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  1. The Lyme Disease Spirochete Borrelia burgdorferi Utilizes Multiple Ligands, Including RNA, for Interferon Regulatory Factor 3-Dependent Induction of Type I Interferon-Responsive Genes ▿

    PubMed Central

    Miller, Jennifer C.; Maylor-Hagen, Heather; Ma, Ying; Weis, John H.; Weis, Janis J.

    2010-01-01

    We recently discovered a critical role for type I interferon (IFN) in the development of murine Lyme arthritis. Borrelia burgdorferi-mediated induction of IFN-responsive genes by bone marrow-derived macrophages (BMDMs) was dependent upon a functional type I IFN receptor but independent of Toll-like receptor 2 (TLR2), TLR4, TLR9, and the adapter molecule MyD88. We now demonstrate that induction of the IFN transcriptional profile in B. burgdorferi-stimulated BMDMs occurs independently of the adapter TRIF and of the cytoplasmic sensor NOD2. In contrast, B. burgdorferi-induced transcription of these genes was dependent upon a rapid STAT1 feedback amplification pathway. IFN profile gene transcription was IRF3 dependent but did not utilize B. burgdorferi-derived DNA or DNase-sensitive ligands. Instead, IFN-responsive gene expression could be induced by B. burgdorferi-derived RNA. Interferon regulatory factor 3 (IRF3)-dependent IFN profile gene transcription was also induced by sonicated bacteria, by the lipoprotein OspA, and by factors released into the BSKII medium during culture of B. burgdorferi. The IFN-stimulatory activity of B. burgdorferi culture supernatants was not destroyed by nuclease treatment. Nuclease digestion also had no effect on IFN profile induction mediated by sonicated B. burgdorferi. Thus, B. burgdorferi-derived RNA, OspA, and non-nucleic acid ligands present in both sonicated bacteria and B. burgdorferi culture medium contribute to type I IFN-responsive gene induction. These findings suggest that B. burgdorferi invasion of joint tissue and the resultant type I IFN induction associated with Lyme arthritis development may involve multiple triggering ligands. PMID:20404081

  2. The chromosome 16q region associated with ankylosing spondylitis includes the candidate gene tumour necrosis factor receptor type 1-associated death domain (TRADD)

    PubMed Central

    Pointon, Jennifer J; Harvey, David; Karaderi, Tugce; Appleton, Louise H; Farrar, Claire; Stone, Millicent A; Sturrock, Roger D; Reveille, John D; Weisman, Michael H; Ward, Michael M; Brown, Matthew A; Wordsworth, B Paul

    2010-01-01

    Objective To replicate and refine the reported association of ankylosing spondylitis (AS) with two non-synonymous single nucleotide polymorphisms (nsSNPs) on chromosome 16q22.1. Methods Firstly, 730 independent UK patients with AS were genotyped for rs9939768 and rs6979 and allele frequencies were compared with 2879 previously typed historic disease controls. Secondly, the two data sets were combined in meta-analyses. Finally, 5 tagging SNPs, located between rs9939768 and rs6979, were analysed in 1604 cases and 1020 controls. Results The association of rs6979 with AS was replicated, p=0.03, OR=1.14 (95% CI 1.01 to 1.28), and a trend for association with rs9939768 detected, p=0.06, OR=1.25 (95% CI 0.99 to 1.57). Meta-analyses revealed association of both SNPs with AS, p=0.0008, OR=1.31 (95% CI 1.12 to 1.54) and p=0.0009, OR=1.15 (95% CI 1.06 to 1.23) for rs9939768 and rs6979, respectively. New associations with rs9033 and rs868213 (p=0.00002, OR=1.23 (95% CI 1.12 to 1.36) and p=0.00002 OR=1.45 (95% CI 1.22 to 1.72), respectively, were identified. Conclusions The region on chromosome 16 that has been replicated in the present work is interesting as the highly plausible candidate gene, tumour necrosis factor receptor type 1 (TNFR1)-associated death domain (TRADD), is located between rs9033 and rs868213. It will require additional work to identify the primary genetic association(s) with AS. PMID:19854717

  3. Cholesterol synthesis is the trigger and isoprenoid dependent interleukin-6 mediated inflammation is the common causative factor and therapeutic target for atherosclerotic vascular disease and age-related disorders including osteoporosis and type 2 diabetes.

    PubMed

    Omoigui, Sota

    2005-01-01

    This is a unifying theory that cholesterol metabolites (isoprenoids) are an integral component of the signaling pathway for interleukin-6 (IL-6) mediated inflammation. IL-6 inflammation is the common causative origin for atherosclerosis, peripheral vascular disease, coronary artery disease, and age-related disorders including osteoporosis, dementia, Alzheimer's disease and type 2 diabetes. Therapeutic effects of bisphosphonates and statins are mediated by isoprenoid depletion. Statins and bisphosphonates act in the cholesterol pathway to deplete isoprenoids. Anti-inflammatory properties of statins and bisphosphonates are due to isoprenoid depletion with subsequent inhibition of IL-6 mediated inflammation. Therapeutic targets for the prevention and control of all the above diseases should focus on cholesterol metabolites and IL-6 mediated inflammation. Prevention of atherosclerotic vascular disease and age-related disorders will be by utilization of cholesterol lowering agents or techniques and/or treatment with statins and/or bisphosphonates to inhibit IL-6 inflammation through regulation of cholesterol metabolism. PMID:15935563

  4. Include All 4 Types of Exercise (Endurance, Strength, Balance, Flexibility)

    MedlinePlus

    ... generally falls into four main types: endurance, strength, balance, and flexibility. Some activities fit into more than ... build strength, and some flexibility exercises also improve balance. ENDURANCE Your goal is to be creative and ...

  5. Important factors included in nondestructive readout of GMR MRAM (abstract)

    NASA Astrophysics Data System (ADS)

    Nakamura, Y.; Wang, Z.

    1996-04-01

    We proposed a new type of magnetoresistive random access memory (MRAM) using a weakly coupled GMR effect. It operates on the general principle of storing a binary digit in hard component and sensing its remanent state by switching the soft component in such a way that the magnetic state of the hard component is unaltered. It is believed that this structure could have nondestructive readout (NDRO) characteristics. However, in experiments we found that NDRO was not always achieved; i.e., NDRO was dependent on the polarity of the excitation field. We take an example for mode ``0'' (corresponding to a + remanent state). Although tests involving 3×108 plus excitation pulses indicated that the element was still stable, stability against minus disturb pulses could not be expected. The remanent state of 0 was degrading gradually and was finally destroyed after nenormous numbers of readout switching. An analytical model, in which the hard component follows the Rayleigh law, can explain the above phenomenon. It is because the irreversible magnetization processes cause disturbed states (0' or 1'). Obviously the worst case for mode 0 is being excited by continous minus pulses whereas the worst case for mode 1 is being excited by continous plus pulses. We think that two methods will be effective to eliminate the unstability. One is to obtain a rectangular hysteresis loop for the hard component. The other is to imporve the excitation method, for example, to employ bipolar pulses for excitation signals.

  6. Photovoltaic Device Including A Boron Doping Profile In An I-Type Layer

    DOEpatents

    Yang, Liyou

    1993-10-26

    A photovoltaic cell for use in a single junction or multijunction photovoltaic device, which includes a p-type layer of a semiconductor compound including silicon, an i-type layer of an amorphous semiconductor compound including silicon, and an n-type layer of a semiconductor compound including silicon formed on the i-type layer. The i-type layer including an undoped first sublayer formed on the p-type layer, and a boron-doped second sublayer formed on the first sublayer.

  7. The spindle-shaped cells in cutaneous Kaposi's sarcoma. Histologic simulators include factor XIIIa dermal dendrocytes.

    PubMed Central

    Nickoloff, B. J.; Griffiths, C. E.

    1989-01-01

    Kaposi's sarcoma is a neoplasm that develops as multifocal lesions, often involving the skin, characterized by a complex histologic picture including numerous vascular spaces, perivascular and interstitial spindle-shaped cells, and extravasated erythrocytes, lymphocytes, and plasma cells. Using an antibody against factor XIIIa, which identifies dermal dendrocytes, numerous factor XIIIa-positive dermal dendrocytes were detected among the spindle-shaped cells in 12 acquired immune deficiency syndrome (AIDS)-associated, and five non-AIDS-associated Kaposi's sarcoma lesions. The factor XIIIa-positive dermal dendrocytes were also increased in histologic simulators of Kaposi's sarcoma such as dermatofibroma, angiomatoid malignant fibrous histiocytoma, granuloma annulare, and early wound healing, but were absent in keloids. The increased number of dermal dendrocytes, which are often in an angiocentric configuration and which also express CD4, lymphocyte function associated antigen-1 (LFA-1), and Leu M3 in Kaposi's sarcoma, may be important to the angioproliferative response. The results suggested that the spindle-shaped cells that are present in a variety of cutaneous lesions are dermal dendrocytes and belong to the reticuloendothelial system, unlike other mesenchymal cell types such as the endothelial cell. Apparently a diverse array of stimuli, including human immunodeficiency virus type-1 (HIV-1) infection and trauma, can stimulate the accumulation of factor XIIIa expressing dermal dendrocytes in the skin. These cells can then participate in different stages of a variety of cutaneous alterations including Kaposi's sarcoma, dermatofibroma, granuloma annulare, and early wound healing. Thus, the factor XIIIa-positive dermal dendrocyte is a common cellular denominator among diverse clinical entities that share some histologic features. Images Figure 1 Figure 2 Figure 3 p797-a PMID:2573283

  8. The spindle-shaped cells in cutaneous Kaposi's sarcoma. Histologic simulators include factor XIIIa dermal dendrocytes.

    PubMed

    Nickoloff, B J; Griffiths, C E

    1989-11-01

    Kaposi's sarcoma is a neoplasm that develops as multifocal lesions, often involving the skin, characterized by a complex histologic picture including numerous vascular spaces, perivascular and interstitial spindle-shaped cells, and extravasated erythrocytes, lymphocytes, and plasma cells. Using an antibody against factor XIIIa, which identifies dermal dendrocytes, numerous factor XIIIa-positive dermal dendrocytes were detected among the spindle-shaped cells in 12 acquired immune deficiency syndrome (AIDS)-associated, and five non-AIDS-associated Kaposi's sarcoma lesions. The factor XIIIa-positive dermal dendrocytes were also increased in histologic simulators of Kaposi's sarcoma such as dermatofibroma, angiomatoid malignant fibrous histiocytoma, granuloma annulare, and early wound healing, but were absent in keloids. The increased number of dermal dendrocytes, which are often in an angiocentric configuration and which also express CD4, lymphocyte function associated antigen-1 (LFA-1), and Leu M3 in Kaposi's sarcoma, may be important to the angioproliferative response. The results suggested that the spindle-shaped cells that are present in a variety of cutaneous lesions are dermal dendrocytes and belong to the reticuloendothelial system, unlike other mesenchymal cell types such as the endothelial cell. Apparently a diverse array of stimuli, including human immunodeficiency virus type-1 (HIV-1) infection and trauma, can stimulate the accumulation of factor XIIIa expressing dermal dendrocytes in the skin. These cells can then participate in different stages of a variety of cutaneous alterations including Kaposi's sarcoma, dermatofibroma, granuloma annulare, and early wound healing. Thus, the factor XIIIa-positive dermal dendrocyte is a common cellular denominator among diverse clinical entities that share some histologic features. PMID:2573283

  9. Environmental risk factors for type 1 diabetes.

    PubMed

    Rewers, Marian; Ludvigsson, Johnny

    2016-06-01

    The incidence of type 1 diabetes has risen considerably in the past 30 years due to changes in the environment that have been only partially identified. In this Series paper, we critically discuss candidate triggers of islet autoimmunity and factors thought to promote progression from autoimmunity to overt type 1 diabetes. We revisit previously proposed hypotheses to explain the growth in the incidence of type 1 diabetes in light of current data. Finally, we suggest a unified model in which immune tolerance to β cells can be broken by several environmental exposures that induce generation of hybrid peptides acting as neoautoantigens. PMID:27302273

  10. Risk Factors for Early Colonoscopic Perforation Include Non-Gastroenterologist Endoscopists: a Multivariable Analysis

    PubMed Central

    Bielawska, Barbara; Day, Andrew G; Lieberman, David A; Hookey, Lawrence C

    2014-01-01

    Background & Aims Bowel perforation is a rare but serious complication of colonoscopy. Its prevalence is increasing with the rapidly growing volume of procedures performed. Although colonoscopies have been performed for decades, the risk factors for perforation are not completely understood. We investigated risk factors for perforation during colonoscopy, assessing variables that included sedation type and endoscopist specialty and level of training. Methods We performed a retrospective multivariate analysis of risk factors for early perforation (occurring at any point during the colonoscopy but recognized during or immediately after the procedure) in adult patients using the Clinical Outcomes Research Initiative National Endoscopic Database. Risk factors were determined from published articles. Additional variables assessed included endoscopist specialty and years of experience, trainee involvement, and sedation with propofol. Results We identified 192 perforation events during 1,144,900 colonoscopies from 85 centers entered into the database from January 2000 through March 2011. On multivariate analysis, increasing age, American Society of Anesthesia class, female sex, hospital setting, any therapy, and polyps >10 mm were significantly associated with increased risk of early perforation. Colonoscopies performed by surgeons and endoscopists of unknown specialty had higher rates of perforation than those performed by gastroenterologists (odds ratio, 2.00; 95% confidence interval, 1.30–3.08). Propofol sedation did not significantly affect risk for perforation. Conclusions In addition to previously established risk factors, non-gastroenterologist specialty was found to affect risk for perforations detected during or immediately after colonoscopy. This finding could result from differences in volume and style of endoscopy training. Further investigation into these observed associations is warranted. PMID:23891916

  11. Cardiovascular Disease Risk Factors in Youth With Type 1 and Type 2 Diabetes: Implications of a Factor Analysis of Clustering

    PubMed Central

    Mayer-Davis, Elizabeth J.; Ma, Bo; Lawson, Andrew; D'Agostino, Ralph B.; Liese, Angela D.; Dabelea, Dana; Dolan, Lawrence; Pettitt, David J.; Rodriguez, Beatriz L.; Williams, Desmond

    2009-01-01

    Abstract Background The extent to which cardiovascular disease (CVD) risk factors cluster in youth with a diagnosis of type 1 (T1DM) or type 2 diabetes mellitus (T2DM) is unclear. Therefore, we aimed to evaluate potential clustering of traditional CVD risk factors that may reflect an unmeasured but unifying single pathology that may explain the phenomenon of the metabolic syndrome in these youths. Methods Youths who participated in the SEARCH for Diabetes in Youth study with diabetes diagnosed <20 years, with current age >10 years (maximum current age, 22 years) were included. Confirmatory factor analysis (CFA) was performed to determine statistical associations among CVD risk factors, including obesity, blood pressure, triglycerides, and high-density lipoprotein cholesterol (HDL-C). Diabetes type was defined by diabetes autoantibodies (DAA) and fasting C-peptide (FCP); type 1 (T1DM, DAA positive, and FCP <0.8 ng/mL, n = 1198) and type 2 (T2DM, DAA negative, and FCP >2.9 ng/mL, n = 95). For T1DM, the sample was split randomly and analyses were conducted separately in each split sample. Results Among five prespecified data structures ranging from a single underlying factor to a hierarchical structure of factors, the worst-fitting model for both of the T1DM split samples was the single-factor structure and the best-fitting model was a three-correlated-factor structure. The three correlated factors identified were obesity, lipids, and blood pressure. Results were very similar for youths with T2DM. Conclusion There is little evidence that a single factor underlies the CVD risk factor pattern in youths with diabetes. The concept of the metabolic syndrome provides a useful description of clinical characteristics but does not efficiently capture a single target for etiologic research among youths with diabetes. PMID:18847385

  12. Robust Programming Problems Based on the Mean-Variance Model Including Uncertainty Factors

    NASA Astrophysics Data System (ADS)

    Hasuike, Takashi; Ishii, Hiroaki

    2009-01-01

    This paper considers robust programming problems based on the mean-variance model including uncertainty sets and fuzzy factors. Since these problems are not well-defined problems due to fuzzy factors, it is hard to solve them directly. Therefore, introducing chance constraints, fuzzy goals and possibility measures, the proposed models are transformed into the deterministic equivalent problems. Furthermore, in order to solve these equivalent problems efficiently, the solution method is constructed introducing the mean-absolute deviation and doing the equivalent transformations.

  13. Analytical expressions for the gate utilization factors of passive multiplicity counters including signal build-up

    SciTech Connect

    Croft, Stephen; Evans, Louise G; Schear, Melissa A

    2010-01-01

    In the realm of nuclear safeguards, passive neutron multiplicity counting using shift register pulse train analysis to nondestructively quantify Pu in product materials is a familiar and widely applied technique. The approach most commonly taken is to construct a neutron detector consisting of {sup 3}He filled cylindrical proportional counters embedded in a high density polyethylene moderator. Fast neutrons from the item enter the moderator and are quickly slowed down, on timescales of the order of 1-2 {micro}s, creating a thermal population which then persists typically for several 10's {micro}s and is sampled by the {sup 3}He detectors. Because the initial transient is of comparatively short duration it has been traditional to treat it as instantaneous and furthermore to approximate the subsequent capture time distribution as exponential in shape. With these approximations simple expressions for the various Gate Utilization Factors (GUFs) can be obtained. These factors represent the proportion of time correlated events i.e. Doubles and Triples signal present in the pulse train that is detected by the coincidence gate structure chosen (predelay and gate width settings of the multiplicity shift register). More complicated expressions can be derived by generalizing the capture time distribution to multiple time components or harmonics typically present in real systems. When it comes to applying passive neutron multiplicity methods to extremely intense (i.e. high emission rate and highly multiplying) neutron sources there is a drive to use detector types with very fast response characteristics in order to cope with the high rates. In addition to short pulse width, detectors with a short capture time profile are also desirable so that a short coincidence gate width can be set in order to reduce the chance or Accidental coincidence signal. In extreme cases, such as might be realized using boron loaded scintillators, the dieaway time may be so short that the build

  14. Systematic chromatin state comparison of epigenomes associated with diverse properties including sex and tissue type

    PubMed Central

    Yen, Angela; Kellis, Manolis

    2015-01-01

    Epigenomic data sets provide critical information about the dynamic role of chromatin states in gene regulation, but a key question of how chromatin state segmentations vary under different conditions across the genome has remained unaddressed. Here we present ChromDiff, a group-wise chromatin state comparison method that generates an information-theoretic representation of epigenomes and corrects for external covariate factors to better isolate relevant chromatin state changes. By applying ChromDiff to the 127 epigenomes from the Roadmap Epigenomics and ENCODE projects, we provide novel group-wise comparative analyses across sex, tissue type, state and developmental age. Remarkably, we find that distinct sets of epigenomic features are maximally discriminative for different group-wise comparisons, in each case revealing distinct enriched pathways, many of which do not show gene expression differences. Our methodology should be broadly applicable for epigenomic comparisons and provides a powerful new tool for studying chromatin state differences at the genome scale. PMID:26282110

  15. A Study of Factors Promoting Success in Computer Science Including Gender Differences

    NASA Astrophysics Data System (ADS)

    Cantwell Wilson, Brenda

    2002-03-01

    This study was conducted to determine factors that promote success in an introductory college computer science course and to determine what, if any, differences appear between genders on those factors. The model included math background, attribution for success/failure, self-efficacy, encouragement, comfort level in the course, work style preference, previous programming experience, previous non-programming computer experience, and gender as possible predictive factors for success in the computer science course. Subjects included 105 students enrolled in an introductory computer science course. The study revealed three predictive factors in the following order of importance: comfort level (with a positive influence), math background (with a positive influence), and attribution to luck (with a negative influence). No significant gender differences were found in these three factors. The study also revealed that both a formal class in programming (which had a positive correlation) and game playing (which had a negative correlation) were predictive of success. The study revealed a significant gender difference in game playing with males reporting more experience with playing games on the computer than females reported.

  16. P and n-type microcrystalline semiconductor alloy material including band gap widening elements, devices utilizing same

    DOEpatents

    Guha, Subhendu; Ovshinsky, Stanford R.

    1988-10-04

    An n-type microcrystalline semiconductor alloy material including a band gap widening element; a method of fabricating p-type microcrystalline semiconductor alloy material including a band gap widening element; and electronic and photovoltaic devices incorporating said n-type and p-type materials.

  17. DNA Damage Response Factors from Diverse Pathways, Including DNA Crosslink Repair, Mediate Alternative End Joining

    PubMed Central

    Howard, Sean M.; Yanez, Diana A.; Stark, Jeremy M.

    2015-01-01

    Alternative end joining (Alt-EJ) chromosomal break repair involves bypassing classical non-homologous end joining (c-NHEJ), and such repair causes mutations often with microhomology at the repair junction. Since the mediators of Alt-EJ are not well understood, we have sought to identify DNA damage response (DDR) factors important for this repair event. Using chromosomal break reporter assays, we surveyed an RNAi library targeting known DDR factors for siRNAs that cause a specific decrease in Alt-EJ, relative to an EJ event that is a composite of Alt-EJ and c-NHEJ (Distal-EJ between two tandem breaks). From this analysis, we identified several DDR factors that are specifically important for Alt-EJ relative to Distal-EJ. While these factors are from diverse pathways, we also found that most of them also promote homologous recombination (HR), including factors important for DNA crosslink repair, such as the Fanconi Anemia factor, FANCA. Since bypass of c-NHEJ is likely important for both Alt-EJ and HR, we disrupted the c-NHEJ factor Ku70 in Fanca-deficient mouse cells and found that Ku70 loss significantly diminishes the influence of Fanca on Alt-EJ. In contrast, an inhibitor of poly ADP-ribose polymerase (PARP) causes a decrease in Alt-EJ that is enhanced by Ku70 loss. Additionally, the helicase/nuclease DNA2 appears to have distinct effects from FANCA and PARP on both Alt-EJ, as well as end resection. Finally, we found that the proteasome inhibitor Bortezomib, a cancer therapeutic that has been shown to disrupt FANC signaling, causes a significant reduction in both Alt-EJ and HR, relative to Distal-EJ, as well as a substantial loss of end resection. We suggest that several distinct DDR functions are important for Alt-EJ, which include promoting bypass of c-NHEJ and end resection. PMID:25629353

  18. Type IV pili mechanochemically regulate virulence factors in Pseudomonas aeruginosa

    PubMed Central

    Persat, Alexandre; Inclan, Yuki F.; Engel, Joanne N.; Stone, Howard A.; Gitai, Zemer

    2015-01-01

    Bacteria have evolved a wide range of sensing systems to appropriately respond to environmental signals. Here we demonstrate that the opportunistic pathogen Pseudomonas aeruginosa detects contact with surfaces on short timescales using the mechanical activity of its type IV pili, a major surface adhesin. This signal transduction mechanism requires attachment of type IV pili to a solid surface, followed by pilus retraction and signal transduction through the Chp chemosensory system, a chemotaxis-like sensory system that regulates cAMP production and transcription of hundreds of genes, including key virulence factors. Like other chemotaxis pathways, pili-mediated surface sensing results in a transient response amplified by a positive feedback that increases type IV pili activity, thereby promoting long-term surface attachment that can stimulate additional virulence and biofilm-inducing pathways. The methyl-accepting chemotaxis protein-like chemosensor PilJ directly interacts with the major pilin subunit PilA. Our results thus support a mechanochemical model where a chemosensory system measures the mechanically induced conformational changes in stretched type IV pili. These findings demonstrate that P. aeruginosa not only uses type IV pili for surface-specific twitching motility, but also as a sensor regulating surface-induced gene expression and pathogenicity. PMID:26041805

  19. Q-Type Factor Analysis of Healthy Aged Men.

    ERIC Educational Resources Information Center

    Kleban, Morton H.

    Q-type factor analysis was used to re-analyze baseline data collected in 1957, on 47 men aged 65-91. Q-type analysis is the use of factor methods to study persons rather than tests. Although 550 variables were originally studied involving psychiatry, medicine, cerebral metabolism and chemistry, personality, audiometry, dichotic and diotic memory,…

  20. Children and adolescents' internal models of food-sharing behavior include complex evaluations of contextual factors.

    PubMed

    Markovits, Henry; Benenson, Joyce F; Kramer, Donald L

    2003-01-01

    This study examined internal representations of food sharing in 589 children and adolescents (8-19 years of age). Questionnaires, depicting a variety of contexts in which one person was asked to share a resource with another, were used to examine participants' expectations of food-sharing behavior. Factors that were varied included the value of the resource, the relation between the two depicted actors, the quality of this relation, and gender. Results indicate that internal models of food-sharing behavior showed systematic patterns of variation, demonstrating that individuals have complex contextually based internal models at all ages, including the youngest. Examination of developmental changes in use of individual patterns is consistent with the idea that internal models reflect age-specific patterns of interactions while undergoing a process of progressive consolidation. PMID:14669890

  1. Rotating bits including a plurality of types of preferential cutting elements

    SciTech Connect

    Bidegaray, D. A.

    1985-04-23

    A rotating bit, particularly a rotary bit, is provided with a plurality of teeth incorporating diamond cutting elements of a first and second type. Each type of tooth is particularly adapted to cut a particular type of rock formation. For example, the plurality of the first type of teeth are particularly designed to cut soft to medium-hard rock formations, and the plurality of the second type of teeth are particularly adapted to cut hard or abrasive rock formations. In one embodiment, the first type of teeth are set on the bit face to have a greater exposure from the bit face than the second type of teeth. In that case, the first type of teeth will engage the rock formation first. A second embodiment has the relative disposition of the first and second types of teeth as measured by their disposition from the axis of rotation on the bit reversed. In the case where the teeth, which are adapted for hard rock cutting, extend furthermost from the bit, the rock formation first comes into contact with these teeth and if it should be a hard rock formation, primary cutting action will be accomplished with the hard rock cutting teeth, while the soft rock cutting teeth are held out of contact from the formation to minimize wear of these softer rock cutting teeth. However, when a soft rock formation is encountered, the hard rock teeth will fully embed into the softer rock formation, thereby allowing full engagement of the softer rock formation cutting teeth.

  2. Thermoelectric material including a multiple transition metal-doped type I clathrate crystal structure

    DOEpatents

    Yang, Jihui; Shi, Xun; Bai, Shengqiang; Zhang, Wenqing; Chen, Lidong; Yang, Jiong

    2012-01-17

    A thermoelectric material includes a multiple transition metal-doped type I clathrate crystal structure having the formula A.sub.8TM.sub.y.sub.1.sup.1TM.sub.y.sub.2.sup.2 . . . TM.sub.y.sub.n.sup.nM.sub.zX.sub.46-y.sub.1.sub.-y.sub.2.sub.- . . . -y.sub.n.sub.-z. In the formula, A is selected from the group consisting of barium, strontium, and europium; X is selected from the group consisting of silicon, germanium, and tin; M is selected from the group consisting of aluminum, gallium, and indium; TM.sup.1, TM.sup.2, and TM.sup.n are independently selected from the group consisting of 3d, 4d, and 5d transition metals; and y.sub.1, y.sub.2, y.sub.n and Z are actual compositions of TM.sup.1, TM.sup.2, TM.sup.n, and M, respectively. The actual compositions are based upon nominal compositions derived from the following equation: z=8q.sub.A-|.DELTA.q.sub.1|y.sub.1-|.DELTA.q.sub.2|y.sub.2- . . . -|.DELTA.q.sub.n|y.sub.n, wherein q.sub.A is a charge state of A, and wherein .DELTA.q.sub.1, .DELTA.q.sub.2, .DELTA.q.sub.n are, respectively, the nominal charge state of the first, second, and n-th TM.

  3. Environmental factors and primary prevention in type 1 diabetes

    PubMed Central

    Ilonen, Jorma; Vaarala, Outi; Åkerblom, Hans K.; Knip, Mikael

    2014-01-01

    The incidence of type 1 diabetes has been increasing rapidly among children in most European countries over the last decades. Despite of the known strong genetic component in the disease only environmental factors can explain such a rapid change. The increase in incidence has been most conspicuous in the youngest age group, which emphasizes the importance of infancy and early environmental exposures. Nutritional and infectious factors affecting the young child or even the mother during pregnancy have been implicated to be important in the pathogenesis. The identification of single factors has been extremely difficult as reflected by many controversial reports on their importance. This difficulty may also be due to the heterogeneity of the disease mechanisms. Multiple mechanisms in different pathways may ultimately be responsible for beta-cell destruction. In most cases the disease is probably caused by a complex interplay between multiple factors including distinct genetic polymorphisms and environmental effects. Exploration of these pathways is needed for the development of effective preventive measures. The implementation of primary prevention trials will ultimately prove the value of various concepts generated for the disease pathogenesis. PMID:20455416

  4. Early life factors and type 2 diabetes mellitus.

    PubMed

    Jiang, Xinli; Ma, Huijie; Wang, Yan; Liu, Yan

    2013-01-01

    Type 2 diabetes mellitus (T2DM) is a multifactorial disease, and its aetiology involves a complex interplay between genetic, epigenetic, and environmental factors. In recent years, evidences from both human and animal experiments have correlated early life factors with programming diabetes risk in adult life. Fetal and neonatal period is crucial for organ development. Many maternal factors during pregnancy may increase the risk of diabetes of offsprings in later life, which include malnutrition, healthy (hyperglycemia and obesity), behavior (smoking, drinking, and junk food diet), hormone administration, and even stress. In neonates, catch-up growth, lactation, glucocorticoids administration, and stress have all been found to increase the risk of insulin resistance or T2DM. Unfavorable environments (socioeconomic situation and famine) or obesity also has long-term negative effects on children by causing increased susceptibility to T2DM in adults. We also address the potential mechanisms that may underlie the developmental programming of T2DM. Therefore, it might be possible to prevent or delay the risk for T2DM by improving pre- and/or postnatal factors. PMID:24455747

  5. Genetic diversity of bovine papillomavirus types, including two putative new types, in teat warts from dairy cattle herds.

    PubMed

    Lunardi, Michele; de Camargo Tozato, Claudia; Alfieri, Alice Fernandes; de Alcântara, Brígida Kussumoto; Vilas-Boas, Laurival Antonio; Otonel, Rodrigo Alejandro Arellano; Headley, Selwyn Arlington; Alfieri, Amauri Alcindo

    2016-06-01

    Teat papillomatosis affects dairy cows worldwide. Milking can become difficult due to teat warts, and maintaining affected cows in the herds may diminish economic profit in the dairy industry. Currently, 13 bovine papillomavirus (BPV) types have been fully characterized, and numerous putative BPV types have been identified through partial L1 gene PCR. In order to identify the viral types present in warts on the udders of dairy cows, 40 teat lesions from 24 cows from 13 cattle farms in three States of Brazil were evaluated by PV L1 gene PCR. The warts that were evaluated contained sequences from BPVs 6-10, the putative BPV types BAPV9 and BAPV4, and two unreported putative papillomavirus (PV) types, named BPV/BR-UEL6 and BPV/BR-UEL7. In addition, mixed infections and coinfections were identified, since more than one lesion was observed on the udders of 13 cows. Phylogenetic analysis showed that BPV/BR-UEL6 is closely related to BPVs belonging to the genus Xipapillomavirus, while BPV/BR-UEL7 clustered with the previously reported strains Cervus timorensis and Pudu puda PVs, which represent a putative new PV type, and it was only distantly related to xi-, epsilon-, delta- and dyoxi-PVs. These results provide information that will assist in the understanding of the association of BPVs 6, 7, 8, 9, and 10, as well as putative BPV types BAPV4 and BAPV9, with mammary papillomatosis. This is the first characterization of putative novel PV types BPV/BR-UEL6 and BPV/BR-UEL7 in teat warts of dairy cows, highlighting the high genetic diversity of BPVs associated with teat papillomatosis. PMID:26997614

  6. ‘LONESOME TOWN’? IS LONELINESS ASSOCIATED WITH THE RESIDENTIAL ENVIRONMENT, INCLUDING HOUSING AND NEIGHBORHOOD FACTORS?

    PubMed Central

    Whitley, Elise; Tannahill, Carol; Ellaway, Anne

    2015-01-01

    This article considers whether feelings of loneliness are associated with aspects of the home and neighborhood of residence. Multinominal logistic regression models were used to explore associations between residential environment and loneliness in 4,000 residents across deprived areas of Glasgow. People who rated their neighborhood environment of higher quality and who used more local amenities were less likely to report loneliness. Respondents who knew more people within the local area were less likely to report loneliness. Those who reported more antisocial behavior problems, who had a weak perception of collective efficacy, and who felt unsafe walking alone at nighttime were more likely to report loneliness. Length of residence and dwelling type were not associated with reported loneliness. The findings indicate the potential importance of several dimensions of the neighborhood physical, service, and social environment, including aspects of both quality and trust, in protecting against or reducing loneliness in deprived areas. PMID:26740728

  7. Method of fabricating n-type and p-type microcrystalline semiconductor alloy material including band gap widening elements

    DOEpatents

    Guha, Subhendu; Ovshinsky, Stanford R.

    1990-02-02

    A method of fabricating doped microcrystalline semiconductor alloy material which includes a band gap widening element through a glow discharge deposition process by subjecting a precursor mixture which includes a diluent gas to an a.c. glow discharge in the absence of a magnetic field of sufficient strength to induce electron cyclotron resonance.

  8. Benefits of caloric restriction for cardiometabolic health, including type 2 diabetes mellitus risk.

    PubMed

    Soare, Andreea; Weiss, Edward P; Pozzilli, Paolo

    2014-03-01

    In the United States, life expectancy has markedly increased during the past century, and population ageing is expected to double within the next 25 years. The process of ageing in a population is associated with the development of chronic diseases, such as type 2 diabetes mellitus, that can be prevented, and even reversed, with the implementation of healthy lifestyle interventions. The evidence to date, consolidated by the numerous epidemiological studies and clinical trials conducted, suggests that caloric restriction is an effective nutritional intervention for preventing most of these age-related conditions. At a metabolic level, caloric restriction with adequate nutrition has been shown to improve insulin sensitivity, reduce fasting glucose and insulin concentration and prevent obesity, type 2 diabetes, hypertension and chronic inflammation. The purpose of this article is to review current knowledge of the metabolic and clinical implications of caloric restriction with adequate nutrition for the prevention of type 2 diabetes and cardiovascular disease. PMID:24532291

  9. 78 FR 26847 - Including Specific Pavement Types in Federal-aid Highway Traffic Noise Analyses

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-08

    ... data from three pavement types: dense-graded asphaltic concrete (DGAC), open-graded asphaltic concrete (OGAC), and Portland cement concrete (PCC). Prediction of future noise levels is based on the ``average... to consider a wider range of asphaltic concrete and PCC pavements within the agency's traffic...

  10. Globular Cluster Populations: Results Including S4G Late-type Galaxies

    NASA Astrophysics Data System (ADS)

    Zaritsky, Dennis; McCabe, Kelsey; Aravena, Manuel; Athanassoula, E.; Bosma, Albert; Comerón, Sébastien; Courtois, Helene M.; Elmegreen, Bruce G.; Elmegreen, Debra M.; Erroz-Ferrer, Santiago; Gadotti, Dimitri A.; Hinz, Joannah L.; Ho, Luis C.; Holwerda, Benne; Kim, Taehyun; Knapen, Johan H.; Laine, Jarkko; Laurikainen, Eija; Muñoz-Mateos, Juan Carlos; Salo, Heikki; Sheth, Kartik

    2016-02-01

    Using 3.6 and 4.5 μm images of 73 late-type, edge-on galaxies from the S4G survey, we compare the richness of the globular cluster populations of these galaxies to those of early-type galaxies that we measured previously. In general, the galaxies presented here fill in the distribution for galaxies with lower stellar mass, M*, specifically {log}({M}*/{M}⊙ )\\lt 10, overlap the results for early-type galaxies of similar masses, and, by doing so, strengthen the case for a dependence of the number of globular clusters per 109M⊙ of galaxy stellar mass, TN, on M*. For 8.5\\lt {log}({M}*/{M}⊙ )\\lt 10.5 we find the relationship can be satisfactorily described as {T}{{N}}={({M}*/{10}6.7)}-0.56 when M* is expressed in solar masses. The functional form of the relationship is only weakly constrained, and extrapolation outside this range is not advised. Our late-type galaxies, in contrast to our early types, do not show the tendency for low-mass galaxies to split into two TN families. Using these results and a galaxy stellar mass function from the literature, we calculate that, in a volume-limited, local universe sample, clusters are most likely to be found around fairly massive galaxies (M* ˜ 1010.8M⊙) and present a fitting function for the volume number density of clusters as a function of parent-galaxy stellar mass. We find no correlation between TN and large-scale environment, but we do find a tendency for galaxies of fixed M* to have larger TN if they have converted a larger proportion of their baryons into stars.

  11. Of mice and (wo)men: factors influencing successful implantation including endocannabinoids.

    PubMed

    Melford, Sarah E; Taylor, Anthony H; Konje, Justin C

    2014-01-01

    BACKGROUND One in six couples suffer from infertility problems requiring in vitro fertilization therapy; however, the average birth rates in the past decade per IVF-embryo transfer cycle have remained static at around 25%. Although implantation failure is considered a major cause of infertility in otherwise healthy women, inadequate uterine receptivity is considered to be responsible for only two-thirds of implantation failures and problems with the embryo itself are responsible for the other third, such that only 30% of oocytes that are contacted by sperm result in successful human term pregnancies. Due to technical and ethical considerations, most research into the factors affecting the success of embryo implantation has been performed in mice, but this may be less than ideal. METHODS Selected relevant literature detailing the similarities and differences between rodent and human reproductive physiology surrounding implantation were nominated for inclusion. Primary papers and review articles (and primary sources within these), published between 1975 and 2012, with a clear indication for a particular ligand or cell being involved in the implantation process or placentation in the mouse or woman, were thoroughly examined and used to construct the review. RESULTS Mice have been identified as suitable models for investigating the processes of early pregnancy in women, for many reasons including their predictable, relatively short gestation and the ability to deliberately breed mice with the absence of a desired gene. There is, however, increasing evidence to suggest that the reproductive systems of humans and mice differ considerably when considering early pregnancy events. CONCLUSIONS In this review, we examine what is already known about the normal implantation process and the intrinsic factors that affect implantation, and then compare the differences between mice models and women in the context of early pregnancy. We highlight numerous differences between the

  12. Determination of the petrologic type of CV3 chondrites by Raman spectroscopy of included organic matter

    NASA Astrophysics Data System (ADS)

    Bonal, Lydie; Quirico, Eric; Bourot-Denise, Michèle; Montagnac, Gilles

    2006-04-01

    This paper reports the first reliable quantitative determination of the thermal metamorphism grade of a series of nine CV3 chondrites: Allende, Axtell, Bali, Mokoia, Grosnaja, Efremovka, Vigarano, Leoville, and Kaba. The maturity of the organic matter in matrix, determined by Raman spectroscopy, has been used as a powerful metamorphic tracer, independent of the mineralogical context and extent of aqueous alteration. This tracer has been used along with other metamorphic tracers such as Fe zoning in type-I chondrules of olivine phenocrysts, presolar grain abundance and noble gas abundance (bulk and P3 component). The study shows that the petrologic types determined earlier by Induced ThermoLuminescence were underestimated and suggests the following values: PT (Allende-Axtell) >3.6; PT (Bali-Mokoia-Grosnaja) ˜3.6; PT (Efremovka-Leoville-Vigarano) = 3.1-3.4; PT (Kaba) ˜3.1. The most commonly studied CV3, Allende, is also the most metamorphosed. Bali is a breccia containing clasts of different petrologic types. The attribution suggested by this study is that of clasts of the highest petrologic types, as pointed out by IOM maturity and noble gas bulk abundance. CV3 chondrites have complex asteroidal backgrounds, with various degrees of aqueous alteration and/or thermal metamorphism leading to complex mineralogical and petrologic patterns. (Fe,Mg) chemical zoning in olivine phenocrysts, on the borders of type I chondrules of porphyritic olivine- and pyroxene-rich textural types, has been found to correlate with the metamorphism grade. This suggests that chemical zoning in some chondrules, often interpreted as exchanges between chondrules and nebular gas, may well have an asteroidal origin. Furthermore, the compositional range of olivine matrix is controlled both by thermal metamorphism and aqueous alteration. This does not support evidence of a nebular origin and does not necessarily mirror the metamorphism grade through (Fe,Mg) equilibration. On the other hand, it may

  13. A decision support system prototype including human factors based on the TOGA meta-theory approach

    SciTech Connect

    Cappelli, M.; Memmi, F.; Gadomski, A. M.; Sepielli, M.

    2012-07-01

    The human contribution to the risk of operation of complex technological systems is often not negligible and sometimes tends to become significant, as shown by many reports on incidents and accidents occurred in the past inside Nuclear Power Plants (NPPs). An error of a human operator of a NPP can derive by both omission and commission. For instance, complex commission errors can also lead to significant catastrophic technological accidents, as for the case of the Three Mile Island accident. Typically, the problem is analyzed by focusing on the single event chain that has provoked the incident or accident. What is needed is a general framework able to include as many parameters as possible, i.e. both technological and human factors. Such a general model could allow to envisage an omission or commission error before it can happen or, alternatively, suggest preferred actions to do in order to take countermeasures to neutralize the effect of the error before it becomes critical. In this paper, a preliminary Decision Support System (DSS) based on the so-called (-) TOGA meta-theory approach is presented. The application of such a theory to the management of nuclear power plants has been presented in the previous ICAPP 2011. Here, a human factor simulator prototype is proposed in order to include the effect of human errors in the decision path. The DSS has been developed using a TRIGA research reactor as reference plant, and implemented using the LabVIEW programming environment and the Finite State Machine (FSM) model The proposed DSS shows how to apply the Universal Reasoning Paradigm (URP) and the Universal Management Paradigm (UMP) to a real plant context. The DSS receives inputs from instrumentation data and gives as output a suggested decision. It is obtained as the result of an internal elaborating process based on a performance function. The latter, describes the degree of satisfaction and efficiency, which are dependent on the level of responsibility related to

  14. 43 CFR 404.9 - What types of infrastructure and facilities may be included in an eligible rural water supply...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... facilities may be included in an eligible rural water supply project? 404.9 Section 404.9 Public Lands... RURAL WATER SUPPLY PROGRAM Overview § 404.9 What types of infrastructure and facilities may be included in an eligible rural water supply project? A rural water supply project may include, but is...

  15. 43 CFR 404.9 - What types of infrastructure and facilities may be included in an eligible rural water supply...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... facilities may be included in an eligible rural water supply project? 404.9 Section 404.9 Public Lands... RURAL WATER SUPPLY PROGRAM Overview § 404.9 What types of infrastructure and facilities may be included in an eligible rural water supply project? A rural water supply project may include, but is...

  16. 43 CFR 404.9 - What types of infrastructure and facilities may be included in an eligible rural water supply...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... facilities may be included in an eligible rural water supply project? 404.9 Section 404.9 Public Lands... RURAL WATER SUPPLY PROGRAM Overview § 404.9 What types of infrastructure and facilities may be included in an eligible rural water supply project? A rural water supply project may include, but is...

  17. 20 CFR 641.507 - What types of income are included and excluded for participant eligibility determinations?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... AND TRAINING ADMINISTRATION, DEPARTMENT OF LABOR PROVISIONS GOVERNING THE SENIOR COMMUNITY SERVICE EMPLOYMENT PROGRAM Services to Participants § 641.507 What types of income are included and excluded...

  18. Gleason-Type Theorem for Projective Measurements, Including Qubits: The Born Rule Beyond Quantum Physics

    NASA Astrophysics Data System (ADS)

    De Zela, F.

    2016-05-01

    Born's quantum probability rule is traditionally included among the quantum postulates as being given by the squared amplitude projection of a measured state over a prepared state, or else as a trace formula for density operators. Both Gleason's theorem and Busch's theorem derive the quantum probability rule starting from very general assumptions about probability measures. Remarkably, Gleason's theorem holds only under the physically unsound restriction that the dimension of the underlying Hilbert space H must be larger than two. Busch's theorem lifted this restriction, thereby including qubits in its domain of validity. However, while Gleason assumed that observables are given by complete sets of orthogonal projectors, Busch made the mathematically stronger assumption that observables are given by positive operator-valued measures. The theorem we present here applies, similarly to the quantum postulate, without restricting the dimension of H and for observables given by complete sets of orthogonal projectors. We also show that the Born rule applies beyond the quantum domain, thereby exhibiting the common root shared by some quantum and classical phenomena.

  19. 36 CFR 1290.4 - Types of materials included in scope of assassination record and additional records and information.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ..., Forests, and Public Property NATIONAL ARCHIVES AND RECORDS ADMINISTRATION JFK ASSASSINATION RECORDS... COLLECTION ACT OF 1992 (JFK ACT) § 1290.4 Types of materials included in scope of assassination record and... information includes, for purposes of interpreting and implementing the JFK Act: (a) Papers, maps, and...

  20. Accurate expressions for solar cell fill factors including series and shunt resistances

    NASA Astrophysics Data System (ADS)

    Green, Martin A.

    2016-02-01

    Together with open-circuit voltage and short-circuit current, fill factor is a key solar cell parameter. In their classic paper on limiting efficiency, Shockley and Queisser first investigated this factor's analytical properties showing, for ideal cells, it could be expressed implicitly in terms of the maximum power point voltage. Subsequently, fill factors usually have been calculated iteratively from such implicit expressions or from analytical approximations. In the absence of detrimental series and shunt resistances, analytical fill factor expressions have recently been published in terms of the Lambert W function available in most mathematical computing software. Using a recently identified perturbative relationship, exact expressions in terms of this function are derived in technically interesting cases when both series and shunt resistances are present but have limited impact, allowing a better understanding of their effect individually and in combination. Approximate expressions for arbitrary shunt and series resistances are then deduced, which are significantly more accurate than any previously published. A method based on the insights developed is also reported for deducing one-diode fits to experimental data.

  1. Latina Resilience in Higher Education: Contributing Factors Including Seasonal Farmworker Experiences

    ERIC Educational Resources Information Center

    Graff, Cristina Santamaria; McCain, Terrence; Gomez-Vilchis, Veronica

    2013-01-01

    Many Latina students overcome multiple obstacles to earn university degrees. Five married Latina women with children and seasonal farmworker backgrounds are the focus of this study which is analyzed through resiliency theory to understand factors contributing to their academic resilience. Variables connected to academic success are explored and…

  2. School Factors Associated with Mainstream Progress in Secondary Education for Included Pupils with Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Osborne, Lisa A.; Reed, Phil

    2011-01-01

    This research examined the factors promoting inclusion of young people with Autism Spectrum Disorders (ASD) in mainstream secondary schools, and noted high levels of behavioral difficulties in these pupils. The size of the secondary school, and the class size, impacted positively on the pupils with Autism, and the number of other pupils with…

  3. Genetic susceptibility factors of Type 1 diabetes in Asians.

    PubMed

    Park, Y; Eisenbarth, G S

    2001-01-01

    Type 1 diabetes is a multifactorial disease in which the insulin producing beta-cells of the pancreas are destroyed by the immune system, a process determined by the activity of major histocompatibility complex (MHC)-restricted T lymphocytes. Progress has been made in elucidating genetic factors involved in Type 1 diabetes in Caucasians, with less data available from Asia. For Asians, the human MHC locus (HLA region), especially the class II region, is the major susceptibility interval. The role of IDDM2, the insulin locus, has been questioned in Asia. In contrast to Caucasians, Asian populations have a very low incidence of Type 1 diabetes (0.4-1.1 cases/year/100 000 individuals). This low incidence rate in the Asian population may be related to the population frequency distribution of susceptible Type 1 diabetes genes, especially of HLA. The overall risk for Type 1 diabetes from HLA DR and DQ is determined by polymorphic residues (alleles) and particular combinations of alleles (haplotypes and genotypes) in a given individual. In Asians, it is very common that a protective DR4 allele is associated with susceptible DQ alleles while neutral/protective DQ alleles are associated with the susceptible DR4 alleles. Our analyses indicate that the counterbalancing between susceptible DRB1 and protective DQB1, and vice versa, is a factor that may contribute to the low incidence of diabetes in Asians. We find that identical HLA DRB1-DQB1 haplotypes of Asians and Caucasians have similar transmission to diabetic children and similar associations with diabetes. Moreover, the association with diabetes and transmission to a diabetic offspring of DR4 haplotypes varies depending on the haplotype borne on the homologous chromosome. This might contribute not only to the synergistic effect of DR3/4, but also to the susceptibility influence of DQB1*0401 haplotypes confined to DR4/X. High-risk DR4 subtypes were predominant in DR4/X, whereas protective DR4 subtypes were observed mainly

  4. Current Changes in Pubertal Timing: Revised Vision in Relation with Environmental Factors Including Endocrine Disruptors.

    PubMed

    Parent, Anne-Simone; Franssen, Delphine; Fudvoye, Julie; Pinson, Anneline; Bourguignon, Jean-Pierre

    2016-01-01

    The aim of this chapter is to revise some common views on changes in pubertal timing. This revision is based on recent epidemiological findings on the clinical indicators of pubertal timing and data on environmental factor effects and underlying mechanisms. A current advancement in timing of female puberty is usually emphasized. It appears, however, that timing is also changing in males. Moreover, the changes are towards earliness for initial pubertal stages and towards lateness for final stages in both sexes. Such observations indicate the complexity of environmental influences on pubertal timing. The mechanisms of changes in pubertal timing may involve both the central neuroendocrine control and peripheral effects at tissues targeted by gonadal steroids. While sufficient energy availability is a clue to the mechanism of pubertal development, changes in the control of both energy balance and reproduction may vary under the influence of common determinants such as endocrine-disrupting chemicals (EDCs). These effects can take place right before puberty as well as much earlier, during fetal and neonatal life. Finally, environmental factors can interact with genetic factors in determining changes in pubertal timing. Therefore, the variance in pubertal timing is no longer to be considered under absolutely separate control by environmental and genetic determinants. Some recommendations are provided for evaluation of EDC impact in the management of pubertal disorders and for possible reduction of EDC exposure along the precautionary principle. PMID:26680578

  5. Experiences with new European standards for calculation of flanged joints including necessary gasket factors

    SciTech Connect

    Bartonicek, J.; Kockelmann, H.; Schoeckle, F.

    1996-12-01

    The correct function of a flanged joint in a given construction (flanges, bolts) and with given loads (pressure, temperature, additional forces) depends on the following: (1) choice of the gasket for the operation environment; (2) determination of the gasket stress for assembly conditions; and (3) gasket stress in operation, i.e., the conditions when leakage has to be minimized. For the correct choice of a gasket it is necessary to have gasket factors available, as given by DIN 28090 (Sept. 95) together with the test procedures. These gasket factors determine the tightening characteristics as well as the deformation capability of the gaskets. Furthermore, these gasket factors must be available for use in calculations. On the basis of calculations a stress analysis (i.e. a limitation of the stresses in flanges and bolts) must be possible as well as the determination of the bolt forces for the assembly state and of the gasket stress for operating conditions. This is one of the goals of the standard pr DIN EN 1591. The paper first introduces the actual European standards. Calculations are reviewed using test data from special test rigs and from real flanged joints. The calculations were made according to DIN 2505 (initial German standard for flanged joints) and pr DIN EN 1591. Additionally, 2D and 3D Finite Element analysis calculations were performed.

  6. Factors that affect postdialysis rebound in serum urea concentration, including the rate of dialysis: results from the HEMO Study.

    PubMed

    Daugirdas, John T; Greene, Tom; Depner, Thomas A; Leypoldt, John; Gotch, Frank; Schulman, Gerald; Star, Robert

    2004-01-01

    Previous studies have suggested that postdialysis urea rebound is related to K/V, the rate of dialysis, but a systematic analysis of factors that affect rebound has not been reported. With the use of 30-min and, in a subset, 60-min postdialysis samples, postdialysis urea rebound was measured to (1) determine how well previously proposed equations based on the rate of dialysis (K/V) predict rebound in a large sample of patients with varying characteristics, (2) determine whether other factors besides K/V affect rebound, and (3) estimate more precise values for coefficients in prediction equations for rebound. Rebound was calculated relative to both immediate and 20-s postdialysis samples to study early components of rebound unrelated to access recirculation. The equilibrated Kt/V (eKt/V) computed by fitting the two-pool variable volume model to the 30-min postdialysis sample agreed well with eKt/V based on the 60-min postdialysis sample. Using the pre-, post-, and 30-min postdialysis samples for 1245 patients with arteriovenous (AV) accesses, the median intercompartmental mass transfer coefficient (Kc) was 797 ml/min for rebound computed relative to the 20-s postdialysis samples and 592 ml/min relative to the immediate postdialysis samples. K/V was the strongest predictor of rebound among 22 factors considered. Other factors associated with greater rebound for 1331 patients using AV accesses or venous catheters included access type, black race, male gender, absence of congestive heart failure, greater age, ultrafiltration rate, and low predialysis or intradialysis systolic BP. Equations of the form eKt/V = single-pool Kt/V - B x (K/V) were fit to the data. With AV access, the optimum values for the slope term (B) were 0.39 and 0.46 (in h(-1)) for single-pool Kt/V calculated based on 20-s postdialysis or immediate postdialysis samples, respectively. For patients using venous catheters, the respective values for B were 0.22 and 0.29. Postdialysis urea rebound can be

  7. Factors Related to Amount and Type of Leisure Time Reading.

    ERIC Educational Resources Information Center

    Greaney, Vincent; Quinn, John

    Diaries showing how 920 Irish fifth graders spent their leisure time on three designated days within one week augmented data about the children's personal, school, and home characteristics to aid in determining the primary factors related to the amount and type of leisure time reading. The children reported spending a median time of 60 minutes per…

  8. Using Situational Factors to Predict Types of Prison Violence.

    ERIC Educational Resources Information Center

    Steinke, Pamela

    1991-01-01

    Tested situational factors as predictors of types of individual aggressive incidents in male prison population. Categorized incidents of violence by whether occurrence of infraction involved aggressive behavior directed at staff, another inmate, self, or property. Found that situational variables did serve as predictors of these categories of…

  9. Role of vascular factors, including angiogenesis, in the mechanisms of action of sucralfate.

    PubMed

    Szabo, S; Vattay, P; Scarbrough, E; Folkman, J

    1991-08-01

    This brief overview of our recent results implicates vascular factors in the mechanisms of acute and chronic actions of sucralfate. Pretreatment of rats with sucralfate and its components, such as SOS and sodium sulfate, prevented the ethanol-induced microvascular injury and maintained blood flow in the gastric mucosa. Thus, preservation of microvascular integrity seems to be one of the mechanisms of acute gastroprotection by sucralfate. Chronic experiments with subcutaneously implanted sponges containing sucralfate or SOS revealed that both compounds stimulated angiogenesis, whereas only sucralfate enhanced the area of granulation tissue. These processes may have a role in the ulcer-healing action of sucralfate. PMID:1715670

  10. Factors affecting numerical typing performance of young adults in a hear-and-type task.

    PubMed

    Lin, Cheng-Jhe; Wu, Changxu

    2011-12-01

    Numerical hear-and-type tasks, i.e. making immediate keypresses according to verbally presented numbers, possess both practical and theoretical importance but received relatively little attention. Effects of speech rates (500-ms vs. 1000-ms interval), urgency (urgent condition: performance-based monetary incentive plus time limit vs. non-urgent condition: flat-rate compensation) and finger strategies (single vs. multi-finger typing) on typing speed and accuracy were investigated. Fast speech rate and multi-finger typing produced more errors and slower typing speed. Urgency improved typing speed but decreased accuracy. Errors were almost doubled under urgent condition, while urgency effect on speed was similar to that of speech rate. Examination of error patterns did not fully support Salthouse's (1986) speculations about error-making mechanisms. The results implied that urgency could play a more important role in error-making than task demands. Numerical keyboard design and error detection could benefit from spatial incidence of errors found in this study. STATEMENT OF RELEVANCE: This study revealed that classic speculations about error-making mechanisms in alphabetical typing do not necessarily translate to numerical typing. Factors other than external task demands such as urgency can affect typing performance to a similar or greater extent. Investigations of intrinsic error-making factors in non-traditional typing tasks are encouraged. PMID:22103724

  11. Including Social Factors in the Analysis of Reminiscence in Elderly Individuals.

    ERIC Educational Resources Information Center

    Lamme, Simone; Baars, Jan

    1993-01-01

    Contends that developmental, determinist, and contextualist psychologists, although all studying reminiscence in older adults, have not fully acknowledged the role the environment plays in establishing reminiscent behavior in elderly people. Suggests including sociological life course theory in the analyses and interpretation of this behavior.…

  12. Cerebrospinal fluid markers including trefoil factor 3 are associated with neurodegeneration in amyloid-positive individuals.

    PubMed

    Paterson, R W; Bartlett, J W; Blennow, K; Fox, N C; Shaw, L M; Trojanowski, J Q; Zetterberg, H; Schott, J M

    2014-01-01

    We aimed to identify cerebrospinal fluid (CSF) biomarkers associated with neurodegeneration in individuals with and without CSF evidence of Alzheimer pathology. We investigated 287 Alzheimer's Disease Neuroimaging Initiative (ADNI) subjects (age=74.9±6.9; 22/48/30% with Alzheimer's disease/mild cognitive impairment/controls) with CSF multiplex analyte data and serial volumetric MRI. We calculated brain and hippocampal atrophy rates, ventricular expansion and Mini Mental State Examination decline. We used false discovery rate corrected regression analyses to assess associations between CSF variables and atrophy rates in individuals with and without amyloid pathology, adjusting in stages for tau, baseline volume, p-tau, age, sex, ApoE4 status and diagnosis. Analytes showing statistically significant independent relationships were entered into reverse stepwise analyses. Adjusting for tau, baseline volume, p-tau, age, sex and ApoE4, 4/83 analytes were significantly independently associated with brain atrophy rate, 1/83 with ventricular expansion and 2/83 with hippocampal atrophy. The strongest CSF predictor for the three atrophy measures was low trefoil factor 3 (TFF3). High cystatin C (CysC) was associated with higher whole brain atrophy and hippocampal atrophy rates. Lower levels of vascular endothelial growth factor and chromogranin A (CrA) were associated with higher whole brain atrophy. In exploratory reverse stepwise analyses, lower TFF3 was associated with higher rates of whole brain, hippocampal atrophy and ventricular expansion. Lower levels of CrA were associated with higher whole brain atrophy rate. The relationship between low TFF3 and increased hippocampal atrophy rate remained after adjustment for diagnosis. We identified a series of CSF markers that are independently associated with rate of neurodegeneration in amyloid-positive individuals. TFF3, a substrate for NOTCH processing may be an important biomarker of neurodegeneration across the Alzheimer

  13. Antibiotic Susceptibility of Staphylococci Isolates from Patients with Chronic Conjunctivitis: Including Associated Factors and Clinical Evaluation

    PubMed Central

    Núñez, María Ximena

    2013-01-01

    Abstract Purpose To determine species of staphylococci in chronic conjunctivitis, their antibiotic susceptibility pattern, patient treatments, clinical course, and clinical conditions. Methods In this prospective study, 243 conjunctival cultures were taken from 191 patients with chronic conjunctivitis, we obtained staphylococci susceptibility patterns with E-test, and they were analyzed in coagulase-positive and negative. The minimum inhibitory concentration for 90% of isolates (MIC90) was determined for Staphylococcus aureus and Staphylococcus epidermidis. Additionally, clinical follow-up and associated factors of all patients were analyzed depending on methicillin resistance (MR) or susceptibility (MS) bacterial state. Results One hundred and eight (44%) cultures were positive; 81 positive cultures were Gram-positive of which, 77 were staphylococci, 29 coagulase-positive with S. aureus as the most prevalent, 89% MS, and 11% MR. And 48 were coagulase-negative with S. epidermidis as the most isolated with 36% of MS and 64% of MR. Poor susceptibility was found in the staphylococcus coagulase-negative/MR group. Moxifloxacin and vancomycin show the best in vitro activity for all isolates. The MIC90 of moxifloxacin and vancomycin were 0.064/1.5, 0.64/3.0, and 1/3.0 for S. aureus-MS, S. epidermidis-MS, and S. epidermidis-MR, respectively. The most frequently associated factors found in patients with positive culture for staphylococcus were exposure to the health care system 23 (29.87%) of 77 patients and dry eye 23 (29.87%) of 77 patients. Both with a proportion of 3 in 10. Conclusion Coagulase-negative staphylococci were the most frequently isolated from the conjunctiva with 58.33% of MR; even though multiresistance was detected, their susceptibility to a fourth-generation fluoroquinolone, commonly used, such as moxifloxacin, was preserved. PMID:23944906

  14. 36 CFR 1290.4 - Types of materials included in scope of assassination record and additional records and information.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... scope of assassination record and additional records and information. 1290.4 Section 1290.4 Parks... COLLECTION ACT OF 1992 (JFK ACT) § 1290.4 Types of materials included in scope of assassination record and additional records and information. The term record in assassination record and additional records...

  15. 36 CFR 1290.4 - Types of materials included in scope of assassination record and additional records and information.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... in scope of assassination record and additional records and information. 1290.4 Section 1290.4 Parks... COLLECTION ACT OF 1992 (JFK ACT) § 1290.4 Types of materials included in scope of assassination record and additional records and information. The term record in assassination record and additional records...

  16. 36 CFR 1290.4 - Types of materials included in scope of assassination record and additional records and information.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... in scope of assassination record and additional records and information. 1290.4 Section 1290.4 Parks... COLLECTION ACT OF 1992 (JFK ACT) § 1290.4 Types of materials included in scope of assassination record and additional records and information. The term record in assassination record and additional records...

  17. 43 CFR 404.9 - What types of infrastructure and facilities may be included in an eligible rural water supply...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 43 Public Lands: Interior 1 2014-10-01 2014-10-01 false What types of infrastructure and facilities may be included in an eligible rural water supply project? 404.9 Section 404.9 Public Lands: Interior Regulations Relating to Public Lands BUREAU OF RECLAMATION, DEPARTMENT OF THE INTERIOR RECLAMATION RURAL WATER SUPPLY PROGRAM Overview §...

  18. 25 CFR 170.137 - What types of activities can a recreation, tourism, and trails program include?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 25 Indians 1 2014-04-01 2014-04-01 false What types of activities can a recreation, tourism, and trails program include? 170.137 Section 170.137 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR LAND AND WATER INDIAN RESERVATION ROADS PROGRAM Indian Reservation Roads Program Policy and Eligibility Recreation, Tourism and Trails...

  19. 10 CFR 719.6 - Are there any types of legal matters not included in the coverage of this part?

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... insurance carrier; (b) Routine intellectual property law support services; (c) Routine workers and... 10 Energy 4 2010-01-01 2010-01-01 false Are there any types of legal matters not included in the coverage of this part? 719.6 Section 719.6 Energy DEPARTMENT OF ENERGY CONTRACTOR LEGAL...

  20. 10 CFR 719.6 - Are there any types of legal matters not included in the coverage of this part?

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... insurance carrier; (b) Routine intellectual property law support services; (c) Routine workers and... 10 Energy 4 2011-01-01 2011-01-01 false Are there any types of legal matters not included in the coverage of this part? 719.6 Section 719.6 Energy DEPARTMENT OF ENERGY CONTRACTOR LEGAL...

  1. 10 CFR 719.6 - Are there any types of legal matters not included in the coverage of this part?

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... intellectual property law support services; and (c) Routine workers and unemployment compensation matters. ... 10 Energy 4 2014-01-01 2014-01-01 false Are there any types of legal matters not included in the coverage of this part? 719.6 Section 719.6 Energy DEPARTMENT OF ENERGY CONTRACTOR LEGAL...

  2. 10 CFR 719.6 - Are there any types of legal matters not included in the coverage of this part?

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... insurance carrier; (b) Routine intellectual property law support services; (c) Routine workers and... 10 Energy 4 2012-01-01 2012-01-01 false Are there any types of legal matters not included in the coverage of this part? 719.6 Section 719.6 Energy DEPARTMENT OF ENERGY CONTRACTOR LEGAL...

  3. 29 CFR 37.34 - What type of notice must a recipient include in publications, broadcasts, and other communications?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 1 2013-07-01 2013-07-01 false What type of notice must a recipient include in publications, broadcasts, and other communications? 37.34 Section 37.34 Labor Office of the Secretary of Labor IMPLEMENTATION OF THE NONDISCRIMINATION AND EQUAL OPPORTUNITY PROVISIONS OF THE WORKFORCE INVESTMENT ACT OF 1998 (WIA) Recordkeeping and...

  4. Targets of the StBEL5 Transcription Factor Include the FT Ortholog StSP6A1[OPEN

    PubMed Central

    Lin, Tian

    2016-01-01

    The BEL1-like family of transcription factors is ubiquitous in plants and plays important roles in regulating development. They function in tandem with KNOTTED1 types to bind to a double TTGAC motif in the upstream sequence of target genes. StBEL5 of potato (Solanum tuberosum) functions as a mobile RNA signal that is transcribed in leaves, moves down into stolons in response to short days, and induces tuber formation. Despite their importance, however, very little is known about the targets of BEL1-like transcription factors. To better understand this network, we made use of a phloem-mobile BEL5 induction model, an ethanol-inducible system coupled with RNA sequencing analysis, and a screen for tandem TTGAC cis-elements in the upstream sequence to catalog StBEL5 target genes. Induction of StBEL5 activated several genes that are also induced by StSP6A (S. tuberosum SELF-PRUNING 6A), a FLOWERING LOCUS T coregulator that functions as a signal for tuberization. Both enhancement and suppression of StBEL5 expression were also closely linked to StSP6A transcriptional activity. Site mutagenesis in tandem TTGAC motifs located in the upstream sequence of StSP6A suppressed the short day-induced activity of its promoter in both young tubers and leaves. The expression profile of StBEL5 induced in stolons from plants grown under long-day conditions revealed almost 10,000 differentially expressed genes, including important tuber marker genes and genes involved in cell growth, transcription, floral development, and hormone metabolism. In a random screen of 200 differentially expressed targets of StBEL5, 92% contained tandem TTGAC motifs in the upstream sequence within 3 kb of the transcription start site. PMID:26553650

  5. Early-Life Events, Including Mode of Delivery and Type of Feeding, Siblings and Gender, Shape the Developing Gut Microbiota

    PubMed Central

    Cetinyurek Yavuz, Aysun; Ben-Amor, Kaouther; Roelofs, Mieke; Ishikawa, Eiji; Kubota, Hiroyuki; Swinkels, Sophie; Sakai, Takafumi; Oishi, Kenji; Kushiro, Akira; Knol, Jan

    2016-01-01

    Colonization of the infant gut is believed to be critically important for a healthy growth as it influences gut maturation, metabolic, immune and brain development in early life. Understanding factors that influence this process is important, since an altered colonization has been associated with a higher risk of diseases later in life. Fecal samples were collected from 108 healthy neonates in the first half year of life. The composition and functionality of the microbiota was characterized by measuring 33 different bacterial taxa by qPCR/RT qPCR, and 8 bacterial metabolites. Information regarding gender, place and mode of birth, presence of siblings or pets; feeding pattern and antibiotic use was collected by using questionnaires. Regression analysis techniques were used to study associations between microbiota parameters and confounding factors over time. Bacterial DNA was detected in most meconium samples, suggesting bacterial exposure occurs in utero. After birth, colonization by species of Bifidobacterium, Lactobacillus and Bacteroides was influenced by mode of delivery, type of feeding and presence of siblings, with differences found at species level and over time. Interestingly, infant-type bifidobacterial species such as B. breve or B. longum subsp infantis were confirmed as early colonizers apparently independent of the factors studied here, while B. animalis subsp. lactis presence was found to be dependent solely on the type of feeding, indicating that it might not be a common infant gut inhabitant. One interesting and rather unexpected confounding factor was gender. This study contributes to our understanding of the composition of the microbiota in early life and the succession process and the evolution of the microbial community as a function of time and events occurring during the first 6 months of life. Our results provide new insights that could be taken into consideration when selecting nutritional supplementation strategies to support the

  6. Early-Life Events, Including Mode of Delivery and Type of Feeding, Siblings and Gender, Shape the Developing Gut Microbiota.

    PubMed

    Martin, Rocio; Makino, Hiroshi; Cetinyurek Yavuz, Aysun; Ben-Amor, Kaouther; Roelofs, Mieke; Ishikawa, Eiji; Kubota, Hiroyuki; Swinkels, Sophie; Sakai, Takafumi; Oishi, Kenji; Kushiro, Akira; Knol, Jan

    2016-01-01

    Colonization of the infant gut is believed to be critically important for a healthy growth as it influences gut maturation, metabolic, immune and brain development in early life. Understanding factors that influence this process is important, since an altered colonization has been associated with a higher risk of diseases later in life. Fecal samples were collected from 108 healthy neonates in the first half year of life. The composition and functionality of the microbiota was characterized by measuring 33 different bacterial taxa by qPCR/RT qPCR, and 8 bacterial metabolites. Information regarding gender, place and mode of birth, presence of siblings or pets; feeding pattern and antibiotic use was collected by using questionnaires. Regression analysis techniques were used to study associations between microbiota parameters and confounding factors over time. Bacterial DNA was detected in most meconium samples, suggesting bacterial exposure occurs in utero. After birth, colonization by species of Bifidobacterium, Lactobacillus and Bacteroides was influenced by mode of delivery, type of feeding and presence of siblings, with differences found at species level and over time. Interestingly, infant-type bifidobacterial species such as B. breve or B. longum subsp infantis were confirmed as early colonizers apparently independent of the factors studied here, while B. animalis subsp. lactis presence was found to be dependent solely on the type of feeding, indicating that it might not be a common infant gut inhabitant. One interesting and rather unexpected confounding factor was gender. This study contributes to our understanding of the composition of the microbiota in early life and the succession process and the evolution of the microbial community as a function of time and events occurring during the first 6 months of life. Our results provide new insights that could be taken into consideration when selecting nutritional supplementation strategies to support the

  7. Computational Prediction and Experimental Verification of New MAP Kinase Docking Sites and Substrates Including Gli Transcription Factors

    PubMed Central

    Whisenant, Thomas C.; Ho, David T.; Benz, Ryan W.; Rogers, Jeffrey S.; Kaake, Robyn M.; Gordon, Elizabeth A.; Huang, Lan; Baldi, Pierre; Bardwell, Lee

    2010-01-01

    In order to fully understand protein kinase networks, new methods are needed to identify regulators and substrates of kinases, especially for weakly expressed proteins. Here we have developed a hybrid computational search algorithm that combines machine learning and expert knowledge to identify kinase docking sites, and used this algorithm to search the human genome for novel MAP kinase substrates and regulators focused on the JNK family of MAP kinases. Predictions were tested by peptide array followed by rigorous biochemical verification with in vitro binding and kinase assays on wild-type and mutant proteins. Using this procedure, we found new ‘D-site’ class docking sites in previously known JNK substrates (hnRNP-K, PPM1J/PP2Czeta), as well as new JNK-interacting proteins (MLL4, NEIL1). Finally, we identified new D-site-dependent MAPK substrates, including the hedgehog-regulated transcription factors Gli1 and Gli3, suggesting that a direct connection between MAP kinase and hedgehog signaling may occur at the level of these key regulators. These results demonstrate that a genome-wide search for MAP kinase docking sites can be used to find new docking sites and substrates. PMID:20865152

  8. Risk Factors for Severity and Type of the Hip Fracture

    PubMed Central

    Cauley, Jane A.; Lui, Li-Yung; Genant, Harry K.; Salamone, Loran; Browner, Warren; Fink, Howard A.; Cohen, Peter; Hillier, Teresa; Bauer, Doug C.; Cummings, Steven R.

    2009-01-01

    More severe hip fractures such as displaced femoral neck (FN) fractures and unstable intertrochanteric (IT) fractures lead to poorer outcomes, but risk factors for severe fractures have not been studied. To identify risk factors for severe types of hip fracture, we performed a prospective cohort study and obtained preoperative hip radiographs from women who sustained an incident hip fracture (excluding traumatic fractures). A single radiologist scored the severity of FN fractures by the Garden System: grades I and II, undisplaced; grades III and IV, displaced. The severity of IT hip fractures was rated by the Kyle System: grades I and II, stable; grades III and IV, unstable. A total of 249 women had FN fractures: 75 (30%) were undisplaced. A total of 213 women had IT fractures: 59 (28%) were stable. Both types of hip fracture increased with age, but older age was even more strongly associated with more severe hip fractures. Low BMD was more strongly related to undisplaced FN fractures (p interaction BMD × FN type, p = 0.0008) and stable IT fractures (p interaction BMD × IT type, p = 0.04). Similar findings were observed for estimated volumetric BMD and hip geometric parameters. Corticosteroid use was only associated with displaced FN fractures, and Parkinson's disease was only associated with stable IT fractures. Little difference was reported in the self-reported circumstances surrounding each type of fracture. In conclusion, the lower the BMD, the greater the likelihood of experiencing a hip fracture that is less displaced and more stable. PMID:19113930

  9. 40 CFR 273.81 - Factors for petitions to include other wastes under 40 CFR part 273.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... wastes under 40 CFR part 273. 273.81 Section 273.81 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) SOLID WASTES (CONTINUED) STANDARDS FOR UNIVERSAL WASTE MANAGEMENT Petitions To Include Other Wastes Under 40 CFR Part 273 § 273.81 Factors for petitions to include other wastes under 40...

  10. Reactions of human and hog intrinsic factors with type I antibody to intrinsic factor

    PubMed Central

    Gullberg, R.

    1970-01-01

    A simple and rapid small-scale gel filtration method was applied in studies of type I antibody to intrinsic factor using radioactive vitamin B12 of high specific activity and purified human and hog intrinsic factor preparations, taking into account the unsaturated B12-binding capacity of the individual pernicious anaemia sera. This procedure allows the use of small amounts of reagents. Evidence was obtained for a close antigenic similarity of determinants of human and hog intrinsic factor. The use of purified intrinsic-factor preparations is important. PMID:4097742

  11. An efficient algorithm for solving coupled Schroedinger type ODE`s, whose potentials include {delta}-functions

    SciTech Connect

    Gousheh, S.S.

    1996-01-01

    I have used the shooting method to find the eigenvalues (bound state energies) of a set of strongly coupled Schroedinger type equations. I have discussed the advantages of the shooting method when the potentials include {delta}-functions. I have also discussed some points which are universal in these kind of problems, whose use make the algorithm much more efficient. These points include mapping the domain of the ODE into a finite one, using the asymptotic form of the solutions, best use of the normalization freedom, and converting the {delta}-functions into boundary conditions.

  12. Nonobese, insulin-deficient Ins2Akita mice develop type 2 diabetes phenotypes including insulin resistance and cardiac remodeling.

