Major causes of inappropriate antibiotic use were prolonged prescriptions (21.7%, 35/161) and use of agents with an excessively broad coverage spectrum (21.1%, 34/161). PAP and AAP varied between wards and antimicrobials. Measurement of PAP and AAP offers valuable information for detecting priorities in hospital settings and monitoring antimicrobial usage prior to the development of antimicrobial stewardship programmes. In our setting, the main areas for improvement are duration of therapy and proper use of broad-spectrum antimicrobials. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  7. Sexual orientation and sexual health services utilization among women in the United States

    PubMed Central

    Agénor, Madina; Muzny, Christina A.; Schick, Vanessa; Austin, Erika L.; Potter, Jennifer

    2017-01-01

    Although sexual minority women are at risk of sexually transmitted infections (STIs) and cervical cancer, few nationally representative studies have assessed sexual orientation disparities in sexual health care among women. Using data from the 2011–2013 and 2013–2015 waves of the National Survey of Family Growth, which provide a national probability sample of U.S. women aged 15–44 years (N=11,300), we used multivariable logistic regression to examine the associations between sexual behavior and sexual identity (modeled separately) and STI testing in the past year, Pap test use in the last 3 years, lifetime HIV testing, and lifetime human papillomavirus (HPV) testing. Women with male and female lifetime sexual partners had higher adjusted odds of being tested for STIs ([odds ratio:] 1.61; [95% confidence interval:] 1.37–1.89), HIV (1.66; 1.29–2.14), and HPV (1.79; 1.41–2.25) and similar adjusted odds of obtaining a Pap test (0.98; 0.76–1.27) than women with only male lifetime sexual partners. Self-identified bisexual women had higher adjusted odds of obtaining an STI (1.43; 1.10–1.86) and HIV (1.69; 1.24–2.30) test but lower adjusted odds of obtaining a Pap test in the last 3 years (0.66; 0.47–0.93) than heterosexual-identified women. Women with only female lifetime sexual partners had lower adjusted odds of receiving an STI (0.14; 0.07–0.28) and Pap (0.10; 0.03–0.27) test than women with only male lifetime sexual partners. Results comparing self-identified lesbian and heterosexual women were similar. Health care facilities should monitor and address sexual orientation disparities in women’s sexual health care and ensure the provision of high-quality sexual health services to all women. PMID:27932056

  8. Sexual orientation and sexual health services utilization among women in the United States.

    PubMed

    Agénor, Madina; Muzny, Christina A; Schick, Vanessa; Austin, Erika L; Potter, Jennifer

    2017-02-01

    Although sexual minority women are at risk of sexually transmitted infections (STIs) and cervical cancer, few nationally representative studies have assessed sexual orientation disparities in sexual health care among women. Using data from the 2011-2013 and 2013-2015 waves of the National Survey of Family Growth, which provide a national probability sample of U.S. women aged 15-44years (N=11,300), we used multivariable logistic regression to examine the associations between sexual behavior and sexual identity (modeled separately) and STI testing in the past year, Pap test use in the last 3years, lifetime HIV testing, and lifetime human papillomavirus (HPV) testing. Women with male and female lifetime sexual partners had higher adjusted odds of being tested for STIs ([odds ratio:] 1.61; [95% confidence interval:] 1.37-1.89), HIV (1.66; 1.29-2.14), and HPV (1.79; 1.41-2.25) and similar adjusted odds of obtaining a Pap test (0.98; 0.76-1.27) than women with only male lifetime sexual partners. Self-identified bisexual women had higher adjusted odds of obtaining an STI (1.43; 1.10-1.86) and HIV (1.69; 1.24-2.30) test but lower adjusted odds of obtaining a Pap test in the last 3years (0.66; 0.47-0.93) than heterosexual-identified women. Women with only female lifetime sexual partners had lower adjusted odds of receiving an STI (0.14; 0.07-0.28) and Pap (0.10; 0.03-0.27) test than women with only male lifetime sexual partners. Results comparing self-identified lesbian and heterosexual women were similar. Health care facilities should monitor and address sexual orientation disparities in women's sexual health care and ensure the provision of high-quality sexual health services to all women. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Pressure-Flow During Exercise Catheterization Predicts Survival in Pulmonary Hypertension.

    PubMed

    Hasler, Elisabeth D; Müller-Mottet, Séverine; Furian, Michael; Saxer, Stéphanie; Huber, Lars C; Maggiorini, Marco; Speich, Rudolf; Bloch, Konrad E; Ulrich, Silvia

    2016-07-01

    Pulmonary hypertension manifests with impaired exercise capacity. Our aim was to investigate whether the mean pulmonary arterial pressure to cardiac output relationship (mPAP/CO) predicts transplant-free survival in patients with pulmonary arterial hypertension (PAH) and inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Hemodynamic data according to right heart catheterization in patients with PAH and CTEPH at rest and during supine incremental cycle exercise were analyzed. Transplant-free survival and predictive value of hemodynamics were assessed by using Kaplan-Meier and Cox regression analyses. Seventy patients (43 female; 54 with PAH, 16 with CTEPH; median (quartiles) age, 65 [50; 73] years; mPAP, 34 [29; 44] mm Hg; cardiac index, 2.8 [2.3; 3.5] [L/min]/m(2)) were followed up for 610 (251; 1256) days. Survival at 1, 3, 5, and 7 years was 89%, 81%, 71%, and 59%. Age, World Health Organization-functional class, 6-min walk test, and mixed-venous oxygen saturation (but not resting hemodynamics) predicted transplant-free survival. Maximal workload (hazard ratio [HR], 0.94 [95% CI, 0.89-0.99]; P = .027), peak cardiac index (HR, 0.51 [95% CI, 0.27-0.95]; P = .034), change in cardiac index, 0.25 [95% CI, 0.06-0.94]; P = .040), and mPAP/CO (HR, 1.02 [95% CI, 1.01-1.03]; P = .003) during exercise predicted survival. Values for mPAP/CO predicted 3-year transplant-free survival with an area under the curve of 0.802 (95% CI, 0.66-0.95; P = .004). In this collective of patients with PAH or CTEPH, the pressure-flow relationship during exercise predicted transplant-free survival and correlated with established markers of disease severity and outcome. Right heart catheterization during exercise may provide important complementary prognostic information in the management of pulmonary hypertension. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  10. Acute Effects of Drop-Jump Protocols on Explosive Performances of Elite Handball Players.

    PubMed

    Dello Iacono, Antonio; Martone, Domenico; Padulo, Johnny

    2016-11-01

    Dello Iacono, A, Martone, D, and Padulo, J. Acute effects of drop-jump protocols on explosive performances of elite handball players. J Strength Cond Res 30(11): 3122-3133, 2016-This study aimed to assess the acute effects of vertical and horizontal drop jump-based postactivation potentiation (PAP) protocols on neuromuscular abilities in tasks such as jumping, sprinting, and change of direction (COD). Eighteen handball players were assessed before and after PAP regimens, consisting of either vertical single-leg drop-jumps (VDJ) or horizontal single-leg drop-jumps (HDJ) single-leg drop-jumps, on countermovement jump (CMJ), linear sprint, shuttle sprint, and agility performance. The HDJ led to greater improvement of the COD performance in comparison with the VDJ (-6.8 vs. -1.3%; p ≤ 0.05), whereas the VDJ caused greater improvement in the CMJ task compared with the HDJs (+6.5 vs. +1%; p ≤ 0.05). Moreover, the VDJ regimens compared with HDJ induced greater changes in most of the kinetic variables associated with vertical jumping performance, such as peak ground reaction forces (+9.6 vs. +1.3%), vertical displacement (-13.4 vs. -5.3%), leg-spring stiffness (+18.6 vs. +3.6%), contact time (-9.2 vs. -1.3%), and reactive strength index (+7.3 vs. +2.4%) (all comparisons with p ≤ 0.05). Conversely, the HDJ regimens were able to improve the COD performance only by reducing the contact time on COD more than the VDJ (-13.3 vs. -2.4% with p ≤ 0.05). The results showed that both PAPs were able to improve the performances that specifically featured similar force-orientation production. This investigation showed the crucial role that different and specific PAP regimens play in optimizing related functional performances. Specifically oriented vertical and horizontal single-leg drop-jump protocols represent viable means for achieving enhanced explosive-based tasks such as jumping and COD.

  11. Phenology, growth and physiological adjustments of oil palm (Elaeis guineensis) to sink limitation induced by fruit pruning

    PubMed Central

    Legros, S.; Mialet-Serra, I.; Caliman, J.-P.; Siregar, F. A.; Clement-Vidal, A.; Fabre, D.; Dingkuhn, M.

    2009-01-01

    Background and Aims Despite its simple architecture and small phenotypic plasticity, oil palm has complex phenology and source–sink interactions. Phytomers appear in regular succession but their development takes years, involving long lag periods between environmental influences and their effects on sinks. Plant adjustments to resulting source–sink imbalances are poorly understood. This study investigated oil palm adjustments to imbalances caused by severe fruit pruning. Methods An experiment with two treatments (control and complete fruit pruning) during 22 months in 2006–2008) and six replications per treatment was conducted in Indonesia. Phenology, growth of above-ground vegetative and reproductive organs, leaf morphology, inflorescence sex differentiation, dynamics of non-structural carbohydrate reserves and light-saturated net photosynthesis (Amax) were monitored. Key Results Artificial sink limitation by complete fruit pruning accelerated development rate, resulting in higher phytomer, leaf and inflorescence numbers. Leaf size and morphology remained unchanged. Complete fruit pruning also suppressed the abortion of male inflorescences, estimated to be triggered at about 16 months before bunch maturity. The number of female inflorescences increased after an estimated lag of 24–26 months, corresponding to time from sex differentiation to bunch maturity. The most important adjustment process was increased assimilate storage in the stem, attaining nearly 50 % of dry weight in the stem top, mainly as starch, whereas glucose, which in controls was the most abundant non-structural carbohydrate stored in oil palm, decreased. Conclusions The development rate of oil palm is in part controlled by source–sink relationships. Although increased rate of development and proportion of female inflorescences constituted observed adjustments to sink limitation, the low plasticity of plant architecture (constant leaf size, absence of branching) limited compensatory growth. Non-structural carbohydrate storage was thus the main adjustment process. PMID:19748908

  12. Young Singaporean women's knowledge of cervical cancer and pap smear screening: a descriptive study.

    PubMed

    Shea, Juanna; Klainin-Yobas, Piyanee; Mackey, Sandra

    2013-12-01

    To assess the knowledge of young female Singaporeans regarding cervical cancer and pap smear, the intention to participate in pap smear and whether there is any relationship between knowledge and intention to participate in pap smear screening. While cervical cancer has poor prognosis in the later stages, pap smear is effective in identifying precancerous lesions, which are more treatable. Pap smear screening is available to women in Singapore, but its uptake is opportunistic. Research has shown that knowledge about pap smear and cervical cancer is important determinant of screening behaviour in Singaporean women. Cross-sectional descriptive correlational design was used. Three hundred and ninety-three young Singaporean undergraduates, aged 18-25 years, were recruited via convenience sampling from a local university over a four-month period. Data were collected through self-administered questionnaires. Majority of the participants knew the term 'pap smear' and its function. However, knowledge of the risk factors for cervical cancer was lacking among the young women. Knowledge of pap smear and cervical cancer had a weak correlation with the intention to go for the future uptake of pap smear. Educational efforts among younger Singaporean women on the knowledge of pap smear and risk factors for cervical cancer are needed. Improving knowledge will enable them to understand the importance of reducing exposure to risk factors and regular pap smear screening. All health professionals working with young Asian women should be prepared to educate and counsel young women to participate in pap smear screening according to current guidelines. In particular, knowledge of the age to attend the first pap smear and the recommended frequency for screening need to be targeted for health education. © 2013 John Wiley & Sons Ltd.

  13. HIP/PAP accelerates liver regeneration and protects against acetaminophen injury in mice.

    PubMed

    Lieu, Hanh-Tu; Batteux, Frédéric; Simon, Marie-Thérèse; Cortes, Alexandre; Nicco, Carole; Zavala, Flora; Pauloin, Alain; Tralhao, José Guilherme; Soubrane, Olivier; Weill, Bernard; Bréchot, Christian; Christa, Laurence

    2005-09-01

    Human hepatocarcinoma-intestine-pancreas/pancreatic-associated protein HIP/PAP is a secreted C-type lectin belonging to group VII, according to Drickamer's classification. HIP/PAP is overexpressed in liver carcinoma; however, its functional role remains unclear. In this study, we demonstrate that HIP/PAP is a paracrine hepatic growth factor promoting both proliferation and viability of liver cells in vivo. First, a low number of implanted hepatocytes deriving from HIP/PAP-transgenic mice (<1:1,000) was sufficient to stimulate overall recipient severe combined immunodeficiency liver regeneration after partial hepatectomy. After a single injection of HIP/PAP protein, the percentages of bromodeoxyuridine-positive nuclei and mitosis were statistically higher than after saline injection, indicating that HIP/PAP acts as a paracrine mitogenic growth factor for the liver. Comparison of the early events posthepatectomy in control and transgenic mice indicated that HIP/PAP accelerates the accumulation/degradation of nuclear phospho-signal transducer activator transcription factor 3 and tumor necrosis factor alpha level, thus reflecting that HIP/PAP accelerates liver regeneration. Second, we showed that 80% of the HIP/PAP-transgenic mice versus 25% of the control mice were protected against lethal acetaminophen-induced fulminate hepatitis. A single injection of recombinant HIP/PAP induced a similar cytoprotective effect, demonstrating the antiapoptotic effect of HIP/PAP. Comparison of Cu/Zn superoxide dismutase activity and glutathione reductase-like effects in control and transgenic liver mice indicated that HIP/PAP exerts an antioxidant activity and prevents reactive oxygen species-induced mitochondrial damage by acetaminophen overdose. In conclusion, the present data offer new insights into the biological functions of C-type lectins. In addition, HIP/PAP is a promising candidate for the prevention and treatment of liver failure.

  14. p-Aminophenol-induced liver toxicity: tentative evidence of a role for acetaminophen.

    PubMed

    Song, H; Chen, T S

    2001-01-01

    p-Aminophenol (PAP) is a widely used industrial chemical and a metabolite of analgesics, such as acetaminophen (APAP). It was found recently that PAP, a known nephrotoxicant, could cause acute hepatotoxicity in mice but not in rats. The mechanism of hepatotoxicity is not known. The aim of this study was to investigate the role of N-acetylation of PAP to APAP in PAP-induced toxicity. Male C57BL/6 mice injected intraperitoneally (i.p.) with various doses of PAP were sacrificed at 12 hours for measurement of serum glutamic-pyruvic transaminase (GPT) and sorbitol dehydrogenase (SDH) levels and determination of the extent of hepatic nonprotein sulfhydryl (NPSH) and glutathione (GSH) depletion. Plasma levels of APAP and its metabolites were measured by HPLC after PAP administration. p-Aminophenol depleted NPSH in a dose- and time-dependent manner. Depletion of NPSH in mouse liver occurred at PAP doses above 400 mg/kg. Buthionine sulfoximine (BSO), an inhibitor of GSH synthesis, potentiated the PAP-induced hepatotoxicity. Ascorbate, a reducing agent, did not affect PAP-induced hepatotoxicity and NPSH depletion. After PAP treatment, APAP and its sulfate and glucuronide conjugates as well as GSH conjugates (APAP-cysteine and APAP-mercapturate) were detected in the plasma. The results suggest the roles of GSH and N-acetylation of PAP to APAP in PAP-induced hepatotoxicity.

  15. Influencing Factors of Intention to Receive Pap Tests in Vietnamese Women who Immigrated to Taiwan for Marriage.

    PubMed

    Lee, Fang-Hsin; Wang, Hsiu-Hung; Yang, Yung-Mei; Huang, Joh-Jong; Tsai, Hsiu-Min

    2016-09-01

    This study aimed to explore the factors associated with the intention to receive a Pap test among married immigrant women of Vietnamese origin living in Taiwan. This was a cross-sectional community-based study. We enrolled 281 women aged 30 years and over in the study, from July 2013 to January 2014. The participants' characteristics, cervical cancer knowledge, Pap test knowledge, attitudes toward cervical cancer, barriers to receiving a Pap test, fatalism, and intention to receive a Pap test, were measured using self-report questionnaires. Hierarchical multiple regression analyses were performed to examine the variables associated with participants' intentions to receive a Pap test. Vietnamese women with low scores on the measures of cervical cancer knowledge and perceived barriers to receiving a Pap test were more willing to receive the test, as were those with high scores on the measures of Pap test knowledge and fatalism. Women who received a Pap test in the previous year were more willing to receive a Pap test within the next 3 years. Preventive healthcare for immigrant women should be a focus of nurses. The development of culturally appropriate health education and strategies should enhance their knowledge of Pap tests and reduce perceived barriers to Pap test participation. This study's results can be a reference for nurses who work with immigrant women. Copyright © 2016. Published by Elsevier B.V.

  16. Reflexes from pulmonary arterial baroreceptors in dogs: interaction with carotid sinus baroreceptors

    PubMed Central

    Moore, Jonathan P; Hainsworth, Roger; Drinkhill, Mark J

    2011-01-01

    Abstract In contrast to the reflex vasodilatation occurring in response to stimulation of baroreceptors in the aortic arch, carotid sinuses and coronary arteries, stimulation of receptors in the wall of pulmonary arteries results in reflex systemic vasoconstriction. It is rare for interventions to activate only one reflexogenic region, therefore we investigated how these two types of reflexes interact. In anaesthetized dogs connected to cardiopulmonary bypass, reflexogenic areas of the carotid sinuses, aortic arch and coronary arteries and the pulmonary artery were subjected to independently controlled pressures. Systemic perfusion pressure (SPP) measured in the descending aorta (constant flow) provided an index of systemic vascular resistance. In other experiments, sympathetic efferent neural activity was recorded in fibres dissected from the renal nerve (RSNA). Physiological increases in pulmonary arterial pressure (PAP) induced significant increases in SPP (+39.1 ± 10.4 mmHg) and RSNA (+17.6 ± 2.2 impulses s−1) whereas increases in carotid sinus pressure (CSP) induced significant decreases in SPP (−42.6 ± 10.8 mmHg) and RSNA (−42.8 ± 18.2 impulses s−1) (P < 0.05 for each comparison; paired t test). To examine possible interactions, PAP was changed at different levels of CSP in both studies. With CSP controlled at 124 ± 2 mmHg, the threshold, ‘set point’ and saturation pressures of the PAP–SPP relationship were higher than those with CSP at 60 ± 1 mmHg; this rightward shift was associated with a significant decrease in the reflex gain. Similarly, increasing CSP produced a rightward shift of the PAP–RSNA relationship, although the effect on reflex gain was inconsistent. Furthermore, the responses to changes in CSP were influenced by setting PAP at different levels; increasing the level of PAP from 5 ± 1 to 33 ± 3 mmHg significantly increased the set point and threshold pressures of the CSP–SPP relationship; the reflex gain was not affected. These results indicate the existence of interaction between pulmonary arterial and carotid sinus baroreceptor reflexes; physiological and pathological states that alter the stimulus to one may alter the reflex responses from the other. PMID:21690195

  17. Assessment of right ventricular longitudinal strain by 2D speckle tracking imaging compared with RV function and hemodynamics in pulmonary hypertension.

    PubMed

    Li, Yidan; Wang, Yidan; Meng, Xiangli; Zhu, Weiwei; Lu, Xiuzhang

    2017-11-01

    The right ventricular longitudinal strain (RVLS) of pulmonary hypertension (PH) patients and its relationship with RV function parameters measured by echocardiography and hemodynamic parameters measured by right heart catheterization was investigated. According to the WHO functional class (FC), 66 PH patients were divided into FC I/II (group 1) and III/IV (group 2). RV function parameters were measured by echocardiographic examinations. Hemodynamic parameters were obtained by right heart catheterization. Patients in group 2 had higher systolic pulmonary artery pressure (sPAP; P < 0.05) than patients in group (1) significant between-group differences were observed in global RVLS (RVLS global ), free wall RVLS (RVLS FW ; P < 0.01), and RV conventional function parameters (all P < 0.05). Moreover, mPAP and PVR increased remarkably and CI decreased significantly in group (2) RVLS global had a positive correlation with 6-min walking distance (6MWD; r = 0.492, P < 0.001) and N-terminal pro-brain natriuretic peptide (NT-proBNP; r = 0.632, P < 0.001), while RVLS FW had a positive correlation with 6MWD (r = 0.483, P < 0.001) and NT-proBNP (r = 0.627, P < 0.001). Hemodynamics analysis revealed that RVLS global had a positive correlation with mPAP (r = 0.594, P < 0.001), PVR (r = 0.573, P < 0.001) and CI (r = 0.366, P = 0.003), while RVLS FW had a positive correlation with mPAP (r = 0.597, P < 0.001), PVR (r = 0.577, P < 0.001) and CI (r = 0.369, P = 0.002). According to receiver operating characteristic curves, the optimal cut-off values of RVLS global (-15.0%) and RVLS FW (-15.3%) for prognosis detection with good sensitivity and specificity. Evidence has shown that RVLS measurement can provide the much-needed and reliable information on RV function and hemodynamics. Therefore, this qualifies as a patient-friendly approach for the clinical management of PH patients.

  18. Bi-level CPAP does not improve gas exchange when compared with conventional CPAP for the treatment of neonates recovering from respiratory distress syndrome.

    PubMed

    Lampland, Andrea L; Plumm, Brenda; Worwa, Cathy; Meyers, Patricia; Mammel, Mark C

    2015-01-01

    We hypothesised that short-term application of bi-level nasal continuous positive airway pressure CPAP (SiPAP) compared with conventional nasal CPAP (nCPAP) at the same mean airway pressure in infants with persistent oxygen need recovering from respiratory distress syndrome would improve CO2 removal with no change in oxygen requirement. Non-blinded, randomised, observational four-period crossover study. Level III NICU; low-birthweight infants requiring CPAP and oxygen while recovering from respiratory distress syndrome. Infants requiring nasal CPAP for >24 h prior to study enrolment, and fraction of inspired oxygen requirement (FiO2) of 0.25-0.5, were randomised to either nCPAP or SiPAP. A crossover design with four 1 h treatment periods was used such that each infant received both treatments twice. Oxygen saturations (SaO2), transcutaneous CO2 (tcCO2) and vital signs were monitored continuously. Polysomnographic recordings were analysed for apnoea, bradycardia and oxygen desaturation. Twenty low-birthweight infants receiving 0.3±0.04% supplemental oxygen on CPAP of 6 cm H2O were studied at an average of 33 days of age (±23 days, SD). There were no differences in tcCO2 or other physiological parameters except mean blood pressure, which was lower during nCPAP (52.3±8.3 vs 54.4±9.1 mm Hg; ±SD; p<0.01). No differences in short or prolonged apnoea, bradycardia or significant desaturation events were observed. At similar mean airway pressures, SiPAP does not improve CO2 removal, oxygenation or other studied physiological parameters with the exception of mean blood pressure, which was not clinically significant. NCT01053455. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  19. Prevalence of Cancer Screening Among Adults With Disabilities, United States, 2013

    PubMed Central

    Townsend, Julie S.; Courtney-Long, Elizabeth A.; Young, Monique

    2017-01-01

    Introduction Many studies on cancer screening among adults with disabilities examined disability status only, which masks subgroup differences. We examined prevalence of receipt of cancer screening tests by disability status and type. Methods We used 2013 National Health Interview Survey data to assess prevalence of 1) guideline-concordant mammography, Papanicolaou (Pap) tests, and endoscopy and stool tests; 2) physicians’ recommendations for these tests; and 3) barriers to health-care access among adults with and without disabilities (defined as difficulty with cognition, hearing, vision, or mobility). Results Reported Pap test use ranged from 66.1% (95% confidence interval [CI], 60.3%–71.4%) to 80.2% (95% CI, 72.4%–86.2%) among women with different types of disabilities compared with 81.4% (95% CI, 80.0%–82.7%) among women without disabilities. Prevalence of mammography among women with disabilities was also lower (range, 61.2% [95% CI, 50.5%–71.0%] to 67.5% [95% CI, 62.8%–71.9%]) compared with women without disabilities (72.8% [95% CI, 70.7%–74.9%]). Screening for colorectal cancer was 57.0% among persons without disabilities, and ranged from 48.6% (95% CI, 40.3%–57.0%) among those with vision limitations to 64.6% (95% CI, 58.5%–70.2%) among those with hearing limitations. Receiving recommendations for Pap tests and mammography increased all respondents’ likelihood of receiving these tests. The most frequently reported barrier to accessing health care reported by adults with disabilities was difficulty scheduling an appointment. Conclusion We observed disparities in receipt of cancer screening among adults with disabilities; however, disparities varied by disability type. Our findings may be used to refine interventions to close gaps in cancer screening among persons with disabilities. PMID:28125399

  20. Triage of women with atypical squamous cells of undetermined significance (ASC-US): results of an Italian multicentric study.

    PubMed

    Del Mistro, Annarosa; Frayle-Salamanca, Helena; Trevisan, Rossana; Matteucci, Mario; Pinarello, Antonella; Zambenedetti, Pamela; Buoso, Rita; Fantin, Gian Piero; Zorzi, Manuel; Minucci, Daria

    2010-04-01

    To compare the performance of immediate colposcopy, repeat Pap test and HPV test as triage options for women diagnosed as having atypical squamous cells of undetermined significance (ASC-US) while attending organised screening for cervical carcinoma in five centres of the Veneto region. Women consecutively diagnosed as having ASC-US were included in a prospective study, and underwent colposcopy and collection of cervico-vaginal cells for conventional Pap test and HPV test (Hybrid Capture 2, High-risk probe set, Digene). Repetition of all three tests was scheduled for 12 months later. DNA was subsequently extracted from residual cells of positive samples, and analysed by polymerase chain reaction with several primers for typing of HPV sequences. Sensitivity, specificity and positive predictive value (PPV) of the different triage options for histology-confirmed cervical intraepithelial neoplasia, grade 2 or worse (CIN2+) were calculated among all women and by age (under and above 35 years). Seven hundred forty-nine women 25-64 years old (median age 42 years) were enrolled in the study. Pap smears at enrolment were read as ASC-US or more severe in 211 (29.4%) cases, colposcopy disclosed an atypical transformation zone in 254 (34.2%) women, and HPV test was positive in 181 (24.2%). High-grade cervical lesions developed in 29/749 (3.9%) women. HPV typing was possible in 163 (90%) of the samples, and carcinogenic types were present in 123. HPV test showed the best performance; overall, it had the highest sensitivity (92.3%), specificity (78.6%) and PPV (14.9%). Copyright 2009 Elsevier Inc. All rights reserved.

  1. Routine Treatment of Cervical Cytological Cell Changes

    PubMed Central

    Huber, J.; Pötsch, B.; Gantschacher, M.; Templ, M.

    2016-01-01

    Introduction: Diagnosis and treatment of vaginal and cervical cytological cell changes are described in European and national guidelines. The aim of this data collection was to evaluate the remission rates of PAP III and PAP III D cytological findings in patients over a period of 3–4 months. Method: The current state of affairs in managing suspicious and cytological findings (PAP III, and III D) in gynecological practice was assessed in the context of a data collection survey. An evaluation over a period of 24 months was conducted on preventative measures, the occurrence and changes to normal/suspect/pathological findings and therapy management (for suspicious or pathological findings). Results: 307 female patients were included in the analysis. At the time of the survey 186 patients (60.6 %) had PAP III and 119 (38.8 %) had PAP III D findings. The spontaneous remission rate of untreated PAP III patients was 6 % and that of untreated PAP III D patients was 11 %. The remission rates of patients treated with a vaginal gel were 77 % for PAP III and 71 % for PAP III D. Conclusion: A new treatment option was used in gynecological practice on patients with PAP III and PAP III D findings between confirmation and the next follow-up with excellent success. PMID:27761030

  2. College Students' Goal Orientations, Situational Motivation and Effort/Persistence in Physical Activity Classes

    ERIC Educational Resources Information Center

    Gao, Zan; Podlog, Leslie W.; Harrison, Louis

    2012-01-01

    The purpose of this study was to examine relationships among college students' 2 x 2 goal orientations (mastery-approach [MAp], mastery-avoidance [MAv], performance-approach [PAp], performance-avoidance [PAv]), situational motivation (intrinsic motivation, identified regulation, external regulation and amotivation) and effort/persistence in…

  3. Pulmonary alveolar proteinosis: a case report and world literature review.

    PubMed

    Huaringa, Armando J; Francis, Wassem H

    2016-11-01

    Pulmonary alveolar proteinosis (PAP) is a lung disorder which was first described in 1958 by Rosen et al. and is indeed rare disease with a prevalence of 0.1 per 100,000 individuals. PAP is characterized by abnormal accumulation of pulmonary surfactant in the alveolar space, which impairs gas exchange leading to a severe hypoxemia. Pulmonary surfactant is an insoluble proteinaceous material that is rich in lipids and stains positive with periodic acid-Schiff (PAS). The most common type of PAP is the so-called autoimmune or idiopathic type. It has been hypothesized that deficiency in granulocyte macrophage-colony stimulating factor (GM-CSF), as a result of the anti-GM-CSF antibody production, is strongly related to impaired surfactant recycling that leads to the accumulation of surfactant in the alveolar space. Its clinical course is variable from spontaneous remission in the best case scenario, going through the entire spectrum of disease severity, towards fatal respiratory failure. Whole lung lavage has been the gold standard therapy in PAP until the advent of GM-CSF. Although the first case was reported to be idiopathic, subsequent analysis revealed that Pneumocystis jirovecii , silica, and other inhalational toxins were able to trigger this reaction. In this study, we report the case of a 52-year-old man who developed PAP syndrome after a 2-year exposure to silica dust. Our review of the world literature that includes 363 cases reported until now, reflects the evolution of science and technology in determining different aetiologies and diagnostic tests that lead to an improved perspective in the life of these patients.

  4. The Role of Chaperone-subunit Usher Domain Interactions in the Mechanism of Bacterial Pilus Biogenesis Revealed by ESI-MS*

    PubMed Central

    Morrissey, Bethny; Leney, Aneika C.; Toste Rêgo, Ana; Phan, Gilles; Allen, William J.; Verger, Denis; Waksman, Gabriel; Ashcroft, Alison E.; Radford, Sheena E.

    2012-01-01

    The PapC usher is a β-barrel outer membrane protein essential for assembly and secretion of P pili that are required for adhesion of pathogenic E. coli, which cause the development of pyelonephritis. Multiple protein subunits form the P pilus, the highly specific assembly of which is coordinated by the usher. Despite a wealth of structural knowledge, how the usher catalyzes subunit polymerization and orchestrates a correct and functional order of subunit assembly remain unclear. Here, the ability of the soluble N-terminal (UsherN), C-terminal (UsherC2), and Plug (UsherP) domains of the usher to bind different chaperone-subunit (PapDPapX) complexes is investigated using noncovalent electrospray ionization mass spectrometry. The results reveal that each usher domain is able to bind all six PapDPapX complexes, consistent with an active role of all three usher domains in pilus biogenesis. Using collision induced dissociation, combined with competition binding experiments and dissection of the adhesin subunit, PapG, into separate pilin and adhesin domains, the results reveal why PapG has a uniquely high affinity for the usher, which is consistent with this subunit always being displayed at the pilus tip. In addition, we show how the different soluble usher domains cooperate to coordinate and control efficient pilus assembly at the usher platform. As well as providing new information about the protein-protein interactions that determine pilus biogenesis, the results highlight the power of noncovalent MS to interrogate biological mechanisms, especially in complex mixtures of species. PMID:22371487

  5. The role of chaperone-subunit usher domain interactions in the mechanism of bacterial pilus biogenesis revealed by ESI-MS.

    PubMed

    Morrissey, Bethny; Leney, Aneika C; Toste Rêgo, Ana; Phan, Gilles; Allen, William J; Verger, Denis; Waksman, Gabriel; Ashcroft, Alison E; Radford, Sheena E

    2012-07-01

    The PapC usher is a β-barrel outer membrane protein essential for assembly and secretion of P pili that are required for adhesion of pathogenic E. coli, which cause the development of pyelonephritis. Multiple protein subunits form the P pilus, the highly specific assembly of which is coordinated by the usher. Despite a wealth of structural knowledge, how the usher catalyzes subunit polymerization and orchestrates a correct and functional order of subunit assembly remain unclear. Here, the ability of the soluble N-terminal (UsherN), C-terminal (UsherC2), and Plug (UsherP) domains of the usher to bind different chaperone-subunit (PapDPapX) complexes is investigated using noncovalent electrospray ionization mass spectrometry. The results reveal that each usher domain is able to bind all six PapDPapX complexes, consistent with an active role of all three usher domains in pilus biogenesis. Using collision induced dissociation, combined with competition binding experiments and dissection of the adhesin subunit, PapG, into separate pilin and adhesin domains, the results reveal why PapG has a uniquely high affinity for the usher, which is consistent with this subunit always being displayed at the pilus tip. In addition, we show how the different soluble usher domains cooperate to coordinate and control efficient pilus assembly at the usher platform. As well as providing new information about the protein-protein interactions that determine pilus biogenesis, the results highlight the power of noncovalent MS to interrogate biological mechanisms, especially in complex mixtures of species.

  6. Pulmonary blood flow and pulmonary hypertension: Is the pulmonary circulation flowophobic or flowophilic?

    PubMed Central

    Kulik, Thomas J.