    PubMed

    Hong, Eun-Gyoung; Jung, Dae Young; Ko, Hwi Jin; Zhang, Zhiyou; Ma, Zhexi; Jun, John Y; Kim, Jae Hyeong; Sumner, Andrew D; Vary, Thomas C; Gardner, Thomas W; Bronson, Sarah K; Kim, Jason K

    2007-12-01

    Although insulin resistance has been traditionally associated with type 2 diabetes, recent evidence in humans and animal models indicates that insulin resistance may also develop in type 1 diabetes. A point mutation of insulin 2 gene in Ins2(Akita) mice leads to pancreatic beta-cell apoptosis and hyperglycemia, and these mice are commonly used to investigate type 1 diabetes and complications. Since insulin resistance plays an important role in diabetic complications, we performed hyperinsulinemic-euglycemic clamps in awake Ins2(Akita) and wild-type mice to measure insulin action and glucose metabolism in vivo. Nonobese Ins2(Akita) mice developed insulin resistance, as indicated by an approximately 80% reduction in glucose infusion rate during clamps. Insulin resistance was due to approximately 50% decreases in glucose uptake in skeletal muscle and brown adipose tissue as well as hepatic insulin action. Skeletal muscle insulin resistance was associated with a 40% reduction in total GLUT4 and a threefold increase in PKCepsilon levels in Ins2(Akita) mice. Chronic phloridzin treatment lowered systemic glucose levels and normalized muscle insulin action, GLUT4 and PKCepsilon levels in Ins2(Akita) mice, indicating that hyperglycemia plays a role in insulin resistance. Echocardiography showed significant cardiac remodeling with ventricular hypertrophy that was ameliorated following chronic phloridzin treatment in Ins2(Akita) mice. Overall, we report for the first time that nonobese, insulin-deficient Ins2(Akita) mice develop type 2 diabetes phenotypes including peripheral and hepatic insulin resistance and cardiac remodeling. Our findings provide important insights into the pathogenesis of metabolic abnormalities and complications affecting type 1 diabetes and lean type 2 diabetes subjects. PMID:17911348

  13. Dietary factors in the development of type 1 diabetes.

    PubMed

    Virtanen, Suvi M

    2016-07-01

    There are several indicators concerning the putative importance of dietary factors during the fetal period lactation, infancy and childhood in the etiology of type 1 diabetes. Among foods, cow's milk consumption has been associated with an increased risk of preclinical and/or clinical type 1 diabetes and sugars with a progression from preclinical to clinical disease. Breast milk, on the other hand, may be protective. Processed foods may be related to a greater risk of type 1 diabetes because they contain higher amounts of advanced glycation end-products. Nitrites or N-nitroso compounds in processed meat products could increase the risk of this disease. Among nutrients, n-3 fatty acids, vitamins D and E, and zinc may protect from preclinical and/or clinical type 1 diabetes. The microbial composition of foods or food's other effects on gut microbiota are receiving increasing attention, also due to their putative role in the development of type 1 diabetes. Still the number of prospective studies in this research field is limited and most of the findings remain to be replicated. PMID:27411437

  14. Meat consumption as a risk factor for type 2 diabetes.

    PubMed

    Barnard, Neal; Levin, Susan; Trapp, Caroline

    2014-01-01

    Disease risk factors identified in epidemiological studies serve as important public health tools, helping clinicians identify individuals who may benefit from more aggressive screening or risk-modification procedures, allowing policymakers to prioritize intervention programs, and encouraging at-risk individuals to modify behavior and improve their health. These factors have been based primarily on evidence from cross-sectional and prospective studies, as most do not lend themselves to randomized trials. While some risk factors are not modifiable, eating habits are subject to change through both individual action and broader policy initiatives. Meat consumption has been frequently investigated as a variable associated with diabetes risk, but it has not yet been described as a diabetes risk factor. In this article, we evaluate the evidence supporting the use of meat consumption as a clinically useful risk factor for type 2 diabetes, based on studies evaluating the risks associated with meat consumption as a categorical dietary characteristic (i.e., meat consumption versus no meat consumption), as a scalar variable (i.e., gradations of meat consumption), or as part of a broader dietary pattern. PMID:24566443

  15. Meat Consumption as a Risk Factor for Type 2 Diabetes

    PubMed Central

    Barnard, Neal; Levin, Susan; Trapp, Caroline

    2014-01-01

    Disease risk factors identified in epidemiological studies serve as important public health tools, helping clinicians identify individuals who may benefit from more aggressive screening or risk-modification procedures, allowing policymakers to prioritize intervention programs, and encouraging at-risk individuals to modify behavior and improve their health. These factors have been based primarily on evidence from cross-sectional and prospective studies, as most do not lend themselves to randomized trials. While some risk factors are not modifiable, eating habits are subject to change through both individual action and broader policy initiatives. Meat consumption has been frequently investigated as a variable associated with diabetes risk, but it has not yet been described as a diabetes risk factor. In this article, we evaluate the evidence supporting the use of meat consumption as a clinically useful risk factor for type 2 diabetes, based on studies evaluating the risks associated with meat consumption as a categorical dietary characteristic (i.e., meat consumption versus no meat consumption), as a scalar variable (i.e., gradations of meat consumption), or as part of a broader dietary pattern. PMID:24566443

  16. Eating Disorders in children and adolescents with Type 1 and Type 2 Diabetes: prevalence, risk factors, warning signs.

    PubMed

    Racicka, Ewa; Bryńska, Anita

    2015-01-01

    Diabetes is associated with increased risk for eating disorders, various dependent on type of diabetes. Binge eating disorder is more common in patient with type 2 diabetes (T2DM). Whereas, intentional omission of insulin doses for the purpose of weight loss occurs mainly in patient with type 1 diabetes (T1DM), however, in some patients with type 2 diabetes omission of oral hypoglycemic drugs can be present. Risk factors for the development of eating disorders in patients with diabetes include: age, female gender, greater body weight, body image dissatisfaction, history of dieting and history of depression. Poor glycemic control, recurrent episodes of ketoacidosis or recurrent episodes of hypoglycemia, secondary to intentional insulin overdose, missed clinical appointments, dietary manipulation and low self-esteem should raise concern. The consequence of eating disorders or disordered eating patterns in patients with diabetes is poor glycemic control and hence higher possibility of complications such as nephropathy, retinopathy and premature death. PMID:26688851

  17. Bayesian Ages for Early-type Stars from Isochrones Including Rotation, and a Possible Old Age for the Hyades

    NASA Astrophysics Data System (ADS)

    Brandt, Timothy D.; Huang, Chelsea X.

    2015-07-01

    We combine recently computed models of stellar evolution using a new treatment of rotation with a Bayesian statistical framework to constrain the ages and other properties of early-type stars. We find good agreement for early-type stars and clusters with known young ages, including β Pictoris, the Pleiades, and the Ursa Majoris moving group. However, we derive a substantially older age for the Hyades open cluster (750 ± 100 Myr compared to 625 ± 50 Myr). This older age results from both the increase in main-sequence lifetime with stellar rotation and from the fact that rotating models near the main-sequence turnoff are more luminous, overlapping with slightly more massive (and shorter-lived) nonrotating ones. Our method uses a large grid of nonrotating models to interpolate between a much sparser rotating grid, and also includes a detailed calculation of synthetic magnitudes as a function of orientation. We provide a web interface at http://www.bayesianstellarparameters.info, where the results of our analysis may be downloaded for individual early-type (B-V≲ 0.25) Hipparcos stars. The web interface accepts user-supplied parameters for a Gaussian metallicity prior and returns posterior probability distributions on mass, age, and orientation.

  18. A predator-prey model with a holling type I functional response including a predator mutual interference

    USGS Publications Warehouse

    Seo, G.; DeAngelis, D.L.

    2011-01-01

    The most widely used functional response in describing predator-prey relationships is the Holling type II functional response, where per capita predation is a smooth, increasing, and saturating function of prey density. Beddington and DeAngelis modified the Holling type II response to include interference of predators that increases with predator density. Here we introduce a predator-interference term into a Holling type I functional response. We explain the ecological rationale for the response and note that the phase plane configuration of the predator and prey isoclines differs greatly from that of the Beddington-DeAngelis response; for example, in having three possible interior equilibria rather than one. In fact, this new functional response seems to be quite unique. We used analytical and numerical methods to show that the resulting system shows a much richer dynamical behavior than the Beddington-DeAngelis response, or other typically used functional responses. For example, cyclic-fold, saddle-fold, homoclinic saddle connection, and multiple crossing bifurcations can all occur. We then use a smooth approximation to the Holling type I functional response with predator mutual interference to show that these dynamical properties do not result from the lack of smoothness, but rather from subtle differences in the functional responses. ?? 2011 Springer Science+Business Media, LLC.

  19. 40 CFR 273.81 - Factors for petitions to include other wastes under 40 CFR part 273.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... wastes under 40 CFR part 273. 273.81 Section 273.81 Protection of Environment ENVIRONMENTAL PROTECTION... Other Wastes Under 40 CFR Part 273 § 273.81 Factors for petitions to include other wastes under 40 CFR... requirements appropriate to be added to 40 CFR 273.13, 273.33, and 273.52; and/or applicable Department...

  20. 40 CFR 273.81 - Factors for petitions to include other wastes under 40 CFR part 273.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... wastes under 40 CFR part 273. 273.81 Section 273.81 Protection of Environment ENVIRONMENTAL PROTECTION... Other Wastes Under 40 CFR Part 273 § 273.81 Factors for petitions to include other wastes under 40 CFR... generic name to identify the waste category (e.g., batteries), the definition of universal waste in §...

  1. 40 CFR 273.81 - Factors for petitions to include other wastes under 40 CFR part 273.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... wastes under 40 CFR part 273. 273.81 Section 273.81 Protection of Environment ENVIRONMENTAL PROTECTION... Other Wastes Under 40 CFR Part 273 § 273.81 Factors for petitions to include other wastes under 40 CFR... requirements appropriate to be added to 40 CFR 273.13, 273.33, and 273.52; and/or applicable Department...

  2. Correlation between B type natriuretic peptide and metabolic risk factors

    PubMed Central

    Zhu, Wen-Hua; Chen, Li-Ying; Dai, Hong-Lei; Chen, Jian-Hua; Chen, Yan

    2016-01-01

    Introduction It has been shown that B type natriuretic peptide (BNP) level can indicate cardiovascular disease. However, the association between BNP and metabolic risk factors is unknown. The aim of this study was to investigate the correlation between N-terminal pro-B type natriuretic peptide (NT-proBNP) and metabolic risk factors. Material and methods A total of 11,508 subjects were selected from those who underwent health examinations in our hospital. NT-proBNP, waist circumference, blood pressure, fasting plasma glucose and lipid profile were measured. The level of NT-proBNP was measured and classified into four stratifications (BNP ≥ 20 pg/ml, ≥ 40 pg/ml, ≥ 60 pg/ml, and ≥ 80 pg/ml) to analyze the relationship between BNP and metabolic risk factors. Results B type natriuretic peptide increased gradually with increasing age (p < 0.001). The BNP levels were significantly higher in women than in men (p < 0.001). Multivariate regression analysis showed a positive association between NT-proBNP levels and systolic blood pressure (p < 0.001), fasting plasma glucose (p < 0.05), and total cholesterol (p < 0.001 in women). The NT-proBNP levels were inversely associated with diastolic blood pressure, waist circumference, triglyceride, high-density lipoprotein, and LDL cholesterol. Logistic regression analysis demonstrated a close relationship between NT-proBNP and systolic blood pressure, fasting plasma glucose, and total cholesterol. In the BNP ≥ 60 pg/ml group, odds ratio (OR) values were 1.80, 1.56 and 1.54 (female) and 3.74, 1.59 and 1.51 (male), respectively. In the BNP ≥ 80 pg/ml group, OR values were 2.45, 1.65 and 1.84 (female) and 4.61, 1.66 and 1.75 (male), respectively. Conclusions NT-proBNP was independently associated with the main metabolic risk factors (systolic blood pressure, fasting plasma glucose, and total cholesterol). These findings suggest that the combined determination of NT-proBNP and the main metabolic risk factors could be

  3. The Type Series of 'Sinemys' Wuerhoensis, a Problematic Turtlefrom the Lower Cretaceous of China, Includes at Least Three Taxa

    SciTech Connect

    Danilov, Igor G.; Parham, James F.

    2007-03-01

    We re-examine the type series of 'Sinemys' wuerhoensis Yeh(at least 20 specimens, including several shells and skulls on threeslabs of matrix and one isolated skull) from the Early Cretaceous TuguluGroup of China. Our study shows that the type series of 'S.'wuerhoensisis actually a chimera made up of at least three distinct taxa. Theholotype of this taxon should be assigned to the basal eucryptodire genusXinjiangchelys Yeh. As there are no characters that distinguish'S.'wuerhoensis from Xinjiangchelys species, we consider it to be a nomendubium. This new assignment of 'S.'wuerhoensis expands the temporal rangeof Xinjiangchelys from the Late Jurassic into the Early Cretaceous inAsia. The majority of the paratypes of 'S.'wuerhoensis (several shells indorsal and ventral aspect and skulls) are referred to the basaleucryptodire genus Ordosemys Brinkman and Peng. We establish a new namefor these specimens, Ordosemys brinkmania sp. nov. One additionalspecimen in the type series of 'S.'wuerhoensis, a skull, is referred tocf. Pantrionychia Joyce, Parham and Gauthier indet.

  4. Increased activity of coagulation factor XII (Hageman factor) causes hereditary angioedema type III.

    PubMed

    Cichon, Sven; Martin, Ludovic; Hennies, Hans Christian; Müller, Felicitas; Van Driessche, Karen; Karpushova, Anna; Stevens, Wim; Colombo, Roberto; Renné, Thomas; Drouet, Christian; Bork, Konrad; Nöthen, Markus M

    2006-12-01

    Hereditary angioedema (HAE) is characterized clinically by recurrent acute skin swelling, abdominal pain, and potentially life-threatening laryngeal edema. Three forms of HAE have been described. The classic forms, HAE types I and II, occur as a consequence of mutations in the C1-inhibitor gene. In contrast to HAE types I and II, HAE type III has been observed exclusively in women, where it appears to be correlated with conditions of high estrogen levels--for example, pregnancy or the use of oral contraceptives. A recent report proposed two missense mutations (c.1032C-->A and c.1032C-->G) in F12, the gene encoding human coagulation factor XII (FXII, or Hageman factor) as a possible cause of HAE type III. Here, we report the occurrence of the c.1032C-->A (p.Thr328Lys) mutation in an HAE type III-affected family of French origin. Investigation of the F12 gene in a large German family did not reveal a coding mutation. Haplotype analysis with use of microsatellite markers is compatible with locus heterogeneity in HAE type III. To shed more light on the pathogenic relevance of the HAE type III-associated p.Thr328Lys mutation, we compared FXII activity and plasma levels in patients carrying the mutation with that of healthy control individuals. Our data strongly suggest that p.Thr328Lys is a gain-of-function mutation that markedly increases FXII amidolytic activity but that does not alter FXII plasma levels. We conclude that enhanced FXII enzymatic plasma activity in female mutation carriers leads to enhanced kinin production, which results in angioedema. Transcription of F12 is positively regulated by estrogens, which may explain why only women are affected with HAE type III. The results of our study represent an important step toward an understanding of the molecular processes involved in HAE type III and provide diagnostic and possibly new therapeutic opportunities. PMID:17186468

  5. Directional reflectance factor distributions for cover types of Northern Africa

    NASA Technical Reports Server (NTRS)

    Kimes, D. S.; Newcomb, W. W.; Tucker, C. J.; Zonneveld, I. S.; Van Wijngaarden, W.

    1985-01-01

    Directional reflectance factors that spanned the entire exitance hemisphere were collected on the ground throughout the morning period for common cover types in Tunisia, Africa. NOAA 7/8 AVHRR bands 1(0.58-0.68 micron) and 2 (0.7301.1 micron) were used in data collection. The cover types reported were a plowed field, annual grassland, steppe grassland, hard wheat, salt plain, and irrigated wheat. Several of these cover types had geometric structures that are extreme as compared to those reported in the literature. Comparisons were made between the dynamics of the observed reflectance distributions and those reported in the literature. It was found that the dynamics of the measured data could be explained by a combination of soil and vegetation scattering components. The data and analysis further validated physical principles that cause the reflectance distribution dynamics as proposed by field and simulation studies in the literature. Finally, the normalized difference transformation (Band 2 - Band 1)/(Band 1 + Band 2), which is useful in monitoring vegetation cover, generally decreased the variation in signal with changing view angle. However, several exceptions were noted.

  6. Visible and near infrared spectroscopic investigation of E-type asteroids, including 2867 Steins, a target of the Rosetta mission

    NASA Astrophysics Data System (ADS)

    Fornasier, S.; Migliorini, A.; Dotto, E.; Barucci, M. A.

    2008-07-01

    We present the results of a visible spectroscopic survey of igneous asteroids belonging to the small and intriguing E-class, including 2867 Steins, a target of the Rosetta mission. The survey was carried out at the 3.5 m Telescopio Nazionale Galileo (TNG), and at the 3.5 m New Technology Telescope (NTT) of the European Southern Observatory. We obtained new visible spectra for eighteen E-type asteroids, and near infrared spectra for eight of them. We confirm the presence of three different mineralogies in the small E-type populations. We classify each object in the E[I], E[II] or E[III] subgroups [Gaffey, M.J., Kelley, M.S., 2004. Lunar Planet. Sci. XXXV. Abstract 1812] on the basis of the spectral behavior and of the eventual presence of absorption features attributed to sulfides (such the 0.49 μm band, on E[II]), or to iron bearing silicates (0.9 μm band, on E[III]). We suggest that some asteroids (i.e. 64 Angelina, 317 Roxane, and 434 Hungaria), which show different spectral behavior comparing our data with those available in literature, have an inhomogeneous surface composition. 2867 Steins, a target of the Rosetta mission, shows a spectral behavior typical of the E[II] subgroup, as already suggested by Barucci et al. [Barucci, M.A., Fulchignoni, M., Fornasier, S., Dotto, E., Vernazza, P., Birlan, M., Binzel, R.P., Carvano, J., Merlin, F., Barbieri, C., Belskaya, I., 2005. Astron. Astrophys. 430, 313-317] and Fornasier et al. [Fornasier, S., Marzari, F., Dotto, E., Barucci, M.A., Migliorini, A., 2007. Astron. Astrophys. 474, 29-32]. Litva and 1990 TN1, initially classified as E-types, show a visible and near infrared behavior consistent with the olivine rich A-class asteroids, while 5806 Archieroy, also supposed to belong to the E-class, has a spectral behavior consistent with the S(V) classification following the Gaffey et al. [Gaffey, M.J., Burbine, T.H., Piatek, J.L., Reed, K.L., Chaky, D.A., Bell, J.F., Brown, R.H., 1993. Icarus 106, 573

  7. The Benefits of Including Clinical Factors in Rectal Normal Tissue Complication Probability Modeling After Radiotherapy for Prostate Cancer

    SciTech Connect

    Defraene, Gilles; Van den Bergh, Laura; Al-Mamgani, Abrahim; Haustermans, Karin; Heemsbergen, Wilma; Van den Heuvel, Frank; Lebesque, Joos V.

    2012-03-01

    Purpose: To study the impact of clinical predisposing factors on rectal normal tissue complication probability modeling using the updated results of the Dutch prostate dose-escalation trial. Methods and Materials: Toxicity data of 512 patients (conformally treated to 68 Gy [n = 284] and 78 Gy [n = 228]) with complete follow-up at 3 years after radiotherapy were studied. Scored end points were rectal bleeding, high stool frequency, and fecal incontinence. Two traditional dose-based models (Lyman-Kutcher-Burman (LKB) and Relative Seriality (RS) and a logistic model were fitted using a maximum likelihood approach. Furthermore, these model fits were improved by including the most significant clinical factors. The area under the receiver operating characteristic curve (AUC) was used to compare the discriminating ability of all fits. Results: Including clinical factors significantly increased the predictive power of the models for all end points. In the optimal LKB, RS, and logistic models for rectal bleeding and fecal incontinence, the first significant (p = 0.011-0.013) clinical factor was 'previous abdominal surgery.' As second significant (p = 0.012-0.016) factor, 'cardiac history' was included in all three rectal bleeding fits, whereas including 'diabetes' was significant (p = 0.039-0.048) in fecal incontinence modeling but only in the LKB and logistic models. High stool frequency fits only benefitted significantly (p = 0.003-0.006) from the inclusion of the baseline toxicity score. For all models rectal bleeding fits had the highest AUC (0.77) where it was 0.63 and 0.68 for high stool frequency and fecal incontinence, respectively. LKB and logistic model fits resulted in similar values for the volume parameter. The steepness parameter was somewhat higher in the logistic model, also resulting in a slightly lower D{sub 50}. Anal wall DVHs were used for fecal incontinence, whereas anorectal wall dose best described the other two endpoints. Conclusions: Comparable

  8. Sequence and chromatin determinants of cell-type-specific transcription factor binding.

    PubMed

    Arvey, Aaron; Agius, Phaedra; Noble, William Stafford; Leslie, Christina

    2012-09-01

    Gene regulatory programs in distinct cell types are maintained in large part through the cell-type-specific binding of transcription factors (TFs). The determinants of TF binding include direct DNA sequence preferences, DNA sequence preferences of cofactors, and the local cell-dependent chromatin context. To explore the contribution of DNA sequence signal, histone modifications, and DNase accessibility to cell-type-specific binding, we analyzed 286 ChIP-seq experiments performed by the ENCODE Consortium. This analysis included experiments for 67 transcriptional regulators, 15 of which were profiled in both the GM12878 (lymphoblastoid) and K562 (erythroleukemic) human hematopoietic cell lines. To model TF-bound regions, we trained support vector machines (SVMs) that use flexible k-mer patterns to capture DNA sequence signals more accurately than traditional motif approaches. In addition, we trained SVM spatial chromatin signatures to model local histone modifications and DNase accessibility, obtaining significantly more accurate TF occupancy predictions than simpler approaches. Consistent with previous studies, we find that DNase accessibility can explain cell-line-specific binding for many factors. However, we also find that of the 10 factors with prominent cell-type-specific binding patterns, four display distinct cell-type-specific DNA sequence preferences according to our models. Moreover, for two factors we identify cell-specific binding sites that are accessible in both cell types but bound only in one. For these sites, cell-type-specific sequence models, rather than DNase accessibility, are better able to explain differential binding. Our results suggest that using a single motif for each TF and filtering for chromatin accessible loci is not always sufficient to accurately account for cell-type-specific binding profiles. PMID:22955984

  9. Air Pollution as a Risk Factor for Type 2 Diabetes

    PubMed Central

    Rao, Xiaoquan; Patel, Priti; Puett, Robin; Rajagopalan, Sanjay

    2015-01-01

    Recent studies in both humans and animals suggest that air pollution is an important risk factor for type 2 diabetes mellitus (T2DM). However, the mechanism by which air pollution mediates propensity to diabetes is not fully understood. While a number of epidemiologic studies have shown a positive association between ambient air pollution exposure and risk for T2DM, some studies have not found such a relationship. Experimental studies in susceptible disease models do support this association and suggest the involvement of tissues involved in the pathogenesis of T2DM such as the immune system, adipose, liver, and central nervous system. This review summarizes the epidemiologic and experimental evidence between ambient outdoor air pollution and T2DM. PMID:25628401

  10. Spectral, spatial and radiometric factors in cover type discrimination

    NASA Technical Reports Server (NTRS)

    Alexander, D.; Buis, J.; Acevedo, W.; Wrigley, R.

    1983-01-01

    The influence of spatial, spectral, and radiometric resolutions on the utilization of Thematic Mapper (TM) and Multispectral Scanner (MSS) data is assessed quantitatively using a 2 x 2 x 2 factorial design experiment. Eight possible factor combinations were examined for agricultural, urban, forestry, range, and water types of land covers for three levels of information. Spectral bandwidths were configured to simulate all four Landsat MSS channels and Landsat TM channels 1, 2, 3, 4, and 7. By means of bar charts and tables it is shown that the 8-bit radiometric and 75-meter spatial resolutions provide a higher overall accuracy than the 6-bit radiometric and 25-meter spatial resolutions. Spectrally, the difference between the four MSS channels and five TM channel configurations is noted to be insignificant.

  11. Therapies for type 2 diabetes: lowering HbA1c and associated cardiovascular risk factors

    PubMed Central

    2010-01-01

    Objectives To summarize data supporting the effects of antidiabetes agents on glucose control and cardiovascular risk factors in patients with type 2 diabetes. Methods Studies reporting on the effects of antidiabetes agents on glycemic control, body weight, lipid levels, and blood pressure parameters are reviewed and summarized for the purpose of selecting optimal therapeutic regimens for patients with type 2 diabetes. Results National guidelines recommend the aggressive management of cardiovascular risk factors in patients with type 2 diabetes, including weight loss and achieving lipid and blood pressure treatment goals. All antidiabetes pharmacotherapies lower glucose; however, effects on cardiovascular risk factors vary greatly among agents. While thiazolidinediones, sulfonylureas, and insulin are associated with weight gain, dipeptidyl peptidase-4 inhibitors are considered weight neutral and metformin can be weight neutral or associated with a small weight loss. Glucagon-like peptide-1 receptor agonists and amylinomimetics (e.g. pramlintide) result in weight loss. Additionally, metformin, thiazolidinediones, insulin, and glucagon-like peptide-1 receptor agonists have demonstrated beneficial effects on lipid and blood pressure parameters. Conclusion Management of the cardiovascular risk factors experienced by patients with type 2 diabetes requires a multidisciplinary approach with implementation of treatment strategies to achieve not only glycemic goals but to improve and/or correct the underlying cardiovascular risk factors. PMID:20804556

  12. Growing TiO2 nanowires by solid-liquid-solid mechanism including two factors (Ti and O)

    NASA Astrophysics Data System (ADS)

    Pishekloo, S. Piri; Dariani, R. S.

    2016-04-01

    Identifying the growth factors of nanowires helps in controlling their structure and morphology and determining their optimal growth conditions. This study investigates the effect of titanium substrate in growing TiO2 nanowires (NWs) with evaporation method. It reveals that the titanium in substrate is indeed the main source of growth. Using the substrate as the only source of growth with regulated amount of accessible oxygen in the furnace, NWs with lengths ranging from 1 to 70 µm were obtained. The results of the experiments show that the nanowires' growth is mainly controlled by diffusion of titanium atoms from the substrate through TiO2 grain boundaries and surface diffusion toward NWs' tips rather than adsorption from vapor phase. The solid-liquid-solid mechanism including two factors (Ti and O) is proposed and discussed for growth of TiO2 NWs.

  13. ASSESSMENT OF RISK FACTORS FOR DIABETES MELLITUS TYPE 2

    PubMed Central

    Begic, Edin; Arnautovic, Amira; Masic, Izet

    2016-01-01

    Introduction: Diabetes is a group of metabolic diseases characterized by hyperglycemia, and represents a disease of the modern age, disease of the 21st century. Prevention of this disease is listed as imperative. Aim of this article was to evaluate questionnaires on the assessment of risk factors for Diabetes Mellitus type 2. Material and Methods: A total of 540 questionnaires handed out randomly to citizens of Canton Sarajevo of all ages, sexes and educational levels (in January 2016) were analyzed. Results: Analyzed questionnaires showed relatively low risk of getting diabetes in the next ten years in the majority of the population. These results are rather encouraging but may in some way be in confrontation with the statistics which show a rapid outburst of diabetes. Conclusion: The life-style is the main reason for such a thing to happen, and looking at these questionnaires, we might get the feeling that we really do live in a, conditionally speaking, physically active society. That, from our everyday experience is not entirely true. It would be wise to continue doing research on this topic on the territory of Bosnia and Herzegovina. PMID:27482159

  14. Effects of benchmarking on the quality of type 2 diabetes care: results of the OPTIMISE (Optimal Type 2 Diabetes Management Including Benchmarking and Standard Treatment) study in Greece

    PubMed Central

    Tsimihodimos, Vasilis; Kostapanos, Michael S.; Moulis, Alexandros; Nikas, Nikos; Elisaf, Moses S.

    2015-01-01

    Objectives: To investigate the effect of benchmarking on the quality of type 2 diabetes (T2DM) care in Greece. Methods: The OPTIMISE (Optimal Type 2 Diabetes Management Including Benchmarking and Standard Treatment) study [ClinicalTrials.gov identifier: NCT00681850] was an international multicenter, prospective cohort study. It included physicians randomized 3:1 to either receive benchmarking for glycated hemoglobin (HbA1c), systolic blood pressure (SBP) and low-density lipoprotein cholesterol (LDL-C) treatment targets (benchmarking group) or not (control group). The proportions of patients achieving the targets of the above-mentioned parameters were compared between groups after 12 months of treatment. Also, the proportions of patients achieving those targets at 12 months were compared with baseline in the benchmarking group. Results: In the Greek region, the OPTIMISE study included 797 adults with T2DM (570 in the benchmarking group). At month 12 the proportion of patients within the predefined targets for SBP and LDL-C was greater in the benchmarking compared with the control group (50.6 versus 35.8%, and 45.3 versus 36.1%, respectively). However, these differences were not statistically significant. No difference between groups was noted in the percentage of patients achieving the predefined target for HbA1c. At month 12 the increase in the percentage of patients achieving all three targets was greater in the benchmarking (5.9–15.0%) than in the control group (2.7–8.1%). In the benchmarking group more patients were on target regarding SBP (50.6% versus 29.8%), LDL-C (45.3% versus 31.3%) and HbA1c (63.8% versus 51.2%) at 12 months compared with baseline (p < 0.001 for all comparisons). Conclusion: Benchmarking may comprise a promising tool for improving the quality of T2DM care. Nevertheless, target achievement rates of each, and of all three, quality indicators were suboptimal, indicating there are still unmet needs in the management of T2DM. PMID:26445642

  15. Staphylococcus aureus strains associated with food poisoning outbreaks in France: comparison of different molecular typing methods, including MLVA

    PubMed Central

    Roussel, Sophie; Felix, Benjamin; Vingadassalon, Noémie; Grout, Joël; Hennekinne, Jacques-Antoine; Guillier, Laurent; Brisabois, Anne; Auvray, Fréderic

    2015-01-01

    Staphylococcal food poisoning outbreaks (SFPOs) are frequently reported in France. However, most of them remain unconfirmed, highlighting a need for a better characterization of isolated strains. Here we analyzed the genetic diversity of 112 Staphylococcus aureus strains isolated from 76 distinct SFPOs that occurred in France over the last 30 years. We used a recently developed multiple-locus variable-number tandem-repeat analysis (MLVA) protocol and compared this method with pulsed field gel electrophoresis (PFGE), spa-typing and carriage of genes (se genes) coding for 11 staphylococcal enterotoxins (i.e., SEA, SEB, SEC, SED, SEE, SEG, SEH, SEI, SEJ, SEP, SER). The strains known to have an epidemiological association with one another had identical MLVA types, PFGE profiles, spa-types or se gene carriage. MLVA, PFGE and spa-typing divided 103 epidemiologically unrelated strains into 84, 80, and 50 types respectively demonstrating the high genetic diversity of S. aureus strains involved in SFPOs. Each MLVA type shared by more than one strain corresponded to a single spa-type except for one MLVA type represented by four strains that showed two different-but closely related-spa-types. The 87 enterotoxigenic strains were distributed across 68 distinct MLVA types that correlated all with se gene carriage except for four MLVA types. The most frequent se gene detected was sea, followed by seg and sei and the most frequently associated se genes were sea-seh and sea-sed-sej-ser. The discriminatory ability of MLVA was similar to that of PFGE and higher than that of spa-typing. This MLVA protocol was found to be compatible with high throughput analysis, and was also faster and less labor-intensive than PFGE. MLVA holds promise as a suitable method for investigating SFPOs and tracking the source of contamination in food processing facilities in real time. PMID:26441849

  16. Factor Analysis of Linear Type Traits and Their Relation with Longevity in Brazilian Holstein Cattle

    PubMed Central

    Kern, Elisandra Lurdes; Cobuci, Jaime Araújo; Costa, Cláudio Napolis; Pimentel, Concepta Margaret McManus

    2014-01-01

    In this study we aimed to evaluate the reduction in dimensionality of 20 linear type traits and more final score in 14,943 Holstein cows in Brazil using factor analysis, and indicate their relationship with longevity and 305 d first lactation milk production. Low partial correlations (−0.19 to 0.38), the medium to high Kaiser sampling mean (0.79) and the significance of the Bartlett sphericity test (p<0.001), indicated correlations between type traits and the suitability of these data for a factor analysis, after the elimination of seven traits. Two factors had autovalues greater than one. The first included width and height of posterior udder, udder texture, udder cleft, loin strength, bone quality and final score. The second included stature, top line, chest width, body depth, fore udder attachment, angularity and final score. The linear regression of the factors on several measures of longevity and 305 d milk production showed that selection considering only the first factor should lead to improvements in longevity and 305 milk production. PMID:25050015

  17. Clinical factors, including All Patient Refined Diagnosis Related Group severity, as predictors of early rehospitalization after COPD exacerbation

    PubMed Central

    Roberts, Melissa H; Mapel, Douglas W; Von Worley, Ann; Beene, Janice

    2015-01-01

    Background: Patients hospitalized for chronic obstructive pulmonary disease (COPD) exacerbations carry a high risk for early rehospitalization. We wished to identify the basic clinical factors associated with a high risk of rehospitalization, and to see how well the standardized All Patient Refined Diagnosis Related Group (APR-DRG) severity of illness (SOI) subclassification predicted rehospitalization if combined with other simple clinical measures. Methods: We identified adult patients aged ≥40 years discharged from a major hospital in the Southwestern USA with a COPD discharge diagnosis during the study index period (1 October 2009 to 30 September 2010). Patients readmitted within 30 days (“early rehospitalization”) and 90 days (“any rehospitalization”) were each compared with those not rehospitalized. Clinical parameters (including demographics, comorbidities) and recent healthcare utilization were examined for their association with rehospitalization. Factors independently associated with rehospitalization were then combined with the index admission APR-DRG SOI assessment using conditional linear regression to find the best models in terms of the highest C-statistic. Results: Among 306 patients hospitalized for COPD, 62 (20.3%) had a rehospitalization within 90 days and 28 (9.2%), an early readmission. An APR-DRG SOI subclassification ≥3 was a modest independent predictor of early or any readmission, with adjusted odds ratios ranging from 2.09 to 3.33. Models that combined the APR-DRG SOI subclassification with clinical factors present before the index hospitalization had strong C-statistics of ≥0.80. Good models without the APR-DRG SOI subclassification but including a history of recent hospitalizations before the index hospitalization were also identified. Conclusions: An APR-DRG SOI subclassification of ≥3 for the index COPD admission is associated with an increased risk of early rehospitalizations, and can be combined with a few historical

  18. Carriage and acquisition rates of Clostridium difficile in hospitalized horses, including molecular characterization, multilocus sequence typing and antimicrobial susceptibility of bacterial isolates.

    PubMed

    Rodriguez, C; Taminiau, B; Brévers, B; Avesani, V; Van Broeck, J; Leroux, A A; Amory, H; Delmée, M; Daube, G

    2014-08-01

    Clostridium difficile has been identified as a significant agent of diarrhoea and enterocolitis in both foals and adult horses. Hospitalization, antibiotic therapy or changes in diet may contribute to the development of C. difficile infection. Horses admitted to a care unit are therefore at greater risk of being colonized. The aim of this study was to investigate the carriage of C. difficile in hospitalized horses and the possible influence of some risk factors in colonization. During a seven-month period, faecal samples and data relating the clinical history of horses admitted to a veterinary teaching hospital were collected. C. difficile isolates were characterized through toxin profiles, cytotoxicity activity, PCR-ribotyping, antimicrobial resistance and multilocus sequence typing (MLST). Ten isolates were obtained with a total of seven different PCR-ribotypes, including PCR-ribotype 014. Five of them were identified as toxinogenic. A high resistance to gentamicin, clindamycin and ceftiofur was found. MLST revealed four different sequencing types (ST), which included ST11, ST26, ST2 and ST15, and phylogenetic analysis showed that most of the isolates clustered in the same lineage. Clinical history suggests that horses frequently harbour toxigenic and non-toxigenic C. difficile and that in most cases they are colonized regardless of the reason for hospitalization; the development of diarrhoea is more unusual. PMID:24894133

  19. Nonsense mutations of the von Willebrand factor gene in patients with von Willebrand disease type III and type I

    SciTech Connect

    Zhang, Z.P.; Lindstedt, M.; Falk, G.; Blombaeck, M.; Egberg, N.; Anvret, M. )

    1992-10-01

    von Willebrand disease (vWD) is the most common inherited bleeding disorder in humans. The disease is caused by qualitative and quantitative abnormalities of the von Willebrand factor (vWF). Genomic DNA from 25 patients with vWD type III, the most severe form of the disease, was studied using PCR followed by restriction-enzyme analysis and direct sequencing of the products. Nonsense mutations (CGA[yields]TGA) were detected in exons 28, 32, and 45 by screening of all 11 CGA arginine codons of the vWF gene. Two patients were found to be homozygous and five heterozygous for the mutation. Both parents and some of the relatives of the homozygous patients carry the mutation. These are the first reported examples of homozygous point mutations associated with the severe form of vWD. In the three heterozygous probands, one of the parents carried the mutation and had vWD type I. Family studies including parents and family members with or without vWD type I indicted that these three heterozygous patients are likely to be compound heterozygous. Twenty-one individuals from these seven families with vWD type I found to be heterozygous for the mutation. 21 refs., 5 figs., 4 tabs.

  20. Parental concern about vaccine safety in Canadian children partially immunized at age 2: A multivariable model including system level factors

    PubMed Central

    MacDonald, Shannon E; Schopflocher, Donald P; Vaudry, Wendy

    2014-01-01

    Children who begin but do not fully complete the recommended series of childhood vaccines by 2 y of age are a much larger group than those who receive no vaccines. While parents who refuse all vaccines typically express concern about vaccine safety, it is critical to determine what influences parents of ‘partially’ immunized children. This case-control study examined whether parental concern about vaccine safety was responsible for partial immunization, and whether other personal or system-level factors played an important role. A random sample of parents of partially and completely immunized 2 y old children were selected from a Canadian regional immunization registry and completed a postal survey assessing various personal and system-level factors. Unadjusted odds ratios (OR) and adjusted ORs (aOR) were calculated with logistic regression. While vaccine safety concern was associated with partial immunization (OR 7.338, 95% CI 4.138– 13.012), other variables were more strongly associated and reduced the strength of the relationship between concern and partial immunization in multivariable analysis (aOR 2.829, 95% CI 1.151 – 6.957). Other important factors included perceived disease susceptibility and severity (aOR 4.629, 95% CI 2.017 – 10.625), residential mobility (aOR 3.908, 95% CI 2.075 – 7.358), daycare use (aOR 0.310, 95% CI 0.144 - 0.671), number of needles administered at each visit (aOR 7.734, 95% CI 2.598 – 23.025) and access to a regular physician (aOR 0.219, 95% CI 0.057 – 0.846). While concern about vaccine safety may be addressed through educational strategies, this study suggests that additional program and policy-level strategies may positively impact immunization uptake. PMID:25483477

  1. Overview of the Taxonomy of Environmental Types and the Factor Structure of the Salter Environmental Type Assessment.

    ERIC Educational Resources Information Center

    Salter, Daniel W.; Vandiver, Beverly J.

    2002-01-01

    The Salter Environmental Type Assessment (SETA) was created to be a commensurate measure for the Myers-Briggs Type Indicator and to improve the efficacy of the person-environmental interaction paradigm to student affairs. A confirmatory factor analysis of SETA profiles supported the four dimensions in environmental type theory. The utility of this…

  2. Type specimens in the Port Elizabeth Museum, South Africa, including the historically important Albany Museum collection. Part 1: Amphibians.

    PubMed

    Conradie, Werner; Branch, William R; Watson, Gillian

    2015-01-01

    The Port Elizabeth Museum houses the consolidated herpetological collections of three provincial museums of the Eastern Cape, South Africa: the Port Elizabeth Museum (Port Elizabeth), the Amatole (previously Kaffarian) Museum (King Williams Town), and the Albany Museum (Grahamstown). Under John Hewitt, Albany Museum was the main centre of herpetological research in South Africa from 1910-1940, and he described numerous new species, many based on material in the museum collection. The types and other material from the Albany Museum are now incorporated into the Port Elizabeth Museum Herpetology collection (PEM). Due to the vague typification of much of Hewitt's material, the loss of the original catalogues in a fire and the subsequent deterioration of specimen labels, the identification of this type material is often troublesome. Significant herpetological research has been undertaken at the PEM in the last 35 years, and the collection has grown to be the third largest in Africa. During this period, numerous additional types have been deposited in the PEM collection, generated by active taxonomic research in the museum. As a consequence, 43 different amphibian taxa are represented by 37 primary and 151 secondary type specimens in the collection. This catalogue provides the first documentation of these types. It provides the original name, the original publication date, journal number and pagination, reference to illustrations, current name, museum collection number, type locality, notes on the type status, and photographs of all holotypes and lectotypes. Where necessary to maintain nomenclatural stability, and where confused type series are housed in the PEM collection, lectotypes and paralectotypes are nominated. PMID:25947420

  3. Mutations in cardiac T-box factor gene TBX20 are associated with diverse cardiac pathologies, including defects of septation and valvulogenesis and cardiomyopathy.

    PubMed

    Kirk, Edwin P; Sunde, Margaret; Costa, Mauro W; Rankin, Scott A; Wolstein, Orit; Castro, M Leticia; Butler, Tanya L; Hyun, Changbaig; Guo, Guanglan; Otway, Robyn; Mackay, Joel P; Waddell, Leigh B; Cole, Andrew D; Hayward, Christopher; Keogh, Anne; Macdonald, Peter; Griffiths, Lyn; Fatkin, Diane; Sholler, Gary F; Zorn, Aaron M; Feneley, Michael P; Winlaw, David S; Harvey, Richard P

    2007-08-01

    The T-box family transcription factor gene TBX20 acts in a conserved regulatory network, guiding heart formation and patterning in diverse species. Mouse Tbx20 is expressed in cardiac progenitor cells, differentiating cardiomyocytes, and developing valvular tissue, and its deletion or RNA interference-mediated knockdown is catastrophic for heart development. TBX20 interacts physically, functionally, and genetically with other cardiac transcription factors, including NKX2-5, GATA4, and TBX5, mutations of which cause congenital heart disease (CHD). Here, we report nonsense (Q195X) and missense (I152M) germline mutations within the T-box DNA-binding domain of human TBX20 that were associated with a family history of CHD and a complex spectrum of developmental anomalies, including defects in septation, chamber growth, and valvulogenesis. Biophysical characterization of wild-type and mutant proteins indicated how the missense mutation disrupts the structure and function of the TBX20 T-box. Dilated cardiomyopathy was a feature of the TBX20 mutant phenotype in humans and mice, suggesting that mutations in developmental transcription factors can provide a sensitized template for adult-onset heart disease. Our findings are the first to link TBX20 mutations to human pathology. They provide insights into how mutation of different genes in an interactive regulatory circuit lead to diverse clinical phenotypes, with implications for diagnosis, genetic screening, and patient follow-up. PMID:17668378

  4. 25 CFR 170.137 - What types of activities can a recreation, tourism, and trails program include?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... interpretative signs; (4) Provision for non-motorized trail activities including pedestrians and bicycles; (5) Provision for motorized trail activities including all terrain vehicles, motorcycles, snowmobiles, etc.; (6...; (8) Maintenance and restoration of existing recreational trails; (9) Development and...

  5. 25 CFR 170.137 - What types of activities can a recreation, tourism, and trails program include?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... interpretative signs; (4) Provision for non-motorized trail activities including pedestrians and bicycles; (5) Provision for motorized trail activities including all terrain vehicles, motorcycles, snowmobiles, etc.; (6...; (8) Maintenance and restoration of existing recreational trails; (9) Development and...

  6. 25 CFR 170.137 - What types of activities can a recreation, tourism, and trails program include?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... interpretative signs; (4) Provision for non-motorized trail activities including pedestrians and bicycles; (5) Provision for motorized trail activities including all terrain vehicles, motorcycles, snowmobiles, etc.; (6...; (8) Maintenance and restoration of existing recreational trails; (9) Development and...

  7. 25 CFR 170.137 - What types of activities can a recreation, tourism, and trails program include?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... interpretative signs; (4) Provision for non-motorized trail activities including pedestrians and bicycles; (5) Provision for motorized trail activities including all terrain vehicles, motorcycles, snowmobiles, etc.; (6...; (8) Maintenance and restoration of existing recreational trails; (9) Development and...

  8. High processed meat consumption is a risk factor of type 2 diabetes in the ATBC study

    PubMed Central

    Männistö, Satu; Kontto, Jukka; Kataja-Tuomola, Merja; Albanes, Demetrius; Virtamo, Jarmo

    2012-01-01

    Relatively small lifestyle modifications related to weight reduction, physical activity and diet has been shown to decrease the risk of type 2 diabetes. Connected with diet, low consumption of meat has been suggested as a protective factor of diabetes. The aim was to examine the association between the consumption of total meat or the specific types of meat and risk of type 2 diabetes. The ATBC cohort included middle aged male smokers. During up to 12 years of follow-up, 1098 incident cases of diabetes were diagnosed from 24,845 participants through the nationwide register. Food consumption was assessed by a validated food frequency questionnaire. In the age and intervention group adjusted model, high total meat consumption was a risk factor of type 2 diabetes (relative risk (RR) 1.50, 95% confidence interval (CI): 1.23, 1.82, highest vs. lowest quintile). The result was similar after adjustment for environmental factors and foods related to diabetes and meat consumption. The RR of type 2 diabetes was 1.37 for processed meat (95% CI: 1.11, 1.71) in the multivariate model. The results were explained more by intakes of sodium than intakes of saturated fatty acids, protein, cholesterol, heme iron, magnesium and nitrate, and were not modified by obesity. No association was found between red meat, poultry and the risk of type 2 diabetes. In conclusion, it may help to prevent the global epidemic of type 2 diabetes by reducing the consumption of processed meat. It seems that sodium of processed meat may explain the association. PMID:20187985

  9. Factors determining insulin requirements in women with type 1 diabetes mellitus during pregnancy: a review

    PubMed Central

    McIntyre, Harold David; Callaway, Leonie

    2014-01-01

    Most women with type 1 diabetes mellitus (T1DM) have increased insulin requirements during pregnancy. However, a minority of women have a fall in insulin requirements. When this occurs in late gestation, it often provokes concern regarding possible compromise of the feto-placental unit. In some centres, this is considered as an indication for delivery, including premature delivery. There are, however, many other factors that affect insulin requirements in pregnancy in women with type 1 diabetes mellitus and the decline in insulin requirements may represent a variant of normal pregnancy. If there is no underlying pathological process, expedited delivery in these women is not warranted and confers increased risks to the newborn. We will explore the factors affecting insulin requirements in gestation in this review. We will also discuss some novel concepts regarding beta-cell function in pregnancy.

  10. Estimation of Cell-Type Composition Including T and B Cell Subtypes for Whole Blood Methylation Microarray Data

    PubMed Central

    Waite, Lindsay L.; Weaver, Benjamin; Day, Kenneth; Li, Xinrui; Roberts, Kevin; Gibson, Andrew W.; Edberg, Jeffrey C.; Kimberly, Robert P.; Absher, Devin M.; Tiwari, Hemant K.

    2016-01-01

    DNA methylation levels vary markedly by cell-type makeup of a sample. Understanding these differences and estimating the cell-type makeup of a sample is an important aspect of studying DNA methylation. DNA from leukocytes in whole blood is simple to obtain and pervasive in research. However, leukocytes contain many distinct cell types and subtypes. We propose a two-stage model that estimates the proportions of six main cell types in whole blood (CD4+ T cells, CD8+ T cells, monocytes, B cells, granulocytes, and natural killer cells) as well as subtypes of T and B cells. Unlike previous methods that only estimate overall proportions of CD4+ T cell, CD8+ T cells, and B cells, our model is able to estimate proportions of naïve, memory, and regulatory CD4+ T cells as well as naïve and memory CD8+ T cells and naïve and memory B cells. Using real and simulated data, we are able to demonstrate that our model is able to reliably estimate proportions of these cell types and subtypes. In studies with DNA methylation data from Illumina's HumanMethylation450k arrays, our estimates will be useful both for testing for associations of cell type and subtype composition with phenotypes of interest as well as for adjustment purposes to prevent confounding in epigenetic association studies. Additionally, our method can be easily adapted for use with whole genome bisulfite sequencing (WGBS) data or any other genome-wide methylation data platform. PMID:26925097

  11. Some flow phenomena in a constant area duct with a Borda type inlet including the critical region

    NASA Technical Reports Server (NTRS)

    Hendricks, R. C.; Simoneau, R. J.

    1978-01-01

    Mass limiting flow characteristics for a 55 L/D tube with a Borda type inlet were assessed over large ranges of temperature and pressure, using fluid nitrogen. Under certain conditions, separation and pressure drop at the inlet was sufficiently strong to permit partial vaporization and the remaining fluid flowed through the tube as if it were a free jet. An empirical relation was determined which defines conditions under which this type of flow can occur. A flow coefficient is presented which enables estimations of flow rates over the experimental range. A flow rate stagnation pressure map for selected stagnation isotherms and pressure profiles document these flow phenomena.

  12. Biochemical and proteomic analysis of spliceosome factors interacting with intron-1 of human papillomavirus type-16.

    PubMed

    Martínez-Salazar, Martha; López-Urrutia, Eduardo; Arechaga-Ocampo, Elena; Bonilla-Moreno, Raul; Martínez-Castillo, Macario; Díaz-Hernández, Job; Del Moral-Hernández, Oscar; Cedillo-Barrón, Leticia; Martines-Juarez, Víctor; De Nova-Ocampo, Monica; Valdes, Jesús; Berumen, Jaime; Villegas-Sepúlveda, Nicolás

    2014-12-01

    The human papillomavirus type 16 (HPV-16) E6/E7 spliced transcripts are heterogeneously expressed in cervical carcinoma. The heterogeneity of the E6/E7 splicing profile might be in part due to the intrinsic variation of splicing factors in tumor cells. However, the splicing factors that bind the E6/E7 intron 1 (In-1) have not been defined. Therefore, we aimed to identify these factors; we used HeLa nuclear extracts (NE) for in vitro spliceosome assembly. The proteins were allowed to bind to an RNA/DNA hybrid formed by the In-1 transcript and a 5'-biotinylated DNA oligonucleotide complementary to the upstream exon sequence, which prevented interference in protein binding to the intron. The hybrid probes bound with the nuclear proteins were coupled to streptavidin magnetic beads for chromatography affinity purification. Proteins were eluted and identified by mass spectrometry (MS). Approximately 170 proteins were identified by MS, 80% of which were RNA binding proteins, including canonical spliceosome core components, helicases and regulatory splicing factors. The canonical factors were identified as components of the spliceosomal B-complex. Although 35-40 of the identified factors were cognate splicing factors or helicases, they have not been previously detected in spliceosome complexes that were assembled using in vivo or in vitro models. PMID:25108200

  13. 43 CFR 404.9 - What types of infrastructure and facilities may be included in an eligible rural water supply...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... may be included in an eligible rural water supply project? 404.9 Section 404.9 Public Lands: Interior Regulations Relating to Public Lands BUREAU OF RECLAMATION, DEPARTMENT OF THE INTERIOR RECLAMATION RURAL WATER... eligible rural water supply project? A rural water supply project may include, but is not limited to,...

  14. Upstream stimulatory factor activates the vasopressin promoter via multiple motifs, including a non-canonical E-box.

    PubMed Central

    Coulson, Judy M; Edgson, Jodie L; Marshall-Jones, Zoe V; Mulgrew, Robert; Quinn, John P; Woll, Penella J

    2003-01-01

    We have described previously a complex E-box enhancer (-147) of the vasopressin promoter in small-cell lung cancer (SCLC) extracts [Coulson, Fiskerstrand, Woll and Quinn, (1999) Biochem. J. 344, 961-970]. Upstream stimulatory factor (USF) heterodimers were one of the complexes binding to this site in vitro. We now report that USF overexpression in non-SCLC (NSCLC) cells can functionally activate vasopressin promoter-driven reporters that are otherwise inactive in this type of lung cancer cell. Site-directed mutagenesis and electrophoretic mobility-shift analysis demonstrate that although the -147 E-box contributes, none of the previously predicted E-boxes (-147, -135, -34) wholly account for this USF-mediated activation in NSCLC. 5' Deletion showed the key promoter region as -52 to +42; however, USF-2 binding was not reliant on the -34 E-box, but on a novel adjacent CACGGG non-canonical E-box at -42 (motif E). This mediated USF binding in both SCLC and USF-2-transfected NSCLC cells. Mutation of motif E or the non-canonical TATA box abolished activity, implying both are required for transcriptional initiation on overexpression of USF-2. Co-transfected dominant negative USF confirmed that binding was required through motif E for function, but that the classical activation domain of USF was not essential. USF-2 bound motif E with 10-fold lower affinity than the -147 E-box. In NSCLC, endogenous USF-2 expression is low, and this basal level appears to be insufficient to activate transcription of arginine vasopressin (AVP). In summary, we have demonstrated a novel mechanism for USF activation, which contributes to differential vasopressin expression in lung cancer. PMID:12403649

  15. Keratinocyte growth factor and hepatocyte growth factor/scatter factor are heparin-binding growth factors for alveolar type II cells in fibroblast-conditioned medium.

    PubMed Central

    Panos, R J; Rubin, J S; Csaky, K G; Aaronson, S A; Mason, R J

    1993-01-01

    Epithelial-mesenchymal interactions mediate aspects of normal lung growth and development and are important in the restoration of normal alveolar architecture after lung injury. To determine if fibroblasts are a source of soluble growth factors for alveolar type II cells, we investigated the effect of fibroblast-conditioned medium (CM) on alveolar type II cell DNA synthesis. Serum-free CM from confluent adult human lung fibroblasts was concentrated fivefold by lyophilization. Type II cells were isolated from adult rats by elastase dissociation and incubated with [3H]thymidine and varying dilutions of concentrated CM and serum from day 1 to 3 of culture. Stimulation of type II cell DNA synthesis by fibroblast-CM was maximal after 48 h of conditioning and required the presence of serum. The activity of the CM was eliminated by boiling and by treatment with trypsin, pepsin, or dithiothreitol and was additive with saturating concentrations of acidic fibroblast growth factor, epidermal growth factor, and insulin. The growth factor activity bound to heparin-Sepharose and was eluted with 0.6 and 1.0 M NaCl. Neutralizing antibody studies demonstrated that the primary mitogens isolated in the 0.6 and 1.0 M NaCl fractions were keratinocyte growth factor (KGF, fibroblast growth factor 7) and hepatocyte growth factor/scatter factor (HGF/SF), respectively. HGF/SF was demonstrated in the crude CM and KGF was detected in the 0.6 M NaCl eluent by immunoblotting. Northern blot analysis confirmed that the lung fibroblasts expressed both KGF and HGF/SF transcripts. Human recombinant KGF and HGF/SF induced a concentration- and serum-dependent increase in rat alveolar type II cell DNA synthesis. We conclude that adult human lung fibroblasts produce at least two soluble heparin-binding growth factors, KGF and HGF/SF, which promote DNA synthesis and proliferation of rat alveolar type II cells in primary culture. KGF and HGF/SF may be important stimuli for alveolar type II cell

  16. A patient with refractory shock induced by several factors, including obstruction because of a posterior mediastinal hematoma.

    PubMed

    Obinata, Mariko; Ishikawa, Kouhei; Osaka, Hiromichi; Mishima, Kentaro; Omori, Kazuhiko; Oode, Yasumasa; Yanagawa, Youichi

    2015-06-01

    A 44-year-old man who drove a motorcycle experienced a collision with the side of another motorcycle. Because he had sustained a high-energy injury to the spinal cord, he was transferred to our hospital. His circulation was unstable, and received tracheal intubation in addition to thoracostomy for the hemothorax. Whole-body computed tomography (CT) revealed multiple fractures, right hemopneumothorax with pulmonary contusion, and minor liver injury. After infusing 5000 mL of lactated Ringer's solution and 10 units of blood, his circulation remained unstable. On a repeat CT examination, the left atrium was found to be compressed by a posterior mediastinal hematoma induced by the fracture of the thoracic spine, and a diagnosis of shock induced by multiple factors, including hemorrhagic, neurogenic, and obstructive mechanisms, was made. After obtaining stable circulation and respirations, internal fixation of the extremities and extubation were performed on the 12th hospital day. Chest CT performed on the 27th day showed the disappearance of compression of the left atrium by the hematoma. PMID:25572646

  17. School factors as barriers to and facilitators of a preventive intervention for pediatric type 2 diabetes.

    PubMed

    Hall, William J; Schneider, Margaret; Thompson, Deborah; Volpe, Stella L; Steckler, Allan; Hall, John M; Fisher, M Randall

    2014-06-01

    School-based interventions are essential to prevent pediatric obesity and type 2 diabetes. School environmental factors influence implementation of these interventions. This article examines how school factors acted as barriers to and facilitators of the HEALTHY intervention. The HEALTHY study was a cluster-randomized trial of a multicomponent intervention implemented in 21 schools. Interview data were analyzed to identify barriers and facilitators. Barriers included teacher frustration that intervention activities detracted from tested subjects, student resistance and misbehavior, classroom management problems, communication equipment problems, lack of teacher/staff engagement, high cost and limited availability of nutritious products, inadequate facility space, and large class sizes. Facilitators included teacher/staff engagement, effective classroom management, student engagement, schools with direct control over food service, support from school leaders, and adequate facilities and equipment. Contextual barriers and facilitators must be taken into account in the design and implementation of school-based health interventions. PMID:24904696

  18. Spanish public awareness regarding DNA profile databases in forensic genetics: what type of DNA profiles should be included?

    PubMed Central

    Gamero, Joaquín J; Romero, Jose‐Luis; Peralta, Juan‐Luis; Carvalho, Mónica; Corte‐Real, Francisco

    2007-01-01

    The importance of non‐codifying DNA polymorphism for the administration of justice is now well known. In Spain, however, this type of test has given rise to questions in recent years: (a) Should consent be obtained before biological samples are taken from an individual for DNA analysis? (b) Does society perceive these techniques and methods of analysis as being reliable? (c) There appears to be lack of knowledge concerning the basic norms that regulate databases containing private or personal information and the protection that information of this type must be given. This opinion survey and the subsequent analysis of the results in ethical terms may serve to reveal the criteria and the degree of information that society has with regard to DNA databases. In the study, 73.20% (SE 1.12%) of the population surveyed was in favour of specific legislation for computer files in which DNA analysis results for forensic purposes are stored. PMID:17906059

  19. Optimizing staining protocols for laser microdissection of specific cell types from the testis including carcinoma in situ.

    PubMed

    Sonne, Si Brask; Dalgaard, Marlene D; Nielsen, John Erik; Hoei-Hansen, Christina E; Rajpert-De Meyts, Ewa; Gjerdrum, Lise Mette; Leffers, Henrik

    2009-01-01

    Microarray and RT-PCR based methods are important tools for analysis of gene expression; however, in tissues containing many different cells types, such as the testis, characterization of gene expression in specific cell types can be severely hampered by noise from other cells. The laser microdissection technology allows for enrichment of specific cell types. However, when the cells are not morphologically distinguishable, it is necessary to use a specific staining method for the target cells. In this study we have tested different fixatives, storage conditions for frozen sections and staining protocols, and present two staining protocols for frozen sections, one for fast and specific staining of fetal germ cells, testicular carcinoma in situ cells, and other cells with embryonic stem cell-like properties that express the alkaline phosphatase, and one for specific staining of lipid droplet-containing cells, which is useful for isolation of the androgen-producing Leydig cells. Both protocols retain a morphology that is compatible with laser microdissection and yield RNA of a quality suitable for PCR and microarray analysis. PMID:19436754

  20. Use of Q-Type Factor Analysis with the Aged.

    ERIC Educational Resources Information Center

    Kleban, Morton H.; And Others

    This paper explores Q-Factor Analysis as a method of organizing data on a large array of variables to describe a group of aged Ss. Forty-seven males, specially selected for their good health (Mean Age: 71.5; SD: 4.8) were measured on 550 biological and behavioral variables. A Q-Factor Analysis was calculated, using a S by variable matrix, which is…

  1. The functions of the A1A2A3 domains in von Willebrand factor include multimerin 1 binding.

    PubMed

    Parker, D'Andra N; Tasneem, Subia; Farndale, Richard W; Bihan, Dominique; Sadler, J Evan; Sebastian, Silvie; de Groot, Philip G; Hayward, Catherine P M

    2016-07-01

    Multimerin 1 (MMRN1) is a massive, homopolymeric protein that is stored in platelets and endothelial cells for activation-induced release. In vitro, MMRN1 binds to the outer surfaces of activated platelets and endothelial cells, the extracellular matrix (including collagen) and von Willebrand factor (VWF) to support platelet adhesive functions. VWF associates with MMRN1 at high shear, not static conditions, suggesting that shear exposes cryptic sites within VWF that support MMRN1 binding. Modified ELISA and surface plasmon resonance were used to study the structural features of VWF that support MMRN1 binding, and determine the affinities for VWF-MMRN1 binding. High shear microfluidic platelet adhesion assays determined the functional consequences for VWF-MMRN1 binding. VWF binding to MMRN1 was enhanced by shear exposure and ristocetin, and required VWF A1A2A3 region, specifically the A1 and A3 domains. VWF A1A2A3 bound to MMRN1 with a physiologically relevant binding affinity (KD: 2.0 ± 0.4 nM), whereas the individual VWF A1 (KD: 39.3 ± 7.7 nM) and A3 domains (KD: 229 ± 114 nM) bound to MMRN1 with lower affinities. VWF A1A2A3 was also sufficient to support the adhesion of resting platelets to MMRN1 at high shear, by a mechanism dependent on VWF-GPIbα binding. Our study provides new information on the molecular basis of MMRN1 binding to VWF, and its role in supporting platelet adhesion at high shear. We propose that at sites of vessel injury, MMRN1 that is released following activation of platelets and endothelial cells, binds to VWF A1A2A3 region to support platelet adhesion at arterial shear rates. PMID:27052467

  2. Transcription factor Bcl11b controls identity and function of mature innate lymphoid cells type II

    PubMed Central

    Califano, Danielle; Cho, Jonathan J.; Uddin, Mohammad N.; Lorentsen, Kyle J.; Yang, Qi; Bhandoola, Avinash; Li, Hongmin; Avram, Dorina

    2015-01-01

    Summary Type-2 innate lymphoid cells (ILC2s) promote anti-helminth responses and contribute to allergies. Here we report that Bcl11b, previously considered a T-cell lineage identity transcription factor, acts directly upstream of the key ILC2 transcription factor Gfi1 to maintain its expression in mature ILC2s. Consequently, Bcl11b−/− ILC2s downregulated Gata3 and downstream genes, including Il1rl1, encoding IL-33 receptor, and upregulated Rorc and type-3 ILC (ILC3) genes. Additionally, independent of Gfi1, Bcl11b directly repressed expression of the ILC3 transcription factor Ahr, further contributing to silencing of ILC3 genes in ILC2s. Thus, Bcl11b−/− ILC2s lost their functions and gained ILC3 functions, expanding in response to the protease allergen papain, while at the same time producing ILC3, and not ILC2 cytokines, and causing increased airway infiltration of neutrophils instead of eosinophils. Our results broaden Bcl11b's role from a T-cell only transcription factor, and establish that Bcl11b sustains mature ILC2 genetic and functional programs and lineage fidelity. PMID:26231117

  3. The Role of Economic Factors, Including the Level of Tuition, in Individual University Participation Decisions in Canada

    ERIC Educational Resources Information Center

    Johnson, David R.; Rahman, Fiona T.

    2005-01-01

    The study uses individual data from the Canadian Labour Force Survey to consider economic factors in university participation decisions by persons aged 17-24 from 1976 to 2003. The level of real tuition is one economic factor that may affect the university participation decision. There is also regional variation in the opportunity cost of…

  4. Curriculum Type as a Differentiating Factor in Medical Licensing Examinations.

    ERIC Educational Resources Information Center

    Shen, Linjun

    This study assessed the effects of the type of medical curriculum on differential item functioning (DIF) and group differences at the test level in Level 1 of the Comprehensive Osteopathic Medical Licensing Examinations (COMLEX). The study also explored the relationship of the DIF and group differences at the test level. There are generally two…

  5. P-Type Factor Analyses of Individuals' Thought Sampling Data.

    ERIC Educational Resources Information Center

    Hurlburt, Russell T.; Melancon, Susan M.

    Recently, interest in research measuring stream of consciousness or thought has increased. A study was conducted, based on a previous study by Hurlburt, Lech, and Saltman, in which subjects were randomly interrupted to rate their thoughts and moods on a Likert-type scale. Thought samples were collected from 27 subjects who carried random-tone…

  6. 43 CFR 404.10 - Are there certain types of infrastructure and facilities that may not be included in a rural...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 43 Public Lands: Interior 1 2013-10-01 2013-10-01 false Are there certain types of infrastructure... RECLAMATION RURAL WATER SUPPLY PROGRAM Overview § 404.10 Are there certain types of infrastructure and... not include: (a) Any infrastructure or facilities that would deliver water for commercial...

  7. 43 CFR 404.10 - Are there certain types of infrastructure and facilities that may not be included in a rural...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 43 Public Lands: Interior 1 2012-10-01 2011-10-01 true Are there certain types of infrastructure... RECLAMATION RURAL WATER SUPPLY PROGRAM Overview § 404.10 Are there certain types of infrastructure and... not include: (a) Any infrastructure or facilities that would deliver water for commercial...

  8. 43 CFR 404.10 - Are there certain types of infrastructure and facilities that may not be included in a rural...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Are there certain types of infrastructure... RECLAMATION RURAL WATER SUPPLY PROGRAM Overview § 404.10 Are there certain types of infrastructure and... not include: (a) Any infrastructure or facilities that would deliver water for commercial...

  9. 43 CFR 404.10 - Are there certain types of infrastructure and facilities that may not be included in a rural...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 43 Public Lands: Interior 1 2011-10-01 2011-10-01 false Are there certain types of infrastructure... RECLAMATION RURAL WATER SUPPLY PROGRAM Overview § 404.10 Are there certain types of infrastructure and... not include: (a) Any infrastructure or facilities that would deliver water for commercial...

  10. 42 CFR 137.202 - What types of information will Self-Governance Tribes be expected to include in the reports?

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 1 2013-10-01 2013-10-01 false What types of information will Self-Governance... SELF-GOVERNANCE Operational Provisions Health Status Reports § 137.202 What types of information will Self-Governance Tribes be expected to include in the reports? Reports will be derived from...

  11. 42 CFR 137.202 - What types of information will Self-Governance Tribes be expected to include in the reports?

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 1 2014-10-01 2014-10-01 false What types of information will Self-Governance... SELF-GOVERNANCE Operational Provisions Health Status Reports § 137.202 What types of information will Self-Governance Tribes be expected to include in the reports? Reports will be derived from...

  12. 42 CFR 137.202 - What types of information will Self-Governance Tribes be expected to include in the reports?

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false What types of information will Self-Governance... SELF-GOVERNANCE Operational Provisions Health Status Reports § 137.202 What types of information will Self-Governance Tribes be expected to include in the reports? Reports will be derived from...

  13. 42 CFR 137.202 - What types of information will Self-Governance Tribes be expected to include in the reports?

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false What types of information will Self-Governance... SELF-GOVERNANCE Operational Provisions Health Status Reports § 137.202 What types of information will Self-Governance Tribes be expected to include in the reports? Reports will be derived from...

  14. 42 CFR 137.202 - What types of information will Self-Governance Tribes be expected to include in the reports?

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false What types of information will Self-Governance... SELF-GOVERNANCE Operational Provisions Health Status Reports § 137.202 What types of information will Self-Governance Tribes be expected to include in the reports? Reports will be derived from...

  15. Hydrogeomorphic Classification of Wetlands on Mt. Desert Island, Maine, Including Hydrologic Susceptibility Factors for Wetlands in Acadia National Park

    USGS Publications Warehouse

    Nielsen, Martha G.

    2006-01-01

    The U.S. Geological Survey, in cooperation with the National Park Service, developed a hydrogeomorphic (HGM) classification system for wetlands greater than 0.4 hectares (ha) on Mt. Desert Island, Maine, and applied this classification using map-scale data to more than 1,200 mapped wetland units on the island. In addition, two hydrologic susceptibility factors were defined for a subset of these wetlands, using 11 variables derived from landscape-scale characteristics of the catchment areas of these wetlands. The hydrologic susceptibility factors, one related to the potential hydrologic pathways for contaminants and the other to the susceptibility of wetlands to disruptions in water supply from projected future changes in climate, were used to indicate which wetlands (greater than 1 ha) in Acadia National Park (ANP) may warrant further investigation or monitoring. The HGM classification system consists of 13 categories: Riverine-Upper Perennial, Riverine-Nonperennial, Riverine- Tidal, Depressional-Closed, Depressional-Semiclosed, Depressional-Open, Depressional-No Ground-Water Input, Mineral Soil Flat, Organic Soil Flat, Tidal Fringe, Lacustrine Fringe, Slope, and Hilltop/Upper Hillslope. A dichotomous key was developed to aid in the classification of wetlands. The National Wetland Inventory maps produced by the U.S. Fish and Wildlife Service provided the wetland mapping units used for this classification. On the basis of topographic map information and geographic information system (GIS) layers at a scale of 1:24,000 or larger, 1,202 wetland units were assigned a preliminary HGM classification. Two of the 13 HGM classes (Riverine-Tidal and Depressional-No Ground-Water Input) were not assigned to any wetlands because criteria for determining those classes are not available at that map scale, and must be determined by more site-specific information. Of the 1,202 wetland polygons classified, which cover 1,830 ha in ANP, 327 were classified as Slope, 258 were

  16. Effects of botulinum toxin type D on secretion of tumor necrosis factor from human monocytes

    SciTech Connect

    Imamura, K.; Spriggs, D.; Ohno, T.; Kufe, D.

    1989-05-01

    Botulinum toxins are potent neurotoxins which block the release of neurotransmitters. The effects of these toxins on hematopoietic cells, however, are unknown. Monocytes secrete a variety of polypeptide growth factors, including tumor necrosis factor (TNF). In the study reported here, the effects of botulinum toxin type D on the secretion of TNF from human monocytes were examined. The results demonstrate that biotulinum toxin type D inhibits the release of TNF from monocytes activated by lipopolysaccharide (LPS) but not by 12-O-tetradecanoylphorbol-13-acetate. Botulinum toxin type D had no detectable effect on intracellular TNF levels in LPS-treated monocytes, indicating that the effects of this toxin involve the secretory process. This inhibitory effect of botulinum toxin type D on TNF secretion from LPS-treated monocytes was partially reversed by treatment with 12-O-tetradecanoylphorbol-13-acetate or introduction of guanosine 5'-(/gamma/-thio)t-riphosphate into these cells. The results demonstrate that TNF secretion is regulated by at least two distinct guanine nucleotide-binding proteins, one responsible for the activation of phospholiphase C and another which acts as a substrate for botulinum toxin type D. ADP-ribosylation of monocyte membranes by botulinum toxin type D demonstrated the presence of three substrates with M/sub r/s of 45,000, 21,000, and 17,000. While the role of these substrates in exocytosis is unknown, the results suggest that the M/sub r/ 21,000 substrate is involved in a process other than TNF secretion.

  17. Phenotype of the fibroblast growth factor receptor 2 Ser351Cys mutation: Pfeiffer syndrome type III.

    PubMed

    Gripp, K W; Stolle, C A; McDonald-McGinn, D M; Markowitz, R I; Bartlett, S P; Katowitz, J A; Muenke, M; Zackai, E H

    1998-07-24

    We present a patient with pansynostosis, hydrocephalus, seizures, extreme proptosis with luxation of the eyes out of the lids, apnea and airway obstruction, intestinal non-rotation, and severe developmental delay. His skeletal abnormalities include bilateral elbow ankylosis, radial head dislocation, and unilateral broad and deviated first toe. The phenotype of this patient is consistent with that previously reported in Pfeiffer syndrome type III, but is unusual for the lack of broad thumbs. Our patient most closely resembles the case described by Kerr et al. [1996: Am J Med Genet 66:138-143] as Pfeiffer syndrome type III with normal thumbs. Mutations in the genes for fibroblast growth factor receptors (FGFR) 1 and 2 have previously been seen in patients with Pfeiffer syndrome type I. The mutation identified in our patient, Ser351Cys in FGFR2, represents the first reported cause of Pfeiffer syndrome type III. An identical mutation was described once previously by Pulleyn et al., in a patient whose brief clinical description included cloverleaf skull, significant developmental delay, and normal hands and feet [Eur. J. Hum. Genet. 4: 283-291, 1996]. In our patient, previously performed single-strand conformation polymorphism analysis failed to detect a band shift; the mutation was identified only after independent sequence analysis. PMID:9714439

  18. Improvement of surface functionalities, including allergenicity attenuation, of whole buckwheat protein fraction by maillard-type glycation with dextran.

    PubMed

    Tazawa, Shigeru; Katayama, Shigeru; Hirabayashi, Masahiro; Yamaguchi, Daiki; Nakamura, Soichiro

    2014-12-01

    The purpose of the current study was to determine the effects of the introduction of polysaccharide chains onto the molecular surface of buckwheat proteins on buckwheat protein surface functionality. The whole buckwheat protein fraction (WBP) was prepared using 50 mM phosphate buffer (pH 7.5) containing 0.5 M NaCl and covalently linked with 6 kDa, 17.5 kDa, 40 kDa, 70 kDa, or 200 kDa dextran by Maillard-type glycation through controlled dry-heating at 60°C and 79% relative humidity for two weeks. Conjugation with 40 kDa dextran improved the water solubility and emulsifying properties of WBP without causing a serious loss of available lysine; 84.9% of the free amino groups were conserved. In addition, we found that the introduction of dextran chains onto the molecular surfaces of WBP attenuated the antigenicity of WBP. PMID:25580398

  19. [Alimentary trigger factors that provoke migraine and tension-type headache].

    PubMed

    Holzhammer, J; Wöber, C

    2006-04-01

    Based on a review of the literature the authors discuss the role of nutrition in the precipitation of migraine and tension-type headache (TTH). The available information relies largely on the subjective assessment of the patients. Controlled trials suggest that alcohol and caffeine withdrawal are the most important nutritional precipitating factors of migraine and TTH. In addition, there is some evidence that missing meals is also an important factor. Dehydration seems to deserve more attention. A selective sensitivity to red wine has been shown in some patients, the importance of chocolate has been doubted seriously, and scientific evidence for cheese as a precipitating factor is lacking. Despite a series of experimental studies demonstrating that NO donors such as nitroglycerin and parenteral histamine cause headache the role of histamine, nitrates, and nitrites in food remains unclear. Similarly, other biogenic amines and aspartame have not been proven to precipitate headache. Sodium glutamate causes adverse reactions including headache probably at large doses ingested on an empty stomach. Therefore, patients should be advised that food plays a limited role as a precipitating factor of migraine and TTH. Subjective sensitivity to certain foods should be examined critically, and proven precipitating factors should be avoided. General dietary restrictions have not been proven to be useful. PMID:15806385

  20. An Examination of the Factor Structure of Four of the Cognitive Abilities Included in the Educational Testing Service Kit of Factor-Referenced Cognitive Tests.

    ERIC Educational Resources Information Center

    Babcock, Renee L.; Laguna, Kerrie

    1997-01-01

    The Educational Testing Service Kit of Factor-Referenced Cognitive Tests contains 72 tests that are supposed to be markers of 23 latent cognitive constructs. Examination of the factor structure of four of these tests with 165 undergraduates suggests caution in using the measures as markers of distinct factors. (SLD)

  1. The Insulin-Like Growth Factor System in Obesity, Insulin Resistance and Type 2 Diabetes Mellitus

    PubMed Central

    Lewitt, Moira S.; Dent, Mairi S.; Hall, Kerstin

    2014-01-01

    The insulin-like growth factor (IGF) system, acting in concert with other hormone axes, is important in normal metabolism. In obesity, the hyperinsulinaemia that accompanies peripheral insulin resistance leads to reduced growth hormone (GH) secretion, while total IGF-I levels are relatively unchanged due to increased hepatic GH sensitivity. IGF-binding protein (IGFBP)-1 levels are suppressed in relation to the increase in insulin levels in obesity and low levels predict the development of type 2 diabetes several years later. Visceral adiposity and hepatic steatosis, along with a chronic inflammation, contribute to the IGF system phenotype in individuals with metabolic syndrome and type 2 diabetes mellitus, including changes in the normal inverse relationship between IGFBP-1 and insulin, with IGFBP-1 concentrations that are inappropriately normal or elevated. The IGF system is implicated in the vascular and other complications of these disorders and is therefore a potential therapeutic target. PMID:26237614

  2. Innate and Adaptive Factors Regulating Human Immunodeficiency Virus Type 1 Genomic Activation

    PubMed Central

    Shah, Sonia; Nonnemacher, Michael R.; Pirrone, Vanessa; Wigdahl, Brian

    2011-01-01

    Over the past decade, antiretroviral therapy targeting the viral entry process, reverse transcriptase, integrase, and protease, has prolonged the lives of people infected with human immunodeficiency virus type 1 (HIV-1). However, despite the development of more effective therapeutic strategies, reservoirs of viral infection remain. This review discusses molecular mechanisms surrounding the development of latency from the site of integration to pre- and post-integration maintenance of latency, including epigenetic factors. In addition, an overview of innate and adaptive cells important to HIV-1 infection are examined from the viewpoint of cytokines released and cytokines that act on these cells to explore an overall understanding of HIV-1 proviral genome activation. Finally, this review is discussed from the viewpoint of how an understanding of the interplay of all of these factors will help guide the next generation of therapies. PMID:20387125

  3. Calculation of heat transfer on shuttle type configurations including the effects of variable entropy at boundary layer edge

    NASA Technical Reports Server (NTRS)

    Dejarnette, F. R.

    1972-01-01

    A relatively simple method is presented for including the effect of variable entropy at the boundary-layer edge in a heat transfer method developed previously. For each inviscid surface streamline an approximate shockwave shape is calculated using a modified form of Maslen's method for inviscid axisymmetric flows. The entropy for the streamline at the edge of the boundary layer is determined by equating the mass flux through the shock wave to that inside the boundary layer. Approximations used in this technique allow the heating rates along each inviscid surface streamline to be calculated independent of the other streamlines. The shock standoff distances computed by the present method are found to compare well with those computed by Maslen's asymmetric method. Heating rates are presented for blunted circular and elliptical cones and a typical space shuttle orbiter at angles of attack. Variable entropy effects are found to increase heating rates downstream of the nose significantly higher than those computed using normal-shock entropy, and turbulent heating rates increased more than laminar rates. Effects of Reynolds number and angles of attack are also shown.

  4. Practical Ranges of Loudness Levels of Various Types of Environmental Noise, Including Traffic Noise, Aircraft Noise, and Industrial Noise

    PubMed Central

    Salomons, Erik M.; Janssen, Sabine A.

    2011-01-01

    In environmental noise control one commonly employs the A-weighted sound level as an approximate measure of the effect of noise on people. A measure that is more closely related to direct human perception of noise is the loudness level. At constant A-weighted sound level, the loudness level of a noise signal varies considerably with the shape of the frequency spectrum of the noise signal. In particular the bandwidth of the spectrum has a large effect on the loudness level, due to the effect of critical bands in the human hearing system. The low-frequency content of the spectrum also has an effect on the loudness level. In this note the relation between loudness level and A-weighted sound level is analyzed for various environmental noise spectra, including spectra of traffic noise, aircraft noise, and industrial noise. From loudness levels calculated for these environmental noise spectra, diagrams are constructed that show the relation between loudness level, A-weighted sound level, and shape of the spectrum. The diagrams show that the upper limits of the loudness level for broadband environmental noise spectra are about 20 to 40 phon higher than the lower limits for narrowband spectra, which correspond to the loudness levels of pure tones. The diagrams are useful for assessing limitations and potential improvements of environmental noise control methods and policy based on A-weighted sound levels. PMID:21776205

  5. Practical ranges of loudness levels of various types of environmental noise, including traffic noise, aircraft noise, and industrial noise.

    PubMed

    Salomons, Erik M; Janssen, Sabine A

    2011-06-01

    In environmental noise control one commonly employs the A-weighted sound level as an approximate measure of the effect of noise on people. A measure that is more closely related to direct human perception of noise is the loudness level. At constant A-weighted sound level, the loudness level of a noise signal varies considerably with the shape of the frequency spectrum of the noise signal. In particular the bandwidth of the spectrum has a large effect on the loudness level, due to the effect of critical bands in the human hearing system. The low-frequency content of the spectrum also has an effect on the loudness level. In this note the relation between loudness level and A-weighted sound level is analyzed for various environmental noise spectra, including spectra of traffic noise, aircraft noise, and industrial noise. From loudness levels calculated for these environmental noise spectra, diagrams are constructed that show the relation between loudness level, A-weighted sound level, and shape of the spectrum. The diagrams show that the upper limits of the loudness level for broadband environmental noise spectra are about 20 to 40 phon higher than the lower limits for narrowband spectra, which correspond to the loudness levels of pure tones. The diagrams are useful for assessing limitations and potential improvements of environmental noise control methods and policy based on A-weighted sound levels. PMID:21776205

  6. Ultrasound measurement of peripheral endothelial dysfunction in type 2 diabetic patients: correlation with risk factors.

    PubMed

    Bosevski, Marijan; Georgievska-Ismail, Ljubica

    2010-05-01

    The purpose of the study was to assess the endothelial dysfunction (ED) in type 2 diabetic patients ultrasonographically and estimate the correlation of ED with glycemia and other cardio-metabolic risk factors. 171 patient (age 60.0 + 8.5 years) with diagnosed type 2 diabetes and coronary artery disease (CAD) were randomly included in a cross sectional study. B-mode ultrasound system with a linear transducer of 7.5 MHz was used for evaluation of flow-mediated vasodilation in brachial artery (FMV). FMV was presented as a change of brachial artery diameter at rest and after limb ischemia, previously provoked by cuff inflation. Peripheral ED was found in 77.2% (132 patients). Multivariate logistic regression model defined: age (OR 1.071, 95% CI 1.003 1,143) and plasma cholesterol (OR 4.083 95% CI 1.080 17,017) as determinants for ED. Linear multivariate analysis presented duration of diabetes (Beta 0.173, Sig 0.024), and glycemia (Beta 0.132, Sig 0.044) to be associated independently with FMV value. Estimated factors influencing FMV, might be potential therapeutic targets for presented endothelial dysfunction in type 2 diabetic patients with coronary artery disease. PMID:20507285

  7. Relationship of Food Security with Type 2 Diabetes and Its Risk Factors in Tehranian Adults

    PubMed Central

    Hasan-Ghomi, Majid; Ejtahed, Hanieh-Sadat; Mirmiran, Parvin; Hosseini-Esfahani, Firozeh; Sarbazi, Narges; Azizi, Fereidoun; Sadeghian, Saeed

    2015-01-01

    Background: As food insecurity has negative effects on health, the aim of this study was to determine tahe relationship between household food security and type 2 diabetes mellitus and its related risk factors. Methods: In this case-control study, 200 individuals with and 200 individuals without type 2 diabetes mellitus, aged over 40 years, were randomly selected from among participants of the Tehran Lipid and Glucose Study. The questionnaire on household food security proposed by the United States Department of Agriculture was completed for them by trained personnel. Logistic regression was used to determine the variable that had the most significant relationship with food security status. Results: The average of food security score was 2.38 ± 2.0 in non-diabetic and 2.25 ± 2.0 in diabetic individuals (P = 0.6). In both groups, the risk for food insecurity in women was more than in men. In the diabetic group, being single and having education levels below high school increased the risk of food insecurity. In the non-diabetic group, the risk of food insecurity in obese individuals was 3.3 times higher than normal individuals (odds ratio = 2.1, 95% confidence interval: 1.2–4.1). Conclusions: There were no significant differences in food security levels of diabetic and non-diabetic groups. However, some risk factors of type 2 diabetes including sex, marital status, educational level, and obesity were associated with food insecurity. PMID:26605019

  8. Receptor modelling of fine particles in Southern England using CMB including comparison with AMS-PMF factors

    NASA Astrophysics Data System (ADS)

    Yin, J.; Cumberland, S. A.; Harrison, R. M.; Allan, J.; Young, D. E.; Williams, P. I.; Coe, H.

    2014-09-01

    PM2.5 was collected during a winter campaign at two southern England sites, urban background North Kensington (NK) and rural Harwell (HAR), in January-February 2012. Multiple organic and inorganic source tracers were analysed and used in a Chemical Mass Balance (CMB) model, which apportioned seven separate primary sources, that explained on average 53% (NK) and 56% (HAR) of the organic carbon (OC), including traffic, woodsmoke, food cooking, coal combustion, vegetative detritus, natural gas and dust/soil. With the addition of source tracers for secondary biogenic aerosol at the NK site, 79% of organic carbon was accounted for. Secondary biogenic sources were represented by oxidation products of α-pinene and isoprene, but only the former made a substantial contribution to OC. Particle source contribution estimates for PM2.5 mass were obtained by the conversion of the OC estimates and combining with inorganic components ammonium nitrate, ammonium sulphate and sea salt. Good mass closure was achieved with 8% (92% with the addition of the secondary biogenic source) and 83% of the PM2.5 mass explained at NK and HAR respectively, with the remainder being secondary organic matter. While the most important sources of OC are vehicle exhaust (21 and 16%) and woodsmoke (15% and 28%) at NK and HAR respectively, food cooking emissions are also significant, particularly at the urban NK site (11% of OC), in addition to the secondary biogenic source, only measured at NK, which represented about 26%. In comparison, the major source components for PM2.5 at NK and HAR are inorganic ammonium salts (51 and 56%), vehicle exhaust emissions (8 and 6%), secondary biogenic (10% measured at NK only), woodsmoke (4 and 7%) and sea salt (7 and 8%), whereas food cooking (4% and 1%) showed relatively smaller contributions to PM2.5. Results from the CMB model were compared with source contribution estimates derived from the AMS-PMF method. The overall mass of organic matter accounted for is

  9. Receptor modelling of fine particles in southern England using CMB including comparison with AMS-PMF factors

    NASA Astrophysics Data System (ADS)

    Yin, J.; Cumberland, S. A.; Harrison, R. M.; Allan, J.; Young, D. E.; Williams, P. I.; Coe, H.

    2015-02-01

    PM2.5 was collected during a winter campaign at two southern England sites, urban background North Kensington (NK) and rural Harwell (HAR), in January-February 2012. Multiple organic and inorganic source tracers were analysed and used in a Chemical Mass Balance (CMB) model, which apportioned seven separate primary sources, that explained on average 53% (NK) and 56% (HAR) of the organic carbon (OC), including traffic, woodsmoke, food cooking, coal combustion, vegetative detritus, natural gas and dust/soil. With the addition of source tracers for secondary biogenic aerosol at the NK site, 79% of organic carbon was accounted for. Secondary biogenic sources were represented by oxidation products of α-pinene and isoprene, but only the former made a substantial contribution to OC. Particle source contribution estimates for PM2.5 mass were obtained by the conversion of the OC estimates and combining with inorganic components ammonium nitrate, ammonium sulfate and sea salt. Good mass closure was achieved with 81% (92% with the addition of the secondary biogenic source) and 83% of the PM2.5 mass explained at NK and HAR respectively, with the remainder being secondary organic matter. While the most important sources of OC are vehicle exhaust (21 and 16%) and woodsmoke (15 and 28%) at NK and HAR respectively, food cooking emissions are also significant, particularly at the urban NK site (11% of OC), in addition to the secondary biogenic source, only measured at NK, which represented about 26%. In comparison, the major source components for PM2.5 at NK and HAR are inorganic ammonium salts (51 and 56%), vehicle exhaust emissions (8 and 6%), secondary biogenic (10% measured at NK only), woodsmoke (4 and 7%) and sea salt (7 and 8%), whereas food cooking (4 and 1%) showed relatively smaller contributions to PM2.5. Results from the CMB model were compared with source contribution estimates derived from the AMS-PMF method. The overall mass of organic matter accounted for is rather

  10. Systematic identification of type I and type II interferon-induced antiviral factors.

    PubMed

    Liu, Su-Yang; Sanchez, David Jesse; Aliyari, Roghiyh; Lu, Sun; Cheng, Genhong

    2012-03-13

    Type I and type II interferons (IFNs) are cytokines that establish the cellular antiviral state through the induction of IFN-stimulated genes (ISGs). We sought to understand the basis of the antiviral activity induced by type I and II IFNs in relation to the functions of their ISGs. Based on gene expression studies, we systematically identified antiviral ISGs by performing blinded, functional screens on 288 type I and type II ISGs. We assessed and validated the antiviral activity of these ISGs against an RNA virus, vesicular stomatitis virus (VSV), and a DNA virus, murine gammaherpes virus (MHV-68). Overall, we identified 34 ISGs that elicited an antiviral effect on the replication of either one or both viruses. Fourteen ISGs have uncharacterized antiviral functions. We further defined ISGs that affect critical life-cycle processes in expression of VSV protein and MHV-68 immediate-early genes. Two previously undescribed antiviral ISGs, TAP1 and BMP2, were further validated. TAP1-deficient fibroblasts were more susceptible to VSV infection but less so to MHV-68 infection. On the other hand, exogenous BMP2 inhibits MHV-68 lytic growth but did not affect VSV growth. These results delineate common and distinct sets of type I and type II IFN-induced genes as well as identify unique ISGs that have either broad or specific antiviral effects on these viruses. PMID:22371602

  11. Type 2 diabetes in children: Clinical aspects and risk factors

    PubMed Central

    Rao, P. V.

    2015-01-01

    A strong link between obesity, insulin resistance, and metabolic syndrome has been reported with development of a new paradigm to type 2 diabetes mellitus (T2DM), with some evidence suggesting that beta-cell dysfunction is present before the onset of impaired glucose tolerance. Differentiating type 1 diabetes mellitus (T1DM) from T2DM is actually not very easy and there exists a number of overlapping characteristics. The autoantibody frequencies of seven antigens in T1DM patients may turn out to be actually having T2DM patients (pre-T2DM). T2DM patients generally have increased C-peptide levels (may be normal at time of diagnosis), usually no auto-antibodies, strong family history of diabetes, obese and show signs of insulin resistance (hypertension, acanthosis, PCOS). The American Academy of Paediatrics recommends lifestyle modifications ± metformin when blood glucose is 126–200 mg/dL and hemoglobin A1c (HbA1c) <8.5. Insulin is recommended when blood glucose is >200 mg/dL and HbA1c >8.5, with or without ketosis. Metformin is not recommended if the patient is ketotic, because this increases the risk of lactic acidosis. Metformin is currently the only oral hypoglycemic that has been approved for use in children. Knowing these subtle differences in mechanism, and knowing how to test patients for which mechanism (s) are causing their diabetes mellitus, may help us eventually tailor treatment programs on an individual basis. PMID:25941651

  12. Risk Factor Analysis in Clinical Isolates of ESBL and MBL (Including NDM-1) Producing Escherichia coli and Klebsiella Species in a Tertiary Care Hospital

    PubMed Central

    Dutta, Renu; Saxena, Sonal; Singhal, Smita

    2015-01-01

    Background Extended-spectrum β-lactamase (ESBL) and metallo-β-lactamase (MBL) producing Gram negative organisms are emerging as a worldwide public health concern. Aim To elucidate risk factors for infection with ESBL and MBL (also NDM-1) producing E. coli and Klebsiella spp. Materials and Methods A prospective observational study was conducted from November 2010 to March 2012. ESBL production was detected using ESBL E-test, MBL by MBL E-test and NDM-1 by polymerase chain reaction (PCR). Risk factors analysed includes age, sex, clinical specimen, type of infection, duration of hospital stay prior to collection of sample, admitting ward, antimicrobial susceptibility, previous antibiotics used, co-morbid illnesses like diabetes mellitus, immunodeficiency, low birth weight, respiratory/neurological/cardiac/haematological/liver diseases, malignancy, urinary or central venous catheter, ventilatory support, surgical procedures and dialysis. Statistical analysis z-test or Fisher’s exact test. Results E. coli – ESBL producing isolates E. coli revealed female preponderance, equal incidence of hospital and community acquired infections, mostly from surgical wards, isolated from urine, age group among females >20-30 years and among males >28 days-1 year. They showed high resistance to cephalosporins, monobactam, penicillin but low resistance to carbapenems and aminoglycosides. Co-morbid conditions observed were surgery, urinary catheterisation, haematological disease, ventilatory support, diabetes mellitus and neurological disease. MBL producing strains were mainly from females, surgical wards, (including both NDM-1 isolates), hospital acquired infections, isolated from body fluids (NDM-1 positive), female genital tract specimen and urine (one NDM-1 positive). NDM-1 positive isolates belonged to age groups >5-10 year and >0-28 days and underwent surgery and urinary catheterisation. Klebsiella spp.- ESBL producing isolates showed female preponderance, hospital acquired

  13. Temperature factor for magnetic instability conditions of type - II superconductors

    NASA Astrophysics Data System (ADS)

    Romanovskii, V.

    2014-10-01

    The macroscopic development of interrelated electrodynamics and thermal states taking place both before and after instability onset in type-II superconductors are studied using the critical state and the flux creep concepts. The physical mechanisms of the non-isothermal formation of the critical state are discussed solving the set of unsteady thermo-electrodynamics equations taking into consideration the unknown moving penetration boundary of the magnetic flux. To make it, the numerical method, which allows to study diffusion phenomena with unknown moving phase-two boundary, is developed. The corresponding non-isothermal flux jump criteria are written. It is proved for the first time that, first, the diffusion phenomena in superconductors have the fission-chain-reaction nature, second, the stability conditions, losses in superconductor and its stable overheating before instability onset are mutually dependent. The results are compared with those following from the existing magnetic instability theory, which does not take into consideration the stable temperature increase of superconductor before the instability onset. It is shown that errors of isothermal approximation are significant for modes closed to adiabatic ones. Therefore, the well-known adiabatic flux jump criterion limits the range of possible stable superconducting states since a correct determination of their stability states must take into account the thermal prehistory of the stable magnetic flux penetration. As a result, the calculation errors in the isothermal approximation will rise when the sweep rate of an external magnetic field or the size of the superconductor’s cross-sectional area increase. The basic conclusions formulated in the framework of the critical state model are verified comparing the experimental results and the numerical analysis of the stability conditions and the temperature dynamics of the helicoid-type superconducting current-carrying element having real voltage

  14. Prevalence of and Risk Factors for Type 2 Diabetes Mellitus in Vietnam: A Systematic Review.

    PubMed

    Nguyen, Chung T; Pham, Ngoc Minh; Lee, Andy H; Binns, Colin W

    2015-09-01

    This systematic review examined trends in the prevalence of type 2 diabetes mellitus (T2DM) and identified its risk factors among adults in Vietnam. PubMed, Web of Science, Wiley Online Library, and Scopus databases were searched to identify relevant literature. The search yielded 10 studies, including 2 national surveys and 8 regional investigations. National prevalence estimates of T2DM were 2.7% in 2002 and 5.4% in 2012. The estimates for the northern region were 1.4% in 1994 and 3.7% in 2012 and those for the southern region were 3.8% in 2004, 7.0% in 2008, and 12.4% in 2010. The major determinants of T2DM included older age, urban residence, high levels of body and abdominal fat, physical inactivity, sedentary lifestyle, genetic factors, and hypertension. The prevalence rate by gender was variable in both national and regional studies. There was insufficient information available on some potentially important risk factors such as smoking, dietary intake, income, and educational level. Our review signifies a rapidly growing prevalence of T2DM in Vietnam and suggests that extra effort is required to prevent and control this disease. PMID:26187848

  15. Persistent organic pollutants as risk factors for type 2 diabetes.

    PubMed

    Ngwa, Elvis Ndonwi; Kengne, Andre-Pascal; Tiedeu-Atogho, Barbara; Mofo-Mato, Edith-Pascale; Sobngwi, Eugene

    2015-01-01

    Type 2 diabetes mellitus (T2DM) is a major and fast growing public health problem. Although obesity is considered to be the main driver of the pandemic of T2DM, a possible contribution of some environmental contaminants, of which persistent organic pollutants (POPs) form a particular class, has been suggested. POPs are organic compounds that are resistant to environmental degradation through chemical, biological, and photolytic processes which enable them to persist in the environment, to be capable of long-range transport, bio accumulate in human and animal tissue, bio accumulate in food chains, and to have potential significant impacts on human health and the environment. Several epidemiological studies have reported an association between persistent organic pollutants and diabetes risk. These findings have been replicated in experimental studies both in human (in-vitro) and animals (in-vivo and in-vitro), and patho-physiological derangements through which these pollutants exercise their harmful effect on diabetes risk postulated. This review summarizes available studies, emphasises on limitations so as to enable subsequent studies to be centralized on possible pathways and bring out clearly the role of POPs on diabetes risk. PMID:25987904

  16. Prevalence, risk factors and complications associated with type 2 diabetes in migrant South Asians.

    PubMed

    Garduño-Diaz, Sara D; Khokhar, Santosh

    2012-01-01

    It is estimated that type 2 diabetes (T2D) currently affects about 246 million people worldwide, with South Asians, especially Indians, having both the largest number of cases and the fastest growing prevalence. South Asian ethnicity has been identified as a major risk factor for the development of T2D with central adiposity, insulin resistance and an unfavourable lipid profile being identified as predominant signals of alarm. Leading databases, including Web of Science, Medline, PubMed and Science Direct, were consulted and manual searches were conducted for cited references in leading diabetes-related journals. In all, 152 articles were included for the final assessment reported in this review. Genetic predisposition, central adiposity and unfavourable lifestyle, including physical inactivity and an unhealthy diet, were associated with the prevalence of T2D in migrant South Asians. 'Westernization', acculturation, socio-economic factors and lack of knowledge about the disease have also been identified as contributors to the development of T2D in this population. Higher prevalence of T2D in migrant South Asians may not be entirely attributed to genetic predisposition; hence, ethnicity and associated modifiable risk factors need further investigation. Preventive measures and appropriate interventions are currently limited by the lack of ethnic-specific cut-off points for anthropometric and biological markers, as well as by the absence of reliable methods for dietary and physical activity assessment. This article describes the prevalence rate, risk factors and complications associated with T2D in migrant South Asians living in different countries. PMID:21591242

  17. The mouse protein synthesis initiation factor 4A gene family includes two related functional genes which are differentially expressed.

    PubMed Central

    Nielsen, P J; Trachsel, H

    1988-01-01

    We have cloned and characterized a family of mouse genomic sequences hybridizing to mouse cDNA probes coding for eIF-4A, one of the protein synthesis initiation factors involved in the binding of mRNA to the ribosome. We estimate that there is a total of approximately 9-13 eIF-4A pseudogenes. We also found an eIF-4A intronless retroposon which, when compared to the cDNA, contains a single nucleotide difference. This possibly functional gene contains a mouse repetitive B1 element integrated in the promoter region. Furthermore, we have cloned two intron-containing eIF-4A genes (termed eIF-4AI and eIF-4AII). The eIF-4AII gene codes for a previously unknown form of eIF-4A. Northern blot hybridization with RNA from several mouse organs shows a variation in eIF-4AI expression within a factor of 7. In contrast, relative to liver, eIF-4AII expression is 20- to 30-times higher in brain and kidney, 10- to 17-fold higher in lung and heart, and is about equally abundant in liver, spleen and thymus. These data suggest that the relative efficiency of protein synthesis initiation for different mRNAs, as reflected by discrimination in messenger 5'-terminal cap recognition and binding to ribosomes, varies in different tissues. Images PMID:3046931

  18. Translationally invariant calculations of form factors, nucleon densities and momentum distributions for finite nuclei with short-range correlations included

    NASA Astrophysics Data System (ADS)

    Shebeko, A. V.; Grigorov, P. A.; Iurasov, V. S.

    2012-11-01

    Relying upon our previous treatment of the density matrices for nuclei (in general, nonrelativistic self-bound finite systems) we are studying a combined effect of center-of-mass motion and short-range nucleon-nucleon correlations on the nucleon density and momentum distributions in light nuclei (4He and 16O). Their intrinsic ground-state wave functions are constructed in the so-called fixed center-of-mass approximation, starting with mean-field Slater determinants modified by some correlator ( e.g., after Jastrow or Villars). We develop the formalism based upon the Cartesian or boson representation, in which the coordinate and momentum operators are linear combinations of the creation and annihilation operators for oscillatory quanta in the three different space directions, and get the own "Tassie-Barker" factors for each distribution and point out other model-independent results. After this separation of the center-of-mass motion effects we propose additional analytic means in order to simplify the subsequent calculations ( e.g., within the Jastrow approach or the unitary correlation operator method). The charge form factors, densities and momentum distributions of 4He and 16O evaluated by using the well-known cluster expansions are compared with data, our exact (numerical) results and microscopic calculations.

  19. Impact of early psychosocial factors (childhood socioeconomic factors and adversities) on future risk of type 2 diabetes, metabolic disturbances and obesity: a systematic review

    PubMed Central

    2010-01-01

    Background Psychological factors and socioeconomic status (SES) have a notable impact on health disparities, including type 2 diabetes risk. However, the link between childhood psychosocial factors, such as childhood adversities or parental SES, and metabolic disturbances is less well established. In addition, the lifetime perspective including adult socioeconomic factors remains of further interest. We carried out a systematic review with the main question if there is evidence in population- or community-based studies that childhood adversities (like neglect, traumata and deprivation) have considerable impact on type 2 diabetes incidence and other metabolic disturbances. Also, parental SES was included in the search as risk factor for both, diabetes and adverse childhood experiences. Finally, we assumed that obesity might be a mediator for the association of childhood adversities with diabetes incidence. Therefore, we carried out a second review on obesity, applying a similar search strategy. Methods Two systematic reviews were carried out. Longitudinal, population- or community-based studies were included if they contained data on psychosocial factors in childhood and either diabetes incidence or obesity risk. Results We included ten studies comprising a total of 200,381 individuals. Eight out of ten studies indicated that low parental status was associated with type 2 diabetes incidence or the development of metabolic abnormalities. Adjustment for adult SES and obesity tended to attenuate the childhood SES-attributable risk but the association remained. For obesity, eleven studies were included with a total sample size of 70,420 participants. Four out of eleven studies observed an independent association of low childhood SES on the risk for overweight and obesity later in life. Conclusions Taken together, there is evidence that childhood SES is associated with type 2 diabetes and obesity in later life. The database on the role of psychological factors such as

  20. SREB, a GATA Transcription Factor That Directs Disparate Fates in Blastomyces dermatitidis Including Morphogenesis and Siderophore Biosynthesis

    PubMed Central

    Gauthier, Gregory M.; Sullivan, Thomas D.; Gallardo, Sergio S.; Brandhorst, T. Tristan; Vanden Wymelenberg, Amber J.; Cuomo, Christina A.; Suen, Garret; Currie, Cameron R.; Klein, Bruce S.

    2010-01-01

    Blastomyces dermatitidis belongs to a group of human pathogenic fungi that exhibit thermal dimorphism. At 22°C, these fungi grow as mold that produce conidia or infectious particles, whereas at 37°C they convert to budding yeast. The ability to switch between these forms is essential for virulence in mammals and may enable these organisms to survive in the soil. To identify genes that regulate this phase transition, we used Agrobacterium tumefaciens to mutagenize B. dermatitidis conidia and screened transformants for defects in morphogenesis. We found that the GATA transcription factor SREB governs multiple fates in B. dermatitidis: phase transition from yeast to mold, cell growth at 22°C, and biosynthesis of siderophores under iron-replete conditions. Insertional and null mutants fail to convert to mold, do not accumulate significant biomass at 22°C, and are unable to suppress siderophore biosynthesis under iron-replete conditions. The defect in morphogenesis in the SREB mutant was independent of exogenous iron concentration, suggesting that SREB promotes the phase transition by altering the expression of genes that are unrelated to siderophore biosynthesis. Using bioinformatic and gene expression analyses, we identified candidate genes with upstream GATA sites whose expression is altered in the null mutant that may be direct or indirect targets of SREB and promote the phase transition. We conclude that SREB functions as a transcription factor that promotes morphogenesis and regulates siderophore biosynthesis. To our knowledge, this is the first gene identified that promotes the conversion from yeast to mold in the dimorphic fungi, and may shed light on environmental persistence of these pathogens. PMID:20368971

  1. Viewpoint: factors involved in type I interferon responses during porcine virus infections.

    PubMed

    Summerfield, Artur

    2012-07-15

    Since type I interferon (IFN-I) is considered a potent antiviral defence mechanism, it is not surprising that during evolution viruses have development of various mechanisms to counteract IFN-I induction or release. Despite this, certain virus infections are associated with very high levels of systemic IFN-I. One explanation for this observation is the presence of plasmacytoid dendritic cells (pDC), which are able to produce high levels of IFN-I despite the presence of viral IFN-I antagonists. Examples of virus infection in pigs including classical swine fever virus, influenza virus, foot-and-mouth disease virus, and porcine circo virus type 2 highlight factors involved in controlling such responses and illustrate potential negative and positive effects for the host. Based on published data, we propose that in addition to the ability to activate pDC, the ability to spread systemically, and the tropism for lymphoid tissue also represent important factors contributing to strong systemic IFN-I responses during certain virus infections. PMID:21458079

  2. The transforming growth factor beta type II receptor can replace the activin type II receptor in inducing mesoderm.

    PubMed Central

    Bhushan, A; Lin, H Y; Lodish, H F; Kintner, C R

    1994-01-01

    The type II receptors for the polypeptide growth factors transforming growth factor beta (TGF-beta) and activin belong to a new family of predicted serine/threonine protein kinases. In Xenopus embryos, the biological effects of activin and TGF-beta 1 are strikingly different; activin induces a full range of mesodermal cell types in the animal cap assay, while TGF-beta 1 has no effects, presumably because of the lack of functional TGF-beta receptors. In order to assess the biological activities of exogenously added TGF-beta 1, RNA encoding the TGF-beta type II receptor was introduced into Xenopus embryos. In animal caps from these embryos, TGF-beta 1 and activin show similar potencies for induction of mesoderm-specific mRNAs, and both elicit the same types of mesodermal tissues. In addition, the response of animal caps to TGF-beta 1, as well as to activin, is blocked by a dominant inhibitory ras mutant, p21(Asn-17)Ha-ras. These results indicate that the activin and TGF-beta type II receptors can couple to similar signalling pathways and that the biological specificities of these growth factors lie in their different ligand-binding domains and in different competences of the responding cells. Images PMID:8196664

  3. Prognostic effect of hENT1, dCK and HuR expression by morphological type in periampullary adenocarcinoma, including pancreatic cancer

    PubMed Central

    Elebro, Jacob; Ben Dror, Liv; Heby, Margareta; Nodin, Björn; Jirström, Karin; Eberhard, Jakob

    2016-01-01

    Abstract Background: Putative biomarkers of gemcitabine response have been extensively studied in pancreatic cancer, but less so in other types of periampullary adenocarcinoma. The most studied biomarker is human equilibrative nucleoside transporter 1 (hENT1), and the activating enzyme deoxycytidine kinase (dCK) has also been linked to treatment response. The RNA-binding protein human antigen R (HuR) has been demonstrated to confer increased dCK levels in vitro and to predict gemcitabine response in vivo. Here, we investigated the prognostic impact of hENT1, dCK and HuR in pancreatobiliary (PB) and intestinal (I) type periampullary cancers, respectively. Material and methods: Immunohistochemical expression of hENT1, dCK and HuR was evaluated in tissue microarrays with all primary tumours and 103 paired lymph node metastases from a consecutive retrospective cohort of 175 patients with resected periampullary adenocarcinomas. Results: In patients with PB-type tumours, neither hENT1 nor dCK expression was prognostic. A high HuR cytoplasmic/nuclear ratio was associated with a significantly reduced five-year overall survival (OS) in patients receiving adjuvant gemcitabine (HR 2.07, 95% CI 1.03–4.17) but not in untreated patients (pinteraction = 0.028). In patients with I-type tumours receiving adjuvant chemotherapy, high dCK expression was significantly associated with a prolonged recurrence-free survival (RFS) (HR 0.09, 95% CI 0.01–0.73, pinteraction = 0.023). Furthermore, HuR expression was associated with a prolonged OS and RFS in unadjusted but not in adjusted analysis and hENT1 expression was an independent predictor of a prolonged RFS (HR 0.24, 95% CI 0.10–0.59), regardless of adjuvant treatment. Conclusion: hENT1 expression is a favourable prognostic factor in I-type, but not in PB-type tumours. High dCK expression is a favourable prognostic factor in patients with I-type tumours receiving adjuvant treatment and a high cytoplasmic/nuclear HuR ratio

  4. Risk factors for diabetic retinopathy in northern Chinese patients with type 2 diabetes mellitus

    PubMed Central

    Yan, Zhi-Peng; Ma, Jing-Xue

    2016-01-01

    AIM To investigate the prevalence and risk factors of diabetic retinopathy (DR) in northern Chinese patients with type 2 diabetes mellitus (T2DM). METHODS This retrospective cross-sectional study was performed between May 2011 and April 2012. A total of 1100 patients (male/female, 483/617) were included in this study. DR was defined following the Early Treatment Diabetic Retinopathy Study (ETDRS) severity scale. All included patients accepted a comprehensive ophthalmic examination including retinal photographs. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence interval (CI) after adjusting for age and gender. RESULTS Retinopathy was present in 307 patients with a prevalence of 27.9%. In univariate logistic analysis, presence of DR was associated with longer duration of diabetes (OR, 5.70; 95%CI, 2.91-12.56), higher concentration of fasting blood glucose (OR, 12.94; 95%CI, 2.40-67.71), higher level of glycosylated hemoglobin HbA1c (OR, 5.50; 95%CI, 3.78-11.97) and insulin treatment (OR, 6.99; 95%CI, 1.39-35.12). The lifestyle of patients with T2DM including smoking, alcohol consumption and regular exercise seemed not associated with the development of DR. CONCLUSION Our study suggests that fasting serum glucose concentration, HbA1c level, duration of diabetes and insulin treatment are potential risk factors for DR in northern Chinese patients with T2DM, while the lifestyle of included patients seems not associated with DR. PMID:27588275

  5. 43 CFR 404.10 - Are there certain types of infrastructure and facilities that may not be included in a rural...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 43 Public Lands: Interior 1 2014-10-01 2014-10-01 false Are there certain types of infrastructure and facilities that may not be included in a rural water supply project? 404.10 Section 404.10 Public Lands: Interior Regulations Relating to Public Lands BUREAU OF RECLAMATION, DEPARTMENT OF THE INTERIOR RECLAMATION RURAL WATER SUPPLY...

  6. Reserve, thin form-factor, hypochlorite-based cells for powering portable systems: Manufacture (including MEMS processes), performance and characterization

    NASA Astrophysics Data System (ADS)

    Cardenas-Valencia, Andres M.; Biver, Carl J.; Langebrake, Larry

    This work focuses on fabrication routes and performance evaluation of thin form-factors, reserve cells, as a powering alternative for expendable and/or remotely operated systems. The catalytic decomposition of sodium hypochlorite solutions is revisited herein with two cost-effective anodes: zinc and aluminum. Aluminum, even though the most expensive of the utilized anodes, constituted cells with double the energy content (up to 55 Wh kg -1) than those fabricated with zinc. Even though the hypochlorite concentration in the solution limits the cells' operational life, attractive performances (1.0 V with a current of 10 mA) for the manufactured cells are obtained. It is shown that micro fabrication processes, allowing for close electrodes interspacing, provided high faradic and columbic efficiencies of up to 70 and 100%, respectively. Obtained specific energies (50-120 Wh kg -1) are in the same order of magnitude than batteries currently used for powering deployable systems. Experimental results show that a simple model that linearly relates over potentials and the electrical load, adequately describe all the cell designs. A mathematical model based on a kinetic-mechanistic scheme that relates the current output as a function of time agrees fairly well with results obtained activating cells with various concentrations of NaOCl solutions.

  7. Correlations Between the Incidence of National Notifiable Infectious Diseases and Public Open Data, Including Meteorological Factors and Medical Facility Resources

    PubMed Central

    Jang, Jin-Hwa; Lee, Ji-Hae; Je, Mi-Kyung; Cho, Myeong-Ji; Bae, Young Mee; Son, Hyeon Seok; Ahn, Insung

    2015-01-01

    Objectives: This study was performed to investigate the relationship between the incidence of national notifiable infectious diseases (NNIDs) and meteorological factors, air pollution levels, and hospital resources in Korea. Methods: We collected and stored 660 000 pieces of publicly available data associated with infectious diseases from public data portals and the Diseases Web Statistics System of Korea. We analyzed correlations between the monthly incidence of these diseases and monthly average temperatures and monthly average relative humidity, as well as vaccination rates, number of hospitals, and number of hospital beds by district in Seoul. Results: Of the 34 NNIDs, malaria showed the most significant correlation with temperature (r=0.949, p<0.01) and concentration of nitrogen dioxide (r=-0.884, p<0.01). We also found a strong correlation between the incidence of NNIDs and the number of hospital beds in 25 districts in Seoul (r=0.606, p<0.01). In particular, Geumcheon-gu was found to have the lowest incidence rate of NNIDs and the highest number of hospital beds per patient. Conclusions: In this study, we conducted a correlational analysis of public data from Korean government portals that can be used as parameters to forecast the spread of outbreaks. PMID:26265666

  8. What are the most important factors determining different vegetation types in the Chapada Diamantina, Brazil?

    PubMed

    Neves, S P S; Funch, R; Conceição, A A; Miranda, L A P; Funch, L S

    2016-06-01

    A transect was used to examine the environmental and biological descriptors of a compact vegetation mosaic in the Chapada Diamantina in northeastern Brazil, including the floristic composition, spectrum of plant life forms, rainfall, and soil properties that defined areas of cerrado (Brazilian savanna), caatinga (seasonally dry tropical forest thorny, deciduous shrub/arboreal vegetation) and cerrado-caatinga transition vegetation. The floristic survey was made monthly from April/2009 to March/2012. A dendrogram of similarity was generated using the Jaccard Index based on a matrix of the species that occurred in at least two of the vegetation types examined. The proportions of life forms in each vegetation type were compared using the chi-square test. Composite soil samples were analyzed by simple variance (ANOVA) to examine relationships between soil parameters of each vegetation type and the transition area. The monthly precipitation levels in each vegetation type were measured and compared using the chi-square test. A total of 323 species of angiosperms were collected distributed in 193 genera and 54 families. The dendrogram demonstrated strong difference between the floristic compositions of the cerrado and caatinga, sharing 2% similarity. The chi-square test did not demonstrate any significant statistical differences between the monthly values of recorded rainfall. The organic matter and clay contents of the soilsin the caatinga increased while sand decreased, and the proportions of therophyte, hemicryptophyte, and chamaephyte life forms decreased and phanerophytes increased. We can therefore conclude that the floristic composition and the spectrum of life forms combined to define the cerrado and caatinga vegetation along the transect examined, with soil being the principal conditioning factor determining the different vegetation types, independent of precipitation levels. PMID:26934155

  9. Granulocyte-colony stimulating factor-producing gallbladder carcinoma-include analysis all case reports: A case report

    PubMed Central

    Izumo, Wataru; Furukawa, Kenji; Katsuragawa, Hideo; Tezuka, Toru; Furukawa, Tatsuya; Hataji, Kenichirou; Komatsu, Akio; Shigematsu, Kyousuke; Yamamoto, Masakazu

    2016-01-01

    Introduction It is extremely rare for gallbladder carcinoma to produce granulocyte-colony stimulating factor (G-CSF) and such tumors have a poor prognosis. Presentation of case A 67-year-old man was admitted with continuous fever. Laboratory tests showed a leukocyte count of 27,980/μL, serum C-reactive protein (CRP) of 9.2 mg/dL and serum G-CSF of 225 pg/mL. Imaging revealed an irregular gallbladder mass about 90 mm in diameter with peripheral enhancement that also involved the liver and transverse colon. G-CSF producing gallbladder carcinoma was diagnosed. We performed cholecystectomy, partial resection of segments 4 and 5 of the liver, partial resection of the transverse colon, and gastrostomy. Histopathological examination showed gallbladder carcinoma (pT3, pN0, M0, G2, and pStage IIIA by the UICC classification, version 7). On immunohistochemical staining, tumor cells were positive for G-CSF. The leukocyte count was normalized postoperatively and fever subsided immediately after surgery. Two months later, the leukocyte count rose to 56,820/μL and metastases to the liver and lymph nodes were detected by CT. Chemotherapy (gemcitabine plus cisplatin) was started and the leukocyte count was normalized after the first course. The patient has continued chemotherapy and has survived for 16 months postoperatively. Discussion G-CSF producing gallbladder carcinoma has a poor prognosis and most patients die within 12 months of starting therapy. It is rare for patients with recurrence to survive for 16 months after surgery, as in the present case. Conclusion Multidisciplinary therapy (surgery and chemotherapy) may prolong the survival of patients with G-CSF producing gallbladder carcinoma, especially those with recurrence. PMID:26945490

  10. Diabetic foot risk factors in type 2 diabetes patients: a cross-sectional case control study

    PubMed Central

    2014-01-01

    Background Diabetic foot is a serious condition in patients with a long lasting diabetes mellitus. Diabetic foot treated improperly may lead not only to delayed ulceration healing, generalized inflammation, unnecessary surgical intervention, but also to the lower limb amputation. The aim of this study was to compare diabetic foot risk factors in population with type 2 diabetes and risk factors for diabetes in healthy subjects. Methods The study included 900 subjects: 145 with diabetic foot, 293 with type 2 diabetes without diabetic foot and 462 healthy controls matched in terms of mean age, gender structure and cardiovascular diseases absence. Study was conducted in Gastroenterology and Metabolic Diseases Department, Medical University of Warsaw, Poland. In statistical analysis a logistic regression model, U Mann-Whitney’s and t-Student test were used. Results The binomial logit models analysis showed that the risk of diabetic foot in patients with type 2 diabetes was decreased by patient’s age (odds ratio [OR] = 0.94; 95% confidence interval [CI]: 0.92-0.96; p = 0.00001) and hyperlipidaemia (OR = 0.54; 95% CI: 0.36-0.81; p = 0.01). In contrast, male gender (OR = 2.83; 95% CI: 1.86-4.28; p = 0.00001) diabetes duration (OR = 1.04; 95% CI: 1.03-1.06; p = 0.0003), weight (OR = 1.04; 95% CI: 1.03-1.06; p = 0.00001), height (OR = 1.08; 95% CI: 1.05-1.11; p = 0.00001) and waist circumference (OR = 1.028; 95% CI: 1.007-1.050; p = 0.006) increase the risk of diabetic foot. The onset of type 2 diabetes in healthy subjects was increased by weight (OR = 1.035; 95% CI: 1.024-1.046; p = 0.00001), WC (OR = 1.075; 95% CI: 1.055-1.096; p = 00001), hip circumference (OR = 1.03; 95% CI: 1.01-1.05; p = 0.005), overweight defined with body mass index (BMI) above 24,9 kg/m2 (OR = 2.49; 95% CI: 1.77-3.51; p = 0.00001) and hyperlipidaemia (OR = 3.53; 95% CI: 2.57-4.84; p = 0.00001). Conclusions Risk factors for Type 2 diabetes and diabetic foot are only partially common. Study proved

  11. Incidence of Depression and Associated Factors in Patients With Type 2 Diabetes in Quebec, Canada

    PubMed Central

    Lunghi, Carlotta; Moisan, Jocelyne; Grégoire, Jean-Pierre; Guénette, Line

    2016-01-01

    Abstract It has been reported that the risk of depression is higher among people with type 2 diabetes compared with a nondiabetic population. Among diabetic patients, depression has been associated with worse self-care behaviors, poor glycemic control, and an increased risk of diabetes complications. Identifying factors associated with the occurrence of depression may help physicians identify earlier diabetic patients at a high risk of developing depression, improve prevention, and accelerate proper treatment. To our knowledge, very few population-based studies have reported on the incidence of clinically diagnosed depression as a consequence of type 2 diabetes over a long follow-up period. The objective of this study was to estimate the incidence of clinically diagnosed depression among type 2 diabetic patients newly treated with oral antidiabetic drugs (ADs) and to identify factors associated with the occurrence of depression. Administrative claims data from the public health insurance plan were used to identify a cohort of new oral AD users aged ≥18 years between 2000 and 2006. Patients were followed from oral AD treatment initiation until the diagnosis of depression, ineligibility for the public drug plan, death, or the end of the study, whichever came first. Incidence rates were determined using person-time analysis. Factors associated with depression were identified using multivariable Cox regression analysis. We identified 114,366 new oral AD users, of which 4808 had a diagnosis of depression. The overall incidence rate of depression was 9.47/1000 person-years (PYs) (10.72/1000 PYs for women and 8.27/1000 PYs for men). The incidence of depression was higher during the year after oral AD treatment initiation. Independent factors associated with depression included having had mental disorders other than depression, hospitalization, a higher number of different drugs taken and of physicians visited during the year before oral AD initiation. Moreover, we

  12. Risk factors associated with elder abuse: the importance of differentiating by type of elder maltreatment.

    PubMed

    Jackson, Shelly L; Hafemeister, Thomas L

    2011-01-01

    Elder abuse research rarely differentiates by the type of elder maltreatment involved when identifying risk factors. The purpose of this study was to compare risk factors across four predominant types of elder maltreatment (financial exploitation, physical abuse, neglect by others, and hybrid financial exploitation [HFE]). Data were collected from two sources: interviews with victims of substantiated elder abuse, responding adult protective services (APS) caseworkers (N = 71), and third-party informants; and a statewide database that contained all substantiated cases over a corresponding 2-year period (N = 2,142). Using chi-square (interview data) and logistic regressions (Adult Services/Adult Protective Services [ASAPS] data), significant differences across the four types of elder maltreatment were found. These two datasets provide converging evidence for the importance of differentiating by type of maltreatment when identifying risk factors for elder maltreatment and for the importance of considering both the elderly victim and the abusive individual when predicting type of elder maltreatment. PMID:22288093

  13. Method Of Bonding A Metal Connection To An Electrode Including A Core Having A Fiber Or Foam Type Structure For An Electrochemical Cell, An

    DOEpatents

    Loustau, Marie-Therese; Verhoog, Roelof; Precigout, Claude

    1996-09-24

    A method of bonding a metal connection to an electrode including a core having a fiber or foam-type structure for an electrochemical cell, in which method at least one metal strip is pressed against one edge of the core and is welded thereto under compression, wherein, at least in line with the region in which said strip is welded to the core, which is referred to as the "main core", a retaining core of a type analogous to that of the main core is disposed prior to the welding.

  14. Analysis of the Potent Prognostic Factors in Luminal-Type Breast Cancer

    PubMed Central

    Kim, Han-Sung; Park, Inseok; Cho, Hyun Jin; Yang, Keunho; Bae, Byung Noe; Kim, Ki Whan; Han, Sehwan; Kim, Hong-Joo; Kim, Young-Duck

    2012-01-01

    Purpose Luminal-type breast cancer has a good prognosis compared to other types, such as human epidermal growth factor receptor 2 and triple negative types. Luminal-type breast cancer is classified into luminal A and B, according to the proliferation index. We investigated the clinicopathological factors that affect the prognosis of the luminal-type subgroups. Methods We reviewed the medical records and the pathologic reports of 159 luminal-type breast cancer patients who were treated between February 2005 and November 2007. We divided luminal-type breast cancer into luminal A and B, according to Ki-67 (cutoff value, 14%) and analyzed the clinicopathologic factors, such as age at diagnosis, intensity score of estrogen receptor and progesterone receptor, histologic grade, and Bcl-2. Moreover, we compared the disease-free survival (DFS) of each group. Results In the univariate analysis, age (p=0.004), tumor size (p=0.010), lymph node metastasis (p=0.001), and Bcl-2 (p=0.002) were statistically significant factors in luminal-type breast cancer. In the multivariate analysis, lymph node (p=0.049) and Bcl-2 (p=0.034) were significant relevant factors in luminal-type breast cancer. In the subgroup analysis, the increased Bcl-2 (cutoff value, 33%) was related with a longer DFS in the luminal B group (p=0.004). Conclusion In our study, luminal A breast cancer showed a longer DFS than luminal B breast cancer, further, Bcl-2 may be a potent prognostic factor in luminal-type breast cancer. PMID:23346168

  15. School factors as barriers to and facilitators of a preventive intervention for pediatric type 2 diabetes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    School-based interventions are essential to prevent pediatric obesity and type 2 diabetes. School environmental factors influence implementation of these interventions. This article examines how school factors acted as barriers to and facilitators of the HEALTHY intervention. The HEALTHY study was a...

  16. Prevalence and Risk Factors of Gastroesophageal Reflux Disease in Patients with Type 2 Diabetes Mellitus

    PubMed Central

    Ha, Jun Ouk; Lee, Tae Hee; Park, Ja Young; Choi, Seong Ho; Park, Hee Seung; Lee, Jae Seung; Lee, Seung Heon; Seo, Eun Hee; Kim, Young Hwan; Kang, Young Woo

    2016-01-01

    Background Gastrointestinal symptoms are common in patients with type 2 diabetes mellitus (T2DM). The prevalence of gastroesophageal reflux disease (GERD) in Korea appears to be increasing. Some studies have shown that T2DM is a risk factor for symptomatic GERD. However, this possibility is still debated, and the pathogenesis of GERD in T2DM is not yet fully understood. The aim of this study was to analyze the prevalence and risk factors (including autonomic neuropathy) of GERD in patients with T2DM. Methods This cross-sectional case-control study enrolled T2DM patients (n=258) and healthy controls (n=184). All participants underwent physical examinations and laboratory tests. We evaluated medical records and long-term diabetes complications, including peripheral and autonomic neuropathy in patients with T2DM. Esophagogastroduodenoscopy was performed in all patients. The Los Angeles (LA) classification was used to grade GERD. GERD was defined as LA grade A (or higher) or minimal change with GERD symptoms. GERD symptoms were examined using a frequency scale. Data were expressed as mean±standard error. Independent t-tests or chi-square tests were used to make comparisons between groups. Results The prevalence of GERD (32.6% vs. 35.9%, P=0.266) and GERD symptoms (58.8% vs. 59.2%, P=0.503) was not significantly different between T2DM patients and controls. We found no significant differences between T2DM patients with GERD and T2DM patients without GERD with respect to diabetic complications, including autonomic neuropathy, peripheral neuropathy, duration of DM, and glucose control. Conclusion The prevalence of GERD in patients with T2DM showed no difference from that of controls. GERD was also not associated with peripheral and cardiovascular autonomic neuropathy, age, or duration of DM in patients with T2DM. PMID:27352149

  17. Type 2 diabetes and cardiovascular disease: Have all risk factors the same strength?

    PubMed Central

    Martín-Timón, Iciar; Sevillano-Collantes, Cristina; Segura-Galindo, Amparo; del Cañizo-Gómez, Francisco Javier

    2014-01-01

    Diabetes mellitus is a chronic condition that occurs when the body cannot produce enough or effectively use of insulin. Compared with individuals without diabetes, patients with type 2 diabetes mellitus have a considerably higher risk of cardiovascular morbidity and mortality, and are disproportionately affected by cardiovascular disease. Most of this excess risk is it associated with an augmented prevalence of well-known risk factors such as hypertension, dyslipidaemia and obesity in these patients. However the improved cardiovascular disease in type 2 diabetes mellitus patients can not be attributed solely to the higher prevalence of traditional risk factors. Therefore other non-traditional risk factors may be important in people with type 2 diabetes mellitus. Cardiovascular disease is increased in type 2 diabetes mellitus subjects due to a complex combination of various traditional and non-traditional risk factors that have an important role to play in the beginning and the evolution of atherosclerosis over its long natural history from endothelial function to clinical events. Many of these risk factors could be common history for both diabetes mellitus and cardiovascular disease, reinforcing the postulate that both disorders come independently from “common soil”. The objective of this review is to highlight the weight of traditional and non-traditional risk factors for cardiovascular disease in the setting of type 2 diabetes mellitus and discuss their position in the pathogenesis of the excess cardiovascular disease mortality and morbidity in these patients. PMID:25126392

  18. Body fat, fat distribution, and psychosocial factors among patients with Type 2 diabetes mellitus.

    PubMed

    Bell, R A; Summerson, J H; Spangler, J G; Konen, J C

    1998-01-01

    Diabetes, a risk factor for cardiovascular disease, requires lifestyle modifications (diet, exercise, weight loss). The relations between body mass index, waist-hip ratio (WHR), and psychosocial indicators, such as affect and stress, among 302 diabetic patients from a clinic and a neighborhood health center were analyzed. Data included stress and mood scale responses, body size (height, weight, and WHR) and potential confounders (physical activity, energy intake, and diabetes duration). In univariate analyses, body mass index was positively associated with stress and inversely associated with positive affect only in women. Multiple regression analyses indicated that stress was associated with body mass index and negative mood was associated with the WHR. The findings suggested that stress and affect may be important correlates of body fat among women with Type 2 diabetes, leading to more complications. Healthcare providers can help women with Type 2 diabetes lose weight and lower the risk of cardiovascular disease by recognizing and helping them deal with these psychosocial issues. PMID:9850808

  19. Type 2 Diabetes Mellitus Screening and Risk Factors Using Decision Tree: Results of Data Mining

    PubMed Central

    Habibi, Shafi; Ahmadi, Maryam; Alizadeh, Somayeh

    2015-01-01

    Objectives: The aim of this study was to examine a predictive model using features related to the diabetes type 2 risk factors. Methods: The data were obtained from a database in a diabetes control system in Tabriz, Iran. The data included all people referred for diabetes screening between 2009 and 2011. The features considered as “Inputs” were: age, sex, systolic and diastolic blood pressure, family history of diabetes, and body mass index (BMI). Moreover, we used diagnosis as “Class”. We applied the “Decision Tree” technique and “J48” algorithm in the WEKA (3.6.10 version) software to develop the model. Results: After data preprocessing and preparation, we used 22,398 records for data mining. The model precision to identify patients was 0.717. The age factor was placed in the root node of the tree as a result of higher information gain. The ROC curve indicates the model function in identification of patients and those individuals who are healthy. The curve indicates high capability of the model, especially in identification of the healthy persons. Conclusions: We developed a model using the decision tree for screening T2DM which did not require laboratory tests for T2DM diagnosis. PMID:26156928

  20. In vivo demonstration of cell types in bone that harbor epidermal growth factor receptors

    SciTech Connect

    Martineau-Doize, B.; Lai, W.H.; Warshawsky, H.; Bergeron, J.J.

    1988-08-01

    The binding and internalization of (/sup 125/I)iodoepidermal growth factor (EGF) by bone cells of the rat was demonstrated in situ by quantitative radioautography. Specific binding sites were observed on a cell profile enriched in endocytic components, including lysosome-like structures, a rough endoplasmic reticulum-rich cell profile, and a cell profile that histologically resembles an undifferentiated precursor cell. By the criteria of gel filtration and precipitability by trichloroacetic acid, most of the bound (/sup 125/I)iodo-EGF was considered intact. By morphological criteria none of the cell profiles that bound (/sup 125/I)iodo-EGF corresponded to fully formed osteoclasts or osteoblasts. The endocytic cell was found in the epiphyseal plate between the invading capillary and the transverse and longitudinal cartilage septa as well as near osteoclasts in the zone of mixed spicules. The rough endoplasmic reticulum-rich cell was present in vacated chondrocyte lacunae of the epiphyseal plate close to the metaphysis, and the poorly differentiated cell was observed between the mixed spicules of the metaphysis. Similar cell types were also found in the alveolar bone surrounding the incisors. These cells may be the origin of established bone cell lines that harbor high concentrations of EGF receptors and may also be responsible for the humoral hypercalcemia in response to the reported actions of injected EGF or transforming growth factor-alpha as well as that of malignancy.

  1. Genetic and environmental factors associated with type 2 diabetes and diabetic vascular complications

    PubMed Central

    Murea, Mariana; Ma, Lijun; Freedman, Barry I.

    2012-01-01

    Faced with a global epidemic of type 2 diabetes (T2D), it is critical that researchers improve our understanding of the pathogenesis of T2D and related vascular complications. These findings may ultimately lead to novel treatment options for disease prevention or delaying progression. Two major paradigms jointly underlie the development of T2D and related coronary artery disease, diabetic nephropathy, and diabetic retinopathy. These paradigms include the genetic risk variants and behavioral/environmental factors. This article systematically reviews the literature supporting genetic determinants in the pathogenesis of T2D and diabetic vasculopathy, and the functional implications of these gene variants on the regulation of beta-cell function and glucose homeostasis. We update the discovery of diabetes and diabetic vasculopathy risk variants, and describe the genetic technologies that have uncovered them. Also, genomic linkage between obesity and T2D is discussed. There is a complementary role for behavioral and environmental factors modulating the genetic susceptibility and diabetes risk. Epidemiological and clinical data demonstrating the effects of behavioral and novel environmental exposures on disease expression are reviewed. Finally, a succinct overview of recent landmark clinical trials addressing glycemic control and its impact on rates of vascular complications is presented. It is expected that novel strategies to exploit the gene- and exposure-related underpinnings of T2D will soon result. PMID:22972441

  2. Cellular transcription factors enhance herpes simplex virus type 1 oriS-dependent DNA replication.

    PubMed

    Nguyen-Huynh, A T; Schaffer, P A

    1998-05-01

    The herpes simplex virus type 1 (HSV-1) origin of DNA replication, oriS, contains three binding sites for the viral origin binding protein (OBP) flanked by transcriptional regulatory elements of the immediate-early genes encoding ICP4 and ICP22/47. To assess the role of flanking sequences in oriS function, plasmids containing oriS and either wild-type or mutant flanking sequences were tested in transient DNA replication assays. Although the ICP4 and ICP22/47 regulatory regions were shown to enhance oriS function, most individual elements in these regions, including the VP16-responsive TAATGARAT elements, were found to be dispensable for oriS function. In contrast, two oriS core-adjacent regulatory (Oscar) elements, OscarL and OscarR, at the base of the oriS palindrome were shown to enhance oriS function significantly and additively. Specifically, mutational disruption of either element reduced oriS-dependent DNA replication by 60 to 70%, and disruption of both elements reduced replication by 90%. The properties of protein-DNA complexes formed in gel mobility shift assays using uninfected and HSV-1-infected Vero cell nuclear extracts demonstrated that both OscarL and OscarR are binding sites for cellular proteins. Whereas OscarR does not correspond to the consensus binding site of any known transcription factor, OscarL contains a consensus binding site for the transcription factor Sp1. Gel mobility shift and supershift experiments using antibodies directed against members of the Sp1 family of transcription factors demonstrated the presence of Sp1 and Sp3, but not Sp2 or Sp4, in the protein-DNA complexes formed at OscarL. The abilities of OscarL and OscarR to bind their respective cellular proteins correlated directly with the efficiency of oriS-dependent DNA replication. Cooperative interactions between the Oscar-binding factors and proteins binding to adjacent OBP binding sites were not observed. Notably, Oscar element mutations that impaired oriS-dependent DNA

  3. A Csr-type regulatory system, including small non-coding RNAs, regulates the global virulence regulator RovA of Yersinia pseudotuberculosis through RovM.

    PubMed

    Heroven, Ann Kathrin; Böhme, Katja; Rohde, Manfred; Dersch, Petra

    2008-06-01

    The MarR-type regulator RovA controls expression of virulence genes of Yersinia pseudotuberculosis in response to environmental signals. Using a genetic strategy to discover components that influence rovA expression, we identified new regulatory factors with homology to components of the carbon storage regulator system (Csr). We showed that overexpression of a CsrB- or a CsrC-type RNA activates rovA, whereas a CsrA-like protein represses RovA synthesis. We further demonstrate that influence of the Csr system on rovA is indirect and occurs through control of the LysR regulator RovM, which inhibits rovA transcription. The CsrA protein had also a major influence on the motility of Yersinia, which was independent of RovM. The CsrB and CsrC RNAs are differentially expressed in Yersinia. CsrC is highly induced in complex but not in minimal media, indicating that medium-dependent rovM expression is mediated through CsrC. CsrB synthesis is generally very low. However, overexpression of the response regulator UvrY was found to activate CsrB production, which in turn represses CsrC synthesis independent of the growth medium. In summary, the post-transcriptional Csr-type components were shown to be key regulators in the co-ordinated environmental control of physiological processes and virulence factors, which are crucial for the initiation of Yersinia infections. PMID:18430141

  4. Biosynthesis of Dictyostelium discoideum differentiation-inducing factor by a hybrid type I fatty acid-type III polyketide synthase.

    PubMed

    Austin, Michael B; Saito, Tamao; Bowman, Marianne E; Haydock, Stephen; Kato, Atsushi; Moore, Bradley S; Kay, Robert R; Noel, Joseph P

    2006-09-01

    Differentiation-inducing factors (DIFs) are well known to modulate formation of distinct communal cell types from identical Dictyostelium discoideum amoebas, but DIF biosynthesis remains obscure. We report complimentary in vivo and in vitro experiments identifying one of two approximately 3,000-residue D. discoideum proteins, termed 'steely', as responsible for biosynthesis of the DIF acylphloroglucinol scaffold. Steely proteins possess six catalytic domains homologous to metazoan type I fatty acid synthases (FASs) but feature an iterative type III polyketide synthase (PKS) in place of the expected FAS C-terminal thioesterase used to off load fatty acid products. This new domain arrangement likely facilitates covalent transfer of steely N-terminal acyl products directly to the C-terminal type III PKS active sites, which catalyze both iterative polyketide extension and cyclization. The crystal structure of a steely C-terminal domain confirms conservation of the homodimeric type III PKS fold. These findings suggest new bioengineering strategies for expanding the scope of fatty acid and polyketide biosynthesis. PMID:16906151

  5. Biosynthesis of Dictyostelium discoideum differentiation-inducing factor by a hybrid type I fatty acid–type III polyketide synthase

    PubMed Central

    Austin, Michael B; Saito, Tamao; Bowman, Marianne E; Haydock, Stephen; Kato, Atsushi; Moore, Bradley S; Kay, Robert R; Noel, Joseph P

    2010-01-01

    Differentiation-inducing factors (DIFs) are well known to modulate formation of distinct communal cell types from identical Dictyostelium discoideum amoebas, but DIF biosynthesis remains obscure. We report complimentary in vivo and in vitro experiments identifying one of two ~3,000-residue D. discoideum proteins, termed ‘steely’, as responsible for biosynthesis of the DIF acylphloroglucinol scaffold. Steely proteins possess six catalytic domains homologous to metazoan type I fatty acid synthases (FASs) but feature an iterative type III polyketide synthase (PKS) in place of the expected FAS C-terminal thioesterase used to off load fatty acid products. This new domain arrangement likely facilitates covalent transfer of steely N-terminal acyl products directly to the C-terminal type III PKS active sites, which catalyze both iterative polyketide extension and cyclization. The crystal structure of a steely C-terminal domain confirms conservation of the homodimeric type III PKS fold. These findings suggest new bioengineering strategies for expanding the scope of fatty acid and polyketide biosynthesis. PMID:16906151

  6. Incineration of different types of medical wastes: emission factors for gaseous emissions

    NASA Astrophysics Data System (ADS)

    Alvim-Ferraz, M. C. M.; Afonso, S. A. V.

    Previous research works showed that to protect public health, the hospital incinerators should be provided with air pollution control devices. As most hospital incinerators do not possess such equipment, efficient methodologies should be developed to evaluate the safety of incineration procedure. Emission factors (EF) can be used for an easy estimation of legal parameters. Nevertheless, the actual knowledge is yet very scarce, mainly because EF previously published do not include enough information about the incinerated waste composition, besides considering many different waste classifications. This paper reports the first EF estimated for CO, SO 2, NO x and HCl, associated to the incineration of medical waste, segregated in different types according to the classification of the Portuguese legislation. The results showed that those EF are strongly influenced by incinerated waste composition, directly affected by incinerated waste type, waste classification, segregation practice and management methodology. The correspondence between different waste classifications was analysed comparing the estimated EF with the sole results previously published for specific waste types, being observed that the correspondence is not always possible. The legal limit for pollutant concentrations could be obeyed for NO x, but concentrations were higher than the limit for CO (11-24 times), SO 2 (2-5 times), and HCl (9-200 times), confirming that air pollution control devices must be used to protect human health. The small heating value of medical wastes with compulsory incineration implied the requirement of a bigger amount of auxiliary fuel for their incineration, which affects the emitted amounts of CO, NO x and SO 2 (28, 20 and practically 100% of the respective values were related with fuel combustion). Nevertheless, the incineration of those wastes lead to the smallest amount of emitted pollutants, the emitted amount of SO 2 and NO x reducing to 93% and the emitted amount of CO

  7. Type of gambling as an independent risk factor for suicidal events in pathological gamblers.

    PubMed

    Bischof, Anja; Meyer, Christian; Bischof, Gallus; John, Ulrich; Wurst, Friedrich Martin; Thon, Natasha; Lucht, Michael; Grabe, Hans-Joergen; Rumpf, Hans-Juergen

    2016-03-01

    Individuals with pathological gambling have an increased risk for suicidal events. Additionally, the prevalence of comorbid psychiatric disorders is high among pathological gamblers. This study analyzes whether the type of gambling is associated with suicidal events in pathological gamblers independently from comorbidity. Participants were recruited in 4 different ways: via random telephone sample from the general population, via individual invitation for study participation in gambling locations, through various media and the distribution of a leaflet in various settings, and via inpatient treatment facilities for pathological gambling. The final sample included 442 participants with a lifetime diagnosis of pathological gambling. A standardized clinical interview was conducted. High financial losses were associated with suicidal events (odds ratio [OR] = 1.94, 95% 95% confidence interval [CI], [1.11, 3.37]), as were mood disorders (OR = 7.70, 95% CI, [4.44, 13.37]) and female gender (OR = 2.52, 95% CI, [1.20, 5.28]). Gambling on electronic gambling machines in gambling halls or bars was associated with increased odds of suicidal events (OR = 2.94, 95% CI, [1.38, 6.24]). Other types of gambling, such as casino games or betting on sports, or the number of DSM-IV criteria for pathological gambling were not associated independently with suicidal events. Our findings suggest that gambling on electronic gambling machines in gambling halls or bars is associated with suicidal events in pathological gamblers independently of comorbidity. This result shows that the type of gambling needs to be considered as a relevant factor in gambling research. (PsycINFO Database Record PMID:26795395

  8. Depression in romanian patients with type 2 diabetes: prevalence and risk factors

    PubMed Central

    MOCAN, ANDREIA S.; IANCU, SILVIA S.; DUMA, LIVIA; MURESEANU, CAMELIA; BABAN, ADRIANA S.

    2016-01-01

    Background and aims Co-existing major depression was found to have a negative impact on the diabetes outcome and the quality of life. The aim of the present study was to assess the prevalence of depressive symptoms in Romanian diabetes patients and to identify the risk factors associated with depression. Methods A total of 144 type 2 diabetes patients were included in the study. Five models of presumed predictors were used to assess the risk factors for depressive symptoms, using hierarchical regression analysis. Together with demographics, disease, lifestyle predictors, previous depressive symptoms and diabetes distress were taken into account. Results In our sample the prevalence of depression was 12.6%. Main risk factors for depressive symptoms were previous depressive symptoms which were associated with depression in both Model 4 (β=0.297, p=0.013) and Model 5 (β=0.239, p=0.017) and diabetes distress in Model 5 (β=0.540, p≤0.001). Employment (β =−0.276, p=0.029) and increased number of diabetes complications (β=0.236, p=0.017) became significant when diabetes distress was added to the analysis. Conclusions The overall prevalence of depressive symptoms was found to be in range with the prevalence identified in the literature. Previous depression and diabetes distress were both independently associated with depression, confirming the bidirectional relationship between depression and diabetes distress. Due to the consequences for daily living, screening for diabetes distress and depression should be done in primary care units both by physicians and trained nurses. PMID:27547056

  9. Hypoxia-inducible factor regulates expression of surfactant protein in alveolar type II cells in vitro.

    PubMed

    Ito, Yoko; Ahmad, Aftab; Kewley, Emily; Mason, Robert J

    2011-11-01

    Alveolar type II (ATII) cells cultured at an air-liquid (A/L) interface maintain differentiation, but they lose these properties when they are submerged. Others showed that an oxygen tension gradient develops in the culture medium as ATII cells consume oxygen. Therefore, we wondered whether hypoxia inducible factor (HIF) signaling could explain differences in the phenotypes of ATII cells cultured under A/L interface or submerged conditions. ATII cells were isolated from male Sprague-Dawley rats and cultured on inserts coated with a mixture of rat-tail collagen and Matrigel, in medium including 5% rat serum and 10 ng/ml keratinocyte growth factor, with their apical surfaces either exposed to air or submerged. The A/L interface condition maintained the expression of surfactant proteins, whereas that expression was down-regulated under the submerged condition, and the effect was rapid and reversible. Under submerged conditions, there was an increase in HIF1α and HIF2α in nuclear extracts, mRNA levels of HIF inducible genes, vascular endothelial growth factor, glucose transporter-1 (GLUT1), and the protein level of pyruvate dehydrogenase kinase isozyme-1. The expression of surfactant proteins was suppressed and GLUT1 mRNA levels were induced when cells were cultured with 1 mM dimethyloxalyl glycine. The expression of surfactant proteins was restored under submerged conditions with supplemented 60% oxygen. HIF signaling and oxygen tension at the surface of cells appears to be important in regulating the phenotype of rat ATII cells. PMID:21454802

  10. Factors Associated with Consumption of Diabetic Diet among Type 2 Diabetic Subjects from Ahmedabad, Western India

    PubMed Central

    Patel, Mayur; Patel, Ina M.; Patel, Yash M.

    2012-01-01

    This cross-sectional study assessed the current situation of and factors associated with consumption of diabetic diet among 399 type 2 diabetes mellitus (T2DM) subjects from Ahmedabad, Western India. The study was performed with diagnosed (at least one year old) diabetic subjects who attended the Department of Diabetology, All India Institute of Diabetes and Research and Yash Diabetes Specialties Centre (Swasthya Hospital), Ahmedabad during July 2010–November 2010. The subjects completed an interviewer-administered questionnaire. The questionnaire included variables, such as sociodemographic factors, family history of diabetes, behavioural profile, risk profile (glycaemic status, hypertension, and obesity), and diet-related history (consumption of diabetic diet, consumption of low fat/skimmed milk, method of cooking, and sources for diet advice). Blood pressure, body mass index, glycosylated haemoglobin (HbA1c) level, and fasting lipid profile were measured. All analyses including multivariate logistic regression were conducted using SPSS, version 11.5. In total, 399 T2DM subjects (65% male, 35% female) with mean age of 53.16±7.95 years were studied. Although 73% of T2DM subjects were consuming diabetic diet, the good glycaemic control (HbA1c level <7%) was achieved only in 35% of the subjects. The majority (75%) of the subjects had a positive family history of diabetes, and 52% were obese. In 77%, the main source of dietary advice was doctor. In 36%, the main methods of cooking were: boiling and roasting. The final multivariate model showed that visit to dietician, level of education, intake of low fat, and family history of diabetes were independent predictors for diabetic diet consumption among T2DM subjects. However, longitudinal and cohort studies are required to establish the association between consumption of diabetic diet and glycaemic control. PMID:23304911

  11. Factors affecting the motivation of healthcare professionals providing care to Emiratis with type 2 diabetes

    PubMed Central

    Alhyas, Layla; Nielsen, Jessica D Jones; Dawoud, Dalia; Majeed, Azeem

    2013-01-01

    Objective We aimed to identify facilitators of and barriers to healthcare professionals' motivation in a diabetes centre in the United Arab Emirates (UAE). Design A qualitative research approach was employed using semistructured interviews to assess perception of and attitudes regarding healthcare professionals' motivation in providing good quality diabetes care. Setting A diabetes centre located in Abu-Dhabi, UAE. Participants Healthcare professionals including specialist physicians, dieticians, podiatrists, health educators and nurses were recruited through purposive sampling. Main outcome measures After data collection, the audiotaped interviews were transcribed verbatim and subjected to content analysis. Results Nine semistructured interviews were conducted with healthcare professionals of various professional backgrounds. Important facilitators and barriers related to patient, professional, organization and cultural factors were identified. Barriers that related to heavy workload, disjointed care, lack of patient compliance and awareness, and cultural beliefs and attitudes about diabetes were common. Key facilitators included the patient's role in achieving therapeutic outcomes as well as compliance, cooperation and communication. Conclusion This qualitative study provides some unique insights about factors affecting healthcare professionals' motivation in providing good quality care. To improve the motivation of healthcare professionals in the management of diabetes and therefore the quality of diabetes care, several steps are needed. Importantly, the role of primary care should be reinforced and strengthened regarding the management of type 2 diabetes mellitus, privacy of the consultation time should be highly protected and regulated, and awareness of the Emirate culture and its impact on health should be disseminated to the healthcare professionals providing care to Emirates with diabetes. Also, greater emphasis should be placed on educating Emiratis with

  12. Empowerment assessment and influential factors among patients with type 2 diabetes

    PubMed Central

    2013-01-01

    Background Diabetic patients need high awareness of disease prevention to adopt self-management behaviors in their daily life. Central to this activity is patients’ empowerment. Current study was conducted to assess empowerment score and its related factors among type 2 diabetic patients. Method A cross-sectional study carried out over a period of nine months during 2010–2011. All patients with a diagnosis of type 2 diabetes including those referring to four hospitals affiliated with Tehran University of Medical Sciences were recruited. A total of 688 diabetic patients were identified who met the inclusion criteria and were all included in the study. Patients’ empowerment was measured by Diabetes Empowerment Scale reflecting three dimensions including managing psychosocial aspect of diabetes, assessing dissatisfaction and readiness to change and Setting and achieving diabetes goal. Collected data was analysed using SPSS software version 11.5. Results As total, 688 were available for analysis, ranging from 37–81 years old with mean of 54.41 years (SD = 8.22). The Mean duration of the disease was approximately 6.67 years (SD = 4.58). Dimensions of ‘managing the psychosocial aspect of diabetes’, ‘assessing dissatisfaction and readiness to change’ and ‘setting and achieving diabetes goal’ were all measured and scored for each patient. The mean score for each domain was 25.75 ± 5.55, 24.78 ± 7.54, 27.63 ± 7.90, respectively. Data analysis revealed a statistically significant reverse relationship between age and ‘assessing dissatisfaction and readiness to change’ and ‘setting and achieving diabetes goal’. In addition, disease duration had a statistically significant reverse relationship with ‘assessing dissatisfaction and readiness to change’. Conclusion Patients with type 2 diabetes have the potential to be empowered to manage their chronic disease if they are actively informed and educated. PMID:23497631

  13. Risk Factors Contributing to Type 2 Diabetes and Recent Advances in the Treatment and Prevention

    PubMed Central

    Wu, Yanling; Ding, Yanping; Tanaka, Yoshimasa; Zhang, Wen

    2014-01-01

    Type 2 diabetes is a serious and common chronic disease resulting from a complex inheritance-environment interaction along with other risk factors such as obesity and sedentary lifestyle. Type 2 diabetes and its complications constitute a major worldwide public health problem, affecting almost all populations in both developed and developing countries with high rates of diabetes-related morbidity and mortality. The prevalence of type 2 diabetes has been increasing exponentially, and a high prevalence rate has been observed in developing countries and in populations undergoing “westernization” or modernization. Multiple risk factors of diabetes, delayed diagnosis until micro- and macro-vascular complications arise, life-threatening complications, failure of the current therapies, and financial costs for the treatment of this disease, make it necessary to develop new efficient therapy strategies and appropriate prevention measures for the control of type 2 diabetes. Herein, we summarize our current understanding about the epidemiology of type 2 diabetes, the roles of genes, lifestyle and other factors contributing to rapid increase in the incidence of type 2 diabetes. The core aims are to bring forward the new therapy strategies and cost-effective intervention trials of type 2 diabetes. PMID:25249787

  14. Risk factors contributing to type 2 diabetes and recent advances in the treatment and prevention.

    PubMed

    Wu, Yanling; Ding, Yanping; Tanaka, Yoshimasa; Zhang, Wen

    2014-01-01

    Type 2 diabetes is a serious and common chronic disease resulting from a complex inheritance-environment interaction along with other risk factors such as obesity and sedentary lifestyle. Type 2 diabetes and its complications constitute a major worldwide public health problem, affecting almost all populations in both developed and developing countries with high rates of diabetes-related morbidity and mortality. The prevalence of type 2 diabetes has been increasing exponentially, and a high prevalence rate has been observed in developing countries and in populations undergoing "westernization" or modernization. Multiple risk factors of diabetes, delayed diagnosis until micro- and macro-vascular complications arise, life-threatening complications, failure of the current therapies, and financial costs for the treatment of this disease, make it necessary to develop new efficient therapy strategies and appropriate prevention measures for the control of type 2 diabetes. Herein, we summarize our current understanding about the epidemiology of type 2 diabetes, the roles of genes, lifestyle and other factors contributing to rapid increase in the incidence of type 2 diabetes. The core aims are to bring forward the new therapy strategies and cost-effective intervention trials of type 2 diabetes. PMID:25249787

  15. Synergistic and multidimensional regulation of plasminogen activator inhibitor type 1 expression by transforming growth factor type β and epidermal growth factor

    SciTech Connect

    Song, Xiaoling; Thalacker, F.W.; Nilsen-Hamilton, Marit

    2012-04-06

    The major physiological inhibitor of plasminogen activator, type I plasminogen activator inhibitor (PAI-1), controls blood clotting and tissue remodeling events that involve cell migration. Transforming growth factor type β (TGFβ) and epidermal growth factor (EGF) interact synergistically to increase PAI-1 mRNA and protein levels in human HepG2 and mink Mv1Lu cells. Other growth factors that activate tyrosine kinase receptors can substitute for EGF. EGF and TGFβ regulate PAI-1 by synergistically activating transcription, which is further amplified by a decrease in the rate of mRNA degradation, the latter being regulated only by EGF. The combined effect of transcriptional activation and mRNA stabilization results in a rapid 2-order of magnitude increase in the level of PAI-1. TGFβ also increases the sensitivity of the cells to EGF, thereby recruiting the cooperation of EGF at lower than normally effective concentrations. The contribution of EGF to the regulation of PAI-1 involves the MAPK pathway, and the synergistic interface with the TGFβ pathway is downstream of MEK1/2 and involves phosphorylation of neither ERK1/2 nor Smad2/3. Synergism requires the presence of both Smad and AP-1 recognition sites in the promoter. This work demonstrates the existence of a multidimensional cellular mechanism by which EGF and TGFβ are able to promote large and rapid changes in PAI-1 expression.

  16. Approximate analytical solutions of the relativistic equations with the Deng-Fan molecular potential including a Pekeris-type approximation to the (pseudo or) centrifugal term

    NASA Astrophysics Data System (ADS)

    Oluwadare, O. J.; Oyewumi, K. J.; Akoshile, C. O.; Babalola, O. A.

    2012-09-01

    By employing the Pekeris-type (or a new improved approximation) to deal with the (pseudo or) centrifugal term, we solve the Klein-Gordon and Dirac equations with equally mixed scalar and vector Deng-Fan molecular potentials for all values of l (orbital the angular momentum quantum number) and κ (spin-orbit coupling quantum number), respectively. Using the formalism of the Nikiforov-Uvarov method, the approximate analytical bound state energy equations and the associated two-component spinors corresponding to the two relativistic equations are obtained. Also, special cases including the non-relativistic limits of the relativistic equation are obtained.

  17. The first familial case of inherited 2q37.3 interstitial deletion with isolated skeletal abnormalities including brachydactyly type E and short stature.

    PubMed

    Jean-Marçais, Nolwenn; Decamp, Matthieu; Gérard, Marion; Ribault, Virginie; Andrieux, Joris; Kottler, Marie-Laure; Plessis, Ghislaine

    2015-01-01

    Albright hereditary osteodystrophy (AHO)-like syndrome is also known as brachydactyly-mental retardation syndrome (BDMR; OMIM 60040). This disorder includes intellectual disability in all patients, skeletal abnormalities, including brachydactyly E (BDE) in approximately half, obesity, and facial dysmorphism. Patients with 2q37 microdeletion or HDAC4 mutation are defined as having an AHO-like phenotype with normal stimulatory G (Gs) function. HDAC4 is involved in neurological, cardiac, and skeletal function. This paper reports the first familial case of 2q37.3 interstitial deletion affecting two genes, HDAC4 and TWIST2. Patients presented with BDE and short stature without intellectual disability, showing that haploinsufficiency of the HDAC4 critical region may lead to a spectrum of phenotypes, ranging from isolated brachydactyly type E to BDMR. PMID:25402011

  18. [Type 2 diabetes mellitus and cardiovascular risk factors: is comprehensive treatment required?].