    2012-01-01

    Increased pulmonary blood flow (PBF) is widely thought to provoke pulmonary vascular obstructive disease (PVO), but the impact of wall shear stress in the lung is actually poorly defined. We examined information from patients having cardiac lesions which impact the pulmonary circulation in distinct ways, as well as experimental studies, asking how altered hemodynamics impact the risk of developing PVO. Our results are as follows: (1) with atrial septal defect (ASD; increased PBF but low PAP), shear stress may be increased but there is little tendency to develop PVO; (2) with normal PBF but increased pulmonary vascular resistance (PVR; mitral valve disease) shear stress may also be increased but risk of PVO still low; (3) with high PVR and PBF (e.g., large ventricular septal defect), wall shear stress is markedly increased and the likelihood of developing PVO is much higher than with high PBF or PAP only; and (4) with ASD, experimental and clinical observations suggest that increased PBF plus another stimulus (e.g., endothelial inflammation) may be required for PVO. We conclude that modestly increased wall shear stress (e.g., ASD) infrequently provokes PVO, and likely requires other factors to be harmful. Likewise, increased PAP seldom causes PVO. Markedly increased wall shear stress may greatly increase the likelihood of PVO, but we cannot discriminate its effect from the combined effects of increased PAP and PBF. Finally, the age of onset of increased PAP may critically impact the risk of PVO. Some implications of these observations for future investigations are discussed. PMID:23130101

  7. Using Natural Language Processing to Extract Abnormal Results From Cancer Screening Reports.

    PubMed

    Moore, Carlton R; Farrag, Ashraf; Ashkin, Evan

    2017-09-01

    Numerous studies show that follow-up of abnormal cancer screening results, such as mammography and Papanicolaou (Pap) smears, is frequently not performed in a timely manner. A contributing factor is that abnormal results may go unrecognized because they are buried in free-text documents in electronic medical records (EMRs), and, as a result, patients are lost to follow-up. By identifying abnormal results from free-text reports in EMRs and generating alerts to clinicians, natural language processing (NLP) technology has the potential for improving patient care. The goal of the current study was to evaluate the performance of NLP software for extracting abnormal results from free-text mammography and Pap smear reports stored in an EMR. A sample of 421 and 500 free-text mammography and Pap reports, respectively, were manually reviewed by a physician, and the results were categorized for each report. We tested the performance of NLP to extract results from the reports. The 2 assessments (criterion standard versus NLP) were compared to determine the precision, recall, and accuracy of NLP. When NLP was compared with manual review for mammography reports, the results were as follows: precision, 98% (96%-99%); recall, 100% (98%-100%); and accuracy, 98% (96%-99%). For Pap smear reports, the precision, recall, and accuracy of NLP were all 100%. Our study developed NLP models that accurately extract abnormal results from mammography and Pap smear reports. Plans include using NLP technology to generate real-time alerts and reminders for providers to facilitate timely follow-up of abnormal results.

  8. The long-term effects of arteriovenous fistula creation on the development of pulmonary hypertension in hemodialysis patients.

    PubMed

    Unal, Aydin; Tasdemir, Kutay; Oymak, Sema; Duran, Mustafa; Kocyigit, Ismail; Oguz, Fatih; Tokgoz, Bulent; Sipahioglu, Murat Hayri; Utas, Cengiz; Oymak, Oktay

    2010-10-01

    The aim of this prospective study was to evaluate long-term effects of arteriovenous fistula (AVF) on the development of pulmonary arterial hypertension (PAH) and the relationship between blood flow rate of AVF and pulmonary artery pressure (PAP) in the patients with end-stage renal disease (ESRD). This prospective study was performed in 20 patients with ESRD. Before an AVF was surgically created for hemodialysis, the patients were evaluated by echocardiography. Then, an AVF was surgically created in all patients. After mean 23.50 ± 2.25 months, the second evaluation was performed by echocardiography. Also, the blood flow rate of AVF was measured at the second echocardiographic evaluation. Pulmonary arterial hypertension was defined as a systolic PAP above 35 mmHg at rest. Mean age of 20 patients with ESRD was 55.05 ± 13.64 years; 11 of 20 patients were males. Pulmonary arterial hypertension was detected in 6 (30%) patients before AVF creation and in 4 (20%) patients after AVF creation. Systolic PAP value was meaningfully lower after AVF creation than before AVF creation (29.95 ± 10.26 mmHg vs. 35.35 ± 7.86 mmHg, respectively, P: 0.047). However, there was no significant difference between 2 time periods in terms of presence of PAH (P>0.05). Pulmonary artery pressure did not correlate with blood flow rate of AVF and duration after AVF creation (P>0.05). In hemodialysis patients, a surgically created AVF has no significant effect on the development of PAH within a long-term period. Similarly, blood flow rate of AVF also did not affect remarkably systolic PAP within the long-term period. © 2010 The Authors. Hemodialysis International © 2010 International Society for Hemodialysis.

  9. The performance of two automatic servo-ventilation devices in the treatment of central sleep apnea.

    PubMed

    Javaheri, Shahrokh; Goetting, Mark G; Khayat, Rami; Wylie, Paul E; Goodwin, James L; Parthasarathy, Sairam

    2011-12-01

    This study was conducted to evaluate the therapeutic performance of a new auto Servo Ventilation device (Philips Respironics autoSV Advanced) for the treatment of complex central sleep apnea (CompSA). The features of autoSV Advanced include an automatic expiratory pressure (EPAP) adjustment, an advanced algorithm for distinguishing open versus obstructed airway apnea, a modified auto backup rate which is proportional to subject's baseline breathing rate, and a variable inspiratory support. Our primary aim was to compare the performance of the advanced servo-ventilator (BiPAP autoSV Advanced) with conventional servo-ventilator (BiPAP autoSV) in treating central sleep apnea (CSA). A prospective, multicenter, randomized, controlled trial. Five sleep laboratories in the United States. Thirty-seven participants were included. All subjects had full night polysomnography (PSG) followed by a second night continuous positive airway pressure (CPAP) titration. All had a central apnea index ≥ 5 per hour of sleep on CPAP. Subjects were randomly assigned to 2 full-night PSGs while treated with either the previously marketed autoSV, or the new autoSV Advanced device. The 2 randomized sleep studies were blindly scored centrally. Across the 4 nights (PSG, CPAP, autoSV, and autoSV Advanced), the mean ± 1 SD apnea hypopnea indices were 53 ± 23, 35 ± 20, 10 ± 10, and 6 ± 6, respectively; indices for CSA were 16 ± 19, 19 ± 18, 3 ± 4, and 0.6 ± 1. AutoSV Advanced was more effective than other modes in correcting sleep related breathing disorders. BiPAP autoSV Advanced was more effective than conventional BiPAP autoSV in the treatment of sleep disordered breathing in patients with CSA.

  10. HvPap-1 C1A Protease and HvCPI-2 Cystatin Contribute to Barley Grain Filling and Germination1

    PubMed Central

    Velasco-Arroyo, Blanca; Cambra, Ines; Gonzalez-Melendi, Pablo; Lopez-Gonzalvez, Angeles; Garcia, Antonia

    2016-01-01

    Proteolysis is an essential process throughout the mobilization of storage proteins in barley (Hordeum vulgare) grains during germination. It involves numerous types of enzymes, with C1A Cys proteases the most abundant key players. Manipulation of the proteolytic machinery is a potential way to enhance grain yield and quality, and it could influence the mobilization of storage compounds along germination. Transgenic barley plants silencing or over-expressing the cathepsin F-like HvPap-1 Cys protease show differential accumulation of storage molecules such as starch, proteins, and free amino acids in the grain. It is particularly striking that the HvPap-1 artificial microRNA lines phenotype show a drastic delay in the grain germination process. Alterations to the proteolytic activities in the over-expressing and knock-down grains associated with changes in the level of expression of several C1A peptidases were also detected. Similarly, down-regulating cystatin Icy-2, one of the proteinaceous inhibitors of the cathepsin F-like protease, also has important effects on grain filling. However, the ultimate physiological influence of manipulating a peptidase or an inhibitor cannot be always predicted, since the plant tries to compensate the modified proteolytic effects by modulating the expression of some other peptidases or their inhibitors. PMID:26912343

  11. Retrospective health-care associated infection surveillance in oral and maxillofacial reconstructive microsurgery.

    PubMed

    Patyi, Márta; Sejben, István; Cserni, Gábor; Sántha, Beáta; Gaál, Zoltán; Pongrácz, Júlia; Oberna, Ferenc

    2014-12-01

    In polymorbid or anaemic patients who receive preoperative radiotherapy or undergo long duration surgery involving potentially infectious sites, perioperative antibiotic prophylaxis (PAP) that is effective against normal oral bacterial flora is mandatory and plays an important role in preventing postoperative infection. In a four-year retrospective analysis, the incidence, outcome, and the efficacy of PAP were evaluated in patients treated at the Department of Oral and Maxillofacial Surgery and Otorhinolaryngology at Kecskemét Hospital. The results were compared with data from the literature to determine if the use of PAP was adequate at the Department.During the study period (between 01/09/2007 and 31/01/2011) 108 patients were evaluated. The mean duration of prophylactic antibiotic treatment was 8.3 ± 5.2 days, with cefotaxime+metronidazole being the most commonly used combination. Surgical site infection occurred in 8 patients (7.5%) in the clean-contaminated category.Our results showed that the perioperative antibiotic prophylaxis administered at our Department was efficient and effective against the oral bacterial flora of patients. Its use is recommended in head and neck microsurgery. To avoid development of antibiotic resistance and to reduce costs, it seems that the duration of antibiotic regimen for primary surgery can be reduced from 8.3 ± 5.2 days to 3 days.

  12. Serial lectin affinity chromatography with concavalin A and wheat germ agglutinin demonstrates altered asparagine-linked sugar-chain structures of prostatic acid phosphatase in human prostate carcinoma.

    PubMed

    Yoshida, K I; Honda, M; Arai, K; Hosoya, Y; Moriguchi, H; Sumi, S; Ueda, Y; Kitahara, S

    1997-08-01

    Differences between human prostate carcinoma (PCA, five cases) and benign prostatic hyperplasia (BPH, five cases) in asparagine-linked (Asn) sugar-chain structure of prostatic acid phosphatase (PAP) were investigated using lectin affinity chromatography with concanavalin A (Con A) and wheat germ agglutinin (WGA). PAP activities were significantly decreased in PCA-derived PAP, while no significant differences between the two PAP preparations were observed in the enzymatic properties (Michaelis-Menten value, optimal pH, thermal stability, and inhibition study). In these PAP preparations, all activities were found only in the fractions which bound strongly to the Con A column and were undetectable in the Con A unbound fractions and in the fractions which bound weakly to the Con A column. The relative amounts of PAP which bound strongly to the Con A column but passed through the WGA column, were significantly greater in BPH-derived PAP than in PCA-derived PAP. In contrast, the relative amounts of PAP which bound strongly to the Con A column and bound to the WGA column, were significantly greater in PCA-derived PAP than in BPH-derived PAP. The findings suggest that Asn-linked sugar-chain structures are altered during oncogenesis in human prostate and also suggest that studies of qualitative differences of sugar-chain structures of PAP might lead to a useful diagnostic tool for PCA.

  13. Specificity of anti-phospholipid antibodies in infectious mononucleosis: a role for anti-cofactor protein antibodies

    PubMed Central

    Sorice, M; Pittoni, V; Griggi, T; Losardo, A; Leri, O; Magno, M S; Misasi, R; Valesini, G

    2000-01-01

    The antigen specificity of anti-phospholipid antibodies in infectious mononucleosis (IM) was studied using ELISA for the detection of anti-β2-glycoprotein I (β2-GPI), anti-annexin V, anti-protein S and anti-prothrombin antibodies and TLC immunostaining for the detection of anti-phospholipid antibodies. This technique enabled us to look at antibodies reacting to ‘pure’ phospholipid antigens in the absence of protein contamination. Sera from 46 patients with IM, 18 with systemic lupus erythematosus (SLE), 21 with primary anti-phospholipid antibody syndrome (PAPS), 50 with Helicobacter pylori infection and 30 healthy blood donors were tested. This study highlights anti-phospholipid antibodies in patients with IM as specific ‘pure’ anti-cardiolipin antibodies, while in PAPS and SLE patients anti-phosphatidylserine and anti-phosphatidylethanolamine antibodies were also found. This investigation also shows that the anti-cardiolipin antibodies found in IM can be present with anti-cofactor protein antibodies. The higher prevalence of anti-cofactor antibodies found in IM sera than in Helicobacter pylori sera may be due to the immunostimulatory effect and/or the polyclonal activation often observed in course of Epstein–Barr virus infection. However, anti-β2-GPI and, to a lesser extent, anti-prothrombin antibodies occur with a significantly lower prevalence in IM than in PAPS patients. This finding suggests that these antibodies should be regarded as the expression of the broad autoimmune syndrome involving the phospholipid-binding plasma proteins. PMID:10792380

  14. Investigation of the Role of Training Health Volunteers in Promoting Pap Smear Test Use among Iranian Women Based on the Protection Motivation Theory.

    PubMed

    Ghahremani, Leila; Harami, Zahra Khiyali; Kaveh, Mohammad Hossein; Keshavarzi, Sareh

    2016-01-01

    Cervical cancer is known as one of the most prevalent types of cancers and a major public health problem in developing countries which can be detected by Pap test, prevented, and treated. Despite the effective role of Pap test in decreasing the incidence and mortality due to cervical cancer, it is still one the most common causes of cancer-related deaths among women, especially in developing countries. Thus, this study aimed to examine the effect of educational interventions implemented by health volunteers based on protection motivation theory (PMT) on promoting Pap test use among women. This quasi-experimental study was conducted on 60 health volunteers and 420 women. The study participants were divided into an intervention and a control group. Data were collected using a valid self-reported questionnaire including demographic variables and PMT constructs which was completed by both groups before and 2 months after the intervention. Then, the data were entered into the SPSS statistical software, version 19 and were analyzed using Chi-square test, independent T-test, and descriptive statistical methods. P<0.05 was considered as statistically significant. The findings of this study showed that the mean scores of PMT constructs (i.e. perceived vulnerability, perceived severity, fear, response-costs, self-efficacy, and intention) increased in the intervention group after the intervention (P<0.001). However, no significant difference was found between the two groups regarding response efficacy after the intervention (P=0.06). The rate of Pap test use also increased by about 62.9% among the study women. This study showed a significant positive relationship between PMT-based training and Pap test use. The results also revealed the successful contribution of health volunteers to training cervical cancer screening. Thus, training interventions based on PMT are suggested to be designed and implemented and health volunteers are recommended to be employed for educational purposes and promoting the community's, especially women's, health.

  15. Factors affecting phosphorus transport at a conventionally-farmed site in Lancaster County, Pennsylvania, 1992-95

    USGS Publications Warehouse

    Galeone, Daniel G.

    1996-01-01

    The U.S. Geological Survey and the Bureau of Land and Water Conservation of the Pennsylvania Department of Environmental Protection conducted a cooperative study to determine the effects of manure application and antecedent soil-phosphorus concentrations on the transport of phosphorus from the soil of a typical farm site in Lancaster County, Pa., from September 1992 to March 1995. The relation between concentrations of soil phosphorus and phosphorus transport needs to be identified because excessive phosphorus concentrations in surface-water bodies promote eutrophication.The objective of the study was to quantify and determine the significance of chemical, physical, and hydrologic factors that affected phosphorus transport. Three study plots less than 1 acre in size were tilled and planted in silage corn. Phosphorus in the form of liquid swine and dairy manure was injected to a depth of 6-8 inches on two of the three study plots in May 1993 and May 1994. Plot 1 received no inputs of phosphorus from manure while plots 2 and 3 received an average of 56 and 126 kilograms of phosphorus per acre, respectively, from the two manure applications. No other fertilizer was applied to any of the study plots. From March 30, 1993, through December 31, 1993, and March 10, 1994, through August 31, 1994 (the study period), phosphorus and selected cations were measured in precipitation, manure, soil, surface runoff, subsurface flow (at 18 inches below land surface), and corn plants before harvest. All storm events that yielded surface runoff and subsurface flow were sampled. Surface runoff was analyzed for dissolved (filtered through a 0.45-micron filter) and total concentrations. Subsurface flow was only analyzed for dissolved constituents. Laboratory soil-flask experiments and geochemical modeling were conducted to determine the maximum phosphate retention capacity of sampled soils after manure applications and primary mineralogic controls in the soils that affect phosphate equilibrium processes.Physical characteristics, such as particle-size distributions in soil, the suspended sediment and particle-size distribution in surface runoff, and surface topography, were quantified. Hydrologic characteristics, such as precipitation intensity and duration, volumes of surface runoff, and infiltration rates of soil, were also monitored during the study period. Volumes of surface runoff differed by plot.Volumes of surface runoff measured during the study period from plots 1 (0.43 acres), 2 (0.23 acres), and 3 (0.28 acres) were 350,000, 350,000, and 750,000 liters per acre, respectively. About 90 percent of the volume of surface runoff occurred after October 1993 because of the lack of intense precipitation from March 30, 1993, through November 30, 1993. For any one precipitation amount, volumes of surface runoff increased with an increase in the maximum intensity of precipitation and decreased with an increase in storm duration. The significantly higher volume of surface runoff for plot 3 relative to plots 1 and 2 was probably caused by lower infiltration rates on plot 3.Soil concentrations of plant-available phosphorus (PAP) for each study plot were high (31-60 parts per million) to excessive (greater than 60 parts per million) for each depth interval (0-6, 6-12, and 12- 24 inches) and sampling period except for some samples collected at depths of 12-24 inches. The high levels of PAP before manure applications made it difficult to detect any changes in the concentration of soil PAP caused by manure applications. Manure applications to the study area prior to this study resulted in relatively high concentrations of soil PAP; however, the manure applications to plot 3 during the study period did cause an increase in the soil concentration of PAP after the second manure application. The percentages of total phosphorus in plant-available and inorganic forms were about 5 and 80 percent, respectively, in the 0-24--inch depth interval of soil on the study plots. Concentrations of total phosphorus on sand, silt, and clay particles from soil were 700, 1,000, and 3,400 parts per million, respectively. About 70 percent of the total mass of phosphorus in soil to a depth of 24 inches was associated with silt and clay particles.Soil-flask experiments indicated that soils from the study plots were not saturated with respect to phosphorus. Soils had the capacity to retain 694 to 1,160 milligrams of phosphorus per kilogram of soil. The measured retention capacity probably exceeded the actual retention capacity of soil because laboratory conditions optimized the contact time between soil and test solutions.Geochemical modeling indicated that the primary mineralogical controls on the concentration of dissolved phosphorus in surface runoff and subsurface flow were aluminum and iron oxides and strengite (if it exists). Aluminum and iron oxides bind phosphate in solution and strengite is an iron-phosphate mineral. The mineralization of organic phosphorus into dissolved inorganic forms could also supply phosphorus to surface runoff and subsurface flow.Phosphorus inputs to the plots during the study period were from precipitation and manure. Phosphorus inputs from precipitation were negligible. The loads of phosphorus to the plots from manure applications in May 1993 and May 1994 were 112 and 251 kilograms per acre for plots 2 and 3, respectively; about 60 percent of the load occurred in 1994.Phosphorus outputs in surface runoff differed between study plots. The cumulative yields of total phosphorus during the study period for plots 1, 2, and 3 were 1.12, 1.24, and 1.69 kilograms per acre, respectively. Differences between plots were primarily evident for dissolved yields of phosphorus. The percentage of the total phosphorus output in surface runoff that was in the dissolved phase varied from 6 percent for plot 1 to 26 percent for plot 3.The cumulative yields of dissolved phosphorus from plots 2 and 3 were 135 and 500 percent greater, respectively, than the dissolved yield from plot 1. Even though volumes of surface runoff were different on the plots, the primary cause of the difference between plots in the yield of dissolved phosphorus in surface runoff was differences in the concentration of dissolved phosphorus. After the second manure application, concentrations of dissolved phosphorus in surface runoff on plots 2 and 3 were significantly higher than the concentration for plot 1.An increase in the concentration of dissolved phosphorus in subsurface flow from plots 2 and 3 was measured after manure applications. The mean concentrations of dissolved phosphorus in subsurface flow after the first manure application were 0.29, 0.57, and 1.45 milligrams per liter of phosphorus for plots 1, 2, and 3, respectively.The loss of dissolved phosphorus in surface runoff was related to the soil concentration of PAP. The model relating dissolved phosphorus in surface runoff to soil PAP indicated that concentrations of dissolved phosphorus in surface runoff would exceed 0.1 milligram per liter if soil concentrations of PAP exceeded 9 parts per million; this PAP concentration was exceeded by each study plot. Over 50 percent of the variation of dissolved phosphorus in surface runoff was explained by soil concentrations of PAP in the 0-6-inch depth interval.The loss of suspended phosphorus in surface runoff was primarily affected by the particle-size distribution of suspended sediment in surface runoff. Surface runoff was enriched with fines relative to the soil matrix. Generally, over 90 percent of sediment in runoff was comprised of silt and clay particles; only 50-60 percent of particle sizes from the intact soil matrix were in the silt- to clay-size range. Concentrations of suspended phosphorus in surface runoff were not significantly related to soil concentrations of total phosphorus in the 0-6-inch depth interval.Concentrations of dissolved phosphorus in subsurface flow were also related to soil concentrations of PAP. The relation indicated that dissolved concentrations of phosphorus in subsurface flow would exceed 0.1 milligram per liter if soil concentrations of PAP in the 0-6-inch depth interval of soil were greater than 49 parts per million; this PAP concentration was exceeded by each study plot.The significant relation of high concentrations of dissolved phosphorus in water to soil concentrations of PAP indicated that soils with comparable concentrations of soil PAP would be potential sources of dissolved phosphorus to surface water and subsurface water tables. The percentage of the total phosphorus lost from a system in the dissolved form increased as soil concentrations of PAP increased. This indicates that best-management practices to reduce phosphorus losses from this system not only need to target suspended forms of phosphorus but also dissolved forms. Practices aimed at reducing the loss of dissolved phosphorus from the system increase in importance with an increase in soil concentrations of PAP.

  16. Comparison of para-aminophenol cytotoxicity in rat renal epithelial cells and hepatocytes.

    PubMed

    Li, Ying; Bentzley, Catherine M; Tarloff, Joan B

    2005-04-01

    Several chemicals, including para-aminophenol (PAP), produce kidney damage in the absence of hepatic damage. Selective nephrotoxicity may be related to the ability of the kidney to reabsorb filtered water, thereby raising the intraluminal concentration of toxicants and exposing tubular epithelial cells to higher concentrations than would be present in other tissues. The present experiments tested the hypothesis that hepatocytes and renal epithelial cells exposed to equivalent concentrations of PAP would be equally susceptible to toxicity. Hepatocytes and renal epithelial cells were prepared by collagenase digestion of tissues obtained from female Sprague-Dawley rats. Toxicity was monitored using trypan blue exclusion, oxygen consumption and ATP content. We measured the rate of PAP clearance and formation of PAP-glutathione conjugate by HPLC. We found that renal epithelial cells accumulated trypan blue and showed declines in oxygen consumption and ATP content at significantly lower concentrations of PAP and at earlier time points than hepatocytes. The half-life of PAP in hepatocyte incubations was significantly shorter (0.71+/-0.07 h) than in renal epithelial cell incubations (1.33+/-0.23 h), suggesting that renal epithelial cells were exposed to PAP for longer time periods than hepatocytes. Renal epithelial cells formed significantly less glutathione conjugates of PAP (PAP-SG) than did hepatocytes, consistent with less efficient detoxification of reactive PAP intermediates by renal epithelial cells. Finally, hepatocytes contained significant more reduced glutathione (NPSH) than did renal epithelial cells, possibly explaining the enhanced formation of PAP-SG by this cell population. In conclusion, our data indicates that renal epithelial cells are intrinsically more susceptible to PAP cytotoxicity than are hepatocytes. This enhanced cytotoxicity may be due to longer exposure to PAP and/or reduced detoxification of reactive intermediates due to lower concentrations of reduced NPSH in renal epithelial cells than in hepatocytes.

  17. Comparison of the virucidal efficacy of peracetic acid, potassium monopersulphate and sodium hypochlorite on bacteriophages P001 and MS2.

    PubMed

    Morin, T; Martin, H; Soumet, C; Fresnel, R; Lamaudière, S; Le Sauvage, A L; Deleurme, K; Maris, P

    2015-09-01

    The phagicidal activity of peroxy products against the virulent bacteriophage P001 infecting lactic acid bacteria and bacteriophage MS2 used as a surrogate of enteric viruses (EVs) was evaluated and compared to sodium hypochlorite using the EN 13610 European suspension test and a surface test developed in our laboratories. Infectivity tests were adapted and/or developed to determine the activity of disinfectants against reference P001 phage of Lactoccocus lactis and F-specific RNA phage MS2 of Escherichia coli in conditions simulating practical use. Similar concentrations of sodium hypochlorite were phagicidal against both bacteriophages, either at 0·05-0·125% of active chlorine using the suspension test or at 0·12-0·5% using the surface test. For Potassium monopersulphate (MPS), phagicidal concentrations varied from 0·006 to 0·012% whatever the type of test and phages. However, for peracetic acid products (PAP) used in suspension, concentrations 55 times higher were necessary against MS2 (0·271%) than against P001 (0·005%). With the surface test, 0·089-0·178% concentrations of PAP were effective against MS2, but these concentrations were 16-32 times greater than needed against P001. Sodium hypochlorite and MPS had similar phagicidal activities against P001 and MS2, but PAP did not. This is the first comparative study to investigate through suspension and surface tests the difference in resistance to peroxy compounds between a reference bacteriophage (P001) used to evaluate phagicidal concentrations in European standards and a surrogate of EVs (MS2). Results underline the importance of validation tests on pertinent surrogates of viruses or bacteriophages to adjust the concentration of disinfectants for use in the food and water industries. © 2015 The Society for Applied Microbiology.

  18. An Investigation of Tenascin-C Levels in Rheumatic Mitral Stenosis and Their Response to Percutaneous Mitral Balloon Valvuloplasty

    PubMed Central

    Celik, Ahmet; Gunebakmaz, Ozgur; Baran, Oguzhan; Dogdu, Orhan; Elcik, Deniz; Kobat, Mehmet Ali; Balin, Mehmet; Erdem, Kenan; Aydin, Suleyman; Ozdogru, Ibrahim; Topsakal, Ramazan

    2012-01-01

    Objective The purpose of this study was to evaluate the tenascin-C levels in severe rheumatic mitral stenosis before and after percutaneous mitral balloon valvuloplasty (PMBV). Subjects and Methods Forty patients with severe mitral stenosis requiring PMBV and 20 age-matched healthy subjects were included in the study. The mitral valve areas, mitral gradients and systolic pulmonary artery pressure (sPAP) were measured by echocardiography. The sPAP values and mitral gradients were also measured by catheterization before and after PMBV. The blood tenascin-C levels were measured before PMBV and 1 month after the procedure. Results The echocardiographic mean mitral gradients had a significant decrease after PMBV (11.7 ± 2.8 vs. 5.6 ± 1.7 mm Hg; p < 0.001) and also those of catheterization (13.9 ± 4.4 vs. 4.0 ± 2.4 mm Hg; p < 0.001). Mitral valve areas increased significantly after PMBV (from 1.1 ± 0.1 to 1.8 ± 0.2 cm2, p < 0.001). Tenascin-C levels decreased significantly in patients after PMBV (from 15.0 ± 3.8 to 10.9 ± 3.1 ng/ml; p < 0.001). Tenascin-C levels were higher in patients with mitral stenosis before PMBV than in healthy subjects (15.0 ± 3.8 and 9.4 ± 2.9 ng/ml; p < 0.001, respectively). There were no significant differences between patients with mitral stenosis after PMBV and healthy subjects (10.9 ± 3.1 and 9.4 ± 2.9 ng/ml; p = 0.09, respectively). There was a significant positive correlation between tenascin-C levels and sPAP (r = 0.508, p < 0.001). In multivariant analysis, tenascin-C predicted mitral stenosis (p = 0.004, OR: 2.31). Conclusions Tenascin-C was an independent predictor for rheumatic mitral stenosis. PMID:22889719

  19. Effects of Modes, Obesity, and Body Position on Non-invasive Positive Pressure Ventilation Success in the Intensive Care Unit: A Randomized Controlled Study.

    PubMed

    Türk, Murat; Aydoğdu, Müge; Gürsel, Gül

    2018-01-01

    Different outcomes and success rates of non-invasive positive pressure ventilation (NPPV) in patients with acute hypercapnic respiratory failure (AHRF) still pose a significant problem in intensive care units. Previous studies investigating different modes, body positioning, and obesity-associated hypoventilation in patients with chronic respiratory failure showed that these factors may affect ventilator mechanics to achieve a better minute ventilation. This study tried to compare pressure support (BiPAP-S) and average volume targeted pressure support (AVAPS-S) modes in patients with acute or acute-on-chronic hypercapnic respiratory failure. In addition, short-term effects of body position and obesity within both modes were analyzed. We conducted a randomized controlled study in a 7-bed intensive care unit. The course of blood gas analysis and differences in ventilation variables were compared between BiPAP-S (n=33) and AVAPS-S (n=29), and between semi-recumbent and lateral positions in both modes. No difference was found in the length of hospital stay and the course of PaCO2, pH, and HCO3 levels between the modes. There was a mean reduction of 5.7±4.1 mmHg in the PaCO2 levels in the AVAPS-S mode, and 2.7±2.3 mmHg in the BiPAP-S mode per session (p<0.05). Obesity didn't have any effect on the course of PaCO2 in both the modes. Body positioning had no notable effect in both modes. Although the decrease in the PaCO2 levels in the AVAPS-S mode per session was remarkably high, the course was similar in both modes. Furthermore, obesity and body positioning had no prominent effect on the PaCO2 response and ventilator mechanics. Post hoc power analysis showed that the sample size was not adequate to detect a significant difference between the modes.

  20. Significance of the Cytological Signs of Human Papillomavirus Infection in Anal Pap Smears of Human Immunodeficiency Virus-Infected Japanese Men Who Have Sex with Men

    PubMed

    Okayama, Kaori; Okodo, Mitsuaki; Kitamura, Hiroshi; Itoda, Ichiro

    2017-11-26

    Purpose: The incidence of invasive anal cancer (IAC) has been increasing among human immunodeficiency virus (HIV)-positive men who have sex with men (MSM). Although cytological diagnosis is the modality of choice for screening cases of IAC, it is associated with lower sensitivity and specificity. Therefore, the present study aimed to evaluate new cytological signs of human papillomavirus (HPV) infection that may contribute to improving anal cytology. Methods: Anal cytology and HPV testing were performed using SurePath liquid-based cytology on samples obtained from 37 HIV-positive Japanese MSM. Subsequently, a histological biopsy based on high-resolution anoscopy was performed in MSM with abnormal cytological findings indicative of atypical squamous cells of undetermined significance (ASC-US) +. Also, anal Papanicolaou (Pap) smears were performed to determine cellularity, presence of dysplastic squamous cells, and other cytological signs of HPV infection. Results: Of the 37 MSM who underwent anal cytology, six tested negative for intraepithelial lesion or malignancy, three cases exhibited ASC-US, 17 exhibited low-grade squamous intraepithelial lesion (LSIL), nine exhibited high-grade squamous intraepithelial lesion (HSIL), and two remained undiagnosed. The anal Pap smears of 28 (96.6%) of the 29 MSM with abnormal cytological findings of ASC-US+ exhibited anal intraepithelial neoplasia (AIN), as revealed by histological biopsy. The median value (minimum–maximum) of the cellularity of anal Pap smears was 12 (0–70.5) nsc/hpf. In 26 MSM with LSIL and HSIL, the median dysplastic squamous cells count was 14 (2–152) dsc/smear and the cytological sign of HPV infection was 11 (2–71) hpv/smear. Of all anal Pap smears that revealed ASC-US+, 96.6% exhibited cytological signs of HPV infection. Compression-positive binucleated cells were the most prevalent among all cytological signs of HPV infection. Conclusion: For anal cytology, instead of considering a small number of dysplastic squamous cells, screening based on cytological signs of HPV infection may be beneficial for improving the diagnosis of AIN. Creative Commons Attribution License

  1. [Audit of preoperative antibiotic prophylaxis in a surgical site infections surveillance network].

    PubMed

    Rioux, C; Blanchon, T; Golliot, F; Berrouane, Y; Chalfine, A; Costa, Y; Laisné, M J; Levy, S; Richard, L; Seguier, J C; Botherel, A H; Astagneau, P

    2002-10-01

    To evaluate the preoperative antibiotic prophylaxis (PAP) prescriptions in a surgical site infection (SSI) surveillance network. Auto-evaluative audit in a prospective multicenter cohort included in a surveillance system. Since 1997, surgical wards in volunteer centers monitored all surgery patients each year during a period of two months. Patients were evaluated for SSI during the 30 days following surgery. Participating centers were asked in 2000 to participate to a PAP practice assessment. For each surgery patient, a questionnaire was completed. The "Guidelines for Antibiotic Prophylaxis Prescription in Surgery" edited in 1999 by the Société française d'anesthésie et de réanimation was used as gold standard. 6109 patients were included in the survey from 34 health care centers and 3881 received PAP. 90% of patients received PAP intravenously and 63% received twice the curative dose. PAP was administered within 90 minutes prior to incision in 70% of cases. 78% of PAP lasted less than 24 hours. PAP indication with regards to the type of surgical procedures was assessed in 4629 patients. PAP guidelines were observed in 1573 (34%) patients: 999 patients in whom PAP was not indicated did not receive PAP and 574 received it in compliance with recommended dose and indications. Efforts should be made to improve PAP prescription according to standards guidelines.

  2. Loaded hip thrust-based PAP protocol effects on acceleration and sprint performance of handball players.

    PubMed

    Dello Iacono, Antonio; Padulo, Johnny; Seitz, Laurent D

    2018-06-01

    This study aimed to investigate the acute effects of two barbell hip thrust-based (BHT) post-activation potentiation (PAP) protocols on subsequent sprint performance. Using a crossover design, eighteen handball athletes performed maximal 15-m sprints before and 15s, 4min and 8min after two experimental protocols consisting of BHT loaded with either 50% or 85% 1RM (50PAP and 85PAP, respectively), in order to profile the transient PAP effects. The resulting sprint performances were significantly impaired at 15s only after the 85PAP protocol, which induced likely and very likely greater decreases compared to the 50PAP. At 4min and 8min, significant improvements and very likely beneficial effects were observed in the 10m and 15m performances following both protocols. Significant differences were found when comparing the two PAPs over time; the results suggested very likely greater performance improvements in 10m following the 85PAP after 4min and 8min, and possible greater performance improvements in 15m after 4min. Positive correlations between BHT 1RMs values and the greatest individual PAP responses on sprint performance were found. This investigation showed that both moderate and intensive BHT exercises can induce a PAP response, but the effects may differ according to the recovery following the potentiating stimulus and the individual`s strength level.