    PubMed

    Nadal, Josep Franch; Gutiérrez, Pedro Conthe

    2013-09-01

    Diabetes mellitus, especially type 2, is a metabolic disease involving the coexistence of several cardiovascular risk factors. Affected patients are therefore at high cardiovascular risk (2-3 times higher than that of men in the general population and 2-6 times higher than that of women). Cardiovascular disease is the main cause of death in the diabetic population, followed by cancer. Cardiovascular risk cannot be compared between diabetic patients and persons who have already shown one or more manifestations of cardiovascular disease (such as myocardial infarction). Single risk factors should be evaluated in combination with other risk factors and a person's cardiovascular risk should be individually assessed. Cardiovascular risk assessment in patients with diabetes through current calculations methods is complex because their ability to predict risk in individuals is very low. Studies such as that by Steno have demonstrated the validity of a comprehensive strategy to control all the risk factors present in persons with type 2 diabetes mellitus, which can reduce the development of micro- and macrovascular complications and mortality by almost 50%. The present article reviews each of the classical cardiovascular risk factors (hypertension, dyslipidemia, smoking, obesity, sedentariness) in relation to diabetes, as well as their recommended targets and the benefits of their control. In view of the above, a comprehensive approach is recommended to control the multiple risk factors that can coexist in persons with type 2 diabetes mellitus. PMID:24444518

  19. Aroma types of flue-cured tobacco in China: spatial distribution and association with climatic factors

    NASA Astrophysics Data System (ADS)

    Yang, Chao; Wu, Wei; Wu, Shu-Cheng; Liu, Hong-Bin; Peng, Qing

    2014-02-01

    Aroma types of flue-cured tobacco (FCT) are classified into light, medium, and heavy in China. However, the spatial distribution of FCT aroma types and the relationships among aroma types, chemical parameters, and climatic variables were still unknown at national scale. In the current study, multi-year averaged chemical parameters (total sugars, reducing sugars, nicotine, total nitrogen, chloride, and K2O) of FCT samples with grade of C3F and climatic variables (mean, minimum and maximum temperatures, rainfall, relative humidity, and sunshine hours) during the growth periods were collected from main planting areas across China. Significant relationships were found between chemical parameters and climatic variables ( p < 0.05). A spatial distribution map of FCT aroma types were produced using support vector machine algorithms and chemical parameters. Significant differences in chemical parameters and climatic variables were observed among the three aroma types based on one-way analysis of variance ( p < 0.05). Areas with light aroma type had significantly lower values of mean, maximum, and minimum temperatures than regions with medium and heavy aroma types ( p < 0.05). Areas with heavy aroma type had significantly lower values of rainfall and relative humidity and higher values of sunshine hours than regions with light and medium aroma types ( p < 0.05). The output produced by classification and regression trees showed that sunshine hours, rainfall, and maximum temperature were the most important factors affecting FCT aroma types at national scale.

  20. Risk factors for adolescent sex offender recidivism: evaluation of predictive factors and comparison of three groups based upon victim type.

    PubMed

    Parks, Gregory A; Bard, David E

    2006-10-01

    This study investigated differences in recidivism risk factors and traits associated with psychopathy among 3 groups of male adolescent sexual offenders (N=156): offenders against children, offenders against peers or adults, and mixed type offenders. Furthermore, those same variables were examined for their association with sexual and nonsexual recidivism and the 3 groups were compared for differences in rates of recidivism. Based upon both juvenile and adult recidivism data, 6.4% of the sample reoffended sexually and 30.1% reoffended nonsexually. Retrospective risk assessments were completed using the Juvenile Sex Offender Assessment Protocol-II (JSOAP-II) and the Psychopathy Checklist:Youth Version (PCL:YV). Comparisons of the 3 preexisting groups for differences on scale and factor scores were conducted using analyses of variance (ANOVAs). Differences among groups for recidivism were measured using survival curve analysis. Associations between risk scales and recidivism were measured using Cox regression analyses. Results suggest significant differences among the 3 offender groups on multiple scales of the JSOAP-II and PCL:YV, with mixed type offenders consistently producing higher risk scores as compared to those who exclusively offend against children or peers/adults. The Impulsive/Antisocial Behavior scale of the JSOAP-II and the Interpersonal and Antisocial factors of the PCL:YV were significant predictors of sexual recidivism. The Behavioral and Antisocial factors of the PCL:YV were significant predictors of nonsexual recidivism. Results supported previous research indicating that most adolescents who sexually offend do not continue offending into adulthood. Such results can lead to improved treatment by targeting specific risk factors for intervention and better use of risk management resources in the community, while preserving the most restrictive treatment options for the highest risk offenders. PMID:17136626

  1. HLA typing with monoclonal antibodies: evaluation of 356 HLA monoclonal antibodies including 181 studied during the 10th International Histocompatibility Workshop.

    PubMed

    Colombani, J; Lepage, V; Raffoux, C; Colombani, M

    1989-08-01

    During the 10th International Histocompatibility Workshop (10th WS), 181 HLA MoAbs were studied using lymphocytotoxicity micro-technique (LCT) and/or enzyme immuno-assay (EIA), and their capacity to serve as typing reagents was evaluated. 129 MoAbs were tested by both techniques. Results obtained with 92 class I and 86 class II polymorphic MoAbs (10th WS) were compared to published data concerning 180 class I and 176 class II polymorphic MoAbs, listed in an HLA-MoAbs Register maintained in our laboratory. The following conclusions can be proposed: 1/HLA-A, B typing by LCT with MoAbs is possible for about 14 specificities. Some specificities are clearly recognized (HLA-A3, B8, B13, Bw4, Bw6), others are recognized as cross-reacting groups (B7+27+w22+40), others are not currently recognized by any MoAb with restricted specificity (B5, B15). Several MoAbs confirmed the existence of shared epitopes between products from a single locus (A2-A28, A25-A32), or from A and B loci (A2-B17, Bw4-A9-A32). A single HLA-Cw MoAb has been described. 2/HLA class II typing by LCT with MoAbs is more difficult than class I typing. DR2, DR3, DR4, DR5 and DR7 as well as DRw52 and DRw53 are well defined; other DR specificities are poorly or not at all defined. Particular associations (DR1+DR4, DR3+DRw6, all DR except DR7) are recognized by several MoAbs. All DQw specificities are well recognized, including new specificities defined only by MoAbs: WA (DQw4), TA10 (DQw7), 2B3 (DQw6+w8+w9). Only two HLA-DP MoAbs have been described. 3/Satisfactory results, similar to those of LCT, were obtained with EIA using lymphoid cell lines as targets. 4/Human MoAbs (12 in the Register) are satisfactory typing reagents. They could represent in the future a significant contribution to HLA typing with MoAbs. PMID:2609328

  2. Source apportionment of PM10 in a North-Western Europe regional urban background site (Lens, France) using Positive Matrix Factorization and including primary biogenic emissions

    NASA Astrophysics Data System (ADS)

    Waked, A.; Favez, O.; Alleman, L. Y.; Piot, C.; Petit, J.-E.; Delaunay, T.; Verlinden, E.; Golly, B.; Besombes, J.-L.; Jaffrezo, J.-L.; Leoz-Garziandia, E.

    2013-10-01

    In this work, the source of ambient particulate matter (PM10) collected over a one year period at an urban background site in Lens (France) were determined and investigated using a~Positive Matrix Factorization receptor model (US EPA PMF v3.0). In addition, a Potential Source Contribution Function (PSCF) was performed by means of the Hysplit v4.9 model to assess prevailing geographical origins of the identified sources. A selective iteration process was followed for the qualification of the more robust and meaningful PMF solution. Components measured and used in the PMF include inorganic and organic species: soluble ionic species, trace elements, elemental carbon (EC), sugars alcohols, sugar anhydride, and organic carbon (OC). The mean PM10 concentration measured from March 2011 to March 2012 was about 21 μg m-3 with typically OM, nitrate and sulfate contributing to most of the mass and accounting respectively for 5.8, 4.5 and 2.3 μg m-3 on a yearly basis. Accordingly, PMF outputs showed that the main emission sources were (in a decreasing order of contribution): secondary inorganic aerosols (28% of the total PM10 mass), aged marine emissions (19%), with probably predominant contribution of shipping activities, biomass burning (13%), mineral dust (13%), primary biogenic emissions (9%), fresh sea salts (8%), primary traffic emissions (6%) and heavy oil combustion (4%). Significant temporal variations were observed for most of the identified sources. In particular, biomass burning emissions were negligible in summer but responsible for about 25% of total PM10 and 50% of total OC at wintertime. Conversely, primary biogenic emissions were found to be negligible in winter but to represent about 20% of total PM10 and 40% of total OC in summer. The latter result calls for more investigations of primary biogenic aerosols using source apportionment studies, which quite usually disregards this type of sources. This study furthermore underlines the major influence of

  3. Source apportionment of PM10 in a north-western Europe regional urban background site (Lens, France) using positive matrix factorization and including primary biogenic emissions

    NASA Astrophysics Data System (ADS)

    Waked, A.; Favez, O.; Alleman, L. Y.; Piot, C.; Petit, J.-E.; Delaunay, T.; Verlinden, E.; Golly, B.; Besombes, J.-L.; Jaffrezo, J.-L.; Leoz-Garziandia, E.

    2014-04-01

    In this work, the source of ambient particulate matter (PM10) collected over a one-year period at an urban background site in Lens (France) was determined and investigated using a positive matrix factorization receptor model (US EPA PMF v3.0). In addition, a potential source contribution function (PSCF) was performed by means of the Hybrid Single-Particle Lagrangian Integrated Trajectory (Hysplit) v4.9 model to assess prevailing geographical origins of the identified sources. A selective iteration process was followed for the qualification of the more robust and meaningful PMF solution. Components measured and used in the PMF included inorganic and organic species: soluble ionic species, trace elements, elemental carbon (EC), sugar alcohols, sugar anhydride, and organic carbon (OC). The mean PM10 concentration measured from March 2011 to March 2012 was about 21 μg m-3 with typically OM, nitrate and sulfate contributing to most of the mass and accounting respectively for 5.8, 4.5 and 2.3 μg m-3 on a yearly basis. Accordingly, PMF outputs showed that the main emission sources were (in decreasing order of contribution) secondary inorganic aerosols (28% of the total PM10 mass), aged marine emissions (19%), with probably predominant contribution of shipping activities, biomass burning (13%), mineral dust (13%), primary biogenic emissions (9%), fresh sea salts (8%), primary traffic emissions (6%) and heavy oil combustion (4%). Significant temporal variations were observed for most of the identified sources. In particular, biomass burning emissions were negligible in summer but responsible for about 25% of total PM10 and 50% of total OC in wintertime. Conversely, primary biogenic emissions were found to be negligible in winter but to represent about 20% of total PM10 and 40% of total OC in summer. The latter result calls for more investigations of primary biogenic aerosols using source apportionment studies, which quite usually disregard this type of source. This study

  4. Mexican American Parents' Perceptions of Childhood Risk Factors for Type 2 Diabetes

    ERIC Educational Resources Information Center

    Head, Barbara J.; Barr, Kathleen L.; Baker, Sharon K.

    2011-01-01

    A study was conducted to identify the norms, values, and perceptions of urban immigrant Mexican American (MA) parents of school children relative to physical activity, healthy eating, and child risk factors for type 2 diabetes. Investigators facilitated five focus groups in an urban elementary school setting and analyzed data using qualitative…

  5. Suicide, Schizophrenia, and Schizoid-Type Psychosis: Role of Life Events and Childhood Factors

    ERIC Educational Resources Information Center

    Tousignant, Michel; Pouliot, Louise; Routhier, Danielle; Vrakas, Georgia; McGirr, Alexander; Turecki, Gustavo

    2011-01-01

    The first objective was to identify the provoking events of suicide in patients with schizophrenia or schizoid-type disorder, and to assess the humiliation component of these events. The second objective was to verify if quality of care during childhood is a vulnerability factor for suicide in patients with schizophrenia or schizoid-type…

  6. Noninvasive Screening for Risk Factors of Type 2 Diabetes in Young, Rural, Caucasian Children

    ERIC Educational Resources Information Center

    Peterson, Sharon; Sheffer, Sarah; Long Roth, Sara; Bennett, Paul A.; Lloyd, Les

    2010-01-01

    School nurses play an important role in identifying students who are at risk for Type 2 diabetes mellitus (T2DM). Few studies have screened Caucasian students, and none have targeted rural, low-income, elementary children. The five noninvasive risk factors used for this study were family history, high body mass index (BMI) for age/sex,…

  7. Differences between Juvenile Offenders with and without Intellectual Disability in Offense Type and Risk Factors

    ERIC Educational Resources Information Center

    Asscher, Jessica J.; van der Put, Claudia E.; Stams, Geert Jan J. M.

    2012-01-01

    The present study aimed to examine differences between American juvenile offenders with and without intellectual disability (ID) in offense type and risk factors. The sample consisted of adolescents with ID (n = 102) and without ID (n = 526) who appeared before the courts for a criminal act and for whom the Washington State Juvenile Court…

  8. Putative paternal factors controlling chilling tolerance in Korean market-type cucumber (Cucumis sativus L.)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Chilling temperatures (<10 degrees C) may cause damage to Korean market-type cucumber (Cucumis sativus L.) plants during winter and early spring growing seasons. Inheritance to chilling in U.S. processing cucumber is controlled by cytoplasmic (maternally) and nuclear factors. To understand inherit...

  9. Contribution of the Nurses’ Health Studies to Uncovering Risk Factors for Type 2 Diabetes: Diet, Lifestyle, Biomarkers, and Genetics

    PubMed Central

    Ley, Sylvia H.; Ardisson Korat, Andres V.; Sun, Qi; Tobias, Deirdre K.; Zhang, Cuilin; Qi, Lu; Willett, Walter C.; Manson, JoAnn E.

    2016-01-01

    Objectives. To review the contribution of the Nurses’ Health Study (NHS) and the NHS II to addressing hypotheses regarding risk factors for type 2 diabetes. Methods. We carried out a narrative review of 1976 to 2016 NHS and NHS II publications. Results. The NHS and NHS II have uncovered important roles in type 2 diabetes for individual nutrients, foods, dietary patterns, and physical activity independent of excess body weight. Up to 90% of type 2 diabetes cases are potentially preventable if individuals follow a healthy diet and lifestyle. The NHS investigations have also identified novel biomarkers for diabetes, including adipokines, inflammatory cytokines, nutrition metabolites, and environmental pollutants, offering new insights into the pathophysiology of the disease. Global collaborative efforts have uncovered many common genetic variants associated with type 2 diabetes and improved our understanding of gene–environment interactions. Continued efforts to identify epigenetic, metagenomic, and metabolomic risk factors for type 2 diabetes have the potential to reveal new pathways and improve prediction and prevention. Conclusions. Over the past several decades, the NHS and NHS II have made major contributions to public health recommendations and strategies designed to reduce the global burden of diabetes. PMID:27459454

  10. [New recurrent extended deletion, including GJB2 and GJB6 genes, results in isolated sensorineural hearing impairment with autosomal recessive type of inheritance].

    PubMed

    Bliznets, E A; Makienko, O N; Okuneva, E G; Markova, T G; Poliakov, A V

    2014-04-01

    Hereditary hearing loss with the autosomal recessive type of inheritance of the DFNB 1 genetic type, caused by mutations in the GJB2 gene, is the main reason of innate non-syndromal hearing impairment in most developed countries of the world (including Russia). Intragenic point mutations prevail among the GJB2 gene defectors; however, extended deletions in the DFNB1 locus are also found with considerable frequency in some populations (for example, Spain, Great Britain, France, United States, and Brazil). Among the four known extended deletions, only one deletion affects directly the GJB2 gene sequence and was described in a single family. A new extended deletion in the GJB2 and GJB6 gene sequences (approximately 101 kb in size; NC_000013.10:g.20,757,021_20,858,394del), detected in three unrelated Russian patients, was described and characterized. Ingush origin of this mutation is assumed. If the new deletion is frequent, its detection is very important for the genetic consulting of families with hereditary hearing impairment. PMID:25715449

  11. Risk factors affecting fatal bus accident severity: Their impact on different types of bus drivers.

    PubMed

    Feng, Shumin; Li, Zhenning; Ci, Yusheng; Zhang, Guohui

    2016-01-01

    While the bus is generally considered to be a relatively safe means of transportation, the property losses and casualties caused by bus accidents, especially fatal ones, are far from negligible. The reasons for a driver to incur fatalities are different in each case, and it is essential to discover the underlying risk factors of bus fatality severity for different types of drivers in order to improve bus safety. The current study investigates the underlying risk factors of fatal bus accident severity to different types of drivers in the U.S. by estimating an ordered logistic model. Data for the analysis are retrieved from the Buses Involved in Fatal Accidents (BIFA) database from the USA for the years 2006-2010. Accidents are divided into three levels by counting their equivalent fatalities, and the drivers are classified into three clusters by the K-means cluster analysis. The analysis shows that some risk factors have the same impact on different types of drivers, they are: (a) season; (b) day of week; (c) time period; (d) number of vehicles involved; (e) land use; (f) manner of collision; (g) speed limit; (h) snow or ice surface condition; (i) school bus; (j) bus type and seating capacity; (k) driver's age; (l) driver's gender; (m) risky behaviors; and (n) restraint system. Results also show that some risk factors only have impact on the "young and elder drivers with history of traffic violations", they are: (a) section type; (b) number of lanes per direction; (c) roadway profile; (d) wet road surface; and (e) cyclist-bus accident. Notably, history of traffic violations has different impact on different types of bus drivers. PMID:26513334

  12. Source geometry factors for HDR 192Ir brachytherapy secondary standard well-type ionization chamber calibrations

    NASA Astrophysics Data System (ADS)

    Shipley, D. R.; Sander, T.; Nutbrown, R. F.

    2015-03-01

    Well-type ionization chambers are used for measuring the source strength of radioactive brachytherapy sources before clinical use. Initially, the well chambers are calibrated against a suitable national standard. For high dose rate (HDR) 192Ir, this calibration is usually a two-step process. Firstly, the calibration source is traceably calibrated against an air kerma primary standard in terms of either reference air kerma rate or air kerma strength. The calibrated 192Ir source is then used to calibrate the secondary standard well-type ionization chamber. Calibration laboratories are usually only equipped with one type of HDR 192Ir source. If the clinical source type is different from that used for the calibration of the well chamber at the standards laboratory, a source geometry factor, ksg, is required to correct the calibration coefficient for any change of the well chamber response due to geometric differences between the sources. In this work we present source geometry factors for six different HDR 192Ir brachytherapy sources which have been determined using Monte Carlo techniques for a specific ionization chamber, the Standard Imaging HDR 1000 Plus well chamber with a type 70010 HDR iridium source holder. The calculated correction factors were normalized to the old and new type of calibration source used at the National Physical Laboratory. With the old Nucletron microSelectron-v1 (classic) HDR 192Ir calibration source, ksg was found to be in the range 0.983 to 0.999 and with the new Isodose Control HDR 192Ir Flexisource ksg was found to be in the range 0.987 to 1.004 with a relative uncertainty of 0.4% (k = 2). Source geometry factors for different combinations of calibration sources, clinical sources, well chambers and associated source holders, can be calculated with the formalism discussed in this paper.

  13. Causes of Death and Prognostic Factors in Multiple Endocrine Neoplasia Type 1: A Prospective Study

    PubMed Central

    Ito, Tetsuhide; Igarashi, Hisato; Uehara, Hirotsugu; Berna, Marc J.; Jensen, Robert T.

    2013-01-01

    Abstract Multiple endocrine neoplasia type 1 (MEN1) is classically characterized by the development of functional or nonfunctional hyperplasia or tumors in endocrine tissues (parathyroid, pancreas, pituitary, adrenal). Because effective treatments have been developed for the hormone excess state, which was a major cause of death in these patients in the past, coupled with the recognition that nonendocrine tumors increasingly develop late in the disease course, the natural history of the disease has changed. An understanding of the current causes of death is important to tailor treatment for these patients and to help identify prognostic factors; however, it is generally lacking. To add to our understanding, we conducted a detailed analysis of the causes of death and prognostic factors from a prospective long-term National Institutes of Health (NIH) study of 106 MEN1 patients with pancreatic endocrine tumors with Zollinger-Ellison syndrome (MEN1/ZES patients) and compared our results to those from the pooled literature data of 227 patients with MEN1 with pancreatic endocrine tumors (MEN1/PET patients) reported in case reports or small series, and to 1386 patients reported in large MEN1 literature series. In the NIH series over a mean follow-up of 24.5 years, 24 (23%) patients died (14 MEN1-related and 10 non-MEN1-related deaths). Comparing the causes of death with the results from the 227 patients in the pooled literature series, we found that no patients died of acute complications due to acid hypersecretion, and 8%–14% died of other hormone excess causes, which is similar to the results in 10 large MEN1 literature series published since 1995. In the 2 series (the NIH and pooled literature series), two-thirds of patients died from an MEN1-related cause and one-third from a non-MEN1-related cause, which agrees with the mean values reported in 10 large MEN1 series in the literature, although in the literature the causes of death varied widely. In the NIH and pooled

  14. Simultaneous determination of multiclass preservatives including isothiazolinones and benzophenone-type UV filters in household and personal care products by micellar electrokinetic chromatography.

    PubMed

    Lopez-Gazpio, Josu; Garcia-Arrona, Rosa; Millán, Esmeralda

    2015-04-01

    In this work, a simple and reliable micellar electrokinetic chromatography method for the separation and quantification of 14 preservatives, including isothiazolinones, and two benzophenone-type UV filters in household, cosmetic and personal care products was developed. The selected priority compounds are widely used as ingredients in many personal care products, and are included in the European Regulation concerning cosmetic products. The electrophoretic separation parameters were optimized by means of a modified chromatographic response function in combination with an experimental design, namely a central composite design. After optimization of experimental conditions, the BGE selected for the separation of the targets consisted of 60 mM SDS, 18 mM sodium tetraborate, pH 9.4 and 10% v/v methanol. The MEKC method was checked in terms of linearity, LODs and quantification, repeatability, intermediate precision, and accuracy, providing appropriate values (i.e. R(2) ≥ 0.992, repeatability RSD values ˂9%, and accuracy 90-115%). Applicability of the validated method was successfully assessed by quantifying preservatives and UV filters in commercial consumer products. PMID:25598506

  15. Risk factors for Type 2 Diabetes Mellitus in college students: association with sociodemographic variables1

    PubMed Central

    Lima, Adman Câmara Soares; Araújo, Márcio Flávio Moura; de Freitas, Roberto Wagner Júnior Freire; Zanetti, Maria Lúcia; de Almeida, Paulo César; Damasceno, Marta Maria Coelho

    2014-01-01

    Objective identify the modifiable risk factors for type 2 diabetes mellitus in college students and associate these factors with their sociodemographic variables. Method cross-sectional study, involving 702 college students from Fortaleza-CE, Brazil. Sociodemographic, anthropometric, physical exercise data and blood pressure and fasting plasma glucose levels were collected. Results the most prevalent risk factor was sedentariness, followed by overweight, central obesity, high fasting plasma glucose and arterial hypertension. A statistically significant association was found between overweight and sex (p=0.000), age (p=0.004) and marital status (p=0.012), as well as between central obesity and age (p=0.018) and marital status (p=0.007) and between high fasting plasma glucose and sex (p=0.033). Conclusion distinct risk factors were present in the study population, particularly sedentariness and overweight. PMID:25029061

  16. [Hand eczema. The clinical classification of the roles of exogenous and endogenous factors in each type].

    PubMed

    Tamiya, Y

    1994-08-01

    Hand eczema is one of the most common dermatological disorders. Although it is a general term referring to eczematous dermatitis of the hands, it actually covers a wide range of diseases. The classification of hand eczema is controversial even now, as definitions of individual diseases have not yet been established. It is well-known that exogenous factors, such as chemicals or water, are associated with the occurrence of hand eczema. In this study, we focused on endogenous factors, especially personal or family history of atopy as a causative factor in hand eczema. According to exogenous and endogenous factors, we classified hand eczema into three types: atopic dermatitis, contact dermatitis and dysidrosis. This classification is useful because it makes the definition of each disease clear. Skin-humidity and sebum measurement are simple and rapid methods of determining personal atopy, skin condition and the effect of treatment on hand eczema patients. PMID:8083333

  17. Mannose-binding lectin and its associated proteases (MASPs) mediate coagulation and its deficiency is a risk factor in developing complications from infection, including disseminated intravascular coagulation

    PubMed Central

    Takahashi, Kazue; Chang, Wei-Chuan; Takahashi, Minoru; Pavlov, Vasile; Ishida, Yumi; La Bonte, Laura; Shi, Lei; Fujita, Teizo; Stahl, Gregory L.; Van Cott, Elizabeth M.

    2010-01-01

    The first line of host defense is the innate immune system that includes coagulation factors and pattern recognition molecules, one of which is mannose-binding lectin (MBL). Previous studies have demonstrated that MBL deficiency increases susceptibility to infection. Several mechanisms are associated with increased susceptibility to infection, including reduced opsonophagocytic killing and reduced lectin complement pathway activation. In this study, we demonstrate that MBL and MBL-associated serine protease (MASP)-1/3 together mediate coagulation factor-like activities, including thrombin-like activity. MBL and/or MASP-1/3 deficient hosts demonstrate in vivo evidence that MBL and MASP-1/3 are involved with hemostasis following injury. Staphylococcus aureus infected MBL null mice developed disseminated intravascular coagulation (DIC), which was associated with elevated blood IL-6 levels (but not TNF-α and multi-organ inflammatory responses). Infected MBL null mice also develop liver injury. These findings suggest that MBL deficiency may manifest into DIC and organ failure during infectious diseases. PMID:20399528

  18. Peroxiredoxin isoforms are associated with cardiovascular risk factors in type 2 diabetes mellitus.

    PubMed

    El Eter, E; Al-Masri, A A

    2015-05-01

    The production of oxygen free radicals in type 2 diabetes mellitus contributes to the development of complications, especially the cardiovascular-related ones. Peroxiredoxins (PRDXs) are antioxidant enzymes that combat oxidative stress. The aim of this study was to investigate the associations between the levels of PRDX isoforms (1, 2, 4, and 6) and cardiovascular risk factors in type 2 diabetes mellitus. Fifty-three patients with type 2 diabetes mellitus (28F/25M) and 25 healthy control subjects (7F/18M) were enrolled. We measured the plasma levels of each PRDX isoform and analyzed their correlations with cardiovascular risk factors. The plasma PRDX1, -2, -4, and -6 levels were higher in the diabetic patients than in the healthy control subjects. PRDX2 and -6 levels were negatively correlated with diastolic blood pressure, fasting blood sugar, and hemoglobin A1c. In contrast, PRDX1 levels were positively correlated with low-density lipoprotein and C-reactive protein levels. PRDX4 levels were negatively correlated with triglycerides. In conclusion, PRDX1, -2, -4, and -6 showed differential correlations with a variety of traditional cardiovascular risk factors. These results should encourage further research into the crosstalk between PRDX isoforms and cardiovascular risk factors. PMID:25742636

  19. The LysR-type transcription factor PacR is a global regulator of photosynthetic carbon assimilation in Anabaena.

    PubMed

    Picossi, Silvia; Flores, Enrique; Herrero, Antonia

    2015-09-01

    Cyanobacteria perform water-splitting photosynthesis and are important primary producers impacting the carbon and nitrogen cycles at global scale. They fix CO2 through ribulose-bisphosphate carboxylase/oxygenase (RuBisCo) and have evolved a distinct CO2 concentrating mechanism (CCM) that builds high CO2 concentrations in the vicinity of RuBisCo favouring its carboxylase activity. Filamentous cyanobacteria such as Anabaena fix CO2 in photosynthetic vegetative cells, which donate photosynthate to heterocysts that rely on a heterotrophic metabolism to fix N2 . CCM elements are induced in response to inorganic carbon limitation, a cue that exposes the photosynthetic apparatus to photodamage by over-reduction. An Anabaena mutant lacking the LysR-type transcription factor All3953 grew poorly and dies under high light. The rbcL operon encoding RuBisCo was induced upon carbon limitation in the wild type but not in the mutant. ChIP-Seq analysis was used to globally identify All3953 targets under carbon limitation. Targets include, besides rbcL, genes encoding CCM elements, photorespiratory pathway- photosystem- and electron transport-related components, and factors, including flavodiiron proteins, with a demonstrated or putative function in photoprotection. Quantitative reverse transcription polymerase chain reaction analysis of selected All3953 targets showed regulation in the wild type but not in the mutant. All3953 (PacR) is a global regulator of carbon assimilation in an oxygenic photoautotroph. PMID:25684321

  20. Distribution Patterns of Infection with Multiple Types of Human Papillomaviruses and Their Association with Risk Factors

    PubMed Central

    Soto-De Leon, Sara; Camargo, Milena; Sanchez, Ricardo; Munoz, Marina; Perez-Prados, Antonio; Purroy, Antonio; Patarroyo, Manuel Elkin; Patarroyo, Manuel Alfonso

    2011-01-01

    Background Infection with multiple types of human papillomavirus (HPV) is one of the main risk factors associated with the development of cervical lesions. In this study, cervical samples collected from 1,810 women with diverse sociocultural backgrounds, who attended to their cervical screening program in different geographical regions of Colombia, were examined for the presence of cervical lesions and HPV by Papanicolau testing and DNA PCR detection, respectively. Principal Findings The negative binomial distribution model used in this study showed differences between the observed and expected values within some risk factor categories analyzed. Particularly in the case of single infection and coinfection with more than 4 HPV types, observed frequencies were smaller than expected, while the number of women infected with 2 to 4 viral types were higher than expected. Data analysis according to a negative binomial regression showed an increase in the risk of acquiring more HPV types in women who were of indigenous ethnicity (+37.8%), while this risk decreased in women who had given birth more than 4 times (−31.1%), or were of mestizo (−24.6%) or black (−40.9%) ethnicity. Conclusions According to a theoretical probability distribution, the observed number of women having either a single infection or more than 4 viral types was smaller than expected, while for those infected with 2–4 HPV types it was larger than expected. Taking into account that this study showed a higher HPV coinfection rate in the indigenous ethnicity, the role of underlying factors should be assessed in detail in future studies. PMID:21379574

  1. Gauge factors of fibre Bragg grating strain sensors in different types of optical fibres

    NASA Astrophysics Data System (ADS)

    Jülich, Florian; Aulbach, Laura; Wilfert, Andre; Kratzer, Peter; Kuttler, Rolf; Roths, Johannes

    2013-09-01

    Gauge factors of fibre Bragg grating (FBG)-based strain sensors that had been inscribed into three different types of optical fibres, which differ in core diameters and doping concentrations, were determined at room temperature with high accuracy. Repeated measurements were carried out with several samples of each type of fibre to allow statistical evaluations. For each type, the gauge factors were measured in two configurations: when the bare fibres were glued on a specimen at the location of the FBG and when they were vertically suspended and not bonded to any structure at the location of the FBG. By combining the results of both configurations, the strain transfer ratio of the gluing process and the strain-optic coefficient, peff, of the different types of fibres were determined. The strain-optic coefficient was found to vary up to 1.5% for the different types of optical fibres. The strain transfer ratio was obtained to be close to unity (>99%), showing the high quality of the gluing technique employed. The investigations demonstrate that highly accurate strain sensing is possible with fibre-optic strain sensors. The results are important for the development of accurate and reliable attaching techniques for coated sensor fibres and fibre-optic sensor patches.

  2. Tumor necrosis factor-alpha inhibitor-induced psoriasis or psoriasiform exanthemata: first 120 cases from the literature including a series of six new patients.

    PubMed

    Wollina, Uwe; Hansel, Gesina; Koch, André; Schönlebe, Jaqueline; Köstler, Erich; Haroske, Gunter

    2008-01-01

    Tumor necrosis factor-alpha (TNFalpha) inhibition is effective in the treatment of moderate-to-severe psoriasis. We report on 120 patients from the literature including six new patients (three women and three men) who developed pustular lesions during treatment with TNFalpha inhibitors. We identified 72 women and 36 men (several papers did not specify the gender of patients) with an age range of 13-78 years (mean 42.3 years). The primary diagnoses were rheumatoid arthritis (n = 61), ankylosing spondylitis (n = 21), psoriasis (n = 10), Crohn disease (n = 8), SAPHO (synovitis acne pustulosis hyperostosis osteitis) syndrome (n = 3), psoriatic arthritis (n = 2), and other diagnoses (n = 15). Psoriasis (except palmoplantar pustular type) was the most common adverse effect during anti-TNFalpha treatment (n = 73), followed by palmoplantar pustular psoriasis (n = 37) and psoriasis of the nail (n = 6), sometimes combined in the same patient. Palmoplantar pustulosis and psoriasiform exanthema was the diagnosis in ten patients each. A positive personal history of psoriasis was recorded in 25 patients. A positive family history was noted in eight patients. No data about personal (n = 7) or family history (n = 46) were available in a number of patients. Newly induced psoriasis was diagnosed in 74 patients whereas an exacerbation or aggravation of a pre-existing psoriasis was noted in another 25 patients. All three TNFalpha inhibitors available on the market were involved: infliximab (63 patients), etanercept (37 patients), and adalimumab (26 patients). Several patients were treated with more than a single TFNalpha inhibitor. The timing of cutaneous adverse effects (psoriasis and psoriasiform rash) varied considerably among patients, ranging from after a single application to a delayed response of up to 63 months after initiation of treatment. The mean time to appearance of the cutaneous adverse effect for all TNFalpha inhibitors was 9.5 months. Cessation of the responsible

  3. Differential sensitivities of transcription factor target genes underlie cell type-specific gene expression profiles

    PubMed Central

    Johnson, Kirby D.; Kim, Shin-Il; Bresnick, Emery H.

    2006-01-01

    Changes in transcription factor levels and activities dictate developmental fate. Such a change might affect the full ensemble of target genes for a factor or only uniquely sensitive targets. We investigated the relationship among activity of the hematopoietic transcription factor GATA-1, chromatin occupancy, and target gene sensitivity. Graded activation of GATA-1 in GATA-1-null cells revealed high-, intermediate-, and low-sensitivity targets. GATA-1 activity requirements for occupancy and transcription often correlated. A GATA-1 amino-terminal deletion mutant severely deregulated the low-sensitivity gene Tac-2. Thus, cells expressing different levels of a cell type-specific activator can have qualitatively distinct target gene expression patterns, and factor mutations preferentially deregulate low-sensitivity genes. Unlike other target genes, GATA-1-mediated Tac-2 regulation was bimodal, with activation followed by repression, and the coregulator Friend of GATA-1 (FOG-1) selectively mediated repression. A GATA-1 mutant defective in FOG-1 binding occupied a Tac-2 regulatory region at levels higher than wild-type GATA-1, whereas FOG-1 facilitated chromatin occupancy at a distinct target site. These results indicate that FOG-1 is a determinant of GATA factor target gene sensitivity by either facilitating or opposing chromatin occupancy. PMID:17043224

  4. Does high sugar consumption exacerbate cardiometabolic risk factors and increase the risk of type 2 diabetes and cardiovascular disease?

    PubMed Central

    Sonestedt, Emily; Øverby, Nina Cecilie; Laaksonen, David E.; Birgisdottir, Bryndis Eva

    2012-01-01

    Consumption of sugar has been relatively high in the Nordic countries; the impact of sugar intake on metabolic risk factors and related diseases has been debated. The objectives were to assess the effect of sugar intake (sugar-sweetened beverages, sucrose and fructose) on association with type 2 diabetes, cardiovascular disease and related metabolic risk factors (impaired glucose tolerance, insulin sensitivity, dyslipidemia, blood pressure, uric acid, inflammation markers), and on all-cause mortality, through a systematic review of prospective cohort studies and randomised controlled intervention studies published between January 2000 and search dates. The methods adopted were as follows: the first search was run in PubMed in October 2010. A second search with uric acid as risk marker was run in April 2011. The total search strategy was rerun in April 2011 in SveMed+. An update was run in PubMed in January 2012. Two authors independently selected studies for inclusion from the 2,743 abstracts according to predefined eligibility criteria. The outcome was that out of the 17 studies extracted, 15 were prospective cohort studies and two were randomised controlled crossover trials. All of the studies included only adults. With respect to incident type 2 diabetes (nine studies), four of six prospective cohort studies found a significant positive association for sugar-sweetened beverage intake. In general, larger cohort studies with longer follow-up more often reported positive associations, and BMI seemed to mediate part of the increased risk. For other metabolic or cardiovascular risk factors or outcomes, too few studies have been published to draw conclusions. In conclusion, data from prospective cohort studies published in the years 2000–2011 suggest that sugar-sweetened beverages probably increase the risk of type 2 diabetes. For related metabolic risk factors, cardiovascular disease or all-cause mortality and other types of sugars, too few studies were available

  5. Population-Level Prediction of Type 2 Diabetes From Claims Data and Analysis of Risk Factors.

    PubMed

    Razavian, Narges; Blecker, Saul; Schmidt, Ann Marie; Smith-McLallen, Aaron; Nigam, Somesh; Sontag, David

    2015-12-01

    We present a new approach to population health, in which data-driven predictive models are learned for outcomes such as type 2 diabetes. Our approach enables risk assessment from readily available electronic claims data on large populations, without additional screening cost. Proposed model uncovers early and late-stage risk factors. Using administrative claims, pharmacy records, healthcare utilization, and laboratory results of 4.1 million individuals between 2005 and 2009, an initial set of 42,000 variables were derived that together describe the full health status and history of every individual. Machine learning was then used to methodically enhance predictive variable set and fit models predicting onset of type 2 diabetes in 2009-2011, 2010-2012, and 2011-2013. We compared the enhanced model with a parsimonious model consisting of known diabetes risk factors in a real-world environment, where missing values are common and prevalent. Furthermore, we analyzed novel and known risk factors emerging from the model at different age groups at different stages before the onset. Parsimonious model using 21 classic diabetes risk factors resulted in area under ROC curve (AUC) of 0.75 for diabetes prediction within a 2-year window following the baseline. The enhanced model increased the AUC to 0.80, with about 900 variables selected as predictive (p < 0.0001 for differences between AUCs). Similar improvements were observed for models predicting diabetes onset 1-3 years and 2-4 years after baseline. The enhanced model improved positive predictive value by at least 50% and identified novel surrogate risk factors for type 2 diabetes, such as chronic liver disease (odds ratio [OR] 3.71), high alanine aminotransferase (OR 2.26), esophageal reflux (OR 1.85), and history of acute bronchitis (OR 1.45). Liver risk factors emerge later in the process of diabetes development compared with obesity-related factors such as hypertension and high hemoglobin A1c. In conclusion

  6. Stages of change for physical activity and dietary habits in persons with type 2 diabetes included in a mobile health intervention: the Norwegian study in RENEWING HEALTH

    PubMed Central

    Holmen, Heidi; Wahl, Astrid; Torbjørnsen, Astrid; Jenum, Anne Karen; Småstuen, Milada Cvancarova; Ribu, Lis

    2016-01-01

    Objective The aim of this study was to investigate stages of change for physical activity and dietary habits using baseline data from persons with type 2 diabetes included in a mobile health intervention. We examined the associations between stages of change for physical activity change and dietary change, and between stages of change for each behavior and individual characteristics, health-related quality of life, self-management, depressive symptoms, and lifestyle. Research design and methods We examined 151 persons with type 2 diabetes with an glycated hemoglobin (HbA1c) level ≥7.1%, aged ≥18 years at baseline of a randomized controlled trial, before testing a mobile app with or without health counseling. Stages of change were dichotomized into ‘pre-action’ and ‘action’. Self-management was measured using the Health Education Impact Questionnaire (heiQ) where a higher score reflects increased self-management, and health-related quality of life was measured with the Short-Form-36 (SF-36). Logistic regression modeling was performed. Results The median HbA1c level was 7.9% (7.1–12.4), 90% were overweight or obese, and 20% had ≥3 comorbidities. 58% were in the preaction stage for physical activity change and 79% in the preaction stage for dietary change. Higher scores of self-management were associated with an increased chance of being in the action stage for both dietary change and physical activity change. Higher body mass index was associated with an 8% reduced chance of being in the action stage for physical activity change (OR 0.92, 95% CI 0.86 to 0.99). Conclusions Being in the action stage was associated with higher scores of self-management, crucial for type 2 diabetes. Over half of the participants were in the preaction stage for physical activity and dietary change, and many had a high disease burden with comorbidities and overweight. Trial registration number NCT01315756. PMID:27239317

  7. Multi-Biomarkers for Early Detection of Type 2 Diabetes, Including 10- and 12-(Z,E)-Hydroxyoctadecadienoic Acids, Insulin, Leptin, and Adiponectin

    PubMed Central

    Umeno, Aya; Yoshino, Kohzoh; Hashimoto, Yoshiko; Shichiri, Mototada; Kataoka, Masatoshi; Yoshida, Yasukazu

    2015-01-01

    We have previously found that fasting plasma levels of totally assessed 10- and 12-(Z,E)-hydroxyoctadecadienoic acid (HODE) correlated well with levels of glycated hemoglobin (HbA1c) and glucose during oral glucose tolerance tests (OGTT); these levels were determined via liquid chromatography—mass spectrometry after reduction and saponification. However, 10- and 12-(Z,E)-HODE alone cannot perfectly detect early impaired glucose tolerance (IGT) and/or insulin resistance, which ultimately lead to diabetes. In this study, we randomly recruited healthy volunteers (n = 57) who had no known history of any diseases, and who were evaluated using the OGTT, the HODE biomarkers, and several additional proposed biomarkers, including retinol binding protein 4 (RBP4), adiponectin, leptin, insulin, glycoalbumin, and high sensitivity-C-reactive protein. The OGTT revealed that our volunteers included normal individuals (n = 44; Group N), “high-normal” individuals (fasting plasma glucose 100–109 mg/dL) with IGT (n = 11; Group HN+IGT), and diabetic individuals (n = 2; Group D). We then used these groups to evaluate the potential biomarkers for the early detection of type 2 diabetes. Plasma levels of RBP4 and glycoalbumin were higher in Group HN+IGT, compared to those in Group N, and fasting levels of 10- and 12-(Z,E)-HODE/linoleic acids were significantly correlated with levels of RBP4 (p = 0.003, r = 0.380) and glycoalbumin (p = 0.006, r = 0.316). Furthermore, we developed a stepwise multiple linear regression models to predict the individuals’ insulin resistance index (the Matsuda Index 3). Fasting plasma levels of 10- and 12-(Z,E)-HODE/linoleic acids, glucose, insulin, and leptin/adiponectin were selected as the explanatory variables for the models. The risks of type 2 diabetes, early IGT, and insulin resistance were perfectly predicted by comparing fasting glucose levels to the estimated Matsuda Index 3 (fasting levels of 10- and 12-(Z,E)-HODE/linoleic acids, insulin

  8. Severe hypoglycaemia in type 1 diabetes: impact of the renin-angiotensin system and other risk factors.

    PubMed

    Pedersen-Bjergaard, Ulrik

    2009-11-01

    Hypoglycaemia is an unavoidable side effect to insulin therapy of diabetes. In daily life some hypoglycaemic episodes are recognised by the patients and corrected by ingestion of glucose, but occasionally unrecognised episodes progress into severe hypoglycaemia with cognitive impairment and the need for assistance from other persons in order to manage the situation. Such episodes represent the most feared side effect to insulin treatment and are regarded as the major limiting factor for achievement of recommended glycaemic targets in type 1 diabetes. The series of studies that constitute this thesis was conducted to assess the significance of severe hypoglycaemia as a clinical problem in the type 1 diabetic population, to evaluate the impact of known risk factors on occurrence of severe hypoglycaemia, and to identify new markers that could contribute to improved prediction of, and inspire to novel preventive measures of, severe hypoglycaemia. Our studies confirm that severe hypoglycaemia is still a major clinical problem in type 1 diabetes. The individual susceptibility to severe hypoglycaemia is highly varying and conventional risk factors - with major contribution from hypoglycaemia unawareness - only account for a limited part of this variation. Results from a case-series suggest that the use of psychoactive substances may be as significant as alcohol for promotion of risk of severe hypoglycaemia - a finding which needs to be confirmed by case-control studies. We identified elevated renin-angiotensin system activity as a novel predictor of risk of severe hypoglycaemia in type 1 diabetes with potential clinical significance. Thus, three sequential renin-angiotensin system-related risk factors were associated with severe hypoglycaemia, and by including these factors in a common model both subjects at low and at high risk within a one-year period were identified. Preliminary data suggest that this is explained by impaired capability of subjects with high renin

  9. Lifestyle risk factors for atherosclerosis in adults with type 1 diabetes.

    PubMed

    Bishop, Franziska K; Maahs, David M; Snell-Bergeon, Janet K; Ogden, Lorraine G; Kinney, Greg L; Rewers, Marian

    2009-10-01

    The objective of this study was to compare the amount of self-reported physical activity, alcohol and tobacco use in a large sample of adults with type 1 diabetes and non-diabetic subjects. A second aim is to test the hypothesis that these lifestyle risk factors are associated cross-sectionally with coronary artery calcification. In 2000-2002, the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study applied validated questionnaires for smoking, alcohol and physical activity to 582 type 1 diabetes subjects and 724 non-diabetic subjects. More type 1 diabetes subjects reported current smoking than non-diabetic subjects (12.3% versus 8.6%, p=0.027). Overall, reported physical activity did not differ by diabetes status (p=0.79). More type 1 diabetes subjects reported never having consumed alcohol (10% versus 4%, p<0.0001) and those who drank consumed less alcohol (p=0.0015) than non-diabetic subjects. Physical activity and smoking were significantly associated with the presence of coronary artery calcification (adjusted OR=0.9, 95% CI: 0.8-0.996, p=0.045, and OR=1.7, CI: 1.1-2.6, p=0.03, respectively). Type 1 diabetes was independently associated with increased odds of coronary artery calcification (OR=3.5, 95% CI: 2.5-5.0, p<0.0001). Differences exist in lifestyle-related cardiovascular risk factors in men and women with type 1 diabetes compared with non-diabetic subjects in the CACTI study. PMID:20368221

  10. CFD-based method of determining form factor k for different ship types and different drafts

    NASA Astrophysics Data System (ADS)

    Wang, Jinbao; Yu, Hai; Zhang, Yuefeng; Xiong, Xiaoqing

    2016-07-01

    The value of form factor k at different drafts is important in predicting full-scale total resistance and speed for different types of ships. In the ITTC community, most organizations predict form factor k using a low-speed model test. However, this method is problematic for ships with bulbous bows and transom. In this article, a Computational Fluid Dynamics (CFD)-based method is introduced to obtain k for different type of ships at different drafts, and a comparison is made between the CFD method and the model test. The results show that the CFD method produces reasonable k values. A grid generating method and turbulence model are briefly discussed in the context of obtaining a consistent k using CFD.

  11. Bone mineral density and factors influencing it in Asian Indian population with type 2 diabetes mellitus

    PubMed Central

    Kamalanathan, Sadishkumar; Nambiar, Vimal; Shivane, Vyankatesh; Bandgar, Tushar; Menon, Padmavathy; Shah, Nalini

    2014-01-01

    Objective: To assess bone mineral density (BMD) in type 2 diabetes mellitus (T2DM) patients and its relation, if any, to clinical, hormonal and metabolic factors. Materials and Methods: A prospective evaluation of 194 T2DM patients (97 men and 97 women) was carried out. BMD was done with dual energy X-ray absorptiometry (DXA) at the lumbar spine and total hip. Physical activity, nutritional intake and sunlight exposure were calculated. Biochemical and hormonal tests included serum 25 hydroxy vitamin D [25(OH) D], parathyroid hormone, estrogen, testosterone and urinary calcium-creatinine ratio. Glycosylated hemoglobin and complete lipid profiles were done in patients with diabetes. Five hundred and seventy one non-diabetic controls (262 males and 309 females) were evaluated for BMD alone. Results: BMD was normal (Z score > -2) in 156 (80.5%) and low (Z score ≤ -2) in 38 (19.5%) patients in the diabetes study group. BMD in the diabetes group was significantly higher than the control group in both sexes at the hip and spine. The difference was no longer significant on analysis of a BMI matched control subgroup. Weight and BMI showed significant correlation to BMD. Duration of T2DM, degree of glycemic control, use of drugs like statins and thiazolidinediones, 25(OH) D levels, calcium intake, sunlight exposure and physical activity did not significantly affect BMD in this cohort of individuals with diabetes. Conclusions: Bone mineral density of Asian Indian T2DM subjects was similar to that of healthy volunteers in this study. PMID:25364679

  12. Arabidopsis GROWTH-REGULATING FACTOR7 Functions as a Transcriptional Repressor of Abscisic Acid– and Osmotic Stress–Responsive Genes, Including DREB2A[W

    PubMed Central

    Kim, June-Sik; Mizoi, Junya; Kidokoro, Satoshi; Maruyama, Kyonoshin; Nakajima, Jun; Nakashima, Kazuo; Mitsuda, Nobutaka; Takiguchi, Yuko; Ohme-Takagi, Masaru; Kondou, Youichi; Yoshizumi, Takeshi; Matsui, Minami; Shinozaki, Kazuo; Yamaguchi-Shinozaki, Kazuko

    2012-01-01

    Arabidopsis thaliana DEHYDRATION-RESPONSIVE ELEMENT BINDING PROTEIN2A (DREB2A) functions as a transcriptional activator that increases tolerance to osmotic and heat stresses; however, its expression also leads to growth retardation and reduced reproduction. To avoid these adverse effects, the expression of DREB2A is predicted to be tightly regulated. We identified a short promoter region of DREB2A that represses its expression under nonstress conditions. Yeast one-hybrid screening for interacting factors identified GROWTH-REGULATING FACTOR7 (GRF7). GRF7 bound to the DREB2A promoter and repressed its expression. In both artificial miRNA-silenced lines and a T-DNA insertion line of GRF7, DREB2A transcription was increased compared with the wild type under nonstress conditions. A previously undiscovered cis-element, GRF7-targeting cis-element (TGTCAGG), was identified as a target sequence of GRF7 in the short promoter region of DREB2A via electrophoretic mobility shift assays. Microarray analysis of GRF7 knockout plants showed that a large number of the upregulated genes in the mutant plants were also responsive to osmotic stress and/or abscisic acid. These results suggest that GRF7 functions as a repressor of a broad range of osmotic stress–responsive genes to prevent growth inhibition under normal conditions. PMID:22942381

  13. Seroprevalence of Herpes Simplex Virus Type 1 and 2 in Taiwan and Risk Factor Analysis, 2007

    PubMed Central

    Chao-Yu, Chen; Chen, Chih-Jung; Lin, Tzou-Yien; Huang, Yhu-Chering

    2015-01-01

    Background Herpes simplex virus type 1 (HSV-1) and 2 (HSV-2) are common human pathogens and might cause severe illness. Following primary infection, the viruses establish lifelong latent infection and are transmitted by close contact, both sexual and nonsexual. However, the information about the seroprevalence of HSV-1 and HSV-2 across all age groups is limited. Methods Residual sera collected during the nationwide serosurvey in 2007 in Taiwan were selected for the study. The enzyme-linked immunosorbent assay was used to detect anti-HSV-1 and anti-HSV-2 type-specific glycoprotein IgG. Demographics and personal health data were used for risk analysis. Results A total of 1411 and 1072 serum samples were included for anti-HSV-1 and anti-HSV-2 seroprevalence analysis, respectively. The weighted overall seroprevalence was 63.2% for HSV-1, and 7.7% for HSV-2, respectively. The HSV-1 seropositive rate was 19.2% for those less than 5 years old, increased to 46.4% for those aged 5–13 years, 60.9% for those aged 14–29 years, and reached as much as 95.0% for those aged over 30 years. In contrast, the HSV-2 seropositve rate was 1.6% for those less than 30 years old, rose to 10.1% for those age 30–39 years, and was up to 31.2% for those aged over 60 years. A significantly higher HSV-2 seropositive rate was noted in females than males aged over 40 years (26.3% v.s. 16.8%), and the overall HSV-2 seropositive rate was almost twice higher in females than males. Smoking history, drinking habit, and educational level were associated with the HSV-1 seropositivity. Female gender and rural residence were independent factors for the HSV-2 seropositivity. Conclusions An obvious increase of primary HSV-1 infection occurred in late adolescents and young adults, joined by the rise of HSV-2 infection in middle-aged adults, especially females. The acquistion and transmission of HSV warrant further studies in the susceptible population. PMID:26252011

  14. Factors associated with psychological and behavioral functioning in people with type 2 diabetes living in France

    PubMed Central

    2010-01-01

    Background To identify demographic and clinical factors associated with psychological and behavioral functioning (PBF) in people with type 2 diabetes living in France. Methods In March 2002, approximately 10,000 adults, who had been reimbursed for at least one hypoglycemic treatment or insulin dose during the last quarter of 2001, received a questionnaire about their health status and PBF (3,646 responders). For this analysis, the 3,090 persons with type 2 diabetes, aged 18-85 years old were selected. PBF was measured with the adapted version of the Diabetes Health Profile for people with type 2 diabetes. This permitted the calculation of three functional scores - psychological distress (PD), barriers to activity (BA), and disinhibited eating (DE) - from 0 (worst) to 100 (best). Results Major negative associations were observed with PBF for microvascular complications (a difference of 6.7 in the BA score between persons with and without microvascular complications) and severe hypoglycemia (difference of 7.9 in the BA score), insulin treatment (-8.5 & -9.5 in the PD & BA scores respectively, as compared to treatment with oral hypoglycemic agents), non-adherence to treatment (-12.3 in the DE score for persons forgetting their weekly treatment), increasing weight (-8.5 & -9.7 in the PD & DE scores respectively, as compared to stable weight), at least one psychiatrist visit in 2001 (-8.9 in the DE score), and universal medical insurance coverage (-7.9 in the PD score) (due to low income). Conclusion Prevention and management of microvascular complications or adherence to treatment (modifiable factors) could be essential to preserving or improving PBF among people with type 2 diabetes. A specific approach to type 2 diabetes management may be required in groups with a low socioeconomic profile (particularly people with universal medical insurance coverage), or other non modifiable factors. PMID:21044345

  15. Evaluation of the predisposing factors and involved outcome of surgical treatment in bisphosphonate-related osteonecrosis of the jaw cases including bone biopsies

    PubMed Central

    2016-01-01

    Objectives This study examined the statistical relevance of whether the systemic predisposing factors affect the prognosis of surgical treatment of bisphosphonate-related osteonecrosis of the jaw (BRONJ). All cases had undergone bone biopsies to determine the characteristics of the mechanisms of BRONJ by optical microscopy. Materials and Methods The data included 54 BRONJ cases who underwent surgery and in whom bone biopsies were performed. The results of surgery were evaluated and the results were classified into 3 categories: normal recovery, delayed recovery, and recurrence after surgery. The medical history, such as diabetes mellitus, medication of steroids, malignancies on other sites was investigated for an evaluation of the systemic predisposing factors in relation to the prognosis. The three factors involved with the medication of bisphosphonate (BP) were the medication route, medication period, and drug holiday of BP before surgery. The serum C-terminal cross-linking telopeptide (CTX) value and presence of microorganism colony in bone biopsy specimens were also checked. Statistical analysis was then carried out to determine the relationship between these factors and the results of surgery. Results The group of patients suffering from diabetes and on steroids tended to show poorer results after surgery. Parenteral medication of BP made the patients have a poorer prognosis after surgery than oral medication. In contrast, the medication period and drug holiday of BP before surgery did not have significance with the results of surgery nor did the serum CTX value and presence of microorganism colony. Necrotic bone specimens in this study typically showed disappearing new bone formation around the osteocytic lacunae and destroyed Howship's lacunae. Conclusion Although many variables exist, this study could in part, predict the prognosis of surgical treatment of BRONJ by taking the patient's medical history. PMID:27595086

  16. [Relationship between main vegetation types and climatic factors in Inner Mongolia].

    PubMed

    Niu, J

    2000-02-01

    The relationship between main vegetation types and climate factors in Inner Mongolia was analyzed by using up-to-date vegetation map, statistics, modeling and spatial simulation of regional climatic factors under the support of GIS. The feasible climatic range of spatial distribution of plant communities was derived from overlaying vegetation map and climate maps. The results showed that the vegetation distribution was obviously in accordance with climate. On the one hand, all the types, not only zonal vegetation, but also mountain, sandy land and low land communities changed gradually from east to west due to the distance to oceans, with a zonal differentiation, Precipitation played an important role in determining this regulation. On the other hand, latitudinal replacement of plant communities occurred with the change of temperature from north to south. In addition, temperature was also the key factor controlling the spatial distribution of vegetation types, such as meadow, steppe, shrub and low land communities on the east and west sides of Daxinganling Mountains. PMID:11766587

  17. Risk Factors for Hypogonadism in Male Patients with Type 2 Diabetes

    PubMed Central

    Zheng, Rendong; Cao, Lin; Cao, Wen; Chu, Xiaoqiu; Hu, Yongxin; Zhang, Huifeng; Xu, Juan; Sun, Hongping; Bao, Weiping; Liu, Kemian; Liu, Chao

    2016-01-01

    Background. Male hypogonadism is an endocrine disease characterized by low levels of serum testosterone and is closely related to the development of diabetes. The purpose of the present study was to observe the risk factors for hypogonadism in male patients with type 2 diabetes. Methods. A total of 213 patients with type 2 diabetes were enrolled and divided into a low total testosterone (TT) group (=75) and a normal TT group (=138). The patients' blood glucose, blood lipids, serum insulin, and sex hormones were measured. The correlations between the patients' metabolic index and sex hormone levels were analyzed. Results. Compared with the normal TT group, body mass index (BMI), fasting insulin (FINS), and HOMA insulin resistance index (HOMA-IR) levels were significantly higher, but the luteinizing hormone (LH) levels were significantly lower in the low TT group (p < 0.05). Correlation analyses found that TT was negatively correlated with BMI, waist circumference (WC), FINS, and HOMA-IR. TT was positively correlated with LH and follicle-stimulating hormone (FSH). Conclusions. Several risk factors of diabetes associated closely with hypogonadism. BMI, metabolic syndrome (MS), HOMA-IR, and LH are independent risk factors for hypogonadism in male patients with type 2 diabetes. PMID:27006953

  18. Observational calibration of the projection factor of Cepheids. I. The type II Cepheid κ Pavonis

    NASA Astrophysics Data System (ADS)

    Breitfelder, J.; Kervella, P.; Mérand, A.; Gallenne, A.; Szabados, L.; Anderson, R. I.; Willson, M.; Le Bouquin, J.-B.

    2015-04-01

    Context. The distance of pulsating stars, in particular Cepheids, are commonly measured using the parallax of pulsation technique. The different versions of this technique combine measurements of the linear diameter variation (from spectroscopy) and the angular diameter variation (from photometry or interferometry) amplitudes, to retrieve the distance in a quasi-geometrical way. However, the linear diameter amplitude is directly proportional to the projection factor (hereafter p-factor), which is used to convert spectroscopic radial velocities (i.e., disk integrated) into pulsating (i.e., photospheric) velocities. The value of the p-factor and its possible dependence on the pulsation period are still widely debated. Aims: Our goal is to measure an observational value of the p-factor of the type-II Cepheid κ Pavonis. Methods: The parallax of the type-II Cepheid κ Pav was measured with an accuracy of 5% using HST/FGS. We used this parallax as a starting point to derive the p-factor of κ Pav, using the SPIPS technique (Spectro-Photo-Interferometry of Pulsating Stars), which is a robust version of the parallax-of-pulsation method that employs radial velocity, interferometric and photometric data. We applied this technique to a combination of new VLTI/PIONIER optical interferometric angular diameters, new CORALIE and HARPS radial velocities, as well as multi-colour photometry and radial velocities from the literature. Results: We obtain a value of p = 1.26 ± 0.07 for the p-factor of κ Pav. This result agrees with several of the recently derived Period-p-factor relationships from the literature, as well as previous observational determinations for Cepheids. Conclusions: Individual estimates of the p-factor are fundamental to calibrating the parallax of pulsation distances of Cepheids. Together with previous observational estimates, the projection factor we obtain points to a weak dependence of the p-factor on period. Based on observations realized with ESO

  19. Modeling Occurrence of Urban Mosquitos Based on Land Use Types and Meteorological Factors in Korea

    PubMed Central

    Kwon, Yong-Su; Bae, Mi-Jung; Chung, Namil; Lee, Yeo-Rang; Hwang, Suntae; Kim, Sang-Ae; Choi, Young Jean; Park, Young-Seuk

    2015-01-01

    Mosquitoes are a public health concern because they are vectors of pathogen, which cause human-related diseases. It is well known that the occurrence of mosquitoes is highly influenced by meteorological conditions (e.g., temperature and precipitation) and land use, but there are insufficient studies quantifying their impacts. Therefore, three analytical methods were applied to determine the relationships between urban mosquito occurrence, land use type, and meteorological factors: cluster analysis based on land use types; principal component analysis (PCA) based on mosquito occurrence; and three prediction models, support vector machine (SVM), classification and regression tree (CART), and random forest (RF). We used mosquito data collected at 12 sites from 2011 to 2012. Mosquito abundance was highest from August to September in both years. The monitoring sites were differentiated into three clusters based on differences in land use type such as culture and sport areas, inland water, artificial grasslands, and traffic areas. These clusters were well reflected in PCA ordinations, indicating that mosquito occurrence was highly influenced by land use types. Lastly, the RF represented the highest predictive power for mosquito occurrence and temperature-related factors were the most influential. Our study will contribute to effective control and management of mosquito occurrences. PMID:26492260

  20. Factors Predictive of Type of Powered Mobility Received by Veterans with Disability

    PubMed Central

    Rabadi, Meheroz H.; Vincent, Andrea S.

    2015-01-01

    Background The goal of this observational study was to determine factors predictive of the type of powered mobility prescribed to veterans with disability. Material/Methods A retrospective chart review was conducted for all veterans (n=170) who received powered mobility from a designated power mobility clinic. Logistic regression analysis was used to determined factors predictive of the type of powered mobility provided. Results Sixty-four (38%) veterans were provided powered wheelchairs and 106 (62%) were provided powered scooters. Of the variables examined, only primary medical conditions for referral and disability severity (as measured by the 2-minute timed walk test; 2-MWT) were predictive of the types of powered mobility prescribed. Veterans who were able to walk longer distances were more likely to be prescribed powered scooters. Age, gender, race, level of education, marital and employment status, number of chronic medical conditions, and upper and lower limb muscle strength were not significant predictors. Conclusions This study suggests that the primary medical conditions for referral and 2-MWT can assist clinicians in the determination of the type of powered mobility to prescribe to veterans with disability. PMID:25955214

  1. Modeling Occurrence of Urban Mosquitos Based on Land Use Types and Meteorological Factors in Korea.

    PubMed

    Kwon, Yong-Su; Bae, Mi-Jung; Chung, Namil; Lee, Yeo-Rang; Hwang, Suntae; Kim, Sang-Ae; Choi, Young Jean; Park, Young-Seuk

    2015-10-01

    Mosquitoes are a public health concern because they are vectors of pathogen, which cause human-related diseases. It is well known that the occurrence of mosquitoes is highly influenced by meteorological conditions (e.g., temperature and precipitation) and land use, but there are insufficient studies quantifying their impacts. Therefore, three analytical methods were applied to determine the relationships between urban mosquito occurrence, land use type, and meteorological factors: cluster analysis based on land use types; principal component analysis (PCA) based on mosquito occurrence; and three prediction models, support vector machine (SVM), classification and regression tree (CART), and random forest (RF). We used mosquito data collected at 12 sites from 2011 to 2012. Mosquito abundance was highest from August to September in both years. The monitoring sites were differentiated into three clusters based on differences in land use type such as culture and sport areas, inland water, artificial grasslands, and traffic areas. These clusters were well reflected in PCA ordinations, indicating that mosquito occurrence was highly influenced by land use types. Lastly, the RF represented the highest predictive power for mosquito occurrence and temperature-related factors were the most influential. Our study will contribute to effective control and management of mosquito occurrences. PMID:26492260

  2. Flux line lattice form factor and paramagnetic effects in type II superconductors

    NASA Astrophysics Data System (ADS)

    Ichioka, Masanori; Machida, Kazushige

    2009-03-01

    Based on the quasiclassical Eilenberger theory, we investigate the vortex structure in type II superconductors with strong Pauli-paramagnetic contributions due to the Zeeman effect. We quantitatively study how the paramagnetic effect suppresses the superconductivity, and evaluate the flux line lattice (FLL) form factor from the calculated internal field distribution both in the s-wave and d-wave pairings. When the paramagnetic effects are strong, the intensity of the FLL form factor increases toward Hc2 as a function of an applied field, instead of exponential decay. This anomalous field dependence is due to the induced paramagnetic moments around the vortex core. We discuss the anomalous field-dependence of the FLL form factor observed by the small angle neutron scattering in CeCoIn5.

  3. Emission factors from biomass burning in three types of appliances: fireplace, woodstove and pellet stove

    NASA Astrophysics Data System (ADS)

    Duarte, Márcio; Vicente, Estela; Calvo, Ana; Nunes, Teresa; Tarelho, Luis; Alves, Célia

    2014-05-01

    In the last years, the importance of biomass fuels has increased mainly for two reasons. One of them is the effort to control the emissions of greenhouse gases, and on the other hand, the increasing costs associated with fossil fuels. Besides that, biomass burning is now recognised as one of the major sources contributing to high concentrations of particulate matter, especially during winter time. Southern European countries have a lack of information regarding emission profiles from biomass burning. Because of that, in most source apportionment studies, the information used comes from northern and alpine countries, whose combustion appliances, fuels and habits are different from those in Mediterranean countries. Due to this lack of information, series of tests using different types of equipment, as well as fuels, were carried out in order to obtain emission profiles and emission factors that correspond to the reality in southern European countries. Tests involved three types of biomass appliances used in Portugal, a fireplace, a woodstove and a modern pellet stove. Emission factors (mg.kg-1 fuel, dry basis) for CO, THC and PM10 were obtained. CO emission factors ranged from 38, for pine on the woodstove, to 84 for eucalyptus in the fireplace. THC emissions were between 4 and 24, for pine in the woodstove and eucalyptus in the fireplace, respectively. PM10 emission factors were in the range from 3.99, for pine in the woodstove, to 17.3 for eucalyptus in the fireplace. On average, the emission factors obtained for the fireplace are 1.5 (CO) to 4 (THC) times higher than those of the woodstove. The fireplace has emission factors for CO, THC and PM10 10, 35 and 32 times, respectively, higher than the pellet stove.

  4. A bHLH-Type Transcription Factor, ABA-INDUCIBLE BHLH-TYPE TRANSCRIPTION FACTOR/JA-ASSOCIATED MYC2-LIKE1, Acts as a Repressor to Negatively Regulate Jasmonate Signaling in Arabidopsis[C][W

    PubMed Central

    Nakata, Masaru; Mitsuda, Nobutaka; Herde, Marco; Koo, Abraham J.K.; Moreno, Javier E.; Suzuki, Kaoru; Howe, Gregg A.; Ohme-Takagi, Masaru

    2013-01-01

    Jasmonates (JAs) are plant hormones that regulate the balance between plant growth and responses to biotic and abiotic stresses. Although recent studies have uncovered the mechanisms for JA-induced responses in Arabidopsis thaliana, the mechanisms by which plants attenuate the JA-induced responses remain elusive. Here, we report that a basic helix-loop-helix–type transcription factor, ABA-INDUCIBLE BHLH-TYPE TRANSCRIPTION FACTOR/JA-ASSOCIATED MYC2-LIKE1 (JAM1), acts as a transcriptional repressor and negatively regulates JA signaling. Gain-of-function transgenic plants expressing the chimeric repressor for JAM1 exhibited substantial reduction of JA responses, including JA-induced inhibition of root growth, accumulation of anthocyanin, and male fertility. These plants were also compromised in resistance to attack by the insect herbivore Spodoptera exigua. Conversely, jam1 loss-of-function mutants showed enhanced JA responsiveness, including increased resistance to insect attack. JAM1 and MYC2 competitively bind to the target sequence of MYC2, which likely provides the mechanism for negative regulation of JA signaling and suppression of MYC2 functions by JAM1. These results indicate that JAM1 negatively regulates JA signaling, thereby playing a pivotal role in fine-tuning of JA-mediated stress responses and plant growth. PMID:23673982

  5. The global impact factors of net primary production in different land cover types from 2005 to 2011.

    PubMed

    Yu, Bo; Chen, Fang

    2016-01-01

    With the seriously polluted environment due to social development, the sustainability of net primary production (NPP), which is used to feed most lives on the earth, has become one of the biggest concerns that we have to consider for the sake of food shortage. There have been many researches analyzing one or two potential impact factors of NPP based on field observation data, which brings about many uncertainties for further calculation. Moreover, the frequently used process-based models heavily depend on the understandings of researchers about the NPP process. The premises of such models hinder the impact factor analysis from being objective and confident. To overcome such shortages, we collected 27 potential impact factors of global NPP in terms of eight land cover types. The feature variables include atmosphere, biosphere, anthroposphere and lithosphere parameters, which can be obtained from public available remote sensed products. The experiment shows that latitude, irradiance ultraviolet and normalized difference vegetation index are dominant factors impacting global NPP. Anthropogenic activities, precipitation and surface emissivity are influencing NPP calculation largely. However, some commonly used biosphere parameters in process-based models are actually not playing that important roles in NPP estimation. This work provides a new insight in analyzing NPP impact factors, being more objective and comprehensive compared with frequently used process-based models. PMID:27536518

  6. Adiponectin as a Protective Factor Against the Progression Toward Type 2 Diabetes Mellitus in Postmenopausal Women

    PubMed Central

    Darabi, Hossein; Raeisi, Alireza; Kalantarhormozi, Mohammad Reza; Ostovar, Afshin; Assadi, Majid; Asadipooya, Kamyar; Vahdat, Katayoun; Dobaradaran, Sina; Nabipour, Iraj

    2015-01-01

    Abstract Serum adiponectin levels have been suggested to be predictors of type 2 diabetes mellitus in diverse populations. However, the relationship between circulating adiponectin levels and the risk of development of type 2 diabetes in postmenopausal women has not been investigated. A total of 382 healthy postmenopausal women who participated in a prospective cohort study were followed for 5.8 years. Type 2 diabetes mellitus was defined according to the criteria set out by the American Diabetes Association. Adiponectin, osteoprotegerin (OPG), and high-sensitivity C-reactive protein (hs-CRP) levels were measured using ELISA. Of 195 women who did not have diabetes at baseline and who were reexamined in the second phase of the study for diabetic status, 35 subjects (17.9%) developed type 2 diabetes mellitus during the 5.8 years follow-up period. The women with type 2 diabetes had lower adiponectin levels than the healthy postmenopausal women. Multiple regression analysis showed that, after adjustments were made for age, cardiovascular risk factors, OPG, and hs-CRP levels, higher baseline adiponectin levels were associated with a lower relative risk (RR) of having type 2 (RR = 0.07, confidence interval [CI]: 0.01–0.66, P = 0.021). Higher baseline adiponectin levels functioned as a predictor of a lower risk of developing type 2 diabetes mellitus among postmenopausal women during a 5.8 years follow-up study. Therefore, it is suggested that elevated adiponectin levels may offer protection against the development of type 2 diabetes mellitus after the menopause. PMID:26287420

  7. Optimal Design of Rotary-Type Voice Coil Motor Using Multisegmented Magnet Array for Small Form Factor Optical Disk Drive

    NASA Astrophysics Data System (ADS)

    Jeong, Jaehwa; Gweon, Dae-Gab

    2007-05-01

    For a small form factor optical disk drive (SFFODD), a high-performance actuator satisfying the requirements for small size, high speed, and low-power consumption simultaneously is required. In this paper, we propose a rotary-type voice coil motor (VCM) using a multisegmented magnet array (MSMA) for the SFFODD. The VCM is designed to move the entire system including miniaturized optical components, which are necessary in reading and writing data. To increase the actuating force of the VCM, the MSMA, a novel magnetic circuit, is adopted because it can provide a higher flux density than a conventional magnet array in the rotary-type VCM. To obtain the best performance from the VCM in the limit of actuator size, design optimization is performed. The manufactured actuator with optimally designed parameters is described and the potential performance of track seeking is evaluated and presented.

  8. Low-sodium Dietary Approaches to Stop Hypertension-type diet including lean red meat lowers blood pressure in postmenopausal women.

    PubMed

    Nowson, Caryl A; Wattanapenpaiboon, Naiyana; Pachett, Annabelle

    2009-01-01

    Low-sodium Dietary Approaches to Stop Hypertension (DASH) diets are base producing but restrict red meat without clear justification. We hypothesized that a vitality diet (VD), a low-sodium DASH-type diet with a low dietary acid load containing 6 servings of 100 g cooked lean red meat per week, would be more effective in reducing blood pressure (BP) compared with a higher acid load reference healthy diet (RHD) based on general dietary guidelines to reduce fat intake and increase intake of breads and cereals. A randomized, parallel dietary intervention study was conducted to compare the BP-lowering effect of these 2 diets in postmenopausal women with high/normal BP. Women were randomly assigned to follow either VD or RHD for 14 weeks. Home BP was measured daily with an automated BP monitor under standard conditions. Of 111 women commencing the study, 95 completed (46 VD, 49 RHD). Systolic BP (SBP) throughout the intervention was lower in the VD group compared to the RHD group (repeated-measures analysis of variance time by diet, P = .04), such that at the end of the study, the VD had a fall of SBP by 5.6 +/- 1.3 mm Hg (mean +/- SEM) compared with a fall of 2.7 +/- 1.0 mm Hg in the RHD (group difference, P = .08). When only those taking antihypertensive medications were assessed, the VD (n = 17) had a significant fall of 6.5 +/- 2.5 mm Hg SBP (P = .02) and 4.6 +/- 1.4 mm Hg diastolic BP (P = .005) after 14 weeks, and their BP was lower than that of the RHD group (n = 18) throughout the study (P < .05). We concluded that a low-sodium DASH diet with a low dietary acid load, which also included lean red meat on most days of the week, was effective in reducing BP in older women, particularly in those taking antihypertensive medications. PMID:19185772

  9. Chronic Kidney Disease and Associated Cardiovascular Risk Factors in Chinese with Type 2 Diabetes

    PubMed Central

    Lou, Qing-Lin; Ouyang, Xiao-Jun; Gu, Liu-Bao; Mo, Yong-Zhen; Ma, Ronald; Nan, Jennifer; Kong, Alice; So, Wing-Yee; Ko, Gary; Chan, Juliana; Chow, Chun-Chung

    2012-01-01

    Background To determine the frequency of chronic kidney disease (CKD) and its associated risk factors in Chinese type 2 diabetic patients, we conducted a cross-sectional study in Nanjing, China, in the period between January 2008 and December 2009. Methods Patients with type 2 diabetes under the care by Jiangsu Province Official Hospital, Nanjing, China were invited for assessment. CKD was defined as the presence of albuminuria or estimated glomerular filtration rate <60 mL/min/1.73 m2. Albuminuria was defined as urinary albumin-to-creatinine ratio ≥30 mg/g. Results We recruited 1,521 urban Chinese patients with type 2 diabetes (mean age, 63.9±12.0 years). The frequency of CKD and albuminuria was 31.0% and 28.9%, respectively. After adjusted by age and sex, hypertension, anemia and duration of diabetes were significantly associated with CKD with odds ratio (95% confidence interval) being 1.93 (1.28 to 2.93), 1.70 (1.09 to 2.64), and 1.03 (1.00 to 1.06), respectively. Conclusion In conclusion, CKD was common in the urban Nanjing Chinese with type 2 diabetes. Strategies to prevent or delay progression of kidney disease in diabetes should be carried out at the early disease course of type 2 diabetes. PMID:23275937

  10. Type of body fat distribution in postmenopausal women and its related factors

    PubMed Central

    Noroozi, Mahnaz; Rastegari, Zahra; Paknahad, Zamzam

    2010-01-01

    BACKGROUND: The type of body fat distribution has an important role for identifying risk of diseases. One of the simple anthropometric indexes for estimating type of body fat distribution is waist circumference index. This study is aimed to determine the type of body fat distribution in postmenopausal women and its related factors. METHODS: This is a cross sectional descriptive analytical study. Samples were 278 postmenopausal women in Isfahan who were selected by stratified sampling and then were invited to 64 health centers of Isfahan. Data was gathered using a questionnaire and standard meter. Data was analyzed using SPSS software and descriptive and inferential statistics. RESULTS: Results showed that in postmenopausal women the mean of waist circumference index was 93.63 (10.66) and its range was 54 to 119 cm. There was a meaningful relation between job, educational status, total pregnancies, total deliveries, age of first pregnancy, lactation history and menopausal age with waist circumference index. CONCLUSIONS: Results showed that the type of body fat distribution of postmenopausal women is of android type. Considering side effects of this kind of distribution, necessary teachings about healthy eating, movement and exercises must be given to women of these ages. PMID:21589746

  11. Spironolactone inhibits production of proinflammatory cytokines, including tumour necrosis factor-α and interferon-γ, and has potential in the treatment of arthritis

    PubMed Central

    BENDTZEN, K; HANSEN, P R; RIENECK, K

    2003-01-01

    Evidence suggests that spironolactone, an aldosterone antagonist, has effects on many cell types independent of its binding to cytosolic mineralocorticoid receptors. We tested the effects of spironolactone on ex vivo-activated human blood leucocytes using gene expression analyses (GeneChip®, 12 000 genes) and enzyme immunoassay for quantitating secreted pro- and anti-inflammatory cytokines. Furthermore, to evaluate the safety and efficacy of spironolactone as an anti-inflammatory drug 21 patients with rheumatoid arthritis (RA), juvenile idiopathic arthritis (JIA) or other arthritides were treated for up to 22 months with 1–3 mg/kg/day. Spironolactone, at in vivo attainable doses, markedly suppressed transcription of several proinflammatory cytokines and, accordingly, inhibited release of tumour necrosis factor, lymphotoxin, interferon-γ, granulocyte-macrophage colony-stimulating factor and interleukin 6 (70–90% inhibition). Release of these cytokines was also suppressed when testing whole blood from RA patients receiving 50 mg spironolactone twice daily, indicating that pharmaceutical use of the drug may suppress the release of inflammatory cytokines. Spironolactone therapy was generally well tolerated, although treatment had to be stopped in two adults on concomitant methotrexate therapy. Sixteen patients (76%) responded favourably. American College of Rheumatology criteria (ACR)20 or better was achieved in six of nine RA patients; four reached ACR70. Eight of nine JIA patients improved. In conclusion, spironolactone inhibits production of several proinflammatory cytokines considered to be of pathogenic importance in many immunoinflammatory diseases and shows positive effect in patients with chronic arthritis. Its effect as an anti-inflammatory drug should be explored, because prolonged spironolactone therapy is reasonably safe and economically attractive compared with many modern anti-inflammatory therapies. PMID:12974768

  12. The association of glutathione S-transferase gene mutations (including GSTT1 and GSTM1) with the prognostic factors and relapse in acute lymphoblastic leukemia.

    PubMed

    Zareifar, Soheila; Monabati, Ahmad; Saeed, Amir; Fakhraee, Farzaneh; Cohan, Nader

    2013-09-01

    Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. It accounts for one fourth of all childhood cancers and approximately 75% of all childhood leukemias. Some prognostic factors determine the outcome of therapy [e.g. age, sex, initial white blood cell count (WBC), etc.]; however, it is believed that other mechanisms such as glutathione S-transferase (GST) gene mutation, the expression of lung resistance protein (LRP), and multidrug resistance-associated protein (MRP) also plays a role in treatment failure. In this study, GST gene mutations including GSTM1 and GSTT1 were evaluated in patients with leukemia. Thirty newly diagnosed ALL patients younger than 15 years of age participated in the present study. Bone marrow aspiration and biopsy were evaluated for immune phenotyping and DNA was extracted for GST genotyping. All data plus sex, age, initial WBC count, central nervous system (CNS) or testicular involvement, immune phenotype, and outcome (relapse or not) were analyzed statistically. Genotyping showed that 46% were double null, 50% were M1 null and 93.3% were T1 null for GST mutations. There was no statistically significant relationship between GSTT1 and GSTM1 mutations, or between double null status, prognostic factors and relapse (P > .05). So, although the results of GST mutations were consistent, it seems that these mutations are not statistically significant. PMID:23444902

  13. Hydrological drought types in cold climates: quantitative analysis of causing factors and qualitative survey of impacts

    NASA Astrophysics Data System (ADS)

    Van Loon, A. F.; Ploum, S. W.; Parajka, J.; Fleig, A. K.; Garnier, E.; Laaha, G.; Van Lanen, H. A. J.

    2015-04-01

    For drought management and prediction, knowledge of causing factors and socio-economic impacts of hydrological droughts is crucial. Propagation of meteorological conditions in the hydrological cycle results in different hydrological drought types that require separate analysis. In addition to the existing hydrological drought typology, we here define two new drought types related to snow and ice. A snowmelt drought is a deficiency in the snowmelt discharge peak in spring in snow-influenced basins and a glaciermelt drought is a deficiency in the glaciermelt discharge peak in summer in glacierised basins. In 21 catchments in Austria and Norway we studied the meteorological conditions in the seasons preceding and at the time of snowmelt and glaciermelt drought events. Snowmelt droughts in Norway were mainly controlled by below-average winter precipitation, while in Austria both temperature and precipitation played a role. For glaciermelt droughts, the effect of below-average summer air temperature was dominant, both in Austria and Norway. Subsequently, we investigated the impacts of temperature-related drought types (i.e. snowmelt and glaciermelt drought, but also cold and warm snow season drought and rain-to-snow-season drought). In historical archives and drought databases for the US and Europe many impacts were found that can be attributed to these temperature-related hydrological drought types, mainly in the agriculture and electricity production (hydropower) sectors. However, drawing conclusions on the frequency of occurrence of different drought types from reported impacts is difficult, mainly because of reporting biases and the inevitably limited spatial and temporal scales of the information. Finally, this study shows that complete integration of quantitative analysis of causing factors and qualitative analysis of impacts of temperature-related droughts is not yet possible. Analysis of selected events, however, points out that it can be a promising research

  14. The Factors Associated With Disease Mismanagement in Young Patients with Type 1 Diabetes: A Qualitative Study

    PubMed Central

    Celik, Selda; Kelleci, Meral; Satman, Ilhan

    2015-01-01

    Background The objective of this qualitative study on young adults with type 1 diabetes was to determine the factors associated with mismanagement of diabetes. Methods In this qualitative study, a descriptive phenomenological and psychological method was followed. Purposeful sampling method was used in this study. 28 young adults aged 18-25 with type 1 diabetes (16 females, 12 males) with HbA1c levels >6.5% were interviewed in-depth. Each interview lasted 40-45 minutes. The recorded interviews were transcribed verbatim, examined line-by-line and coded using open coding techniques and managed by QSR NVivo 7. During the research period, Guba ve Lincolln criteria were used to ensure the accuracy and precision of the study findings. Results The study identified seven themes which affect the diabetes management of the patients. These themes were negative emotions about the disease, difficulties arising from living condition, difficulties arising from the treatment treatment process, lack of social support, not solution oriented coping methods, concerns about the future and issues of developing knowledge and attitude regarding diabetes management. Conclusion There are multiple factors affecting the management of diabetes in young adults with type 1 diabetes. Diabetes has a biopsychosocial impact on young adults’ lives, developing a negative attitude toward their future and that of their family. PMID:26005688

  15. Yeast GAL11 protein is a distinctive type transcription factor that enhances basal transcription in vitro.

    PubMed Central

    Sakurai, H; Hiraoka, Y; Fukasawa, T

    1993-01-01

    The yeast auxiliary transcription factor GAL11, a candidate for the coactivator, was partially purified from yeast cells, and its function was characterized in a cell-free transcription system. The partially purified GAL11 protein stimulated basal transcription from the CYC1 core promoter by a factor of 4-5 at the step of preinitiation complex formation. GAL11 protein also enhanced transcription activated by general regulatory factor 1, GAL4-AH, or GAL4-VP16 to the same extent as the basal transcription. Therefore, the apparent potentiation of the activators by GAL11 was attributable to the stimulation of basal transcription. The wild-type GAL11 protein (but not a mutant-type protein) produced in bacteria stimulated transcription as effectively as GAL11 from yeast. These results suggest that GAL11 functions as a positive cofactor of basal and activator-induced transcription in a cell-free transcription system. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:8378310

  16. Basic-Zipper-Type Transcription Factor FlbB Controls Asexual Development in Aspergillus nidulans▿ †

    PubMed Central

    Etxebeste, Oier; Ni, Min; Garzia, Aitor; Kwon, Nak-Jung; Fischer, Reinhard; Yu, Jae-Hyuk; Espeso, Eduardo A.; Ugalde, Unai

    2008-01-01

    The fungal colony is a complex multicellular unit consisting of various cell types and functions. Asexual spore formation (conidiation) is integrated through sensory and regulatory elements into the general morphogenetic plan, in which the activation of the transcription factor BrlA is the first determining step. A number of early regulatory elements acting upstream of BrlA (fluG and flbA-E) have been identified, but their functional relations remain to be further investigated. In this report we describe FlbB as a putative basic-zipper-type transcription factor restricted to filamentous fungi. FlbB accumulates at the hyphal apex during early vegetative growth but is later found in apical nuclei, suggesting that an activating modification triggers nuclear import. Moreover, proper temporal and quantitative expression of FlbB is a prerequisite for brlA transcription, and misscheduled overexpression inhibits conidiation. We also present evidence that FlbB activation results in the production of a second diffusible signal, acting downstream from the FluG factor, to induce conidiation. PMID:17993569

  17. Incidence of and risk factors for ischemic-type biliary lesions following orthotopic liver transplantation.

    PubMed

    Heidenhain, Christoph; Pratschke, Johann; Puhl, Gero; Neumann, Ulf; Pascher, Andreas; Veltzke-Schlieker, Winfried; Neuhaus, Peter

    2010-01-01

    Ischemic-type biliary lesions (ITBL) account for a major part of patients' morbidity and mortality after orthotopic liver transplantation (OLT). The exact origin of this type of biliary complication remains unknown. This study retrospectively evaluated 1843 patients. Patients with primary sclerosing cholangitis were excluded from this study. The diagnosis of ITBL was established only when all other causes of destruction of the biliary tree were ruled out. Donor age (P = 0.028) and cold ischemic time (CIT) (P = 0.002) were found to be significant risk factors for the development of ITBL. Organs that were perfused with University of Wisconsin (UW) solution developed ITBL significantly more often than Histidine-Tryptophan-Ketoglutarate (HTK)-perfused organs (P = 0.036). The same applied to organs harvested externally and shipped to our center versus those that were procured locally by our harvest teams (P < 0.001). Pressure perfusion via the hepatic artery significantly reduced the risk of ITBL (P = 0.001). The only recipient factor that showed a significant influence was Child-Pugh score status C (P = 0.021). Immunologic factors had no significant impact on ITBL. The clinical consequences of this study for our institution have been the strict limitation of CIT to <10 h and the exclusive use of HTK solution. We further advocate that all organ procurement teams perform pressure perfusion on harvested organs. PMID:19691661

  18. Type 1 Diabetes Patients Using Continuous Subcutaneous Insulin Infusion Therapy: Feeling Burdened Correlated with Factors

    PubMed Central

    Nishio, Ikuko; Chujo, Masami

    2015-01-01

    Background The purpose of this study was to investigate factors related to feelings of being burdened in type 1 diabetes patients using continuous subcutaneous insulin infusion (CSII) therapy. Methods Participants were 106 subscribers to the Diabetes Network’s e-mail newsletter. An online survey was used. Eligible participants were aged at least 20 years, had type 1 diabetes, and were using CSII. Survey questions concerned whether participants found CSII burdensome, and seven potential reasons for feelings of burden. Analysis calculated correlations among participants’ demographic and treatment-related factors, and among participants’ reasons for feeling CSII to be burdensome. Results Regarding demographic and treatment-related factors, gender was found to be weakly negatively correlated with the following variables: employment status, and whether participants had discussed their concerns with a doctor. Employment status was found to be weakly correlated with diabetes duration; employment status and diabetes duration were found to be weakly correlated with age. Regarding reasons for finding CSII therapy burdensome, “It takes too much time” was found to be strongly positively correlated with “It interferes with work responsibilities”; 16 weak positive correlations were also found. Conclusion To explain our results, we suggest that medical expenses, glycemic control, scheduling outpatient visits around home and work responsibilities, and interacting with medical staff may have caused participants to find CSII therapy burdensome. Most participants had never discussed their treatment concerns with a doctor. This suggests that nurses may be able to mitigate feeling burdened in participants using CSII therapy. PMID:26538798

  19. The Presence of Family History and the Development of Type 2 Diabetes Mellitus Risk Factors in Rural Children

    ERIC Educational Resources Information Center

    Adams, Marsha Howell; Barnett Lammon, Carol Ann

    2007-01-01

    Type 2 diabetes mellitus is reaching epidemic proportions among children and adolescents. School health fairs offer an opportunity to identify children with risk factors for the development of type 2 diabetes mellitus. This study identified selected risk factors (i.e., high-risk racial/ethnic group, obesity, elevated blood pressure, elevated…

  20. Anthropometric measures and lipid CHD risk factors in Korean Immigrants with Type 2 Diabetes

    PubMed Central

    Choi, Sarah; Tan, Edwin

    2010-01-01

    Objectives The purpose of this study was to 1) describe anthropometric measures among Korean immigrants with type 2 diabetes (T2DM); and, 2) examine the relationships between measures of obesity with several forms of dyslipidemia in this group. Background Obesity and dyslipidemia are commonly associated with T2DM and they are risk factors for coronary heart disease (CHD), the leading cause of death for people with diabetes. Asians are predisposed to abdominal obesity and experience significant CHD risk at lower BMI levels. Despite high prevalence of diabetes among Korean immigrants, relationships among anthropometric measures and lipid-related CHD risk factors have not been examined. Methods A convenience sample of 143 adult Korean immigrants with T2DM between the ages of 30–80 participated in the study. Body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) were obtained using standardized procedures. Total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL), and high-density lipoprotein cholesterol (HDL) were assessed using a finger stick blood test. Hierarchical linear regressions were conducted to identify which of the anthropometric measures was significantly related to individuals’ cholesterol levels. Results Central obesity measures, not BMI, were significantly associated with dyslipidemia in Korean immigrants with T2DM independent of potential confounds such as hemoglobin A1C, cigarette smoking, age, and cholesterol medication. Different central obesity measures were associated with different cholesterol types for Korean diabetic men and women. In men, WHR was positively associated with LDL and TC levels. In women, WC was negatively associated with HDL. Conclusions Central obesity measures (WC and WHR) are better indicators for assessing lipid-related CHD risk factor among Korean immigrants with T2DM than BMI. Gender difference in the association between central obesity measures and lipid types should

  1. Factors associated with dietary diversity score among individuals with type 2 diabetes mellitus.

    PubMed

    Tiew, Kee Fong; Chan, Yoke Mun; Lye, Munn Sann; Loke, Seng Cheong

    2014-12-01

    Studies on diet quality among individuals with type 2 diabetes mellitus (T2DM) are scarce. This crosssectional study aimed to assess the diet quality and to determine its associated factors among individuals with T2DM at the Medical Outpatients Department, Serdang Hospital, Selangor, Malaysia, from July 2010 to March 2011. Subjects were interviewed for sociodemographic data. Diabetes history was retrieved from the hospital's e-database. Usual dietary intake was measured using a food frequency questionnaire, from which a dietary diversity score was obtained with two measures: Food Group Score and Serving Score were constructed based on the Malaysian Dietary Guidelines. Food Group Score was computed from the number of food groups consumed from five major food groups (grains, vegetables, fruits, meat, and dairy products) whereas Serving Score was computed from the number of servings consumed from the various food groups. Anthropometric measures, including weight, height, waist- and hip-circumference were examined. For data analyses, descriptive statistics, simple and multiple linear regression were conducted using IBM SPSS Statis- tics 20.0. A total of 113 subjects (50.4% female), with mean?SD age of 54.05 +/- 10.30 years and duration of diabetes of 11.25?9.05 years were studied. The mean Food Group Score and Serving Score were 4.12 +/- 0.79 and 12.75+3.50 respectively. Slightly more than one-third of the subjects achieved five food groups a day while less than 2% consumed a desirable number of servings from all food groups. Among the five food groups, dairy, and fruits were the least-frequently consumed foods. Lower education, lower personal income, working, non-insulin, overweight and obese subjects had significantly lower Food Group Score than their counterparts [F (6,106)=4.924, p<0.0001] whereas lower education, lower waist-to-hip ratio, overweight and obese subjects had significantly lower Serving Score than their counterparts [F (4,108)=7.520, p<0.0001]. There

  2. Factors Associated with Dietary Diversity Score among Individuals with Type 2 Diabetes Mellitus

    PubMed Central

    Tiew, Kee Fong; Lye, Munn Sann; Loke, Seng Cheong

    2014-01-01

    ABSTRACT Studies on diet quality among individuals with type 2 diabetes mellitus (T2DM) are scarce. This cross-sectional study aimed to assess the diet quality and to determine its associated factors among individuals with T2DM at the Medical Outpatients Department, Serdang Hospital, Selangor, Malaysia, from July 2010 to March 2011. Subjects were interviewed for sociodemographic data. Diabetes history was retrieved from the hospital's e-database. Usual dietary intake was measured using a food frequency questionnaire, from which a dietary diversity score was obtained with two measures: Food Group Score and Serving Score were constructed based on the Malaysian Dietary Guidelines. Food Group Score was computed from the number of food groups consumed from five major food groups (grains, vegetables, fruits, meat, and dairy products) whereas Serving Score was computed from the number of servings consumed from the various food groups. Anthropometric measures, including weight, height, waist- and hip-circumference were examined. For data analyses, descriptive statistics, simple and multiple linear regression were conducted using IBM SPSS Statistics 20.0. A total of 113 subjects (50.4% female), with mean±SD age of 54.05±10.30 years and duration of diabetes of 11.25±9.05 years were studied. The mean Food Group Score and Serving Score were 4.12±0.79 and 12.75±3.50 respectively. Slightly more than one-third of the subjects achieved five food groups a day while less than 2% consumed a desirable number of servings from all food groups. Among the five food groups, dairy, and fruits were the least-frequently consumed foods. Lower education, lower personal income, working, non-insulin, overweight and obese subjects had significantly lower Food Group Score than their counterparts [F (6,106)=4.924, p<0.0001] whereas lower education, lower waist-to-hip ratio, overweight and obese subjects had significantly lower Serving Score than their counterparts [F (4,108)=7.520, p<0

  3. Beverage Consumption Patterns and Associations with Metabolic Risk Factors Among Low-Income Latinos with Uncontrolled Type 2 Diabetes

    PubMed Central

    Wang, Monica L.; Lemon, Stephenie C.; Olendzki, Barbara; Rosal, Milagros C.

    2013-01-01

    In the U.S., Latinos experience disproportionately higher rates of type 2 diabetes and diabetes-related complications than non-Latino whites. Sugar-sweetened beverage (SSB) consumption is strongly associated with increased risk of developing type 2 diabetes. Reducing caloric intake, particularly from energy-dense, low-nutrient foods or beverages, can be an effective and key strategy for metabolic and weight control. However, little is known about the contribution of various types of beverages, including but not limited to SSBs, to total caloric intake among Latinos with type 2 diabetes. Low-income Latinos (87.7% Puerto Rican) participating in a diabetes self-management intervention trial (N=238) provided cross-sectional, descriptive data on beverage consumption patterns, anthropometric outcomes, and metabolic characteristics. Beverages accounted for one-fifth of the total daily caloric intake. SSBs and milk beverages, respectively, contributed 9.6% of calories to overall daily caloric intake. Interventions directed at diabetes risk factors among low-income Latinos with diabetes may benefit from consideration of beverage consumption behaviors as an important strategy to reduce caloric and sugar intake. PMID:23999278

  4. Biomarkers predicting resistance to epidermal growth factor receptor-targeted therapy in metastatic colorectal cancer with wild-type KRAS

    PubMed Central

    Liu, Jiang; Hu, Jing; Cheng, Lei; Ren, Wei; Yang, Mi; Liu, Baorui; Xie, Li; Qian, Xiaoping

    2016-01-01

    EGFR pathway is an important therapeutic target in human tumors, including metastatic colorectal cancer (mCRC). The advent of EGFR-targeted monoclonal antibodies panitumumab and cetuximab has generated promise for the treatment of mCRC and has largely improved patients’ progression-free survival (PFS) and overall survival (OS). However, treatment with anti-EGFR monoclonal antibodies is only effective in a subset of mCRC patients with wild-type KRAS. This indicates that there are other factors affecting the efficacy of anti-EGFR monoclonal antibodies. Existing studies have demonstrated that among colorectal cancer patients with wild-type KRAS, harboring mutations of BRAF, PIK3CA, NRAS, or PTEN-null may demonstrate resistance to anti-EGFR-targeted therapy, and biomarkers detection can provide better-personalized treatment for mCRC patients. How to identify and reverse the secondary resistance to anti-EGFR monoclonal antibody therapy is also another great challenge to improve the anti-EGFR efficacy in wild-type KRAS mCRC patients. Finally, both of the molecular mechanisms of response and acquired resistance would be important for the directions of future research. This review focuses on how to further improve the predictive value of anti-EGFR therapies and how to also try and avoid futile treatment for wild-type KRAS colorectal cancer patients. PMID:26869800

  5. Obesity as an Important Risk Factor for Certain Types of Cancer

    PubMed Central

    Davoodi, Sayed Hossain; Malek-Shahabi, Talieh; Malekshahi-Moghadam, Ali; Shahbazi, Roghieh; Esmaeili, Saeideh

    2013-01-01

    Cancer could be described as the uncontrolled and unrestricted growth of malignant cells in any place of the body. It is a multifactorial disease which either heredity or environmental factors (such as nutrition, physical inactivity, alcohol, obesity, exposure to sun, environmental pollutants, infections) chip in incidence of cancer. In recent years, several researchers have focused on obesity as a potent cancer risk factor. Scientificevidences have suggested that obesity has associated with increased risk for a plenty of different types of cancer. The evidences are the most consistent for endometrial cancer, breast cancer between the postmenopausal women, and renal cell cancer. More contradictoryresults have reported about the colorectal, prostate, and pancreatic cancer. Although numerous studies have done according to the obesity and cancer relation or joint, but the molecular mechanisms in which obesity could increase the risks of cancer, have been poorly understood. PMID:25250133

  6. [Type 1 Diabetes Mellitus: brief review of the main associated psychological factors].

    PubMed

    Gómez-Rico, I; Pérez-Marín, M; Montoya-Castilla, I

    2015-01-01

    Type 1 Diabetes Mellitus (T1DM) is a widespread chronic disease among children and adolescents. Diagnosis and evolution usually involves a significant burden on the patient, and their families must change various aspects of their lifestyle to fulfill the demands of treatment. This study aims to identify the main psychological, family, and adjustment to illness features of children and adolescents diagnosed with DM1 and, in particular to highlight the associated psychopathological factors. The methodology involved a systematic literature search in the main scientific databases. Due to the biopsychosocial impact of DM1 usually assumed in the life of the child and family, and how it may compromise the quality of life and emotional well-being of both, different studies have agreed on the importance of identifying the set of psychological factors involved in healthy adjustment to illness in the child and adolescent with DM1. PMID:24809830

  7. Prediction of Giant Thermoelectric Power Factor in Type-VIII Clathrate Si46

    NASA Astrophysics Data System (ADS)

    Norouzzadeh, Payam; Myles, Charles W.; Vashaee, Daryoosh

    2014-11-01

    Clathrate materials have been the subject of intense interest and research for thermoelectric application. Nevertheless, from the very large number of conceivable clathrate structures, only a small fraction of them have been examined. Since the thermal conductivity of clathrates is inherently small due to their large unit cell size and open-framework structure, the current research on clathrates is focused on finding the ones with large thermoelectric power factor. Here we predict an extraordinarily large power factor for type-VIII clathrate Si46. We show the existence of a large density of closely packed elongated ellipsoidal carrier pockets near the band edges of this so far hypothetical material structure, which is higher than that of the best thermoelectric materials known today. The high crystallographic symmetry near the energy band edges for Si46-VIII clathrates is responsible for the formation of such a large number of carrier pockets.

  8. Prediction of giant thermoelectric power factor in type-VIII clathrate Si46.

    PubMed

    Norouzzadeh, Payam; Myles, Charles W; Vashaee, Daryoosh

    2014-01-01

    Clathrate materials have been the subject of intense interest and research for thermoelectric application. Nevertheless, from the very large number of conceivable clathrate structures, only a small fraction of them have been examined. Since the thermal conductivity of clathrates is inherently small due to their large unit cell size and open-framework structure, the current research on clathrates is focused on finding the ones with large thermoelectric power factor. Here we predict an extraordinarily large power factor for type-VIII clathrate Si(46). We show the existence of a large density of closely packed elongated ellipsoidal carrier pockets near the band edges of this so far hypothetical material structure, which is higher than that of the best thermoelectric materials known today. The high crystallographic symmetry near the energy band edges for Si(46)-VIII clathrates is responsible for the formation of such a large number of carrier pockets. PMID:25391971

  9. Transcription factor AP-2 regulates human immunodeficiency virus type 1 gene expression.

    PubMed Central

    Perkins, N D; Agranoff, A B; Duckett, C S; Nabel, G J

    1994-01-01

    Human immunodeficiency virus type 1 (HIV-1) gene expression is regulated by an enhancer region composed of multiple potential cis-acting regulatory sites. Here, we describe binding sites for the transcription factor AP-2 in the HIV-1 long terminal repeat which modulate HIV enhancer function. One site is embedded within the two previously described kappa B elements, and a second site is detected further downstream. DNase I footprinting and electrophoretic mobility shift assay experiments demonstrated that AP-2 binds to the site between the kappa B elements. Interestingly, AP-2 and NF-kappa B bind to this region in a mutually exclusive manner. Mutations which disrupt this AP-2-binding site lower basal levels of transcription but do not affect NF-kappa B-mediated induction by tumor necrosis factor alpha in Jurkat T leukemia cells. Images PMID:8084021

  10. Trigger factors of migraine and tension-type headache: experience and knowledge of the patients.

    PubMed

    Wöber, Christian; Holzhammer, Julia; Zeitlhofer, Josef; Wessely, Peter; Wöber-Bingöl, Ciçek

    2006-09-01

    The objective was to examine potential trigger factors of migraine and tension-type headache (TTH) in clinic patients and in subjects from the population and to compare the patients' personal experience with their theoretical knowledge. A cross-sectional study was carried out in a headache centre. There were 120 subjects comprising 66 patients with migraine and 22 with TTH from a headache outpatient clinic and 32 persons with headache (migraine or TTH) from the population. A semistructured interview covering biographic data, lifestyle, medical history, headache characteristics and 25 potential trigger factors differentiating between the patients' personal experience and their theoretical knowledge was used. The most common trigger factors experienced by the patients were weather (82.5%), stress (66.7%), menstruation (51.4%) and relaxation after stress (50%). The vast majority of triggers occurred occasionally and not consistently. The patients experienced 8.9+/-4.3 trigger factors (range 0-20) and they knew 13.2+/-6.0 (range 1-27). The number of experienced triggers was smallest in the population group (p=0.002), whereas the number of triggers known did not differ in the three study groups. Comparing theoretical knowledge with personal experience showed the largest differences for oral contraceptives (65.0 vs. 14.7%, p<0.001), chocolate (61.7 vs. 14.3%, p>0.001) and cheese (52.5 vs. 8.4%, p<0.001). In conclusion, almost all trigger factors are experienced occasionally and not consistently by the majority of patients. Subjects from the population experience trigger factors less often than clinic patients. The difference between theoretical knowledge and personal experience is largest for oral contraceptives, chocolate and cheese. PMID:16897622

  11. Potential Risk Factors for the Onset of Complex Regional Pain Syndrome Type 1: A Systematic Literature Review

    PubMed Central

    Shipton, Edward A.; Mulder, Roger T.

    2015-01-01

    Anaesthetists in the acute and chronic pain teams are often involved in treating Complex Regional Pain Syndromes. Current literature about the risk factors for the onset of Complex Regional Pain Syndrome Type 1 (CRPS 1) remains sparse. This syndrome has a low prevalence, a highly variable presentation, and no gold standard for diagnosis. In the research setting, the pathogenesis of the syndrome continues to be elusive. There is a growing body of literature that addresses efficacy of a wide range of interventions as well as the likely mechanisms that contribute to the onset of CRPS 1. The objective for this systematic search of the literature focuses on determining the potential risk factors for the onset of CRPS 1. Eligible articles were analysed, dated 1996 to April 2014, and potential risk factors for the onset of CRPS 1 were identified from 10 prospective and 6 retrospective studies. Potential risk factors for the onset of CRPS 1 were found to include being female, particularly postmenopausal female, ankle dislocation or intra-articular fracture, immobilisation, and a report of higher than usual levels of pain in the early phases of trauma. It is not possible to draw definite conclusions as this evidence is heterogeneous and of mixed quality, relevance, and weighting strength against bias and has not been confirmed across multiple trials or in homogenous studies. PMID:25688265

  12. Prevalence and risk factors of gastroparesis-related symptoms among patients with type 2 diabetes

    PubMed Central

    Almogbel, Rakan A; Alhussan, Fulwa A; Alnasser, Sulaiman A; Algeffari, Metab A

    2016-01-01

    Background The prevalence of gastroparesis in type 2 diabetes mellitus (T2DM) vary widely. Our aim is to estimate the prevalence of clinical symptoms of gastroparesis among patients with type 2 diabetes mellitus and explore the relationship between gastroparesis and other risk factors. Methods A cross-sectional study evaluating 147 type 2 diabetics using the Gastroparesis Cardinal Symptoms Index (GCSI). A GCSI Total Score ≥ 1.90 were chosen as having definite symptoms of gastroparesis. All patients completed a demographic questionnaire and interviewed to complete the. Demographic Data, disease duration, Medication, comorbidities, recent blood glucose and HbA1C were collected and investigated. Results The prevalence of clinical symptoms of gastroparesis among type 2 diabetics was 10.8%. Clinical symptoms of gastroparesis were significantly correlated to HbA1c (p=0.001), blood glucose (p= 0.003), duration of diabetes (p= 0.02) and comorbidities (p=0.009). The most common symptoms were bloating, stomach fullness and early satiety (63.94%, 55.1% and 48.3% respectively). In logistic regression analysis, female gender emerged as significant independent predictors of the presence of at least one symptom. Conclusions The prevalence of clinical symptoms of gastroparesis observed in the Saudi patientsdiagnosedwithtype2 diabetes was 10.8% and is independently associated with poor controlled diabetes, hyperglycemia, and long duration of diabetes and history of Co-morbid conditions. PMID:27610063

  13. Predicting factors of hypoglycaemia in elderly type 2 diabetes patients: Contributions of the GERODIAB study.

    PubMed

    Bordier, L; Buysschaert, M; Bauduceau, B; Doucet, J; Verny, C; Lassmann Vague, V; Le Floch, J P

    2015-09-01

    The burden of hypoglycaemia is important, particularly in elderly type 2 diabetes (T2D) patients. Unfortunately, however, few studies are available concerning this population. GERODIAB is a prospective, multicentre, observational study that aims to describe the 5-year morbidity and mortality of 987 T2D patients aged 70 years and older. After analyzing the frequency of and factors associated with hypoglycaemia in the 6 months prior to study inclusion, it was found that hypoglycaemia was associated with retinopathy, lower levels of LDL cholesterol and altered mini-Geriatric Depression Scale (GDS) scores. PMID:25845279

  14. The SEB-1 Transcription Factor Binds to the STRE Motif in Neurospora crassa and Regulates a Variety of Cellular Processes Including the Stress Response and Reserve Carbohydrate Metabolism.

    PubMed

    Freitas, Fernanda Zanolli; Virgilio, Stela; Cupertino, Fernanda Barbosa; Kowbel, David John; Fioramonte, Mariana; Gozzo, Fabio Cesar; Glass, N Louise; Bertolini, Maria Célia

    2016-01-01

    When exposed to stress conditions, all cells induce mechanisms resulting in an attempt to adapt to stress that involve proteins which, once activated, trigger cell responses by modulating specific signaling pathways. In this work, using a combination of pulldown assays and mass spectrometry analyses, we identified the Neurospora crassa SEB-1 transcription factor that binds to the Stress Response Element (STRE) under heat stress. Orthologs of SEB-1 have been functionally characterized in a few filamentous fungi as being involved in stress responses; however, the molecular mechanisms mediated by this transcription factor may not be conserved. Here, we provide evidences for the involvement of N. crassa SEB-1 in multiple cellular processes, including response to heat, as well as osmotic and oxidative stress. The Δseb-1 strain displayed reduced growth under these conditions, and genes encoding stress-responsive proteins were differentially regulated in the Δseb-1 strain grown under the same conditions. In addition, the SEB-1-GFP protein translocated from the cytosol to the nucleus under heat, osmotic, and oxidative stress conditions. SEB-1 also regulates the metabolism of the reserve carbohydrates glycogen and trehalose under heat stress, suggesting an interconnection between metabolism control and this environmental condition. We demonstrated that SEB-1 binds in vivo to the promoters of genes encoding glycogen metabolism enzymes and regulates their expression. A genome-wide transcriptional profile of the Δseb-1 strain under heat stress was determined by RNA-seq, and a broad range of cellular processes was identified that suggests a role for SEB-1 as a protein interconnecting these mechanisms. PMID:26994287

  15. The SEB-1 Transcription Factor Binds to the STRE Motif in Neurospora crassa and Regulates a Variety of Cellular Processes Including the Stress Response and Reserve Carbohydrate Metabolism

    PubMed Central

    Freitas, Fernanda Zanolli; Virgilio, Stela; Cupertino, Fernanda Barbosa; Kowbel, David John; Fioramonte, Mariana; Gozzo, Fabio Cesar; Glass, N. Louise; Bertolini, Maria Célia

    2016-01-01

    When exposed to stress conditions, all cells induce mechanisms resulting in an attempt to adapt to stress that involve proteins which, once activated, trigger cell responses by modulating specific signaling pathways. In this work, using a combination of pulldown assays and mass spectrometry analyses, we identified the Neurospora crassa SEB-1 transcription factor that binds to the Stress Response Element (STRE) under heat stress. Orthologs of SEB-1 have been functionally characterized in a few filamentous fungi as being involved in stress responses; however, the molecular mechanisms mediated by this transcription factor may not be conserved. Here, we provide evidences for the involvement of N. crassa SEB-1 in multiple cellular processes, including response to heat, as well as osmotic and oxidative stress. The Δseb-1 strain displayed reduced growth under these conditions, and genes encoding stress-responsive proteins were differentially regulated in the Δseb-1 strain grown under the same conditions. In addition, the SEB-1-GFP protein translocated from the cytosol to the nucleus under heat, osmotic, and oxidative stress conditions. SEB-1 also regulates the metabolism of the reserve carbohydrates glycogen and trehalose under heat stress, suggesting an interconnection between metabolism control and this environmental condition. We demonstrated that SEB-1 binds in vivo to the promoters of genes encoding glycogen metabolism enzymes and regulates their expression. A genome-wide transcriptional profile of the Δseb-1 strain under heat stress was determined by RNA-seq, and a broad range of cellular processes was identified that suggests a role for SEB-1 as a protein interconnecting these mechanisms. PMID:26994287

  16. Postdinner resistance exercise improves postprandial risk factors more effectively than predinner resistance exercise in patients with type 2 diabetes

    PubMed Central

    Heden, Timothy D.; Winn, Nathan C.; Mari, Andrea; Booth, Frank W.; Rector, R. Scott; Thyfault, John P.

    2014-01-01

    Abnormally elevated postprandial glucose and triacylglycerol (TAG) concentrations are risk factors for cardiovascular disease in type 2 diabetes. The most effective time to exercise to lower postprandial glucose and TAG concentrations is unknown. Thus the aim of this study was to determine what time is more effective, either pre- or postdinner resistance exercise (RE), at improving postprandial risk factors in patients with type 2 diabetes. Thirteen obese patients with type 2 diabetes completed three trials in a random order in which they consumed a dinner meal with 1) no RE (NoRE), 2) predinner RE (RE → M), and 3) postdinner RE beginning 45 min after dinner (M → RE). Clinical outcome measures included postprandial glucose and TAG concentrations. In addition, postprandial acetaminophen (gastric emptying), endocrine responses, free fatty acids, and β-cell function (mathematical modeling) were measured to determine whether these factors were related to changes in glucose and TAG. The TAG incremental area under the curve (iAUC) was ∼92% lower (P ≤ 0.02) during M → RE compared with NoRE and RE → M, an effect due in part to lower very-low-density lipoprotein-1 TAG concentrations. The glucose iAUC was reduced (P = 0.02) by ∼18 and 30% during the RE → M and M → RE trials, respectively, compared with NoRE, with no difference between RE trials. RE → M and M → RE reduced the insulin iAUC by 35 and 48%, respectively, compared with NoRE (P < 0.01). The glucagon-like peptide-1 iAUC was ∼50% lower (P ≤ 0.02) during M → RE compared with NoRE and RE → M. Given that predinner RE only improves postprandial glucose concentrations, whereas postdinner RE improves both postprandial glucose and TAG concentrations, postdinner RE may lower the risk of cardiovascular disease more effectively. PMID:25539939

  17. Modelling the Interplay between Lifestyle Factors and Genetic Predisposition on Markers of Type 2 Diabetes Mellitus Risk.

    PubMed

    Walker, Celia G; Solis-Trapala, Ivonne; Holzapfel, Christina; Ambrosini, Gina L; Fuller, Nicholas R; Loos, Ruth J F; Hauner, Hans; Caterson, Ian D; Jebb, Susan A

    2015-01-01

    The risk of developing type 2 diabetes mellitus (T2DM) is determined by a complex interplay involving lifestyle factors and genetic predisposition. Despite this, many studies do not consider the relative contributions of this complex array of factors to identify relationships which are important in progression or prevention of complex diseases. We aimed to describe the integrated effect of a number of lifestyle changes (weight, diet and physical activity) in the context of genetic susceptibility, on changes in glycaemic traits in overweight or obese participants following 12-months of a weight management programme. A sample of 353 participants from a behavioural weight management intervention were included in this study. A graphical Markov model was used to describe the impact of the intervention, by dividing the effects into various pathways comprising changes in proportion of dietary saturated fat, physical activity and weight loss, and a genetic predisposition score (T2DM-GPS), on changes in insulin sensitivity (HOMA-IR), insulin secretion (HOMA-B) and short and long term glycaemia (glucose and HbA1c). We demonstrated the use of graphical Markov modelling to identify the importance and interrelationships of a number of possible variables changed as a result of a lifestyle intervention, whilst considering fixed factors such as genetic predisposition, on changes in traits. Paths which led to weight loss and change in dietary saturated fat were important factors in the change of all glycaemic traits, whereas the T2DM-GPS only made a significant direct contribution to changes in HOMA-IR and plasma glucose after considering the effects of lifestyle factors. This analysis shows that modifiable factors relating to body weight, diet, and physical activity are more likely to impact on glycaemic traits than genetic predisposition during a behavioural intervention. PMID:26154605

  18. Modelling the Interplay between Lifestyle Factors and Genetic Predisposition on Markers of Type 2 Diabetes Mellitus Risk

    PubMed Central

    Holzapfel, Christina; Ambrosini, Gina L.; Fuller, Nicholas R.; Loos, Ruth J. F.; Hauner, Hans; Caterson, Ian D.; Jebb, Susan A.

    2015-01-01

    The risk of developing type 2 diabetes mellitus (T2DM) is determined by a complex interplay involving lifestyle factors and genetic predisposition. Despite this, many studies do not consider the relative contributions of this complex array of factors to identify relationships which are important in progression or prevention of complex diseases. We aimed to describe the integrated effect of a number of lifestyle changes (weight, diet and physical activity) in the context of genetic susceptibility, on changes in glycaemic traits in overweight or obese participants following 12-months of a weight management programme. A sample of 353 participants from a behavioural weight management intervention were included in this study. A graphical Markov model was used to describe the impact of the intervention, by dividing the effects into various pathways comprising changes in proportion of dietary saturated fat, physical activity and weight loss, and a genetic predisposition score (T2DM-GPS), on changes in insulin sensitivity (HOMA-IR), insulin secretion (HOMA-B) and short and long term glycaemia (glucose and HbA1c). We demonstrated the use of graphical Markov modelling to identify the importance and interrelationships of a number of possible variables changed as a result of a lifestyle intervention, whilst considering fixed factors such as genetic predisposition, on changes in traits. Paths which led to weight loss and change in dietary saturated fat were important factors in the change of all glycaemic traits, whereas the T2DM-GPS only made a significant direct contribution to changes in HOMA-IR and plasma glucose after considering the effects of lifestyle factors. This analysis shows that modifiable factors relating to body weight, diet, and physical activity are more likely to impact on glycaemic traits than genetic predisposition during a behavioural intervention. PMID:26154605

  19. Significant Type I and Type III Collagen Production from Human Periodontal Ligament Fibroblasts in 3D Peptide Scaffolds without Extra Growth Factors

    PubMed Central

    Kumada, Yoshiyuki; Zhang, Shuguang

    2010-01-01

    We here report the development of two peptide scaffolds designed for periodontal ligament fibroblasts. The scaffolds consist of one of the pure self-assembling peptide scaffolds RADA16 through direct coupling to short biologically active motifs. The motifs are 2-unit RGD binding sequence PRG (PRGDSGYRGDS) and laminin cell adhesion motif PDS (PDSGR). RGD and laminin have been previously shown to promote specific biological activities including periodontal ligament fibroblasts adhesion, proliferation and protein production. Compared to the pure RADA16 peptide scaffold, we here show that these designer peptide scaffolds significantly promote human periodontal ligament fibroblasts to proliferate and migrate into the scaffolds (for ∼300 µm/two weeks). Moreover these peptide scaffolds significantly stimulated periodontal ligament fibroblasts to produce extracellular matrix proteins without using extra additional growth factors. Immunofluorescent images clearly demonstrated that the peptide scaffolds were almost completely covered with type I and type III collagens which were main protein components of periodontal ligament. Our results suggest that these designer self-assembling peptide nanofiber scaffolds may be useful for promoting wound healing and especially periodontal ligament tissue regeneration. PMID:20421985

  20. Subclavian central venous catheter-related thrombosis in trauma patients: incidence, risk factors and influence of polyurethane type

    PubMed Central

    2013-01-01

    Introduction The incidence of deep venous thrombosis (DVT) related to a central venous catheter varies considerably in ICUs depending on the population included. The aim of this study was to determine subclavian central venous catheter (SCVC)-related DVT risk factors in severely traumatized patients with regard to two kinds of polyurethane catheters. Methods Critically ill trauma patients needing a SCVC for their usual care were prospectively included in an observational study. Depending on the month of inclusion, patients received one of the two available products in the emergency unit: either an aromatic polyurethane SCVC or an aliphatic polyurethane SCVC. Patients were screened weekly by ultrasound for SCVC-related DVT. Potential risk factors were collected, including history-related, trauma-related and SCVC-related characteristics. Results A total of 186 patients were included with a median Injury Severity Sore of 30 and a high rate of severe brain injuries (21% of high intracranial pressure). Incidence of SCVC-related DVT was 37% (95% confidence interval: 26 to 40) in patients or 20/1,000 catheter-days. SCVC-related DVT occurred within 8 days in 65% of cases. There was no significant difference in DVT rates between the aromatic polyurethane and aliphatic polyurethane SCVC groups (38% vs. 36%). SCVC-related DVT independent risk factors were age >30 years, intracranial hypertension, massive transfusion (>10 packed red blood cell units), SCVC tip position in the internal jugular or in the innominate vein, and ipsilateral jugular catheter. Conclusion SCVC-related DVT concerned one-third of these severely traumatized patients and was mostly clinically silent. Incidence did not depend on the type of polyurethane but was related to age >30 years, intracranial hypertension or misplacement of the SCVC. Further studies are needed to assess the cost-effectiveness of routine screening in these patients in whom thromboprophylaxis may be hazardous. PMID:23718723

  1. Transcription factor Sp1 regulates T-type Ca(2+) channel CaV 3.1 gene expression.

    PubMed

    González-Ramírez, Ricardo; Martínez-Hernández, Elizabeth; Sandoval, Alejandro; Felix, Ricardo

    2014-05-01

    Voltage-gated T-type Ca(2+) (CaV 3) channels mediate a number of physiological events in developing and mature cells, and are implicated in neurological and cardiovascular diseases. In mammals, there are three distinct T-channel genes (CACNA1G, CACNA1H, and CACNA1I) encoding proteins (CaV 3.1-CaV 3.3) that differ in their localization as well as in molecular, biophysical, and pharmacological properties. The CACNA1G is a large gene that contains 38 exons and is localized in chromosome 17q22. Only basic characteristics of the CACNA1G gene promoter region have been investigated classifying it as a TATA-less sequence containing several potential transcription factor-binding motifs. Here, we cloned and characterized a proximal promoter region and initiated the analysis of transcription factors that control CaV 3.1 channel expression using the murine Cacna1g gene as a model. We isolated a ∼1.5 kb 5'-upstream region of Cacna1g and verified its transcriptional activity in the mouse neuroblastoma N1E-115 cell line. In silico analysis revealed that this region possesses a TATA-less minimal promoter that includes two potential transcription start sites and four binding sites for the transcription factor Sp1. The ability of one of these sites to interact with the transcription factor was confirmed by electrophoretic mobility shift assays. Consistent with this, Sp1 over-expression enhanced promoter activity while siRNA-mediated Sp1 silencing significantly decreased the level of CaV 3.1 protein and reduced the amplitude of whole-cell T-type Ca(2+) currents expressed in the N1E-115 cells. These results provide new insights into the molecular mechanisms that control CaV 3.1 channel expression. PMID:23868804

  2. Mutation Analysis of NR5A1 Encoding Steroidogenic Factor 1 in 77 Patients with 46, XY Disorders of Sex Development (DSD) Including Hypospadias

    PubMed Central

    Brauner, Raja; Lourenço, Diana; Boudjenah, Radia; Karageorgou, Vasiliki; Trivin, Christine; Lottmann, Henri; Lortat-Jacob, Stephen; Nihoul-Fékété, Claire; De Dreuzy, Olivier; McElreavey, Ken; Bashamboo, Anu

    2011-01-01

    Background Mutations of the NR5A1 gene encoding steroidogenic factor-1 have been reported in association with a wide spectrum of 46,XY DSD (Disorder of Sex Development) phenotypes including severe forms of hypospadias. Methodology/Principal Findings We evaluated the frequency of NR5A1 gene mutations in a large series of patients presenting with 46,XY DSD and hypospadias. Based on their clinical presentation 77 patients were classified either as complete or partial gonadal dysgenesis (uterus seen at genitography and/or surgery, n = 11), ambiguous external genitalia without uterus (n = 33) or hypospadias (n = 33). We identified heterozygous NR5A1 mutations in 4 cases of ambiguous external genitalia without uterus (12.1%; p.Trp279Arg, pArg39Pro, c.390delG, c140_141insCACG) and a de novo missense mutation in one case with distal hypospadias (3%; p.Arg313Cys). Mutant proteins showed reduced transactivation activity and mutants p.Arg39Pro and p.Arg313Cys did not synergize with the GATA4 cofactor to stimulate reporter gene activity, although they retained their ability to physically interact with the GATA4 protein. Conclusions/Significance Mutations in NR5A1 were observed in 5/77 (6.5%) cases of 46,XY DSD including hypospadias. Excluding the cases of 46,XY gonadal dysgenesis the incidence of NR5A1 mutations was 5/66 (7.6%). An individual with isolated distal hypopadias carried a de novo heterozygous missense mutation, thus extending the range of phenotypes associated with NR5A1 mutations and suggesting that this group of patients should be screened for NR5A1 mutations. PMID:22028768

  3. Diabetic retinopathy and the associated risk factors in diabetes type 2 patients in Abha, Saudi Arabia

    PubMed Central

    Ahmed, Razia A.; Khalil, Shamsun N.; Al-Qahtani, Mohammad A. A.

    2016-01-01

    Objectives: To assess the proportion and grades of retinopathy and its risk factors in diabetes type 2 patients. Materials and Methods: This was a cross-sectional study of 401 type 2 diabetic patients. A questionnaire and checklist were used to collect the data. Retinopathy was diagnosed and graded by fundus photographs and slit lamp examination. The duration of diabetes, age of patients, age at onset of diabetes, body mass index, hemoglobin A1c level, blood pressure, and complications were noted. Results: The mean age of male and female patients was 54.93 and 54.25 years; 57.6% were males. The mean age of onset and mean duration of diabetes were 43.91 and 13.4 years, respectively. The proportion of retinopathy was 36.4%. Grades of retinopathy were: Mild 57.5%, moderate 19.9%, severe nonproliferative 11%, and proliferative retinopathy 11.6%; 7.2% of patients had maculopathy. Retinopathy was significantly associated with older age, younger age at onset, longer duration of disease, poorly controlled blood sugar, hypertension, insulin use; the presence of neuropathy and nephropathy appeared as a significant risk. Younger age at onset, longer duration, and insulin use appeared as the strongest predictors for diabetic retinopathy. Conclusions: More than a third (36.4%) of the diabetic patients attending a diabetic center had retinopathy. The control of the risk factors may reduce both prevalence and consequences of retinopathy. PMID:26929725

  4. Autoradiographic localization of epidermal growth factor receptors to all major uterine cell types

    SciTech Connect

    Lin, T.H.; Mukku, V.R.; Verner, G.; Kirkland, J.L.; Stancel, G.M.

    1988-03-01

    We have recently studied the structure and function of the uterine epidermal growth factor (EGF) receptor, its hormonal regulation, and its possible role in estrogen-induced uterine DNA synthesis. Since the uterus is composed of multiple cell types, we sought, in the work reported here, to localize EGF binding in this organ by autoradiography. Prior to the actual autoradiography, we performed a companion series of experiments to insure that EGF binding to uterine tissue in situ represented a true receptor interaction. Uteri from immature female rats were incubated in vitro with 125I-EGF at 25 degrees C. Tissue binding was maximal within 120 min and remained constant for at least an additional 120 min. This binding of labeled EGF was largely abolished by excess unlabeled EGF but not by other growth factors, indicating that binding was to specific receptors. The binding of 125I-EGF was saturable and reached a plateau at 4-8 nM; specific binding was half-maximal at 1-2 nM EGF. In situ cross-linking studies revealed that 125I-EGF was bound predominantly to a 170,000 MW EGF receptor similar to that seen in isolated uterine membranes. Incubation of uteri with 125I-EGF followed by autoradiography revealed binding to epithelial cells, stroma, and myometrium. These results provide evidence for the presence of specific EGF receptors in all major uterine cell types of the immature rat.

  5. Transcription factors binding to the mouse HTF9 housekeeping promoter differ between cell types.

    PubMed Central

    Somma, M P; Gambino, I; Lavia, P

    1991-01-01

    The mouse CpG island HTF9 harbours a bidirectional promoter shared by two housekeeping genes that are arranged head-to-head. We have previously identified several protein binding-elements across the CpG island, yet a short region around the initiation region was found to be capable of bidirectional transcription in transient expression assays, suggesting that the multiple elements of the HTF9 promoter are functionally redundant. We have now compared the binding activities in nuclear extracts from different cell types. Two protein-binding elements of HTF9 interact with widely distributed factors. A potentially strong Sp1 binding site was also identified, however Sp1 appeared to bind efficiently to its target sequence with extracts prepared from proliferating cultured cells, but not from adult organs. On the other hand, the CCAAT box upstream of one gene (HTF9-A) interacted with a liver-enriched factor, whereas no binding was detected with cultured fibroblasts extracts. Consistently, deletion of the CCAAT box affected transient expression from the HTF9-A promoter in hepatocyte, but not in fibroblast, cultures. Our results suggest that ubiquitous expression of housekeeping promoters results from the activation of alternative elements in different cell types. Images PMID:1886769

  6. Causative factors for formation of toxic islet amyloid polypeptide oligomer in type 2 diabetes mellitus

    PubMed Central

    Jeong, Hye Rin; An, Seong Soo A

    2015-01-01

    Human islet amyloid polypeptide (h-IAPP) is a peptide hormone that is synthesized and cosecreted with insulin from insulin-secreting pancreatic β-cells. Recently, h-IAPP was proposed to be the main component responsible for the cytotoxic pancreatic amyloid deposits in patients with type 2 diabetes mellitus (T2DM). Since the causative factors of IAPP (or amylin) oligomer aggregation are not fully understood, this review will discuss the various forms of h-IAPP aggregation. Not all forms of IAPP aggregates trigger the destruction of β-cell function and loss of β-cell mass; however, toxic oligomers do trigger these events. Once these toxic oligomers form under abnormal metabolic conditions in T2DM, they can lead to cell disruption by inducing cell membrane destabilization. In this review, the various factors that have been shown to induce toxic IAPP oligomer formation will be presented, as well as the potential mechanism of oligomer and fibril formation from pro-IAPPs. Initially, pro-IAPPs undergo enzymatic reactions to produce the IAPP monomers, which can then develop into oligomers and fibrils. By this mechanism, toxic oligomers could be generated by diverse pathway components. Thus, the interconnections between factors that influence amyloid aggregation (eg, absence of PC2 enzyme, deamidation, reduction of disulfide bonds, environmental factors in the cell, genetic mutations, copper metal ions, and heparin) will be presented. Hence, this review will aid in understanding the fundamental causative factors contributing to IAPP oligomer formation and support studies for investigating novel T2DM therapeutic approaches, such as the development of inhibitory agents for preventing oligomerization at the early stages of diabetic pathology. PMID:26604727

  7. Causative factors for formation of toxic islet amyloid polypeptide oligomer in type 2 diabetes mellitus.

    PubMed

    Jeong, Hye Rin; An, Seong Soo A

    2015-01-01

    Human islet amyloid polypeptide (h-IAPP) is a peptide hormone that is synthesized and cosecreted with insulin from insulin-secreting pancreatic β-cells. Recently, h-IAPP was proposed to be the main component responsible for the cytotoxic pancreatic amyloid deposits in patients with type 2 diabetes mellitus (T2DM). Since the causative factors of IAPP (or amylin) oligomer aggregation are not fully understood, this review will discuss the various forms of h-IAPP aggregation. Not all forms of IAPP aggregates trigger the destruction of β-cell function and loss of β-cell mass; however, toxic oligomers do trigger these events. Once these toxic oligomers form under abnormal metabolic conditions in T2DM, they can lead to cell disruption by inducing cell membrane destabilization. In this review, the various factors that have been shown to induce toxic IAPP oligomer formation will be presented, as well as the potential mechanism of oligomer and fibril formation from pro-IAPPs. Initially, pro-IAPPs undergo enzymatic reactions to produce the IAPP monomers, which can then develop into oligomers and fibrils. By this mechanism, toxic oligomers could be generated by diverse pathway components. Thus, the interconnections between factors that influence amyloid aggregation (eg, absence of PC2 enzyme, deamidation, reduction of disulfide bonds, environmental factors in the cell, genetic mutations, copper metal ions, and heparin) will be presented. Hence, this review will aid in understanding the fundamental causative factors contributing to IAPP oligomer formation and support studies for investigating novel T2DM therapeutic approaches, such as the development of inhibitory agents for preventing oligomerization at the early stages of diabetic pathology. PMID:26604727

  8. The Main Suppressing Factors of Dry Forage Intake in Large-type Goats

    PubMed Central

    Van Thang, Tran; Sunagawa, Katsunori; Nagamine, Itsuki; Kishi, Tetsuya; Ogura, Go

    2012-01-01

    In large-type goats that were fed on dry forage twice daily, dry forage intake was markedly suppressed after 40 min of feeding had elapsed. The objective of this study was to determine whether or not marked decreases in dry forage intake after 40 min of feeding are mainly caused by the two factors, that is, ruminal distension and increased plasma osmolality induced thirst produced by dry forage feeding. Six large-type male esophageal- and ruminal-fistulated goats (crossbred Japanese Saanen/Nubian, aged 2 to 6 years, weighing 85.1±4.89 kg) were used in two experiments. The animals were fed ad libitum a diet of roughly crushed alfalfa hay cubes for 2 h from 10:00 to 12:00 am during two experiments. Water was withheld during feeding in both experiments but was available for a period of 30 min after completion of the 2 h feeding period. In experiment 1, saliva lost via the esophageal fistula was replenished by an intraruminal infusion of artificial parotid saliva (RIAPS) in sham feeding conditions (SFC) control, and the treatment was maintained under normal feeding conditions (NFC). In experiment 2, a RIAPS and non-insertion of a balloon (RIAPS-NB) control was conducted in the same manner as the SFC control of experiment 1. The intraruminal infusion of hypertonic solution and insertion of a balloon (RIHS-IB) treatment was carried out simultaneously to reproduce the effects of changing salt content and ruminal distension due to feed entering the rumen. The results of experiment 1 showed that due to the effects of multiple dry forage suppressing factors when feed boluses entered the rumen, eating rates in the NFC treatment decreased (p<0.05) after 40 min of feeding and cumulative dry forage intake for the 2 h feeding period reduced to 43.8% of the SFC control (p<0.01). The results of experiment 2 indicated that due to the two suppressing factors of ruminal distension and increased plasma osmolality induced thirst, eating rates in the RIHS-IB treatment were, as observed

  9. Extension of the Legionella pneumophila sequence-based typing scheme to include strains carrying a variant of the N-acylneuraminate cytidylyltransferase gene.

    PubMed

    Mentasti, M; Underwood, A; Lück, C; Kozak-Muiznieks, N A; Harrison, T G; Fry, N K

    2014-07-01

    Sequence-based typing (SBT) combined with monoclonal antibody subgrouping of Legionella pneumophila isolates is at present considered to be the reference standard during epidemiological investigation of Legionnaires' disease outbreaks. In some isolates of L. pneumophila, the seventh allele of the standard SBT scheme, neuA, is not amplified, because a homologue that is refractory to amplification with the standard neuA primers is present. Consequently, a complete seven-allele profile, and hence a sequence type, cannot be obtained. Subsequently, primers were designed to amplify both neuA and the homologue, but these yielded suboptimal sequencing results. In this study, novel primers specific for the neuA homologue were designed and internationally validated by members of the ESCMID Study Group for Legionella Infections at national and regional Legionella reference laboratories with a modified version of the online L. pneumophila sequence quality tool. To date, the addition of the neuAh target to the SBT protocol has allowed full typing data to be obtained for 108 isolates of 11 different serogroups, namely 1, 2, 3, 4, 5, 6, 7, 8, 10, 13, and 14, which could not previously be typed with the standard SBT neuA primers. Further studies are necessary to determine why it is still not possible to obtain either a neuA or a neuAh allele from three serogroup 11 isolates. PMID:24245827

  10. Prevalence of Non-Volitional Sex Types and Associated Factors: A National Sample of Young People

    PubMed Central

    Dukers-Muijrers, Nicole H. T. M.; Somers, Carlijn; de Graaf, Hanneke; Meijer, Suzanne; Hoebe, Christian J. P. A.

    2015-01-01

    Background Non-volitional sex (NVS) in young people continues to be a major public health problem with long-term negative health outcomes. For the first time, the prevalence of different types of NVS and associated factors are compared between young people with same-sex sexual activities and those who have not. Methods We obtained data from 10,401 young women and men (aged 12 to 25 years) who participated in a population study on sexual health, the Netherlands. We calculated and compared the prevalence of six types of NVS between women who had sex with men (yWSM) or women (yWSW), and men who had sex with women (yMSW) or men (yMSM). In sexually experienced participants (n = 5986) logistic regression analyses were applied to assess associations with NVS by assault or penetration. Analyses were weighted to represent the Dutch population. Results The prevalence of NVS ranged from 1% to 61%, depending on type. Prevalence was higher for young women (any: 40.6%) than men (any: 20.4%), and highest for yMSM and yWSW. Prevalence of NVS by assault or penetration was related to a range of socio-demographic, behavioral and social factors, which were largely similar regardless of sex or same-sex-experiences. The NVS perpetrators were in over 70% of cases known to the victim; 1 in 4 cases of NVS by penetration were accompanied by violence. Conclusion A substantial proportion of young people in the Netherlands have experienced NVS. Medical professionals, educators and caregivers should integrate services to continue to address NVS by targeting young people’s multifaceted risk profiles and evidenced based interventions for doing so are needed. PMID:26214829

  11. Chemokine Receptor-5Delta32 Mutation is No Risk Factor for Ischemic-Type Biliary Lesion in Liver Transplantation.

    PubMed

    Heidenhain, Christoph; Puhl, Gero; Moench, Christian; Lautem, Anja; Neuhaus, Peter

    2009-01-01

    It has been shown that certain chemokine receptor polymorphisms may correspond to certain complications after organ transplantation. Ischemic-type biliary lesion (ITBL) encounters for major morbidity and mortality in liver transplant recipients. So far, the exact cause for ITBL remains unclear. Certain risk factors for the development of ITBL like donor age and cold ischemic time are well described. In a previous study, a 32-nucleotide deletion of the chemokine receptor-5Delta32 (CCR-5Delta32) was strongly associated with the incidence of ITBL in adult liver transplantation. This study re-evaluates the association of CCR-5Delta32 gene polymorphism and the incidence of ITBL. 169 patients were included into this retrospective analysis. 134 patients were homozygous for wild-type CCR-5, 33 patients heterozygous, and 2 patients were homozygous for CCR-5Delta32 mutation. There were no major differences in donor or recipients demographics. No association was found between CCR-5Delta32 mutation and the development of ITBL. We conclude that CCR-5Delta32 is no risk factor for the development of ITBL in our patient cohort. PMID:20107582

  12. Can Time Efficient Exercise Improve Cardiometabolic Risk Factors in Type 2 Diabetes? A Pilot Study

    PubMed Central

    Revdal, Anders; Hollekim-Strand, Siri M.; Ingul, Charlotte B.

    2016-01-01

    Exercise is considered a cornerstone in the prevention and treatment of type 2 diabetes, but few individuals with type 2 diabetes exercise according to guidelines. We investigated the effect of two time efficient high intensity exercise interventions on exercise capacity, glycemic control and other cardiometabolic risk factors in patients with type 2 diabetes. Twenty-one individuals with type 2 diabetes were randomly assigned to low volume high intensity interval exercise (HIIE; 27 minutes/bout; 10x1-minute at 90 % of HRmax; n = 10) or extremely low volume sprint interval exercise (SIE; 10 minutes/bout; 2x20 seconds at maximum achievable intensity; n = 11) 3 days/week for 12 weeks. Aerobic exercise capacity (VO2peak), glycosylated hemoglobin (HbA1c), blood pressure and body composition were measured at baseline and post test. Both HIIE and SIE improved VO2peak (3.3 mL·min-1·kg-1, 10.4 %), p < 0.01, and 1.4 mL·min-1·kg-1 (4.6 %), p = 0.03, respectively). Only HIIE reduced body fat percentage (4.5 %, p = 0.04) and two minute heart rate recovery (11.0 bpm, p = 0.02). Neither HIIE nor SIE improved HbA1c. In conclusion, this study indicates that substantially lower exercise volumes than recommended in current guidelines can improve aerobic exercise capacity in individuals with type 2 diabetes. However, 12 weeks of time efficient high intensity exercise did not improve glycemic control, and interventions of longer duration should be investigated. Key points Low volume high-intensity interval exercise can improve peak oxygen uptake in previously sedentary individuals with type 2 diabetes The weekly exercise volumes in the two intervention groups of 81 and 30 minutes respectively, is substantially lower than recommended in current exercise guidelines and could reduce the time-barrier associated with exercise among patients with type 2 diabetes. However, 12 weeks of structured, supervised low-volume exercise did not improve glycemic control, indicating a need for

  13. Can Time Efficient Exercise Improve Cardiometabolic Risk Factors in Type 2 Diabetes? A Pilot Study.

    PubMed

    Revdal, Anders; Hollekim-Strand, Siri M; Ingul, Charlotte B

    2016-06-01

    Exercise is considered a cornerstone in the prevention and treatment of type 2 diabetes, but few individuals with type 2 diabetes exercise according to guidelines. We investigated the effect of two time efficient high intensity exercise interventions on exercise capacity, glycemic control and other cardiometabolic risk factors in patients with type 2 diabetes. Twenty-one individuals with type 2 diabetes were randomly assigned to low volume high intensity interval exercise (HIIE; 27 minutes/bout; 10x1-minute at 90 % of HRmax; n = 10) or extremely low volume sprint interval exercise (SIE; 10 minutes/bout; 2x20 seconds at maximum achievable intensity; n = 11) 3 days/week for 12 weeks. Aerobic exercise capacity (VO2peak), glycosylated hemoglobin (HbA1c), blood pressure and body composition were measured at baseline and post test. Both HIIE and SIE improved VO2peak (3.3 mL·min(-1)·kg(-1), 10.4 %), p < 0.01, and 1.4 mL·min(-1)·kg(-1) (4.6 %), p = 0.03, respectively). Only HIIE reduced body fat percentage (4.5 %, p = 0.04) and two minute heart rate recovery (11.0 bpm, p = 0.02). Neither HIIE nor SIE improved HbA1c. In conclusion, this study indicates that substantially lower exercise volumes than recommended in current guidelines can improve aerobic exercise capacity in individuals with type 2 diabetes. However, 12 weeks of time efficient high intensity exercise did not improve glycemic control, and interventions of longer duration should be investigated. Key pointsLow volume high-intensity interval exercise can improve peak oxygen uptake in previously sedentary individuals with type 2 diabetesThe weekly exercise volumes in the two intervention groups of 81 and 30 minutes respectively, is substantially lower than recommended in current exercise guidelines and could reduce the time-barrier associated with exercise among patients with type 2 diabetes.However, 12 weeks of structured, supervised low-volume exercise did not improve glycemic control, indicating a need for

  14. Differences in Factors Affecting Various Crash Types with High Numbers of Fatalities and Injuries in China

    PubMed Central

    Wang, Kai; He, Jie; Ding, Jianxun; Shi, Qin; Wang, Changjun; Li, Pingfan

    2016-01-01

    Objectives Road traffic crashes that involve very high numbers of fatalities and injuries arouse public concern wherever they occur. In China, there are two categories of such crashes: a crash that results in 10–30 fatalities, 50–100 serious injuries or a total cost of 50–100 million RMB ($US8-16m) is a “serious road traffic crash” (SRTC), while a crash that is even more severe or costly is a “particularly serious road traffic crash” (PSRTC). The aim of this study is to identify the main factors affecting different types of these crashes (single-vehicle, head-on, rear-end and side impact) with the ultimate goal of informing prevention activities and policies. Methods Detailed descriptions of the SRTCs and PSRTCs that occurred from 2007 to 2014 were collected from the database “In-depth Investigation and Analysis System for Major Road Traffic Crashes” (IIASMRTC), which is maintained by the Traffic Management Research Institute of the Ministry of Public Security of China (TMRI). 18 main risk factors, which were categorized into four areas (participant, vehicle, road and environment-related) were chosen as potential independent variables for the multinomial logistic regression analysis. Comparisons were made among the single-vehicle, head-on, rear-end and side impact crashes in terms of factors affecting crash occurrence. Findings Five risk factors were significant for the six multinomial logistic regression models, which were location, vertical alignment, roadside safety rating, driver distraction and overloading of cargo. It was indicated that intersections were more likely to have side impact SRTCs and PSRTCs, especially with poor visibility at night. Overloaded freight vehicles were more likely to be involved in a rear-end crash than other freight vehicles. Driver distraction is an important risk factor for head-on crashes, while vertical alignment and roadside safety rating are positively associated with single-vehicle crashes. Conclusion Based

  15. Genetic and epigenetic factors in etiology of diabetes mellitus type 1.

    PubMed

    Stankov, Karmen; Benc, Damir; Draskovic, Dragan

    2013-12-01

    Diabetes mellitus type 1 (T1D) is a complex disease resulting from the interplay of genetic, epigenetic, and environmental factors. Recent progress in understanding the genetic basis of T1D has resulted in an increased recognition of childhood diabetes heterogeneity. After the initial success of family-based linkage analyses, which uncovered the strong linkage and association between HLA gene variants and T1D, genome-wide association studies performed with high-density single-nucleotide polymorphism genotyping platforms provided evidence for a number of novel loci, although fine mapping and characterization of these new regions remains to be performed. T1D is one of the most heritable common diseases, and among autoimmune diseases it has the largest range of concordance rates in monozygotic twins. This fact, coupled with evidence of various epigenetic modifications of gene expression, provides convincing proof of the complex interplay between genetic and environmental factors. In T1D, epigenetic phenomena, such as DNA methylation, histone modifications, and microRNA dysregulation, have been associated with altered gene expression. Increasing epidemiologic and experimental evidence supports the role of genetic and epigenetic alterations in the etiopathology of diabetes. We discuss recent results related to the role of genetic and epigenetic factors involved in development of T1D. PMID:24190679

  16. Different types of stainless steel used in equipment in meat plants do not affect the initial microbial transfer, including pathogens, from pork skin

    PubMed Central

    Larivière-Gauthier, Guillaume; Quessy, Sylvain; Fournaise, Sylvain; Letellier, Ann; Fravalo, Philippe

    2015-01-01

    This study describes and measures the impact of different compositions and finishes of stainless steel used in equipment in the meat industry on the transfer of natural flora and selected pathogens from artificially contaminated pork skin. It is known that the adhesion to surfaces of Listeria monocytogenes and Salmonella, 2 pathogens frequently found in contaminated pork meat, depends on the nature and roughness of the surface. Our results show no statistically significant differences in microbial transfer regardless of the types of stainless steel considered, with the highest measured transfer difference being 0.18 log colony-forming units (CFUs)/800 cm2. Moreover, no differences in total microbial community were observed after transfer on the 5 types of stainless steel using single-strand conformation polymorphism (SSCP). It was concluded that the different characteristics of the stainless steel tested did not affect the initial bacterial transfer in this study. PMID:26130860

  17. Synergistic inhibition of replication of human immunodeficiency virus type 1, including that of a zidovudine-resistant isolate, by zidovudine and 2',3'-dideoxycytidine in vitro.

    PubMed Central

    Eron, J J; Johnson, V A; Merrill, D P; Chou, T C; Hirsch, M S

    1992-01-01

    The combination of zidovudine (AZT) and 2',3'-dideoxycytidine synergistically inhibits human immunodeficiency virus type 1 (HIV-1) replication in vitro with AZT-sensitive and AZT-resistant clinical isolates and HIV-1IIIB. Synergy was determined by the median-effect principle and isobologram techniques. Cytotoxicity of the agents was not observed. Clinical trials are ongoing to define the combination's role in HIV-1 therapy. PMID:1324648

  18. Initiation on the divergent Type I cadicivirus IRES: factor requirements and interactions with the translation apparatus.

    PubMed

    Asnani, Mukta; Pestova, Tatyana V; Hellen, Christopher U T

    2016-04-20

    Cadicivirus (CDV) is unique amongst picornaviruses in having a dicistronic genome with internal ribosomal entry sites (IRESs) preceding both open reading frames. Here, we investigated initiation on the 5'-terminal IRES. We report that the 982-nt long 5'UTR comprises 12 domains (d1-d12), five of which (d8-d12, nts 341-950) constitute a divergent Type I IRES. It comprises central elements (the apex of d10, d11 and the following polypyrimidine tract) that are homologous to corresponding elements in canonical Type 1 IRESs, and non-canonical flanking domains (d8, d9 and d12).In vitroreconstitution revealed that as with canonical Type I IRESs, 48S complex formation requires eukaryotic initiation factors (eIFs) 1, 1A, 2, 3, 4A, 4B and 4G, and the poly(C) binding protein 2 (PCBP2), and starts with specific binding of eIF4G/eIF4A to d11. However, in contrast to canonical Type I IRESs, subsequent recruitment of 43S ribosomal complexes does not require direct interaction of their eIF3 constituent with the IRES-bound eIF4G. On the other hand, the CDV IRES forms a 40S/eIF3/IRES ternary complex, with multiple points of contact. These additional interactions with translational components could potentially stimulate recruitment of the 43S complex and alleviate the necessity for direct eIF4G/eIF3 interaction. PMID:26873921

  19. Daintain/AIF-1 (Allograft Inflammatory Factor-1) accelerates type 1 diabetes in NOD mice

    SciTech Connect

    Zhao, Yan-Ying; Huang, Xin-Yuan; Chen, Zheng-Wang

    2012-10-26

    Highlights: Black-Right-Pointing-Pointer Daintain/AIF-1 is over-expressed in the blood of NOD mice suffering from insulitis. Black-Right-Pointing-Pointer Daintain/AIF-1 stimulates white blood cell proliferation in NOD mice. Black-Right-Pointing-Pointer Daintain/AIF-1 increases blood glucose levels and triggers type 1 diabetes. Black-Right-Pointing-Pointer Daintain/AIF-1 accelerates insulitis, while its antibody prevents insulitis. Black-Right-Pointing-Pointer Daintain/AIF-1 enhances the levels of nitric oxide in the pancreases of NOD mice. -- Abstract: A large body of experimental evidence suggests that cytokines trigger pancreatic {beta}-cell death in type 1 diabetes mellitus. Daintain/AIF-1 (Allograft Inflammatory Factor-1), a specific marker for activated macrophages, is accumulated in the pancreatic islets of pre-diabetic BB rats. In the present study, we demonstrate that daintain/AIF-1 is released into blood and the levels of daintain/AIF-1 in the blood of type 1 diabetes-prone non-obese diabetic (NOD) mice suffering from insulitis are significantly higher than that in healthy NOD mice. When injected intravenously into NOD mice, daintain/AIF-1 stimulates white blood cell proliferation, increases the concentrations of blood glucose, impairs insulin expression, up-regulates nitric oxide (NO) production in pancreases and accelerates diabetes in NOD mice, while the antibody against daintain/AIF-1 delays or prevents insulitis in NOD mice. These results imply daintain/AIF-1 triggers type 1 diabetes probably via arousing immune cells activation and induction of NO production in pancreas of NOD mice.

  20. Initiation on the divergent Type I cadicivirus IRES: factor requirements and interactions with the translation apparatus

    PubMed Central

    Asnani, Mukta; Pestova, Tatyana V.; Hellen, Christopher U.T.

    2016-01-01

    Cadicivirus (CDV) is unique amongst picornaviruses in having a dicistronic genome with internal ribosomal entry sites (IRESs) preceding both open reading frames. Here, we investigated initiation on the 5′-terminal IRES. We report that the 982-nt long 5′UTR comprises 12 domains (d1-d12), five of which (d8-d12, nts 341–950) constitute a divergent Type I IRES. It comprises central elements (the apex of d10, d11 and the following polypyrimidine tract) that are homologous to corresponding elements in canonical Type 1 IRESs, and non-canonical flanking domains (d8, d9 and d12). In vitro reconstitution revealed that as with canonical Type I IRESs, 48S complex formation requires eukaryotic initiation factors (eIFs) 1, 1A, 2, 3, 4A, 4B and 4G, and the poly(C) binding protein 2 (PCBP2), and starts with specific binding of eIF4G/eIF4A to d11. However, in contrast to canonical Type I IRESs, subsequent recruitment of 43S ribosomal complexes does not require direct interaction of their eIF3 constituent with the IRES-bound eIF4G. On the other hand, the CDV IRES forms a 40S/eIF3/IRES ternary complex, with multiple points of contact. These additional interactions with translational components could potentially stimulate recruitment of the 43S complex and alleviate the necessity for direct eIF4G/eIF3 interaction. PMID:26873921

  1. Vascular endothelial growth factor-induced elimination of the type 1 interferon receptor is required for efficient angiogenesis.

    PubMed

    Zheng, Hui; Qian, Juan; Carbone, Christopher J; Leu, N Adrian; Baker, Darren P; Fuchs, Serge Y

    2011-10-01

    Angiogenesis is stimulated by vascular endothelial growth factor (VEGF) and antagonized by type 1 interferons, including IFN-α/β. On engaging their respective receptors (VEGFR2 and IFNAR), both stimuli activate protein kinase D2 (PKD2) and type 1 IFNs require PKD2 activation and recruitment to IFNAR1 to promote the phosphorylation-dependent ubiquitination, down-regulation, and degradation of the cognate receptor chain, IFNAR1. Data reveal that PKD2 activity is dispensable for VEGF-stimulated down-regulation of VEGFR2. Remarkably, VEGF treatment promotes the recruitment of PKD2 to IFNAR1 as well as ensuing phosphorylation, ubiquitination, and degradation of IFNAR1. In cells exposed to VEGF, phosphorylation-dependent degradation of IFNAR1 leads to an inhibition of type 1 IFN signaling and is required for efficient VEGF-stimulated angiogenesis. Importance of this mechanism for proangiogenic or antiangiogenic responses in cells exposed to counteracting stimuli and the potential medical significance of this regulation are discussed. PMID:21832278

  2. Type A factors as predictors of somatic risk factors of coronary heart disease in young Finns--a six-year follow-up study.

    PubMed

    Keltikangas-Järvinen, L; Räikkönen, K

    1990-01-01

    Type A factors related to the level of somatic risk factors of coronary heart disease were studied in 1209 healthy young Finns. They were 12-, 15- and 18-year-old adolescents who were clinically examined three times within a six-year follow-up period. The risk and non-risk groups were constructed on the basis of their risk level over three testings, separately in each somatic risk variable. Type A behavior was evaluated during the six-year follow-up using the AFMS questionnaire. The results showed that of the Type A factors 'hard-driving' had the strongest association with the somatic risk level. 'Aggression-competitiveness' was also related to the risk but not very strongly. 'Impatience' was of no importance while 'engagement-involvement' was likely to be a protective factor: a low score on it correlated with the risk. PMID:2313616

  3. Analyzing the Role of Periplasmic Folding Factors in the Biogenesis of OMPs and Members of the Type V Secretion System.