  3. Heated, Humidified High-Flow Nasal Cannula vs Nasal Continuous Positive Airway Pressure for Respiratory Distress Syndrome of Prematurity: A Randomized Clinical Noninferiority Trial.

    PubMed

    Lavizzari, Anna; Colnaghi, Mariarosa; Ciuffini, Francesca; Veneroni, Chiara; Musumeci, Stefano; Cortinovis, Ivan; Mosca, Fabio

    2016-08-08

    Heated, humidified high-flow nasal cannula (HHHFNC) has gained increasing popularity as respiratory support for newborn infants thanks to ease of use and improved patient comfort. However, its role as primary therapy for respiratory distress syndrome (RDS) of prematurity needs to be further elucidated by large, randomized clinical trials. To determine whether HHHFNC provides respiratory support noninferior to nasal continuous positive airway pressure (nCPAP) or bilevel nCPAP (BiPAP) as a primary approach to RDS in infants older than 28 weeks' gestational age (GA). An unblinded, monocentric, randomized clinical noninferiority trial at a tertiary neonatal intensive care unit. Inborn infants at 29 weeks 0 days to 36 weeks 6 days of GA were eligible if presenting with mild to moderate RDS requiring noninvasive respiratory support. Criteria for starting noninvasive respiratory support were a Silverman score of 5 or higher or a fraction of inspired oxygen higher than 0.3 for a target saturation of peripheral oxygen of 88% to 93%. Infants were ineligible if they had major congenital anomalies or severe RDS requiring early intubation. Infants were enrolled between January 5, 2012, and June 28, 2014. Randomization to either HHHFNC at 4 to 6 L/min or nCPAP/BiPAP at 4 to 6 cm H2O. Need for mechanical ventilation within 72 hours from the beginning of respiratory support. The absolute risk difference in the primary outcome and its 95% confidence interval were calculated to determine noninferiority (noninferiority margin, 10%). An intention-to-treat analysis was performed. A total of 316 infants were enrolled in the study: 158 in the HHHFNC group (mean [SD] GA, 33.1 [1.9] weeks; 52.5% female) and 158 in the nCPAP/BiPAP group (mean [SD] GA, 33.0 [2.1] weeks; 47.5% female). The use of HHHFNC was noninferior to nCPAP with regard to the primary outcome: failure occurred in 10.8% vs 9.5% of infants, respectively (95% CI of risk difference, -6.0% to 8.6% [within the noninferiority margin]; P = .71). Significant between-group differences in secondary outcomes were not found between the HHHFNC and nCPAP/BiPAP groups, including duration of respiratory support (median [interquartile range], 4.0 [2.0 to 6.0] vs 4.0 [2.0 to 7.0] days; 95% CI of difference in medians, -1.0 to 0.5; P = .45), need for surfactant (44.3% vs 46.2%; 95% CI of risk difference, -9.8 to 13.5; P = .73), air leaks (1.9% vs 2.5%; 95% CI of risk difference, -3.3 to 4.5; P = .70), and bronchopulmonary dysplasia (4.4% vs 5.1%; 95% CI of risk difference, -3.9 to 7.2; P = .79). In this study, HHHFNC showed efficacy and safety similar to those of nCPAP/BiPAP when applied as a primary approach to mild to moderate RDS in preterm infants older than 28 weeks' GA. clinicaltrials.gov Identifier: NCT02570217.

  4. Trends in Pap Test Practices and Results: An 11-Year Review of the Annual ACHA Pap Test and STI Survey

    ERIC Educational Resources Information Center

    Eastman-Mueller, Heather P.; Oswalt, Sara B.

    2017-01-01

    Objective: To conduct a trend analysis of Pap test practices, Pap test results and related women's services and guidelines of college health centers. Participants: College health centers who participated in the annual ACHA Pap Test and STI (sexually transmitted infection) Survey years 2004-2014 (n ranged from 127 to 181 depending on year).…

  5. Biotransformation pathways of fluorotelomer-based polyfluoroalkyl substances: a review.

    PubMed

    Butt, Craig M; Muir, Derek C G; Mabury, Scott A

    2014-02-01

    The study reviews the current state of knowledge regarding the biotransformation of fluorotelomer-based compounds, with a focus on compounds that ultimately degrade to form perfluoroalkyl carboxylates (PFCAs). Most metabolism studies have been performed with either microbial systems or rats and mice, and comparatively few studies have used fish models. Furthermore, biotransformation studies thus far have predominately used the 8:2 fluorotelomer alcohol (FTOH) as the substrate. However, there have been an increasing number of studies investigating 6:2 FTOH biotransformation as a result of industry's transition to shorter-chain fluorotelomer chemistry. Studies with the 8:2 FTOH metabolism universally show the formation of perfluorooctanoate (PFOA) and, to a smaller fraction, perfluorononanoate (PFNA) and lower-chain-length PFCAs. In general, the overall yield of PFOA is low, presumably because of the multiple branches in the biotransformation pathways, including conjugation reactions in animal systems. There have been a few studies of non-FTOH biotransformation, which include polyfluoroalkyl phosphates (PAPs), 8:2 fluorotelomer acrylate (8:2 FTAC), and fluorotelomer carboxylates (FTCAs, FTUCAs). The PAPs compounds and 8:2 FTAC were shown to be direct precursors to FTOHs and thus follow similar degradation pathways. © 2013 SETAC.

  6. Predictors of positive airway pressure therapy adherence in children: a prospective study.

    PubMed

    DiFeo, Natalie; Meltzer, Lisa J; Beck, Suzanne E; Karamessinis, Laurie R; Cornaglia, Mary Anne; Traylor, Joel; Samuel, John; Gallagher, Paul R; Radcliffe, Jerilynn; Beris, Heidi; Menello, Mary Kate; Marcus, Carole L

    2012-06-15

    Children with obstructive sleep apnea are increasingly being treated with positive airway pressure (PAP), particularly if they have underlying medical conditions. Although PAP is an effective treatment, its use is challenging due to poor adherence. We hypothesized that demographic, psychosocial, and polysomnographic parameters would be related to PAP adherence. We therefore prospectively collected data potentially pertaining to PAP adherence, and correlated it with PAP use. Fifty-six patients and their parents completed a series of psychosocial questionnaires prior to PAP initiation. Objective adherence data were obtained after 1 and 3 months of PAP use. The population was primarily obese; 23% had neurodevelopmental disabilities. PAP adherence varied widely, with PAP being worn 22 ± 8 nights in month-1, but mean use was only 3 ± 3 h/night. The greatest predictor of use was maternal education (p = 0.002 for nights used; p = 0.033 for mean h used/night). Adherence was lower in African American children vs other races (p = 0.021). In the typically developing subgroup, adherence correlated inversely with age. Adherence did not correlate with severity of apnea, pressure levels, or psychosocial parameters other than a correlation between family social support and nights of PAP use in month-3. PAP adherence in children and adolescents is related primarily to family and demographic factors rather than severity of apnea or measures of psychosocial functioning. Further research is needed to determine the relative contributions of maternal education, socioeconomic status and cultural beliefs to PAP adherence in children, in order to develop better adherence programs.

  7. Who is getting Pap smears in urban Peru?

    PubMed Central

    Paz Soldan, Valerie A; Lee, Frank H; Carcamo, Cesar; Holmes, King K; Garnett, Geoff P; Garcia, Patricia

    2008-01-01

    Background Cervical cancer, although usually preventable by Pap smear screening, remains the leading cause of cancer-related deaths among women in Peru. The percentages and characteristics of women in Peru who have or have not had a Pap smear have not been defined. Methods In an urban community randomized trial of sexually transmitted infection (STI)/HIV prevention in Peru, 6712 randomly selected women between the ages of 18 and 29 from 20 cities were interviewed regarding having had cervical Pap smears. Results Among women sampled, only 30.9% had had a Pap smear. By multivariate analysis, the main predictors of having a Pap smear were having had sex, having had children, completion of secondary education and increasing age. Regional variations were also found: women from the highlands and rainforest were less likely to have had Pap smears than women from the coast. Conclusion A norm of seeking and receiving Pap smears has not been established among sexually active young Peruvian women. To improve Pap smear coverage in Peru, promotion efforts should target underserved women and regions with less coverage. PMID:18653515

  8. Enhancement of Chlorogenic Acid Production in Hairy Roots of Platycodon grandiflorum by Over-Expression of An Arabidopsis thaliana Transcription Factor AtPAP1

    PubMed Central

    Tuan, Pham Anh; Kwon, Do Yeon; Lee, Sanghyun; Arasu, Mariadhas Valan; Al-Dhabi, Naif Abdullah; Park, Nam Il; Park, Sang Un

    2014-01-01

    To improve the production of chlorogenic acid (CGA) in hairy roots of Platycodon grandiflorum, we induced over-expression of Arabidopsis thaliana transcription factor production of anthocyanin pigment (AtPAP1) using an Agrobacterium rhizogenes-mediated transformation system. Twelve hairy root lines showing over-expression of AtPAP1 were generated. In order to investigate the regulation of AtPAP1 on the activities of CGA biosynthetic genes, the expression levels of seven P. grandiflorum CGA biosynthetic genes were analyzed in the hairy root line that had the greatest accumulation of AtPAP1 transcript, OxPAP1-1. The introduction of AtPAP1 increased the mRNA levels of all examined CGA biosynthetic genes and resulted in a 900% up-regulation of CGA accumulation in OxPAP1-1 hairy roots relative to controls. This suggests that P. grandiflorum hairy roots that over-express the AtPAP1 gene are a potential alternative source of roots for the production of CGA. PMID:25153629

  9. Knowledge of cervical cancer, attitude and husband’s support of Pap smear among multiparous women which have Pap’s smear examination in Aviati clinic Padang Bulan Medan

    NASA Astrophysics Data System (ADS)

    Feriyawati, L.; Anggraini, D. R.; Fitrie, A. A.; Anggreini, R. N.

    2018-03-01

    Cervical cancer is a serious health problem and stated as the second cause of death of woman worldwide. Several studies have noted a higher incidence of cervical cancer with increasing parity. Early detection with Pap smear is proven to reduce mortality of patients. Knowledge, attitude and husband’s support contributed to theled womanto follow Pap smear examination. This study explores the knowledge of cervical cancer, attitude and husband’ s support of Pap smearin multiparous women that have Pap smear examination. This research is a quantitative study with cross sectional approach recruited 50 respondents as multiparous women that have Pap smear examination inAviati Clinic, Padang Bulan, Medan. The data were collected by self-reports using structured objectives by questionnaires. The result of this study showed that 66% respondents have high knowledge of cervical cancer and 76% respondents have ahigh attitude of Pap smear, but they almost have low husband’s support of Pap smear including information support (62%), emotional support (46%) and real support (50%). This study has revealed that multiparous women that had Pap smear examination generally had high knowledge about cervical cancer and positive attitude about Pap smear, even most of them had low husband’s support.

  10. 42 CFR 493.945 - Cytology; gynecologic examinations.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... dysplasia/CIN-2 and severe dysplasia/carcinoma in-situ/CIN-3. (2) Squamous cell carcinoma. (3... gynecologic examinations (Pap smears) in cytology, a program must provide test sets composed of 10- and 20..., provided the slides have been retained by the laboratory for the required period specified in §§ 493.1105(a...

  11. Routine Treatment of Cervical Cytological Cell Changes: Diagnostic Standard, Prevention and Routine Treatment of Cervical Cytological Cell Changes - An Assessment of Primary and Secondary Prevention and Routine Treatment Data in the Context of an Anonymous Data Collection from Practicing Gynaecologists; an Academic, Non-Interventional Study.

    PubMed

    Huber, J; Pötsch, B; Gantschacher, M; Templ, M

    2016-10-01

    Introduction: Diagnosis and treatment of vaginal and cervical cytological cell changes are described in European and national guidelines. The aim of this data collection was to evaluate the remission rates of PAP III and PAP III D cytological findings in patients over a period of 3-4 months. Method: The current state of affairs in managing suspicious and cytological findings (PAP III, and III D) in gynecological practice was assessed in the context of a data collection survey. An evaluation over a period of 24 months was conducted on preventative measures, the occurrence and changes to normal/suspect/pathological findings and therapy management (for suspicious or pathological findings). Results: 307 female patients were included in the analysis. At the time of the survey 186 patients (60.6 %) had PAP III and 119 (38.8 %) had PAP III D findings. The spontaneous remission rate of untreated PAP III patients was 6 % and that of untreated PAP III D patients was 11 %. The remission rates of patients treated with a vaginal gel were 77 % for PAP III and 71 % for PAP III D. Conclusion: A new treatment option was used in gynecological practice on patients with PAP III and PAP III D findings between confirmation and the next follow-up with excellent success.

  12. Predictors of Very Late Events After Percutaneous Mitral Valvuloplasty in Patients With Mitral Stenosis.

    PubMed

    Jorge, Elisabete; Pan, Manuel; Baptista, Rui; Romero, Miguel; Ojeda, Soledad; Suárez de Lezo, Javier; Faria, Henrique; Calisto, João; Monteiro, Pedro; Pêgo, Mariano; Suárez de Lezo, José

    2016-06-15

    Data on long-term outcomes of percutaneous mitral valvuloplasty (PMV) are still scarce. In addition, the persistence of pulmonary hypertension (PH) after PMV is a complication for which mechanisms and prognostic implications are unclear. Our aims were (1) to report the long-term outcomes of patients with rheumatic mitral stenosis treated with PMV; (2) to determine the risk factors for long-term poor outcomes; and (3) to analyze the prevalence and predictors of persistent PH. We prospectively enrolled 532 patients who underwent PMV from 1987 to 2011 at 2 hospitals. The following end points were assessed after PMV: all-cause mortality, mitral reintervention, a composite end point of all-cause mortality and mitral reintervention, and PH persistence. Survival status was available for 97% patients; the median follow-up was 10 years (interquartile range 4 to 18 years). Procedural success was achieved in 85% patients. During the follow-up, 21% patients died and 27% required mitral reintervention. Before PMV, 74% patients had PH that persisted after PMV in 45% of patients (p <0.001). Unfavorable valve anatomy (Wilkins score >8) and post-PMV mean pulmonary arterial pressure (PAP) were independent predictors of all-cause mortality, mitral reintervention, and the composite end point. Post-PMV mean PAP was significantly correlated with a mitral valve area (MVA) <2.5 cm(2) (p <0.001); in addition, on the echocardiographic follow-up, MVA was an independent predictor of systolic PAP (p <0.001). In conclusion, PMV represents an advantageous therapeutic option for patients with mitral stenosis in terms of long-term outcomes. Unfavorable valve anatomy and persistent PH were the most important predictors of long-term outcomes. The persistence of PH is associated with the MVA obtained after PMV. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. The importance of preoperative oxygen saturation as a predictor of pulmonary arterial hypertension after surgery of atrial septal defects.

    PubMed

    Park, Han Ki; Shin, Hong Ju; Park, Young Hwan; Ma, Bo Gyoung

    2016-09-01

    There is no concrete predictor of the change of pulmonary arterial pressure after surgical closure of an atrial septal defect (ASD) in patients with pulmonary arterial hypertension (PAH). The aim of this study was to investigate the role of preoperative room air arterial oxygen saturation (SaO2) (arterial blood gas data) as a predictor of postoperative PAH. The medical records of 36 patients [>20 years, mean pulmonary arterial pressure (mPAP) ≥25 mmHg] who underwent surgical closure of an ASD between March 2004 and January 2014 were retrospectively reviewed. The median age was 47 years (range, 24.6-65.9 years) and mPAP was 38 ± 14 mmHg. The mean pulmonary vascular resistance (Rp) was 3.9 ± 4.2 Wood units, and fenestration was performed in 12 (33%) patients. Only 1 patient received anti-PAH medication preoperatively. The median follow-up period was 4 years (range, 0-10 years). There were two hospital deaths, one of which was related to PAH. At the last follow-up, PAH (estimated tricuspid regurgitation velocity >3 m/s) existed in 7 patients (19%), and 10 patients (28%) were receiving anti-PAH medications (considered as clinical PAH). Univariate analysis for persistent clinical PAH revealed that mPAP, Qp/Qs, Rp, room air arterial oxygen saturation and postoperative functional class were significant risk factors. Only SaO2 remained a significant risk factor in multivariate analysis (P = 0.03). Preoperative room air SaO2 is a useful predictor of persistent PAH in adult patients undergoing surgical closure of an ASD. © The Author 2016. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

  14. Cervical Cancer Screening in an Early Diagnosis and Screening Center in Mersin, Turkey.

    PubMed

    Nayir, Tufan; Okyay, Ramazan Azim; Nazlican, Ersin; Yesilyurt, Hakki; Akbaba, Muhsin; Ilhan, Berrin; Kemik, Aytekin

    2015-01-01

    Cancer is a major public health problem due to the jeavy disease burden, fatality and tendency for increased incidence. Of all cancer types, cervical cancer is reported to be the fourth most common cancer in women, and the seventh overall, with an estimated 528,000 new cases worldwide in 2012. It features a long preclinical phase with slowly progressing precancerous lesions such as CIN 2 and 3 and adenocarcinoma in situ. Therefore, screening programs such as with Pap smear tests may play an important role in cervical cancer prevention. The purpose of this study was to present results of a Pap smear screening survey for cervical cancer targeting women living in an urban area in the province of Mersin, located in the Mediterranean region of Turkey. This community- based descriptive study included women living at Akdeniz county of Mersin province. A total of 1,032 screened women between 30 and 65 ages within the routine screening programme constituted the study population. The mean age of the participants was 43.8 ± 8.6 (min. 30, max. 65) years. The percentage of the participants who had previously undergone smears was 40.6%. Epithelial cell changes were found in 26 (2.5%) participants, with ASC-US in 18 (1.7%), ASC-H in 2 (0.2%), LSIL in 5 (0.5%) and HSIL in 1 (0.1%). The most common clinical presentation together with epithelial changes was abnormal vaginal discharge. Taking into account the presence of women who had never undergone Pap test; it should be offered at primary level of health care in the form of a community-based service to achieve reduced morbidity and mortality rates.

  15. Characterization of the regulatory network of BoMYB2 in controlling anthocyanin biosynthesis in purple cauliflower.

    PubMed

    Chiu, Li-Wei; Li, Li

    2012-10-01

    Purple cauliflower (Brassica oleracea L. var. botrytis) Graffiti represents a unique mutant in conferring ectopic anthocyanin biosynthesis, which is caused by the tissue-specific activation of BoMYB2, an ortholog of Arabidopsis PAP2 or MYB113. To gain a better understanding of the regulatory network of anthocyanin biosynthesis, we investigated the interaction among cauliflower MYB-bHLH-WD40 network proteins and examined the interplay of BoMYB2 with various bHLH transcription factors in planta. Yeast two-hybrid studies revealed that cauliflower BoMYBs along with the other regulators formed the MYB-bHLH-WD40 complexes and BobHLH1 acted as a bridge between BoMYB and BoWD40-1 proteins. Different BoMYBs exhibited different binding activity to BobHLH1. Examination of the BoMYB2 transgenic lines in Arabidopsis bHLH mutant backgrounds demonstrated that TT8, EGL3, and GL3 were all involved in the BoMYB2-mediated anthocyanin biosynthesis. Expression of BoMYB2 in Arabidopsis caused up-regulation of AtTT8 and AtEGL3 as well as a subset of anthocyanin structural genes encoding flavonoid 3'-hydroxylase, dihydroflavonol 4-reductase, and leucoanthocyanidin dioxygenase. Taken together, our results show that MYB-bHLH-WD40 network transcription factors regulated the bHLH gene expression, which may represent a critical feature in the control of anthocyanin biosynthesis. BoMYB2 together with various BobHLHs specifically regulated the late anthocyanin biosynthetic pathway genes for anthocyanin biosynthesis. Our findings provide additional information for the complicated regulatory network of anthocyanin biosynthesis and the transcriptional regulation of transcription factors in vegetable crops.

  16. Nasal versus oronasal continuous positive airway pressure masks for obstructive sleep apnea: a pilot investigation of pressure requirement, residual disease, and leak.

    PubMed

    Bakker, Jessie P; Neill, Alister M; Campbell, Angela J

    2012-09-01

    This single-blinded, randomized, controlled pilot study aimed to investigate whether there is a difference between nasal and oronasal masks in therapeutic continuous positive airway pressure (CPAP) requirement, residual disease, or leak when treating obstructive sleep apnea (OSA) and if differences were related to measures of upper airway size. Patients with severe OSA currently using CPAP at ≥4 h/night with a nasal mask were examined (including Mallampati scale, incisal relationship, and mandibular protrusion) and then randomized to receive auto-positive airway pressure (PAP) or fixed CPAP at a manually titrated pressure for 1 week each at home, with immediate crossover. Within each week, a nasal mask and two oronasal masks were to be used for two or three nights each in random order. Data were downloaded from the device. Twelve patients completed the trial (mean ± SD AHI 59.8 ± 28.6 events/h; CPAP 11.1 ± 3.2 cmH(2)O; BMI 37.7 ± 5.0 kg/m(2)). During auto-PAP, the median 95th percentile pressure delivered with all masks was within 0.5 cmH(2)O (p > 0.05). During CPAP, median residual AHI was 0.61 (IQR = 1.18) for the nasal mask, 1.70 (IQR = 4.04) for oronasal mask 1, and 2.48 (IQR = 3.74) for oronasal mask 2 (p = 0.03). The 95th percentile leak was lowest with the nasal mask during both CPAP and auto-PAP (both p < 0.01). Differences in pressure or residual disease were not related to measures of upper airway shape or body habitus. In obese OSA patients changing from a nasal to oronasal mask increased leak and residual AHI but did not affect the therapeutic pressure requirement. The findings of the current study highlight mask leak as the major difficulty in the use of oronasal masks.

  17. A Venom Serpin Splicing Isoform of the Endoparasitoid Wasp Pteromalus puparum Suppresses Host Prophenoloxidase Cascade by Forming Complexes with Host Hemolymph Proteinases*

    PubMed Central

    Yan, Zhichao; Fang, Qi; Liu, Yang; Xiao, Shan; Yang, Lei; Wang, Fei; An, Chunju; Werren, John H.; Ye, Gongyin

    2017-01-01

    To ensure successful parasitism, parasitoid wasps inject venom along with their eggs into their hosts. The venom serves to suppress host immune responses, including melanization. Venom from Pteromalus puparum, a pupal endoparasitoid, inhibits melanization of host hemolymph in vitro in a dose-dependent manner. Using assay-guided fractionation, a serpin splicing isoform with phenoloxidase inhibitory activity was identified as P. puparum serpin-1, venom isoform (PpS1V). This serpin gene has 16 predicted splicing isoforms that differ only in the C-terminal region. RT-PCR results show that the specific serpin isoform is differentially expressed in the venom gland. Recombinant PpS1V (rPpS1V) suppresses host prophenoloxidase (PPO) activation rather than inhibiting the phenoloxidase directly. Pulldown assays show that PpS1V forms complexes with two host hemolymph proteins, here named Pieris rapae hemolymph proteinase 8 (PrHP8) and P. rapae prophenoloxidase-activating proteinase 1 (PrPAP1), based on gene sequence blasting and phylogenetic analysis. The role of rPrPAP1 in the PPO activation cascade and its interaction with rPpS1V were confirmed. The stoichiometry of inhibition of PrPAP1 by PpS1V is 2.3. PpS1V also inhibits PPO activation in a non-natural host, Ostrinia furnacalis, through forming a complex with O. furnacalis serine protease 13 (OfSP13), an ortholog to PrPAP1. Our results identify a venom-enriched serpin isoform in P. puparum that inhibits host PPO activation, probably by forming a complex with host hemolymph proteinase PrPAP1. PMID:27913622

  18. Reliability of unaided naked-eye examination as a screening test for cervical lesions in a developing country setup.

    PubMed

    Darwish, Atef M; Abdulla, Sayed A; Zahran, Kamal M; Abdel-Fattah, Nermat A

    2013-04-01

    This study aimed to test the reliability of unaided naked-eye examination (UNEE) of the cervix as a sole cervical cancer screening test in a developing country setup compared with the standard cervical cytology. A total of 3,500 nonpregnant women aged between 25 and 55 years were included. An unlubricated bivalve speculum was inserted into the vagina under good light to visualize the cervix. A thorough UNEE of the cervix was done to detect any apparent lesions. Cervical smears were obtained using the long tip of an Ayre spatula. An additional endocervical sample was obtained by cytobrush. Women with abnormal Pap smears or visible cervical lesions by UNEE were scheduled for colposcopic examination. A biopsy specimen was obtained in every abnormal colposcopic examination. Of 3,500 cases, there were 9 (2.57%) preinvasive cervical lesions (cervical intraepithelial neoplasia 1-3) diagnosed with various diagnostic tools used in the study and confirmed by histopathologic examination. Of 3,500 cases, invasive cervical lesions were diagnosed in 6 (1.71%). The sensitivity of UNEE is much better than that of Pap smear (80% vs 60%) but less than that of colposcopy (86.7%). However, the specificity of UNEE (100%) is lower than that of Pap smear (91.16%) and better than that colposcopy (83.12%). The UNEE has a poor positive predictive value (3.75%) when compared with Pap smear (100%) and colposcopy (20%). The negative predictive values of the 3 tests were nearly comparable. Whenever access to Pap smear is limited, UNEE performed by general gynecologists and well-trained nurses is an acceptable alternative for detecting cervical premalignant or malignant lesions especially in low-resource settings.

  19. Acute Effects of Back Squats on Countermovement Jump Performance Across Multiple Sets of A Contrast Training Protocol in Resistance-Trained Males.

    PubMed

    Bauer, Pascal; Sansone, Pierpaolo; Mitter, Benedikt; Makivic, Bojan; Seitz, Laurent B; Tschan, Harald

    2018-01-03

    The present study was designed to evaluate the voluntary post-activation potentiation (PAP) effects of moderate (MI) or high intensity (HI) back squat exercises on countermovement jump (CMJ) performance across multiple sets of a contrast training protocol. Sixty resistance-trained male subjects (age, 23.3 ± 3.3 y; body mass, 86.0 ± 13.9 kg; parallel back squat 1-repetition maximum [1-RM], 155.2 ± 30.0 kg) participated in a randomized, cross-over study. After familiarization, the subjects visited the laboratory on three separate occasions. They performed a contrast PAP protocol comprising three sets of either MI (6×60% of 1-RM) or HI back squats (4x90% of 1-RM) or 20 s of recovery (CTRL) alternated with seven CMJs that were performed at 15 s, and 1, 3, 5, 7, 9 and 11 min after the back squats or recovery. Jump height and relative peak power output recorded with a force platform during MI and HI conditions were compared to those recorded during control condition to calculate the voluntary PAP effect. CMJ performance was decreased immediately after the squats but increased across all three sets of MI and HI between 3 - 7 minutes post-recovery. However, voluntary PAP effects were small or trivial and no difference between the three sets could be found. These findings demonstrate that practitioners can use MI and HI back squats to potentiate CMJs across a contrast training protocol, but a minimum of 3 min of recovery after the squats is needed to benefit from voluntary PAP.

  20. Knowledge, opinions and attitudes of Italian mothers towards HPV vaccination and Pap test.

    PubMed

    La Torre, Giuseppe; De Vito, Elisabetta; Ficarra, Maria Giovanna; Firenze, Alberto; Gregorio, Pasquale; Miccoli, Silvia; Giraldi, Guglielmo; Unim, Brigid; De Belvis, Giulio; Boccia, Antonio; Saulle, Rosella; Semyonov, Leda; Ferrara, Maria; Langiano, Elisa; Capizzi, Silvio; Nardella, Rosaria; Marsala, Maria Grazia Laura; Bonanno, Valentina; Ferrara, Clara; Guidi, Enrica; Bergamini, Mauro; Lupi, Silvia

    2015-01-01

    This study evaluated the knowledge and attitudes of Italian mothers - whose daughters had been vaccinated in 2012 - towards primary (anti-HPV vaccination) and secondary (Pap test screening) cervical cancer prevention, as well as sources of information and mother-daughter communication on health issues. The survey - part of a multicenter study carried out in 4 Italian cities (Ferrara, Rome, Cassino and Palermo) - was conducted through self-administered questionnaires. The first univariate analysis evaluated differences between mothers of under-18s and over-18s relative to knowledge and attitudes on HPV vaccination and Pap test. The second univariate analysis evaluated differences between the 2 groups of mothers and possible geographical variations regarding the sources of information on HPV and Pap test. The sample proved knowledgeable about the correlation between HPV and cervical cancer (>85%) but less aware of other HPV-related diseases. HPV vaccination should be administered before first sexual intercourse according to mothers of over-18s, and to 14- to 17-year-olds according to mothers of under-18s. Up to 88% of mothers of under-18s and 80% of mothers of over-18s declared that the vaccine should be given free of charge. More mothers of under-18s consulted a general practitioner (GP) or gynecologist before deciding to vaccinate their daughters. Mothers of under-18s received information on HPV vaccination mainly from GPs and gynecologists, while mothers of over-18s were informed through TV and books/journals. Over 80% of the sample declared satisfaction with the information received from their gynecologist during the Pap test. The findings provide useful information for the development of effective public health interventions that may help improve acceptance of HPV vaccination among mothers.

  1. A pilot study of minocycline for the prevention of paclitaxel-associated neuropathy: ACCRU study RU221408I.

    PubMed

    Pachman, Deirdre R; Dockter, Travis; Zekan, Patricia J; Fruth, Briant; Ruddy, Kathryn J; Ta, Lauren E; Lafky, Jacqueline M; Dentchev, Todor; Le-Lindqwister, Nguyet Anh; Sikov, William M; Staff, Nathan; Beutler, Andreas S; Loprinzi, Charles L

    2017-11-01

    Paclitaxel is associated with both an acute pain syndrome (P-APS) and chronic chemotherapy-induced peripheral neuropathy (CIPN). Given that extensive animal data suggest that minocycline may prevent chemotherapy-induced neurotoxicity, the purpose of this pilot study was to investigate the efficacy of minocycline for the prevention of CIPN and the P-APS. Patients with breast cancer were enrolled prior to initiating neoadjuvant or adjuvant weekly paclitaxel for 12 weeks and were randomized to receive minocycline 200 mg on day 1 followed by 100 mg twice daily or a matching placebo. Patients completed (1) an acute pain syndrome questionnaire daily during chemotherapy to measure P-APS and (2) the EORTC QLQ-CIPN20 questionnaire at baseline, prior to each dose of paclitaxel, and monthly for 6 months post treatment, to measure CIPN. Forty-seven patients were randomized. There were no remarkable differences noted between the minocycline and placebo groups for the overall sensory neuropathy score of the EORTC QLQ-CIPN20 or its individual components, which evaluate tingling, numbness and shooting/burning pain in hands and feet. However, patients taking minocycline had a significant reduction in the daily average pain score attributed to P-APS (p = 0.02). Not only were no increased toxicities reported with minocycline, but there was a significant reduction in fatigue (p = 0.02). Results of this pilot study do not support the use of minocycline to prevent CIPN, but suggest that it may reduce P-APS and decrease fatigue; further study of the impact of this agent on those endpoints may be warranted.

  2. Virulence factors, serogroups and antimicrobial resistance properties of Escherichia coli strains in fermented dairy products.

    PubMed

    Dehkordi, Farhad Safarpoor; Yazdani, Farshad; Mozafari, Jalal; Valizadeh, Yousef

    2014-04-07

    From a clinical perspective, it is essential to know the microbial safety of fermented dairy products. Doogh and kashk are fermented dairies. These products are used by millions of people but their microbial qualities are unknown. Shiga toxin producing Escherichia coli (STEC) is one of the most commonly detected pathogens in the cases of food poisoning and food-borne illnesses. The present investigation was carried out in order to study the molecular characterization and antimicrobial resistance properties of STEC strains isolated from fermented dairy products. Six hundred fermented dairy samples were collected and immediately transferred to the laboratory. All samples were cultured immediately and those that were E. coli-positive were analyzed for the presence of O157 , O26, O103, O111, O145, O45, O91, O113, O121 and O128 STEC serogroups, tetA, tetB, blaSHV, CITM, cmlA, cat1, aadA1, dfrA1, qnr, aac (3)-IV, sul1 and ereA antibiotic resistance genes and stx1, stx2, eaeA, ehly, cnf1, cnf2, iutA, cdtB, papA, traT, sfaS and fyuA virulence factors using PCR. Antimicrobial susceptibility testing was performed also using disk diffusion methodology with Mueller-Hinton agar. Fifty out of 600 (8.33%) dairy samples harbored E. coli. In addition, yoghurt was the most commonly contaminated dairy. O157 (26%) and O26 (12%) were the most commonly detected serogroups. A significant difference was found between the frequency of Attaching and Effacing E. coli and Enterohaemorrhagic E. coli (P <0.05). Stx1 (44%), eae (36%), papA (32%) stx2 (30%), and ehly (28%) were the most commonly detected virulence factors. The genes encode resistance against tetracycline (tetA and tetB) (76% and 70%, respectively), cephalothin (blaSHV) (38%), ampicillin (CITM) (36%) and gentamicin (aac (3)-IV) (32%) were the most commonly detected. High resistance levels to tetracycline (84%), penicillin (46%), ampicillin (38%) and streptomycin (36%) were observed. Fermented dairy products can easily become contaminated by antibiotic resistant STEC strains. Our findings should raise awareness about antibiotic resistance in Iran. Clinicians should exercise caution when prescribing antibiotics, especially in veterinary treatments.