    PubMed

    Bodelón, Gustavo; Marín, Elvira; Fernández, Luis Ángel

    2015-01-01

    The outer membrane (OM) of gram-negative bacteria is highly packed with OM proteins (OMPs) and the trafficking and assembly of OMPs in gram-negative bacteria is a subject of intense research. Structurally, OMPs vary in the number of β-strands and in the size and complexity of extra-membrane domains, with extreme examples being the members of the type V protein secretion system (T5SS), such as the autotransporter (AT) and intimin/invasin families of secreted proteins, in which a large extracellular "passenger" domain is linked to a β-barrel that inserts in the OM. Despite their structural and functional diversity, OMPs interact in the periplasm with a relatively small set of protein chaperones that facilitate their transport from the inner membrane (IM) to the β-barrel assembly machinery (BAM complex), preventing aggregation and assisting their folding in various aspects including disulfide bond formation. This chapter is focused on the periplasmic folding factors involved in the biogenesis of integral OMPs and members of T5SS in E. coli, which are used as a model system in this field. Background information on these periplasmic folding factors is provided along with genetic methods to generate conditional mutants that deplete these factors from E. coli and biochemical methods to analyze the folding, surface display, disulfide formation and oligomerization state of OMPs/T5SS in these mutants. PMID:26427678

  4. Prevalence and risk factors of type 2 diabetes in older Vietnam-born Australians.

    PubMed

    Tran, Duong Thuy; Jorm, Louisa R; Johnson, Maree; Bambrick, Hilary; Lujic, Sanja

    2014-02-01

    Vietnamese immigrants in Australia represent the second largest Vietnamese community in developed countries, following the United States. However, limited information is available about prevalence of type 2 diabetes (T2D) and the relative roles of socio-demographic characteristics, lifestyle factors, and Vietnamese ethnicity per se in this population. This study investigated the prevalence of T2D and its risk factors in older Vietnam-born Australians, in comparison to native-born Australians. The study used baseline questionnaire data from 787 Vietnam- and 196,866 Australia-born individuals (≥45 years), who participated in the 45 and Up Study, which is Australia's largest population-based cohort study. Country of birth specific prevalence of T2D and its risk factors were age-standardised to the 2006 Australian population (≥45 years). Multivariable logistic regression models were built for each group to assess the relationship between T2D and socio-demographic characteristics, family history of diabetes, lifestyle factors and health status. Compared to Australia-born counterparts, Vietnam-born individuals had significantly (p < 0.001) higher age-standardised prevalence of T2D (14.7 vs 7.4 %) and significantly (p < 0.001) lower levels of vegetable consumption (≥5 serves/day, 19.4 vs 33.5 %), physical activity (≥5 sessions/week, 68.7 vs 78.5 %) and overweight and obesity (body mass index ≥25 kg/m(2), 21.5 vs 62.7 %). The increased risk of T2D associated with a family history of diabetes for Vietnam-born people [adjusted odds ratio (OR) 7.14, 95 % CI 4.15-12.28] was almost double that for Australia-born people (OR 3.77, 95 % CI 3.63-3.90). The patterns of association between T2D and other factors were similar between the two groups. The findings suggest a genetic predisposition to T2D in people of Vietnamese ethnicity. Reducing lifestyle risk factors for diabetes and better management of diabetes are priorities for Vietnam-born populations. PMID

  5. Zirconium-titanium placers of the Voronezh Anteclise: Types, epochs and factors of formation, and forecast

    NASA Astrophysics Data System (ADS)

    Savko, A. D.; Zvonarev, A. E.; Ivanov, D. A.

    2012-02-01

    The early and late Frasnian, Barremian-Aptian, Cenomanian, early Santonian, early Campanian, and Oligocene-Miocene epochs of the formation of various types of zirconium-titanium placers are distinguished in the Voronezh Anteclise. The factors of their formation are considered, and a forecast of prospecting has been made. Lower Frasnian sedimentary rocks occur in the southeast, where the placers are related to the ilmenite-bearing volcanosedimentary rocks of the Yastrebovo Sequence. The upper Frasnian productive quartz sand of the Petino Sequence occurs in the central part of the Voronezh Anteclise. The Barremian-Aptian productive quartz sand and kaolinite clay occur in the northern and northeastern parts of the anteclise (Ryazan and Lipetsk oblasts). The placers formed in the Cenomanian are known in the Tambov oblast in the northeast of the Voronezh Anteclise and are related to phosphate-bearing glauconite-quartz sand. The early Campanian phosphorite-glauconite-quartz formation is widespread in the northwest of the Voronezh Anteclise at the junction with the northeastern wall of the Dnieper-Donets Basin (Bryansk oblast). The Oligocene-Miocene epoch was characterized by quartz sands abundant in the northwestern and south-western areas. The formation of zirconium-titanium placers is controlled by structural-tectonic, facies, volcanic, paleogeographic, stratigraphic, and evolutional factors. The indispensable condition for heavy mineral concentration is existence of positive forms of underwater topography. These are mostly structural elements of the third and fourth orders on the slopes of the Voronezh Anteclise at the boundaries of the adjacent negative structures. As concerns the facies factor, the occurrence of coastal and shallow-water marine facies with alternating and medium hydrodynamic activity and predominance of sand fractions 0.25-0.05 mm are criteria of elevated concentration of heavy minerals in sand. One of the conditions providing concentration of heavy

  6. Transforming growth factor-beta 1 stimulates glomerular mesangial cell synthesis of the 72-kd type IV collagenase.

    PubMed Central

    Marti, H. P.; Lee, L.; Kashgarian, M.; Lovett, D. H.

    1994-01-01

    Transforming growth factor-beta 1 (TGF-beta 1) is generally considered to exert positive effects on the accumulation of extracellular matrices. These occur as the net result of enhanced matrix protein synthesis, diminished matrix metalloproteinase (MMP) synthesis, and augmented production of specific inhibitors, including the tissue inhibitor of metalloproteinases (TIMP-1). Given that glomerular TGF-beta 1 synthesis is induced by inflammation, the effects of this cytokine on synthesis of the 72-kd type IV collagenase and TIMP-1 by cultured human mesangial cells were evaluated. Concentrations of TGF-beta 1 of 5 ng/ml and above specifically stimulated the synthesis of the 72-kd type IV collagenase. This effect was independent of the stimulatory effect of TGF-beta 1 on TIMP-1 synthesis, which was maximal in a lower concentration range (0.1 to 1 ng/ml). Most significantly, the net effect at the higher concentrations of TGF-beta 1 was an excess of enzyme over the TIMP-1 inhibitor. Northern blot analysis of TGF-beta 1-stimulated human mesangial cells demonstrated a specific increase in the abundance of the 3.1 kb mRNA transcript encoding the 72-kd type IV collagenase, presumably mediated by a direct stimulation of 72-kd type IV collagenase mRNA transcription observed as early as 3 hours after exposure to TGF-beta 1. These studies were extended to an analysis of the expression of TGF-beta 1 and 72-kd type IV collagenase mRNAs in normal and nephritic rats. In normal animals, basal TGF-beta 1 and 72-kd type IV collagenase mRNA expression was observed in a strictly mesangial distribution. After induction of acute immune complex-mediated glomerulonephritis, there was a major increase in TGF-beta 1 and 72-kd type IV collagenase mRNA expression, which was strictly limited to the expanded, hypercellular mesangial compartment. Enhanced synthesis of the mesangial type IV collagenase in response to TGF-beta 1 released during glomerular inflammatory processes could have an important

  7. Similar cardiovascular risk factor profile in screen-detected and known type 2 diabetic subjects

    PubMed Central

    Heldgaard, Poul Erik; Henriksen, Jan Erik; Sidelmann, Johannes J.; Olivarius, Niels de Fine; Siersma, Volkert D.; Gram, Jørgen B.

    2011-01-01

    Objective To compare the cardiovascular disease (CVD) risk factor profile in subjects with screen-detected type 2 diabetes (SDM) and subjects with known type 2 diabetes (KDM). Design Population-based, cross-sectional survey. Setting and subjects In a single, semi-rural general practice 2082 subjects were between 20 and 69 years. Of those, 1970 subjects were invited, and a total of 1374 (69.7%) subjects were examined by blood tests, anthropometric measures, and self-administered questionnaires. Results Before the survey 19 persons were known to have type 2 diabetes. The screening revealed another 31 individuals with type 2 diabetes, diagnosed according to the 1999 World Health Organization criteria. Age, levels of blood pressure, BMI, and dyslipidaemia, and markers of haemostasis and inflammation were comparable in the two groups. Median age in the KDM group was 58 vs. 57 years in the SDM group, p = 0.82, 79% were male vs. 61%, p = 0.23. In both groups 74% had blood pressure ≥ 130/85 mmHg, p = 1.00. In both groups 90% had BMI ≥ 25, p = 1.00, and about half in both groups had BMI ≥ 30, p = 0.56. In the KDM group 63% had dyslipidaemia (low HDL cholesterol or elevated triglycerides) vs. 80% in the SDM group, p = 0.32. Median levels of plasminogen-activator-inhibitor (PAI-1), tissue plasminogen activator (t-PA), as well as fibrinogen and C-reactive protein (CRP) were without statistically significant differences in the two groups, p > 0.1. In contrast, in markers of glycaemic regulation statistically significant differences were found between groups. Median HbA1 was 8.0 vs. 6.5, p < 0.001. Median fasting whole blood glucose level was 8.8 mmol/L vs. 6.3 mmol/L, p < 0.001, and glucose at two hours during OGTT was 16.9 mmol/L vs. 11.2 mmol/L, p < 0.001. Median fasting serum insulin level was 52 pmol/L vs. 80 pmol/L, p = 0.039 and at two hours 127 pmol/L vs. 479 pmol/L, p < 0.001. Conclusions The CVD risk-factor profile of SDM patients was similar to the expected

  8. Increased Blood Levels of Growth Factors, Proinflammatory Cytokines, and Th17 Cytokines in Patients with Newly Diagnosed Type 1 Diabetes

    PubMed Central

    Heilman, Kaire; Peet, Aleksandr; Varik, Karin; Uibo, Raivo

    2015-01-01

    The production of several cytokines could be dysregulated in type 1 diabetes (T1D). In particular, the activation of T helper (Th) type 1 (Th1) cells has been proposed to underlie the autoimmune pathogenesis of the disease, although roles for inflammatory processes and the Th17 pathway have also been shown. Nevertheless, despite evidence for the role of cytokines before and at the onset of T1D, the corresponding findings are inconsistent across studies. Moreover, conflicting data exist regarding the blood cytokine levels in T1D patients. The current study was performed to investigate genetic and autoantibody markers in association with the peripheral blood cytokine profiles by xMap multiplex technology in newly diagnosed young T1D patients and age-matched healthy controls. The onset of young-age T1D was characterized by the upregulation of growth factors, including granulocyte macrophage-colony stimulating factor (GM-CSF) and interleukin (IL)-7, the proinflammatory cytokine IL-1β (but not IL-6 or tumor necrosis factor [TNF]-α), Th17 cytokines, and the regulatory cytokines IL-10 and IL-27. Ketoacidosis and autoantibodies (anti-IA-2 and -ZnT8), but not human leukocyte antigen (HLA) genotype, influenced the blood cytokine levels. These findings broaden the current understanding of the dysregulation of systemic levels of several key cytokines at the young-age onset of T1D and provide a further basis for the development of novel immunoregulatory treatments in this disease. PMID:26636339

  9. Role of adiponectin and some other factors linking type 2 diabetes mellitus and obesity

    PubMed Central

    Chakraborti, Chandra Kanti

    2015-01-01

    Because of the intimate association of obesity with type 2 diabetes mellitus (T2DM), during the last two decades, extensive research work is being conducted to find out whether the coexistence of the two is a simple association or there is a positive correlating link between the two. In this article, an attempt has been made to collect and analyse the recent developments in this field and to arrive at a conclusion on the subject. The possible role of several important factors (obtained from adipocytes/not of adipocyte origin) in linking the two has been discussed in detail. Some of the agents, specifically adiponectin, are beneficial (i.e., reduce the incidence of both), while others are harmful (i.e., increase their incidence). From the analysis, it appears that obesity and T2DM are intimately linked. PMID:26557957

  10. Hall scattering factors in p-type 4H-SiC with various doping concentrations

    NASA Astrophysics Data System (ADS)

    Asada, Satoshi; Okuda, Takafumi; Kimoto, Tsunenobu; Suda, Jun

    2016-04-01

    The Hall scattering factor (γH) in p-type 4H-SiC with various aluminum doping concentrations of 5.8 × 1014-7.1 × 1018 cm-3 was investigated from 300 to 900 K. γH was determined by comparing the Hall coefficient with the theoretical carrier concentration derived from acceptor and donor concentrations obtained from secondary ion mass spectrometry and capacitance-voltage measurements. γH decreased with increasing temperature or doping concentration; γH = 1-0.4 for the doping concentration of 5.8 × 1014 cm-3 and γH = 0.5-0.2 for the doping concentration of 7.1 × 1018 cm-3. The dependence might be caused by the anisotropic and nonparabolic valence band structure of 4H-SiC.

  11. [Psychogenic factors participating in the development of vegetovascular dystonia of the hypertensive type in children].

    PubMed

    Isaev, D N; Efremov, K D

    1983-01-01

    Sixty patients with a prehypertonic condition (aged 7 to 13 years) were studied to assess their clinical-psychological characteristics as well as microsocial psychogenic factors involved. It was established that in 80% of the families studied, despite their apparent "normality and respectability", there were some adverse familial relations which exerted both pathoplastic and pathogenetic influence on the formation of vegetative-vascular dystonia of a hypertonic type. The degree and the range of attending psychosomatic disturbances depend on the severity of the conflict and on the nature (acute or chronic) of a psychotrauma as well as on the child's awareness of the problem. It is important that the elicited characteristics of the concrete mechanisms of the development of psychic traumas should be considered in devising psychotherapeutic method of the prophylaxis and treatment of these patients. PMID:6659792

  12. Evaluation of a Multiplex PCR Assay (Bruce-ladder) for Molecular Typing of All Brucella Species, Including the Vaccine Strains▿ †

    PubMed Central

    López-Goñi, I.; García-Yoldi, D.; Marín, C. M.; de Miguel, M. J.; Muñoz, P. M.; Blasco, J. M.; Jacques, I.; Grayon, M.; Cloeckaert, A.; Ferreira, A. C.; Cardoso, R.; Corrêa de Sá, M. I.; Walravens, K.; Albert, D.; Garin-Bastuji, B.

    2008-01-01

    An evaluation of a multiplex PCR assay (Bruce-ladder) was performed in seven laboratories using 625 Brucella strains from different animal and geographical origins. This robust test can differentiate in a single step all of the classical Brucella species, including those found in marine mammals and the S19, RB51, and Rev.1 vaccine strains. PMID:18716225

  13. Environmental factors in the etiology of type 1 diabetes, celiac disease, and narcolepsy.

    PubMed

    Lernmark, Åke

    2016-07-01

    The etiology of human leukocyte antigen (HLA)-associated organ-specific autoimmune diseases is incomplete. In type 1 diabetes and celiac disease, the strongest associations are with the HLA-DR3-DQ2 and DR4-DQ8 haplotypes, whereas the DQB1*06:02 allele has a strong negative association. In contrast, narcolepsy, especially as recently triggered by the Pandemrix(®) H1N1 vaccine (GlaxoKlineSmith (GSK), Brentford, Middlesex, UK), did not seem to develop without at least one copy of the latter allele. The overall hypothesis is that the role of these different HLA haplotypes, especially in Finland and Sweden, is related to the immune response to infectious agents that are common in these two populations. The high incidence of both type 1 diabetes and celiac disease in Scandinavia may be the result of the HLA-DR3-DQ2 and DR4-DQ8 haplotypes, and the DQB1*06:02 allele are common because they protected people from succumbing to common infections. The timing of dissecting the autoimmune response is critical to understand the possible role of environmental factors. First, an etiological trigger may be a common virus infecting beta cells or with antigens inducing beta-cell cross reactivity. Second, an autoimmune reaction may ensue, perhaps in response to beta-cell apoptosis or autophagy, resulting in autoantigen-specific T cells and autoantibodies. It is critical in at-risk children to dissect the immune response prior to the appearance of autoantibodies in order to identify cellular reactions in response to environmental factors that are able to induce an HLA-associated immune reaction. PMID:27411439

  14. Identification of a cleavage site directing the immunochemical detection of molecular abnormalities in type IIA von Willebrand factor.

    PubMed Central

    Dent, J A; Berkowitz, S D; Ware, J; Kasper, C K; Ruggeri, Z M

    1990-01-01

    Proteolytic cleavage of the von Willebrand factor subunit may be important for processing and/or function of the molecule and is altered in certain subtypes of von Willebrand disease. It results in the generation of two main fragments with apparent molecular masses of 140 kDa and 176 kDa from the 225-kDa subunit. We have now obtained chemical evidence to locate the protease-sensitive bond between residues Tyr-842 and Met-843, a site that appears to reflect the specificity of calcium-dependent neutral proteases (calpains). Antibodies were raised against four synthetic peptides that represented sequences immediately preceding or following or including the cleavage site. One antibody (against the fragment from Ala-837 through Asp-851) reacted only with the intact subunit, and its epitope included the cleavage site. All others reacted specifically with either the 140-kDa or the 176-kDa fragment, demonstrating their origin from a single cleavage. In samples of purified von Willebrand factor from four of five patients with type IIA von Willebrand disease, the anti-peptide antibodies showed markedly decreased reactivity with either the 140-kDa or the 176-kDa fragment, suggesting the existence of distinct molecular abnormalities clustered around the cleavage site. Thus, in the majority of type IIA patients, a common pathogenetic mechanism may lead to the disappearance of the larger multimers as a consequence of structural changes that may expose a sensitive bond to the action of specific proteases. These studies demonstrate the use of anti-peptide antibodies directed at a relevant structural domain for the immunochemical differentiation of normal and mutant molecules. Images PMID:2385594

  15. Topological insulator homojunctions including magnetic layers: The example of n-p type (n-QLs Bi2Se3/Mn-Bi2Se3) heterostructures

    NASA Astrophysics Data System (ADS)

    Vališka, M.; Warmuth, J.; Michiardi, M.; Vondráček, M.; Ngankeu, A. S.; Holý, V.; Sechovský, V.; Springholz, G.; Bianchi, M.; Wiebe, J.; Hofmann, P.; Honolka, J.

    2016-06-01

    Homojunctions between Bi2Se3 and its Mn-doped phase are investigated as a sample geometry to study the influence of spin degrees of freedom on topological insulator properties. n quintuple layers of Bi2Se3 are grown on top of Mn-doped Bi2Se3 by molecular beam epitaxy for 0 ≤n ≤30 QLs , allowing to unhamperedly monitor the development of electronic and topological properties by surface sensitive techniques like angle resolved photoemission spectroscopy. With increasing n, a Mn-induced gap at the Dirac point is gradually filled in an "hourglass" fashion to reestablish a topological surface state at n ˜9 QLs . Our results suggest a competition of upward and downward band bending effects due to the presence of an n-p type interface, which can be used to tailor topological and quantum well states independently.

  16. Anti-Vascular Endothelial Growth Factor Treatment for Proliferative Macular Telangiectasia Type 2.

    PubMed

    Alkin, Zeynep; Yilmaz, Ihsan; Ozkaya, Abdullah; Yazici, Ahmet Taylan

    2016-01-01

    Idiopathic macular telangiectasia type 2 (IMT 2), is the most common type of a heterogeneous group of disorders, characterized by telangiectatic alterations of the juxtafoveolar capillary network. Vision loss is due to retinal atrophy and subretinal neovascularization (SRN). Here, we report the outcomes of intravitreal anti-vascular endothelial growth factor injections, bevacizumab or ranibizumab, in four cases with proliferative IMT 2. Baseline best corrected visual acuity (VA) ranged from 20/50 to 20/100. Follow-up time ranged from 12 months to 24 months. One of four patients received one injection, two patients received three injections, and one patient received seven injections. VA improved in three eyes (≥1 line improvement) and decreased in one eye (≥1 line decrease) over time. Final acuity ranged from 20/30 to 20/100. There were no cases of leakage after the cessation of treatment. SRN, which is a complication of IMT 2, should be recognized and treated accordingly. PMID:27162458

  17. Transcription Factor Runx2 Promotes Aortic Fibrosis and Stiffness in Type 2 Diabetes

    PubMed Central

    Raaz, Uwe; Schellinger, Isabel N.; Chernogubova, Ekaterina; Warnecke, Christina; Kayama, Yosuke; Penov, Kiril; Hennigs, Jan K.; Salomons, Florian; Eken, Suzanne; Emrich, Fabian C.; Zheng, Wei H.; Adam, Matti; Jagger, Ann; Nakagami, Futoshi; Toh, Ryuji; Toyama, Kensuke; Deng, Alicia; Buerke, Michael; Maegdefessel, Lars; Hasenfuß, Gerd; Spin, Joshua M.; Tsao, Philip S.

    2015-01-01

    Rationale Accelerated arterial stiffening is a major complication of diabetes with no specific therapy available up to date. Objective The present study investigates the role of the osteogenic transcription factor Runx2 as a potential mediator and therapeutic target of aortic fibrosis and aortic stiffening in diabetes. Methods and Results Using a murine model of type 2 diabetes (db/db mice) we identify progressive structural aortic stiffening that precedes the onset of arterial hypertension. At the same time, Runx2 is aberrantly upregulated in the medial layer of db/db aortae as well as in thoracic aortic samples from type 2 diabetic patients. Vascular smooth muscle-specific overexpression of Runx2 in transgenic mice increases expression of its target genes, Col1a1 and Col1a2, leading to medial fibrosis and aortic stiffening. Interestingly, increased Runx2 expression per se is not sufficient to induce aortic calcification. Using in vivo and in vitro approaches, we further demonstrate that Runx2 expression in diabetes is regulated via a redox-sensitive pathway that involves a direct interaction of NF-κB with the Runx2 promoter. Conclusion In conclusion this study highlights Runx2 as a previously unrecognized inducer of vascular fibrosis in the setting of diabetes, promoting arterial stiffness irrespective of calcification. PMID:26208651

  18. Gene duplication of type-B ARR transcription factors systematically extends transcriptional regulatory structures in Arabidopsis

    PubMed Central

    Choi, Seung Hee; Hyeon, Do Young; Lee, ll Hwan; Park, Su Jin; Han, Seungmin; Lee, In Chul; Hwang, Daehee; Nam, Hong Gil

    2014-01-01

    Many of duplicated genes are enriched in signaling pathways. Recently, gene duplication of kinases has been shown to provide genetic buffering and functional diversification in cellular signaling. Transcription factors (TFs) are also often duplicated. However, how duplication of TFs affects their regulatory structures and functions of target genes has not been explored at the systems level. Here, we examined regulatory and functional roles of duplication of three major ARR TFs (ARR1, 10, and 12) in Arabidopsis cytokinin signaling using wild-type and single, double, and triple deletion mutants of the TFs. Comparative analysis of gene expression profiles obtained from Arabidopsis roots in wild-type and these mutants showed that duplication of ARR TFs systematically extended their transcriptional regulatory structures, leading to enhanced robustness and diversification in functions of target genes, as well as in regulation of cellular networks of target genes. Therefore, our results suggest that duplication of TFs contributes to robustness and diversification in functions of target genes by extending transcriptional regulatory structures. PMID:25425016

  19. Anti-Vascular Endothelial Growth Factor Treatment for Proliferative Macular Telangiectasia Type 2

    PubMed Central

    Alkin, Zeynep; Yilmaz, Ihsan; Ozkaya, Abdullah; Yazici, Ahmet Taylan

    2016-01-01

    Idiopathic macular telangiectasia type 2 (IMT 2), is the most common type of a heterogeneous group of disorders, characterized by telangiectatic alterations of the juxtafoveolar capillary network. Vision loss is due to retinal atrophy and subretinal neovascularization (SRN). Here, we report the outcomes of intravitreal anti-vascular endothelial growth factor injections, bevacizumab or ranibizumab, in four cases with proliferative IMT 2. Baseline best corrected visual acuity (VA) ranged from 20/50 to 20/100. Follow-up time ranged from 12 months to 24 months. One of four patients received one injection, two patients received three injections, and one patient received seven injections. VA improved in three eyes (≥1 line improvement) and decreased in one eye (≥1 line decrease) over time. Final acuity ranged from 20/30 to 20/100. There were no cases of leakage after the cessation of treatment. SRN, which is a complication of IMT 2, should be recognized and treated accordingly. PMID:27162458

  20. Defective glycosylation of coagulation factor XII underlies hereditary angioedema type III

    PubMed Central

    Björkqvist, Jenny; de Maat, Steven; Lewandrowski, Urs; Di Gennaro, Antonio; Oschatz, Chris; Schönig, Kai; Nöthen, Markus M.; Drouet, Christian; Braley, Hal; Nolte, Marc W.; Sickmann, Albert; Panousis, Con; Maas, Coen; Renné, Thomas

    2015-01-01

    Hereditary angioedema type III (HAEIII) is a rare inherited swelling disorder that is associated with point mutations in the gene encoding the plasma protease factor XII (FXII). Here, we demonstrate that HAEIII-associated mutant FXII, derived either from HAEIII patients or recombinantly produced, is defective in mucin-type Thr309-linked glycosylation. Loss of glycosylation led to increased contact-mediated autoactivation of zymogen FXII, resulting in excessive activation of the bradykinin-forming kallikrein-kinin pathway. In contrast, both FXII-driven coagulation and the ability of C1-esterase inhibitor to bind and inhibit activated FXII were not affected by the mutation. Intravital laser-scanning microscopy revealed that, compared with control animals, both F12–/– mice reconstituted with recombinant mutant forms of FXII and humanized HAEIII mouse models with inducible liver-specific expression of Thr309Lys-mutated FXII exhibited increased contact-driven microvascular leakage. An FXII-neutralizing antibody abolished bradykinin generation in HAEIII patient plasma and blunted edema in HAEIII mice. Together, the results of this study characterize the mechanism of HAEIII and establish FXII inhibition as a potential therapeutic strategy to interfere with excessive vascular leakage in HAEIII and potentially alleviate edema due to other causes. PMID:26193639

  1. Microsatellite mutation of type II transforming growth factor-beta receptor is rare in atherosclerotic plaques.

    PubMed

    Clark, K J; Cary, N R; Grace, A A; Metcalfe, J C

    2001-04-01

    A somatic mutation within a microsatellite polyA tract in the coding region of the type II transforming growth factor (TGF)-beta receptor gene was reported to occur in human atherosclerotic and restenotic lesions. This mutation occurs frequently in colorectal cancer with the replication error repair phenotype and results in loss of sensitivity to the growth inhibitory effects of TGF-beta in cells from the tumors. The mutation was proposed to account for the clonal expansion of vascular smooth muscle cells observed in atherosclerotic plaques, through loss of the growth inhibitory effect of TGF-beta. The frequency of the mutation and the extent of clonal expansion of the mutated cells have major implications for the mechanism of atherogenesis and therapeutic strategies. We analyzed a set of 22 coronary arterial and 9 aortic samples containing early to advanced atherosclerotic lesions for the mutation in the type II TGF-beta receptor polyA tract. Only 1 coronary arterial sample from an advanced lesion showed detectable amounts of the mutation, present at a low level (8% of the DNA sample). The data imply that the mutation occurs only at low frequency and is not a major mechanistic contributor to the development of atherosclerosis. PMID:11304472

  2. Defective glycosylation of coagulation factor XII underlies hereditary angioedema type III.

    PubMed

    Björkqvist, Jenny; de Maat, Steven; Lewandrowski, Urs; Di Gennaro, Antonio; Oschatz, Chris; Schönig, Kai; Nöthen, Markus M; Drouet, Christian; Braley, Hal; Nolte, Marc W; Sickmann, Albert; Panousis, Con; Maas, Coen; Renné, Thomas

    2015-08-01

    Hereditary angioedema type III (HAEIII) is a rare inherited swelling disorder that is associated with point mutations in the gene encoding the plasma protease factor XII (FXII). Here, we demonstrate that HAEIII-associated mutant FXII, derived either from HAEIII patients or recombinantly produced, is defective in mucin-type Thr309-linked glycosylation. Loss of glycosylation led to increased contact-mediated autoactivation of zymogen FXII, resulting in excessive activation of the bradykinin-forming kallikrein-kinin pathway. In contrast, both FXII-driven coagulation and the ability of C1-esterase inhibitor to bind and inhibit activated FXII were not affected by the mutation. Intravital laser-scanning microscopy revealed that, compared with control animals, both F12-/- mice reconstituted with recombinant mutant forms of FXII and humanized HAEIII mouse models with inducible liver-specific expression of Thr309Lys-mutated FXII exhibited increased contact-driven microvascular leakage. An FXII-neutralizing antibody abolished bradykinin generation in HAEIII patient plasma and blunted edema in HAEIII mice. Together, the results of this study characterize the mechanism of HAEIII and establish FXII inhibition as a potential therapeutic strategy to interfere with excessive vascular leakage in HAEIII and potentially alleviate edema due to other causes. PMID:26193639

  3. Transforming growth factor receptor type II (ec-TβR II) behaves as a halophile.

    PubMed

    Saini, Komal; Khan, M Ashhar I; Chakrapani, Sumit; Deep, Shashank

    2015-01-01

    The members of transforming growth factor β family (TGF-β) are multifunctional proteins but their main role is to control cell proliferation and differentiation. Polypeptides of TGF-β family function by binding to two related, functionally distinct transmembrane receptor kinases, first to the type II (TβR II) followed by type I receptor (TβR I). The paper describes, in details, the stability of wt-ec-TβR II under different conditions. The stability of wt-ec-TβR II was observed at different pH and salt concentration using fluorescence spectroscopy. Stability of ec-TβR II decreases with decrease in pH. Interestingly, the addition of salt increases the stability of the TβRII at pH 5.0 as observed for halophiles. Computational analysis using DELPHI suggests that this is probably due to the decrease in repulsion between negatively charged residues at surface on the addition of salt. This is further confirmed by the change in the stability of receptor on mutation of some of the residues (D32A) at surface. PMID:25316422

  4. Effects of two types of cobra venom factor on porcine complement activation and pulmonary artery pressure.

    PubMed Central

    Cheung, A K; Parker, C J; Wilcox, L

    1989-01-01

    Autologous porcine plasma that has been incubated with cuprophan haemodialysis membranes causes pulmonary hypertension and peripheral leucopenia following reinfusion into swine. These effects appear to be mediated by biologically active fragments of C3 and C5 that are generated as a consequence of ex vivo activation of complement. Putatively, C5a induces the leucopenia; however, the specific contributions of products of C3 and C5 activation to the pulmonary vasoconstriction have not been elucidated. In the present study, the effects of in vivo infusion of two different types of cobra venom factor (CVF) on peripheral leucocyte count and pulmonary artery pressure in the swine are reported. The CVF from Naja n. naja (CVF(TN)) was shown to activate both porcine C3 and C5, whereas the CVF from Naja h. haje (CVF(NH)) activated only C3. Both types of CVF produced pulmonary hypertension. Significant peripheral leucopenia, however, was observed only with CVF(TN). These results suggest that activation products of C3 contribute to the pulmonary hypertension but not to the peripheral leucopenia observed during haemodialysis using dialysis membranes that activate complement. PMID:12412765

  5. Edaphic factors affecting the vertical distribution of radionuclides in the different soil types of Belgrade, Serbia.

    PubMed

    Dragović, Snežana; Gajić, Boško; Dragović, Ranko; Janković-Mandić, Ljiljana; Slavković-Beškoski, Latinka; Mihailović, Nevena; Momčilović, Milan; Ćujić, Mirjana

    2012-01-01

    The specific activities of natural radionuclides ((40)K, (226)Ra and (232)Th) and Chernobyl-derived (137)Cs were measured in soil profiles representing typical soil types of Belgrade (Serbia): chernozems, fluvisols, humic gleysols, eutric cambisols, vertisols and gleyic fluvisols. The influence of soil properties and content of stable elements on radionuclide distribution down the soil profiles (at 5 cm intervals up to 50 cm depth) was analysed. Correlation analysis identified associations of (40)K, (226)Ra and (137)Cs with fine-grained soil fractions. Significant positive correlations were found between (137)Cs specific activity and both organic matter content and cation exchange capacity. Saturated hydraulic conductivity and specific electrical conductivity were also positively correlated with the specific activity of (137)Cs. The strong positive correlations between (226)Ra and (232)Th specific activities and Fe and Mn indicate an association with oxides of these elements in soil. The correlations observed between (40)K and Cr, Ni, Pb and Zn and also between (137)Cs and Cd, Cr, Pb and Zn could be attributed to their common affinity for clay minerals. These results provide insight into the main factors that affect radionuclide migration in the soil, which contributes to knowledge about radionuclide behaviour in the environment and factors governing their mobility within terrestrial ecosystems. PMID:22072061

  6. Repression of the human papillomavirus type 18 enhancer by the cellular transcription factor Oct-1.

    PubMed Central

    Hoppe-Seyler, F; Butz, K; zur Hausen, H

    1991-01-01

    The role of cellular factors involved in the transcriptional regulation of the cancer-associated human papillomavirus type 18 (HPV18) is yet poorly understood. The presence of an Oct-1-binding site within the HPV18 upstream regulatory region led us to investigate the influence of Oct-1 on viral transcription. Cotransfection of Oct-1 expression plasmids together with luciferase reporter constructs containing HPV18 regulatory sequences indicated that Oct-1 can transcriptionally repress the HPV18 upstream regulatory region. In contrast, heterologous control regions were not affected by Oct-1. HPV18 cis elements that can be repressed by Oct-1 mapped to a 135-bp subregion of the viral constitutive enhancer. Analysis of an Oct-1 mutant defective in DNA binding suggested that HPV18 down-modulation does not require direct binding of Oct-1 to DNA. These results make Oct-1 a candidate factor involved in the intracellular surveillance of HPV18 transcription and support the notion of a host cell mechanism that can specifically repress HPV E6-E7 transforming gene expression. Images PMID:1654457

  7. Do Personal Factors or Types of Physical Tasks Predict Workplace Injury?

    PubMed

    Oranye, Nelson Ositadimma; Wallis, Bernadine; Roer, Kim; Archer-Heese, Gail; Aguilar, Zaklina

    2016-04-01

    Occupational health research has shown that certain worker and job characteristics are risk factors for workplace injuries. Workers who engage in physically demanding jobs, especially those jobs that involve repetitive motion, are at greater risk for work-related musculoskeletal disorders (WMSD). These risks are particularly prevalent in the health care sector. It is often reported that nurses are at higher risk of workplace musculoskeletal injury than other health care workers due to frequent lifting and transfer of patients and the prevalence of workplace violence. However, many analyses of the physical requirements of jobs do not consider the modifying effect of time spent on a physical task and the risk of WMSD. This study compared the risks of WMSD among workers in health care facilities based on the type of physical tasks and amount of time workers spent on such tasks. Workers who worked longer on a physical task reported more WMSD than those who spent less time on the same physical task. The risk of WMSD was twice as high (odds ratio [OR] = 2.3) among workers who sit less than 2 hours each day compared with those who sit longer. This study found that physical tasks associated with health care jobs and the amount of time spent on these tasks constitutes serious risk factors for WMSD. PMID:27056936

  8. Risk Factors for Early Failure of Arteriovenous Vascular Access Among Patients With Type 2 Diabetes Mellitus.

    PubMed

    Yap, Yit-Sheung; Chuang, Hung-Yi; Wu, Chien-Hung; Chi, Wen-Che; Lin, Cheng-Hao; Liu, Yi-Chun

    2016-04-01

    The aim of the study was to identify the potential risk factors for early arteriovenous access failure in a diabetic population. The data of 223 end-stage renal disease (ESRD) patients with type 2 diabetes who had an arteriovenous fistula (AVF) or arteriovenous graft (AVG) placed as their initial vascular accesses were retrospectively reviewed. The association between clinical factors and risk for early failure was then analyzed. In multivariate analysis, the predictors associated with early failure were female gender (odds ratio (95% confidence interval): 2.52 (1.32-4.81); P = 0.005), AVF with prior peritoneal dialysis (3.26 (1.05-10.11); P = 0.039), and lower hemoglobin level (P = 0.015). The results of significant predictors in the AVF group remained similar to the entire study population. In conclusion, there was an association of female gender, AVF with prior peritoneal dialysis and lower hemoglobin level with early arteriovenous access failure in a diabetic ESRD population. PMID:26916506

  9. Canine pancreatic islet cell tumours secreting insulin-like growth factor type 2: a rare entity.

    PubMed

    Finotello, R; Ressel, L; Arvigo, M; Baroni, G; Marchetti, V; Romanelli, G; Burrow, R; Mignacca, D; Blackwood, L

    2016-06-01

    Insulin-like growth factor type II (IGF-II) is the main cause of non-islet cell tumour hypoglycaemia (NICTH) and insulin is thought to be the only factor causing hypoglycaemia in insulinomas. However, two case reports of pancreatic neuroendocrine tumours (PNETs) producing IGF-II have been previously published: a human and a canine patient. In this study, we investigated clinical, histopathological, immunohistochemical and ultrastructural features, and biological behaviour of canine pancreatic IGF-II-omas, a subgroup of PNETs that has not been previously characterized. Case records of 58 dogs with confirmed PNETs and hypoglycaemia were reviewed: six patients were affected by IGF-II-omas. Surgery was performed in all cases and two dogs had metastases. Four patients remained alive and in remission at 370, 440, 560 and 890 days post-diagnosis; two died of non-tumour-related causes. IGF-II-omas can be differentiated from insulinomas through hypoinsulinaemia, IGF-II positive and insulin negative immunostaining. The prevalence of this neoplasia is low, accounting for just 6% of PNETs. PMID:24428588

  10. Risk factors and gene type for infections of MRSA in diabetic foot patients in Tianjin, China.

    PubMed

    Feng, Shu-Hong; Chu, Yue-Jie; Wang, Peng-Hua; Jun, Xu; Min, Ding; Li, Xue-Mei

    2013-06-01

    The objective was to study risk factors and gene type of DF patients infected with MRSA. A total of 429 DF patients were recruited. The patients with S aureus infections were divided into MRSA and MSSA groups. MRSA were genotyped by SCCmec. pvl and lukE-lukD were detected. A total of 559 pathogens were isolated from them, with G+ bacteria firstly(59.0%), followed G- bacilli (37.7%) and true fungi (3.3%). The 3 most frequently isolated pathogens were S aureus (35.2%), S epidermidis (12.3%), and Pseudomonas aeruginosa (11.2%). SCCmec III MRSA and SCCmec IVa MRSA had the same antibacterial spectrum. mecA positive rate was 100%. lukE-lukD and pvl positive rates were 100% and 0%, respectively. 28 strains belonged to SCCmec III and the others belonged to SCCmec IVa. The G+ cocci were the main pathogens, S aureus and S epidermidis were predominant among them. Antibiotic usage in 6 months prior to hospitalization, long course of ulcer, osteomyelitis and hypoproteinemia are risk factors for MRSA. SCCmec IVa is high in proportion to MRSA isolates, suggesting that CA-MRSA has become major pathogen of DF infection. All the MRSA were harboring lukE-lukD, which has been reported to present poor leucotoxin compared to pvl, and may be a response to atypical local inflammatory reaction in DF infection. PMID:23771611

  11. Pre-morbid Type 2 Diabetes Mellitus is not a prognostic factor in ALS

    PubMed Central

    Paganoni, Sabrina; Hyman, Theodore; Shui, Amy; Allred, Peggy; Harms, Matthew; Liu, Jingxia; Maragakis, Nicholas; Schoenfeld, David; Yu, Hong; Atassi, Nazem; Cudkowicz, Merit; Miller, Timothy M.

    2015-01-01

    Objective To determine whether history of pre-morbid type 2 diabetes mellitus (DM2) is a prognostic factor in amyotrophic lateral sclerosis (ALS). Methods The relationship between DM2 and survival was analyzed in a study population consisting of 1,322 participants from six clinical trials. Results Survival did not differ by diabetes status (Log-Rank Test, p=0.98), but did differ by body mass index (BMI) (Log-Rank Test, p=0.008). In multivariate analysis, there was no significant association between diabetes and survival (p=0.18), but the risk of reaching a survival endpoint decreased by 4% for each unit increase in baseline BMI (HR 0.96, 95% CI 0.94–0.99, p=0.001). DM2 was less prevalent among ALS clinical trial participants than predicted. Conclusions History of pre-morbid DM2 is not an independent prognostic factor in ALS clinical trial databases. The low DM2 prevalence rate should be examined in a large, prospective study to determine whether DM2 affects ALS risk. PMID:25900666

  12. The type III transforming growth factor beta receptor regulates vascular and osteoblast development during palatogenesis

    PubMed Central

    Hill, Cynthia R.; Jacobs, Britni H.; Brown, Christopher B.; Barnett, Joey V.; Goudy, Steven L.

    2015-01-01

    Background Cleft palate occurs in up to 1:1000 live births and is associated with mutations in multiple genes. Palatogenesis involves a complex choreography of palatal shelf elongation, elevation, and fusion. Transforming growth factor β (TGFβ) and bone morphogenetic protein 2 (BMP2) canonical signaling is required during each stage of palate development. The type III TGFβ receptor (TGFβR3) binds all three TGFβ ligands and BMP2, but its contribution to palatogenesis is unknown. Results The role of TGFβR3 during palate formation was found to be during palatal shelf elongation and elevation. Tgfbr3-/- embryos displayed reduced palatal shelf width and height, changes in proliferation and apoptosis, and reduced vascular and osteoblast differentiation. Abnormal vascular plexus organization as well as aberrant expression of arterial (Notch1, Alk1), venous (EphB4), and lymphatic (Lyve1) markers was also observed. Decreased osteoblast differentiation factors (Runx2, alk phos, osteocalcin, col1A1, and col1A2) demonstrated poor mesenchymal cell commitment to the osteoblast lineage within the maxilla and palatal shelves in Tgfbr3-/- embryos. Additionally, in vitro bone mineralization induced by osteogenic medium (OM+BMP2) was insufficient in Tgfbr3-/- palatal mesenchyme, but mineralization was rescued by overexpression of TGFβR3. Conclusions These data reveal a critical, previously unrecognized role for TGFβR3 in vascular and osteoblast development during palatogenesis. PMID:25382630

  13. Identification of 17 HrpX-regulated proteins including two novel type III effectors, XOC_3956 and XOC_1550, in Xanthomonas oryzae pv. oryzicola.

    PubMed

    Xue, Xiao-bo; Zou, Li-fang; Ma, Wen-xiu; Liu, Zhi-yang; Chen, Gong-you

    2014-01-01

    The function of some hypothetical proteins, possibly regulated by key hrp regulators, in the pathogenicity of phytopathogenic bacteria remains largely unknown. In the present study, in silicon microarray data demonstrated that the expression of 17 HrpX-regulated protein (Xrp) genes of X. oryzae pv. oryzicola (Xoc), which causes bacterial leaf streak in rice, were either positively or negatively regulated by HrpX or/and HrpG. Bioinformatics analysis demonstrated that five Xrps possess a putative type III secretion (T3S) signal in the first 50 N-terminal amino acids, six xrp genes contain a PIP-box-like sequence (TTCGB-NX-TTCGB, 9 ≤ X ≤ 25) in the promoter regions, and two Xrps have both motifs. Twelve Xrps are widely conserved in Xanthomonas spp., whereas four are specific for X. oryzae (Xrp6) or Xoc (Xrp8, Xrp14 and Xrp17). In addition to the regulation by HrpG/HrpX, some of the 17 genes were also modulated by another hrp regulator HrpD6. Mutagenesis of these 17 genes indicated that five Xrps (Xrp1, Xrp2, Xrp5, Xrp8 and Xrp14) were required for full virulence and bacterial growth in planta. Immunoblotting assays and fusion with N-terminally truncated AvrXa10 indicated that Xrp3 and Xrp5 were secreted and translocated into rice cells through the type-III secretion system (T3S), suggesting they are novel T3S effectors. Our results suggest that Xoc exploits an orchestra of proteins that are regulated by HrpG, HrpX and HrpD6, and these proteins facilitate both infection and metabolism. PMID:24675748

  14. Identification of 17 HrpX-Regulated Proteins Including Two Novel Type III Effectors, XOC_3956 and XOC_1550, in Xanthomonas oryzae pv. oryzicola

    PubMed Central

    Xue, Xiao-bo; Zou, Li-fang; Ma, Wen-xiu; Liu, Zhi-yang; Chen, Gong-you

    2014-01-01

    The function of some hypothetical proteins, possibly regulated by key hrp regulators, in the pathogenicity of phytopathogenic bacteria remains largely unknown. In the present study, in silicon microarray data demonstrated that the expression of 17 HrpX-regulated protein (Xrp) genes of X. oryzae pv. oryzicola (Xoc), which causes bacterial leaf streak in rice, were either positively or negatively regulated by HrpX or/and HrpG. Bioinformatics analysis demonstrated that five Xrps possess a putative type III secretion (T3S) signal in the first 50 N-terminal amino acids, six xrp genes contain a PIP-box-like sequence (TTCGB-NX-TTCGB, 9≤X≤25) in the promoter regions, and two Xrps have both motifs. Twelve Xrps are widely conserved in Xanthomonas spp., whereas four are specific for X. oryzae (Xrp6) or Xoc (Xrp8, Xrp14 and Xrp17). In addition to the regulation by HrpG/HrpX, some of the 17 genes were also modulated by another hrp regulator HrpD6. Mutagenesis of these 17 genes indicated that five Xrps (Xrp1, Xrp2, Xrp5, Xrp8 and Xrp14) were required for full virulence and bacterial growth in planta. Immunoblotting assays and fusion with N-terminally truncated AvrXa10 indicated that Xrp3 and Xrp5 were secreted and translocated into rice cells through the type-III secretion system (T3S), suggesting they are novel T3S effectors. Our results suggest that Xoc exploits an orchestra of proteins that are regulated by HrpG, HrpX and HrpD6, and these proteins facilitate both infection and metabolism. PMID:24675748

  15. 40 CFR Table C-1 to Subpart C of... - Default CO2 Emission Factors and High Heat Values for Various Types of Fuel

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Heat Values for Various Types of Fuel C Table C-1 to Subpart C of Part 98 Protection of Environment... Emission Factors and High Heat Values for Various Types of Fuel Default CO2 Emission Factors and High Heat Values for Various Types of Fuel Fuel type Default high heat value Default CO2 emission factor Coal...

  16. 40 CFR Table C-1 to Subpart C of... - Default CO2 Emission Factors and High Heat Values for Various Types of Fuel

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Heat Values for Various Types of Fuel C Table C-1 to Subpart C of Part 98 Protection of Environment... Emission Factors and High Heat Values for Various Types of Fuel Default CO2 Emission Factors and High Heat Values for Various Types of Fuel Fuel type Default high heat value Default CO2 emission factor Coal...

  17. Antiviral factors and type I/III interferon expression associated with regulatory factors in the oral epithelial cells from HIV-1-serodiscordant couples.

    PubMed

    Cervantes, Cesar A C; Oliveira, Luanda M S; Manfrere, Kelly C G; Lima, Josenilson F; Pereira, Natalli Z; Duarte, Alberto J S; Sato, Maria N

    2016-01-01

    Individuals who remain HIV-seronegative despite repeated unprotected exposure to the virus are defined as exposed seronegative (ESN) individuals. Innate and adaptive immunity, as well as genetic factors, provide ESNs with important advantages that allow for low infection susceptibility. The majority of HIV-1-infected individuals undergo antiretroviral therapy, which can decrease the level of HIV-1 exposure in ESNs. We analyzed type I interferon (IFN)-related antiviral and regulatory factors in peripheral blood mononuclear cells (PBMCs) and oral epithelial cells from serodiscordant couples. Our findings revealed that ESNs did not induce the expression of antiviral factors (APOBEC-3G, TRIM5-α, SAMDH1, STING, TBk1) or regulatory factors (Trex, Foxo3, Socs3, IL-10) in PBMCs, unlike their HIV-1-infected partners. In contrast, ESNs upregulated APOBEC-3G and type I/III IFNs (IFNs-α,-β/-λ) in oral mucosal epithelial cells similar to their HIV-infected partners. The serodiscordant groups exhibited an increased expression of type I IFN-induced regulators, such as Trex and Foxo3, in oral epithelial cells. TLR7, TLR8 and TLR9 were expressed in oral epithelial cells of both ESNs and HIV-1-infected subjects. These findings revealed evidence of antiviral factors, type I/III interferon and regulatory factor expression only in the oral mucosal compartment of ESNs, while HIV-1-infected partners systemically and oral mucosal expressed the antiviral profile. PMID:27168019

  18. Antiviral factors and type I/III interferon expression associated with regulatory factors in the oral epithelial cells from HIV-1-serodiscordant couples

    PubMed Central

    Cervantes, Cesar A. C.; Oliveira, Luanda M. S.; Manfrere, Kelly C. G.; Lima, Josenilson F.; Pereira, Natalli Z.; Duarte, Alberto J. S.; Sato, Maria N.

    2016-01-01

    Individuals who remain HIV-seronegative despite repeated unprotected exposure to the virus are defined as exposed seronegative (ESN) individuals. Innate and adaptive immunity, as well as genetic factors, provide ESNs with important advantages that allow for low infection susceptibility. The majority of HIV-1-infected individuals undergo antiretroviral therapy, which can decrease the level of HIV-1 exposure in ESNs. We analyzed type I interferon (IFN)-related antiviral and regulatory factors in peripheral blood mononuclear cells (PBMCs) and oral epithelial cells from serodiscordant couples. Our findings revealed that ESNs did not induce the expression of antiviral factors (APOBEC-3G, TRIM5-α, SAMDH1, STING, TBk1) or regulatory factors (Trex, Foxo3, Socs3, IL-10) in PBMCs, unlike their HIV-1-infected partners. In contrast, ESNs upregulated APOBEC-3G and type I/III IFNs (IFNs-α,-β/-λ) in oral mucosal epithelial cells similar to their HIV-infected partners. The serodiscordant groups exhibited an increased expression of type I IFN-induced regulators, such as Trex and Foxo3, in oral epithelial cells. TLR7, TLR8 and TLR9 were expressed in oral epithelial cells of both ESNs and HIV-1-infected subjects. These findings revealed evidence of antiviral factors, type I/III interferon and regulatory factor expression only in the oral mucosal compartment of ESNs, while HIV-1-infected partners systemically and oral mucosal expressed the antiviral profile. PMID:27168019

  19. Physiological and behavioral risk factors of type 2 diabetes mellitus in rural India

    PubMed Central

    Barik, Anamitra; Mazumdar, Sumit; Chowdhury, Abhijit; Rai, Rajesh Kumar

    2016-01-01

    Background The dynamics of physiological and behavioral risk factors of diabetes in rural India is poorly understood. Using data from a health and demographic surveillance site of Birbhum district in West Bengal, India, this study aims to assess the risk factors associated with type 2 diabetes mellitus. Research design and methods A total of 7674 individuals aged ≥18 years participated in a cross-sectional study. Venous plasma glucose method was used for measuring and reporting glucose concentrations in blood, categorized as individuals with diabetes, pre-diabetes or impaired, and normoglycemic. Aside from a set of physiological and behavioral risk factors, a range of socioeconomic confounders of diabetes was computed. Bivariate analysis with χ2 test, and multivariate ordered logit regression methods were deployed to attain the study's objective. Results Overall 2.95% and 3.34% of study participants were diagnosed as individuals with diabetes and pre-diabetes or impaired, respectively. Compared to the poorest, the richest have higher probability (β: 0.730; 95% CI 0.378 to 1.083) of being diagnosed with diabetes. As compared to people with normal body mass index, overweight/obese people are more prone to being diagnosed with diabetes (β: 0.388; 95% CI 0.147 to 0.628). With a decreasing level of physical activity, people are more likely to be diagnosed with diabetes. Conclusions To curb the level of diabetes, this study recommends a culturally sensitive, focused intervention for the adoption of physical activity with more traditional dietary practices, to control the level of overweight/obesity. Attention should be paid to relatively older patients with diabetes or adults with pre-diabetes. PMID:27547420

  20. Reduction of cardiovascular risk factors in subjects with type 2 diabetes by Pycnogenol supplementation.

    PubMed

    Zibadi, Sherma; Rohdewald, Peter J; Park, Danna; Watson, Ronald Ross

    2008-05-01

    Patients with type 2 diabetes are at considerable risk of excessive morbidity and mortality from cardiovascular disease (CVD). We investigated the clinical effectiveness of Pycnogenol, a flavonoid-rich dietary supplement, in reducing antihypertensive medication use and CVD risk factors in subjects with type 2 diabetes. Forty-eight individuals were enrolled in a randomized, double-blind, placebo-controlled trial with parallel-group design. Patients were diagnosed with both type 2 diabetes and mild to moderate hypertension and were undergoing treatment with angiotensin-converting enzyme (ACE) inhibitors. Subjects were randomly assigned to receive either Pycnogenol pill (125 mg daily) or matched placebo for 12 weeks. According to the values of blood pressure (BP) measured at 2-week intervals, the pretrial ACE inhibitor dosage was left unchanged, reduced by 50%, or brought back to the pretrial dosage until a stable BP was obtained. Fasting plasma glucose, low-density lipoprotein (LDL) cholesterol, glycosylated hemoglobin (HbA1c), serum endothelin-1, and urinary albumin were evaluated monthly. Pycnogenol treatment achieved BP control in 58.3% of subjects at the end of the 12 weeks with 50% reduction in individual pretrial dose of ACE-inhibitors (P <.05). Plasma endothelin-1 decreased by 3.9 pg/mL in Pycnogenol-treated group vs 0.5 pg/mL increase in control group (P < .001). Mean HbA1c dropped by 0.8% in Pycnogenol-treated group (P < .05), whereas it decreased by 0.1% in control group. Fasting plasma glucose declined by 23.7 mg/dL in Pycnogenol-treated group vs 5.7 mg/dL in control group (P < .0001). Low-density lipoprotein cholesterol improved significantly in Pycnogenol-treated group, declining by 12.7 mg/dL (P < .001). A significant decrease in urinary albumin level was observed at week 8 compared with the control group (P < .05). However, this reduction was not significant at 12th week. After 12 weeks of supplementation, Pycnogenol resulted in improved diabetes

  1. Mining the Brassica oleracea genome for Q-type C2H2 zinc finger transcription factor proteins

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Q-type zinc finger proteins have been studied in several plant species and have been associated with response to stress. A whole genome analysis of Arabidopsis identified 176 putative C2H2 transcription factors (TF). Q-type C2H2 TFs containing the QALGGH motif and are a subset of these. In Arabidops...

  2. Risk factors for type 2 diabetes in a sixth-grade multi-racial cohort: The HEALTHY study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    HEALTHY is a 3-year middle school intervention program designed to reduce risk factors for type 2 diabetes. The prevalence of diabetes risk factors at baseline in a cohort of 6,358 sixth-grade students is reported. Forty-two schools at seven U.S. sites were randomly assigned to intervention or contr...

  3. Redescription of Philometra globiceps (Rudolphi, 1819) (Nematoda: Philometridae), the type species of Philometra Costa, 1845, including the first data obtained by SEM.

    PubMed

    Moravec, František; Tedesco, Perla

    2015-12-01

    A redescription of Philometra globiceps (Rudolphi 1819), the type species of Philometra Costa 1845 (Philometridae), is provided on the basis of specimens collected from the gonads, stomach, pyloric caeca, intestine and gallbladder of the marine fish Uranoscopus scaber Linnaeus (Uranoscopidae, Perciformes) caught in the Ionian Sea off Ugento, southern Italy. Light microscopical and scanning electron microscopical examinations (latter used for the first time in this species) of the specimens revealed some previously unreported morphological features, such as the location of submedian pairs of cephalic papillae of external circle on four elevated cuticular lobes in gravid females, the presence of amphids, genital papillae and phasmids in males, the lamellate structure of the distal end of gubernaculum appearing as a dorsal protuberance in lateral view and the structure of the male caudal end. A taxonomically important feature of P. globiceps is the details in the dorsal transverse lamella-like structures on the distal end of the gubernaculum, by which this species can be separated from other gonad-infecting species of this genus. Apparently, P. globiceps is a specific parasite of U. scaber and all previous records of this species from hosts belonging to other fish families are evidently based on misidentifications. PMID:26319523

  4. Potential Role of Preoperative Conventional MRI Including Diffusion Measurements in Assessing Epidermal Growth Factor Receptor Gene Amplification Status in Patients with Glioblastoma

    PubMed Central

    Young, R.J.; Gupta, A.; Shah, A.D.; Graber, J.J.; Schweitzer, A.D.; Prager, A.; Shi, W.; Zhang, Z.; Huse, J.; Omuro, A.M.P.

    2016-01-01

    BACKGROUND AND PURPOSE Epidermal growth factor receptor amplification is a common molecular event in glioblastomas. The purpose of this study was to examine the potential usefulness of morphologic and diffusion MR imaging signs in the prediction of epidermal growth factor receptor gene amplification status in patients with glioblastoma. MATERIALS AND METHODS We analyzed pretreatment MR imaging scans from 147 consecutive patients with newly diagnosed glioblastoma and correlated MR imaging features with tumor epidermal growth factor receptor amplification status. The following morphologic tumor MR imaging features were qualitatively assessed: 1) border sharpness, 2) cystic/necrotic change, 3) hemorrhage, 4) T2-isointense signal, 5) restricted water diffusion, 6) nodular enhancement, 7) subependymal enhancement, and 8) multifocal discontinuous enhancement. A total of 142 patients had DWI available for quantitative analysis. ADC maps were calculated, and the ADCmean, ADCmin, ADCmax, ADCROI, and ADCratio were measured. RESULTS Epidermal growth factor receptor amplification was present in 60 patients (40.8%) and absent in 87 patients (59.2%). Restricted water diffusion correlated with epidermal growth factor receptor amplification (P = .04), whereas the other 7 morphologic MR imaging signs did not (P > .12). Quantitative DWI analysis found that all ADC measurements correlated with epidermal growth factor receptor amplification, with the highest correlations found with ADCROI (P = .0003) and ADCmean (P = .0007). CONCLUSIONS Our results suggest a role for diffusion MR imaging in the determination of epidermal growth factor receptor amplification status in glioblastoma. Additional work is necessary to confirm these results and isolate new imaging biomarkers capable of noninvasively characterizing the molecular status of these tumors. PMID:23811973

  5. Monte Carlo calculations of electron beam quality conversion factors for several ion chamber types

    SciTech Connect

    Muir, B. R.; Rogers, D. W. O.

    2014-11-01

    Purpose: To provide a comprehensive investigation of electron beam reference dosimetry using Monte Carlo simulations of the response of 10 plane-parallel and 18 cylindrical ion chamber types. Specific emphasis is placed on the determination of the optimal shift of the chambers’ effective point of measurement (EPOM) and beam quality conversion factors. Methods: The EGSnrc system is used for calculations of the absorbed dose to gas in ion chamber models and the absorbed dose to water as a function of depth in a water phantom on which cobalt-60 and several electron beam source models are incident. The optimal EPOM shifts of the ion chambers are determined by comparing calculations of R{sub 50} converted from I{sub 50} (calculated using ion chamber simulations in phantom) to R{sub 50} calculated using simulations of the absorbed dose to water vs depth in water. Beam quality conversion factors are determined as the calculated ratio of the absorbed dose to water to the absorbed dose to air in the ion chamber at the reference depth in a cobalt-60 beam to that in electron beams. Results: For most plane-parallel chambers, the optimal EPOM shift is inside of the active cavity but different from the shift determined with water-equivalent scaling of the front window of the chamber. These optimal shifts for plane-parallel chambers also reduce the scatter of beam quality conversion factors, k{sub Q}, as a function of R{sub 50}. The optimal shift of cylindrical chambers is found to be less than the 0.5 r{sub cav} recommended by current dosimetry protocols. In most cases, the values of the optimal shift are close to 0.3 r{sub cav}. Values of k{sub ecal} are calculated and compared to those from the TG-51 protocol and differences are explained using accurate individual correction factors for a subset of ion chambers investigated. High-precision fits to beam quality conversion factors normalized to unity in a beam with R{sub 50} = 7.5 cm (k{sub Q}{sup ′}) are provided. These

  6. Association of Comorbid and Metabolic Factors with Optimal Control of Type 2 Diabetes Mellitus

    PubMed Central

    Roy, Satyajeet; Sherman, Anthony; Monari-Sparks, Mary Joan; Schweiker, Olga; Jain, Navjot; Sims, Etty; Breda, Michelle; Byraiah, Gita P; Belecanech, Ryan George; Coletta, Michael Domenic; Barrios, Cristian Javier; Hunter, Krystal; Gaughan, John P

    2016-01-01

    Background: Type 2 diabetes mellitus (T2DM) is a poorly controlled epidemic worldwide that demands active research into mitigation of the factors that are associated with poor control. Aims: The study was to determine the factors associated with suboptimal glycemic control. Materials and Methods: Electronic medical records of 263 adult patients with T2DM in our suburban internal medicine office were reviewed. Patients were divided into two groups: Group 1 [optimal diabetes control with glycosylated hemoglobin (HbA1c) of 7% or less] and Group 2 (suboptimal diabetes control with HbA1c greater than 7%). The influence of factors such as age, gender, race, social history, comorbid conditions, gestational diabetes, family history of diabetes, diabetes management, statin use, aspirin use, angiotensin convertase enzyme inhibitor (ACE-I) or angiotensin receptor blocker (ARB) use, body mass index (BMI), blood pressures, lipid profile, and urine microalbumin level were analyzed in the two groups. Results: In the suboptimal diabetes control group (N = 119), the majority (86.6%) of the patients were 41-80 years old. Factors associated with the suboptimal control were male gender [odds ratio (OR) 2.6, 95% confidence interval (CI), 1.579-4.321], Asian ethnicity (OR 1.4, 95% CI, 0.683-3.008), history of peripheral arterial disease (PAD; OR 3.9, 95% CI, 1.017-14.543), history of congestive heart failure (CHF; OR 3.9, 95% CI, 1.017-14.543), elevated triglycerides (OR 1.004, 95% CI, 1.000-1.007), and elevated urine microalbumin level of 30 mg/24 h or above (OR 4.5, 95% CI, 2.446-8.380). Patients with suboptimal diabetes control had a 3.8 times greater odds (95% CI, 1.493-6.885) of receiving the insulin and oral hypoglycemic agent together. Conclusions: In adult patients with T2DM, male gender, Asian ethnicity, CHF, PAD, management with insulin along with oral hypoglycemic agents, hypertriglyceridemia, and microalbuminuria were associated with suboptimal control. PMID:27011945

  7. Dihydropyrimidinone positive modulation of delta-subunit-containing gamma-aminobutyric acid type A receptors, including an epilepsy-linked mutant variant.

    PubMed

    Lewis, Ryan W; Mabry, John; Polisar, Jason G; Eagen, Kyle P; Ganem, Bruce; Hess, George P

    2010-06-15

    Gamma-aminobutyric acid type A receptors (GABA(A) receptors) are ligand-gated chloride channels that play a central role in signal transmission within the mammalian central nervous system. Compounds that modulate specific GABA(A) receptor subtypes containing the delta-subunit are scarce but would be valuable research tools and starting points for potential therapeutic agents. Here we report a class of dihydropyrimidinone (DHPM) heterocycles that preferentially potentiate peak currents of recombinant GABA(A) receptor subtypes containing the delta-subunit expressed in HEK293T cells. Using the three-component Biginelli reaction, 13 DHPMs with structural features similar to those of the barbiturate phenobarbital were synthesized; one DHPM used (monastrol) is commercially available. An up to approximately 3-fold increase in the current from recombinant alpha1beta2delta receptors was observed with the DHPM compound JM-II-43A or monastrol when co-applied with saturating GABA concentrations, similar to the current potentiation observed with the nonselective potentiating compounds phenobarbital and tracazolate. No agonist activity was observed for the DHPMs at the concentrations tested. A kinetic model was used in conjunction with dose-dependent measurements to calculate apparent dissociation constant values for JM-II-43A (400 muM) and monastrol (200 microM) at saturating GABA concentrations. We examined recombinant receptors composed of combinations of subunits alpha1, alpha4, alpha5, alpha6, beta2, beta3, gamma2L, and delta with JM-II-43A to demonstrate the preference for potentiation of delta-subunit-containing receptors. Lastly, reduced currents from receptors containing the mutated delta(E177A) subunit, described by Dibbens et al. [(2004) Hum. Mol. Genet. 13, 1315-1319] as a heritable susceptibility allele for generalized epilepsy with febrile seizures plus, are also potentiated by these DHPMs. PMID:20450160

  8. A 725 kb deletion at 22q13.1 chromosomal region including SOX10 gene in a boy with a neurologic variant of Waardenburg syndrome type 2.

    PubMed

    Siomou, Elisavet; Manolakos, Emmanouil; Petersen, Michael; Thomaidis, Loretta; Gyftodimou, Yolanda; Orru, Sandro; Papoulidis, Ioannis

    2012-11-01

    Waardenburg syndrome (WS) is a rare (1/40,000) autosomal dominant disorder resulting from melanocyte defects, with varying combinations of sensorineural hearing loss and abnormal pigmentation of the hair, skin, and inner ear. WS is classified into four clinical subtypes (WS1-S4). Six genes have been identified to be associated with the different subtypes of WS, among which SOX10, which is localized within the region 22q13.1. Lately it has been suggested that whole SOX10 gene deletions can be encountered when testing for WS. In this study we report a case of a 13-year-old boy with a unique de novo 725 kb deletion within the 22q13.1 chromosomal region, including the SOX10 gene and presenting clinical features of a neurologic variant of WS2. PMID:22842075

  9. Petrographic and Geochemical Characterization of Ore-Bearing Intrusions of the Noril'sk type, Siberia; With Discussion of Their Origin, Including Additional Datasets and Core Logs

    USGS Publications Warehouse

    Czamanske, Gerald K., (compiler)

    2002-01-01

    The Noril'sk I, Talnakh, and Kharaelakh intrusions of the Noril'sk district host one of the outstanding metal concentrations in the world; contained Cu-Ni resources are comparable to the deposits at Sudbury, Ontario and the platinum group element (PGE) resource is second only to that of the Bushveld Complex. Our opportunity to cooperatively sample and study this district in Siberian Russia arose in 1990 through a memorandum of understanding between the U.S. Geological Survey and the former Ministry of Geology of the U.S.S.R. The world-class significance of these deposits and the possibility that understanding their geologic context, including construction of a credible 'ore-deposit model,' will lead to discovery of similar deposits elsewhere, inspired extensive studies of the ores, the mafic-intrusions which host them, and associated flood basalts.

  10. The Quality of Different Types of Child Care at 10 and 18 Months: A Comparison between Types and Factors Related to Quality

    ERIC Educational Resources Information Center

    Leach, Penelope; Barnes, Jacqueline; Malmberg, Lars-Erik; Sylva, Kathy; Stein, Alan

    2008-01-01

    The quality of care offered in four different types of non-parental child care to 307 infants at 10 months old and 331 infants at 18 months old was compared and factors associated with higher quality were identified. Observed quality was lowest in nurseries at each age point, except that at 18 months they offered more learning activities. There…

  11. Gastric juice in congenital pernicious anemia contains no immunoreactive intrinsic factor molecule: study of three kindreds with variable ages at presentation, including a patient first diagnosed in adulthood.

    PubMed Central

    Carmel, R

    1983-01-01

    The mechanism responsible for the isolated intrinsic factor deficiency in congenital pernicious anemia is unknown. A new second-antibody radioimmunoassay capable of recognizing intrinsic factor independent of the molecule's ability to bind added cobalamin was used to study six patients from three kindreds with this disorder. One of the patients was first diagnosed at age 23 because of unusual circumstances in her case; yet the other patients also demonstrated great age variability at presentation of this presumably congenital disorder, even within the same kindred. The radioimmunoassay failed to detect immunoreactive intrinsic factor in any of the six patients, suggesting that elaboration of an abnormal molecule was not the pathogenetic mechanism. An unexpected incidental finding, contrasting with this observation in congenital pernicious anemia, was immunologic evidence that a previously described patient with familial R binder deficiency clearly elaborated an abnormal R binder molecule. PMID:6823973

  12. Human factors issues and approaches in the spatial layout of a space station control room, including the use of virtual reality as a design analysis tool

    NASA Technical Reports Server (NTRS)

    Hale, Joseph P., II

    1994-01-01

    Human Factors Engineering support was provided for the 30% design review of the late Space Station Freedom Payload Control Area (PCA). The PCA was to be the payload operations control room, analogous to the Spacelab Payload Operations Control Center (POCC). This effort began with a systematic collection and refinement of the relevant requirements driving the spatial layout of the consoles and PCA. This information was used as input for specialized human factors analytical tools and techniques in the design and design analysis activities. Design concepts and configuration options were developed and reviewed using sketches, 2-D Computer-Aided Design (CAD) drawings, and immersive Virtual Reality (VR) mockups.

  13. Ethnicity-specific obesity cut-points in the development of Type 2 diabetes – a prospective study including three ethnic groups in the United Kingdom

    PubMed Central

    Tillin, T; Sattar, N; Godsland, I F; Hughes, A D; Chaturvedi, N; Forouhi, N G

    2015-01-01

    Aims Conventional definitions of obesity, e.g. body mass index (BMI) ≥ 30 kg/m2 or waist circumference cut-points of 102 cm (men) and 88 cm (women), may underestimate metabolic risk in non-Europeans. We prospectively identified equivalent ethnicity-specific obesity cut-points for the estimation of diabetes risk in British South Asians, African-Caribbeans and Europeans. Methods We studied a population-based cohort from London, UK (1356 Europeans, 842 South Asians, 335 African-Caribbeans) who were aged 40–69 years at baseline (1988–1991), when they underwent anthropometry, fasting and post-load (75 g oral glucose tolerance test) blood tests. Incident Type 2 diabetes was identified from primary care records, participant recall and/or follow-up biochemistry. Ethnicity-specific obesity cut-points in association with diabetes incidence were estimated using negative binomial regression. Results Diabetes incidence rates (per 1000 person years) at a median follow-up of 19 years were 20.8 (95% CI: 18.4, 23.6) and 12.0 (8.3, 17.2) in South Asian men and women, 16.5 (12.7, 21.4) and 17.5 (13.0, 23.7) in African-Caribbean men and women, and 7.4 (6.3, 8.7), and 7.2 (5.3, 9.8) in European men and women. For incidence rates equivalent to those at a BMI of 30 kg/m2 in European men and women, age- and sex-adjusted cut-points were: South Asians, 25.2 (23.4, 26.6) kg/m2; and African-Caribbeans, 27.2 (25.2, 28.6) kg/m2. For South Asian and African-Caribbean men, respectively, waist circumference cut-points of 90.4 (85.0, 94.5) and 90.6 (85.0, 94.5) cm were equivalent to a value of 102 cm in European men. Waist circumference cut-points of 84.0 (74.0, 90.0) cm in South Asian women and 81.2 (71.4, 87.4) cm in African-Caribbean women were equivalent to a value of 88 cm in European women. Conclusions In prospective analyses, British South Asians and African-Caribbeans had equivalent diabetes incidence rates at substantially lower obesity levels than the conventional European cut

  14. Taxonomy of two endemic Indian skinks, Eutropis bibronii (Gray, 1838)
    and E. nagarjunensis (Sharma, 1969) (Reptilia: Scincidae), including redescriptions of their types.

    PubMed

    Amarasinghe, A A Thasun; Campbell, Patrick D; Chandramouli, S R; Deuti, Kaushik; Raha, Sujoy; Karunarathna, D M S Suranjan; Ineich, Ivan

    2016-01-01

    Tiliqua bibronii was described by J.E. Gray in December, 1838 based on two syntypes (MNHN-RA 2940, 7076), but the details for locality was missing. These syntypes are currently housed at the Muséum national d'Histoire naturelle, Paris, France (MNHN-RA). The same species (based on the same type specimens) was described by A.M.C. Duméril & G. Bibron in November, 1839 nearly one year after Gray's publication. As such, Gray's publication must therefore be given priority. Another species, Euprepis trilineatus, from Madras, Tamil Nadu, India, was described by Gray in 1846, and it is morphologically similar to E. bibronii. Later, Boulenger (1885) synonymised it with E. bibronii. Eutropis bibronii has subsequently been recorded from other parts of India and Sri Lanka by various authors. Many years later, a closely related species, Mabuya nagarjuni (sic) Sharma, 1969, was described from Andhra Pradesh, India, based on two specimens (a holotype and a paratype) housed at the Zoological Survey of India, Kolkata (ZSI). Here we make a correction for the species epithet as "nagarjunensis" which should be a toponym, not a patronym. Among the skink collections at the Natural History Museum, London (BMNH), ZSI, and MNHN-RA we found E. bibronii specimens collected from various locations in India, but we were unable to find any specimens from Sri Lanka. Based on morphological evidence, E. bibronii represents a single, fairly widespread, species which has to be considered endemic to India. Although, recent phylogenetic studies reveal a distinct genetic divergence between E. bibronii and E. nagarjunensis, both species are morphologically very similar to each other. Here, we examine the morphology of E. nagarjunensis based on the ZSI specimens. A comprehensive comparison between the syntypes of E. bibronii and Euprepis trilineatus confirms that the latter nomen is a junior synonym of the former. The original description of E. bibronii is extremely concise and lacks most of the

  15. Cardiovascular Risk Factors Increase the Risks of Diabetic Peripheral Neuropathy in Patients With Type 2 Diabetes Mellitus

    PubMed Central

    Yang, Chun-Pai; Lin, Cheng-Chieh; Li, Chia-Ing; Liu, Chiu-Shong; Lin, Wen-Yuan; Hwang, Kai-Lin; Yang, Sing-Yu; Chen, Hsuan-Ju; Li, Tsai-Chung

    2015-01-01

    Abstract This study aimed to examine whether poor glycemic control, measured by glycated hemoglobin A1C (HbA1c) and other cardiovascular risk factors, can predict diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes mellitus (DM). Patients aged ≥30 years with type 2 DM, enrolled in the National Diabetes Care Management Program, and free of DPN (n = 37,375) in the period 2002 to 2004 were included and followed up until 2011. The related factors were analyzed using Cox proportional hazards regression models. For an average follow-up of 7.00 years, 8379 cases of DPN were identified, with a crude incidence rate of 32.04/1000 person-years. After multivariate adjustment, patients with HbA1c levels 7 to 8%, 8 to 9%, 9 to 10%, and ≥10% exhibited higher risk of DPN (adjusted HR: 1.11 [1.04–1.20], 1.30 [1.21–1.40], 1.32 [1.22–1.43], and 1.62 [1.51–1.74], respectively) compared with patients with HbA1c level 6 to 7%. There was a significant linear trend in DPN incidence with increasing HbA1c (P < 0.001) and significant HRs of DPN for patients with HbA1c level ≥7%, blood pressure ≥130/85 mm Hg, triglycerides (TG) ≥150 mg/dL, high density of lipoprotein-cholesterol (HDL-C) <40 mg/dL in males and <50 mg/dL in females, low density of lipoprotein-cholesterol (LDL-C) ≥100 mg/dL, and estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Patients with type 2 DM and HbA1c ≥7.0% exhibit increased risk of DPN, demonstrating a linear relationship. The incidence of DPN is also associated with poor glucose control and cardiovascular risk factors like hypertension, hyper-triglyceridemia, low HDL-C, high LDL-C, and decreased eGFR. PMID:26496307

  16. Cold Heat Storage Characteristics of O/W-type Latent Heat Emulsion Including Continuum Phase of Water Treated with a Freezing Point Depression

    NASA Astrophysics Data System (ADS)

    Inaba, Hideo; Morita, Shin-Ichi

    This paper deals with flow and cold heat storage characteristics of the oil (tetradecane, C14H30, freezing point 278.9 K, Latent heat 229 kJ/kg)/water emulsion as a latent heat storage material having a low melting point. The test emulsion includes a water-urea solution as a continuum phase. The freezing point depression of the continuum phase permits enhancement of the heat transfer rate of the emulison, due to the large temperature difference between the latent heat storage material and water-urea solution. The velocity of emulsion flow and the inlet temperature of coolant in a coiled double tube heat exchanger are chosen as the experimental parameters. The pressure drop, the heat transfer coefficient of the emulsion in the coiled tube are measured in the temperture region over solid and liquid phase of the latent heat storage material. The finishing time of the cold heat storage is defined experimentally in the range of sensible and latent heat storage. It is clarified that the flow behavior of the emulsion as a non-Newtonian fluid has an important role in cold heat storage. The useful nondimentional correlation equations for the additional pressure loss coefficient, the heat transfer coefficient and the finishing time of the cold heat storage are derived in terms of Dean number and heat capacity ratio.

  17. Genomic markers of panitumumab resistance including ERBB2/HER2 in a phase II study of KRAS wild-type (wt) metastatic colorectal cancer (mCRC)

    PubMed Central

    Barry, Garrett S.; Cheang, Maggie C.; Chang, Hector Li; Kennecke, Hagen F.