  3. Electrochemical Detection of p-Aminophenol by Flexible Devices Based on Multi-Wall Carbon Nanotubes Dispersed in Electrochemically Modified Nafion

    PubMed Central

    Scandurra, Graziella; Antonella, Arena; Ciofi, Carmine; Saitta, Gaetano; Lanza, Maurizio

    2014-01-01

    A conducting composite prepared by dispersing multi-walled carbon nanotubes (MWCNTs) into a host matrix consisting of Nafion, electrochemically doped with copper, has been prepared, characterized and used to modify one of the gold electrodes of simply designed electrochemical cells having copier grade transparency sheets as substrates. Electrical measurements performed in deionized water show that the Au/Nafion/Au-MWCNTs–Nafion:Cu cells can be successfully used in order to detect the presence of p-aminophenol (PAP) in water, without the need for any supporting electrolyte. The intensity of the redox peaks arising when PAP is added to deionized water is found to be linearly related to the analyte in the range from 0.2 to 1.6 μM, with a detection limit of 90 nM and a sensitivity of 7 μA·(μM−1)·cm−2. PMID:24854357

  4. Roles of phagocytosis activating protein (PAP) in Aeromonas hydrophila infected Cyprinus carpio.

    PubMed

    Wonglapsuwan, Monwadee; Kongmee, Pataraporn; Suanyuk, Naraid; Chotigeat, Wilaiwan

    2016-06-01

    Cyprinus carpio (koi) is one of the most popular ornamental fish. A major problem for C. carpio farming is bacterial infections especially by Aeromonas hydrophila. Previously studies had shown that the Phagocytosis Activating Protein (PAP) gene was involved in the innate immune response of animals. Therefore, we attempted to identify a role for the PAP gene in the immunology of C. carpio. The expression of the PAP was found in C. carpio whole blood and increased when the fish were stimulated by inactivated A. hydrophila. In addition, PAP-phMGFP DNA was injected as an immunostimulant. The survival rate and the phagocytic index were significantly increased in the A. hydrophila infected fish that received the PAP-phMGFP DNA immunostimulant. A chitosan-PAP-phMGFP nanoparticle was then developed and feeded into fish which infected with A. hydrophila. These fish had a significantly lower mortality rate than the control. Therefore, this research confirmed a key role for PAP in protection fish from bacterial infection and the chitosan-PAP-phMGFP nanoparticle could be a good prototype for fish immunostimulant in the future. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Medium- and Large-Sized Autologous Breast Reconstruction using a Fleur-de-lys Profunda Femoris Artery Perforator Flap Design: A Report Comparing Results with the Horizontal Profunda Femoris Artery Perforator Flap.

    PubMed

    Hunsinger, Vincent; Lhuaire, Martin; Haddad, Kevin; Wirz, Francesco-Saverio; Abedalthaqafi, Samah; Obadia, Déborah; Derder, Mohamed; Marchac, Alexandre; Benjoar, Marc David; Hivelin, Mikael; Lantieri, Laurent

    2018-06-02

     The volume of the profunda femoris artery perforator (PAP) flap limits its indications to small- and medium-sized breast reconstructions after modified radical mastectomy for cancer. We report a modified PAP flap design, including not only a vertical extension that increases its volume but also the skin surface, which suits larger breasts requiring immediate or delayed breast reconstructions and compare the results with our horizontal skin paddle PAP flap experience.  In our center between November 2014 and November 2016, 51 consecutive patients underwent a PAP flap breast reconstruction following breast cancer. A retrospective analysis on the collected data was performed to compare 34 patients with a bra cup smaller than C who underwent 41 horizontal PAP flap procedures, with those ( n  = 17) of a bra cup greater than or equal to C who underwent 21 fleur-de-lys PAP flap procedures. Demographic, anthropometric, flap and surgical characteristics, postoperative complication rates, and hospital stay were compared between the two groups.  The average flap weight was 480 g (range: 340-735 g) for the fleur-de-lys PAP flap group compared with 222 g (range: 187-325 g) for the horizontal PAP flap procedure ( p  < 0.001). The mean flap dimensions were 25 × 18 cm for the fleur-de-lys PAP flap group compared with 25 × 7 cm in the horizontal PAP flap group. No flap failure was observed in the fleur-de-lys PAP flap group compared with two flap failures secondary to venous thrombosis in the horizontal PAP flap group ( NS ). Three patients (14%) experienced delayed healing at the donor site compared with four patients (10%) in the horizontal PAP flap group ( NS ).  The fleur-de-lys skin paddle design not only allows an increase of the horizontal PAP flap volume, but also increases the skin surface, with an acceptable donor site morbidity. For medium- or large-sized breasts, the fleur-de-lys PAP flap seems to be ideal when a DIEP flap-based reconstruction is contraindicated. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  6. Bi-level positive airway pressure ventilation for treating heart failure with central sleep apnea that is unresponsive to continuous positive airway pressure.

    PubMed

    Dohi, Tomotaka; Kasai, Takatoshi; Narui, Koji; Ishiwata, Sugao; Ohno, Minoru; Yamaguchi, Tetsu; Momomura, Shin-Ichi

    2008-07-01

    Cheyne-Stokes respiration with central sleep apnea (CSR-CSA) is associated with a poor prognosis in patients with heart failure (HF). However, some patients do not respond to continuous positive airway pressure (CPAP), so other therapeutic modalities should be considered, such as bi-level positive airway pressure (PAP), which also assists respiration and might be effective for such patients. The 20 patients with HF because of left ventricular systolic dysfunction were assessed: 8 had ischemic etiology, and all had severe CSA according to the apnea - hypopnea index (AHI) determined by polysomnography. All diagnosed patients underwent repeat polysomnography using CPAP. The AHI improved significantly in 11 (AHI <15), but only slightly in 9, in whom the AHI remained high (>or=15). Bi-level PAP titration significantly improved the AHI in the latter group. Those who were unresponsive to CPAP had significantly lower PaCO(2), higher plasma brain natriuretic peptide (BNP), longer mean duration of CSR and fewer obstructive episodes than CPAP responders. After 6 months of positive airway support with either CPAP (n=9) or bi-level PAP (n=7), BNP levels significantly decreased and left ventricular ejection fraction significantly increased. Bi-level PAP could be an effective alternative for patients with HF and pure CSR-CSA who are unresponsive to CPAP.

  7. U.S. Preventive Services Task Force recommendations and cancer screening among female Medicare beneficiaries.

    PubMed

    Salloum, Ramzi G; Kohler, Racquel E; Jensen, Gail A; Sheridan, Stacey L; Carpenter, William R; Biddle, Andrea K

    2014-03-01

    Medicare covers several cancer screening tests not currently recommended by the U.S. Preventive Services Task Force (Task Force). In September 2002, the Task Force relaxed the upper age limit of 70 years for breast cancer screening recommendations, and in March 2003 an upper age limit of 65 years was introduced for cervical cancer screening recommendations. We assessed whether mammogram and Pap test utilization among women with Medicare coverage is influenced by changes in the Task Force's recommendations for screening. We identified female Medicare beneficiaries aged 66-80 years and used bivariate probit regression to examine the receipt of breast (mammogram) and cervical (Pap test) cancer screening reflecting changes in the Task Force recommendations. We analyzed 9,760 Medicare Current Beneficiary Survey responses from 2001 to 2007. More than two-thirds reported receiving a mammogram and more than one-third a Pap test in the previous 2 years. Lack of recommendation was given as a reason for not getting screened among the majority (51% for mammogram and 75% for Pap). After controlling for beneficiary-level socioeconomic characteristics and access to care factors, we did not observe a significant change in breast and cervical cancer screening patterns following the changes in Task Force recommendations. Although there is evidence that many Medicare beneficiaries adhere to screening guidelines, some women may be receiving non-recommended screening services covered by Medicare.

  8. Clinical significance of HPV DNA cotesting in Korean women with ASCUS or ASC-H.

    PubMed

    Lee, Sanghoon; Kim, Jae Won; Hong, Jin Hwa; Song, Jae Yun; Lee, Jae Kwan; Kim, In Sun; Lee, Nak Woo

    2014-12-01

    The purpose of this study was to evaluate the clinical significance of Human papillomavirus (HPV) DNA cotesting in Korean women with abnormal Papanicolaou (Pap) smear results based on colposcopic pathology. A total of 1012 women underwent liquid-based Pap smears and hybrid capture II HPV DNA tests followed by colposcopy at the Korea University Hospital from January 2007 to May 2012. Of these women, 832 women were included in this retrospective study. The mean patient age was 45.4 ± 13.7 years (range:15-80). The distribution of Pap smear results was normal (4.7%), atypical squamous cells of uncertain significance (ASCUS) (42.1%), low-grade squamous intraepithelial lesion (26.8%), ASC-H (7.0%), and high-grade squamous intraepithelial lesion (HSIL) (19.5%). In women with ASCUS, none of the 87 HPV-negative had ≥cervical intraepithelial neoplasia (CIN2) (P < 0.001). In women with ASC-H, only one out of 17 HPV-negative vs. 14 out of 41 HPV-positive had ≥CIN2 (P = 0.025). In patients with HSIL, 54.5% of HPV-negative had ≥CIN2, as compared to 80.8% of HPV-positive with ≥CIN2 (P = 0.039). Patients were further analyzed by age groups: <30 and ≥30 years. In HPV-negative women, there was a significant difference in the ratio of ≥CIN2 (30.8% <30 vs. 4.5% ≥30, P = 0.005). When the HPV DNA test was negative in women ≥30, the risk of ≥CIN2 was significantly lower (P < 0.001). HPV DNA cotesting in women with ASCUS and ASC-H furnish healthcare providers with informative data. There is a lower proportion of ≥CIN2 in HPV-negative women and a higher proportion of ≥CIN2 in HPV-positive. When HPV data were further evaluated by age group, the risk of ≥CIN2 was lower in HPV-negative women, especially in women ≥30. © 2014 Wiley Periodicals, Inc.

  9. The effect of health education on the knowledge, attitude, and uptake of free Pap smear among female teachers in Birnin-Kebbi, North-Western Nigeria.

    PubMed

    Adamu, A N; Abiola, A O; Ibrahim, Mto

    2012-01-01

    The Routine Pap smear test has successfully reduced the incidence of invasive cervical cancer in the presence of a proper structure for its implementation. This study was designed to assess the effect of health education on the knowledge, attitude, and uptake of Pap smear among female teachers. It was a quasi-experimental, controlled study with a pre-test, post-test design. A total of 100 respondents were recruited for each of the intervention and control groups, by the multistage sampling technique. The mean knowledge score of cervical cancer was low in both the interventions (25.5% ± 10.5) and control groups (18.9% ± 10.0) at baseline; a significant rise to 57.2% ± 20.7 was recorded after the intervention in the Intervention group (P<0.0001). The baseline mean attitude score was also low in the intervention and control groups (17.1% ± 6.3 and 14.1% ± 6.4, respectively); post intervention there was a significant rise of up to 28.0% ± 12.8 in the Intervention group (P<0.0001). The proportion of respondents with a reported practice of Pap smear was low and similar in both the groups at baseline (1.1 and 4.9% in the intervention and control groups, respectively, P=0.16). Uptake of free Pap smear was poor at the post-intervention phase in both the groups (P=0.45). Reported reasons for poor uptake included the respondents' dislike for the test (38.4%) and the belief that the test was not necessary (24.4%). About 20% of the respondents did not have any reason at all. Health education had no significant effect on the uptake of a free Pap smear among teachers. Despite the significant improvement in the attitude toward the test, many respondents did not like the test after than before the intervention. Sociocultural issues such as the gender of the sample collector, and system factors like few service delivery points, and the time required to access the service could have contributed to the poor uptake recorded in this study. A program designed to improve routine cervical cancer screening by Pap smear should therefore address not only the knowledge and cost, but also the sociocultural and systemic factors.

  10. Distinct regulation of alternative polyadenylation and gene expression by nuclear poly(A) polymerases

    PubMed Central

    Li, Wencheng; Laishram, Rakesh S.; Hoque, Mainul; Ji, Zhe

    2017-01-01

    Abstract Polyadenylation of nascent RNA by poly(A) polymerase (PAP) is important for 3′ end maturation of almost all eukaryotic mRNAs. Most mammalian genes harbor multiple polyadenylation sites (PASs), leading to expression of alternative polyadenylation (APA) isoforms with distinct functions. How poly(A) polymerases may regulate PAS usage and hence gene expression is poorly understood. Here, we show that the nuclear canonical (PAPα and PAPγ) and non-canonical (Star-PAP) PAPs play diverse roles in PAS selection and gene expression. Deficiencies in the PAPs resulted in perturbations of gene expression, with Star-PAP impacting lowly expressed mRNAs and long-noncoding RNAs to the greatest extent. Importantly, different PASs of a gene are distinctly regulated by different PAPs, leading to widespread relative expression changes of APA isoforms. The location and surrounding sequence motifs of a PAS appear to differentiate its regulation by the PAPs. We show Star-PAP-specific PAS usage regulates the expression of the eukaryotic translation initiation factor EIF4A1, the tumor suppressor gene PTEN and the long non-coding RNA NEAT1. The Star-PAP-mediated APA of PTEN is essential for DNA damage-induced increase of PTEN protein levels. Together, our results reveal a PAS-guided and PAP-mediated paradigm for gene expression in response to cellular signaling cues. PMID:28911096

  11. Application of the Carolina Framework for Cervical Cancer Prevention.

    PubMed

    Moss, Jennifer L; McCarthy, Schatzi H; Gilkey, Melissa B; Brewer, Noel T

    2014-03-01

    The Carolina Framework for Cervical Cancer Prevention describes 4 main causes of cervical cancer incidence: human papillomavirus (HPV) infection, lack of screening, screening errors, and not receiving follow-up care. We present 2 applications of the Carolina Framework in which we identify high-need counties in North Carolina and generate recommendations for improving prevention efforts. We created a cervical cancer prevention need index (CCPNI) that ranked counties on cervical cancer mortality, HPV vaccine initiation and completion, Pap smear screening, and provision of Pap tests to rarely- or never-screened women. In addition, we conducted in-depth interviews with 19 key informants from programs and agencies involved in cervical cancer prevention in North Carolina. North Carolina's 100 counties varied widely on individual CCPNI components, including annual cervical cancer mortality (median 2.7/100,000 women; range 0.0-8.0), adolescent girls' HPV vaccine initiation (median 42%; range 15%-62%), and Pap testing in the previous 3 years among Medicaid-insured adult women (median 59%; range 40%-83%). Counties with the greatest prevention needs formed 2 distinct clusters in the northeast and south-central regions of the state. Interviews generated 9 recommendations to improve cervical cancer prevention in North Carolina, identifying applications to specific programs and policies in the state. This study found striking geographic disparities in cervical cancer prevention need in North Carolina. Future prevention efforts in the state should prioritize high-need regions as well as recommended strategies and applications in existing programs. Other states can use the Carolina Framework to increase the impact of their cervical cancer prevention efforts. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. The SAL-PAP Chloroplast Retrograde Pathway Contributes to Plant Immunity by Regulating Glucosinolate Pathway and Phytohormone Signaling.

    PubMed

    Ishiga, Yasuhiro; Watanabe, Mutsumi; Ishiga, Takako; Tohge, Takayuki; Matsuura, Takakazu; Ikeda, Yoko; Hoefgen, Rainer; Fernie, Alisdair R; Mysore, Kirankumar S

    2017-10-01

    Chloroplasts have a crucial role in plant immunity against pathogens. Increasing evidence suggests that phytopathogens target chloroplast homeostasis as a pathogenicity mechanism. In order to regulate the performance of chloroplasts under stress conditions, chloroplasts produce retrograde signals to alter nuclear gene expression. Many signals for the chloroplast retrograde pathway have been identified, including chlorophyll intermediates, reactive oxygen species, and metabolic retrograde signals. Although there is a reasonably good understanding of chloroplast retrograde signaling in plant immunity, some signals are not well-understood. In order to understand the role of chloroplast retrograde signaling in plant immunity, we investigated Arabidopsis chloroplast retrograde signaling mutants in response to pathogen inoculation. sal1 mutants (fry1-2 and alx8) responsible for the SAL1-PAP retrograde signaling pathway showed enhanced disease symptoms not only to the hemibiotrophic pathogen Pseudomonas syringae pv. tomato DC3000 but, also, to the necrotrophic pathogen Pectobacterium carotovorum subsp. carotovorum EC1. Glucosinolate profiles demonstrated the reduced accumulation of aliphatic glucosinolates in the fry1-2 and alx8 mutants compared with the wild-type Col-0 in response to DC3000 infection. In addition, quantification of multiple phytohormones and analyses of their gene expression profiles revealed that both the salicylic acid (SA)- and jasmonic acid (JA)-mediated signaling pathways were down-regulated in the fry1-2 and alx8 mutants. These results suggest that the SAL1-PAP chloroplast retrograde pathway is involved in plant immunity by regulating the SA- and JA-mediated signaling pathways.

  13. Enlarged squamous cell nuclei in cervical cytologic specimens from perimenopausal women ("PM Cells") : a cause of ASC overdiagnosis.

    PubMed

    Cibas, Edmund S; Browne, Tara-Jane; Bassichis, Michelle H Mantel; Lee, Kenneth R

    2005-07-01

    We studied the appropriateness of interpreting squamous cells with enlarged, smooth, bland nuclei in perimenopausal women ("PM cells") as atypical squamous cells (ASCs). Papanicolaou smears (Paps) from 100 women (40-55 years old) with a cytologic interpretation of ASC of undetermined significance (ASCUS) and human papillomavirus (HPV) testing or a biopsy within 6 months were reviewed by 2 observers without knowledge of the biopsy diagnosis or HPV results. Cases in which both reviewers agreed that the Paps were diagnosed more properly as "negative for intraepithelial lesion or malignancy" were compared with cases of "true ASCUS," using histologic squamous intraepithelial lesion and/or a positive high-risk HPV test as a positive outcome (abnormal follow-up). Of 100 cases, 28 were reclassified as benign by both observers. In 15 of these, the original ASCUS interpretation was based on cells with bland nuclear enlargement (2-3 times the area of intermediate cell nuclei), smooth nuclear membranes, and fine chromatin. Abnormal follow-up was identified in 1 (7%) of 15 benign cases but in 30 (42%) of 72 true ASCUS cases (P = .023). PM cells are a significant cause of ASC overdiagnosis in women 40 to 55 years old. Cervical Paps with cells no more atypical than these can be interpreted safely as negative for intraepithelial lesion or malignancy.

  14. Change of the human taste bud volume over time.

    PubMed

    Srur, Ehab; Stachs, Oliver; Guthoff, Rudolf; Witt, Martin; Pau, Hans Wilhelm; Just, Tino

    2010-08-01

    The specific aim of this study is to measure the taste volume in healthy human subjects over a 2.5-month period and to demonstrate morphological changes of the peripheral taste organs. Eighteen human taste buds in four fungiform papillae (fPap) were examined over a 10-week period. The fungiform papillae investigated were selected based on the form of the papillae or the arrangement of surface taste pores. Measurements were performed over 10 consecutive weeks, with five scans in a day once a week. The following parameters were measured: height and diameter of the taste bud, diameter of the fungiform papilla and diameter of the taste pore. The findings of this exploratory study indicated that (1) taste bud volumes changed over a 10-week period, (2) the interval between two volume maxima within the 10-week period was 3-5 weeks, and (3) the diameter of the fPap did not correlate with the volume of a single taste bud or with the volume of all taste buds in the fPap within the 10-week period. This exploratory in vivo study revealed changes in taste bud volumes in healthy humans with age-related gustatory sensitivity. These findings need to be considered when studying the effect of denervation of fungiform papillae in vivo using confocal microscopy. Crown Copyright 2009. Published by Elsevier Ireland Ltd. All rights reserved.

  15. HvPap-1 C1A Protease and HvCPI-2 Cystatin Contribute to Barley Grain Filling and Germination.

    PubMed

    Diaz-Mendoza, Mercedes; Dominguez-Figueroa, Jose D; Velasco-Arroyo, Blanca; Cambra, Ines; Gonzalez-Melendi, Pablo; Lopez-Gonzalvez, Angeles; Garcia, Antonia; Hensel, Goetz; Kumlehn, Jochen; Diaz, Isabel; Martinez, Manuel

    2016-04-01

    Proteolysis is an essential process throughout the mobilization of storage proteins in barley (Hordeum vulgare) grains during germination. It involves numerous types of enzymes, with C1A Cys proteases the most abundant key players. Manipulation of the proteolytic machinery is a potential way to enhance grain yield and quality, and it could influence the mobilization of storage compounds along germination. Transgenic barley plants silencing or over-expressing the cathepsin F-like HvPap-1 Cys protease show differential accumulation of storage molecules such as starch, proteins, and free amino acids in the grain. It is particularly striking that the HvPap-1 artificial microRNA lines phenotype show a drastic delay in the grain germination process. Alterations to the proteolytic activities in the over-expressing and knock-down grains associated with changes in the level of expression of several C1A peptidases were also detected. Similarly, down-regulating cystatin Icy-2, one of the proteinaceous inhibitors of the cathepsin F-like protease, also has important effects on grain filling. However, the ultimate physiological influence of manipulating a peptidase or an inhibitor cannot be always predicted, since the plant tries to compensate the modified proteolytic effects by modulating the expression of some other peptidases or their inhibitors. © 2016 American Society of Plant Biologists. All Rights Reserved.

  16. Non-invasive monitoring of pulmonary artery pressure from timing information by EIT: experimental evaluation during induced hypoxia.

    PubMed

    Proença, Martin; Braun, Fabian; Solà, Josep; Adler, Andy; Lemay, Mathieu; Thiran, Jean-Philippe; Rimoldi, Stefano F

    2016-06-01

    Monitoring of pulmonary artery pressure (PAP) in pulmonary hypertensive patients is currently limited to invasive solutions. We investigate a novel non-invasive approach for continuous monitoring of PAP, based on electrical impedance tomography (EIT), a safe, low-cost and non-invasive imaging technology. EIT recordings were performed in three healthy subjects undergoing hypoxia-induced PAP variations. The pulmonary pulse arrival time (PAT), a timing parameter physiologically linked to the PAP, was automatically calculated from the EIT signals. Values were compared to systolic PAP values from Doppler echocardiography, and yielded strong correlation scores ([Formula: see text]) for all three subjects. Results suggest the feasibility of non-invasive, unsupervised monitoring of PAP.

  17. World-Wide Indoor Exposure to Polyfluoroalkyl Phosphate Esters (PAPs) and other PFASs in Household Dust.

    PubMed

    Eriksson, Ulrika; Kärrman, Anna

    2015-12-15

    Human exposure to perfluorooctanoic acid (PFOA) and other per- and polyfluoroalkyl substances (PFASs) is ongoing and in some cases increasing, despite efforts made to reduce emissions. The role of precursor compounds such as polyfluorinated phosphate esters (PAPs) has received increasing attention, but there are knowledge gaps regarding their occurrence and impact on human exposure. In this study, mono-, di-, and triPAPs, perfluorinated alkyl acids (PFAAs), saturated, and unsaturated fluorotelomer carboxylic acids (FTCA/FTUCAs), perfluoroalkane sulfonamides, and sulfonamidethanols (FOSA/FOSEs), and one fluorotelomer sulfonic acid (FTSA)) were compared in household dust samples from Canada, the Faroe Islands, Sweden, Greece, Spain, Nepal, Japan, and Australia. Mono-, di-, and triPAPs, including several diPAP homologues, were frequently detected in dust from all countries, revealing an ubiquitous spread in private households from diverse geographic areas, with significant differences between countries. The median levels of monoPAPs and diPAPs ranged from 3.7 ng/g to 1 023 ng/g and 3.6 ng/g to 692 ng/g, respectively, with the lowest levels found in Nepal and the highest in Japan. The levels of PAPs exceeded those of the other PFAS classes. These findings reveal the importance of PAPs as a source of PFAS exposure worldwide.

  18. Pediatric Patients with High Pulmonary Arterial Pressure in Congenital Heart Disease Have Increased Tracheal Diameters Measured by Computed Tomography.

    PubMed

    Ohashi, Nobuko; Imai, Hidekazu; Seino, Yutaka; Baba, Hiroshi

    2017-12-06

    Determination of the appropriate tracheal tube size using formulas based on age or height often is inaccurate in pediatric patients with congenital heart disease (CHD), particularly in those with high pulmonary arterial pressure (PAP). Here, the authors compared tracheal diameters between pediatric patients with CHD with high PAP and low PAP. Retrospective clinical study. Hospital. Pediatric patients, from birth to 6 months of age, requiring general anesthesia and tracheal intubation who underwent computed tomography were included. Patients with mean pulmonary artery pressure >25 mmHg were allocated to the high PAP group, and the remaining patients were allocated to the low PAP group. The primary outcome was the tracheal diameter at the cricoid cartilage level, and the secondary goal was to observe whether the size of the tracheal tube was appropriate compared with that obtained using predictable formulas based on age or height. The mean tracheal diameter was significantly larger in the high PAP group than in the low PAP group (p < 0.01). Pediatric patients with high PAP required a larger tracheal tube size than predicted by formulas based on age or height (p = 0.04 for age and height). Pediatric patients with high PAP had larger tracheal diameters than those with low PAP and required larger tracheal tubes compared with the size predicted using formulas based on age or height. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. A questionnaire study of cervical cancer screening beliefs and practices of Chinese and Caucasian mother-daughter pairs living in Canada.

    PubMed

    Chang, Sabrina C H; Woo, Jane S T; Gorzalka, Boris B; Brotto, Lori A

    2010-03-01

    Papanicolaou (Pap) testing rates among Chinese women remain low compared with their Caucasian counterparts despite extensive efforts to raise awareness of the importance of regular screening. We examined three potential predictors of Pap testing behaviour in Chinese women: acculturation, cervical cancer screening belief accuracy, and intergenerational transmission. Caucasian (n = 78) and Chinese (n = 93) female university students and their mothers completed questionnaires concerning acculturation, Pap testing beliefs, and behaviours. Ethnic group comparisons revealed that Chinese daughters and mothers had lower Pap testing rates and less accurate beliefs regarding cervical cancer screening. Among women who had had at least one Pap test, there was no ethnic difference in the proportion of women who adhered to the recommended screening frequency. Among the Chinese women, lower heritage acculturation was correlated with higher cancer screening belief accuracy in both the daughters and their mothers. Maternal Pap testing behaviour was predicted by level of cancer screening belief accuracy, whereas daughters' Pap testing behaviour was predicted by previous experience of sexual intercourse and heritage acculturation. No intergenerational transmission of Pap testing beliefs or behaviours was found. The accuracy of cancer screening beliefs, level of acculturation and experience of sexual intercourse may be predictors of Pap testing behaviour in Chinese women. Contrary to our prediction, we found no support for intergenerational transmission, suggesting that Pap testing beliefs and behaviours of Chinese women are independent of the beliefs and behaviours of their mothers.

  20. Hemodynamic heterogeneity of connective tissue disease patients with borderline mean pulmonary artery pressure and its distinctive characters from those with normal pulmonary artery pressure: a retrospective study.

    PubMed

    Asari, Yusa; Yamasaki, Yoshioki; Tsuchida, Kosei; Suzuki, Kengo; Akashi, Yoshihiro J; Okazaki, Takahiro; Ozaki, Shoichi; Yamada, Hidehiro; Kawahata, Kimito

    2018-05-18

    To clarify whether patients with connective tissue disease (CTD)-associated borderline mean pulmonary artery pressure (mPAP) have distinctive hemodynamic characteristics from those with normal mPAP and whether pathogenesis is as heterogeneous as manifest pulmonary hypertension (PH). Seventy-five CTD patients who underwent right heart catheterization (RHC) from 2008 through 2016 were retrospectively analyzed. We compared between-group differences in clinical and hemodynamic findings: normal mPAP (n = 35), borderline mPAP (n = 15), and PH (n = 25). A therapeutic intervention trial based on RHC results was performed in nine patients. The values of tricuspid regurgitation pressure gradient (TRPG) in patients with borderline mPAP were comparable at rest but became higher after exercise compared to those with a normal mPAP (P = 0.01). Pulmonary artery wedge pressure in patients with borderline mPAP was higher than in those with normal mPAP (P < 0.0001) and comparable to those with PH. Each of the three patients was treated for pre-capillary and post-capillary disease and two for interstitial lung disease (ILD). During the mean follow-up period of 40 months, mPAP or TRPG normalized in all patients treated for pre-capillary and post-capillary disease. One patient with severe ILD developed to PH and died from it. CTD patients with borderline mPAP, the underlining pathogenesis of which is heterogeneous as PH, have distinctive hemodynamic characteristics from those with normal mPAP. Whether a specific treatment targeting the inflammatory process or local hemodynamics may alter the clinical course to PH is a topic for future research.

  1. Species and tissues specific differentiation of processed animal proteins in aquafeeds using proteomics tools.

    PubMed

    Rasinger, J D; Marbaix, H; Dieu, M; Fumière, O; Mauro, S; Palmblad, M; Raes, M; Berntssen, M H G

    2016-09-16

    The rapidly growing aquaculture industry drives the search for sustainable protein sources in fish feed. In the European Union (EU) since 2013 non-ruminant processed animal proteins (PAP) are again permitted to be used in aquafeeds. To ensure that commercial fish feeds do not contain PAP from prohibited species, EU reference methods were established. However, due to the heterogeneous and complex nature of PAP complementary methods are required to guarantee the safe use of this fish feed ingredient. In addition, there is a need for tissue specific PAP detection to identify the sources (i.e. bovine carcass, blood, or meat) of illegal PAP use. In the present study, we investigated and compared different protein extraction, solubilisation and digestion protocols on different proteomics platforms for the detection and differentiation of prohibited PAP. In addition, we assessed if tissue specific PAP detection was feasible using proteomics tools. All work was performed independently in two different laboratories. We found that irrespective of sample preparation gel-based proteomics tools were inappropriate when working with PAP. Gel-free shotgun proteomics approaches in combination with direct spectral comparison were able to provide quality species and tissue specific data to complement and refine current methods of PAP detection and identification. To guarantee the safe use of processed animal protein (PAP) in aquafeeds efficient PAP detection and monitoring tools are required. The present study investigated and compared various proteomics workflows and shows that the application of shotgun proteomics in combination with direct comparison of spectral libraries provides for the desired species and tissue specific classification of this heat sterilized and pressure treated (≥133°C, at 3bar for 20min) protein feed ingredient. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Perspectives on Pap Test Follow Up Care Among Rural Appalachian Women

    PubMed Central

    Schoenberg, Nancy; Baltisberger, Julie; Bardach, Shoshana; Dignan, Mark

    2010-01-01

    Approximately one to three quarters of women notified of abnormal Pap test results do not receive appropriate follow up care, dramatically elevating their risk for invasive cervical cancer (ICC). We explored barriers to/facilitators of follow up care for women in two counties in Appalachian Kentucky, where ICC incidence and mortality are significantly higher than the national average. In-depth interviews were conducted among 27 Appalachian women and seven local health department personnel. Those who had been told of an atypical Pap test result tended to have one of three reactions; (1) not alarmed and generally did not obtain follow-up care; (2) alarmed and obtained follow up care; or (3) alarmed, but did not obtain care. Each of these typologies appeared to be shaped by a differing set of three categories of influences: personal factors; procedure/provider/system factors; and ecological/community factors. Recommendations to increase appropriate follow up care included pursuing research on explanations for these typologies and developing tailored interventions specific to women in each of the response types. PMID:20981638

  3. Vaginal flora changes on Pap smears after insertion of levonorgestrel-releasing intrauterine device.

    PubMed

    Donders, Gilbert G G; Berger, Judith; Heuninckx, Hélène; Bellen, Gert; Cornelis, Ann

    2011-04-01

    The levonorgestrel intrauterine system (LNG-IUS) combines a uterine foreign body and the continuous release of low-dose levonorgestrel for contraception. Its influence on the rate of vulvovaginal infections and flora disturbance is insufficiently known, but important for contraceptive advice in women, especially those who develop recurrent vaginosis or Candida vulvovaginitis. Slides of 286 women who had a Pap smear taken before and 1 to 2 years after placement of a LNG-IUS were blindly reviewed for the presence of abnormal vaginal flora (AVF), bacterial vaginosis (BV), aerobic vaginitis (AV) and Candida vaginitis (CV). Prior to insertion, there were no differences in vaginal flora abnormalities between women using different kinds of contraception. LNG-IUS users did not have different rates of AVF, BV, AV or CV, but the general risk to develop any infection was increased. Uterine bleeding after insertion did not seem to predict a different flora type. We found that Pap smears suggested more vaginal infections after 1 year of LNG-IUS use than prior to insertion of the device. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Breast and cervical cancer screening among Hispanic subgroups in the USA: estimates from the National Health Interview Survey 2008, 2010, and 2013.

    PubMed

    Shoemaker, Meredith L; White, Mary C

    2016-03-01

    This study examined patterns in mammography and Pap test use across and within subpopulations of Hispanic women. Based on data from the National Health Interview Survey (2008, 2010, and 2013), we estimated the proportion of Hispanic women reporting testing for breast and cervical cancer for specific subgroups. We examined test use by demographic characteristics using Chi-square tests. Overall, the proportion of women aged 50-74 years who reported a mammogram within the past 2 years did not differ significantly across Hispanic subgroups. Among publically and uninsured women, however, proportions of mammography utilization varied significantly across Hispanic subgroups. The proportion of women aged 21-65 years who received a Pap test within the past 3 years differed significantly across Hispanic subgroups. Among subgroups of Hispanic women, patterns in mammography and Pap test use vary by insurance status, length of US residency, and type of screening. Certain subgroups of Hispanic women may benefit from culturally tailored efforts to promote breast and cervical cancer screening.

  5. The shoot stem cell niche in angiosperms: expression patterns of WUS orthologues in rice and maize imply major modifications in the course of mono- and dicot evolution.

    PubMed

    Nardmann, Judith; Werr, Wolfgang

    2006-12-01

    In Arabidopsis, stem cell homeostasis in the shoot apical meristem (SAM) is controlled by a feedback loop between WUS and CLV functions. We have identified WUS orthologues in maize and rice by a detailed phylogenetic analysis of the WOX gene family and subsequent cloning. A single WUS orthologue is present in the rice genome (OsWUS), whereas the allotetraploid maize genome contains 2 WUS paralogues (ZmWUS1 and ZmWUS2). None of the isolated grass WUS orthologues displays an organizing center-type expression pattern in the vegetative SAM as in Arabidopsis. In contrast, the grass-specific expression patterns relate to the specification of new phytomers consistent with the transcriptional expression patterns of TD1 and FON1 (CLV1 orthologues of maize and rice, respectively). Moreover, the grass WUS and CLV1 orthologues are coexpressed in all reproductive meristems, where fasciation and supernumerary floral organs occur in td1 or fon1 loss-of-function mutants. The expression patterns of WUS orthologues in both grass species compared with those of dicots imply that major changes in WUS function, which are correlated with changes in CLV1 signaling, have occurred during angiosperm evolution and raise doubts about the uniqueness of the WUS/CLV antagonism in the maintenance of the shoot stem cell niche in grasses.

  6. T-piece resuscitators: how do they compare?

    PubMed

    Hinder, Murray; McEwan, Alistair; Drevhammer, Thomas; Donaldson, Snorri; Tracy, Mark Brian

    2018-05-04

    The T-piece resuscitator (TPR) has seen increased use as a primary resuscitation device with newborns. Traditional TPR design uses a high resistance expiratory valve to produce positive end expiratory pressure (PEEP) or continuous positive airway pressure (CPAP) at resuscitation. A new TPR device that uses a dual flow ratio valve (fluidic flip) to produce PEEP/CPAP is now available (rPAP). We aimed to compare the measured ventilation performance of different TPR devices in a controlled bench test study. Single operator provided positive pressure ventilation to an incremental testlung compliance (Crs) model (0.5-5 mL/cmH 2 O) with five different brands of TPR device (Atom, Neopuff, rPAP, GE Panda warmer and Draeger Resuscitaire). At recommended peak inflation pressure (PIP) 20 cmH 2 O, PEEP of 5 cmH 2 O and rate of 60 inflations per minute. 1864 inflations were analysed. Four of the five devices tested demonstrated inadvertent elevations in mean PEEP (5.5-10.3 cmH 2 O, p<0.001) from set value as Crs was increased, while one device (rPAP) remained at the set value. Measured PIP exceeded the set value in two infant warmer devices (GE and Draeger) with inbuilt TPR at Crs of 0.5 (24.5 and 23.5 cmH 2 O, p<0.001). Significant differences were seen in tidal volumes across devices particularly at higher Crs (p<0.001). Results show important variation in delivered ventilation from set values due to inherent TPR device design characteristics with a range of lung compliances expected at birth. Device-generated inadvertent PEEP and overdelivery of PIP may be clinically deleterious for term and preterm newborns or infants with larger Crs during resuscitation. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  7. An in vitro study of the effects of t-PA and tranexamic acid on whole blood coagulation and fibrinolysis.

    PubMed

    Godier, Anne; Parmar, Kiran; Manandhar, Karuna; Hunt, Beverley J

    2017-02-01

    Acute traumatic coagulopathy is characterised by fibrinolysis and low fibrinogen. It is unclear how much fibrinogenolysis contributes to reduce fibrinogen levels. The study aim was to: investigate in vitro the effects of tissue-plasminogen activator (t-PA) and tranexamic acid (TXA) on coagulation and fibrinolysis. Whole blood was spiked with varying t-PA concentrations. Clauss fibrinogen levels and thrombelastography (TEG, Haemonetics) were performed, including functional fibrinogen level (FLEV). TXA effects were assessed using four TXA concentrations. Recorded parameters from kaolin activated TEG included maximal amplitude (MA), clot strength (G), percentage lysis (LY). Plasmin-antiplasmin complex (PAP), endogenous thrombin potential (ETP), prothrombin fragment 1+2 (PF1+2), factor V and factor VIII levels were all measured. t-PA induced fibrinolysis: it increased PAP and LY, but decreased MA and G. t-PA induced fibrinogenolysis, with a concentration-dependant decrease in fibrinogen from 2.7 (2.6-3.1) to 0.8 (0.8-0.9) g/L with 60 nM t-PA. FLEV and fibrinogen levels were well correlated. High t-PA doses increased PF1+2, decreased ETP of 19% and FVIII of 63% but not FV. TXA had no effect on plasmin generation as evidenced by no change in PAP. It corrected LY, MA and G and partly protected fibrinogen against fibrinogenolysis: 0.03 mg/mL TXA reduced the fibrinogen fall induced by t-PA 20 nM from 43% to 14%. TXA halved the FVIII fall and increased ETP. t-PA induced plasminogen activation and fibrinogenolysis in a concentration-dependant manner. TXA did not affect plasmin activation but reduced fibrinogenolysis. These results suggest that TXA given early in bleeding patients may prevent fibrinogenolysis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  8. Milrinone Use is Associated With Postoperative Atrial Fibrillation Following Cardiac Surgery

    PubMed Central

    Fleming, Gregory A.; Murray, Katherine T.; Yu, Chang; Byrne, John G.; Greelish, James P.; Petracek, Michael R.; Hoff, Steven J.; Ball, Stephen K.; Brown, Nancy J.; Pretorius, Mias

    2009-01-01

    Background Postoperative atrial fibrillation (AF), a frequent complication following cardiac surgery, causes morbidity and prolongs hospitalization. Inotropic drugs are commonly used perioperatively to support ventricular function. This study tested the hypothesis that the use of inotropic drugs is associated with postoperative AF. Methods and Results We evaluated perioperative risk factors in 232 patients who underwent elective cardiac surgery. All patients were in sinus rhythm at surgery. Sixty-seven (28.9%) patients developed AF a mean of 2.9±2.1 days after surgery. Patients who developed AF stayed in the hospital longer (P<0.001) and were more likely to die (P=0.02). Milrinone use was associated with an increased risk of postoperative AF (58.2% versus 26.1% in non-users, P<0.001). Older age (63.4±10.7 versus 56.7±12.3 years, P<0.001), hypertension (P=0.04), lower preoperative ejection fraction (P=0.03), mitral valve surgery (P=0.02), right ventricular dysfunction (P=0.03), and higher mean pulmonary artery pressure (PAP) (27.1±9.3 versus 21.8±7.5 mmHg, P=0.001) were also associated with postoperative AF. In multivariable logistic regression, age (P<0.001), ejection fraction (P=0.02), and milrinone use (odds ratio 4.86, 95% CI 2.31-10.25, P<0.001) independently predicted postoperative AF. When data only from patients with pulmonary artery catheters were analyzed and PAP was included in the model, age, milrinone use (odds ratio 4.45, 95% CI 2.01-9.84, P<0.001), and higher PAP (P=0.02) were associated with an increased risk of postoperative AF. Adding other potential confounders or stratifying analysis by mitral valve surgery did not change the association of milrinone use with postoperative AF. Conclusion Milrinone use is an independent risk factor for postoperative AF following elective cardiac surgery. PMID:18824641

  9. Severity of nocturnal hypoxia and daytime hypercapnia predicts CPAP failure in patients with COPD and obstructive sleep apnea overlap syndrome.

    PubMed

    Kuklisova, Zuzana; Tkacova, Ruzena; Joppa, Pavol; Wouters, Emiel; Sastry, Manuel

    2017-02-01

    Obstructive sleep apnea (OSA) and chronic obstructive pulmonary disease (COPD) are independent risk factors for cardiovascular diseases. In patients with OSA and concurrent COPD, continuous positive airway pressure (CPAP) therapy improves survival. Nevertheless, a significant proportion of such patients do not tolerate CPAP. The aim of the present study was to analyze early predictors of CPAP failure in patients with OSA and concurrent COPD, and to evaluate the effects of bilevel positive airway pressure (BiPAP) in this high-risk group of patients. A post hoc analysis from the database of 2100 patients diagnosed with OSA between 2012 and 2014 identified 84 subjects as having concomitant COPD and meeting inclusion criteria. Demographic data, pulmonary function tests, OSA parameters, blood gases, response to CPAP and BiPAP titration, and two months of therapy were collected. A multivariate model was generated to find determinants of CPAP failure. Primary CPAP failure was found in 23% of patients who were more obese (p = 0.018), had worse lung function, lower PO 2 (p = 0.023) and higher PCO 2 while awake (p < 0.001), and more sleep time with an SpO 2  < 90% (CT90%) (p < 0.001) compared to those who responded to CPAP. In multivariate analysis, PCO 2 while awake [odds ratio (OR) 29.5, confidence interval (CI) 2.22-391, p = 0.010] and CT90% (OR 1.06, CI 1.01-1.11, p = 0.017) independently predicted CPAP failure after adjustments for covariates. The BiPAP therapy was well tolerated and effectively alleviated hypercapnia in all patients with primary CPAP failure. Daytime hypercapnia and nocturnal hypoxia are independent predictors of early CPAP failure in patients with the OSA-COPD overlap syndrome. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Diagnostic Approach to Patients with Atypical Squamous Cells of Undetermined Significance Cytologic Findings on Cervix

    PubMed Central

    Jahic, Mahira; Jahic, Elmir

    2016-01-01

    Background: Atypical squamous cells of undetermined significance (ASCUS) is a term that refers to inflammatory, reactive and reparative processes which are atypical and of higher level and insufficient to be classified as cervical intraepithelial lesions (CIN). Aims: Examine of frequency of HPV infection in ASCUS lesions and regression, stagnation and progression during six-month period. Subjects and Methods: Prospective study was conducted over a period of 3 years. In private gynecological ambulance „Dr Mahira Jahic”. Analysis of PAP smears and HPV typization have been done in 50 patients and PAP test has been repeated after six months. X² test was used for statistical analysis. Results: Analysis of 1784 PAP smears showed normal results in 86,6% (N-1530), and abnormal in 13% (N-254). ASCUS in 7,4% (N-133) and ASC-H in 0,5% (N-9), LSIL in 4,4% (N-80), HSIL in 1,3% (N-24), CIN II in 1,2% (N-20), CIN III in 0,2% (N-4). Progression occurred in 18% (9), persistence in 74% (37) and regression in 8%. Patients with ASC-H lesion 0,5% (N-9), PH results showed 22% (N-2) Carcinoma in situ, 33% (N-3) CIN II, 22% (N-2) CIN I and 22% (N-2) chronic cervicitis. Patients with CIN I in 88% (N-7) were positive on HPV of high risk. Patients with persistent ASCUS result were positive in 51% (N-19). The number of CIN I lesions found in women with ASCUS is bigger and statistically significant (p<0,05) in relation to number of CIN I findings found in regular examinations. Conclusion: Monitoring women with ASCUS lesion, especially HPV positive to high risk group is the best way of selection of women who should be treated and monitored in order to prevent cervical cancer. PMID:27703293

  11. Applying Sparse Machine Learning Methods to Twitter: Analysis of the 2012 Change in Pap Smear Guidelines. A Sequential Mixed-Methods Study.

    PubMed

    Lyles, Courtney Rees; Godbehere, Andrew; Le, Gem; El Ghaoui, Laurent; Sarkar, Urmimala

    2016-06-10

    It is difficult to synthesize the vast amount of textual data available from social media websites. Capturing real-world discussions via social media could provide insights into individuals' opinions and the decision-making process. We conducted a sequential mixed methods study to determine the utility of sparse machine learning techniques in summarizing Twitter dialogues. We chose a narrowly defined topic for this approach: cervical cancer discussions over a 6-month time period surrounding a change in Pap smear screening guidelines. We applied statistical methodologies, known as sparse machine learning algorithms, to summarize Twitter messages about cervical cancer before and after the 2012 change in Pap smear screening guidelines by the US Preventive Services Task Force (USPSTF). All messages containing the search terms "cervical cancer," "Pap smear," and "Pap test" were analyzed during: (1) January 1-March 13, 2012, and (2) March 14-June 30, 2012. Topic modeling was used to discern the most common topics from each time period, and determine the singular value criterion for each topic. The results were then qualitatively coded from top 10 relevant topics to determine the efficiency of clustering method in grouping distinct ideas, and how the discussion differed before vs. after the change in guidelines . This machine learning method was effective in grouping the relevant discussion topics about cervical cancer during the respective time periods (~20% overall irrelevant content in both time periods). Qualitative analysis determined that a significant portion of the top discussion topics in the second time period directly reflected the USPSTF guideline change (eg, "New Screening Guidelines for Cervical Cancer"), and many topics in both time periods were addressing basic screening promotion and education (eg, "It is Cervical Cancer Awareness Month! Click the link to see where you can receive a free or low cost Pap test.") It was demonstrated that machine learning tools can be useful in cervical cancer prevention and screening discussions on Twitter. This method allowed us to prove that there is publicly available significant information about cervical cancer screening on social media sites. Moreover, we observed a direct impact of the guideline change within the Twitter messages.

  12. Physiological changes in rumen fermentation during acidosis induction and its control using a multivalent polyclonal antibody preparation in heifers.

    PubMed

    Blanch, M; Calsamiglia, S; DiLorenzo, N; DiCostanzo, A; Muetzel, S; Wallace, R J

    2009-05-01

    Physiological changes in rumen fermentation during acidosis induction and its control using a multivalent polyclonal antibody preparation (PAP) were studied in a completely randomized experiment using 12 crossbred heifers (452 +/- 20 kg of BW). Treatments were control (CTR) or PAP. The acidosis induction protocol consisted of 3 periods: 3 mo of 100% fescue hay fed for ad libitum intake, 10 d (from d 1 to 10 of the experiment) of adaptation to the treatment (100% forage feeding + 10 mL/d of PAP top-dressed to the treatment group), and 5 d (from d 11 to 15 of the experiment) of transition, which consisted of increasing the concentrate (16.5% CP) 2.5 kg/d up to 12.5 kg/d while maintaining ad libitum intake of fescue and providing 10 mL/d of PAP to the treated heifers. Concentrate feeding of 12.5 kg/d was maintained until heifers developed acidosis (from d 16 to 22 of the experiment). When an animal was considered acidotic, it was changed to a 50:50 forage:concentrate diet, monitored for 4 d, and removed from the experiment. Samples of ruminal fluid were collected before and 6 h after feeding to determine pH, VFA, lactate, protozoa counts, and DNA extraction for quantitative real-time PCR and denaturing gradient gel electrophoresis analyses. Only samples collected during adaptation to the treatment, at 3 and 1 d before acidosis, on the acidosis day, and at 1 and 4 d after acidosis were analyzed. Differences were declared at P < 0.05. Heifers (83% for CTR, and 50% for PAP) entered into acidosis 5.25 +/- 0.17 d after the beginning of the transition. The fermentation profile of animals with acidosis was similar between treatments. From 3 d before acidosis to acidosis day, decreases in pH and in acetate-to-propionate ratio and increases in total VFA, butyrate, and entodiniomorph counts were observed. However, the greatest concentrations of Streptococcus bovis and Megasphaera elsdenii (79 +/- 54 and 104 +/- 73 ng of DNA/mL of ruminal fluid, respectively) and a decrease in DMI (10.6 vs. 6.46 kg, respectively) were recorded 1 d after acidosis. Compared with CTR heifers, heifers fed PAP had greater pH before feeding on d 6 (6.70 vs. 6.11), 8 (6.54 vs. 5.95), and 9 (7.26 vs. 6.59) after the beginning of the feeding challenge. Heifers fed PAP tended to have greater total VFA concentrations than CTR (124 and 114 +/- 4.0 mM, respectively). These results indicate that PAP may be effective in controlling acidosis of heifers during a rapid transition to a high-concentrate diet.

  13. Rules for scoring respiratory events in sleep: update of the 2007 AASM Manual for the Scoring of Sleep and Associated Events. Deliberations of the Sleep Apnea Definitions Task Force of the American Academy of Sleep Medicine.

    PubMed

    Berry, Richard B; Budhiraja, Rohit; Gottlieb, Daniel J; Gozal, David; Iber, Conrad; Kapur, Vishesh K; Marcus, Carole L; Mehra, Reena; Parthasarathy, Sairam; Quan, Stuart F; Redline, Susan; Strohl, Kingman P; Davidson Ward, Sally L; Tangredi, Michelle M

    2012-10-15

    The American Academy of Sleep Medicine (AASM) Sleep Apnea Definitions Task Force reviewed the current rules for scoring respiratory events in the 2007 AASM Manual for the Scoring and Sleep and Associated Events to determine if revision was indicated. The goals of the task force were (1) to clarify and simplify the current scoring rules, (2) to review evidence for new monitoring technologies relevant to the scoring rules, and (3) to strive for greater concordance between adult and pediatric rules. The task force reviewed the evidence cited by the AASM systematic review of the reliability and validity of scoring respiratory events published in 2007 and relevant studies that have appeared in the literature since that publication. Given the limitations of the published evidence, a consensus process was used to formulate the majority of the task force recommendations concerning revisions.The task force made recommendations concerning recommended and alternative sensors for the detection of apnea and hypopnea to be used during diagnostic and positive airway pressure (PAP) titration polysomnography. An alternative sensor is used if the recommended sensor fails or the signal is inaccurate. The PAP device flow signal is the recommended sensor for the detection of apnea, hypopnea, and respiratory effort related arousals (RERAs) during PAP titration studies. Appropriate filter settings for recording (display) of the nasal pressure signal to facilitate visualization of inspiratory flattening are also specified. The respiratory inductance plethysmography (RIP) signals to be used as alternative sensors for apnea and hypopnea detection are specified. The task force reached consensus on use of the same sensors for adult and pediatric patients except for the following: (1) the end-tidal PCO(2) signal can be used as an alternative sensor for apnea detection in children only, and (2) polyvinylidene fluoride (PVDF) belts can be used to monitor respiratory effort (thoracoabdominal belts) and as an alternative sensor for detection of apnea and hypopnea (PVDFsum) only in adults.The task force recommends the following changes to the 2007 respiratory scoring rules. Apnea in adults is scored when there is a drop in the peak signal excursion by ≥ 90% of pre-event baseline using an oronasal thermal sensor (diagnostic study), PAP device flow (titration study), or an alternative apnea sensor, for ≥ 10 seconds. Hypopnea in adults is scored when the peak signal excursions drop by ≥ 30% of pre-event baseline using nasal pressure (diagnostic study), PAP device flow (titration study), or an alternative sensor, for ≥ 10 seconds in association with either ≥ 3% arterial oxygen desaturation or an arousal. Scoring a hypopnea as either obstructive or central is now listed as optional, and the recommended scoring rules are presented. In children an apnea is scored when peak signal excursions drop by ≥ 90% of pre-event baseline using an oronasal thermal sensor (diagnostic study), PAP device flow (titration study), or an alternative sensor; and the event meets duration and respiratory effort criteria for an obstructive, mixed, or central apnea. A central apnea is scored in children when the event meets criteria for an apnea, there is an absence of inspiratory effort throughout the event, and at least one of the following is met: (1) the event is ≥ 20 seconds in duration, (2) the event is associated with an arousal or ≥ 3% oxygen desaturation, (3) (infants under 1 year of age only) the event is associated with a decrease in heart rate to less than 50 beats per minute for at least 5 seconds or less than 60 beats per minute for 15 seconds. A hypopnea is scored in children when the peak signal excursions drop is ≥ 30% of pre-event baseline using nasal pressure (diagnostic study), PAP device flow (titration study), or an alternative sensor, for ≥ the duration of 2 breaths in association with either ≥ 3% oxygen desaturation or an arousal. In children and adults, surrogates of the arterial PCO(2) are the end-tidal PCO(2) or transcutaneous PCO(2) (diagnostic study) or transcutaneous PCO(2) (titration study). For adults, sleep hypoventilation is scored when the arterial PCO(2) (or surrogate) is > 55 mm Hg for ≥ 10 minutes or there is an increase in the arterial PCO(2) (or surrogate) ≥ 10 mm Hg (in comparison to an awake supine value) to a value exceeding 50 mm Hg for ≥ 10 minutes. For pediatric patients hypoventilation is scored when the arterial PCO(2) (or surrogate) is > 50 mm Hg for > 25% of total sleep time. In adults Cheyne-Stokes breathing is scored when both of the following are met: (1) there are episodes of ≥ 3 consecutive central apneas and/or central hypopneas separated by a crescendo and decrescendo change in breathing amplitude with a cycle length of at least 40 seconds (typically 45 to 90 seconds), and (2) there are five or more central apneas and/or central hypopneas per hour associated with the crescendo/decrescendo breathing pattern recorded over a minimum of 2 hours of monitoring.

  14. Costs and Cost Effectiveness of Three Approaches for Cervical Cancer Screening among HIV-Positive Women in Johannesburg, South Africa

    PubMed Central

    Lince-Deroche, Naomi; Phiri, Jane; Michelow, Pam; Smith, Jennifer S.; Firnhaber, Cindy

    2015-01-01

    Background South Africa has high rates of HIV and HPV and high incidence and mortality from cervical cancer. However, cervical cancer is largely preventable when early screening and treatment are available. We estimate the costs and cost-effectiveness of conventional cytology (Pap), visual inspection with acetic acid (VIA) and HPV DNA testing for detecting cases of CIN2+ among HIV-infected women currently taking antiretroviral treatment at a public HIV clinic in Johannesburg, South Africa. Methods Method effectiveness was derived from a validation study completed at the clinic. Costs were estimated from the provider perspective using micro-costing between June 2013-April 2014. Capital costs were annualized using a discount rate of 3%. Two different service volume scenarios were considered. Threshold analysis was used to explore the potential for reducing the cost of HPV DNA testing. Results VIA was least costly in both scenarios. In the higher volume scenario, the average cost per procedure was US$ 3.67 for VIA, US$ 8.17 for Pap and US$ 54.34 for HPV DNA. Colposcopic biopsies cost on average US$ 67.71 per procedure. VIA was least sensitive but most cost-effective at US$ 17.05 per true CIN2+ case detected. The cost per case detected for Pap testing was US$ 130.63 using a conventional definition for positive results and US$ 187.52 using a more conservative definition. HPV DNA testing was US$ 320.09 per case detected. Colposcopic biopsy costs largely drove the total and per case costs. A 71% reduction in HPV DNA screening costs would make it competitive with the conservative Pap definition. Conclusions Women need access to services which meet their needs and address the burden of cervical dysplasia and cancer in this region. Although most cost-effective, VIA may require more frequent screening due to low sensitivity, an important consideration for an HIV-positive population with increased risk for disease progression. PMID:26569487

  15. Costs and Cost Effectiveness of Three Approaches for Cervical Cancer Screening among HIV-Positive Women in Johannesburg, South Africa.

    PubMed

    Lince-Deroche, Naomi; Phiri, Jane; Michelow, Pam; Smith, Jennifer S; Firnhaber, Cindy

    2015-01-01

    South Africa has high rates of HIV and HPV and high incidence and mortality from cervical cancer. However, cervical cancer is largely preventable when early screening and treatment are available. We estimate the costs and cost-effectiveness of conventional cytology (Pap), visual inspection with acetic acid (VIA) and HPV DNA testing for detecting cases of CIN2+ among HIV-infected women currently taking antiretroviral treatment at a public HIV clinic in Johannesburg, South Africa. Method effectiveness was derived from a validation study completed at the clinic. Costs were estimated from the provider perspective using micro-costing between June 2013-April 2014. Capital costs were annualized using a discount rate of 3%. Two different service volume scenarios were considered. Threshold analysis was used to explore the potential for reducing the cost of HPV DNA testing. VIA was least costly in both scenarios. In the higher volume scenario, the average cost per procedure was US$ 3.67 for VIA, US$ 8.17 for Pap and US$ 54.34 for HPV DNA. Colposcopic biopsies cost on average US$ 67.71 per procedure. VIA was least sensitive but most cost-effective at US$ 17.05 per true CIN2+ case detected. The cost per case detected for Pap testing was US$ 130.63 using a conventional definition for positive results and US$ 187.52 using a more conservative definition. HPV DNA testing was US$ 320.09 per case detected. Colposcopic biopsy costs largely drove the total and per case costs. A 71% reduction in HPV DNA screening costs would make it competitive with the conservative Pap definition. Women need access to services which meet their needs and address the burden of cervical dysplasia and cancer in this region. Although most cost-effective, VIA may require more frequent screening due to low sensitivity, an important consideration for an HIV-positive population with increased risk for disease progression.

  16. Cytological Anal Squamous Intraepithelial Lesions Associated with Anal High-Risk Human Papillomavirus Infections among Men Who Have Sex with Men in Northern Thailand

    PubMed Central

    Ruanpeng, Darin; Kaewpoowat, Quanhathai; Supindham, Taweewat; Settakorn, Jongkolnee; Sukpan, Kornkanok; Utaipat, Utaiwan; Miura, Toshiyuki; Kosashunhanan, Natthapol; Saokhieo, Pongpun; Songsupa, Radchanok; Wongthanee, Antika

    2016-01-01

    Background Anal cancer, one of human papillomavirus (HPV) related malignancies, has increased in recent decades, particularly among men who have sex with men (MSM) and HIV-infected (HIV+) persons. We aimed to explore the prevalence of anal squamous intraepithelial lesions (ASIL) using Papanicolau (Pap) screening among MSM in northern Thailand and its associated factors. Methods Two hundreds MSM aged ≥18 years reporting receptive anal intercourse in the prior 6 months were recruited from July 2012 through January 2013. Medical history and behavioral data were collected by staff interview and computer-assisted self interview. Anal Pap smear, HPV genotyping, and HIV testing were performed. Two pathologists blinded to HPV and HIV status reported cytologic results by Bethesda classification. Results Mean age was 27.2 years (range 18–54). Overall, 86 (43.0%) had ASIL: 28 (14.2%) with atypical cells of undetermined significance (ASCUS), 1 (0.5%) with atypical squamous cells—cannot exclude high-grade squamous intraepithelial lesion (ASC-H), 56 (28.4%) with low-grade squamous intraepithelial lesion (LSIL), and 1 (0.5%) with high-grade squamous intraepithelial lesion (HSIL). ASIL was associated by univariate analysis (p ≤0.05) with older age, gender identity other than bisexual (i.e., gay men and transgender women), rectal douching, anal symptoms, genital warts, HIV positivity, and high-risk-HPV infection. However, on multiple logistic regression ASIL was associated only with high-risk HPV type (p = 0.002) and HIV infection (p = 0.01). Conclusions ASIL is quite common in high-risk MSM in northern Thailand and is associated with high-risk HPV types and HIV infection. Routine anal Pap screening should be considered, given the high frequency of ASIL, particularly in the HIV+. High resolution anoscopy (HRA), not done here, should be to confirm PAP smears whose sensitivity and specificity are quite variable. Timely HPV vaccination should be considered for this population. PMID:27227684

  17. Cytological Anal Squamous Intraepithelial Lesions Associated with Anal High-Risk Human Papillomavirus Infections among Men Who Have Sex with Men in Northern Thailand.

    PubMed

    Ruanpeng, Darin; Chariyalertsak, Suwat; Kaewpoowat, Quanhathai; Supindham, Taweewat; Settakorn, Jongkolnee; Sukpan, Kornkanok; Utaipat, Utaiwan; Miura, Toshiyuki; Kosashunhanan, Natthapol; Saokhieo, Pongpun; Songsupa, Radchanok; Wongthanee, Antika

    2016-01-01

    Anal cancer, one of human papillomavirus (HPV) related malignancies, has increased in recent decades, particularly among men who have sex with men (MSM) and HIV-infected (HIV+) persons. We aimed to explore the prevalence of anal squamous intraepithelial lesions (ASIL) using Papanicolau (Pap) screening among MSM in northern Thailand and its associated factors. Two hundreds MSM aged ≥18 years reporting receptive anal intercourse in the prior 6 months were recruited from July 2012 through January 2013. Medical history and behavioral data were collected by staff interview and computer-assisted self interview. Anal Pap smear, HPV genotyping, and HIV testing were performed. Two pathologists blinded to HPV and HIV status reported cytologic results by Bethesda classification. Mean age was 27.2 years (range 18-54). Overall, 86 (43.0%) had ASIL: 28 (14.2%) with atypical cells of undetermined significance (ASCUS), 1 (0.5%) with atypical squamous cells-cannot exclude high-grade squamous intraepithelial lesion (ASC-H), 56 (28.4%) with low-grade squamous intraepithelial lesion (LSIL), and 1 (0.5%) with high-grade squamous intraepithelial lesion (HSIL). ASIL was associated by univariate analysis (p ≤0.05) with older age, gender identity other than bisexual (i.e., gay men and transgender women), rectal douching, anal symptoms, genital warts, HIV positivity, and high-risk-HPV infection. However, on multiple logistic regression ASIL was associated only with high-risk HPV type (p = 0.002) and HIV infection (p = 0.01). ASIL is quite common in high-risk MSM in northern Thailand and is associated with high-risk HPV types and HIV infection. Routine anal Pap screening should be considered, given the high frequency of ASIL, particularly in the HIV+. High resolution anoscopy (HRA), not done here, should be to confirm PAP smears whose sensitivity and specificity are quite variable. Timely HPV vaccination should be considered for this population.

  18. Prevalence and cumulative incidence of abnormal cervical cytology among HIV-infected Thai women: a 5.5-year retrospective cohort study

    PubMed Central

    2011-01-01

    Background Cervical cancer is one of the most common AIDS-related malignancies in Thailand. To prevent cervical cancer, The US Public Health Service and The Infectious Disease Society of America have recommended that all HIV-infected women should obtain 2 Pap smears 6 months apart after the initial HIV diagnosis and, if results of both are normal, should undergo annual cytological screening. However, there has been no evidence in supporting whether this guideline is appropriate in all settings - especially in areas where HIV-infected women are living in resource-constrained condition. Methods To determine the appropriate interval of Pap smear screenings for HIV-infected Thai women and risk factors for subsequent abnormal cervical cytology, we assessed the prevalence, cumulative incidence and associated factors of cervical cell abnormalities (atypical squamous cell of undetermined significance or higher grades, ASCUS+) among this group of patients. Results The prevalence of ASCUS+ was 15.4% at the first visit, and the cumulative incidence of ASCUS+ gradually increased to 37% in the first 3.5 years of follow-up appointments (first 7 times), and tended to plateau in the last 2 years. For multivariate correlation analysis, women with a CD4 count <350 cells/μL had a significant correlation with ASCUS+ (P = 0.043). There were no associations of subsequent ASCUS+ with age, pregnancy, contraceptive method, highly active anti-retroviral treatment, assumed duration of infection, or the CD4 count nadir level. Conclusion There are high prevalence and cumulative incidence of ASCUS+ in HIV-infected Thai women. With a high lost-to-follow-up rate, an appropriate interval of Pap smear screening cannot be concluded from the present study. Nevertheless, the HIV-infected Thai women may require more than two normal semi-annual Pap smears before shifting to routinely annual cytologic screening. PMID:21211065

  19. Mitral valve resistance determines hemodynamic consequences of severe rheumatic mitral stenosis and immediate outcomes of percutaneous valvuloplasty.

    PubMed

    Sanati, Hamidreza; Zolfaghari, Reza; Samiei, Niloufar; Rezaei, Yousef; Chitsazan, Mitra; Zahedmehr, Ali; Shakerian, Farshad; Kiani, Reza; Firouzi, Ata; Rezaei Tabrizi, Reza

    2017-02-01

    The mitral valve area (MVA) poorly reflects the hemodynamic status of (MS). In this study, we compared the MVA with mitral valve resistance (MVR) with regard to the determination of hemodynamic consequences of MS and the immediate outcomes of percutaneous balloon mitral valvuloplasty (PBMV). In a prospective study, 36 patients with severe rheumatic MS with left ventricular ejection fraction (LVEF) >50% were evaluated. They underwent transthoracic echocardiography (TTE) and catheterization. The MVA was measured by two-dimensional planimetry and pressure half-time (PHT), and the MVR was calculated using the equation: 1333 × transmitral pressure gradient mean transmitral diastolic flow rate. The patients' mean age was 47.8±10.5 years. MVR ≥140.6 dynes·s/cm 5 detected systolic pulmonary arterial pressure (sPAP) >55 mm Hg with a sensitivity of 100% and a specificity of 74%. The sensitivity and specificity of MVA<0.75 cm 2 to discriminate elevated sPAP were 81% and 89%, respectively. PHT ≥323.5 mseconds had a sensitivity of 78% and a specificity of 96% to detect an elevated sPAP. To predict a successful PBMV, preprocedural MVR ≥106.1 dynes·s/cm 5 had a sensitivity of 100% and a specificity of 67% (area under the curve [AUC]=0.763; 95% confidence interval [CI]=0.520-1.006; P=.034); preprocedural MVA <0.95 cm 2 had a sensitivity of 78% and a specificity of 73% (AUC=0.730; 95% CI=0.503-0.956; P=.065); and preprocedural PHT ≥210.5 mseconds had a sensitivity of 73% and a specificity of 78% (AUC=0.707; 95% CI=0.474-0.941; P=.095). MVR seems to be more accurate than MVA in determining the hemodynamic consequences of severe MS as determined by sPAP. In addition, preprocedural MVR detected successful PBMVs. © 2017, Wiley Periodicals, Inc.