    2016-01-01

    A prospective study was conducted to identify biomarkers associated with resistance to panitumumab monotherapy in patients with metastatic colorectal cancer (mCRC). Patients with previously treated, codon 12/13 KRAS wt, mCRC were prospectively administered panitumumab 6 mg/kg IV q2weeks. Of 34 panitumumab-treated patients, 11 (32%) had progressive disease at 8 weeks and were classified as non-responders. A Nanostring nCounter-based assay identified a 5-gene expression signature (ERBB2, MLPH, IRX3, MYRF, and KLK6) associated with panitumumab resistance (P = 0.001). Immunohistochemistry and in situ hybridization determined that the HER2 (ERBB2) protein was overexpressed in 4/11 non-responding and 0/21 responding cases (P = 0.035). Two non-responding tumors had ERBB2 gene amplification only, and one demonstrated both ERBB2 amplification and mutation. A non-codon 12/13 KRAS mutation occurred in one panitumumab-resistant patient and was mutually exclusive with ERBB2/HER2 abnormalities. This study identifies a 5-gene signature associated with non-response to single agent panitumumab, including a subgroup of non-responders with evidence of aberrant ERBB2/HER2 signaling. KRAS wt tumors resistant to EGFRi may be identified by gene signature analysis, and the HER2 pathway plays an important role in resistance to therapy. PMID:26980732

  18. Hypovitaminosis D: a novel risk factor for coronary heart disease in type 2 diabetes?

    PubMed

    Muscogiuri, Giovanna; Nuzzo, Vincenzo; Gatti, Adriano; Zuccoli, Alfonso; Savastano, Silvia; Di Somma, Carolina; Pivonello, Rosario; Orio, Francesco; Colao, Annamaria

    2016-02-01

    Vitamin D (25(OH)D) levels have been associated with cardiovascular disease. Thus, the aim of our study was to investigate the association of 25(OH)D levels with coronary heart disease (CHD) in 698 consecutive type 2 diabetic outpatients. 698 consecutive type 2 diabetic outpatients (25.2 % men, age 66 ± 9 years) and 100 (90 % men, age 65 ± 13 years) age-matched non-diabetic volunteers were enrolled. 25(OH)D assay and the main cardiovascular risk factors were explored. 25(OH)D concentration was 22 ± 10 ng/ml in control subjects and 18.23 ± 10 ng/ml in diabetic patients (p < 0.01). The prevalence of hypovitaminosis D was higher in diabetic patients than in control subjects (90 vs. 83 %, p < 0.01). Diabetic subjects with hypovitaminosis D had higher prevalence of high values of A1C (p < 0.01), BMI (p < 0.01), LDL cholesterol (p < 0.01), triglycerides (p < 0.01), and glycemia (p < 0.01) than their vitamin D-sufficient counterparts. 25(OH)D and HDL cholesterol were lower (p < 0.01), while BMI (p < 0.01), age (p < 0.01), systolic (p < 0.01) and diastolic blood pressure (p < 0.01), diabetes duration (p < 0.01), A1C (p < 0.01), glycemia (p < 0.01), fibrinogen (p < 0.01), triglycerides (p < 0.01), and total (p < 0.01) and LDL cholesterol (p < 0.01) were higher in diabetic subjects with CHD than diabetic subjects without CHD. At the logistic regression analysis, the association of vitamin D with CHD was lost, while sex (p = 0.026), diabetes duration (p = 0.023), and age (p = 0.024) were the most powerful predictors of CHD. The current study demonstrates that 25(OH)D does not have a direct effect on CHD but may have an indirect effect mediated by cardiovascular risk factors such as diabetes duration, age, and sex. PMID:25931413

  19. Risk Factors Associated with Different Types of Intimate Partner Violence (IPV): An Emergency Department Study

    PubMed Central

    Bazargan-Hejazi, Shahrzad; Kim, Eunjin; Lin, Johnny; Ahmadi, Alireza; Khamesi, Mojdeh T; Teruya, Stacey

    2014-01-01

    Background Domestic intimate partner violence (IPV) is a serious healthcare concern, which may be mitigated by early detection, screening and intervention. Objectives We examine posited predictors in IPV and non-IPV groups, and in four different IPV profiles. Possible factors include a) alcohol use, b) drug use, d) depression, e) impulsivity, f) age, and g) any childhood experience in observing parental violence. We also introduce a new “Five Steps in Screening for IPV” quick reference tool, which may assist ED physicians in detection and treatment. Methods This was a cross-sectional study using survey data from 412 inner-city ED patients. Associations were explored using a chi-squared test of independence, independent-samples t-tests, and a one way analysis of variance. Results Nearly 16% had experienced IPV. As a group, they were younger, and more depressed and impulsive than the non-IPV group. They were more likely to engage in binge drinking, use drugs, and had more childhood exposure to violence. In the IPV group, 31% were perpetrators, 20% victims, and 49% both victims and perpetrators. The latter group was younger, more impulsive and depressed, used drugs, and was more likely to have observed parental violence as a child. Conclusion Correlates in groups affected by IPV indicate the same general risk factors, which appear to more acutely affect those who are both perpetrators and victims. Alcohol and drug use, depressive symptoms and childhood exposure to violence may be factors and signs for which emergency physicians should screen in the context of IPV. PMID:25281170

  20. Constitutively Active MAVS Inhibits HIV-1 Replication via Type I Interferon Secretion and Induction of HIV-1 Restriction Factors

    PubMed Central

    Gupta, Sachin; Termini, James M.; Issac, Biju; Guirado, Elizabeth; Stone, Geoffrey W.

    2016-01-01

    Type I interferon is known to inhibit HIV-1 replication through the induction of interferon stimulated genes (ISG), including a number of HIV-1 restriction factors. To better understand interferon-mediated HIV-1 restriction, we constructed a constitutively active form of the RIG-I adapter protein MAVS. Constitutive MAVS was generated by fusion of full length MAVS to a truncated form of the Epstein Barr virus protein LMP1 (ΔLMP1). Supernatant from ΔLMP1-MAVS-transfected 293T cells contained high levels of type I interferons and inhibited HIV replication in both TZM-bl and primary human CD4+ T cells. Supernatant from ΔLMP1-MAVS-transfected 293T cells also inhibited replication of VSV-G pseudotyped single cycle SIV in TZM-bl cells, suggesting restriction was post-entry and common to both HIV and SIV. Gene array analysis of ΔLMP1-MAVS-transfected 293T cells and trans-activated CD4+ T cells showed significant upregulation of ISG, including previously characterized HIV restriction factors Viperin, Tetherin, MxB, and ISG56. Interferon blockade studies implicated interferon-beta in this response. In addition to direct viral inhibition, ΔLMP1-MAVS markedly enhanced secretion of IFN-β and IL-12p70 by dendritic cells and the activation and maturation of dendritic cells. Based on this immunostimulatory activity, an adenoviral vector (Ad5) expressing ΔLMP1-MAVS was tested as a molecular adjuvant in an HIV vaccine mouse model. Ad5-Gag antigen combined with Ad5-ΔLMP1-MAVS enhanced control of vaccinia-gag replication in a mouse challenge model, with 4/5 animals showing undetectable virus following challenge. Overall, ΔLMP1-MAVS is a promising reagent to inhibit HIV-1 replication in infected tissues and enhance vaccine-mediated immune responses, while avoiding toxicity associated with systemic type I interferon administration. PMID:26849062

  1. Impact of environmental factors and biological soil crust types on soil respiration in a desert ecosystem.

    PubMed

    Feng, Wei; Zhang, Yuqing; Jia, Xin; Wu, Bin; Zha, Tianshan; Qin, Shugao; Wang, Ben; Shao, Chenxi; Liu, Jiabin; Fa, Keyu

    2014-01-01

    The responses of soil respiration to environmental conditions have been studied extensively in various ecosystems. However, little is known about the impacts of temperature and moisture on soils respiration under biological soil crusts. In this study, CO2 efflux from biologically-crusted soils was measured continuously with an automated chamber system in Ningxia, northwest China, from June to October 2012. The highest soil respiration was observed in lichen-crusted soil (0.93 ± 0.43 µmol m-2 s-1) and the lowest values in algae-crusted soil (0.73 ± 0.31 µmol m-2 s-1). Over the diurnal scale, soil respiration was highest in the morning whereas soil temperature was highest in the midday, which resulted in diurnal hysteresis between the two variables. In addition, the lag time between soil respiration and soil temperature was negatively correlated with the soil volumetric water content and was reduced as soil water content increased. Over the seasonal scale, daily mean nighttime soil respiration was positively correlated with soil temperature when moisture exceeded 0.075 and 0.085 m3 m-3 in lichen- and moss-crusted soil, respectively. However, moisture did not affect on soil respiration in algae-crusted soil during the study period. Daily mean nighttime soil respiration normalized by soil temperature increased with water content in lichen- and moss-crusted soil. Our results indicated that different types of biological soil crusts could affect response of soil respiration to environmental factors. There is a need to consider the spatial distribution of different types of biological soil crusts and their relative contributions to the total C budgets at the ecosystem or landscape level. PMID:25050837

  2. Functional alterations of type I insulin-like growth factor receptor in placenta of diabetic rats.

    PubMed Central

    Hauguel-de Mouzon, S; Louizeau, M; Girard, J

    1992-01-01

    The presence of type I insulin-like growth factor (IGF-I) receptors on placental membranes led to the hypothesis that these receptors might play a critical role in the rapid growth of this organ. Diabetes induces feto-placental overgrowth, but it is not known whether it modifies IGF-I receptor activity in fetal and/or placental tissues. To answer this question, we have partially purified and characterized placental receptors from normal and streptozotocin-induced diabetic rats. In normal rats, binding of 125I-IGF-I to a 140 kDa protein corresponding to the alpha subunit of the receptor was observed in cross-linking experiments performed under reducing conditions. Stimulation by IGF-I induces the autophosphorylation of a 105 kDa phosphoprotein representing the beta subunit of the receptor. In rats made hyperglycaemic and insulinopenic by streptozotocin injection on day 1 of pregnancy, placental IGF-I receptor-binding parameters were not different from controls on day 20 of pregnancy. In contrast, the autophosphorylation and kinase activity of IGF-I receptors of diabetic rats were increased 2-3-fold in the basal state and after IGF-I stimulation. The present study indicates that the rat placental IGF-I receptor possesses structural characteristics similar to that reported for fetal-rat muscle, and suggests that the high-molecular-mass beta subunit could represent a type of receptor specifically expressed during prenatal development. In addition, it clearly demonstrates that diabetes induces functional alterations in IGF-I receptor kinase activity that may play a major role in the placental overgrowth in diabetic pregnancy. Images Fig. 1 Fig. 3 Fig. 5 PMID:1445271

  3. Vascular oxidative stress upregulates angiotensin II type I receptors via mechanisms involving nuclear factor kappa B.

    PubMed

    Bhatt, Siddhartha R; Lokhandwala, Mustafa F; Banday, Anees Ahmad

    2014-01-01

    Abstract The association of oxidative stress with hypertension is well known. However, a causal role of oxidative stress in hypertension is unclear. Vascular angiotensin II type 1 receptor (AT1R) upregulation is a prominent contributor to pathogenesis of hypertension. However, the mechanisms causing this upregulation are unknown. Oxidative stress is an important regulator of protein expression via activation of transcription factors such as nuclear factor kappa B (NFκB). The present study was carried out to test the hypothesis that oxidative stress contributes to vascular AT1R upregulation via NFκB in human aortic smooth muscle cells (HASMC) and spontaneously hypertensive rats (SHR). HASMC exposed to oxidative stress exhibited a robust increase in AT1R mRNA in HASMC. Furthermore, oxidative stress failed to upregulate AT1Rs in the presence of either an antioxidant catalase or siRNA against p65 subunit of NFκB. To test the role of oxidative stress and NFκB in hypertension, prehypertensive SHR were treated with NFκB inhibitor pyrrolidine dithiocarbamate from 5 weeks to 11-12 weeks of age. At 11-12 weeks of age, SHR exhibited increased NFκB expression, AT1R upregulation and exaggerated Ang II-induced vasoconstriction as compared to age-matched Wistar Kyoto (WKY) rats. PDTC treatment of SHR lowered NFκB expression, normalized AT1R expression and Ang II-induced vasoconstriction. More importantly, PDTC treatment significantly attenuated hypertension development in SHR. In conclusion, vascular oxidative can upregulate AT1R, via mechanisms involving NFκB, and contribute to the development of hypertension. PMID:25198883

  4. Health-risk behaviors among a sample of US pre- adolescents: Types, frequency, and predictive factors

    PubMed Central

    Riesch, Susan K.; Kedrowski, Karen; Brown, Roger L.; Temkin, Barbara Myers; Wang, Kevin; Henriques, Jeffrey; Jacobson, Gloria; Giustino-Kluba, Nina

    2012-01-01

    Background Children as young as 10 years old report curiosity and participation in health-risk behaviors, yet most studies focus upon adolescent samples. Objective To document the types and frequencies of health risk behavior among pre-adolescents and to examine the child, family, and environment factors that predict them. Method A sample of 297 pre-adolescents (mean age = 10.5, SD = 0.6) from two Midwestern US cities and their parents (child-parent dyads) provided data about demographic characteristics, health risk behavior participation, child self-esteem, child pubertal development, child and adult perception of their neighborhood, and parent monitoring. Their participation was at intake to a 5-year clustered randomized controlled trial. Results Pre-adolescents participated in an average of 3.7 health-risk behaviors (SD = 2.0), primarily those that lead to unintentional (helmet and seatbelt use) and intentional (feeling unsafe, having something stolen, and physical fighting) injury. Factors predictive of unintentional injury risk behavior were self-esteem, pubertal development, parent monitoring, and parent perception of the neighborhood environment. Boys were 1.8 times less likely than girls to use helmets and seatbelts. Pre-adolescents whose parents were not partnered were 2.8 times more likely than pre-adolescents whose parents were partnered to report intentional risk behavior. Recommendations These data demonstrate trends that cannot be ignored. We recommend, focused specifically upon boys and non-partnered families, that (a) developmentally-appropriate, appealing prevention messages be developed and delivered for parents and pre-adolescents and community interventions targeting both parent and pre-adolescent together be provided to help them establish and monitor behavioral expectations and (b) organized nursing endorse policy in the US and globally that assures adequate family environments for children. PMID:23177901

  5. Etiopathogenesis of type 1 diabetes mellitus: prognostic factors for the evolution of residual β cell function

    PubMed Central

    2009-01-01

    Type 1A diabetes mellitus (T1ADM) is a progressive autoimmune disease mediated by T lymphocytes with destruction of beta cells. Up to now, we do not have precise methods to assess the beta cell mass, "in vivo" or "ex-vivo". The studies about its genetic susceptibility show strong association with class II antigens of the HLA system (particularly DQ). Others genetics associations are weaker and depend on the population studied. A combination of precipitating events may occur at the beginning of the disease. There is a silent loss of immune-mediated beta cells mass which velocity has an inverse relation with the age, but it is influenced by genetic and metabolic factors. We can predict the development of the disease primarily through the determination of four biochemically islet auto antibodies against antigens like insulin, GAD65, IA2 and Znt8. Beta cell destruction is chronically progressive but at clinical diagnosis of the disease a reserve of these cells still functioning. The goal of secondary disease prevention is halt the autoimmune attack on beta cells by redirecting or dampening the immune system. It is remains one of the foremost therapeutic goals in the T1ADM. Glycemic intensive control and immunotherapeutic agents may preserve beta-cell function in newly diagnosed patients with T1ADM. It may be assessed through C-peptide values, which are important for glycemic stability and for the prevention of chronic complications of this disease. This article will summarize the etiopathogenesis mechanisms of this disease and the factors can influence on residual C-peptide and the strategies to it preservation. PMID:19961609

  6. The conjectured S-type retrograde planet in ν Octantis: more evidence including four years of iodine-cell radial velocities

    NASA Astrophysics Data System (ADS)

    Ramm, D. J.; Nelson, B. E.; Endl, M.; Hearnshaw, J. B.; Wittenmyer, R. A.; Gunn, F.; Bergmann, C.; Kilmartin, P.; Brogt, E.

    2016-08-01

    We report 1212 radial-velocity (RV) measurements obtained in the years 2009-2013 using an iodine cell for the spectroscopic binary ν Octantis (K1 III/IV). This system (a_{bin} ˜ 2.6 au, P ˜ 1050 d) is conjectured to have a Jovian planet with a semimajor axis half that of the binary host. The extreme geometry only permits long-term stability if the planet is in a retrograde orbit. Whilst the reality of the planet (P ˜ 415 d) remains uncertain, other scenarios (stellar variability or apsidal motion caused by a yet unobserved third star) continue to appear substantially less credible based on cross-correlation function bisectors, line-depth ratios and many other independent details. If this evidence is validated but the planet is disproved, the claims of other planets using RVs will be seriously challenged. We also describe a significant revision to the previously published RVs and the full set of 1437 RVs now encompasses nearly 13 yr. The sensitive orbital dynamics allow us to constrain the 3D architecture with a broad prior probability distribution on the mutual inclination, which with posterior samples obtained from an N-body Markov chain Monte Carlo is found to be 152.5°±^{0.7}_{0.6}. None of these samples are dynamically stable beyond 106 yr. However, a grid search around the best-fitting solution finds a region that has many models stable for 107 yr, and includes one model within 1σ that is stable for at least 108 yr. The planet's exceptional nature demands robust independent verification and makes the theoretical understanding of its formation a worthy challenge.

  7. The conjectured S-type retrograde planet in ν Octantis: more evidence including four years of iodine-cell radial velocities

    NASA Astrophysics Data System (ADS)

    Ramm, D. J.; Nelson, B. E.; Endl, M.; Hearnshaw, J. B.; Wittenmyer, R. A.; Gunn, F.; Bergmann, C.; Kilmartin, P.; Brogt, E.

    2016-08-01

    We report 1212 radial-velocity (RV) measurements obtained in the years 2009-2013 using an iodine cell for the spectroscopic binary nu Octantis (K1III/IV). This system (a_bin~2.6 au, P~1050 days) is conjectured to have a Jovian planet with a semi-major axis half that of the binary host. The extreme geometry only permits long-term stability if the planet is in a retrograde orbit. Whilst the reality of the planet (P~415 days) remains uncertain, other scenarios (stellar variability or apsidal motion caused by a yet unobserved third star) continue to appear substantially less credible based on CCF bisectors, line-depth ratios and many other independent details. If this evidence is validated but the planet is disproved, the claims of other planets using RVs will be seriously challenged. We also describe a significant revision to the previously published RVs and the full set of 1437 RVs now encompasses nearly 13 years. The sensitive orbital dynamics allow us to constrain the three-dimensional architecture with a broad prior probability distribution on the mutual inclination, which with posterior samples obtained from an N-body Markov chain Monte Carlo is found to be 158.4 +/- 1.2 deg. None of these samples are dynamically stable beyond 1 Myr. However, a grid search around the best-fitting solution finds a region that has many models stable for 10 Myr, and includes one model within 1-sigma that is stable for at least 100 Myr. The planet's exceptional nature demands robust independent verification and makes the theoretical understanding of its formation a worthy challenge.

  8. Competitive binding of viral E2 protein and mammalian core-binding factor to transcriptional control sequences of human papillomavirus type 8 and bovine papillomavirus type 1.

    PubMed Central

    Schmidt, H M; Steger, G; Pfister, H

    1997-01-01

    The promoter P7535 of human papillomavirus type 8 and the promoter P7185 of bovine papillomavirus type 1 are negatively regulated by viral E2 proteins via the promoter proximal binding sites P2 and BS1, respectively. Mutations of these E2 binding sites can reduce basal promoter activity. This suggests binding of a transcription-stimulating factor and may indicate that repression by E2 is due to competitive binding of viral and cellular proteins. A computer search revealed putative binding sites for core-binding factor (CBF; also referred to as PEA2, PEBP2, or AML), overlapping with P2 and BS1. Binding of recombinant CBF proteins to these sites was confirmed by band shift analysis. Competition of CBF and E2 protein for DNA binding was shown for both human papillomavirus type 8 and bovine papillomavirus type 1. The importance of CBF-E2 competition in E2-mediated repression could be demonstrated by comparing the E2 effect on P7185 activity in two cell lines containing different amounts of endogenous CBF. In cells with large amounts of CBF, E2 repressed P7185 wild-type constructs to the basal promoter activity of a mutant (50%) that could not bind this protein any more. In contrast, in a cell line containing small amounts of CBF, the promoter activities of constructs with wild-type and mutated CBF binding sites hardly differed and specific repression by E2 was not detectable. PMID:9311900

  9. Impact of Modifiable Risk Factors on B-type Natriuretic Peptide and Cardiac Troponin T Concentrations.

    PubMed

    Srivastava, Pratyaksh K; Pradhan, Aruna D; Cook, Nancy R; Ridker, Paul M; Everett, Brendan M

    2016-02-01

    Alcohol use, physical activity, diet, and cigarette smoking are modifiable cardiovascular risk factors that have a substantial impact on the risk of myocardial infarction, stroke, and cardiovascular death. We hypothesized that these behaviors may alter concentrations of cardiac troponin, a marker of myocyte injury, and B-type natriuretic peptide, a marker of myocyte stress. Both markers have shown strong association with adverse cardiovascular outcomes. In 519 women with no evidence of cardiovascular disease, we measured circulating concentrations of cardiac troponin T, using a high-sensitivity assay (hsTnT), and the N-terminal fragment of B-type natriuretic peptide (NT-proBNP). We used logistic regression to determine if these behaviors were associated with hsTnT ≥ 3 ng/l or with NT-proBNP in the highest quartile (≥ 127.3 ng/l). The median (Q1 to Q3) NT-proBNP of the cohort was 68.8 ng/l (40.3 to 127.3 ng/l), and 30.8% (160 of 519) of the cohort had circulating hsTnT ≥ 3 ng/l. In adjusted models, women who drank 1 to 6 drinks/week had lower odds of having a hsTnT ≥ 3 ng/l (odds ratio 0.58, 95% confidence interval 0.34 to 0.96) and lower odds of having an elevated NT-proBNP (odds ratio 0.55, 95% confidence interval 0.32 to 0.96). We were subsequently able to validate the results for B-type natriuretic peptide in a large independent cohort. In conclusion, our results suggest that regular alcohol consumption is associated with lower concentrations of hsTnT and NT-proBNP, 2 cardiovascular biomarkers associated with cardiovascular risk, and raise the hypothesis that the beneficial effects of alcohol consumption may be mediated by direct effects on the myocardium. PMID:26739393

  10. Regulation of type II transforming-growth-factor-beta receptors by protein kinase C iota.

    PubMed Central

    Chuang, Lea-Yea; Guh, Jinn-Yuh; Liu, Shu-Fen; Hung, Min-Yuan; Liao, Tung-Nan; Chiang, Tai-An; Huang, Jau-Shyang; Huang, Yu-Lun; Lin, Chi-Fong; Yang, Yu-Lin

    2003-01-01

    TGF-beta (transforming growth factor-beta) is implicated in the pathogenesis of diabetic nephropathy. We previously demonstrated that up-regulation of type II TGF-beta receptor (TbetaRII) induced by high glucose might contribute to distal tubular hypertrophy [Yang, Guh, Yang, Lai, Tsai, Hung, Chang and Chuang (1998) J. Am. Soc. Nephrol. 9, 182-193]. We have elucidated the mechanism by using cultured Madin-Darby canine kidney cells. Enhancer assay and electrophoretic-mobility-shift assay were used to estimate the involvement of transcription factors. Western blotting and an in vitro kinase assay were used to evaluate the level and activity of protein kinase. We showed that glucose (100-900 mg/dl) induced an increase in mRNA level and promoter activity of TbetaRII (note: 'mg/dl' are the units commonly used in diabetes studies). The promoter region -209 to -177 appeared to contribute to positive transactivation of TbetaRII promoter by comparing five TbetaRII-promoter-CAT (chloramphenicol acetyl-transferase) plasmids. Moreover, the transcription factor AP-1 (activator protein 1) was significantly activated and specifically binds to TbetaRII promoter (-209 to -177). More importantly, we found that atypical PKC iota might be pivotal for high glucose-induced increase in both AP-1 binding and TbetaRII promoter activity. First, high glucose induced cytosolic translocation, activation and autophosphorylation of PKC iota. Secondly, antisense PKC iota expression plasmids attenuated high-glucose-induced increase in AP-1 binding and TbetaRII promoter activity; moreover, sense PKC iota expression plasmids enhanced these instead. Finally, we showed that antisense PKC iota expression plasmids might partly attenuate a high-glucose/TGF-beta1-induced increase in fibronectin. We conclude that PKC iota might mediate high-glucose-induced increase in TbetaRII promoter activity. In addition, antisense PKC iota expression plasmid effectively suppressed up-regulation of TbetaRII and

  11. Patient and surgery related factors associated with fatigue type polyethylene wear on 49 PCA and DURACON retrievals at autopsy and revision

    PubMed Central

    Rohrbach, Markus; Lüem, Martin; Ochsner, Peter E

    2008-01-01

    Background Polyethylene wear is an important factor for longevity of total knee arthroplasty. Proven and suspicious factors causing wear can be grouped as material, patient and surgery related. There are more studies correlating design and/or biomaterial factors to in vivo wear than those to patient and surgery related factors. Many retrieval studies just include revision implants and therefore may not be representative. This study is aimed to correlate patient- and surgery- related factors to visual wear score by minimizing design influence and include both autopsy and revision implants. Comparison between the groups was expected to unmask patient and surgery-related factors responsible for wear. Methods The amount of joint side wear on polyethylene retrievals was measured using a modification of an established visual wear score. Fatigue type wear was defined as summation of the most severe wear modes of delamination, pitting and cracks. Analysis of patient and surgery related variables suspicious to cause wear included prospectively sampled patient activity which was measured by self reported walking capacity. Statistical analysis was done by univariate analysis of variance. Activity level and implantation time were merged to an index of use and correlated to the wear score. Results Wear score after comparable implantation time was significantly less in the autopsy group. Even so, fatigue type wear accounted for 84 and 93 % of total wear score on autopsy and revision implants respectively. A highly significant influence on wear score was found in time of implantation (p = 0.002), level of activity (p = 0.025) and inserts belonging to revision group (p = 0.006). No influence was found for the kind of patella replacement (p = 0.483). Body mass index and accuracy of component alignment had no significant influence on visual wear score. Fatigue-type wear in the medial compartment was closely correlated to the index of use in the autopsy (R2 = 0.383) and the revision

  12. Increased circulating concentrations of mesencephalic astrocyte-derived neurotrophic factor in children with type 1 diabetes.

    PubMed

    Galli, Emilia; Härkönen, Taina; Sainio, Markus T; Ustav, Mart; Toots, Urve; Urtti, Arto; Yliperttula, Marjo; Lindahl, Maria; Knip, Mikael; Saarma, Mart; Lindholm, Päivi

    2016-01-01

    Mesencephalic astrocyte-derived neurotrophic factor (MANF) was recently shown to be essential for the survival and proliferation of pancreatic β-cells in mice, where deletion of MANF resulted in diabetes. The current study aimed at determining whether the concentration of circulating MANF is associated with the clinical manifestation of human type 1 diabetes (T1D). MANF expression in T1D or MANF levels in serum have not been previously studied. We developed an enzyme-linked immunosorbent assay (ELISA) for MANF and measured serum MANF concentrations from 186 newly diagnosed children and adolescents and 20 adults with longer-term T1D alongside with age-matched controls. In healthy controls the mean serum MANF concentration was 7.0 ng/ml. High MANF concentrations were found in children 1-9 years of age close to the diagnosis of T1D. The increased MANF concentrations were not associated with diabetes-predictive autoantibodies and autoantibodies against MANF were extremely rare. Patients with conspicuously high MANF serum concentrations had lower C-peptide levels compared to patients with moderate MANF concentrations. Our data indicate that increased MANF concentrations in serum are associated with the clinical manifestation of T1D in children, but the exact mechanism behind the increase remains elusive. PMID:27356471

  13. Increased circulating concentrations of mesencephalic astrocyte-derived neurotrophic factor in children with type 1 diabetes

    PubMed Central

    Galli, Emilia; Härkönen, Taina; Sainio, Markus T.; Ustav, Mart; Toots, Urve; Urtti, Arto; Yliperttula, Marjo; Lindahl, Maria; Knip, Mikael; Saarma, Mart; Lindholm, Päivi

    2016-01-01

    Mesencephalic astrocyte-derived neurotrophic factor (MANF) was recently shown to be essential for the survival and proliferation of pancreatic β-cells in mice, where deletion of MANF resulted in diabetes. The current study aimed at determining whether the concentration of circulating MANF is associated with the clinical manifestation of human type 1 diabetes (T1D). MANF expression in T1D or MANF levels in serum have not been previously studied. We developed an enzyme-linked immunosorbent assay (ELISA) for MANF and measured serum MANF concentrations from 186 newly diagnosed children and adolescents and 20 adults with longer-term T1D alongside with age-matched controls. In healthy controls the mean serum MANF concentration was 7.0 ng/ml. High MANF concentrations were found in children 1–9 years of age close to the diagnosis of T1D. The increased MANF concentrations were not associated with diabetes-predictive autoantibodies and autoantibodies against MANF were extremely rare. Patients with conspicuously high MANF serum concentrations had lower C-peptide levels compared to patients with moderate MANF concentrations. Our data indicate that increased MANF concentrations in serum are associated with the clinical manifestation of T1D in children, but the exact mechanism behind the increase remains elusive. PMID:27356471

  14. Factors in the Design of Centrifugal Type Injection Valves for Oil Engines

    NASA Technical Reports Server (NTRS)

    Joachim, W F; Beardsley, E G

    1928-01-01

    This research was undertaken in connection with a general study of the application of the fuel injection engine to aircraft. The purpose of the investigation was to determine the effect of four important factors in the design of a centrifugal type automatic injection valve on the penetration, general shape, and distribution of oil sprays. The general method employed was to record the development of single sprays by means of special high-speed photographic apparatus capable of taking 25 consecutive pictures of the moving spray at a rate of 4,000 per second. Investigations were made concerning the effects on spray characteristics, of the helix angle of helical grooves, the ratio of the cross-sectional area of the orifice to that of the grooves, the ratio of orifice length to diameter, and the position of the seat. Maximum spray penetration was obtained with a ratio of orifice length to diameter of about 1.5. Slightly greater penetration was obtained with the seat directly before the orifice.

  15. Conserved Ser residues in the basic region of the bZIP-type transcription factor HBP-1a(17): importance in DNA binding and possible targets for phosphorylation.

    PubMed

    Meshi, T; Moda, I; Minami, M; Okanami, M; Iwabuchi, M

    1998-01-01

    HBP-1a(17) is representative of a group of plant bZIP-type transcription factors which includes HBP-1a proteins and G-box-binding factors. We found kinase activity in wheat nuclear extract that phosphorylated HBP-1a(17). Experiments using recombinant HBP-1a(17) derivatives as substrates revealed that all three of the Ser residues in the basic region, Ser-261, Ser-265, and Ser-269, were phosphorylated in a Ca(2+)-stimulated manner. DNA-binding analysis of mutants with a Ser-to-Glu change, prepared to mimic the phosphorylated proteins, indicated that introduction of a negative charge at position 265 or 269 prevents HBP-1a(17) from binding DNA not only in the homodimer of mutants but also in heterodimers with a wild-type protein. It is therefore suggested that the phosphorylation regulates the function of HBP-1a(17) at least at the level of DNA binding. Since Ser-265 and Ser-269 are highly conserved among the plant bZIP-type factors known to date, a common Ca(2+)-mediated regulatory mechanism may exert an effect on the bZIP-type factors through phosphorylation of these conserved Ser residues. PMID:9484468

  16. The seal tuberculosis agent, Mycobacterium pinnipedii, infects domestic cattle in New Zealand: epidemiologic factors and DNA strain typing.

    PubMed

    Loeffler, Scott H; de Lisle, Geoffrey W; Neill, Mark A; Collins, Desmond M; Price-Carter, Marian; Paterson, Brent; Crews, Kevin B

    2014-04-01

    The fur seal (Arctocephalus forsteri), which is abundant in coastal areas of New Zealand, harbors several zoonotic pathogens, including Mycobacterium pinnipedii, a member of the Mycobacterium tuberculosis complex. We describe the microbiology and epidemiology of seven cases of M. pinnipedii infection in beef cattle (Bos primigenius) in coastal areas of New Zealand in 1991-2011. Epidemiologic factors were analyzed on six case farms and a telephone survey of 55 neighboring farms. A DNA-strain typing, using analysis of variable number tandem repeats and the direct repeats (VNTR/DR) of those isolates, was used to compare them to M. bovis isolates commonly found in New Zealand cattle and wildlife. In all cases of M. pinnipedii in cattle, only one animal in the herd was found to be infected. In six of seven cases, the lesions were in the thoracic lymph nodes, indicating a likely aerosol pathway. The lack of multiple cases within a herd suggests that cow-to-cow transmission is uncommon, if it occurs at all. There was no significant difference between case and control farms in distance to sea, herd size, herd type, or farming practice. The odds ratio for access to the beach for cattle on the Chatham Islands was significantly higher than it was for farms on the mainland coastal areas (odds ratio [OR] = 3.6, 95% CI = 1.1-11.4) Likewise, the odds ratio for acquiring tuberculosis was increased when farmers had seen seals on the property (OR =  9, 95% CI = 1.4-56.1 ). In all case farms, cattle had access to seals by beach grazing areas or waterways connecting directly with the ocean. The VNTR/DR typing of the isolates showed some variation in the M. pinnipedii isolates, with only two being identical; all isolates were easily distinguishable from M. bovis isolates. PMID:24484478

  17. A Mouse Model for Chikungunya: Young Age and Inefficient Type-I Interferon Signaling Are Risk Factors for Severe Disease

    PubMed Central

    Disson, Olivier; Brigitte, Madly; Guivel-Benhassine, Florence; Touret, Yasmina; Barau, Georges; Cayet, Nadège; Schuffenecker, Isabelle; Desprès, Philippe; Arenzana-Seisdedos, Fernando; Michault, Alain

    2008-01-01

    Chikungunya virus (CHIKV) is a re-emerging arbovirus responsible for a massive outbreak currently afflicting the Indian Ocean region and India. Infection from CHIKV typically induces a mild disease in humans, characterized by fever, myalgia, arthralgia, and rash. Cases of severe CHIKV infection involving the central nervous system (CNS) have recently been described in neonates as well as in adults with underlying conditions. The pathophysiology of CHIKV infection and the basis for disease severity are unknown. To address these critical issues, we have developed an animal model of CHIKV infection. We show here that whereas wild type (WT) adult mice are resistant to CHIKV infection, WT mouse neonates are susceptible and neonatal disease severity is age-dependent. Adult mice with a partially (IFN-α/βR+/−) or totally (IFN-α/βR−/−) abrogated type-I IFN pathway develop a mild or severe infection, respectively. In mice with a mild infection, after a burst of viral replication in the liver, CHIKV primarily targets muscle, joint, and skin fibroblasts, a cell and tissue tropism similar to that observed in biopsy samples of CHIKV-infected humans. In case of severe infections, CHIKV also disseminates to other tissues including the CNS, where it specifically targets the choroid plexuses and the leptomeninges. Together, these data indicate that CHIKV-associated symptoms match viral tissue and cell tropisms, and demonstrate that the fibroblast is a predominant target cell of CHIKV. These data also identify the neonatal phase and inefficient type-I IFN signaling as risk factors for severe CHIKV-associated disease. The development of a permissive small animal model will expedite the testing of future vaccines and therapeutic candidates. PMID:18282093

  18. Identification of Bacterial Factors Involved in Type 1 Fimbria Expression using an Escherichia coli K12 Proteome Chip*

    PubMed Central

    Chen, Yi-Wen; Teng, Ching-Hao; Ho, Yu-Hsuan; Jessica Ho, Tien Yu; Huang, Wen-Chun; Hashimoto, Masayuki; Chiang, I-Yuan; Chen, Chien-Sheng

    2014-01-01

    Type 1 fimbriae are filamentous structures on Escherichia coli. These structures are important adherence factors. Because binding to the host cells is the first step of infection, type 1 fimbria is an important virulence factor of pathogenic E. coli. Expression of type 1 fimbria is regulated by a phase variation in which each individual bacterium can alternate between fimbriated (phase-ON) and nonfimbriated (phase-OFF) states. The phase variation is regulated by the flipping of the 314-bp fimS fragment, which contains the promoter driving the expression of the genes required for the synthesis of type 1 fimbria. Thus, the bacterial proteins able to interact with fimS are likely to be involved in regulating the expression of type 1 fimbria. To identify novel type 1 fimbria-regulating factors, we used an E. coli K12 proteome chip to screen for the bacterial factors able to interact with a 602-bp DNA fragment containing fimS and its adjacent regions. The Spr protein was identified by the proteome chip-based screening and further confirmed to be able to interact with fimS by electrophoretic mobility shift assay. Deletion of spr in the neonatal meningitis E. coli strain RS218 significantly increased the ratio of the bacterial colonies that contained the type 1 fimbria phase-ON cells on agar plates. In addition, Spr interfered with the interactions of fimS with the site-specific recombinases, FimB and FimE, which are responsible for mediating the flipping of fimS. These results suggest that Spr is involved in the regulation of type 1 fimbria expression through direct interaction with the invertible element fimS. These findings facilitate our understanding of the regulation of type 1 fimbria. PMID:24692643

  19. Apocynin Attenuates Cardiac Injury in Type 4 Cardiorenal Syndrome via Suppressing Cardiac Fibroblast Growth Factor-2 With Oxidative Stress Inhibition

    PubMed Central

    Liu, Yang; Liu, Yu; Liu, Xun; Chen, Jie; Zhang, Kun; Huang, Feifei; Wang, Jing-Feng; Tang, Wanchun; Huang, Hui

    2015-01-01

    Background Type 4 cardiorenal syndrome (CRS) refers to the cardiac injury induced by chronic kidney disease. We aimed to assess oxidative stress and cardiac injury in patients with type 4 CRS, determine whether the antioxidant apocynin attenuated cardiac injury in rats with type 4 CRS, and explore potential mechanisms. Methods and Results A cross-sectional study was conducted among patients with type 4 CRS (n=17) and controls (n=16). Compared with controls, patients with type 4 CRS showed elevated oxidative stress, which was significantly correlated with cardiac hypertrophy and decreased ejection fraction. In vivo study, male Sprague-Dawley rats underwent 5/6 subtotal nephrectomy and sham surgery, followed with apocynin or vehicle treatment for 8 weeks. Eight weeks after surgery, the 5/6 subtotal nephrectomy rats mimicked type 4 CRS, showing increased serum creatinine, cardiac hypertrophy and fibrosis, and decreased ejection fraction compared with sham-operated animals. Cardiac malondialdehyde, NADPH oxidase activity, fibroblast growth factor-2, and extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation increased significantly in the 5/6 subtotal nephrectomy rats. These changes were significantly attenuated by apocynin. In vitro study showed that apocynin reduced angiotensin II–induced NADPH oxidase–dependent oxidative stress, upregulation of fibroblast growth factor-2 and fibrosis biomarkers, and ERK1/2 phosphorylation in cardiac fibroblasts. Importantly, the ERK1/2 inhibitor U0126 reduced the upregulation of fibroblast growth factor-2 and fibrosis biomarkers in angiotensin II–treated fibroblasts. Conclusions Oxidative stress is a candidate mediator for type 4 CRS. Apocynin attenuated cardiac injury in type 4 CRS rats via inhibiting NADPH oxidase–dependent oxidative stress-activated ERK1/2 pathway and subsequent fibroblast growth factor-2 upregulation. Our study added evidence to the beneficial effect of apocynin in type 4 CRS. PMID:26109504

  20. Factors associated with early adoption of the HPV vaccine in US male adolescents include Hispanic ethnicity and receipt of other vaccines.

    PubMed

    Kepka, Deanna; Ding, Qian; Hawkins, Amy J; Warner, Echo L; Boucher, Kenneth M

    2016-12-01

    Adolescent males' HPV vaccine initiation and completion in the United States is far below the Healthy People 2020 goal of 80% 3-dose completion among boys. In 2012, less than 7% of males ages 13-17 years had completed the 3-dose series. The Diffusion of Innovations framework guided this investigation of factors related to early adoption of HPV vaccination among male adolescents. Provider-validated data from the 2012 National Immunization Survey-Teen (NIS-Teen) for male adolescents ages 13-17 years were analyzed via a multivariable Poisson regression to estimate prevalence ratios for factors associated with HPV vaccine initiation and completion. Adolescent males who are Hispanic and those who are up to date on other recommended adolescent vaccinations were most likely to complete the HPV vaccine. Public health interventions are needed to improve low HPV vaccination rates among adolescent males in the United States. Description of early adopters of the HPV vaccine provides historical context of HPV vaccination acceptance that is needed to inform the design of targeted vaccination interventions to prevent negative HPV-associated outcomes. PMID:27413668

  1. Risk factor for ischemic-type biliary lesion after ABO-incompatible living donor liver transplantation

    PubMed Central

    Bang, Jun Bae; Kim, Bong-Wan; Kim, Young Bae; Wang, Hee-Jung; Lee, Hyun Yeong; Sim, Joohyun; Kim, Taegyu; Lee, Kyeong Lok; Hu, Xu-Guang; Mao, Wei

    2016-01-01

    AIM: To evaluate the risk factors for ischemic-type biliary lesion (ITBL) after ABO-incompatible (ABO-I) adult living donor liver transplantation (ALDLT). METHODS: Among 141 ALDLTs performed in our hospital between 2008 and 2014, 27 (19%) were ABO-I ALDLT and 114 were ABO-identical/compatible ALDLT. In this study, we extensively analyzed the clinico-pathological data of the 27 ABO-I recipients to determine the risk factors for ITBL after ABO-I ALDLT. All ABO-I ALDLT recipients underwent an identical B-cell depletion protocol with preoperative rituximab, plasma exchange (PE), and operative splenectomy. The median follow-up period after transplantation was 26 mo. The clinical outcomes of the 27 ABO-I ALDLT recipients were compared with those of 114 ABO-identical/compatible ALDLT recipients. RESULTS: ITBL occurred in four recipients (14.8%) between 45 and 112 d after ABO-I ALDLT. The overall survival rates were not different between ABO-I ALDLT and ABO-identical/compatible ALDLT (P = 0.303). Among the ABO-I ALDLT recipients, there was no difference between patients with ITBL and those without ITBL in terms of B-cell and T-cell count, serum isoagglutinin titers, number of PEs, operative time and transfusion, use of graft infusion therapy, or number of remnant B-cell follicles and plasma cells in the spleen. However, the perioperative NK cell counts in the blood of patients with ITBL were significantly higher than those in the patients without ITBL (P < 0.05). Preoperative NK cell count > 150/μL and postoperative NK cell count > 120/μL were associated with greater relative risks (RR) for development of ITBL (RR = 20 and 14.3, respectively, P < 0.05). CONCLUSION: High NK cell counts in a transplant recipient’s blood are associated with ITBL after ABO-I ALDLT. Further research is needed to elucidate the molecular mechanism of NK cell involvement in the development of ITBL. PMID:27570428

  2. Expression of Recombinant Human Insulin-like Growth Factor Type 1 (rhIGF-1) in Escherichia coli

    PubMed Central

    Iranpoor, Hamidreza; Omidinia, Eskandar; Vatankhah, Venus; Gharanjik, Vahid; Shahbazi, Majid

    2015-01-01

    Background: Human insulin-like growth factor type 1 (hIGF-1) is a protein consisting of 70 amino acids (MW=7.6 kDa) and mainly synthesized by liver. Mecasermin (Trade name INCRELEX) is the synthetic form of the protein which is used as an effective treatment for particular disorders such as short stature, type 1 and 2 diabetes, and wound healing. Current study was aimed to investigate the expression of human insulin-like growth factor type1 in Escherichia coli (E. coli) BL21 (DE3) expression system in order to produce an active recombinant form of the protein. Methods: For the purpose of the study, firstly codon optimization was done for hIGF-1 gene, using bioinformatics databases. Then, the gene was synthesized and inserted in pET-24a vector by a cutting strategy included NdeI and BamHI-HF enzymes. In the next step, gene was run in agarose gel and purified. The constructed expression cassette was transformed into E. coli BL21 (DE3) cells through CaCl 2 heat shock method. Identification and confirmation of the transformed colonies were performed using screening PCR method. Synthesis of hIGF-1 was induced by IPTG. The expression in induced strains was analyzed by SDS-PAGE and western blotting techniques. Confirmation of cloning and IGF-1 expression cassette was carried out through genetic engineering procedures. Results: Analysis of transformed E. coli strain with SDS-PAGE and western blotting techniques confirmed that gene was expressed in host cells. Molecular weight of the expressed protein was estimated to be 7.6 kDa. Conclusion: hIGF-1 expression cassette for cloning and expression in E. coli was designed and the protein of interest was successfully induced and identified. In addition, E. coli BL21 (DE3) can be used as a suitable host for production of recombinant hIGF-1 and this technology has a potential to be localized. PMID:26306149

  3. Effect of Improved Fitness beyond Weight Loss on Cardiovascular Risk Factors in Individuals with Type 2 Diabetes in the Look AHEAD Study

    PubMed Central

    Gibbs, Bethany Barone; Brancati, Frederick L.; Chen, Haiying; Coday, Mace; Jakicic, John M.; Lewis, Cora; Stewart, Kerry J.; Clark, Jeanne M.

    2013-01-01

    Background Because lifestyle-induced improvements in cardiovascular risk factors vary substantially across individuals with type 2 diabetes, we investigated the extent to which increases in fitness explain cardiovascular risk factor improvements independent of weight loss in a lifestyle intervention. Methods We studied 1-year changes in Look AHEAD, a randomized trial comparing an intensive lifestyle intervention (ILI) to a diabetes support and education control group (DSE) in adults with type 2 diabetes. Assessments included weight, fitness, blood pressure (BP), glucose, HbA1c, and lipids. We evaluated the effects of changes in weight and fitness on changes in cardiovascular risk factors by study arm, using R2 from multiple linear regression. Results Analyses included participants with fitness data at baseline and 1-year (n=4,408; 41% male, 36% non-White, mean age 58.7± 6.8 years). Weight change alone improved R2 for explaining changes in risk factors up to 8.2% in ILI and 1.7% in DSE. Fitness change alone improved R2 up to 3.9% in ILI and 0.8% in DSE. After adjusting for weight change, fitness was independently associated (p<0.05) with improvements in R2 for glucose (+0.7%), HbA1c (+1.1 %), HDL cholesterol (+0.4%) and triglycerides (+0.2%) in ILI and DBP (+0.3%), glucose (+0.3%), HbA1c (+0.4%), and triglycerides (+0.1%) in DSE. Taken together, weight and fitness changes explained from 0.1–9.3% of the variability in cardiovascular risk factor changes. Conclusion Increased fitness explained statistically significant but small improvements in several cardiovascular risk factors beyond weight loss. Further research identifying other factors that explain cardiovascular risk factor change is needed. PMID:23012688

  4. An Analysis of Factor Extraction Strategies: A Comparison of the Relative Strengths of Principal Axis, Ordinary Least Squares, and Maximum Likelihood in Research Contexts That Include Both Categorical and Continuous Variables

    ERIC Educational Resources Information Center

    Coughlin, Kevin B.

    2013-01-01

    This study is intended to provide researchers with empirically derived guidelines for conducting factor analytic studies in research contexts that include dichotomous and continuous levels of measurement. This study is based on the hypotheses that ordinary least squares (OLS) factor analysis will yield more accurate parameter estimates than…

  5. Advanced glycation end products as environmental risk factors for the development of type 1 diabetes.

    PubMed

    Yap, Felicia Y T; Kantharidis, Phillip; Coughlan, Melinda T; Slattery, Robyn; Forbes, Josephine M

    2012-04-01

    The globally rising incidence of Type 1 diabetes (T1D) is no longer restricted to individuals with higher risk genotypes, but is now significantly increasing in a population with lower risk genotypes, likely as the result of environmental factors. In this review, we discuss the potential of advanced glycation end products (AGEs) as environmental contributors to the development of T1D. AGEs are nonenzymatically formed protein modifications found in the body, as well as, consumed in our daily diets. To date, many studies have provided evidence of AGE involvement in β cell dysfunction, whether by AGE modification itself or via interaction with AGE receptors. The receptor for AGE (RAGE) and AGE-receptor-1 (AGE-R1) are of particular interest, given that studies have demonstrated the deleterious effects of RAGE modulation and the protection afforded by AGE-R1 in the context of diabetes. More interestingly, we have recently found that two RAGE polymorphism are predictive of T1D in humans while the third is protective. Moreover, soluble RAGE (sRAGE) levels (a circulating competitive inhibitor of RAGE) were greatly reduced at seroconversion to autoantibodies in both children on high risk of T1D background and in an animal model of autoiummune diabetes. Taken together with the fact that AGEs have also shown to be involved in immunomodulation, it is tempting to postulate that dietary AGEs, RAGE and even AGE-R1 could be working synergistically or independently to breach the tightly regulated immune system, providing a missing link in the development of T1D. PMID:22250649

  6. Differential Regulation of Human Papillomavirus Type 8 by Interferon Regulatory Factors 3 and 7▿

    PubMed Central

    Oldak, Monika; Tolzmann, Liv; Wnorowski, Artur; Podgórska, Marta Justyna; Silling, Steffi; Lin, Rongtuan; Hiscott, John; Müller, Cornelia Sigrid Lissi; Vogt, Thomas; Smola, Hans; Smola, Sigrun

    2011-01-01

    The genus β human papillomavirus (HPV) type 8 is associated with nonmelanoma skin cancer in patients with epidermodysplasia verruciformis, and evidence for its protumorigenic potential in the general population increases. To date, strategies to suppress genus β HPV infections are limited. Interferon regulatory factors IRF-3 and IRF-7 play key roles in the activation of the innate immune response to viral infections. In this study, we show for the first time that both IRF-3 and IRF-7 regulate transcription of a papillomavirus, but with opposing effects. IRF-7, expressed in the suprabasal layers of human epidermis, increased HPV8 late promoter activity via direct binding to viral DNA. UV-B light-induced activation of the HPV8 promoter involved IRF-7 as a downstream effector. In contrast, IRF-3, expressed in all layers of human epidermis, induced strong HPV8 suppression in primary keratinocytes. IRF-3-mediated suppression prevailed over IRF-7-induced HPV8 transcription. Unlike the E6 oncoprotein of the mucosal high-risk HPV16, the HPV8 E6 protein did not bind to IRF-3 and only weakly antagonized its activity. Strong antiviral activity was also observed, when keratinocytes were treated with potent IRF-3 activators, poly(I:C) or RNA bearing 5′ phosphates. In conclusion, we show that IRF-3 activation induces a state of cell-autonomous immunity against HPV in primary human keratinocytes. Our study suggests that local application of IRF-3-activating compounds might constitute an attractive novel therapeutic strategy against HPV8-associated diseases, particularly in epidermodysplasia verruciformis patients. PMID:20980500

  7. Serum prolactin concentrations as risk factor of metabolic syndrome or type 2 diabetes?

    PubMed Central

    2013-01-01

    Background To investigate potential associations of serum prolactin concentration (PRL) with metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM), previously observed in small and selected study samples, in a large population-based cohort. Methods Data from 3,993 individuals (2,027 women) aged 20-79 years from the population-based Study of Health of Pomerania (SHIP) were used to analyse cross-sectional and longitudinal associations of PRL with MetS and T2DM risk in age- and multivariable-adjusted Poisson regression models. PRL were log-transformed and modelled as continuous (per standard deviation (SD) increase) and categorical predictor (sex-specific quartiles) variable, separately for men and woman. Results Cross-sectional analyses showed an inverse association between low PRL concentrations and prevalent T2DM risk in men and women after multivariable-adjustment (men: Q1 vs. Q4: relative risk (RR), 1.55; 95% confidence interval (CI), 1.13 – 2.14; women: Q1 vs. Q4: RR, 1.70; 95% CI, 1.10 – 2.62). Likewise, higher PRL concentrations were associated with significantly lower T2DM risk (RR per SD increase in log-PRL: 0.83; 95% CI, 0.72 – 0.95 in men, and 0.84; 95% CI, 0.71 – 0.98 in women, respectively). An inverse association between PRL and MetS risk was not retained after multivariable adjustment. Longitudinal analyses yielded no association of PRL with incident MetS or T2DM. Conclusion The present study is the first large population-based study reporting a cross-sectional inverse association between PRL and prevalent T2DM in both genders. But the absent longitudinal associations do not support a causal role of PRL as a risk factor of incident MetS or T2DM. PMID:23517652

  8. MPZP: a novel small molecule corticotropin-releasing factor type 1 receptor (CRF1) antagonist.

    PubMed

    Richardson, Heather N; Zhao, Yu; Fekete, Eva M; Funk, Cindy K; Wirsching, Peter; Janda, Kim D; Zorrilla, Eric P; Koob, George F

    2008-02-01

    The extrahypothalamic stress peptide corticotropin-releasing factor (CRF) system is an important regulator of behavioral responses to stress. Dysregulation of CRF and the CRF type 1 receptor (CRF(1)) system is hypothesized to underlie many stress-related disorders. Modulation of the CRF(1) system by non-peptide antagonists currently is being explored as a therapeutic approach for anxiety disorders and alcohol dependence. Here, we describe a new, less hydrophilic (cLogP approximately 2.95), small molecule, non-peptide CRF(1) antagonist with high affinity (K(i)=4.9 nM) and specificity for CRF(1) receptors: N,N-bis(2-methoxyethyl)-3-(4-methoxy-2-methylphenyl)-2,5-dimethyl-pyrazolo[1,5-a] pyrimidin-7-amine (MPZP). The compound was systemically administered to adult male rats in two behavioral models dependent on the CRF(1) system: defensive burying (0, 5, 20 mg/kg, n=6-11 for each dose) and alcohol dependence (0, 5, 10, 20 mg/kg, n=8 for each self-administration group). Acute administration of MPZP reduced burying behavior in the defensive burying model of active anxiety-like behavior. MPZP also attenuated withdrawal-induced excessive drinking in the self-administration model of alcohol dependence without affecting nondependent alcohol drinking or water consumption. The present findings support the proposed significance of the CRF(1) system in anxiety and alcohol dependence and introduce a promising new compound for further development in the treatment of alcohol dependence and stress-related disorders. PMID:18031798

  9. Allotyping human complement factor B in Asian Indian type 1 diabetic patients.

    PubMed

    Kumar, N; Kaur, G; Tandon, N; Mehra, N K

    2008-12-01

    Human complement factor B (BF) is an essential component of the alternate complement pathway and therefore important in innate immune and autoimmune responses. The BF gene is located in the central region of major histocompatibility complex (MHC) and is known to encode more than 30 protein variants that can be resolved by isoelectric focusing and gel electrophoresis. There are three BF alleles - BF*S, BF*FB and BF*FA - that differ in codon 7 at nucleotide positions 94 and 95. These alleles have CGG, TGG or CAG triplets at their codon 7, respectively, that code for Arg, Trp or Gln residues. We have developed a novel polymerase chain reaction using sequence-specific primers-based allotyping assay that can identify nucleotide substitutions in codon 7 in all the three BF alleles. The assay was validated by sequencing and amplified fragment length polymorphism. Using this SSP assay, we report the BF alleles located on the multiple human leukocyte antigen (HLA)-DR3 haplotypes that are unique in the Indian population and are associated with autoimmunity. The common type 1 diabetes (T1D)-favoring Caucasian haplotype HLA-A1-B8-DR3 (ancestral haplotype AH8.1) carries BF*S. However, in the North Indian T1D patients, the most common haplotype is HLA-A26-B8-DR3 (AH8.2) and this carried BF*FB. Because of its association with AH8.2, the BF*FB was overrepresented in the patients (51.03%) compared with healthy controls (32.7%, OR = 2.148, 95% CI = 1.34-3.44, P = 0.002). Similar studies on allotyping BF alleles in different haplotypes in various populations could have important implications in understanding mechanisms of MHC haplotypic diversifications and disease associations and designing future therapeutic approaches. PMID:19000152

  10. Risk factors of type-2 diabetes mellitus in rural Wardha: A community based study

    PubMed Central

    Khatib, Nazli M.; Quazi, Zahiruddin S.; Gaidhane, Abhay M.; Waghmare, Trupti S.; Goyal, R. C.

    2008-01-01

    CONTEXT: The rise in diabetes mellitus (DM) portends a disaster of major proportion worldwide. AIM: To study the determinants of type-2 DM in people who are ≥45 years of age by selective screening methodology in rural area of Wardha district. SETTINGS AND DESIGN: A cross-sectional study in a rural area of Wardha district. METHODOLOGY: A cross-sectional population-based study was conducted among those who are at risk of developing DM, as per the WHO guidelines on Laboratory Diagnosis and monitoring of Diabetes Mellitus 2002. Blood glucose estimation was done using a blood glucose meter. STATISTICAL ANALYSIS USED: Multiple Logistic Regression. RESULTS: Eight point four nine percent of the 306 persons above the age of 45 years were diabetic. This study also revealed that the proportion of people diagnosed with DM increases with increasing age groups. Mean fasting and post meal blood glucose level (in mg%) among the study participants (nondiabetics) were 83.6 ± 1.6 and 129.9 ± 1.9 and mean fasting and post meal blood glucose level among diabetics were 138.8 ± 2.1 and 220.7 ± 1.9, respectively. The difference between the post meal blood glucose level among the diabetics and nondiabetics was statistically significant. The proportion of diabetics was more among those who had family history of diabetes (8.6%), BMI more than 25 (24.1%) and those with sedentary lifestyle (10.4%). CONCLUSIONS: Implementation of preventive measures to reduce the burden of diabetes is needed. Identification of the environmental factors adversely related to glucose intolerance helps evolve preventive strategies. PMID:19902039

  11. Response to Therapy and Outcomes in Oropharyngeal Cancer Are Associated With Biomarkers Including Human Papillomavirus, Epidermal Growth Factor Receptor, Gender, and Smoking

    SciTech Connect

    Kumar, Bhavna; Cordell, Kitrina G.; Lee, Julia S.; Prince, Mark E.; Tran, Huong H.; Wolf, Gregory T.; Urba, Susan G.; Worden, Francis P.; Chepeha, Douglas B.; Teknos, Theodoros N.; Eisbruch, Avraham; Tsien, Christina I.; Taylor, Jeremy; D'Silva, Nisha J.; Yang, Kun; Kurnit, David M.; Bradford, Carol R.

    2007-10-01

    Induction chemotherapy and concurrent chemoradiation for responders or immediate surgery for non-responders is an effective treatment strategy head and neck squamous cell carcinoma (HNSCC) of the larynx and oropharynx. Biomarkers that predict outcome would be valuable in selecting patients for therapy. In this study, the presence and titer of high risk human papilloma virus (HPV) and expression of epidermal growth factor receptor (EGFR) in pre-treatment biopsies, as well as smoking and gender were examined in oropharynx cancer patients enrolled in an organ sparing trial. HPV16 copy number was positively associated with response to therapy and with overall and disease specific survival, whereas EGFR expression, current or former smoking behavior, and female gender (in this cohort) were associated with poor response and poor survival in multivariate analysis. Smoking cessation and strategies to target EGFR may be useful adjuncts for therapy to improve outcome in the cases with the poorest biomarker profile.

  12. Progenitor Cell Therapy in a Porcine Acute Myocardial Infarction Model Induces Cardiac Hypertrophy, Mediated by Paracrine Secretion of Cardiotrophic Factors Including TGFβ1

    PubMed Central

    Doyle, Brendan; Sorajja, Paul; Hynes, Brian; Kumar, Arun H.S.; Araoz, Phillip A.; Stalboerger, Paul G.; Miller, Dylan; Reed, Cynthia; Schmeckpeper, Jeffrey; Wang, Shaohua; Liu, Chunsheng; Terzic, Andre; Kruger, David; Riederer, Stephen

    2008-01-01

    Administration of endothelial progenitor cells (EPC) is a promising therapy for post-infarction cardiac repair. However, the mechanisms that underlie apparent beneficial effects on myocardial remodeling are unclear. In a porcine model of acute myocardial infarction, we investigated the therapeutic effects of a mixed population of culture modified peripheral blood mononuclear cells (termed hereafter porcine EPC). Porcine EPC were isolated using methods identical to those previously adopted for harvest of EPC in human cell therapy studies. In addition the therapeutic effects of paracrine factors secreted by these cells was evaluated in vitro and in vivo. Intracoronary injection of autologous porcine EPC was associated with increased infarct territory mass and improved regional ventricular systolic function at 2 months compared to control. Treatment with conditioned media derived from autologous EPC was associated with similar improved effects on infarct territory mass and function. Histologic analysis of the infarct territory revealed significantly increased cardiomyocyte size in EPC and conditioned media treated groups, when compared to controls. A paracrine EPC effect was also verified in a pure myocardial preparation in which cardiomyocytes devoid of fibroblast, neuronal and vascular elements directly responded by increasing cell mass when exposed to the same conditioned media. Analysis of conditioned media revealed elevated levels of TGFβ1 (human 267.3±11.8 pg/ml, porcine 57.1±6.1 pg/ml), a recognized mediator of hypertrophic signaling in the heart. Neutralizing antibodies to TGFβ1 attenuated the pro-hypertrophic effect of conditioned media, and use of recombinant TGFβ1 added to fresh media replicated the pro-hypertrophic effects of conditioned media in vitro. These data demonstrate the potential of paracrine factors secreted from endothelial progenitor cells to induce cardiomyocyte hypertrophy contributing to increased infarct territory LV mass, with

  13. Type 1 diabetes mellitus: psychosocial factors and adjustment of pediatric patient and his/her family. Review.

    PubMed

    Pérez-Marín, Marián; Gómez-Rico, Irene; Montoya-Castilla, Inmaculada

    2015-04-01

    Type 1 diabetes mellitus is the most common chronic endocrine disease in children, with a very low incidence in the first months of life and reaching its peak during puberty (10-15 years old is the age group with the highest incidence at the time of onset). Based on the review of the scientific literature, our objective is to study the main psychosocial factors associated with the adjustment of these pediatric patients and their families. Research underscore the following risk factors: situational (stressful life events), personal (additional physical diseases, low self-esteem, emotional disturbances), and interpersonal (family breakdown and conflicts), and also protection factors (coping strategies, social support, fluent communication). There is a pressing need to deal with the disturbances that affect these diabetic patients and their families, by implementing effective health care psychological interventions that take into account psychosocial factors associated with the course of type 1 diabetes mellitus. PMID:25727829

  14. Postmitotic diversification of olfactory neuron types is mediated by differential activities of the HMG-box transcription factor SOX-2.

    PubMed

    Alqadah, Amel; Hsieh, Yi-Wen; Vidal, Berta; Chang, Chieh; Hobert, Oliver; Chuang, Chiou-Fen

    2015-10-14

    Diversification of neuron classes is essential for functions of the olfactory system, but the underlying mechanisms that generate individual olfactory neuron types are only beginning to be understood. Here we describe a role of the highly conserved HMG-box transcription factor SOX-2 in postmitotic specification and alternative differentiation of the Caenorhabditis elegans AWC and AWB olfactory neurons. We show that SOX-2 partners with different transcription factors to diversify postmitotic olfactory cell types. SOX-2 functions cooperatively with the OTX/OTD transcription factor CEH-36 to specify an AWC "ground state," and functions with the LIM homeodomain factor LIM-4 to suppress this ground state and drive an AWB identity instead. Our findings provide novel insights into combinatorial codes that drive terminal differentiation programs in the nervous system and reveal a biological function of the deeply conserved Sox2 protein that goes beyond its well-known role in stem cell biology. PMID:26341465

  15. Characterization of transforming growth factor-beta (TGF-beta) receptors on BeWo choriocarcinoma cells including the identification of a novel 38-kDa TGF-beta binding glycoprotein.

    PubMed Central

    Mitchell, E J; Lee, K; O'Connor-McCourt, M D

    1992-01-01

    Transforming growth factor-beta (TGF-beta) is a potential mediator of placental trophoblast functions, including differentiation, hormone production, endometrial invasion, and immunosuppression. Equilibrium binding and affinity-labeling assays were used to investigate the binding characteristics of TGF-beta 1 and TGF-beta 2 on an established human choriocarcinoma trophoblastic cell line (BeWo). The equilibrium binding experiments indicated that the BeWo cells exhibited similar average affinities and total number of binding sites for TGF-beta 1 and TGF-beta 2. The Kd values obtained from Scatchard analyses were approximately 65 pM for 125I-TGF-beta 1 and approximately 40 pM for 125I-TGF-beta 2, with 70,000 and 85,000 sites per cell, respectively. Competitive equilibrium binding experiments indicated that TGF-beta 1 and TGF-beta 2 were equipotent (apparent half maximal inhibition [IC50] approximately 70 pM) and that all binding sites were capable of recognizing both isoforms. Affinity-labeling studies with 125I-TGF-beta 1 and 125I-TGF-beta 2 and the chemical cross-linking agent bis(sulfosuccinimidyl)suberate (BS3) revealed a predominant type III/betaglycan receptor, a low level of apparently heterogeneous type I and II receptors and an additional novel 38-kDa TGF-beta binding glycoprotein that was present both under reducing and nonreducing conditions on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Affinity-labeling saturation and competition studies indicated that the type III/betaglycan component appears to have a 7-fold higher capacity for TGF-beta 1 than for -beta 2 yet exhibits a 5- to 10-fold higher affinity for TGF-beta 2 than for -beta 1. The 38-kDa TGF-beta binding component, an N-linked glycoprotein, exhibits a higher affinity for TGF-beta 2 than for -beta 1 that is strikingly similar to that of the type III/betaglycan receptor. This 38-kDa binding protein appears to be upregulated after methotrexate-induced differentiation of the

  16. Increased Melatonin Signaling Is a Risk Factor for Type 2 Diabetes.

    PubMed

    Tuomi, Tiinamaija; Nagorny, Cecilia L F; Singh, Pratibha; Bennet, Hedvig; Yu, Qian; Alenkvist, Ida; Isomaa, Bo; Östman, Bjarne; Söderström, Johan; Pesonen, Anu-Katriina; Martikainen, Silja; Räikkönen, Katri; Forsén, Tom; Hakaste, Liisa; Almgren, Peter; Storm, Petter; Asplund, Olof; Shcherbina, Liliya; Fex, Malin; Fadista, João; Tengholm, Anders; Wierup, Nils; Groop, Leif; Mulder, Hindrik

    2016-06-14

    Type 2 diabetes (T2D) is a global pandemic. Genome-wide association studies (GWASs) have identified >100 genetic variants associated with the disease, including a common variant in the melatonin receptor 1 b gene (MTNR1B). Here, we demonstrate increased MTNR1B expression in human islets from risk G-allele carriers, which likely leads to a reduction in insulin release, increasing T2D risk. Accordingly, in insulin-secreting cells, melatonin reduced cAMP levels, and MTNR1B overexpression exaggerated the inhibition of insulin release exerted by melatonin. Conversely, mice with a disruption of the receptor secreted more insulin. Melatonin treatment in a human recall-by-genotype study reduced insulin secretion and raised glucose levels more extensively in risk G-allele carriers. Thus, our data support a model where enhanced melatonin signaling in islets reduces insulin secretion, leading to hyperglycemia and greater future risk of T2D. The findings also imply that melatonin physiologically serves to inhibit nocturnal insulin release. PMID:27185156

  17. Inadvertent Propagation of Factor VII Deficiency in a Canine Mucopolysaccharidosis Type I Research Breeding Colony

    PubMed Central

    Carlstrom, Lucas P; Jens, Jackie K; Dobyns, Marley E; Passage, Merry; Dickson, Patricia I; Ellinwood, N Matthew

    2009-01-01

    Issues of cost and genetics can result in inbreeding of canine genetic disease colonies. Beagles often are used to maintain such colonies, providing stock for outcrosses. Factor VII (FVII) deficiency is a hemostatic disorder found at increased frequency in beagles and has been characterized at the DNA level. Deficiency of FVII presents obstacles in colonies founded with beagles. An initial finding of a FVII-deficient pup from a longstanding colony prompted us to evaluate FVII deficiency fully in this colony. Current and archival records and tissues were used to reconstruct the colony pedigree, assess the contribution from beagles, and test samples to document the source and frequency of the mutant FVII allele. As part of this study we developed a PCR-based diagnostic assay that was simpler than what was previously available. Pedigree analysis revealed a founder effect implicating beagles that led to high frequency (55%) of the mutant allele. In addition, affected animals were identified. The complete picture of the clinical effect within the colony remains unclear, but unusual neonatal presentations, including hemoabdomen, have occurred in pups affected with FVII deficiency. Use of a PCR-based diagnostic assay to screen all potential beagle breeding stock will prevent similar occurrences of FVII deficiency in future canine research colonies. PMID:19712579

  18. Emotional disorders in patients with different types of pituitary adenomas and factors affecting the diagnostic process.

    PubMed

    Flitsch, J; Spitzner, S; Lüdecke, D K

    2000-01-01

    A prospective study of 48 patients with pituitary adenomas, 19 adenomas causing Cushing's disease, 18 adenomas causing acromegaly, and 11 clinically hormone-inactive adenomas (inactive adenomas), was performed to study emotional disorders occurring before and after transsphenoidal microsurgery. Factors which led to an obvious delay in the diagnostic process were identified. - The tools utilised were an interview and repeated personality assessments. The personality assessments were begun preoperatively and continued for about half a year postoperatively. The interview data, including retrospective statements regarding somatic difficulties, was analysed. - The thesis of a uniform psychopathology due to the influence of elevated hormone levels, and a lack in patients' sensitivity towards their changed appearance in acromegaly could not be confirmed. A high variability of reported emotional problems was found. The most common psychopathological signs for Cushing's disease were excitability and depression, for acromegaly fatigue/loss of energy was the most frequent complaint. Six to eight months postoperatively, a majority of patients noticed an increase of physical well-being. In acromegaly, the time span between first consultation and diagnosis averaged 6.2 years, in Cushing's disease it was 4.3 years, and in inactive adenomas it was 3.9 years. Only a small part of the delay in diagnosis, less than two years, could be attributed to the patients' hesitation to consult a physician. PMID:11083069

  19. The significance of relative dose intensity in adjuvant chemotherapy of pancreatic ductal adenocarcinoma-including the analysis of clinicopathological factors influencing relative dose intensity.

    PubMed

    Yabusaki, Norimitsu; Fujii, Tsutomu; Yamada, Suguru; Murotani, Kenta; Sugimoto, Hiroyuki; Kanda, Mitsuro; Nakayama, Goro; Koike, Masahiko; Fujiwara, Michitaka; Kodera, Yasuhiro

    2016-07-01

    Recently, it has been reported that the relative dose intensity (RDI) of adjuvant chemotherapy (AC) influences survival in various cancers, but there are very few reports about RDI in pancreatic ductal adenocarcinoma (PDAC). The optimal timing for initiation of AC for PDAC also remains unknown. The aim of this study was to identify the significance of RDI and the time interval between surgery and initiation of AC on survival of patients with PDAC. Clinicopathological factors that affect RDI were also investigated.A total of 311 consecutive PDAC patients who underwent curative resection between May 2005 and January 2015 were enrolled. Patients who underwent neoadjuvant chemoradiation, had UICC stage IV disease, or had early recurrences within 6 months were excluded, and the remaining 168 cases were analyzed.Patients with RDIs ≥80% (n = 79) showed significantly better overall survival (OS) compared to patients with RDIs <80% (n = 55) (median survival time (MST): 45.6 months, 26.0 months, P < 0.001). Patients with no AC (n = 34) showed the worst OS (MST: 20.8 months). Whether the AC was initiated earlier or later than 8 weeks after surgery did not influence survival, either in patients with RDIs ≥80% (P = 0.79) or in those with <80% (P = 0.73). Patients in the S-1 monotherapy group (n = 49) showed significantly better OS than patients in the gemcitabine monotherapy group (n = 51) (MST: 95.0 months, 26.0 months, respectively; P = 0.001). Univariate analysis conducted after adjusting for the chemotherapeutic drug used identified several prognostic factors; male gender (P = 0.01), intraoperative blood transfusion (P = 0.005), lymph node metastasis (P = 0.03), and postoperative WBC count (P = 0.03). Multivariate analysis identified intra-plus postoperative blood transfusion (P = 0.002) and high postoperative platelet-to-lymphocyte ratios (PLR) (P = 0.04) as independent predictors of poor RDI.Efforts to

  20. Kynurenine Pathway Pathologies: do Nicotinamide and Other Pathway Co-Factors have a Therapeutic Role in Reduction of Symptom Severity, Including Chronic Fatigue Syndrome (CFS) and Fibromyalgia (FM).

    PubMed

    Blankfield, Adele

    2013-01-01

    The definition of dual tryptophan pathways has increased the understanding of the mind-body, body-mind dichotomy. The serotonergic pathway highlights the primary (endogenous) psychiatric disorders. The up-regulation of the kynurenine pathway by physical illnesses can cause neuropathic and immunological disorders1 associated with secondary neuropsychiatric symptoms. Tryptophan and nicotinamide deficiencies fall within the protein energy malnutrition (PEM) spectrum. They can arise if the kynurenine pathway is stressed by primary or secondary inflammatory conditions and the consequent imbalance of available catabolic/anabolic substrates may adversely influence convalescent phase efficiency. The replacement of depleted or reduced NAD+ levels and other cofactors can perhaps improve the clinical management of these disorders. Chronic fatigue syndrome (CFS) and fibromyalgia (FM) appear to meet the criteria of a tryptophan-kynurenine pathway disorder with potential neuroimmunological sequelae. Aspects of some of the putative precipitating factors have been previously outlined.2,3 An analysis of the areas of metabolic dysfunction will focus on future directions for research and management. PMID:23922501

  1. Diethylnitrosamine-induced expression of germline-specific genes and pluripotency factors, including vasa and oct4, in medaka somatic cells.

    PubMed

    Shen, Jialing; Yokota, Shinpei; Yokoi, Hayato; Suzuki, Tohru

    2016-09-16

    Various methods have been developed to reprogram mammalian somatic cells into pluripotent cells as well as to directly reprogram somatic cells into other cell lineages. We are interested in applying these methods to fish, and here, we examined whether mRNA expression of germline-specific genes (vasa, nanos2, -3) and pluripotency factors (oct4, sox2, c-myc, nanog) is inducible in somatic cells of Japanese medaka (Oryzias latipes). We found that the expression of vasa is induced in the gut and regenerating fin by exposure to a carcinogen, diethylnitrosamine (DEN). Induction of vasa in the gut started on the 5th day of treatment with >50 ppm DEN. In addition, nanos2, -3, oct4, sox2, klf4, c-myc, and nanog were also expressed simultaneously in some vasa-positive gut and regenerating fin samples. Vasa-positive cells were detected by immunohistochemistry (IHC) in the muscle surrounding the gut and in the wound epidermis, blastema, and fibroblast-like cells in regenerating fin. In vasa:GFP transgenic medaka, green fluorescent protein (GFP) fluorescence appeared in the wound epidermis and fibroblast-like cells in the regenerating fin following DEN exposure, in agreement with the IHC data. Our data show that mRNA expression of genes relevant to germ cell specification and pluripotency can be induced in fish somatic cells by exposure to DEN, suggesting the possibility of efficient and rapid cell reprogramming of fish somatic cells. PMID:27514449

  2. Translationally Invariant Calculations of Form Factors, Densities and Momentum Distributions for Finite Nuclei with Short-Range Correlations Included: A Fresh Look

    NASA Astrophysics Data System (ADS)

    Shebeko, A.; Grigorov, P.; Iurasov, V.

    2014-08-01

    The approach proposed in the 70s (Dementiji et al. in Sov J Nucl Phys 22:6-9, 1976), when describing the elastic and inelastic electron scattering off 4 He, and elaborated in (Shebeko et al.in Eur Phys J A27:143-155, 2006) for calculations of the one-body, two-body and more complex density matrices of finite bound systems has been applied (Shebeko and Grigorov in Ukr J Phys 52:830-842, 2007; Shebeko et al. in Eur. Phys. J. A48:153-172, 2012) in studying a combined effect of the center-of-mass motion and nucleon-nucleon short-range correlations on the nucleon density and momentum distributions in light nuclei beyond the independent particle model. Unlike a common practice, suitable for infinite bound systems, these distributions are determined as expectation values of appropriate intrinsic operators that depend upon the relative coordinates and momenta (Jacobi variables) and act on the intrinsic ground-state wave functions (WFs). The latter are constructed in the so-called fixed center-of-mass approximation, starting with a mean-field Slater determinant modified by some correlator (e.g., after Jastrow or Villars). Our numerical calculations of the charge form factors ( F CH ( q)), densities and momentum distributions have been carried out for nuclei 4 He and 16 O choosing, respectively, the 1 s and 1 s-1 p Slater determinants of the harmonic oscillator model as trial, nontranslationally invariant WFs.