  20. Barriers to Pap Smear Test for the Second Time in Women Referring to Health Care Centers in the South of Tehran: A Qualitative Approach

    PubMed Central

    Hassani, Laleh; Dehdari, Tahereh; Hajizadeh, Ebrahim; Shojaeizadeh, Davoud; Abedini, Mehrandokht; Nedjat, Saharnaz

    2017-01-01

    ABSTRACT Background: Cervical cancer is a preventable disease with a regular screening program. Many studies have reported a large number of barriers that women had for the first time, but this study decided to find other barriers for the second time pap smear. Methods: In this qualitative research, data were gathered through in-depth interviews and expressed through conventional content analysis in the form of constant comparison. The participants were 15 women with family profile at 30 health care centers who lived in the south of Tehran and had done Pap smear for one time but didn’t do it for the second time. Results: Three main themes emerged from the analysis of the interviews: negative experiences of the first Pap test were as follows: results of the first time test, readiness for performing the test, getting the test itself, and the site of the first Pap test. Personal barriers to getting the second Pap test were: inattention to time, physical barriers to the second Pap test, and inhibitory beliefs. Perceived social barriers to getting the second Pap test with two sub-themes included social supports and abstract norms. Conclusion: This study provided other barriers about Pap smear including lack of the spouse’s support, the role of health care providers and physicians in screening program for early diagnosis in women. PMID:29043283

  1. Prostatic acid phosphatase is an ectonucleotidase and suppresses pain by generating adenosine

    PubMed Central

    Zylka, Mark J.; Sowa, Nathaniel A.; Taylor-Blake, Bonnie; Twomey, Margaret A.; Herrala, Annakaisa; Voikar, Vootele; Vihko, Pirkko

    2008-01-01

    SUMMARY Thiamine monophosphatase (TMPase, also known as Fluoride-Resistant Acid Phosphatase) is a classic histochemical marker of small-diameter dorsal root ganglia neurons. The molecular identity of TMPase is currently unknown. We found that TMPase is identical to the transmembrane isoform of Prostatic Acid Phosphatase (PAP), an enzyme with unknown molecular and physiological functions. We then found that PAP knockout mice have normal acute pain sensitivity but enhanced sensitivity in chronic inflammatory and neuropathic pain models. In gain-of-function studies, intraspinal injection of PAP protein has potent anti-nociceptive, anti-hyperalgesic and anti-allodynic effects that last longer than the opioid analgesic morphine. PAP suppresses pain by functioning as an ecto-5’-nucleotidase. Specifically, PAP dephosphorylates extracellular adenosine monophosphate (AMP) to adenosine and activates A1-adenosine receptors in dorsal spinal cord. Our studies reveal molecular and physiological functions for PAP in purine nucleotide metabolism and nociception and suggest a novel use for PAP in the treatment of chronic pain. PMID:18940592

  2. Plastic spatula with narrow long tip provides higher satisfactory smears for Pap test.

    PubMed

    Kaur, Pervinder; Kushtagi, Pralhad

    2013-07-01

    Ayre spatula for cervical smear collection is being used despite the suggestion that different modified spatulas provide more satisfactory sampling. To see whether the cytological pickup improves with the use of long tipped spatula. Rurally based University Hospital; crossover study. Pap smear using Ayre spatula in 500 and with plastic narrow long tip (Szalay) spatula in 500 clinic attending women was taken and analyzed. Crossover smears were taken with modified spatula in 163 and using Ayre spatula in 187 women after 2 weeks of initial smears. The same pathologist made cytological reporting for all smears and was unaware of the type of spatula used. Smears from Ayre spatula had significantly higher reports of inadequate smears (94 of 500 vs. 68 of 500 for Ayre and Szalay, respectively; P = 0.032) and it remained so even after crossover (94 of 187 vs. 70 of 163 for Ayre and Szalay, respectively; P = 0.2). Cellular quality appeared better with smears taken using Szalay spatula, but the overall abnormal smear detection rate remained similar with either collection tool (χ(2) = 1.5; P = 0.2). Proportion of satisfactory smears is higher when long tip plastic spatula is used for collection of sample.

  3. Breast and cervical cancer-screening uptake among females in Ardabil, northwest Iran: a community-based study.

    PubMed

    Farzaneh, Esmaeil; Heydari, Heshmatolah; Shekarchi, Ali Akbar; Kamran, Aziz

    2017-01-01

    Breast and cervical cancers are the most commonly diagnosed type of cancer and cause of cancer-related deaths in Iranian females. In contrast to previous studies, this study was carried out with a large sample size for assessment of breast self-examination (BSE)-, clinical breast examination (CBE)-, mammography-, and Pap smear-uptake rates and determination of associations among these screening behaviors with sociodemographic and cognitive variables in Azeri females. This was a cross-sectional, community-based study that was carried out among 1,134 females 20-60 years old during March-June 2016. Data-collection variables included sociodemographic questions, screening behaviors for breast and cervical cancer, self-efficacy, beliefs, and barriers to breast and cervical cancer screening. Collected data were analyzed by SPSS version 13 using χ 2 , Mann-Whitney U , and logistic regression tests. Among the 1,134 participants, 53.9%, 9.8%, and 28.1% had done BSE, CBE, and Pap smear tests, respectively, and among the 625 females aged >40 years, 187 (29.9%) had done the mammography test. Moreover, 416 (36.7%), 103 (16.5%), and 64 (5.6%) females had done BSE, mammography, and CBE regularly, respectively. Beliefs, barriers, income, health insurance, number of children, and age were all important factors for BSE and regular BSE and mammography. Females who had high belief scores were more likely to undertake mammography (odds ratio [OR]: 1.2, 95% confidence interval [CI]: 1.03-1.5), regular mammography (OR: 4.2, 95% CI: 1.9-9.3), regular CBE (OR: 1.25, 95% CI: 1.2-1.3), and Pap smears (OR: 1.2, 95% CI: 1.1-1.4). Also, females who had high self-efficacy scores were more likely to perform regular BSE (OR: 1.8, 95% CI: 1.4-2.5) and mammography (OR: 2.5, 95% CI: 1.4-4.6) than females with lower self-efficacy scores. The frequency of breast and cervical cancer screening was low in our study. The findings of this study indicated that beliefs, self-efficacy, and barriers were important predictive factors of cancer-screening behavior among the females studied.

  4. Breast and cervical cancer screening among women in metropolitan areas of the United States by county-level commuting time to work and use of public transportation, 2004 and 2006.

    PubMed

    Coughlin, Steven S; King, Jessica

    2010-03-19

    Commuting times and behaviors have been associated with a variety of chronic disease outcomes and health behaviors. We examined the relationships between ecologic measures of commuting time and use of public transportation in relation to breast and cervical cancer screening among women in U.S. metropolitan areas who participated in the 2004 and 2006 Behavioral Risk Factor Surveillance System (BRFSS) surveys. Self-reported county of residence was used to classify respondents as residents of metropolitan statistical areas (MSAs). Only BRFSS respondents who resided in the 39 MSAs with a population of > or = 1.5 million in 2007--representing a total of 337 counties--were included in this analysis. A total of 76,453 women aged > or = 40 years were included in analyses on mammography. Analyses on Pap testing were limited to women aged > or =18 years with no history of hysterectomy (n = 80,959). Area-based measures of socio-economic status (SES) were obtained by utilizing county-level information from the 2000 U.S. Census. With adjustment for age, no important associations were observed between receipt of a recent mammogram and either a county-level measure of commute time or residence in an area where more residents had access to a car. Similarly, women living in counties where at least four percent of the residents used public transportation were as likely to have had a recent mammogram or Pap test compared with women in areas where less than four percent of residents used public transportation. However, women living in counties where < 2% of residents had no access to a car were somewhat more likely to have had a Pap test in the past 3 years than women in areas where > or = 3% of the residents had no access to a car (87.3% versus 84.5%; p-value for test for trend < 0.01). In multivariate analysis, living in a county with a median commute time of at least 30 minutes was not significantly associated with having had a Pap test in the past 3 years (adjusted odds ratio (OR) = 1.1, 95% CI 0.9-1.2, p = .50), or with having had a mammogram in the past 2 years (adjusted OR = 0.9, 95% CI 0.9-1.1, p = .28). A weak positive association was observed between residence in a county with less use of public transportation and having had a Pap test in the past 3 years, which was of borderline significance (adjusted OR 1.2, 95% CI 1.0-1.4, p = .05). In large U.S. metropolitan areas, transportation issues may play a role in whether a woman obtains cancer screening along with other factors (e.g., Hispanic ethnicity, low income, and no physician visit in the past year). In this contextual analysis, a longer commute time was not associated with breast and cervical cancer screening.

  5. Attitudes of women after the age of 50 towards preventive screening.

    PubMed

    Skórzyńska, Hanna; Krawczyk-Suszek, Marlena; Kulik, Teresa B; Pacian, Anna; Stefanowicz, Agata; Skowronek, Anna

    2017-12-23

    Prevention is one of the major branches of the health sector. The National Health Programme encompasses main risk factors, elimination of which may lead to a reduced incidence of illnesses in the society. At the same time, the criteria of selecting people eligible for preventive screening are established according to risk groups determined by sex, as well as age in the population of women. The perimenopausal and menopausal period contributes to occurrence of numerous systemic diseases and to an increased risk of illnesses, especially cancers. The objective of the research was to evaluate the performance of preventive screening tests of women after 50 aimed at early detection of cervical and breast cancer. Furthermore, the research estimated frequency of pathological lesions detected and regularity of their monitoring. The research covered 150 women after 50 years of age. The database was statistically examined with STATISTICA software. A low percentage of the respondents, in comparison to the risk increasing with age, had a Pap test (61.3%) and mammography (51.3%) in the last two years. In the case of women whose latest Pap test or mammography showed abnormalities and was the basis for diagnosing pathological lesions, 69.2% of them were under regular medical supervision if abnormalities were identified by a Pap test and 68.7% if lesions were detected in breast structure. In the examined group we observed a small percentage of women undergo Pap tests and mammography. Furthermore, medical recommendations regarding early detection of cancers are frequently ignored and disregarded by patients.

  6. Adherence to positive airway pressure therapy in U.S. military personnel with sleep apnea improves sleepiness, sleep quality, and depressive symptoms.

    PubMed

    Mysliwiec, Vincent; Capaldi, Vincent F; Gill, Jessica; Baxter, Tristin; O'Reilly, Brian M; Matsangas, Panagiotis; Roth, Bernard J

    2015-04-01

    Obstructive sleep apnea (OSA) is frequently diagnosed in U.S. military personnel. OSA is associated with sleepiness, poor sleep quality, and service-related illnesses of insomnia, depression, post-traumatic stress disorder, and traumatic brain injury. Observational study of active duty military personnel with OSA and adherence to positive airway pressure (PAP) assessed with smart chip technology. 58 men with mean age 36.2 ± 7.7 years, mean body mass index 31.4 ± 3.7 with mean apnea-hypopnea index (AHI) 19.1 ± 19.0 are reported. 23 (39.7%) participants were adherent to PAP, and 35 (60.3%) were nonadherent. No significant differences in baseline demographics, apnea-hypopnea index, service-related illnesses, or clinical instrument scores. Military personnel adherent to PAP had significantly improved sleepiness (p = 0.007), sleep quality (p = 0.013), depressive symptoms (p = 0.01), energy/fatigue (p = 0.027), and emotional well-being (p = 0.024). Participants with moderate-severe OSA were more likely to be in the adherent group when compared with participants diagnosed with mild OSA. Military personnel with OSA have low adherence to PAP. Adherence is associated with improved depressive symptoms, sleepiness, sleep quality, energy/fatigue, emotional well-being, and social functioning. Future research should focus on interventions to improve the management of OSA in military personnel. Reprint & Copyright © 2015 Association of Military Surgeons of the U.S.

  7. Cervical Dysplasia and High-Risk Human Papillomavirus Infections among HIV-Infected and HIV-Uninfected Adolescent Females in South Africa

    PubMed Central

    Mrubata, Megan; Williamson, Anna-Lise; Bekker, Linda-Gail

    2014-01-01

    Background. HIV-infected adolescents may be at higher risk for high-grade cervical lesions than HIV-uninfected adolescents. The purpose of this study was to compare the prevalence of high-risk HPV (HR-HPV) infections and Pap smear abnormalities between these two groups. Methods. In this cross-sectional study, we compared the HPV DNA and Pap smear results between 35 HIV-infected and 50 HIV-uninfected adolescents in order to determine the prevalence of HR-HPV genotypes and cervical cytological abnormalities. Comparisons were made using Pearson χ 2 and independent-samples t-tests analyses, and associations between demographic and behavioral characteristics and HPV infections were examined. Results. HIV-infected participants were more likely to be infected with any HPV (88.6% versus 48.0%; P < 0.001) and with at least one HR-HPV (60.0% versus 24.0%; P = 0.001), and to have multiple concurrent HPV infections (68.6% versus 22.0%; P < 0.001). HPV 16 and 18 were relatively underrepresented among HR-HPV infections. Abnormal Pap test results were more common among HIV-infected participants (28.8% versus 12.0%; P = 0.054). A history of smoking was associated with HR-HPV infection. Conclusions. HIV-infected adolescents have an increased risk of infection with HR-HPV and of Pap test abnormalities. The majority of HR-HPV infections among our participants would not be prevented by the currently available vaccinations against HPV. PMID:25389377

  8. Artificial neural network assisted kinetic spectrophotometric technique for simultaneous determination of paracetamol and p-aminophenol in pharmaceutical samples using localized surface plasmon resonance band of silver nanoparticles

    NASA Astrophysics Data System (ADS)

    Khodaveisi, Javad; Dadfarnia, Shayessteh; Haji Shabani, Ali Mohammad; Rohani Moghadam, Masoud; Hormozi-Nezhad, Mohammad Reza

    2015-03-01

    Spectrophotometric analysis method based on the combination of the principal component analysis (PCA) with the feed-forward neural network (FFNN) and the radial basis function network (RBFN) was proposed for the simultaneous determination of paracetamol (PAC) and p-aminophenol (PAP). This technique relies on the difference between the kinetic rates of the reactions between analytes and silver nitrate as the oxidizing agent in the presence of polyvinylpyrrolidone (PVP) which is the stabilizer. The reactions are monitored at the analytical wavelength of 420 nm of the localized surface plasmon resonance (LSPR) band of the formed silver nanoparticles (Ag-NPs). Under the optimized conditions, the linear calibration graphs were obtained in the concentration range of 0.122-2.425 μg mL-1 for PAC and 0.021-5.245 μg mL-1 for PAP. The limit of detection in terms of standard approach (LODSA) and upper limit approach (LODULA) were calculated to be 0.027 and 0.032 μg mL-1 for PAC and 0.006 and 0.009 μg mL-1 for PAP. The important parameters were optimized for the artificial neural network (ANN) models. Statistical parameters indicated that the ability of the both methods is comparable. The proposed method was successfully applied to the simultaneous determination of PAC and PAP in pharmaceutical preparations.

  9. JPRS Report, East Europe.

    DTIC Science & Technology

    1990-04-06

    Andrasfalvy 2 Pecs Zoltan Trombitas Sandor Szeles Mrs. Kaposi, Dr. -Andras Pap Sandor Gyulai; Maria Dunai Jozsef Kuller; Dr. Istvan Marton 3 Pecs Dr. Andrea ...Csizmadia Mrs. Szabo, Erzsebet Kovacs 5 Varpalota Peter Patonai Laszlo Czifra Janos Csovari Janos Kovacs Ferenc Schmidt Tibor Fakasz 6 Veszprem -Ferenc

  10. Cytomorphology of cervicovaginal melanoma: ThinPrep versus conventional Papanicolaou tests.

    PubMed

    Setia, Namrata; Goulart, Robert A; Leiman, Gladywn; Otis, Christopher N; Modem, Rukmini; Pantanowtiz, Liron

    2010-12-31

    Primary cervicovaginal melanoma is a rare malignancy associated with a high risk of recurrence. Prior studies discussing the cytomorphology of cervicovaginal melanoma have been based primarily on review of conventional Papanicolaou (Pap) smears. The aim of this study was to evaluate cervicovaginal melanomas identified in liquid-based Pap tests, in comparison with features seen on conventional Pap smear preparation. Cases of cervicovaginal melanoma identified on Pap tests with concurrent or subsequent histopathologic confirmation were collected from the Baystate Medical Center cytopathology files and personal archives of the authors over a total period of 34 years. All cytopathology (n = 6) and the available histology slides (n = 5) were reviewed. Cases were analyzed regarding clinical, histopathologic and cytomorphological findings. A total of six cases with invasive cervicovaginal melanoma diagnosed on Pap tests were identified. Most patients were postmenopausal with contact bleeding, correlating with surface ulceration (identified in biopsy/excision material in 5/5 cases). Most cases had deeply invasive tumors (5/5: modified Breslow's thickness > 5 mm and Chung's level of invasion IV/V). Pap tests included four ThinPrep and two conventional smears. Overall, ThinPrep Pap tests exhibited a higher ratio of tumor cells to background squamous cells. While all Pap tests were bloodstained, tumor diathesis was prominent only within conventional smears. Melanoma cells were present both as clusters and scattered single cells in each Pap test type. Both the preparations contained epithelioid tumor cells, whereas spindled tumor cells were seen in only two ThinPrep cases. Prominent nucleoli and binucleation of tumor cells were seen in both the preparations. Melanin pigment was identified in only ThinPrep (3/4) cases and nuclear pseudo-inclusions in one conventional Pap smear. Cell blocks were made in three ThinPrep cases and immunocytochemistry (S-100, HMB45, Melan-A) performed on additional vial material (one ThinPrep slide and one cell block) was immunoreactive in melanoma cells. Primary cervicovaginal melanoma, a rare malignancy seen predominantly in postmenopausal women, may be successfully diagnosed in either ThinPrep Pap tests or conventional Pap smears. While ThinPrep Pap tests did not demonstrate morphological advantage over conventional smears, liquid-based cytology specimens did provide additional material for cellblock preparation and immunocytochemical evaluation in a subset of cases.

  11. Cytomorphology of cervicovaginal melanoma: ThinPrep versus conventional Papanicolaou tests

    PubMed Central

    Setia, Namrata; Goulart, Robert A; Leiman, Gladywn; Otis, Christopher N; Modem, Rukmini; Pantanowtiz, Liron

    2010-01-01

    Background: Primary cervicovaginal melanoma is a rare malignancy associated with a high risk of recurrence. Prior studies discussing the cytomorphology of cervicovaginal melanoma have been based primarily on review of conventional Papanicolaou (Pap) smears. The aim of this study was to evaluate cervicovaginal melanomas identified in liquid-based Pap tests, in comparison with features seen on conventional Pap smear preparation. Materials and Methods: Cases of cervicovaginal melanoma identified on Pap tests with concurrent or subsequent histopathologic confirmation were collected from the Baystate Medical Center cytopathology files and personal archives of the authors over a total period of 34 years. All cytopathology (n = 6) and the available histology slides (n = 5) were reviewed. Cases were analyzed regarding clinical, histopathologic and cytomorphological findings. Results: A total of six cases with invasive cervicovaginal melanoma diagnosed on Pap tests were identified. Most patients were postmenopausal with contact bleeding, correlating with surface ulceration (identified in biopsy/excision material in 5/5 cases). Most cases had deeply invasive tumors (5/5: modified Breslow's thickness > 5 mm and Chung's level of invasion IV/V). Pap tests included four ThinPrep and two conventional smears. Overall, ThinPrep Pap tests exhibited a higher ratio of tumor cells to background squamous cells. While all Pap tests were bloodstained, tumor diathesis was prominent only within conventional smears. Melanoma cells were present both as clusters and scattered single cells in each Pap test type. Both the preparations contained epithelioid tumor cells, whereas spindled tumor cells were seen in only two ThinPrep cases. Prominent nucleoli and binucleation of tumor cells were seen in both the preparations. Melanin pigment was identified in only ThinPrep (3/4) cases and nuclear pseudo-inclusions in one conventional Pap smear. Cell blocks were made in three ThinPrep cases and immunocytochemistry (S-100, HMB45, Melan-A) performed on additional vial material (one ThinPrep slide and one cell block) was immunoreactive in melanoma cells. Conclusion: Primary cervicovaginal melanoma, a rare malignancy seen predominantly in postmenopausal women, may be successfully diagnosed in either ThinPrep Pap tests or conventional Pap smears. While ThinPrep Pap tests did not demonstrate morphological advantage over conventional smears, liquid-based cytology specimens did provide additional material for cellblock preparation and immunocytochemical evaluation in a subset of cases. PMID:21298024

  12. Retrospective, nonrandomized controlled study on autoadjusting, dual-pressure positive airway pressure therapy for a consecutive series of complex insomnia disorder patients

    PubMed Central

    Krakow, Barry; McIver, Natalia D; Ulibarri, Victor A; Nadorff, Michael R

    2017-01-01

    Purpose Emerging evidence shows that positive airway pressure (PAP) treatment of obstructive sleep apnea (OSA) and upper airway resistance syndrome (UARS) in chronic insomnia patients (proposed “complex insomnia” disorder) leads to substantial decreases in insomnia severity. Although continuous PAP (CPAP) is the pressure mode most widely researched, intolerance to fixed pressurized air is rarely investigated or described in comorbidity patients. This retrospective study examined dual pressure, autoadjusting PAP modes in chronic, complex insomnia disorder patients. Patients and methods Chronic insomnia disorder patients (mean [SD] insomnia severity index [ISI] =19.11 [3.34]) objectively diagnosed with OSA or UARS and using either autobilevel PAP device or adaptive servoventilation (ASV) device after failing CPAP therapy (frequently due to intolerance to pressurized air, poor outcomes, or emergence of CSA) were divided into PAP users (≥20 h/wk) and partial users (<20 h/wk) for comparison. Subjective and objective baseline and follow-up measures were analyzed. Results Of the 302 complex insomnia patients, PAP users (n=246) averaged 6.10 (1.78) nightly hours and 42.71 (12.48) weekly hours and partial users (n=56) averaged 1.67 (0.76) nightly hours and 11.70 (5.31) weekly hours. For mean (SD) decreases in total ISI scores, a significant (group × time) interaction was observed (F[1,300]=13.566; P<0.0001) with PAP users (–7.59 [5.92]; d=1.63) showing superior results to partial users (−4.34 [6.13]; d=0.81). Anecdotally, patients reported better tolerability with advanced PAP compared to previous experience with CPAP. Both adaptive servoventilation and autobilevel PAP showed similar ISI score improvement without statistical differences between devices. Total weekly hours of PAP use correlated inversely with change in insomnia symptoms (r=−0.256, P<0.01). Conclusion Insomnia severity significantly decreased in patients using autoadjusting PAP devices, but the study design restricts interpretation to an association. Future research must elucidate the interaction between insomnia and OSA/UARS as well as the adverse influence of pressure intolerance on PAP adaptation in complex insomnia patients. Randomized controlled studies must determine whether advanced PAP modes provide benefits over standard CPAP modes in these comorbidity patients. PMID:28331381

  13. Enhancing Propriospinal Relays to Improve Functional Recovery After SCI

    DTIC Science & Technology

    2017-10-01

    injury to the spinal cord. We have completed experiments for subtask 1 – 4 of specific aim 1 and subtasks 1 for specific aim 2. This Aim 2 of the...previously observed PAP2 to induce robust regeneration in a dorsal hemisection model and thought it might enhance regeneration and sprouting after the more...spontaneous recovery is often observed after incomplete injuries, leading to partial recovery over time. Spontaneous recovery is thought to be

  14. Comparison of three approaches to model grapevine organogenesis in conditions of fluctuating temperature, solar radiation and soil water content.

    PubMed

    Pallas, B; Loi, C; Christophe, A; Cournède, P H; Lecoeur, J

    2011-04-01

    There is increasing interest in the development of plant growth models representing the complex system of interactions between the different determinants of plant development. These approaches are particularly relevant for grapevine organogenesis, which is a highly plastic process dependent on temperature, solar radiation, soil water deficit and trophic competition. The extent to which three plant growth models were able to deal with the observed plasticity of axis organogenesis was assessed. In the first model, axis organogenesis was dependent solely on temperature, through thermal time. In the second model, axis organogenesis was modelled through functional relationships linking meristem activity and trophic competition. In the last model, the rate of phytomer appearence on each axis was modelled as a function of both the trophic status of the plant and the direct effect of soil water content on potential meristem activity. The model including relationships between trophic competition and meristem behaviour involved a decrease in the root mean squared error (RMSE) for the simulations of organogenesis by a factor nine compared with the thermal time-based model. Compared with the model in which axis organogenesis was driven only by trophic competition, the implementation of relationships between water deficit and meristem behaviour improved organogenesis simulation results, resulting in a three times divided RMSE. The resulting model can be seen as a first attempt to build a comprehensive complete plant growth model simulating the development of the whole plant in fluctuating conditions of temperature, solar radiation and soil water content. We propose a new hypothesis concerning the effects of the different determinants of axis organogenesis. The rate of phytomer appearance according to thermal time was strongly affected by the plant trophic status and soil water deficit. Furthermore, the decrease in meristem activity when soil water is depleted does not result from source/sink imbalances.

  15. Phenology and growth adjustments of oil palm (Elaeis guineensis) to photoperiod and climate variability

    PubMed Central

    Legros, S.; Mialet-Serra, I.; Caliman, J.-P.; Siregar, F. A.; Clément-Vidal, A.; Dingkuhn, M.

    2009-01-01

    Background and Aims Oil palm flowering and fruit production show seasonal maxima whose causes are unknown. Drought periods confound these rhythms, making it difficult to analyse or predict dynamics of production. The present work aims to analyse phenological and growth responses of adult oil palms to seasonal and inter-annual climatic variability. Methods Two oil palm genotypes planted in a replicated design at two sites in Indonesia underwent monthly observations during 22 months in 2006–2008. Measurements included growth of vegetative and reproductive organs, morphology and phenology. Drought was estimated from climatic water balance (rainfall – potential evapotranspiration) and simulated fraction of transpirable soil water. Production history of the same plants for 2001–2005 was used for inter-annual analyses. Key Results Drought was absent at the equatorial Kandista site (0°55′N) but the Batu Mulia site (3°12′S) had a dry season with variable severity. Vegetative growth and leaf appearance rate fluctuated with drought level. Yield of fruit, a function of the number of female inflorescences produced, was negatively correlated with photoperiod at Kandista. Dual annual maxima were observed supporting a recent theory of circadian control. The photoperiod-sensitive phases were estimated at 9 (or 9 + 12 × n) months before bunch maturity for a given phytomer. The main sensitive phase for drought effects was estimated at 29 months before bunch maturity, presumably associated with inflorescence sex determination. Conclusion It is assumed that seasonal peaks of flowering in oil palm are controlled even near the equator by photoperiod response within a phytomer. These patterns are confounded with drought effects that affect flowering (yield) with long time-lag. Resulting dynamics are complex, but if the present results are confirmed it will be possible to predict them with models. PMID:19748909

  16. Goal orientation in surgical residents: a study of the motivation behind learning.

    PubMed

    Hoffman, Rebecca L; Hudak-Rosander, Cristina; Datta, Jashodeep; Morris, Jon B; Kelz, Rachel R

    2014-08-01

    The subconscious way in which an individual approaches learning, goal orientation (GO), has been shown to influence job satisfaction, job performance, and burnout in nonmedical cohorts. The aim of this study was to adapt and validate an instrument to assess GO in surgical residents, so that in the future, we can better understand how differences in motivation affect professional development. Residents were recruited to complete a 17-item survey adapted from the Patterns of Adaptive Learning Scales (PALS). The survey included three scales assessing GO in residency-specific terms. Items were scored on a 5-point Likert scale, and the psychometric properties of the adapted and original PALS were compared. Ninety-five percent of residents (61/64) participated. Median age was 30 y and 33% were female. Mean (standard deviation) scale scores for the adapted PALS were: mastery 4.30 (0.48), performance approach (PAP) 3.17 (0.99), and performance avoid 2.75 (0.88). Mean (standard deviation) scale scores for the original PALS items were: mastery 3.35 (1.02), PAP 2.76 (1.15), and performance avoid 2.41 (0.91). Cronbach alpha were α = 0.89 and α = 0.84 for the adapted PAP and avoid scales, respectively, which were comparable with the original scales. For the adapted mastery scale, α = 0.54. Exploratory factor analysis revealed five factors, and factor loadings for individual mastery items did not load consistently onto a single factor. This study represents the first steps in the development of a novel tool to measure GO among surgical residents. Understanding motivational psychology in residents may facilitate improved education and professional development. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Application of the Carolina Framework for Cervical Cancer Prevention

    PubMed Central

    Moss, Jennifer L.; McCarthy, Schatzi H.; Gilkey, Melissa B.; Brewer, Noel T.

    2014-01-01

    Objective The Carolina Framework for Cervical Cancer Prevention describes 4 main causes of cervical cancer incidence: human papillomavirus (HPV) infection, lack of screening, screening errors, and not receiving follow-up care. We present 2 applications of the Carolina Framework in which we identify high-need counties in North Carolina and generate recommendations for improving prevention efforts. Methods We created a cervical cancer prevention need index (CCPNI) that ranked counties on cervical cancer mortality, HPV vaccine initiation and completion, Pap smear screening, and provision of Pap tests to rarely- or never-screened women. In addition, we conducted in-depth interviews with 19 key informants from programs and agencies involved in cervical cancer prevention in North Carolina. Results North Carolina’s 100 counties varied widely on individual CCPNI components, including annual cervical cancer mortality (median 2.7/100,000 women; range 0.0–8.0), adolescent girls’ HPV vaccine initiation (median 42%; range 15%–62%), and Pap testing in the previous 3 years among Medicaid-insured adult women (median 59%; range 40%–83%). Counties with the greatest prevention needs formed 2 distinct clusters in the northeast and south-central regions of the state. Interviews generated 9 recommendations to improve cervical cancer prevention in North Carolina, identifying applications to specific programs and policies in the state. Conclusions This study found striking geographic disparities in cervical cancer prevention need in North Carolina. Future prevention efforts in the state should prioritize high-need regions as well as recommended strategies and applications in existing programs. Other states can use the Carolina Framework to increase the impact of their cervical cancer prevention efforts. PMID:24333357

  18. Acute effects of the combination of sildenafil and inhaled treprostinil on haemodynamics and gas exchange in pulmonary hypertension.

    PubMed

    Voswinckel, Robert; Reichenberger, Frank; Enke, Beate; Kreckel, Andre; Krick, Stefanie; Gall, Henning; Schermuly, Ralph Theo; Grimminger, Friedrich; Rubin, Lewis J; Olschewski, Horst; Seeger, Werner; Ghofrani, Hossein A

    2008-10-01

    Inhaled treprostinil was recently developed for the treatment of pulmonary arterial hypertension (PAH). We investigated the safety and acute haemodynamic effects of the combination oral sildenafil and inhaled treprostinil in an open label study in patients with precapillary pulmonary hypertension. Inhaled nitric oxide (20ppm; n=50), sildenafil (50mg; n=50) and inhaled treprostinil (15microg; n=25 or 30microg; n=25) were applied in subsequent order during right heart catheter investigation to consecutive patients with pulmonary arterial hypertension (PAH; n=28), non-operable chronic thromboembolic pulmonary hypertension (CTEPH; n=17) and pulmonary fibrosis associated pulmonary hypertension (n=5). Inhaled nitric oxide reduced pulmonary vascular resistance (PVR) to 87.3+/-5.1% of baseline values, reduced mean pulmonary arterial pressure (PAP) to 89.7+/-3.5% and increased cardiac output (CO) to 102.4+/-2.9%. Sildenafil reduced PVR to 80.1+/-5.0%, mPAP to 86.5+/-2.9% and increased CO to 103.8+/-3.2%. Treprostinil, inhaled 1h after sildenafil, reduced PVR to 66.3+/-3.8%, mPAP to 77.8+/-3.3%, and increased CO to 107.1+/-3.3% (mean+/-95% confidence interval). Subgroup analysis showed similar acute haemodynamic effects in PAH and CTEPH patients. Ventilation/perfusion distribution measurement in six patients with pre-existing gas exchange limitations was not changed by sildenafil and treprostinil. Relevant side effects were not observed. The combination of sildenafil and inhaled treprostinil was well tolerated and induced additive, pulmonary selective vasodilatation in pulmonary hypertension patients. This could be of relevance also for long-term treatment of PAH and CTEPH patients.

  19. Metabolites contributing to Rhizoctonia solani AG-1-IA maturation and sclerotial differentiation revealed by UPLC-QTOF-MS metabolomics.

    PubMed

    Hu, Wenjin; Pan, Xinli; Abbas, Hafiz Muhammad Khalid; Li, Fengfeng; Dong, Wubei

    2017-01-01

    Rhizoctonia solani is a causative agent of sheath blight, which results in huge economic losses every year. During its life cycle, the formation of sclerotia helps Rhizoctonia solani withstand a variety of unfavorable factors. Oxidative stress is a key factor that induces sclerotium formation. The differentiated and undifferentiated phenotypes of R. solani AG-1-IA were obtained by controlling aerial conditions. Metabolomics based on the mass spectrometry technique combined with multivariate and univariate analyses was used to investigate the metabolic variation in vegetative, differentiated and undifferentiated mycelia. Our results revealed that during maturation, the metabolic levels of N2-acetyl-L-ornithine, 3,1'-(OH)2-Gamma-carotene, (5Z,7E)-(1S,3R)-24,24-difluoro-24a-homo-9,10-seco-5,7,10(19)-cholestatrien-1,3,25-triol, stoloniferone O, PA(O-18:0/12:0), PA(P-16:0/14:0), PA(P-16:0/16:(19Z)) and PA(P-16:0/17:2(9Z,12Z)) were suppressed in both differentiated and undifferentiated mycelia. The concentrations of PE(20:1(11Z)/14:1(9Z)), PE(P-16:0/20:4(5Z,8Z,11Z,13E)(15OH[S])) and PS(12:0/18:1(9Z)) were increased in the differentiated group, while increased levels of N(gamma)-nitro-L-arginine, tenuazonic acid and 9S,10S,11R-trihydroxy-12Z,15Z-octadecadienoic acid were found in the undifferentiated group. Our results suggest that different levels of these metabolites may act as biomarkers for the developmental stages of R. solani AG-1-IA. Moreover, the mechanisms of sclerotium formation and mycelium differentiation were elucidated at the metabolic level.

  20. Metabolites contributing to Rhizoctonia solani AG-1-IA maturation and sclerotial differentiation revealed by UPLC-QTOF-MS metabolomics

    PubMed Central

    Hu, Wenjin; Pan, Xinli; Abbas, Hafiz Muhammad Khalid; Li, Fengfeng

    2017-01-01

    Rhizoctonia solani is a causative agent of sheath blight, which results in huge economic losses every year. During its life cycle, the formation of sclerotia helps Rhizoctonia solani withstand a variety of unfavorable factors. Oxidative stress is a key factor that induces sclerotium formation. The differentiated and undifferentiated phenotypes of R. solani AG-1-IA were obtained by controlling aerial conditions. Metabolomics based on the mass spectrometry technique combined with multivariate and univariate analyses was used to investigate the metabolic variation in vegetative, differentiated and undifferentiated mycelia. Our results revealed that during maturation, the metabolic levels of N2-acetyl-L-ornithine, 3,1'-(OH)2-Gamma-carotene, (5Z,7E)-(1S,3R)-24,24-difluoro-24a-homo-9,10-seco-5,7,10(19)-cholestatrien-1,3,25-triol, stoloniferone O, PA(O-18:0/12:0), PA(P-16:0/14:0), PA(P-16:0/16:(19Z)) and PA(P-16:0/17:2(9Z,12Z)) were suppressed in both differentiated and undifferentiated mycelia. The concentrations of PE(20:1(11Z)/14:1(9Z)), PE(P-16:0/20:4(5Z,8Z,11Z,13E)(15OH[S])) and PS(12:0/18:1(9Z)) were increased in the differentiated group, while increased levels of N(gamma)-nitro-L-arginine, tenuazonic acid and 9S,10S,11R-trihydroxy-12Z,15Z-octadecadienoic acid were found in the undifferentiated group. Our results suggest that different levels of these metabolites may act as biomarkers for the developmental stages of R. solani AG-1-IA. Moreover, the mechanisms of sclerotium formation and mycelium differentiation were elucidated at the metabolic level. PMID:28489938

  1. Perception and practices on screening and vaccination for carcinoma cervix among female healthcare professional in tertiary care hospitals in Bangalore, India.

    PubMed

    Swapnajaswanth, M; Suman, G; Suryanarayana, S P; Murthy, N S

    2014-01-01

    Cervical cancer is potentially the most preventable and treatable cancer. Despite the known efficacy of cervical screening, a significant number of women do not avail themselves of the procedure due to lack of awareness. This study was conducted to elicit information on the knowledge, attitude and practice (KAP) regarding screening (Pap test) and vaccination for carcinoma cervix among female doctors and nurses in a tertiary care hospital in Bangalore and to assess barriers to acceptance of the Pap test. A cross-sectional, descriptive study was conducted with semi-structured, self-administered questionnaire among female health professionals. The study subjects were interviewed for KAP regarding risk factors for cancer cervix, Pap test and HPV vaccination for protection against carcinoma cervix. Higher proportion of doctors 45 (78.9%) had very good knowledge as compared to only 13 (13.3%) of the nurses, about risk factors for cancer cervix and Pap test (p=0.001). As many as 138(89.6%) of the study subjects had favorable attitude towards Pap test and vaccination, but 114 (73.6%) of the study subjects never had a Pap test and the most common reason 35 (31%) for not practicing was absence of disease symptoms. In spite of good knowledge and attitudes towards cancer cervix and Pap test being good, practice remained low among the study subjects and most common reasons for not undergoing Pap test was absence of disease symptoms. The independent predictors of ever having a Pap test done was found to be the occupation and duration of married life above 9 yrs. Hence there is a strong need to improve uptake of Pap test by health professionals by demystifying the barriers.

  2. Effect of palatal augmentation prosthesis on pharyngeal manometric pressure in a patient with functional dysphagia: A case report.

    PubMed

    Ohno, Tomohisa; Ohno, Ryo; Fujishima, Ichiro

    2017-10-01

    A 53-year-old institutionalized male patient with a history of postoperative bilateral hypoglossal nerve injury was admitted for treatment of dysphagia. He experienced dysphagia involving oral cavity-to-pharynx bolus transportation because of restricted tongue movement and was treated with a palatal augmentation prosthesis (PAP), which resulted in improved bolus transportation, pharyngeal swallowing pressure, and clearance of oral and pharyngeal residue. The mean pharyngeal swallowing pressure at tongue base with the PAP (145.5±7.5mmHg) was significantly greater than that observed immediately after removal of the PAP (118.3±10.1mmHg; p<0.05; independent t-test). Dysphagia rehabilitation with the PAP was continued. Approximately 1 month after PAP application, the patient could orally consume three meals, with the exception of foods particularly difficult to swallow. The supporting contact between the tongue and palate enabled by the PAP resulted in improvement of bolus transportation, which is the most important effect of a PAP. The increase in pharyngeal swallowing pressure at the tongue base because of PAP-enabled tongue-palate contact might play an important role in this improvement. Since a PAP augments the volume of the palate, it enables easy contact between the tongue and palate, resulting in the formation of an anchor point for tongue movement during swallowing. Thus, application of a PAP increases the tongue force, especially that of the basal tongue. A palatal augmentation prosthesis helps improve pharyngeal swallowing pressure at the basal tongue region and might contribute to the decrease of oral as well as pharyngeal residue. Copyright © 2017 Japan Prosthodontic Society. Published by Elsevier Ltd. All rights reserved.

  3. Cervical cancer screening in rural mountainous Honduras: knowledge, attitudes and barriers.

    PubMed

    Pryor, Rachel J; Masroor, Nadia; Stevens, Michael; Sanogo, Kakotan; Hernández O'Hagan, Pedro José; Bearman, Gonzalo

    2017-01-01

    Because cervical cancer is the leading cause of cancer mortality in Honduras, this study assessed knowledge, attitudes and barriers to cervical cancer screening services by Papanicolaou smear (pap smear) for women in rural, remote Honduras served by Virginia Commonwealth University's Global Health and Health Disparities Program (GH2DP). Two interviewers administered an institutional review board approved, 20 question survey by convenience sample methodology to adult female patients visiting GH2DP clinics in June 2014. A total of 146 surveys were completed. Of the respondents, 30 were living in La Hicaca, the largest and wealthiest village in the region, and 116 were living in surrounding, less affluent, villages. On average, women from La Hicaca had 2.9 children whereas women from surrounding villages had 4.3 children (p=0.0095). There were no significant differences between La Hicaca and surrounding villages in average respondent age, age of first intercourse and number of sexual partners. Seventy three percent (22/30) of women from La Hicaca and 60% (70/116) from surrounding villages reported undergoing cervical cancer screening by pap smear (p=0.1890). Eighty-two percent (18/22) of the respondents from La Hicaca and 84% (59/70) from surrounding villages were screened in the past two years (p=0.7846). The majority of the women from surrounding villages (81%, 57/70) and 23% (5/22) from La Hicaca traveled >1 h to receive a pap smear (p≤0.0001). Women from La Hicaca (86%, 19/22) were more likely to receive their pap smear results than women from surrounding villages (60%, 42/70) (p=0.0225). Although 17% (5/30) of respondents from La Hicaca and 11% (13/116) (p=0.4175) from surrounding villages were aware of the cause of cervical cancer, 60% (18/30) of women in La Hicaca and 82% (95/116) in surrounding villages (p=0.0106) believed it is preventable. Of the 106 women (73%) who had heard of cervical cancer screening, only 92 women (63%) had been screened (p<0.0001). Women undergoing cervical cancer screening were more likely to believe that cervical cancer is preventable (n=78, p=0.0054). The most common screening barriers were lack of awareness and fear (19/54, 35%; 15/54, 28%). Although yearly screening services are available in this community, knowledge and access barriers exist for increased implementation. Notification of pap smear results is suboptimal. These findings will guide regional and collaborative effort to improve cervical cancer screening services.

  4. Social network characteristics and cervical cancer screening among Quechua women in Andean Peru.

    PubMed

    Luque, John S; Opoku, Samuel; Ferris, Daron G; Guevara Condorhuaman, Wendy S

    2016-02-24

    Peru has high cervical cancer incidence and mortality rates compared to other Andean countries. Therefore, partnerships between governmental and international organizations have targeted rural areas of Peru to receive cervical cancer screening via outreach campaigns. Previous studies have found a relationship between a person's social networks and cancer screening behaviors. Screening outreach campaigns conducted by the nonprofit organization CerviCusco created an opportunity for a social network study to examine cervical cancer screening history and social network characteristics in a rural indigenous community that participated in these campaigns in 2012 and 2013. The aim of this study was to explore social network characteristics in this community related to receipt of cervical cancer screening following the campaigns. An egocentric social network questionnaire was used to collect cross-sectional network data on community participants. Each survey participant (ego) was asked to name six other women they knew (alters) and identify the nature of their relationship or tie (family, friend, neighbor, other), residential closeness (within 5 km), length of time known, frequency of communication, topics of conversation, and whether they lent money to the person, provided childcare or helped with transportation. In addition, each participant was asked to report the nature of the relationship between all alters identified (e.g., friend, family, or neighbor). Bivariate and multivariate analyses were used to explore the relationship between Pap test receipt at the CerviCusco outreach screening campaigns and social network characteristics. Bivariate results found significant differences in percentage of alter composition for neighbors and family, and for mean number of years known, mean density, and mean degree centrality between women who had received a Pap test (n = 19) compared to those who had not (n = 50) (p's < 0.05). The final logistic regression model was statistically significant (χ2 (2) = 20.911, p < .001). The model included the variables for percentage of family alter composition and mean density, and it explained 37.8% (Nagelkerke R(2)) of the variance in Pap test receipt, correctly classifying 78.3% of cases. Those women with higher percentages of family alter composition and higher mean density in their ego networks were less likely to have received a Pap test at the CerviCusco campaigns. According to this exploratory study, female neighbors more than family members may have provided an important source of social support for healthcare related decisions related to receipt of a Pap test. Future studies should collect longitudinal social network data on participants to measure the network effects of screening interventions in rural indigenous communities in Latin American countries experiencing the highest burden of cervical cancer.

  5. Cognitive predictors of cervical cancer screening’s stages of change among sample of Iranian women health volunteers: A path analysis

    PubMed Central

    Miri, Mohammad Reza; Moodi, Mitra; Sharif-Zadeh, Gholam-Reza; Malaki Moghadam, Hakimeh; Miri, Maryam; Norozi, Ensiyeh

    2018-01-01

    Introduction The uptake of Pap smear among Iranian women is low, resulting in a high rate of casualties from cervical cancer in Iran. The present study used the Health Belief Model (HBM) and the Stages of Change theory as theoretical frameworks for understanding the predictors of the behaviour of Iranian Women Health Volunteers (WHVs) with respect to cervical cancer screening. Methods Data from the 1,253 WHVs were analyzed using path analysis to assess the effects of cognitive factors (including knowledge, perceived susceptibility to cervical cancer, perceived severity of cervical cancer, Pap smear benefits, Pap smear barriers, and Pap smear self-efficacy) on the stages of change for Pap-smear behaviour. Results The majority of the respondents (71.5%) reported that they had not taken previous Pap smear tests; only 3% had received a regular Pap test. The perceived benefits to cervical cancer screening, the perceived barriers to cervical cancer screening, and the perceived self-efficacy to perform cervical cancer screening emerged as the predictors of cervical cancer screening’s stages of change; perceived threat to cervical cancer, however, did not. Discussion Uptake of regular cervical screening for Iranian WHVs was very low. Different interventions, such as media campaigns and educational interventions could provide an opportunity to improve women's knowledge on cervical cancer and Pap test benefits, address any misconceptions or fears about the procedure of the Pap test, and finally increase the cervical screening uptake by Iranian women. PMID:29558488

  6. Barriers to early detection of cervical-uterine cancer in Mexico.

    PubMed

    Lazcano-Ponce, E C; Castro, R; Allen, B; Nájera, P; Alonso de Ruíz, P A; Hernández-Avila, M

    1999-04-01

    In Mexico, a woman dies of cervical-uterine cancer every 2 hours, indicating a low impact by the national program for early detection of this cancer, principally because of problems related to quality and coverage. Through a qualitative study, we identified the principal barriers to use of the detection program from the point of view of actual and potential program users. Four focus groups were organized in standard conditions in Mexico City (urban, developed) and in the southern state of Oaxaca (rural, economically disadvantaged area). Participants were either women with at least one previous Papanicolaou (Pap) test or women who had never had the test. Barriers to Pap test use included (1) lack of knowledge about cervical-uterine cancer etiology, (2) not knowing that the Pap test exists, (3) the conception that cancer is an inevitably fatal disease, (4) problems in doctor/medical institution-patient relationships, (5) giving priority to unmet needs related to extreme poverty, (6) opposition by the male sexual partner, (7) rejection of the pelvic examination, (8) long waits for sample collection and receiving results, and (9) perceived high costs for care. To increase coverage of the early detection program for cervical-uterine cancer in Mexico, the needs, perceptions, and beliefs of women and their partners must be taken into account when developing policy and planning, given the role these factors play in the decision-making process that leads to their participation or nonparticipation in this program.

  7. Effect of Postactivation Potentiation Induced by Elastic Resistance on Kinematics and Performance in a Roundhouse Kick of Trained Martial Arts Practitioners.

    PubMed

    Aandahl, Håkon S; Von Heimburg, Erna; Van den Tillaar, Roland

    2018-04-01

    Aandahl, HS, Von Heimburg, E, and Van den Tillaar, R. Effect of postactivation potentiation induced by elastic resistance on kinematics and performance in a roundhouse kick of trained martial arts practitioners. J Strength Cond Res 32(4): 990-996, 2018-The aim of this study was to examine whether kicking with elastic resistance during warm-up could initiate postactivation potentiation (PAP), and thereby positively influence kinematics and performance on subsequent explosive roundhouse kicking. Five women and 11 men (n = 16) with a background in kickboxing (n = 10) or taekwondo (n = 6) performed 2 warm-up strategies with 3 subsequent test kicks 5-8 minutes after a PAP-inducing exercise. Kicking performance, defined as roundhouse kicking velocity with the foot, was measured using 3D motion capture (500 Hz) with a 15 marker lower-body 3D model. In addition, electromyography of the prime movers-vastus lateralis, vastus medialis, and rectus femoris muscles-was measured to confirm the presence of PAP. Kicking velocity of the foot increased by 3.3% after performing a warming-up strategy including kicking with elastic resistance (p = 0.009, η = 0.32). Increases were also recorded in muscle activity in vastus medialis (35.2%, p = 0.05, η = 0.18) and rectus femoris (43.9%, p = 0.04, η = 0.20). These findings indicate that performing a warm-up strategy including kicking with elastic resistance can have a positive effect on kicking performance in a roundhouse kick.

  8. Inflammation on the Cervical Papanicolaou Smear: Evidence for Infection in Asymptomatic Women?

    PubMed Central

    Tsirmpa, Ioanna; Chasiakou, Anthia; Tsouma, Iliana; Politi, Ekaterina; Gennimata, Vassiliki; Kouskouni, Evangelia

    2013-01-01

    Background. The significance of the possible presence of infection on the Pap smear of asymptomatic women based on cytological criteria is practically unknown. Materials and Methods. A total of 1117 asymptomatic nonpregnant women had Pap smear tests and vaginal as well as cervical cultures completed (622 with and 495 without inflammation on the Pap smear). Results. Out of the 622 women with inflammation on Pap test, 251 (40.4%) had negative cultures (normal flora present), while 371 (59.6%) women had positive cultures with different pathogens. In contrast, the group of women without inflammation on Pap test displayed significantly increased percentage of negative cultures (67.1%, P < 0.001) and decreased percentage of positive cultures (32.9%, P < 0.001). Bacterial vaginosis was diagnosed more frequently in both groups and significantly more in the group with inflammation on Pap smear compared to the group without inflammation (P < 0.02). Conclusions. A report of inflammatory changes on the cervical Pap smear cannot be used to reliably predict the presence of a genital tract infection, especially in asymptomatic women. Nevertheless, the isolation of different pathogens in about 60% of the women with inflammation on the Pap smear cannot be overlooked and must be regarded with concern. PMID:24204103

  9. Fabrication technique for a custom face mask for the treatment of obstructive sleep apnea.

    PubMed

    Prehn, Ronald S; Colquitt, Tom

    2016-05-01

    The development of the positive airway pressure custom mask (TAP-PAP CM) has changed the treatment of obstructive sleep apnea. The TAP-PAP CM is used in continuous positive airway pressure therapy (CPAP) and is fabricated from the impression of the face. This mask is then connected to a post screwed into the mechanism of the TAP3 (Thornton Anterior Positioner) oral appliance. This strapless CPAP face mask features an efficient and stable CPAP interface with mandibular stabilization (Hybrid Therapy). A technique with a 2-stage polyvinyl siloxane face impression is described that offers improvements over the established single-stage face impression. This 2-stage impression technique eliminates problems inherent in the single-stage face impression, including voids, compressed tissue, inadequate borders, and a rushed experience due to the setting time of the single stage. The result is a custom mask with an improved seal to the CPAP device. Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

  10. Antioxidant and antitumor effects of polysaccharides from the fungus Pleurotus abalonus.

    PubMed

    Ren, Daoyuan; Jiao, Yadong; Yang, Xingbin; Yuan, Li; Guo, Jianjun; Zhao, Yan

    2015-07-25

    Dietary supplement of edible Pleurotus abalonus (P. abalonus) rich in fungal polysaccharides is associated with anticancer health benefit. We here isolated the polysaccharides (PAP) from the fruiting bodies of P. abalonus, and evaluated the antiproliferative activity of the polysaccharides in human colorectal carcinoma LoVo cells. HPLC analysis showed that PAP consisted of D-mannose, D-ribose, l-rhamnose, D-glucuronic acid, D-glucose and D-galactose, and their corresponding mole percentages were 3.4%, 1.1%, 1.9%, 1.4%, 87.9% and 4.4%, respectively. PAP was shown to exert a high antioxidant activity in vitro and a dose-dependent antiproliferative effect against LoVo cancer cells. Flow cytometry analysis demonstrated that PAP exhibited a stimulatory effect on apoptosis of LoVo cells, and induced the cell-cycle arrest at the S phase. We also found that PAP could increase the generation of intracellular ROS which was a critical mediator in PAP-induced cell growth inhibition. These findings suggest that PAP may serve as a potential novel dietary agent for human colon cancer chemoprevention. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  11. Reproducibility of self-reported pap test utilization in middle-aged African-American women.

    PubMed

    Hoyo, Cathrine; Ostbye, Truls; Skinner, Celette S; Yarnall, Kimberly S H; Chowdhary, Jaspreet

    2005-01-01

    Both clinicians who perform Pap tests and prescribe re-screens and public health officials, who periodically evaluate the success of Pap test screening programs, often depend on women to self-report their most recent Pap test. However, reliability of self-reported Pap test utilization is putatively low, and even lower in African-American women compared to Whites. Between 2001 and 2002, Pap test screening histories were obtained from 144 African-American women, aged 45 to 64 years at two in-person interviews conducted three to six weeks apart. Reproducibility of self-reported Pap test was substantial (kappa=0.64; 95% confidence interval: .46-.82), with the highest agreement among women with greater income and educational attainment, and those who were younger. This level of reproducibility is likely sufficient both to evaluate the population coverage of public health screening programs and for prescribing re-screens among younger African-American women and those of higher income and education. Not using self-reports to base clinic decisions may still be prudent among those with less education.

  12. Emerging Roles of Human Prostatic Acid Phosphatase

    PubMed Central

    Kong, Hoon Young; Byun, Jonghoe

    2013-01-01

    Prostate cancer is one of the most prevalent non-skin related cancers. It is the second leading cause of cancer deaths among males in most Western countries. If prostate cancer is diagnosed in its early stages, there is a higher probability that it will be completely cured. Prostatic acid phosphatase (PAP) is a non-specific phosphomonoesterase synthesized in prostate epithelial cells and its level proportionally increases with prostate cancer progression. PAP was the biochemical diagnostic mainstay for prostate cancer until the introduction of prostate-specific antigen (PSA) which improved the detection of early-stage prostate cancer and largely displaced PAP. Recently, however, there is a renewed interest in PAP because of its usefulness in prognosticating intermediate to high-risk prostate cancers and its success in the immunotherapy of prostate cancer. Although PAP is believed to be a key regulator of prostate cell growth, its exact role in normal prostate as well as detailed molecular mechanism of PAP regulation is still unclear. Here, many different aspects of PAP in prostate cancer are revisited and its emerging roles in other environment are discussed. PMID:24009853

  13. Role of Atf1 and Pap1 in the induction of the catalase gene of fission yeast schizosaccharomyces pombe.

    PubMed

    Nakagawa, C W; Yamada, K; Mutoh, N

    2000-02-01

    We examined the induction of the catalase gene (ctt1(+)) of fission yeast Schizosaccharomyces pombe in response to several stresses by using mutants of transcription factors (Atf1 and Pap1) and a series of deletion mutants of the ctt1(+) promoter region. A transcription factor, Atf1, and its binding site are necessary for the induction of ctt1(+) by osmotic stress, UV irradiation, and heat shock. Induction by menadione treatment, which produces superoxide anion, required element A, the region from -111 to -90 (numbered with the transcription start site as +1). The factor responsible for the induction of the gene by oxidative stress via element A was identified as the transcription factor Pap1. We also found that Atf1 is activated by menadione treatment in pap1 mutant cells, although it is not activated by menadione treatment in pap1(+) cells. The activity of catalase is not increased in pap1 cells by several stresses, despite mRNA induction, suggesting that Pap1 plays some role in the expression of catalase activity.

  14. Motion control system of MAX IV Laboratory soft x-ray beamlines

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sjöblom, Peter, E-mail: peter.sjoblom@maxlab.lu.se; Lindberg, Mirjam, E-mail: mirjam.lindberg@maxlab.lu.se; Forsberg, Johan, E-mail: johan.forsberg@maxlab.lu.se

    2016-07-27

    At the MAX IV Laboratory, five new soft x-ray beamlines are under development. The first is Species and it will be used to develop and set the standard of the control system, which will be common across the facility. All motion axes at MAX IV will be motorized using stepper motors steered by the IcePAP motion controller and a mixture of absolute and incremental encoders following a predefined coordinate system. The control system software is built in Tango and uses the Python-based Sardana framework. The user controls the entire beamline through a synoptic overview and Sardana is used to runmore » the scans.« less

  15. Activity-guided isolation of a sirtuin2 inhibiting compound from coffee: structural and activity confirmation of Javamide-II (N-caffeoyltryptophan)and its cellular effects on histone H3 and alpha-tubulin

    USDA-ARS?s Scientific Manuscript database

    Coffee is a most consumed drink worldwide, with potential health effects on several chronic diseases including neuronal degenerative diseases. Interestingly, recent studies suggest that the inhibition of sirtuin2 may be beneficial in restoring cognition in Alzheimer’s disease. Therefore, in this pap...

  16. The stability of prostatic acid phosphatase, as measured by a capture immunoenzyme assay.

    PubMed

    Lin, T M; Chin-See, M W; Halbert, S P

    1984-03-27

    A capture immunoenzyme assay (CIEA) for prostatic acid phosphatase (PAP) was developed and used to study the stability of this isoenzyme. Immunospecifically purified goat antibodies to PAP were covalently bound to special discs and used to capture the enzyme in serum samples in a weakly acidic medium during the first incubation (2 h) at 37 degrees C. The capture enzyme was then measured by its catalytic activity with p-nitrophenyl phosphate as substrate during the second incubation (1 h) at 37 degrees C. As much as 98% of the PAP in test specimens was captured and measured by this CIEA. The test results were expressed as enzymatic activity (U/l), extrapolated from a standard curve which was linear between 0.026 and 70 U/l. In test sera stored at 4 degrees C, the PAP was variably stable for 7 to 70 days, but the enzyme was quite stable in serum when stored at -20 degrees C for at least 156 days. At room temperature, when the sera were appropriately acidified, there was no loss of enzymatic activity for periods of 15 days, and in some cases, a large proportion of activity was still intact after 70 days. At 4 degrees C, as well as -20 degrees C, acidified serum and the partially purified PAP standard showed complete stability for at least 7 months. The CIEA reactivity of positive test specimens was inhibited by L(+)-tartaric acid, but not by cupric sulfate. The acid phosphatases of blood cell extracts were non-reactive in the CIEA procedure. The CIEA results of 224 serum samples from patients with and without prostate cancer correlated very well with those obtained by two direct enzymatic and two commercial RIA procedures, with correlation coefficients between 0.960 and 0.993, and diagnostic agreement between 86% and 100%.

  17. Cervical pre-malignant lesions in HIV infected women attending Care and Treatment Centre in a tertiary hospital, Dar es Salaam, Tanzania.

    PubMed

    Balandya, Belinda S; Pembe, Andrea B; Mwakyoma, Henry A

    2011-09-01

    The aims of this study was to determine proportion of HIV infected women with cervical pre-malignant lesions; and compare the use of Visual Inspection of the cervix after application of Acetic acid (VIA) and Papanicolau (Pap) smear in screening for cervical premalignant lesions in HIV positive women attending Care and Treatment Centre (CTC) at Muhimbili National Hospital (MNH), Dar es Salaam, Tanzania. A total of 316 women aged 18-70 years had a Pap smear taken for cytology, followed by spraying onto the cervix with 4% acetic acid and then inspecting it. Cytology was considered negative when there was no Cervical Intraepithelial Neoplasia (CIN) lesion reported from the Pap smear taken, and positive if CIN lesion 1, 2 or 3 was reported. Detection of a well-defined, opaque acetowhite lesion close to the squamocolumnar junction or close to the external cervical os constituted a positive VIA. Out of 316 women, 132 women had acetowhite lesions on VIA, making the proportion of abnormal cervical lesions to be 42.4%. One hundred and one out of 312 women (32.4%) had CIN lesions detected on Pap smear. The proportion of agreement between these two tests was 0.3. The proportion of agreement was moderate in women with advanced WHO HIV clinical stage of the disease and in women not on ART (Anti Retroviral Therapy). Women with CD-4 count less than 200 cells/mm3 had more abnormal cervical lesions. There is considerable proportion of HIV positive women with premalignant lesions of the cervix. Considering the proportion of HIV women with abnormal lesions and the difficulty in logistics of doing Pap smear in low resource settings, these results supports the recommendation to introduce screening of premalignant lesions of the cervix using VIA to all HIV infected women.

  18. Effectiveness of VIA, Pap, and HPV DNA Testing in a Cervical Cancer Screening Program in a Peri-Urban Community in Andhra Pradesh, India

    PubMed Central

    Gravitt, Patti E.; Paul, Proma; Katki, Hormuzd A.; Vendantham, Haripriya; Ramakrishna, Gayatri; Sudula, Mrudula; Kalpana, Basany; Ronnett, Brigitte M.; Vijayaraghavan, K.; Shah, Keerti V.

    2010-01-01

    Background While many studies have compared the efficacy of Pap cytology, visual inspection with acetic acid (VIA) and human papillomavirus (HPV) DNA assays for the detection cervical intraepithelial neoplasia and cancer, few have evaluated the program effectiveness. Methods and Findings A population-based sample of 5603 women from Medchal Mandal in Andhra Pradesh, India were invited to participate in a study comparing Pap cytology, VIA, and HPV DNA screening for the detection of CIN3+. Participation in primary screening and all subsequent follow-up visits was rigorously tracked. A 20% random sample of all women screened, in addition to all women with a positive screening test result underwent colposcopy with directed biopsy for final diagnosis. Sensitivity, specificity, positive and negative predictive values were adjusted for verification bias. HPV testing had a higher sensitivity (100%) and specificity (90.6%) compared to Pap cytology (sensitivity  =  78.2%; specificity = 86.0%) and VIA (sensitivity = 31.6%; specificity = 87.5%). Since 58% of the sample refused involvement and another 28% refused colposcopy or biopsy, we estimated that potentially 87.6% of the total underlying cases of CIN3 and cancer may have been missed due to program failures. Conclusions We conclude that despite our use of available resources, infrastructure, and guidelines for cervical cancer screening implementation in resource limited areas, community participation and non-compliance remain the major obstacles to successful reduction in cervical cancer mortality in this Indian population. HPV DNA testing was both more sensitive and specific than Pap cytology and VIA. The use of a less invasive and more user-friendly primary screening strategy (such as self-collected swabs for HPV DNA testing) may be required to achieve the coverage necessary for effective reduction in cervical cancer mortality. PMID:21060889

  19. The impact of concomitant pulmonary hypertension on early and late outcomes following surgery for mitral stenosis.

    PubMed

    Yang, Bo; DeBenedictus, Christina; Watt, Tessa; Farley, Sean; Salita, Alona; Hornsby, Whitney; Wu, Xiaoting; Herbert, Morley; Likosky, Donald; Bolling, Steven F

    2016-08-01

    To provide initial evidence on the management of mitral stenosis and pulmonary hypertension (PH) based on short-term and long-term outcomes following mitral valve surgery. Consecutive patients with mitral stenosis (n = 317) who had undergone mitral valve surgery between 1992 and 2014 with recorded pulmonary artery pressure (PAP) data were reviewed. PH severity, based on systolic PAP, was categorized as mild (35 to 44 mm Hg), moderate (45 to 59 mm Hg), or severe (>60 mm Hg). Primary outcomes were 30-day mortality and long-term survival. There were no significant between-group differences in age or preoperative comorbidities. Mitral valve surgery included mitral valve replacement (78%) and repair (22%). The severe PH group had more mitral valve replacement (81%; P = .04), severe tricuspid valve regurgitation (31%; P = .003), right heart failure (17%; P = .02), and concomitant tricuspid valve procedures (46%; P < .001). For severe PH, 30-day mortality was 9%, with no significant group differences. Ten- and 12-year survival were significantly worse in the moderate-severe PH group (58% and 51%, respectively) compared with the normal PAP-mild PH group (83% and 79%, respectively) with a hazard ratio of 2.98 (95% confidence interval, 1.55-5.75; P = .001). Ten-year survival after mitral valve surgery for mitral stenosis was inversely associated with preoperative PAP. Mitral valve surgery can be performed with acceptable 30-day mortality for patients with mitral stenosis and moderate to severe PH, but long-term survival is impaired by moderate to severe PH. Patients with mitral stenosis and mild PH (systolic PAP 35-44 mm Hg) should be considered for mitral valve surgery. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  20. The Cellient automated cell block system is useful in the differential diagnosis of atypical glandular cells in Papanicolaou tests.

    PubMed

    Xing, Wei; Hou, April Y; Fischer, Andrew; Owens, Christopher L; Jiang, Zhong

    2014-01-01

    Atypical glandular cells (AGC) is a very important diagnosis in gynecological cytology. In the current study, the authors investigated the usefulness of Cellient cell blocks (CB) for characterizing AGC on Papanicolaou (Pap) tests. A total of 148 patients with an AGC diagnosis based on Pap tests by cytotechnologists and referred to cytopathologists were studied. Among these patients, there were 68 patients with CB preparations and 80 patients with Pap tests only (TP-AGC group). Follow-up results by Pap tests or biopsies were obtained in 117 of 148 patients. The median follow-up was 13 months (range, 1 month-36 months). Of the 68 patients with CBs, 31 (46%) were reclassified as negative for dysplasia or low-grade intraepithelial lesion; 30 patients (44%) retained a diagnosis of AGC (CB-AGC group); and 7 patients (10%) were given specific diagnoses of high-grade intraepithelial lesion (3 patients), endocervical adenocarcinoma in situ (1 patient), and invasive adenocarcinoma (3 patients). On follow-up, the CB-AGC group was found to have a significantly lower rate of negative/low-grade squamous intraepithelial lesion diagnoses compared with the TP-AGC group (55% vs 85%; P= .006). The CB-AGC group had a significantly higher rate of endocervical or endometrial adenocarcinoma compared with the TP-AGC group (36% vs 8%; P= .003) at the time of follow-up. The rates of high-grade squamous intraepithelial lesion were not found to be statistically different between these 2 groups (9% vs 7%; P= .66). The Cellient CB is a useful technique to further categorize a diagnosis of AGC on Pap tests. Using the Cellient CB system, the pathologist has the ability to improve the diagnostic accuracy of AGC so that unnecessary colposcopic evaluation or biopsies can be avoided. © 2013 American Cancer Society.

  1. Exercise hypoxaemia as a predictor of pulmonary hypertension in COPD patients without severe resting hypoxaemia.

    PubMed

    Nakahara, Yoshio; Taniguchi, Hiroyuki; Kimura, Tomoki; Kondoh, Yasuhiro; Arizono, Shinichi; Nishimura, Koichi; Sakamoto, Koji; Ito, Satoru; Ando, Masahiko; Hasegawa, Yoshinori

    2017-01-01

    Pulmonary hypertension (PH) in COPD is associated with morbidity and mortality. Previous studies showed a relationship between resting hypoxaemia and PH, but little is known about the relationship between exercise hypoxaemia and PH in COPD without resting hypoxaemia. A retrospective observational study of COPD patients without resting hypoxaemia was conducted to evaluate the relationships between exercise hypoxaemia and pulmonary haemodynamics. Clinical characteristics, pulmonary function, blood gas analysis, 6-min walk distance (6MWD) and oxygen saturation of peripheral artery (SpO 2 ) at the end of the 6-min walk test (6MWT) were reviewed. Correlation analysis and stepwise regression analysis were performed to identify the predictor of mean pulmonary artery pressure (mPAP). Eighty-four consecutive patients with a mean predicted forced expiratory volume in 1 s (FEV 1 ) of 47 ± 21% were evaluated. In univariate analysis, mPAP had negative correlations with age (r = -0.27, P < 0.05), arterial partial pressure of oxygen (PaO 2 , r = -0.24, P < 0.05), % predicted forced vital capacity (FVC, r = -0.28, P < 0.05), % predicted FEV 1 (r = -0.40, P < 0.001), FEV 1 /FVC ratio (r = -0.33, P < 0.005), % predicted diffusion capacity for carbon monoxide (DL CO , r = -0.40, P < 0.001), 6MWD (r = -0.40, P < 0.001) and SpO 2 at the end of the 6MWT (r = -0.74, P < 0.001). In stepwise regression analysis, SpO 2 at the end of the 6MWT and 6MWD remained as independent predictors of mPAP (R 2  = 0.60). In receiver operating characteristic (ROC) analysis, SpO 2 at the end of the 6MWT presented an area under the curve of 0.896 for the prediction of PH, with a sensitivity of 0.86 and specificity of 0.84 for the cut-off point of 81%. In addition to 6MWD, exercise hypoxaemia indicates PH in patients with COPD without resting hypoxaemia. © 2016 Asian Pacific Society of Respirology.

  2. Detection of Heart Sounds in Children with and without Pulmonary Arterial Hypertension―Daubechies Wavelets Approach

    PubMed Central

    Elgendi, Mohamed; Kumar, Shine; Guo, Long; Rutledge, Jennifer; Coe, James Y.; Zemp, Roger; Schuurmans, Dale; Adatia, Ian

    2015-01-01

    Background Automatic detection of the 1st (S1) and 2nd (S2) heart sounds is difficult, and existing algorithms are imprecise. We sought to develop a wavelet-based algorithm for the detection of S1 and S2 in children with and without pulmonary arterial hypertension (PAH). Method Heart sounds were recorded at the second left intercostal space and the cardiac apex with a digital stethoscope simultaneously with pulmonary arterial pressure (PAP). We developed a Daubechies wavelet algorithm for the automatic detection of S1 and S2 using the wavelet coefficient ‘D 6’ based on power spectral analysis. We compared our algorithm with four other Daubechies wavelet-based algorithms published by Liang, Kumar, Wang, and Zhong. We annotated S1 and S2 from an audiovisual examination of the phonocardiographic tracing by two trained cardiologists and the observation that in all subjects systole was shorter than diastole. Results We studied 22 subjects (9 males and 13 females, median age 6 years, range 0.25–19). Eleven subjects had a mean PAP < 25 mmHg. Eleven subjects had PAH with a mean PAP ≥ 25 mmHg. All subjects had a pulmonary artery wedge pressure ≤ 15 mmHg. The sensitivity (SE) and positive predictivity (+P) of our algorithm were 70% and 68%, respectively. In comparison, the SE and +P of Liang were 59% and 42%, Kumar 19% and 12%, Wang 50% and 45%, and Zhong 43% and 53%, respectively. Our algorithm demonstrated robustness and outperformed the other methods up to a signal-to-noise ratio (SNR) of 10 dB. For all algorithms, detection errors arose from low-amplitude peaks, fast heart rates, low signal-to-noise ratio, and fixed thresholds. Conclusion Our algorithm for the detection of S1 and S2 improves the performance of existing Daubechies-based algorithms and justifies the use of the wavelet coefficient ‘D 6’ through power spectral analysis. Also, the robustness despite ambient noise may improve real world clinical performance. PMID:26629704

  3. Structural and kinetic properties of a novel purple acid phosphatase from phosphate-starved tomato (Lycopersicon esculentum) cell cultures.

    PubMed Central

    Bozzo, Gale G; Raghothama, Kashchandra G; Plaxton, William C

    2004-01-01

    An intracellular acid phosphatase (IAP) from P(i)-starved (-P(i)) tomato ( Lycopersicon esculentum ) suspension cells has been purified to homogeneity. IAP is a purple acid phosphatase (PAP), as the purified protein was violet in colour (lambda(max)=546 nm) and was insensitive to L-tartrate. PAGE, periodic acid-Schiff staining and peptide mapping demonstrated that the enzyme exists as a 142 kDa heterodimer composed of an equivalent ratio of glycosylated and structurally dissimilar 63 (alpha-subunit) and 57 kDa (beta-subunit) polypeptides. However, the nine N-terminal amino acids of the alpha- and beta-subunits were identical, exhibiting similarity to the deduced N-terminal portions of several putative plant PAPs. Quantification of immunoblots probed with rabbit anti-(tomato acid phosphatase) immune serum revealed that the 4-fold increase in IAP activity due to P(i)-deprivation was correlated with similar increases in the amount of antigenic IAP alpha- and beta-subunits. IAP displayed optimal activity at pH 5.1, was activated 150% by 10 mM Mg(2+), but was potently inhibited by Zn(2+), Cu(2+), Fe(3+), molybdate, vanadate, fluoride and P(i). Although IAP demonstrated broad substrate selectivity, its specificity constant ( V (max)/ K (m)) with phosphoenolpyruvate was >250% greater than that obtained with any other substrate. IAP exhibited significant peroxidase activity, which was optimal at pH 9.0 and insensitive to Mg(2+) or molybdate. This IAP is proposed to scavenge P(i) from intracellular phosphate esters in -P(i) tomato. A possible secondary IAP role in the metabolism of reactive oxygen species is discussed. IAP properties are compared with those of two extracellular PAP isoenzymes that are secreted into the medium of -P(i) tomato cells [Bozzo, Raghothama and Plaxton (2002) Eur. J. Biochem. 269, 6278-6286]. PMID:14521509

  4. Comparison of Human Papillomavirus Detection by Aptima HPV and cobas HPV Tests in a Population of Women Referred for Colposcopy following Detection of Atypical Squamous Cells of Undetermined Significance by Pap Cytology

    PubMed Central

    Castle, Philip E.; Eaton, Barbara; Reid, Jennifer; Dockter, Janel

    2015-01-01

    Few studies have compared the cobas HPV test to the Aptima HPV assay (AHPV) and the Aptima HPV 16 18/45 genotype assay (AHPV GT) for high-risk human papillomavirus (hrHPV) detection, clinical performance in detecting cervical intraepithelial neoplasia grade 2 (CIN2) or more severe (CIN2+) diagnoses, and risk stratification by partial HPV genotyping. The cobas HPV test is a DNA test that separately and concurrently detects HPV16, HPV18, and a pool of 12 other hrHPV types. AHPV is an RNA test for a pool of 14 hrHPV genotypes, and AHPV GT is an RNA test run on AHPV-positive results to detect HPV16 separately from HPV18 and HPV45, which are detected together. In a population of patients (n = 988) referred for colposcopy because of a cervical Pap cytology result of atypical squamous cells of undetermined significance (ASC-US), a cervical scrape specimen was taken, placed into a ThinPrep Pap test vial containing PreservCyt liquid cytology medium, and tested in a blinded fashion with cobas and AHPV and with AHPV GT for AHPV-positive results. The final diagnoses were based on a consensus panel review of the biopsy specimen histology. AHPV and cobas were equally sensitive for CIN2+ diagnoses (89.4% each; P = 1.000), and AHPV was more specific than cobas (63.1% versus 59.3%; P ≤ 0.001). The percent total agreement, percent positive agreement, and kappa value were 90.9%, 81.1%, and 0.815, respectively. Risk stratification using partial HPV genotyping was similar for the two assays. AHPV and AHPV GT had similar sensitivity and risk stratification to cobas HPV, but they were more specific than cobas HPV. PMID:25653409

  5. The transverse musculo-cutaneous gracilis flap for breast reconstruction: How to avoid complications.

    PubMed

    Bodin, Frédéric; Dissaux, Caroline; Dupret-Bories, Agnes; Schohn, Thomas; Fiquet, Caroline; Bruant-Rodier, Catherine

    2016-01-01

    The transverse musculocutaneous gracilis (TMG) flap has become a common solution for breast reconstruction. However, the safe skin paddle limits are not yet understood. In this study, we attempted to address this issue based on our experiences with inferior and posterior skin paddle extension. Forty-four breast reconstructions with TMG flaps performed between November 2010 and January 2014 were analyzed retrospectively. For the first 20 cases, the flap skin paddle was extended 3 cm posteriorly to the middle thigh (group 1). For the next 20 flaps (group 2), the posterior tip was limited to this line, whereas more fat was recruited inferiorly. In the four cases of group 3, the skin flap was extended posteriorly with a second vascular pedicle from the profunda artery perforator (PAP) flap. The weights and the dimensions of the flaps, operating durations, and postoperative complications of the entire series were analyzed. Groups 1 and 2 were statistically compared. Flap complications were statistically more frequent in group 1 compared with group 2 (45 vs. 0%, P = 0.0012); 40% posterior flap tip necrosis was observed in group 1. Conversely, donor site complications were statistically more frequent in group 2 than in group 1 (40 vs. 5%, P = 0.019) with 35% inner thigh dehiscence. In the TMG with extended PAP flap group, the operating duration was 77 min longer compared with the rest of the series with no donor site complications. In one case, limited necrosis occurred at the anterior skin tip. Harvesting the posterior portion of the TMG up to the middle of the posterior thigh may lead to partial flap necrosis. Extending subcutaneous fat removal under the inferior skin incision may increase the risk of donor site complications. Adding a second vascular pedicle from the PAP flap may improve posterior TMG tip perfusion at the expense of a longer operation. © 2015 Wiley Periodicals, Inc.

  6. [APPLICATION VALUE OF INDOCYANINE GREEN ANGIOGRAPHY IN FLAP RECONSTRUCTIVE SURGERY].

    PubMed

    Yang, Kai; Mu, Lan; Liu, Yan; Peng, Zhe; Li, Guangxue

    2015-09-01

    To investigate the utility of indocyanine green angiography in flap reconstructive surgery and possibility of decrease the complications. Indocyanine green angiography was performed on 14 patients undergoing flap reconstructive surgery between February and December 2014 to evaluate the blood perfusion of the flap and to adjust the operation plan. Of 14 cases, 2 were male and 12 were female, aged 23-58 years (mean, 35.5 years); 11 flaps were used for breast reconstruction [including 3 free deep inferior epigastric antery perforator (DIEP) flaps, 4 pedicled transverse rectus abdominis myocutaneous flaps (TRAM), 2 pedicled TRAM and free TRAM, and 2 pedicled latissimus dorsi myocutaneous flaps and prosthesis], 1 pedicled latissimus dorsi myocutaneous flap for repairing chest wall defect, 1 pedicled profunda artery perforator (PAP) flap for upper leg defect, and 1 pedicled descending genicular artery perforator flap for knee defect. The size of the flaps ranged from 9 cm x 6 cm to 26 cm x 12 cm. A total of 32 indocyanine green angiography were performed. There was no adverse reactions to the infusion of indocyanine green. The surgery management was adjusted according to results of indocyanine green angiography findings in 5 of 14 cases. The distal part of flap were discarded because of poor perfusion in 3 cases (1 DIEP flap, 1 TRAM, and 1 PAP flap) and the other 2 cases (pedicled TRAM) needed additional free anastomosis to ensure sufficient blood supply (pedicled TRAM and free TRAM); the other flaps were harvested according to preoperative plan and repaired defect successfully. The mean follow-up was 5 months (range, 1-9 months). The other flaps survived without infection or fat necrosis except 1 PAP flap with distal necrosis. Intraoperative indocyanine green angiography can provide real-time information of flap perfusion and then the operation plan can be adjusted in time to ensure the flap survival.

  7. Perceptions and concerns of women undergoing Pap smear examination in a tertiary care hospital of India.

    PubMed

    Tiwari, A; Kishore, J; Tiwari, A

    2011-01-01

    Cervical cancer is one of the major causes of deaths due to cancer among women in India. Pap smear is one of the best methods to detect early changes in cervix. However, there is lack of data on awareness level of women about Pap smear and various risk factors for cervical cancer. To study the awareness about various risk factors for cervical cancer, health-seeking behavior and hygienic practices among women and to assess the distress experienced by these women before the Pap smear examination. This cross-sectional study was carried out on women coming for a Pap smear examination in a tertiary teaching hospital in New Delhi. A pretested interview schedule was used to get information after obtaining their informed consent. Fifty-seven percent stated that they did not consult a doctor when they noticed the symptoms the first time. Sixty-one percent did not know what a cervical cancer is and a same percentage of women did not know what a Pap smear examination was. Older age group, Muslim and literate women had higher number of abnormal Pap smear results. Women who reported being stressed in their lives had higher number of abnormal smears as compared to women who claimed to lead a stress free life. Poor hygienic practices among these women from urban areas were also associated with abnormal Pap smear results. The study concluded that factors such as poor awareness, shyness, poor hygiene, and old age could be responsible for abnormal Pap smears and this needs special attention in cancer prevention activities of the government.

  8. The pancreas responds to remote damage and systemic stress by secretion of the pancreatic secretory proteins PSP/regI and PAP/regIII.

    PubMed

    Reding, Theresia; Palmiere, Cristian; Pazhepurackel, Clinsyjos; Schiesser, Marc; Bimmler, Daniel; Schlegel, Andrea; Süss, Ursula; Steiner, Sabrina; Mancina, Leandro; Seleznik, Gitta; Graf, Rolf

    2017-05-02

    In patients with infection and sepsis serum levels of Pancreatic Stone protein/regenerating protein I (PSP) are highly elevated. The origin of PSP during these conditions is presumably the pancreas, however, an intestinal origin cannot be excluded. Similarly, pancreatitis-associated protein (PAP) was identified in the pancreas. These proteins were also localized in intestinal organs. Here we aim to elucidate the bio-distribution of PSP and PAP in animal models of sepsis and in healthy humans. PSP and PAP responded to remote lesions in rats although the pancreatic response was much more pronounced than the intestinal. Tissue distribution of PSP demonstrated a 100-fold higher content in the pancreas compared to any other organ while PAP was most abundant in the small intestine. Both proteins responded to CLP or sham operation in the pancreas. PSP also increased in the intestine during CLP. The distribution of PSP and PAP in human tissue mirrored the distribution in the murine models. Distribution of PSP and PAP was visualized by immunohistochemistry. Rats and mice underwent midline laparotomies followed by mobilization of tissue and incision of the pancreatic duct or duodenum. Standard cecum-ligation-puncture (CLP) procedures or sham laparotomies were performed. Human tissue extracts were analyzed for PSP and PAP. The pancreas reacts to remote lesions and septic insults in mice and rats with increased PSP synthesis, while PAP is selectively responsive to septic events. Furthermore, our results suggest that serum PSP in septic patients is predominantly derived through an acute phase response of the pancreas.

  9. Overall accuracy of cervical cytology and clinicopathological significance of LSIL cells in ASC-H cytology.

    PubMed

    Kim, S H; Lee, J M; Yun, H G; Park, U S; Hwang, S U; Pyo, J-S; Sohn, J H

    2017-02-01

    The aims of this study were (i) to investigate the diagnostic accuracy of Papanicolaou (Pap) smears and (ii) to evaluate the clinicopathological significance of the presence of low-grade squamous intraepithelial lesion (LSIL) cells in atypical squamous cells cannot exclude high-grade squamous intraepithelial lesion (HSIL) (ASC-H) cytology. We retrospectively reviewed paired cytological and histological findings from 3141 patients. ASC-H cytology was classified as either ASC-H or LSIL with some features suggestive of the presence of a concurrent HSIL (LSIL-H). Clinicopathological characteristics were evaluated through a retrospective study and meta-analysis. The accuracy of the cytological diagnosis was 93.7% (2942 of 3141 cases). The positive predictive value (PPV) of ASC-H for cervical intraepithelial neoplasia grade 2 or worse (CIN 2+ ) was 51.4%. In cases of LSIL-H, CIN 2+ histology was more prevalent in the pre-menopausal period (19-44 years) than in peri- and postmenopausal periods (older than 45 years) (P = 0.024). There was no difference in the ability of LSIL-H and ASC-H to predict CIN 2+. The Pap smear is a good cervical cancer screening method. Although there was no difference in the predictive value for CIN 2+ between LSIL-H and ASC-H, the presence of definite LSIL cells was more predictive of CIN 2+ in younger patients than in older patients. © 2016 John Wiley & Sons Ltd.

  10. Semi- and thiosemicarbazide Mn(II) complexes: Characterization, DFT and biological studies

    NASA Astrophysics Data System (ADS)

    Yousef, T. A.; Alduaij, O. K.; Ahmed, Sara F.; Abu El-Reash, G. M.; El-Gammal, O. A.

    2016-09-01

    One NO and two NOS donor ligands have been prepared by addition ethanolic suspension of 2-hydrazino-2-oxo-N-phenyl-acetamide to phenyl isocyanate (H2PAPS), phenyl isothiocyanate (H2PAPT) and benzoyl isothiocyanate (H2PABT). The Mn (II) complexes were prepared from the chloride salt and characterized by conventional techniques. The isolated complexes were assigned the formulaes, [Mn(HPAPS)2], [Mn(HPAPT)Cl] and [Mn(HPABT)Cl(H2O)2], respectively. The IR study of ligands and their complexes shows that H2PAPS behaves as a mononegative tridentate via both CO of hydrazide moiety in keto and deprotonated enol form and CN (azomethine) due to enolization of CO cyanate moiety without deprotonation. H2PAPT behaves as mononegative tridentate via CO of hydrazide moiety, deprotonated thiol CS and NH group. Finally H2PABT behaves as mononegative tridentate via deprotonated enolized CO of hydrazide moiety, CO of benzoyl moiety and NH group. The IR spectra of ligands from DFT calculations are compared with those obtained experimentally. Also, HOMO, LUMO, the bond lengths, bond angles, and dipole moments have been calculated. The calculated HOMO-LUMO energy gap reveals that charge transfer occurs within the molecule. The binding energy values display the high stability of complexes. The kinetic and thermodynamic parameters were determined by Coats-Redfern and Horowitz-Metzger methods. The antibacterial activities were also tested against Bacillus subtilis and Escherichia coli bacteria. Finally, the antitumor activities of the Ligands and their Mn(II) complexes have been evaluated against liver (HePG2) and breast (MCF-7) cancer cells.

  11. Sleep Disordered Breathing in Patients with Heart Failure: Pathophysiology and Management

    PubMed Central

    Sharma, Bhavneesh; McSharry, David; Malhotra, Atul

    2013-01-01

    Opinion statement Sleep disordered breathing (SDB) is common in heart failure patients across the range of ejection fractions and is associated with adverse prognosis. Although effective pharmacologic and device-based treatment of heart failure may reduce the frequency or severity of SDB, heart failure treatment alone may not be adequate to restore normal breathing during sleep. Continuous positive airway pressure (CPAP) is the major treatment for SDB in heart failure, especially if obstructive rather than central sleep apnea (CSA) predominates. Adequate suppression of CSA by PAP is associated with a heart transplant-free survival benefit, although randomized trials are ongoing. Bilevel PAP (BPAP) may be as effective as CPAP in treating SDB and may be preferable over CPAP in patients who experience expiratory pressure discomfort. Adaptive (or auto) servo-ventilation (ASV), which adjusts the PAP depending on the patient’s airflow or tidal volume, may be useful in congestive heart failure patients if CPAP is ineffective. Other therapies that have been proposed for SDB in congestive heart failure include nocturnal oxygen, CO2 administration (by adding dead space), theophylline, and acetazolamide; most of which have not been systematically studied in outcome-based prospective randomized trials. PMID:21894522

  12. The small-x gluon distribution in centrality biased pA and pp collisions

    DOE PAGES

    Dumitru, Adrian; Kapilevich, Gary; Skokov, Vladimir

    2018-04-04

    Here, the nuclear modification factor R pA(p T) provides information on the small- x gluon distribution of a nucleus at hadron colliders. Several experiments have recently measured the nuclear modification factor not only in minimum bias but also for central pA collisions. In this paper we analyze the bias on the configurations of soft gluon fields introduced by a centrality selection via the number of hard particles. Such bias can be viewed as reweighting of configurations of small- x gluons. We find that the biased nuclear modification factor Q pA(p T) for central collisions is above R pA(p T) formore » minimum bias events, and that it may redevelop a “Cronin peak” even at small x . The magnitude of the peak is predicted to increase approximately like 1/A ⊥ ν, ν~0.6±0.1 , if one is able to select more compact configurations of the projectile proton where its gluons occupy a smaller transverse area A ⊥. We predict an enhanced Q pp(p T)–1~1/(p T 2) ν and a Cronin peak even for central pp collisions.« less

  13. The small-x gluon distribution in centrality biased pA and pp collisions

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dumitru, Adrian; Kapilevich, Gary; Skokov, Vladimir

    Here, the nuclear modification factor R pA(p T) provides information on the small- x gluon distribution of a nucleus at hadron colliders. Several experiments have recently measured the nuclear modification factor not only in minimum bias but also for central pA collisions. In this paper we analyze the bias on the configurations of soft gluon fields introduced by a centrality selection via the number of hard particles. Such bias can be viewed as reweighting of configurations of small- x gluons. We find that the biased nuclear modification factor Q pA(p T) for central collisions is above R pA(p T) formore » minimum bias events, and that it may redevelop a “Cronin peak” even at small x . The magnitude of the peak is predicted to increase approximately like 1/A ⊥ ν, ν~0.6±0.1 , if one is able to select more compact configurations of the projectile proton where its gluons occupy a smaller transverse area A ⊥. We predict an enhanced Q pp(p T)–1~1/(p T 2) ν and a Cronin peak even for central pp collisions.« less

  14. An Evaluation Study of Enzyme-Linked Immunosorbent Assay (ELISA) Using Recombinant Protein Pap31 for Detection of Antibody against Bartonella bacilliformis Infection among the Peruvian Population

    PubMed Central

    Angkasekwinai, Nasikarn; Atkins, Erin H.; Romero, Sofia; Grieco, John; Chao, Chien Chung; Ching, Wei Mei

    2014-01-01

    Reliable laboratory testing is of great importance to detect Bartonella bacilliformis infection. We evaluated the sensitivity and specificity of the enzyme-linked immunosorbent assay (ELISA) using recombinant protein Pap31 (rPap31) for the detection of antibodies against B. bacilliformis as compared with immunofluorescent assay (IFA). Of the 302 sera collected between 1997 and 2000 among an at-risk Peruvian population, 103 and 34 samples tested positive for IFA-immunoglobulin G (IgG) and IFA-IgM, respectively. By using Youden's index, the cutoff values of ELISA-IgG at 0.915 gave a sensitivity of 84.5% and specificity of 94%. The cutoff values of ELISA-IgM at 0.634 gave a sensitivity of 88.2% and specificity of 85.1%. Using latent class analysis, estimates of sensitivity and specificity of almost all the assays were slightly higher than those of a conventional method of calculation. The test is proved beneficial for discriminating between infected and non-infected individuals with the advantage of low-cost and high-throughput capability. PMID:24515944

  15. Bi-level positive airway pressure (BiPAP) and acute cardiogenic pulmonary oedema (ACPO) in the emergency department.

    PubMed

    Murray, Sarah

    2002-05-01

    Patients in acute respiratory failure (ARF) frequently present to the emergency department (ED). Traditionally management has involved mechanical ventilation via endotracheal intubation. Such invasive forms of treatment, however, correlate with a higher incidence of infection, mortality, length of stay and contribute to the costs of intensive care. Non-invasive positive pressure ventilation (NIPPV) such as bi-level positive airway pressure (BiPAP) may therefore provide an alternative and preferable form of treatment. Whilst contemporary literature supports the use of BiPAP in hypercapnic ARF, its role in acute hypoxaemic presentations remains elusive. Specifically, the efficacy and safety of BiPAP in the treatment of acute cardiogenic pulmonary oedema (ACPO) remains a contentious issue. The aim of this paper is to explore the physiological rationale for treatment of ACPO with BiPAP. Particular attention will focus on the comparative theoretical advantages of BiPAP in relation to continuous positive airway pressure (CPAP), and a review of recent research. Discussion will incorporate timeliness in the application of BiPAP, indicators of successful treatment, appropriate manipulation of pressure settings, nursing workload and management of patients beyond the ED. Whilst the theoretical advantages of BiPAP ventilation are acknowledged, larger randomised controlled research studies are recommended in order to clearly ensure its safe and effective application in the treatment of ACPO.

  16. Postactivation Potentiation of the Plantar Flexors Does Not Directly Translate to Jump Performance in Female Elite Young Soccer Players.

    PubMed

    Prieske, Olaf; Maffiuletti, Nicola A; Granacher, Urs

    2018-01-01

    High-intensity muscle actions have the potential to temporarily improve muscle contractile properties (i.e., postactivation potentiation, PAP) thereby inducing acute performance enhancements. There is evidence that balance training can improve performance during strength exercises. Taking these findings together, the purpose of this study was to examine the acute effects of a combined balance and strength (B+S) exercise vs. a strength only (S) exercise on twitch contractile properties, maximum voluntary strength, and jump performance in young athletes. Female elite young soccer players ( N = 12) aged 14-15 years conducted three experimental conditions in randomized order: S included 3 sets of 8-10 dynamic leg extensions at 80% of the 1-repetition maximum, B+S consisted of 3 sets of 40 s double-leg stances on a balance board prior to leg extensions (same as S), and a resting control period. Before and 7 min after exercise, participants were tested for their electrically-evoked isometric twitches (i.e., twitch peak torque, twitch rate of torque development) and maximal voluntary contraction (MVC) torque of the plantar flexor muscles. Additionally, countermovement (CMJ) and drop jump (DJ) performances (i.e., CMJ/DJ height, DJ ground contact time) were assessed. Significant effects of condition on twitch contractile properties ( p < 0.05, d = 1.1) and jump performance outputs ( p < 0.05, 1.1 ≤ d ≤ 1.2) were found. Post-hoc tests revealed that S compared to control produced larger PAP for twitch peak torques by trend ( p = 0.07, d = 1.8, 33 vs. 21%) and significantly larger PAP for twitch rate of torque development ( p < 0.05, d = 2.4, 55 vs. 43%). Following B+S compared to control, significant improvements in CMJ height ( p < 0.01, d = 1.9, 3%) and DJ contact time were found ( p < 0.01, d = 2.0, 10%). This study revealed protocol-specific acute performance improvements. While S resulted in significant increases in twitch contractile properties, B+S produced significant enhancements in jump performance. It is concluded that PAP effects in the plantar flexors may not directly translate to improved jump performance in female elite young soccer players. Therefore, the observed gains in jump performance following B+S are most likely related to neuromuscular changes (e.g., intramuscular coordination) rather than improved contractile properties.

  17. Effects of four different positive airway pressures on right internal jugular vein catheterisation.

    PubMed

    Zhou, Qinghe; Xiao, Wangpin; An, Erdan; Zhou, Hongmei; Yan, Min

    2012-05-01

    The right internal jugular vein (RIJV) is often used for central venous catheterisation in patients undergoing major surgery. The efficacy of this route correlates with the diameter of the vein which can be influenced by airway pressure. To investigate four positive airway pressures (PAPs) in mechanically ventilated patients and to determine the most suitable of these for RIJV catheterisation. Prospective, randomised, controlled study. Two Chinese medical centres. Two hundred and forty patients scheduled for gastrointestinal tract surgery under general anaesthesia (male-to-female ratio, 135 : 105; American Society of Anesthesiologists' physical status class, I-III; age range, 19-81 years); patients were excluded from the study if they had a history of haematological disease, external neck injury, RIJV catheterisation, severe cardiovascular disease, RIJV thrombosis, injection-site infection, pneumothorax and pulmonary bulla. They were randomised into four groups of 60, each to undergo RIJV catheterisation at a PAP of 0 (1 cmH2O = 0.098 kPa, group A); 15 (group B); 20 (group C); and 25 cmH2O (group D). Primary outcomes were central venous pressure (CVP) and RIJV cross-sectional area which were measured before and during PAP; the number of catheterisations completed in 30 s; the number of first pass punctures; heart rate and mean arterial pressure which were monitored continuously; and the incidence of complications which included local haematoma, pneumothorax and internal carotid artery (ICA) puncture. Two patients were excluded following ICA puncture, leaving 238 for analysis. In groups C and D, the CVP and the cross-sectional area of RIJV were significantly larger; the number completing catheterisation within 30 s and the number of first pass punctures increased significantly and was comparable between these two groups. Compared with groups A and B, the incidences of hypotension and bradycardia were significantly increased in groups C and D. The incidence of local haematoma was significantly increased in group D compared with other groups. RIJV catheterisation was completed successfully in all but two patients in group A. A PAP of 20 cmH2O seems most suitable for successful RIJV catheterisation in mechanically ventilated patients. It is associated with an increase in cross-sectional RIJV area and CVP, which facilitate cannulation, and results in fewer puncture-related complications. However, meticulous haemodynamic monitoring is needed to avoid hypotension and bradycardia.

  18. Postactivation Potentiation of the Plantar Flexors Does Not Directly Translate to Jump Performance in Female Elite Young Soccer Players

    PubMed Central

    Prieske, Olaf; Maffiuletti, Nicola A.; Granacher, Urs

    2018-01-01

    High-intensity muscle actions have the potential to temporarily improve muscle contractile properties (i.e., postactivation potentiation, PAP) thereby inducing acute performance enhancements. There is evidence that balance training can improve performance during strength exercises. Taking these findings together, the purpose of this study was to examine the acute effects of a combined balance and strength (B+S) exercise vs. a strength only (S) exercise on twitch contractile properties, maximum voluntary strength, and jump performance in young athletes. Female elite young soccer players (N = 12) aged 14–15 years conducted three experimental conditions in randomized order: S included 3 sets of 8–10 dynamic leg extensions at 80% of the 1-repetition maximum, B+S consisted of 3 sets of 40 s double-leg stances on a balance board prior to leg extensions (same as S), and a resting control period. Before and 7 min after exercise, participants were tested for their electrically-evoked isometric twitches (i.e., twitch peak torque, twitch rate of torque development) and maximal voluntary contraction (MVC) torque of the plantar flexor muscles. Additionally, countermovement (CMJ) and drop jump (DJ) performances (i.e., CMJ/DJ height, DJ ground contact time) were assessed. Significant effects of condition on twitch contractile properties (p < 0.05, d = 1.1) and jump performance outputs (p < 0.05, 1.1 ≤ d ≤ 1.2) were found. Post-hoc tests revealed that S compared to control produced larger PAP for twitch peak torques by trend (p = 0.07, d = 1.8, 33 vs. 21%) and significantly larger PAP for twitch rate of torque development (p < 0.05, d = 2.4, 55 vs. 43%). Following B+S compared to control, significant improvements in CMJ height (p < 0.01, d = 1.9, 3%) and DJ contact time were found (p < 0.01, d = 2.0, 10%). This study revealed protocol-specific acute performance improvements. While S resulted in significant increases in twitch contractile properties, B+S produced significant enhancements in jump performance. It is concluded that PAP effects in the plantar flexors may not directly translate to improved jump performance in female elite young soccer players. Therefore, the observed gains in jump performance following B+S are most likely related to neuromuscular changes (e.g., intramuscular coordination) rather than improved contractile properties. PMID:29628898

  19. Comparative cost-effectiveness of HPV vaccines in the prevention of cervical cancer in Malaysia.

    PubMed

    Ezat, Sharifa W P; Aljunid, Syed

    2010-01-01

    Cervical cancer (CC) had the second highest incidence of female cancers in Malaysia in 2003-2006. Prevention is possible by both Pap smear screening and HPV vaccination with either the bivalent vaccine (BV) or the quadrivalent vaccine (QV). In the present study, cost effectiveness options were compared for three programs i.e. screening via Pap smear; modeling of HPV vaccination (QV and BV) and combined strategy (screening plus vaccination). A scenario based sensitivity analysis was conducted using screening population coverages (40-80%) and costs of vaccines (RM 100-200/dose) were calculated. This was an economic burden, cross sectional study in 2006-2009 of respondents interviewed from six public Gynecology-Oncology hospitals. Methods included expert panel discussions to estimate treatment costs of CC, genital warts and vulva/vagina cancers by severity and direct interviews with respondents using costing and SF-36 quality of life questionnaires. A total of 502 cervical cancer patients participated with a mean age at 53.3±11.2 years and a mean marriage length of 27.7±12.1 years, Malays accounting for 44.2%. Cost/quality adjusted life year (QALY) for Pap smear in the base case was RM 1,215 and RM 1,100 at increased screening coverage. With QV only, in base case it was RM 15,662 and RM 24,203 when the vaccination price was increased. With BV only, the respective figures were RM 1,359,057 and RM 2,530,018. For QV combined strategy cost/QALY in the base case it was RM 4,937, reducing to RM 3,395 in the best case and rising to RM 7,992 in the worst case scenario. With the BV combined strategy, these three cost/QALYs were RM 6,624, RM 4,033 and RM 10,543. Incremental cost-effectiveness ratio (ICER) showed that screening at 70% coverage or higher was highly cost effective at RM 946.74 per QALYs saved but this was preceded by best case combined strategy with QV at RM 515.29 per QALYs saved. QV is more cost effective than BV. The QV combined strategy had a higher CE than any method including Pap smear screening at high population coverage.

  20. The high burden of cervical cancer in Fiji, 2004-07.

    PubMed

    Law, Irwin; Fong, James J; Buadromo, Eka M; Samuela, Josaia; Patel, Mahomed S; Garland, Suzanne M; Mulholland, E Kim; Russell, Fiona M

    2013-05-01

    There are few population-based data on the disease burden of cervical cancer from developing countries, especially South Pacific islands. This study aimed to determine the incidence and mortality associated with cervical cancer and the coverage of Papanicolaou (Pap) cervical cytology in 20- to 69-year-old women in Fiji from 2004 to 2007. National data on the incident cases of histologically confirmed cervical cancer and the associated deaths, and on Pap smear results were collected from all pathology laboratories, and cancer and death registries in Fiji from 2004 to 2007. There were 413 incident cases of cervical cancer and 215 related deaths during the study timeframe. The annualised incidence and mortality rates in 20- to 69-year-old Melanesian Fijian women, at 49.7 per 100?000 (95% confidence interval (CI): 43.7-56.4) and 32.3 per 100?000 (95% CI: 26.9-38.4) respectively, were significantly higher than among 20- to 69-year-old Indo-Fijian women at 35.2 per 100?000 (P<0.001, 95% CI: 29.5-41.7) and 19.8 per 100?000 (P=0.002, 95% CI: 15.1-25.5) respectively. Of 330 cases diagnosed between 2004 and 2006, 186 (56%) had died by 31 December 2006. Pap smear coverage for this period was 8.0% (95% CI: 7.9-8.1) of the target population. The incidence and mortality related to cervical cancer in Fiji is high, whereas Pap smear coverage is very low. Greater investment in alternative screening strategies and preventive measures should be integrated into a comprehensive, strategic cervical cancer control program in Fiji.

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