  3. Kynurenine Pathway Pathologies: do Nicotinamide and Other Pathway Co-Factors have a Therapeutic Role in Reduction of Symptom Severity, Including Chronic Fatigue Syndrome (CFS) and Fibromyalgia (FM)

    PubMed Central

    Blankfield, Adele

    2013-01-01

    The definition of dual tryptophan pathways has increased the understanding of the mind-body, body-mind dichotomy. The serotonergic pathway highlights the primary (endogenous) psychiatric disorders. The up-regulation of the kynurenine pathway by physical illnesses can cause neuropathic and immunological disorders1 associated with secondary neuropsychiatric symptoms. Tryptophan and nicotinamide deficiencies fall within the protein energy malnutrition (PEM) spectrum. They can arise if the kynurenine pathway is stressed by primary or secondary inflammatory conditions and the consequent imbalance of available catabolic/anabolic substrates may adversely influence convalescent phase efficiency. The replacement of depleted or reduced NAD+ levels and other cofactors can perhaps improve the clinical management of these disorders. Chronic fatigue syndrome (CFS) and fibromyalgia (FM) appear to meet the criteria of a tryptophan-kynurenine pathway disorder with potential neuroimmunological sequelae. Aspects of some of the putative precipitating factors have been previously outlined.2,3 An analysis of the areas of metabolic dysfunction will focus on future directions for research and management. PMID:23922501

  4. Human Campylobacteriosis in Luxembourg, 2010–2013: A Case-Control Study Combined with Multilocus Sequence Typing for Source Attribution and Risk Factor Analysis

    PubMed Central

    Mossong, Joël; Mughini-Gras, Lapo; Penny, Christian; Devaux, Anthony; Olinger, Christophe; Losch, Serge; Cauchie, Henry-Michel; van Pelt, Wilfrid; Ragimbeau, Catherine

    2016-01-01

    Campylobacteriosis has increased markedly in Luxembourg during recent years. We sought to determine which Campylobacter genotypes infect humans, where they may originate from, and how they may infect humans. Multilocus sequence typing was performed on 1153 Campylobacter jejuni and 136 C. coli human strains to be attributed to three putative animal reservoirs (poultry, ruminants, pigs) and to environmental water using the asymmetric island model. A nationwide case-control study (2010–2013) for domestic campylobacteriosis was also conducted, including 367 C. jejuni and 48 C. coli cases, and 624 controls. Risk factors were investigated by Campylobacter species, and for strains attributed to different sources using a combined case-control and source attribution analysis. 282 sequence types (STs) were identified: ST-21, ST-48, ST-572, ST-50 and ST-257 were prevailing. Most cases were attributed to poultry (61.2%) and ruminants (33.3%). Consuming chicken outside the home was the dominant risk factor for both Campylobacter species. Newly identified risk factors included contact with garden soil for either species, and consuming beef specifically for C. coli. Poultry-associated campylobacteriosis was linked to poultry consumption in wintertime, and ruminant-associated campylobacteriosis to tap-water provider type. Besides confirming chicken as campylobacteriosis primary source, additional evidence was found for other reservoirs and transmission routes. PMID:26860258

  5. Interleukin-10- and Transforming Growth Factor β-Independent Regulation of CD8+ T Cells Expressing Type 1 and Type 2 Cytokines in Human Lymphatic Filariasis

    PubMed Central

    Anuradha, Rajamanickam; George, Parakkal Jovvian; Kumaran, Paul; Nutman, Thomas B.

    2014-01-01

    Lymphatic filariasis is known to be associated with diminished CD4+ Th1 and elevated CD4+ Th2 responses to parasite-specific antigens. The roles of cytokine-expressing CD8+ T cells in immune responses to filarial infections are not well defined. To study the roles of CD8+ T cells expressing type 1, type 2, and type 17 cytokines in filarial infections, we examined the frequencies of these cells in clinically asymptomatic, patently infected (INF) individuals, directly ex vivo and in response to parasite or nonparasite antigens; these frequencies were compared with the results for individuals with filarial lymphedema (i.e., clinical pathology [CP]) and those without active infection or pathology (i.e., endemic normal [EN]). INF individuals exhibited significant decreases in the frequencies of CD8+ T cells expressing tumor necrosis factor alpha (TNF-α), gamma interferon (IFN-γ), and interleukin-22 (IL-22) at baseline and/or in response to filarial antigens, compared with CP and EN individuals. In contrast, the same individuals exhibited significant increases in the frequencies of CD8+ T cells expressing IL-4, IL-5, IL-9, IL-13, and IL-21, compared with CP and/or EN individuals. Curative treatment resulted in significantly increased frequencies of CD8+ T cells expressing IL-2 and significantly decreased frequencies of CD8+ T cells expressing type 2 cytokines. Finally, the regulation of these responses appears to be independent of IL-10 and transforming growth factor β (TGF-β), since blockade of IL-10 or TGF-β signaling did not significantly alter the frequencies of type 1 or type 2 cytokine-expressing CD8+ T cells. Our findings suggest that alterations in the frequencies of cytokine-expressing CD8+ T cells are characteristic features of lymphatic filarial infections. PMID:25253667

  6. Heparin-binding growth factor type 1 (acidic fibroblast growth factor): a potential biphasic autocrine and paracrine regulator of hepatocyte regeneration.

    PubMed Central

    Kan, M; Huang, J S; Mansson, P E; Yasumitsu, H; Carr, B; McKeehan, W L

    1989-01-01

    Heparin-binding growth factor type 1 (HBGF-1; sometimes termed acidic fibroblast growth factor) is potentially an important factor in liver regeneration. HBGF-1 alone (half-maximal effect at 60 pM) stimulated hepatocyte DNA synthesis and bound to a high-affinity receptor (Kd = 62 pM; 5000 per cell). Epidermal growth factor (EGF) neutralized or masked the mitogenic effect of HBGF-1 concurrent with appearance of low-affinity HBGF-1 binding sites. HBGF-1 reduced the inhibitory effect of transforming growth factor type beta (TGF-beta) on the EGF stimulus. Nanomolar levels of HBGF-1 decreased the EGF stimulus. An increase in hepatic HBGF-1 gene expression after partial hepatectomy precedes increases in expression of the EGF homolog, TGF-alpha, and nonparenchymal-cell-derived TGF-beta in the regenerating liver. Expression of HBGF-1 mRNA occurs in both hepatocytes and nonparenchymal cells and persists for 7 days in liver tissue after partial hepatectomy. HBGF-1 acting through a high-affinity receptor is a candidate for the early autocrine stimulus that drives hepatocyte DNA synthesis prior to or concurrent with the EGF/TGF-alpha stimulus. It may allow hepatocyte proliferation to proceed in the presence of low levels of TGF-beta. An EGF/TGF-alpha-dependent change in HBGF-1 receptor phenotype and increasing levels of nonparenchymal-cell-derived HBGF-1 and TGF-beta may serve to limit hepatocyte proliferation. Images PMID:2477840

  7. Assignment of human transforming growth factor-{beta} type I and type III receptor genes (TGFBR1 and TGFBR3) to 9q33-q34 and 1p32-p33, respectively

    SciTech Connect

    Johnson, D.W.; Qumsiyeh, M.; Marchuk, D.A.; Benkhalifa, M.

    1995-07-20

    Transforming growth factor-{Beta} (TGF-{beta}) is a multifunctional cytokine, known to modulate several tissue development and repair processes, including cell differentiation, cell cycle progression, cellular migration, adhesion, and extracellular matrix production. The TGF-{beta} receptors and cell surface binding proteins mediate the diverse effects of TGF-{beta}. An endothelial cell-specific TGF-{beta} binding protein, endoglin, is mutated in hereditary hemorrhagic telangiectasia type 1, an autosomal dominant disorder of vascular dysplasia. Mutations in other TGF-{beta} binding protein genes may also lead to disease. We have used PCR with a cell hybrid DNA panel, and fluorescence in situ chromosomal hybridization (FISH), to localize two other TGF-{beta} receptor genes. These are the TGF-{beta} type I and type II receptors (also known as ALK-5 and betaglycan, respectively). The corresponding gene loci are designated TGFBR1 and TGFBR3. 10 refs., 1 fig., 1 tab.

  8. TIL-type protease inhibitors may be used as targeted resistance factors to enhance silkworm defenses against invasive fungi.

    PubMed

    Li, Youshan; Zhao, Ping; Liu, Huawei; Guo, Xiaomeng; He, Huawei; Zhu, Rui; Xiang, Zhonghuai; Xia, Qingyou

    2015-02-01

    Entomopathogenic fungi penetrate the insect cuticle using their abundant hydrolases. These hydrolases, which include cuticle-degrading proteases and chitinases, are important virulence factors. Our recent findings suggest that many serine protease inhibitors, especially TIL-type protease inhibitors, are involved in insect resistance to pathogenic microorganisms. To clarify the molecular mechanism underlying this resistance to entomopathogenic fungi and identify novel genes to improve the silkworm antifungal capacity, we conducted an in-depth study of serine protease inhibitors. Here, we cloned and expressed a novel silkworm TIL-type protease inhibitor, BmSPI39. In activity assays, BmSPI39 potently inhibited the virulence protease CDEP-1 of Beauveria bassiana, suggesting that it might suppress the fungal penetration of the silkworm integument by inhibiting the cuticle-degrading proteases secreted by the fungus. Phenol oxidase activation studies showed that melanization is involved in the insect immune response to fungal invasion, and that fungus-induced excessive melanization is suppressed by BmSPI39 by inhibiting the fungal cuticle-degrading proteases. To better understand the mechanism involved in the inhibition of fungal virulence by protease inhibitors, their effects on the germination of B. bassiana conidia was examined. BmSPI38 and BmSPI39 significantly inhibited the germination of B. bassiana conidia. Survival assays showed that BmSPI38 and BmSPI39 markedly improved the survival rates of silkworms, and can therefore be used as targeted resistance proteins in the silkworm. These results provided new insight into the molecular mechanisms whereby insect protease inhibitors confer resistance against entomopathogenic fungi, suggesting their potential application in medicinal or agricultural fields. PMID:25453359

  9. Basal and postprandial change in serum fibroblast growth factor-21 concentration in type 1 diabetic mellitus and in healthy controls.

    PubMed

    Zibar, Karin; Blaslov, Kristina; Bulum, Tomislav; Ćuća, Jadranka Knežević; Smirčić-Duvnjak, Lea

    2015-04-01

    Fibroblast growth factor-21 (FGF-21) appears to have an important role in glucose and lipid metabolism. FGF-21 secretion is mainly determined by nutritional status. The aim of this study was to measure basal and postprandial FGF-21 and postprandial change of FGF-21 concentration in type 1 diabetes mellitus (T1DM) patients and in healthy controls, and to investigate the differences between the groups. The cross-sectional study included 30 C-peptide negative T1DM patients, median age 37 years (20-59), disease duration 22 years (3-45), and nine healthy controls, median age 30 years (27-47). Basal and postprandial FGF-21 concentrations were measured by ELISA. The associations of FGF-21 with glucose, lipids, and insulin were analyzed. Individuals with T1DM showed significantly lower basal FGF-21 concentration (P=0.046) when compared with healthy controls (median value 28.2 vs 104 pg/mL) and had significantly different postprandial change (∆ 30'-0') of FGF-21 (P=0.006) in comparison with healthy controls (median value -1.1 vs -20.5 pg/mL). The glucose and lipid status did not correlate with FGF-21. In healthy controls, postprandial insulin level correlated with basal FGF-21 (ρ=0.7, P=0.036). Multiple regression analysis showed that they are independently associated after adjustment for confounding factors (β=1.824, P=0.04). We describe the pathological pattern of basal and postprandial change of FGF-21 secretion not associated with glucose, lipid levels, or insulin therapy in patients with T1DM. Since FGF-21 has numerous protective metabolic effects in the experimental model, the lower basal FGF-21 concentration in T1DM patients opens the question about the potential role of recombinant FGF-21 therapy. PMID:25194937

  10. Type II PI4-kinases control Weibel-Palade body biogenesis and von Willebrand factor structure in human endothelial cells

    PubMed Central

    Lopes da Silva, Mafalda; O'Connor, Marie N.; Kriston-Vizi, Janos; White, Ian J.; Al-Shawi, Raya; Simons, J. Paul; Mössinger, Julia; Haucke, Volker

    2016-01-01

    ABSTRACT Weibel-Palade bodies (WPBs) are endothelial storage organelles that mediate the release of molecules involved in thrombosis, inflammation and angiogenesis, including the pro-thrombotic glycoprotein von Willebrand factor (VWF). Although many protein components required for WPB formation and function have been identified, the role of lipids is almost unknown. We examined two key phosphatidylinositol kinases that control phosphatidylinositol 4-phosphate levels at the trans-Golgi network, the site of WPB biogenesis. RNA interference of the type II phosphatidylinositol 4-kinases PI4KIIα and PI4KIIβ in primary human endothelial cells leads to formation of an increased proportion of short WPB with perturbed packing of VWF, as exemplified by increased exposure of antibody-binding sites. When stimulated with histamine, these cells release normal levels of VWF yet, under flow, form very few platelet-catching VWF strings. In PI4KIIα-deficient mice, immuno-microscopy revealed that VWF packaging is also perturbed and these mice exhibit increased blood loss after tail cut compared to controls. This is the first demonstration that lipid kinases can control the biosynthesis of VWF and the formation of WPBs that are capable of full haemostatic function. PMID:27068535

  11. Fluoxetine-induced transactivation of the platelet-derived growth factor type β receptor reveals a novel heterologous desensitization process.

    PubMed

    Kruk, Jeff S; Vasefi, Maryam S; Gondora, Nyasha; Ahmed, Nawaz; Heikkila, John J; Beazely, Michael A

    2015-03-01

    Many G protein-coupled receptors (GPCRs), including serotonin (5-HT) receptors promote the activity of receptor tyrosine kinases (RTKs) via intracellular signaling pathways in a process termed transactivation. Although transactivation pathways are commonly initiated by a GPCR, a recent report demonstrated that serotonin-selective reuptake inhibitors (SSRIs) were able to block 5-HT-induced transactivation of the platelet-derived growth factor (PDGF) type β receptor. We show that a 45 min pretreatment of SH-SY5Y cells with the SSRI fluoxetine indeed blocked 5-HT-induced transactivation of the PDGFβ receptor. However, upon further examination, we discovered that during the pretreatment period, fluoxetine itself was transiently transactivating the PDGFβ receptor via 5-HT2 receptor activation. After 45min, the increase in PDGFβ receptor phosphorylation induced by fluoxetine had returned to baseline, but a subsequent transactivating stimulus (5-HT) failed to "re-transactivate" the PDGFβ receptor. We further demonstrate that 45min, but not 3h, 5-HT pretreatment blocks dopamine-induced PDGFβ receptor transactivation. This did not involve changes in PDGF receptor function, since ligand (PDGF)-induced PDGFβ receptor activation was not inhibited by 5-HT pretreatment. To our knowledge this is the first demonstration of the heterologous desensitization of an RTK transactivation pathway and reveals a previously unknown short-term "blackout" period where no additional transactivation signaling is possible. PMID:25702926

  12. Effects of Type 1 Insulin-Like Growth Factor Receptor Silencing in a Human Adrenocortical Cell Line.

    PubMed

    Ribeiro, T C; Jorge, A A; Montenegro, L R; Almeida, M Q; Ferraz-de-Souza, B; Nishi, M Y; Mendonca, B B; Latronico, A C

    2016-07-01

    Type 1 insulin-like growth factor receptor (IGF-1R) is overexpressed in a variety of human cancers, including adrenocortical tumors. The aim of the work was to investigate the effects of IGF-1R downregulation in a human adrenocortical cell line by small interfering RNA (siRNA). The human adrenocortical tumor cell line NCI H295R was transfected with 2 specific IGF1R siRNAs (# 1 and # 2) and compared with untreated cells and a negative control siRNA. IGF1R expression was determined by quantitative reverse-transcription PCR (qRTPCR) and Western blot. The effects of IGF-1R downregulation on cell proliferation and apoptosis were assessed. IGF-1R levels were significantly decreased in cells treated with IGF-1R siRNA # 1 or # 2. Relative expression of IGF1R mRNA decreased approximately 50% and Western blot analysis revealed a 30% of reduction in IGF-1R protein. Downregulation of this gene resulted in 40% reduction in cell growth in vitro and 45% increase in apoptosis using siRNA # 2. These findings demonstrate that decreasing IGF-1R mRNA and protein expression in NCI H295R cells can partially inhibit adrenal tumor cell growth in vitro. Targeting IGF1R is a promising therapy for pediatric malignant adrenocortical tumor and can still be an option for adult adrenocortical cancer based on personalized genomic tumor profiling. PMID:27246621

  13. Notch maintains Drosophila type II neuroblasts by suppressing expression of the Fez transcription factor Earmuff.

    PubMed

    Li, Xiaosu; Xie, Yonggang; Zhu, Sijun

    2016-07-15

    Notch signaling is crucial for maintaining neural stem cell (NSC) self-renewal and heterogeneity; however, the underlying mechanism is not well understood. In Drosophila, loss of Notch prematurely terminates the self-renewal of larval type II neuroblasts (NBs, the Drosophila NSCs) and transforms type II NBs into type I NBs. Here, we demonstrate that Notch maintains type II NBs by suppressing the activation of earmuff (erm) by Pointed P1 (PntP1). We show that loss of Notch or components of its canonical pathway leads to PntP1-dependent ectopic Erm expression in type II NBs. Knockdown of Erm significantly rescues the loss-of-Notch phenotypes, and misexpression of Erm phenocopies the loss of Notch. Ectopically expressed Erm promotes the transformation of type II NBs into type I NBs by inhibiting PntP1 function and expression in type II NBs. Our work not only elucidates a key mechanism of Notch-mediated maintenance of type II NB self-renewal and identity, but also reveals a novel function of Erm. PMID:27151950

  14. Energy partitioning and environmental influence factors in different vegetation types in the GEWEX Asian Monsoon Experiment

    NASA Astrophysics Data System (ADS)

    Liu, Fengshan; Tao, Fulu; Li, Shenggong; Zhang, Shuai; Xiao, Dengpan; Wang, Meng

    2014-12-01

    Environmental influences upon energy balance in areas of different vegetation types (i.e., forest at Kog-Ma in Thailand and at Yakutsk in Russia, grassland at Amdo in Chinese Tibet and at Arvaikheer in Mongolia, and mixed farmland at Tak in Thailand) in the GEWEX Asian Monsoon Experiment were investigated. The sites we investigated are geographically and climatologically different; and consequently had quite large variations in temperature ( T), water vapor pressure deficit (VPD), soil moisture (SM), and precipitation (PPT). During May-October, the net radiation flux ( R n) (in W·m-2) was 406.21 at Tak, 365.57 at Kog-Ma, 390.97 at Amdo, 316.65 at Arvaikheer, and 287.10 at Yakutsk. During the growing period, the R n partitioned into latent heat flux ( λE/ R n) was greater than that partitioned into sensible heat flux ( H/ R n) at Tak and at Kog-Ma. In contrast, λE/ R n was lower than H/ R n at Arvaikheer, H/ R n was less than λE/ R n between DOY 149 and DOY 270 at Amdo, and between DOY 165 and DOY 235 at Yakutsk. The R n partitioned into ground heat flux was generally less than 0.15. The short-wave albedo was 0.12, 0.18, and 0.20 at the forest, mixed land, and grass sites, respectively. At an hourly scale, energy partitions had no correlation with environmental factors, based on average summer halfhourly values. At a seasonal scale energy partitions were linearly correlated (usually p<0.05) with T, VPD, and SM. The λE/ R n increased with increases in SM, T, and VPD at forest areas. At mixed farmlands, λE/ R n generally had positive correlations with SM, T, and VPD, but was restrained at extremely high values of VPD and T. At grasslands, λE/ R n was enhanced with increases of SM and T, but was decreased with VPD.

  15. Two novel PRPF31 premessenger ribonucleic acid processing factor 31 homolog mutations including a complex insertion-deletion identified in Chinese families with retinitis pigmentosa

    PubMed Central

    Dong, Bing; Chen, Jieqiong; Zhang, Xiaohui; Pan, Zhe; Bai, Fengge

    2013-01-01

    Objective To identify the causative mutations in two Chinese families with retinitis pigmentosa (RP), and to describe the associated phenotype. Methods Individuals from two unrelated families underwent full ophthalmic examinations. After informed consent was obtained, genomic DNA was extracted from the venous blood of all participants. Linkage analysis was performed on the known genetic loci for autosomal dominant retinitis pigmentosa with a panel of polymorphic markers in the two families, and then all coding exons of the PRP31 premessenger ribonucleic acid processing factor 31 homolog (PRPF31) gene were screened for mutations with direct sequencing of PCR-amplified DNA fragments. Allele-specific PCR was used to validate a substitution in all available family members and 100 normal controls. A large deletion was detected with real-time quantitative PCR (RQ-PCR) using a panel of primers from regions around the PRPF31 gene. Long-range PCR, followed by DNA sequencing, was used to define the breakpoints. Results Clinical examination and pedigree analysis revealed two four-generation families (RP24 and RP106) with autosomal dominant retinitis pigmentosa. A significant two-point linkage odd disequilibrium score was generated at marker D19S926 (Zmax=3.55, θ=0) for family RP24 and D19S571 (Zmax=3.21, θ=0) for family RP106, and further linkage and haplotype studies confined the disease locus to chromosome 19q13.42 where the PRPF31 gene is located. Mutation screening of the PRPF31 gene revealed a novel deletion c.1215delG (p.G405fs+7X) in family RP106. The deletion cosegregated with the family’s disease phenotype, but was not found in 100 normal controls. No disease-causing mutation was detected in family RP24 with PCR-based sequencing analysis. RQ-PCR and long-range PCR analysis revealed a complex insertion-deletion (indel) in the patients of family RP24. The deletion is more than 19 kb and encompasses part of the PRPF31 gene (exons 1–3), together with three adjacent

  16. Risk of skin and soft tissue infections (including shingles) in patients exposed to anti-tumour necrosis factor therapy: results from the British Society for Rheumatology Biologics Register

    PubMed Central

    Galloway, James B; Mercer, Louise K; Moseley, Alison; Dixon, William G; Ustianowski, Andrew P; Helbert, Matthew; Watson, Kath D; Lunt, Mark; Hyrich, Kimme L; Symmons, Deborah PM

    2013-01-01

    Introduction Anti-tumour necrosis factor (TNF) therapy is a mainstay of treatment in rheumatoid arthritis (RA). In 2001, BSRBR was established to evaluate the safety of these agents. This paper addresses the safety of anti-TNF therapy in RA with specific reference to serious skin and soft tissue infections (SSSI) and shingles. Methods A cohort of anti-TNF-treated patients was recruited alongside a comparator group with active RA treated with non-biological disease-modifying antirheumatic drugs (nbDMARD). 11 881 anti-TNF and 3673 nbDMARD patients were analysed. Follow-up was by 6-monthly questionnaires to patients and clinicians. Analyses considered SSSI and shingles separately. Incidence rates (IR) were calculated and then compared using survival analyses. Results The crude IR for SSSI were: anti-TNF 1.6/100 patient-years (95% CI 1.4 to 1.8); nbDMARD 0.7/100 patient-years (95% CI 0.5 to 1.0) and shingles: anti-TNF 1.6/100 patient-years (95% CI 1.3 to 2.0); nbDMARD 0.8/100 patient-years (95% CI 0.6 to 1.1). Adjusted HR were SSSI 1.4 (95% CI 0.9 to 2.4), shingles 1.8 (95% CI 1.2 to 2.8). For SSSI, no significant differences were seen between anti-TNF agents. For shingles, the lowest risk was observed for adalimumab (adjusted HR vs nbDMARD) 1.5 (95% CI 1.1 to 2.0) and highest for infliximab (HR 2.2; 95% CI 1.4 to 3.4)). Conclusion A significantly increased risk of shingles was observed in the anti-TNF-treated cohort. The risk of SSSI tended towards being greater with anti-TNF treatment but was not statistically significant. As with any observational dataset cause and effect cannot be established with certainty as residual confounding may remain. This finding would support the evaluation of zoster vaccination in this population. PMID:22532633

  17. Analysis of some predictive factors of quality of life among type 2 diabetic patients

    PubMed Central

    Tol, Azar; Sharifirad, Gholamreza; Eslami, Ahmadali; Shojaeizadeh, Davoud; Alhani, Fatemeh; Tehrani, Mohamadreza Mohajeri

    2015-01-01

    Introduction: Considering the chronic nature of diabetes and its significant effect on quality of life of patients, the present study was conducted to evaluate predictors of quality of life in these patients in order to facilitate planning health promotion intervention programs. Materials and Methods: The present study was designed as a cross-sectional study on 140 type 2 diabetic patients of Om-ol-Banin Diabetes Center of Isfahan. Data collection tool was a multidimensional questionnaire including demographic and disease related data (12 items), the standard scale for diabetes distress (17 items), the standard scale for self-efficacy in diabetic patients (8 items), and standard scale for specific quality of life of diabetic patients (15 items). Collected data were evaluated by SPSS version 11.5 using the Chi-square test, Independent T-test, ANOVA, Pearson correlation and multivariate regression analysis. Results: Results showed that the quality of life of diabetic patients had a statistically significant correlation with diabetes distress variable (P < 0.001) and self-efficacy variable (P < 0.001). In this study R2 (predictive power) was 0.66. Multivariate regression model indicated diabetes distress (β = -0.277, P = 0.01) and self-efficacy (β = -0.161, P < 0.001) as variables influencing adjusted self-management for other variables. Conclusion: The result of the present study urges that in planning health promotion interventions in the field of diabetes, more attention be paid to self-efficacy and diabetes distress variables in order to improve the efficiency and effectiveness of the interventions carried out. PMID:25767820

  18. Lessons learned from the HEALTHY primary prevention trial of risk factors for type 2 diabetes in middle school youth

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The HEALTHY trial was designed to take a primary prevention approach to risk factors for type 2 diabetes in youth, primarily obesity. The study involved over 6,000 students at 42 middle schools across the U.S. Half received an integrated intervention program of components addressing the school food ...

  19. EFFECT OF GROWTH FACTOR-FIBRONECTIN MATRIX INTERACTION ON RAT TYPE II CELL ADHESION AND DNA SYTHESIS

    EPA Science Inventory

    ABSTRACT

    Type II cells attach, migrate and proliferate on a provisional fibronectin-rich matrix during alveolar wall repair after lung injury. The combination of cell-substratum interactions via integrin receptors and exposure to local growth factors are likely to initiat...

  20. Factors in the Adjustment of Khashm El-Girba Tenants to a New Location and a New Type of Agriculture.

    ERIC Educational Resources Information Center

    Abdelrahman, Ahmed Elamin

    The main objectives of the study were: to analyze factors related to adjustment to resettlement; to find the relationship of attitudes to behavior in relation to two major social changes -- adjustment to new location and to a new type of agriculture; to identify the characteristics of unadjusted tenants; to identify the environmental elements…

  1. Human papillomaviruses and cervical cancer in Bangkok. I. Risk factors for invasive cervical carcinomas with human papillomavirus types 16 and 18 DNA.

    PubMed

    Thomas, D B; Ray, R M; Koetsawang, A; Kiviat, N; Kuypers, J; Qin, Q; Ashley, R L; Koetsawang, S

    2001-04-15

    Personal interviews, tests for antibodies to herpes simplex virus type 2, Treponema pallidum, and hepatitis B, tests for hepatitis B surface antigen (HBsAg), and polymerase chain reaction-based assays for human papillomavirus (HPV) DNA in cervical scrapings were obtained from 190 women with squamous cell and 42 women with adenomatous cervical carcinoma and from 291 hospitalized controls diagnosed in Bangkok, Thailand, between September 1991 and September 1993. Risk was strongly associated with oncogenic HPV types, with types 16 and 18 predominating in squamous and adenomatous lesions, respectively. The 126 cases with HPV-16 and the 42 cases with HPV-18 were compared with 250 controls with no evidence of any HPV. The risk of both viral tumor types increased with decreasing age at first intercourse in this predominantly monogamous population, which may be explained by more visits to prostitutes by the husbands of cases with early than late age at first intercourse. HPV-16 tumors were weakly associated with HBsAg carrier state and smoking. The risk of tumors of both viral types increased with parity and use of oral contraceptives but not with injectable progestogens. Factors that may predispose to persistent, oncogenic HPV-16 or -18 infection may include estrogens or progestins in the presence of estrogens, immunosuppression, and smoking, but other factors related to low socioeconomic status are also involved. PMID:11296143

  2. emm and sof gene sequence variation in relation to serological typing of opacity-factor-positive group A streptococci.

    PubMed

    Beall, B; Gherardi, G; Lovgren, M; Facklam, R R; Forwick, B A; Tyrrell, G J

    2000-05-01

    Approximately 40-60% of group A streptococcal (GAS) isolates are capable of opacifying sera, due to the expression of the sof (serum opacity factor) gene. The emm (M protein gene) and sof 5' sequences were obtained from a diverse set of GAS reference strains and clinical isolates, and correlated with M serotyping and anti-opacity-factor testing results. Attempts to amplify sof from strains with M serotypes or emm types historically associated with the opacity-factor-negative phenotype were negative, except for emm12 strains, which were found to contain a highly conserved sof sequence. There was a strong correlation of certain M serotypes with specific emm sequences regardless of strain background, and likewise a strong association of specific anti-opacity-factor (AOF) types to sof gene sequence types. In several examples, M type identity, or partial identity shared between strains with differing emm types, was correlated with short, highly conserved 5' emm sequences likely to encode M-type-specific epitopes. Additionally, each of three pairs of historically distinct M type reference strains found to share the same 5' emm sequence, were also found to share M serotype specificity. Based upon sof sequence comparisons between strains of the same and of differing AOF types, an approximately 450 residue domain was determined likely to contain key epitopes required for AOF type specificity. Analysis of two Sof sequences that were not highly homologous, yet shared a common AOF type, further implicated a 107 aa portion of this 450-residue domain in putatively containing AOF-specific epitopes. Taken together, the serological data suggest that AOF-specific epitopes for all Sof proteins may reside within a region corresponding to this 107-residue sequence. The presence of specific, hypervariable emm/sof pairs within multiple isolates appears likely to be a reliable indicator of their overall genetic relatedness, and to be very useful for accurate subtyping of GAS isolates by

  3. Regional Differences of Undiagnosed Type 2 Diabetes and Prediabetes Prevalence Are Not Explained by Known Risk Factors

    PubMed Central

    Tamayo, Teresa; Schipf, Sabine; Meisinger, Christine; Schunk, Michaela; Maier, Werner; Herder, Christian; Roden, Michael; Nauck, Matthias; Peters, Annette; Völzke, Henry; Rathmann, Wolfgang

    2014-01-01

    Background We have previously found regional differences in the prevalence of known type 2 diabetes between northeastern and southern Germany. We aim to also provide prevalence estimates for prediabetes (isolated impaired fasting glucose (i-IFG), isolated glucose intolerance (i-IGT), combined IFG and IGT) and unknown type 2 diabetes for both regions. Methods Prevalence (95%CI) of prediabetes (i-IFG: fasting glucose 5.6–6.9 mmol/l; i-IGT: 2 h postchallenge gluose 7.8–11.0 mmol/l, oral glucose tolerance test (OGTT), ≥8 h overnight fasting) and unknown diabetes were analyzed in two regional population-based surveys (age group 35–79 years): SHIP-TREND (Study of Health in Pomerania (northeast), 2008–2012) and KORA F4 (Cooperative Health Research in the region of Augsburg (south), 2006–2008). Both studies used similar methods, questionnaires, and identical protocols for OGTT. Overall, 1,980 participants from SHIP-TREND and 2,617 participants from KORA F4 were included. Results Age-sex-standardized prevalence estimates (95%CI) of prediabetes and unknown diabetes were considerably higher in the northeast (SHIP-TREND: 43.1%; 40.9–45.3% and 7.1%; 5.9–8.2%) than in the south of Germany (KORA F4: 30.1%; 28.4–31.7% and 3.9%; 3.2–4.6%), respectively. In particular, i-IFG (26.4%; 24.5–28.3% vs. 17.2%; 15.7–18.6%) and IFG+IGT (11.2%; 9.8–12.6% vs. 6.6%; 5.7–7.5%) were more frequent in SHIP-TREND than in KORA. In comparison to normal glucose tolerance, the odds of having unknown diabetes (OR, 95%CI: 2.59; 1.84–3.65) or prediabetes (1.98; 1.70–2.31) was higher in the northeast than in the south after adjustment for known risk factors (obesity, lifestyle). Conclusions The regional differences of prediabetes and unknown diabetes are in line with the geographical pattern of known diabetes in Germany. The higher prevalences in the northeast were not explained by traditional risk factors. PMID:25402347

  4. Mice devoid of interferon regulatory factor 1 (IRF-1) show normal expression of type I interferon genes.

    PubMed Central

    Reis, L F; Ruffner, H; Stark, G; Aguet, M; Weissmann, C

    1994-01-01

    The transcription factor interferon regulatory factor 1 (IRF-1) binds tightly to the interferon (IFN)-beta promoter and has been implicated in the induction of type I IFNs. We generated mice devoid of functional IRF-1 by targeted gene disruption. As reported by others, IRF-1-deficient mice showed a discrete phenotype: the CD4/CD8 ratio was increased and IFN-gamma-induced levels of macrophage iNO synthase mRNA were strongly diminished. However, type I IFN induction in vivo by virus or double-stranded RNA was unimpaired, as evidenced by serum IFN titers and IFN mRNA levels in spleen, liver and lung. There was also no impairment in the response of type I IFN-inducible genes. Therefore, IRF-1 is not essential for these processes in vivo. Images PMID:7957048

  5. Novel Risk Factors for Type 2 Diabetes in African-Americans.

    PubMed

    Chatterjee, Ranee; Maruthur, Nisa M; Edelman, David

    2015-12-01

    In the USA, compared to whites, African-Americans are disproportionately impacted by the diabetes epidemic. Traditional diabetes risk factors, such as obesity, are more common among African-Americans, but these traditional risk factors do not explain all of the disparity in diabetes risk. Recent research has identified novel environmental, lifestyle, physiologic, and genetic risk factors for diabetes, some of which appear to impact African-Americans more than whites. This manuscript reviews the recent literature to highlight some of these novel risk factors that may be contributing to the racial disparity in diabetes risk. Further study is needed of the modifiable risk factors for development of interventions to reduce the risk of diabetes in African-Americans, as well as other high-risk populations. PMID:26458374

  6. Proteinase-resistant factors in human erythrocyte membranes mediate CD4-dependent fusion with cells expressing human immunodeficiency virus type 1 envelope glycoproteins.

    PubMed Central

    Dragic, T; Picard, L; Alizon, M

    1995-01-01

    Murine CD4+ cells are resistant to human immunodeficiency virus type 1 (HIV-1) entry and to fusion with cells expressing HIV-1 envelope glycoproteins (Env). The role of human-specific factors in Env/CD4-mediated fusion is shown by the ability of transient cell hybrids formed between CD4+ murine cells and human HeLa cells to fuse with Env+ cells. Fusion events were observed when other human cells, including erythrocytes, were substituted for HeLa cells in the hybrids. Experiments with erythrocyte ghosts showed that the factors allowing Env/CD4-mediated fusion are located in the plasma membrane. These factors were fully active after extensive digestion of erythrocytes with proteinase K or pronase. Nonprotein components of human plasma membranes, possibly glycolipids, could therefore be required for Env/CD4-mediated fusion and virus entry. PMID:7815477

  7. Risk and Protective Factors of Suicidal Ideation and Attempt among Adolescents with Different Types of School Bullying Involvement.

    PubMed

    Yen, Cheng-Fang; Liu, Tai-Ling; Yang, Pinchen; Hu, Huei-Fan

    2015-01-01

    Suicide has been found to be prevalent among adolescents involved in bullying; however, there has been a lack of research examining whether the risk and protective factors of suicidal ideation and attempt are different among adolescents with different types of bullying involvement. The aims of this study were to examine the risk and protective factors of suicidal ideation and attempt among adolescents with different experiences of bullying involvement, victimization, and perpetration. A total of 4,533 adolescents participated in this study. Different groups of bullying involvement, victimization, and perpetration were determined through use of the Chinese version of the School Bullying Experience Questionnaire. The associations of suicidal ideation and attempt with possible risk factors (domestic violence, overweight, depression, anxiety, and alcohol abuse) and protective factors (family support and self-esteem) were examined using logistic regression analysis. Pure victims, pure perpetrators, and victim-perpetrators were more likely to report suicidal ideation and attempt than the neutral group. The risk and protective factors of suicidal ideation and attempt were different across adolescents with different experiences of bullying involvement, victimization, and perpetrators. The risk of suicide should be monitored among adolescents who are involved in any type of bullying. The risk and protective factors of suicide identified in this study should be taken into consideration in prevention and intervention programs for suicide in adolescents involved in bullying. PMID:26566860

  8. Risk factors for distal stent graft-induced new entry following endovascular repair of type B aortic dissection

    PubMed Central

    Li, Qing; Wang, Long-Fei; Ma, Wei-Guo; Xu, Shang-Dong; Zheng, Jun; Xing, Xiao-Yan

    2015-01-01

    Background Distal stent graft-induced new entry (DSINE) has been increasingly observed following thoracic endovascular aortic repair (TEVAR) for type B aortic dissection (TBAD). We seek to identify the risk factors for DSINE following TEVAR in patients with TBAD. Methods Between January 2009 and January 2013, we performed TEVAR for 579 patients with TBAD. The clinical data were retrospectively analyzed with univariate and multivariate analyses to identify the risk factors for DSINE. Results Two patients (0.3%) died after the initial TEVAR. Morbidity included spinal cord injury in 2 (0.3%), stroke in 3 (0.5%) and endoleak in 12 (2.1%) patients. Clinical and radiological follow-up was complete in 100% (577/577) averaging 47±16 months. Late death occurred in 6 patients. DSINE occurred in 39 patients (6.7%) at mean 22±17 months after the initial TEVAR, which was managed with re-TEVAR in 25 and medically in 14. At 33±18 months after DSINE, 11 of patients managed medically (11/14) and all patients managed with re-TEVAR (25/25) survived (P=0.048). Freedom from DSINE was 92.7% at 5 years (95% CI: 90.0-94.7%). Using tapered stent grafts with a proximal end 4-8 mm larger than the distal end, TEVAR performed in the acute phase (≤14 days from onset) was associated with a significantly lower incidence of DSINE than TEVAR performed in the chronic phase (4.3%, 7/185 vs. 13.9%, 15/108; P=0.003). Risk factors for DSINE were stent grafts less than 145 mm in length [odds ratio (OR) 2.268; 95% CI: 1.121-4.587; P=0.023] and TEVAR performed in the chronic phase (OR 1.935; 95% CI: 1.004-3.731; P=0.049). Conclusions Our results show that TEVAR performed during the acute phase and using stent grafts longer than 145 mm could decrease the incidence of DSINE in patients with TBAD. Tapered stent grafts with a proximal end 4-8 mm larger than the distal end may be helpful in preventing DSINE after TEVAR performed in the acute phase than TEVAR performed in the chronic phase, due to the

  9. Evaluating risk factors for endemic human Salmonella Enteritidis infections with different phage types in Ontario, Canada using multinomial logistic regression and a case-case study approach

    PubMed Central

    2012-01-01

    Background Identifying risk factors for Salmonella Enteritidis (SE) infections in Ontario will assist public health authorities to design effective control and prevention programs to reduce the burden of SE infections. Our research objective was to identify risk factors for acquiring SE infections with various phage types (PT) in Ontario, Canada. We hypothesized that certain PTs (e.g., PT8 and PT13a) have specific risk factors for infection. Methods Our study included endemic SE cases with various PTs whose isolates were submitted to the Public Health Laboratory-Toronto from January 20th to August 12th, 2011. Cases were interviewed using a standardized questionnaire that included questions pertaining to demographics, travel history, clinical symptoms, contact with animals, and food exposures. A multinomial logistic regression method using the Generalized Linear Latent and Mixed Model procedure and a case-case study design were used to identify risk factors for acquiring SE infections with various PTs in Ontario, Canada. In the multinomial logistic regression model, the outcome variable had three categories representing human infections caused by SE PT8, PT13a, and all other SE PTs (i.e., non-PT8/non-PT13a) as a referent category to which the other two categories were compared. Results In the multivariable model, SE PT8 was positively associated with contact with dogs (OR=2.17, 95% CI 1.01-4.68) and negatively associated with pepper consumption (OR=0.35, 95% CI 0.13-0.94), after adjusting for age categories and gender, and using exposure periods and health regions as random effects to account for clustering. Conclusions Our study findings offer interesting hypotheses about the role of phage type-specific risk factors. Multinomial logistic regression analysis and the case-case study approach are novel methodologies to evaluate associations among SE infections with different PTs and various risk factors. PMID:23057531

  10. Epidemiology of type 2 diabetic foot problems and predictive factors for amputation in China.

    PubMed

    Jiang, Yufeng; Ran, Xingwu; Jia, Lijing; Yang, Chuan; Wang, Penghua; Ma, Jianhua; Chen, Bing; Yu, Yanmei; Feng, Bo; Chen, Lili; Yin, Han; Cheng, Zhifeng; Yan, Zhaoli; Yang, Yuzhi; Liu, Fang; Xu, Zhangrong

    2015-03-01

    To determine incidence and clinically relevant risk factors for diabetic amputation in a large cohort study of diabetic foot ulceration patients in China, we investigated a total of 669 diabetic foot ulceration patients, who were assessed at baseline for demographic information, medical and social history, peripheral neuropathy screening, periphery artery disease screening, assessment of nutritional status and diabetic control, physical examination including foot deformity in 15 Grade III-A hospitals. Of the 669 patients, 435 were male and 201 were female, with the mean age being 64.0 years. Of all patients, 110 had neuropathic ulcers, 122 had ischemic ulcers, 276 had neuroischemic ulcers, and 12 cases were unclassified. Wagner classification showed 61 cases were grade I, 216 cases grade II, 159 cases grade III, 137 cases grade IV, and 7 cases grade V. The overall amputation rate among diabetic foot patients was 19.03%, and major and minor amputation rates were 2.14% and 16.88%, respectively. By univariate analysis, statistically significant differences were found in smoking, rest pain, ulcer history, revascularization history, amputation history, gangrene, infection, Wagner grades, duration of diabetes, and postprandial blood glucose, aldehyde, total protein, globulin, albumin, white blood cell (WBC), hemoglobin, HbA1c, ulcer property, body mass index, as well as creatinine. Binary logistic regression model showed that increased WBC (odds ratio 1.25) and ulcer history (odds ratio 6.8) were associated with increased risks from diabetic foot ulcer to major amputation; increased duration of diabetes (odds ratio 1.004), WBC (odds ratio 1.102), infection (odds ratio 2.323), foot deformity (odds ratio 1.973), revascularization history (odds ratio 2.662), and decreased postprandial blood sugar (odds ratio 0.94) were associated with increased risks from diabetic foot ulcer to minor amputation. It is of great importance to give better management to diabetic patients at

  11. 150-kD von Willebrand factor binding protein extracted from human vascular subendothelium is type VI collagen.

    PubMed Central

    Rand, J H; Patel, N D; Schwartz, E; Zhou, S L; Potter, B J

    1991-01-01

    We have previously shown that von Willebrand factor (vWF), a glycoprotein which plays a critical role in the adhesion of platelets to injured blood vessels, is present within vascular subendothelium. We investigated the identity of the subendothelial binding site(s) for vWF by examining vWF binding to subendothelial constituents and solubilized a 150-kD protein with SDS-urea that bound vWF. This protein had an amino-acid composition similar to that of the type VI collagen alpha-1/alpha-2 chains, was recognized by specific polyclonal antibodies against type VI collagen, and had a similar acidic isoelectric point. Furthermore, we found that purified type VI collagen also bound vWF. Thus, we have identified the extracted 150-kD protein as type VI collagen. This protein may play a significant role in the binding of vWF to vascular subendothelium in vivo. Images PMID:2056120

  12. Challenges and Opportunities in the Management of Cardiovascular Risk Factors in Youth With Type 1 Diabetes: Lifestyle and Beyond.

    PubMed

    Katz, Michelle; Giani, Elisa; Laffel, Lori

    2015-12-01

    Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in persons with type 1 diabetes (T1D). Specific risk factors associated with diabetes, such as hyperglycemia and kidney disease, have been demonstrated to increase the incidence and progression of CVD. Nevertheless, few data exist on the effects of traditional risk factors such as dyslipidemia, obesity, and hypertension on CVD risk in youth with T1D. Improvements in understanding and approaches to the evaluation and management of CVD risk factors, specifically for young persons with T1D, are desirable. Recent advances in noninvasive techniques to detect early vascular damage, such as the evaluation of endothelial dysfunction and aortic or carotid intima-media thickness, provide new tools to evaluate the progression of CVD in childhood. In the present review, current CVD risk factor management, challenges, and potential therapeutic interventions in youth with T1D are described. PMID:26520142

  13. EPR g factors and defect structures for V4+ and Cr5+ in the rutile-type crystals

    NASA Astrophysics Data System (ADS)

    Wang, Minjie; Zhu, Lianxuan

    2016-08-01

    The g-factor formulas for V4+ and Cr5+ ions in the rutile-type crystals are deduced from Jahn-Teller effect and contributions of the charge transfer levels. The tetragonal distortions ΔR = -0.0045, -0.0045 and -0.0067 nm, and Δθ = 0°, -0.001° and 0°, for GeO2:V4+, TiO2:V4+ and TiO2:Cr5+, respectively. The calculations of the g-factors agree well with the experimental values. The contributions of the charge transfer levels to g factors increase with the increasing valence state. It must be taken into account in the precise calculations of g factors for the high valence state d1 ions in crystals.

  14. Effect of the amount and type of dietary fat on cardiometabolic risk factors and risk of developing type 2 diabetes, cardiovascular diseases, and cancer: a systematic review.

    PubMed

    Schwab, Ursula; Lauritzen, Lotte; Tholstrup, Tine; Haldorssoni, Thorhallur; Riserus, Ulf; Uusitupa, Matti; Becker, Wulf

    2014-01-01

    The effects of both the amount and quality of dietary fat have been studied intensively during the past decades. Previously, low-fat diets were recommended without much attention to the quality of fat, whereas there is general emphasis on the quality of fat in current guidelines. The objective of this systematic review (SR) was to assess the evidence of an effect of the amount and type of dietary fat on body weight (BW), risk factors, and risk of non-communicable diseases, that is, type 2 diabetes (T2DM), cardiovascular diseases (CVD), and cancer in healthy subjects or subjects at risk for these diseases. This work was performed in the process of updating the fourth edition of the Nordic Nutrition Recommendations from 2004. The literature search was performed in October 2010 covering articles published since January 2000. A complementary search was done in February 2012 covering literature until December 2011. Two authors independently selected articles for inclusion from a total of about 16,000 abstracts according to predefined criteria. Randomized controlled trials (RCT) and prospective cohort studies (PCS) were included as well as nested case-control studies. A few retrospective case-control studies were also included when limited or no data were available from other study types. Altogether 607 articles were quality graded and the observed effects in these papers were summarized. Convincing evidence was found that partial replacement of saturated fat (SFA) with polyunsaturated fat (PUFA) or monounsaturated fat (MUFA) lowers fasting serum/plasma total and LDL cholesterol concentrations. The evidence was probable for a decreasing effect of fish oil on concentration of serum/plasma total triglycerides as compared with MUFA. Beneficial effect of MUFA both on insulin sensitivity and fasting plasma/serum insulin concentration was considered as probable in comparisons of MUFA and carbohydrates versus SFA, whereas no effect was found on fasting glucose concentration in

  15. Effect of the amount and type of dietary fat on cardiometabolic risk factors and risk of developing type 2 diabetes, cardiovascular diseases, and cancer: a systematic review

    PubMed Central

    Schwab, Ursula; Lauritzen, Lotte; Tholstrup, Tine; Haldorsson, Thorhallur I.; Riserus, Ulf; Uusitupa, Matti; Becker, Wulf

    2014-01-01

    The effects of both the amount and quality of dietary fat have been studied intensively during the past decades. Previously, low-fat diets were recommended without much attention to the quality of fat, whereas there is general emphasis on the quality of fat in current guidelines. The objective of this systematic review (SR) was to assess the evidence of an effect of the amount and type of dietary fat on body weight (BW), risk factors, and risk of non-communicable diseases, that is, type 2 diabetes (T2DM), cardiovascular diseases (CVD), and cancer in healthy subjects or subjects at risk for these diseases. This work was performed in the process of updating the fourth edition of the Nordic Nutrition Recommendations from 2004. The literature search was performed in October 2010 covering articles published since January 2000. A complementary search was done in February 2012 covering literature until December 2011. Two authors independently selected articles for inclusion from a total of about 16,000 abstracts according to predefined criteria. Randomized controlled trials (RCT) and prospective cohort studies (PCS) were included as well as nested case–control studies. A few retrospective case–control studies were also included when limited or no data were available from other study types. Altogether 607 articles were quality graded and the observed effects in these papers were summarized. Convincing evidence was found that partial replacement of saturated fat (SFA) with polyunsaturated fat (PUFA) or monounsaturated fat (MUFA) lowers fasting serum/plasma total and LDL cholesterol concentrations. The evidence was probable for a decreasing effect of fish oil on concentration of serum/plasma total triglycerides as compared with MUFA. Beneficial effect of MUFA both on insulin sensitivity and fasting plasma/serum insulin concentration was considered as probable in comparisons of MUFA and carbohydrates versus SFA, whereas no effect was found on fasting glucose concentration

  16. Bi-Exact Groups, Strongly Ergodic Actions and Group Measure Space Type III Factors with No Central Sequence

    NASA Astrophysics Data System (ADS)

    Houdayer, Cyril; Isono, Yusuke

    2016-05-01

    We investigate the asymptotic structure of (possibly type III) crossed product von Neumann algebras {M = B rtimes Γ} arising from arbitrary actions {Γ &ucedil;rvearrowright B} of bi-exact discrete groups (e.g. free groups) on amenable von Neumann algebras. We prove a spectral gap rigidity result for the central sequence algebra {N' \\cap M^ω} of any nonamenable von Neumann subalgebra with normal expectation {N subset M} . We use this result to show that for any strongly ergodic essentially free nonsingular action {Γ &ucedil;rvearrowright (X, μ)} of any bi-exact countable discrete group on a standard probability space, the corresponding group measure space factor {L^∞(X) rtimes Γ} has no nontrivial central sequence. Using recent results of Boutonnet et al. (Local spectral gap in simple Lie groups and applications, 2015), we construct, for every {0 < λ ≤ 1} , a type {III_λ} strongly ergodic essentially free nonsingular action F_∞ &ucedil;rvearrowright (X_λ, μ_λ) of the free group F_∞ on a standard probability space so that the corresponding group measure space type {III_λ} factor {L^∞(X_λ, μ_λ) rtimes F_∞ has no nontrivial central sequence by our main result. In particular, we obtain the first examples of group measure space type {III} factors with no nontrivial central sequence.

  17. Job Strain as a Risk Factor for Type 2 Diabetes: A Pooled Analysis of 124,808 Men and Women

    PubMed Central

    Fransson, Eleonor I.; Heikkilä, Katriina; Ahola, Kirsi; Alfredsson, Lars; Bjorner, Jakob B.; Borritz, Marianne; Burr, Hermann; Dragano, Nico; Goldberg, Marcel; Hamer, Mark; Jokela, Markus; Knutsson, Anders; Koskenvuo, Markku; Koskinen, Aki; Kouvonen, Anne; Leineweber, Constanze; Madsen, Ida E.H.; Magnusson Hanson, Linda L.; Marmot, Michael G.; Nielsen, Martin L.; Nordin, Maria; Oksanen, Tuula; Pejtersen, Jan H.; Pentti, Jaana; Rugulies, Reiner; Salo, Paula; Siegrist, Johannes; Steptoe, Andrew; Suominen, Sakari; Theorell, Töres; Väänänen, Ari; Vahtera, Jussi; Virtanen, Marianna; Westerholm, Peter J.M.; Westerlund, Hugo; Zins, Marie; Batty, G. David; Brunner, Eric J.; Ferrie, Jane E.; Singh-Manoux, Archana

    2014-01-01

    OBJECTIVE The status of psychosocial stress at work as a risk factor for type 2 diabetes is unclear because existing evidence is based on small studies and is subject to confounding by lifestyle factors, such as obesity and physical inactivity. This collaborative study examined whether stress at work, defined as “job strain,” is associated with incident type 2 diabetes independent of lifestyle factors. RESEARCH DESIGN AND METHODS We extracted individual-level data for 124,808 diabetes-free adults from 13 European cohort studies participating in the IPD-Work Consortium. We measured job strain with baseline questionnaires. Incident type 2 diabetes at follow-up was ascertained using national health registers, clinical screening, and self-reports. We analyzed data for each study using Cox regression and pooled the study-specific estimates in fixed-effect meta-analyses. RESULTS There were 3,703 cases of incident diabetes during a mean follow-up of 10.3 years. After adjustment for age, sex, and socioeconomic status (SES), the hazard ratio (HR) for job strain compared with no job strain was 1.15 (95% CI 1.06–1.25) with no difference between men and women (1.19 [1.06–1.34] and 1.13 [1.00–1.28], respectively). In stratified analyses, job strain was associated with an increased risk of diabetes among those with healthy and unhealthy lifestyle habits. In a multivariable model adjusted for age, sex, SES, and lifestyle habits, the HR was 1.11 (1.00–1.23). CONCLUSIONS Findings from a large pan-European dataset suggest that job strain is a risk factor for type 2 diabetes in men and women independent of lifestyle factors. PMID:25061139

  18. Hepatocyte growth factor reduces sensitivity to the epidermal growth factor receptor-tyrosine kinase inhibitor, gefitinib, in lung adenocarcinoma cells harboring wild-type EGFR

    PubMed Central

    Yang, Hua; Wang, Rong; Peng, Shunli; Chen, Longhua; Li, Qi; Wang, Wei

    2016-01-01

    Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy is an option for lung cancers harboring wild-type EGFR when chemotherapeutic reagents have failed. In this study, we found that the EGFR-TKI, gefitinib, modestly suppressed proliferation of the lung cancer cell lines, A549 and H358, which both harbor wild-type EGFR. Treatment with hepatocyte growth factor (HGF) reduced the sensitivity to gefitinib, whereas sensitivity was restored by treatment with an HGF antibody, a MET inhibitor, or depletion of MET but not ErbB3 gene. Moreover, both PI3K/mTOR inhibitors and MEK inhibitors suppressed proliferation of A549 cells, whereas only PI3K/mTOR inhibitors effectively suppressed cell viability of EGFR mutant PC-9 cells. Our findings suggest that HGF reduced the gefitinib sensitivity through MET and downstream PI3K and MAPK pathways. Combined use of EGFR-TKI and MET inhibitors or inhibition of downstream signaling molecules might be a better second or third line choice for a group of patients with advanced lung cancer harboring wild-type EGFR. PMID:26919104

  19. The insulin-like growth factor 1 receptor causes acquired resistance to erlotinib in lung cancer cells with the wild-type epidermal growth factor receptor.

    PubMed

    Suda, Kenichi; Mizuuchi, Hiroshi; Sato, Katsuaki; Takemoto, Toshiki; Iwasaki, Takuya; Mitsudomi, Tetsuya

    2014-08-15

    Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy often provides a dramatic response in lung cancer patients with EGFR mutations. In addition, moderate clinical efficacy of the EGFR-TKI, erlotinib, has been shown in lung cancer patients with the wild-type EGFR. Numerous molecular mechanisms that cause acquired resistance to EGFR-TKIs have been identified in lung cancers with the EGFR mutations; however, few have been reported in lung cancers with the wild-type EGFR. We used H358 lung adenocarcinoma cells lacking EGFR mutations that showed modest sensitivity to erlotinib. The H358 cells acquired resistance to erlotinib via chronic exposure to the drug. The H358 erlotinib-resistant (ER) cells do not have a secondary EGFR mutation, neither MET gene amplification nor PTEN downregulation; these have been identified in lung cancers with the EGFR mutations. From comprehensive screening of receptor tyrosine kinase phosphorylation, we observed increased phosphorylation of insulin-like growth factor 1 receptor (IGF1R) in H358ER cells compared with parental H358 cells. H358ER cells responded to combined therapy with erlotinib and NVP-AEW541, an IGF1R-TKI. Our results indicate that IGF1R activation is a molecular mechanism that confers acquired resistance to erlotinib in lung cancers with the wild-type EGFR. PMID:24458568

  20. The first scintigraphic detection of tumor necrosis factor-alpha in patients with complex regional pain syndrome type 1.

    PubMed

    Bernateck, Michael; Karst, Matthias; Gratz, Klaus F; Meyer, Geerd J; Fischer, Michael J; Knapp, Wolfram H; Koppert, Wolfgang; Brunkhorst, Thomas

    2010-01-01

    Tumor necrosis factor (TNF)-alpha has been identified as a pathogenic factor in many immunologically based diseases and complex regional pain syndrome (CRPS). In this case series, we used radiolabeled technetium anti-TNF-alpha antibody to scintigraphically image TNF-alpha in 3 patients with type 1 CRPS. The results show that TNF-alpha was localized only in affected hands of patients with early-stage CRPS. No uptake was seen in clinically unaffected hands and late-stage CRPS. Our findings support the growing evidence for neuroimmune disturbance in patients with CRPS and may have important further implications for specific anticytokine treatment in patients with CRPS. PMID:19910617

  1. Altered interaction and distribution of glycosaminoglycans and growth factors in mucopolysaccharidosis type I bone disease.

    PubMed

    Kingma, Sandra D K; Wagemans, Tom; IJlst, Lodewijk; Bronckers, Antonius L J J; van Kuppevelt, Toin H; Everts, Vincent; Wijburg, Frits A; van Vlies, Naomi

    2016-07-01

    The mucopolysaccharidoses (MPSs) comprise a group of lysosomal storage disorders characterized by deficient degradation and subsequent accumulation of glycosaminoglycans (GAGs). Progressive bone and joint disease are a major cause of morbidity, and current therapeutic strategies have limited effect on these symptoms. By elucidating pathophysiological mechanisms underlying bone disease, new therapeutic targets may be identified. Longitudinal growth is regulated by interaction between GAGs and growth factors. Because GAGs accumulate in the MPSs, we hypothesized that altered interaction between growth factors and GAGs contribute to the pathogenesis of MPS bone disease. In this study, binding between GAGs from MPS I chondrocytes and fibroblast growth factor 2 (FGF2) was not significantly different from binding of FGF2 to GAGs from control chondrocytes. FGF2 signaling, however, was increased in MPS I chondrocytes after incubation with FGF2, as compared to control chondrocytes. Using bone cultures, we demonstrated decreased growth of WT mouse bones after incubation with FGF2, but no effect on MPS I bone growth. However, MPS I bones showed decreased growth in the presence of GAGs from MPS I chondrocytes. Finally, we demonstrate altered GAG distribution in MPS I chondrocytes, and altered GAG, FGF2 and Indian hedgehog distribution in growth plates from MPS I mice. In summary, our results suggest that altered interaction and distribution of growth factors and accumulated GAGs may contribute to the pathogenesis of MPS bone disease. In the future, targeting growth factor regulation or the interaction between in growth factors and GAGs might be a promising therapeutic strategy for MPS bone disease. PMID:27105565

  2. Estimated Insulin Sensitivity and Cardiovascular Disease Risk Factors in Adolescents with and without Type 1 Diabetes

    PubMed Central

    Specht, Brian J; Wadwa, R Paul; Snell-Bergeon, Janet K; Nadeau, Kristen J; Bishop, Franziska K; Maahs, David M.

    2012-01-01

    Objective To test the hypothesis that cardiovascular disease (CVD) risk factors are similar in adolescents with and without diabetes (T1D) in the most insulin sensitive (IS) tertile and CVD risk factors are more atherogenic with decreasing IS in adolescents with T1D. Study design Adolescents with IS T1D (n=292; age=15.4±2.1 years; duration=8.8±3.0 years, HbA1c=8.9±1.6%) and non-diabetic (non-DM) controls (n=89; age=15.4±2.1 years) was estimated using the model: logeIS=4.64725 – 0.02032(waist, cm) – 0.09779(HbA1c, %) – 0.00235(triglycerides, mg/dl). CVD risk factors (blood pressure, fasting total, LDL and HDL-cholesterol, hs-CRP, and BMI Z-score) were compared between all non-DM adolescents and those with T1D in the most IS tertile, and then examined for a linear trend by IS tertile in adolescents with T1D, adjusted for sex, race/ethnicity and Tanner Stage. Results Estimated IS was significantly lower in adolescents with T1D compared with those without (T1D=7.8±2.4, non-DM=11.5±2.9; p<0.0001). CVD risk factors were similar for non-DM compared with the adolescents with most IS T1D, except for higher HDL-c and DBP in adolescents with T1D (p<0.05). Among adolescents with T1D, all CVD risk factors except for HDL-c, were more atherogenic across decreasing IS tertiles in linear regression analysis (p<0.05). Conclusion Adolescents with T1D who are the most IS have similar CVD risk factors compared with non-DM adolescents. CVD risk factors are inversely associated with adolescents with IS T1D. IS may be an important therapeutic target for reducing CVD risk factors in adolescents with T1D. PMID:22921593

  3. The InterAct Project: An Examination of the Interaction of Genetic and Lifestyle Factors on the Incidence of Type 2 Diabetes in the EPIC Study

    PubMed Central

    Langenberg, C; Sharp, S; Forouhi, NG; Franks, P; Schulze, MB; Kerrison, N; Ekelund, U; Barroso, I; Panico, S; Tormo, M; Spranger, J; Griffin, S; van der Schouw, YT; Amiano, P; Ardanaz, E; Arriola, L; Balkau, B; Barricarte, A; Beulens, JWJ; Boeing, H; Bueno-de-Mesquita, HB; Buijsse, BB; Chirlaque Lopez, MD; Clavel-Chapelon, F; Crowe, FL; de Lauzon-Guillan, B; Deloukas, P; Dorronsoro, M; Drogan, DD; Froguel, P; Gonzalez, C; Grioni, S; Groop, L; Groves, C; Hainaut, P; Halkjaer, J; Hallmans, G; Hansen, T; Kaaks, R; Key, TJ; Khaw, K; Koulman, A; Mattiello, A; Navarro, C; Nilsson, P; Norat, T; Overvad, K; Palla, L; Palli, D; Pedersen, O; Peeters, PH; Quirós, JR; Ramachandran, A; Rodriguez-Suarez, L; Rolandsson, O; Romaguera, D; Romieu, I; Sacerdote, C; Sánchez, M; Sandbaek, A; Slimani, N; Sluijs, I; Spijkerman, AMW; Teucher, B; Tjonneland, A; Tumino, R; van der A, DL; Verschuren, WMM; Tuomilehto, J; Feskens, E; McCarthy, M; Riboli, E; Wareham, NJ

    2014-01-01

    Background Studying gene-lifestyle interaction may help to identify lifestyle factors that modify genetic susceptibility and uncover genetic loci exerting important subgroup effects. Adequately powered studies with prospective, unbiased, standardised assessment of key behavioural factors for gene-lifestyle studies are lacking. Objective To establish a type 2 diabetes case-cohort study designed to investigate how genetic and potentially modifiable lifestyle and behavioral factors, particularly diet and physical activity, interact in their influence on the risk of developing type 2 diabetes. Methods Funded by the Sixth European Framework Programme, InterAct consortium partners ascertained and verified incident cases of type 2 diabetes occurring in European Prospective Investigation into Cancer and Nutrition (EPIC) cohorts between 1991 and 2007 from 8 of the 10 EPIC countries. A pragmatic, high sensitivity approach was used for case ascertainment including multiple sources at each EPIC centre, followed by diagnostic verification. Prentice-weighted Cox regression and random effects meta-analyses were used to investigate differences in diabetes incidence by age and sex. Results A total of 12,403 verified incident cases of type 2 diabetes occurred during 3.99 million person-years of follow-up of 340,234 EPIC participants eligible for InterAct. We defined a centre stratified subcohort of 16,154 individuals for comparative analyses. Individuals with incident diabetes that were randomly selected into the subcohort (n=778) were included as cases in the analyses. All prevalent diabetes cases were excluded from the study. InterAct cases were followed-up for an average of 6.9 years, 49.7% were men. Mean baseline age and age at diagnosis were 55.6 and 62.5 years, mean BMI and waist were 29.4 kg/m2 and 102.7 cm in men, and 30.1 kg/m2 and 92.8 cm in women, respectively. Risk of type 2 diabetes increased linearly with age, with an overall hazard ratio (95% CI) of 1.56 (1.48; 1

  4. All-Atom Structural Models of the Transmembrane Domains of Insulin and Type 1 Insulin-Like Growth Factor Receptors

    PubMed Central

    Mohammadiarani, Hossein; Vashisth, Harish

    2016-01-01

    The receptor tyrosine kinase superfamily comprises many cell-surface receptors including the insulin receptor (IR) and type 1 insulin-like growth factor receptor (IGF1R) that are constitutively homodimeric transmembrane glycoproteins. Therefore, these receptors require ligand-triggered domain rearrangements rather than receptor dimerization for activation. Specifically, binding of peptide ligands to receptor ectodomains transduces signals across the transmembrane domains for trans-autophosphorylation in cytoplasmic kinase domains. The molecular details of these processes are poorly understood in part due to the absence of structures of full-length receptors. Using MD simulations and enhanced conformational sampling algorithms, we present all-atom structural models of peptides containing 51 residues from the transmembrane and juxtamembrane regions of IR and IGF1R. In our models, the transmembrane regions of both receptors adopt helical conformations with kinks at Pro961 (IR) and Pro941 (IGF1R), but the C-terminal residues corresponding to the juxtamembrane region of each receptor adopt unfolded and flexible conformations in IR as opposed to a helix in IGF1R. We also observe that the N-terminal residues in IR form a kinked-helix sitting at the membrane–solvent interface, while homologous residues in IGF1R are unfolded and flexible. These conformational differences result in a larger tilt-angle of the membrane-embedded helix in IGF1R in comparison to IR to compensate for interactions with water molecules at the membrane–solvent interfaces. Our metastable/stable states for the transmembrane domain of IR, observed in a lipid bilayer, are consistent with a known NMR structure of this domain determined in detergent micelles, and similar states in IGF1R are consistent with a previously reported model of the dimerized transmembrane domains of IGF1R. Our all-atom structural models suggest potentially unique structural organization of kinase domains in each receptor. PMID

  5. Metabolic factors, adipose tissue, and plasminogen activator inhibitor-1 levels in Type 2 diabetes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plasminogen activator inhibitor-1 (PAI-1) production by adipose tissue is increased in obesity, and its circulating levels are high in type 2 diabetes. PAI-1 increases cardiovascular risk by favoring clot stability, interfering with vascular remodeling, or both. We investigated in obese diabetic per...

  6. Satisfaction with Life and Psychosocial Factors among Underserved Minorities with Type 2 Diabetes

    ERIC Educational Resources Information Center

    Phelps, Kenneth W.; Hodgson, Jennifer L.; Lamson, Angela L.; Swanson, Melvin S.; White, Mark B.

    2012-01-01

    The objective of this study was to examine the association between biomedical markers of disease management and psychosocial constructs, while also assessing the correlates and predictors of variability for satisfaction with life (SWL) among African American and Hispanic participants with type 2 diabetes. Data were collected from 142 participants…

  7. Type I Diabetes Mellitus: Genetic Factors and Presumptive Enteroviral Etiology or Protection

    PubMed Central

    Precechtelova, Jana; Borsanyiova, Maria; Sarmirova, Sona

    2014-01-01

    We review type 1 diabetes and host genetic components, as well as epigenetics and viruses associated with type 1 diabetes, with added emphasis on the enteroviruses, which are often associated with triggering the disease. Genus Enterovirus is classified into twelve species of which seven (Enterovirus A, Enterovirus B, Enterovirus C, and Enterovirus D and Rhinovirus A, Rhinovirus B, and Rhinovirus C) are human pathogens. These viruses are transmitted mainly by the fecal-oral route; they may also spread via the nasopharyngeal route. Enterovirus infections are highly prevalent, but these infections are usually subclinical or cause a mild flu-like illness. However, infections caused by enteroviruses can sometimes be serious, with manifestations of meningoencephalitis, paralysis, myocarditis, and in neonates a fulminant sepsis-like syndrome. These viruses are often implicated in chronic (inflammatory) diseases as chronic myocarditis, chronic pancreatitis, and type 1 diabetes. In this review we discuss the currently suggested mechanisms involved in the viral induction of type 1 diabetes. We recapitulate current basic knowledge and definitions. PMID:25574400

  8. A Factor-Analytic Investigation of Role Types and Profiles of Higher Education Department Chairs.

    ERIC Educational Resources Information Center

    Carroll, James B.; Gmelch, Walter H.

    This paper reports on a study that investigated the role, attitudes, and behaviors of department chairs in higher education. Specifically, the study investigated four objectives: (1) to examine role factors of effective chair performance; (2) to assess the impact of antecedent variables such as individual characteristics (gender, marital status,…

  9. Academic Skills in Children with Early-Onset Type 1 Diabetes: The Effects of Diabetes-Related Risk Factors

    ERIC Educational Resources Information Center

    Hannonen, Riitta; Komulainen, Jorma; Riikonen, Raili; Ahonen, Timo; Eklund, Kenneth; Tolvanen, Asko; Keskinen, Paivi; Nuuja, Anja

    2012-01-01

    Aim: The study aimed to assess the effects of diabetes-related risk factors, especially severe hypoglycaemia, on the academic skills of children with early-onset type 1 diabetes mellitus (T1DM). Method: The study comprised 63 children with T1DM (31 females, 32 males; mean age 9y 11mo, SD 4mo) and 92 comparison children without diabetes (40…

  10. Is there a role for epidermal growth factor receptor tyrosine kinase inhibitors in epidermal growth factor receptor wild-type non-small cell lung cancer?

    PubMed Central

    Arriola, Edurne; Taus, Álvaro; Casadevall, David

    2015-01-01

    Non-small cell lung cancer (NSCLC) is the most common type of lung cancer with a world-wide annual incidence of around 1.3 million. The majority of patients are diagnosed with advanced disease and survival remains poor. However, relevant advances have occurred in recent years through the identification of biomarkers that predict for benefit of therapeutic agents. This is exemplified by the efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors for the treatment of EGFR mutant patients. These drugs have also shown efficacy in unselected populations but this point remains controversial. Here we have reviewed the clinical data that demonstrate a small but consistent subgroup of EGFR wild-type patients with NSCLC that obtain a clinical benefit from these drugs. Moreover, we review the biological rationale that may explain this benefit observed in the clinical setting. PMID:26266101

  11. Heterogeneity in the costs of type 1 diabetes in a developing country: what are the determining factors?

    PubMed Central

    2013-01-01

    Background and aims Regional differences in the clinical care of Type 1 diabetes (T1D) in Brazil have been recently described. This study aimed to estimate the costs of T1D from the public health care system’s perspective across the regions of Brazil and to determine the components that influence these costs. Methods This was a retrospective, cross-sectional and nationwide multicenter study conducted between December 2008 and December 2010 in 28 public clinics in 20 Brazilian cities. The study included 3,180 T1D subjects receiving healthcare from the National Brazilian Healthcare System (NBHCS) with a follow-up of at least one year. The direct medical costs were derived from the costs of medications, supplies, examinations, visits to the center, medical procedures and hospitalizations that occurred during the previous year. Clinical and demographic factors that determined the differences in the cost across four geographic regions (southeast, south, north/northeast and mid-west) were investigated. Results The per capita mean annual direct medical costs of T1D in US$ were 1,466.36, 1,252.83, 1,148.09 and 1,396.30 in southeast, south, north/northeast and mid-west regions, respectively. The costs of T1D in the southeast region were higher compared to south (p < 0.001) and north/northeast regions (p = < 0.001), but not to the mid-west (p = 0.146) region. The frequency of self-monitoring of blood glucose (SMBG) was different across the regions as well as the daily number of SMBG, use of insulin pumps or basal or prandial insulin analogs. Age, ethnicity, duration of diabetes, level of care, socioeconomic status and the prevalence of chronic diabetic complications differed among the regions. In a regression model the determinants of the costs were the presence of microvascular diabetes-related complications (p < 0.001), higher economic status (p < 0.001), and being from the southeast region (p < 0.001). Conclusions The present data reinforce the regional

  12. Impaired Contextual Fear Extinction Learning is Associated with Aberrant Regulation of CHD-Type Chromatin Remodeling Factors

    PubMed Central

    Wille, Alexandra; Maurer, Verena; Piatti, Paolo; Whittle, Nigel; Rieder, Dietmar; Singewald, Nicolas; Lusser, Alexandra

    2015-01-01

    Successful attenuation of fearful memories is a cognitive process requiring initiation of highly coordinated transcription programs. Chromatin-modulating mechanisms such as DNA methylation and histone modifications, including acetylation, are key regulators of these processes. However, knowledge concerning the role of ATP-dependent chromatin remodeling factors (ChRFs) being required for successful fear extinction is lacking. Underscoring the potential importance of these factors that alter histone-DNA contacts within nucleosomes are recent genome-wide association studies linking several ChRFs to various human cognitive and psychiatric disorders. To better understand the role of ChRFs in the brain, and since to date little is known about ChRF expression in the brain, we performed a comprehensive survey of expression levels of 24 ATP-dependent remodelers across different brain areas, and we identified several distinct high molecular weight complexes by chromatographic methods. We next aimed to gain novel insight into the potential regulation of ChRFs in different brain regions in association with normal and impaired fear extinction learning. To this end, we established the 129S1/SvImJ (S1) laboratory mouse strain as a model for compromised contextual fear extinction learning that can be rescued by dietary zinc restriction (ZnR). Using this model along with genetically related but fear extinction-competent 129S6/SvEv (S6) mice as controls, we found that impaired fear extinction in S1 was associated with enhanced ventral hippocampal expression of CHD1 and reduced expression of CHD5 that was normalized following successful rescue of impaired fear extinction. Moreover, a select reduction in CHD3 expression was observed in the ventral hippocampus (vHC) following successful rescue of fear extinction in S1 mice. Taken together, these data provide novel insight into the regulation of specific ChRFs following an impaired cognitive process and its rescue, and they suggest that

  13. Impaired Contextual Fear Extinction Learning is Associated with Aberrant Regulation of CHD-Type Chromatin Remodeling Factors.

    PubMed

    Wille, Alexandra; Maurer, Verena; Piatti, Paolo; Whittle, Nigel; Rieder, Dietmar; Singewald, Nicolas; Lusser, Alexandra

    2015-01-01

    Successful attenuation of fearful memories is a cognitive process requiring initiation of highly coordinated transcription programs. Chromatin-modulating mechanisms such as DNA methylation and histone modifications, including acetylation, are key regulators of these processes. However, knowledge concerning the role of ATP-dependent chromatin remodeling factors (ChRFs) being required for successful fear extinction is lacking. Underscoring the potential importance of these factors that alter histone-DNA contacts within nucleosomes are recent genome-wide association studies linking several ChRFs to various human cognitive and psychiatric disorders. To better understand the role of ChRFs in the brain, and since to date little is known about ChRF expression in the brain, we performed a comprehensive survey of expression levels of 24 ATP-dependent remodelers across different brain areas, and we identified several distinct high molecular weight complexes by chromatographic methods. We next aimed to gain novel insight into the potential regulation of ChRFs in different brain regions in association with normal and impaired fear extinction learning. To this end, we established the 129S1/SvImJ (S1) laboratory mouse strain as a model for compromised contextual fear extinction learning that can be rescued by dietary zinc restriction (ZnR). Using this model along with genetically related but fear extinction-competent 129S6/SvEv (S6) mice as controls, we found that impaired fear extinction in S1 was associated with enhanced ventral hippocampal expression of CHD1 and reduced expression of CHD5 that was normalized following successful rescue of impaired fear extinction. Moreover, a select reduction in CHD3 expression was observed in the ventral hippocampus (vHC) following successful rescue of fear extinction in S1 mice. Taken together, these data provide novel insight into the regulation of specific ChRFs following an impaired cognitive process and its rescue, and they suggest that

  14. Basal insulin persistence, associated factors, and outcomes after treatment initiation among people with type 2 diabetes mellitus in the US.

    PubMed

    Perez-Nieves, Magaly; Kabul, Samaneh; Desai, Urvi; Ivanova, Jasmina I; Kirson, Noam Y; Cummings, Alice Kate; Birnbaum, Howard G; Duan, Ran; Cao, Dachuang; Hadjiyianni, Irene

    2016-04-01

    Objective To assess basal insulin persistence, associated factors, and economic outcomes for insulin-naïve people with type 2 diabetes mellitus (T2DM) in the US. Research design and methods People aged ≥18 years diagnosed with T2DM initiating basal insulin between April 2006 and March 2012 (index date), no prior insulin use, and continuous insurance coverage for 6 months before (baseline) and 24 months after index date (follow-up period) were selected using de-identified administrative claims data in the US. Based on whether there were ≥30 day gaps in basal insulin use in the first year post-index, patients were classified as continuers (no gap), interrupters (≥1 prescription after gap), and discontinuers (no prescription after gap). Main outcome measures Factors associated with persistence - assessed using multinomial logistic regression model; annual healthcare resource use and costs during follow-up period - compared separately between continuers and interrupters, and continuers and discontinuers. Results Of the 19,110 people included in the sample (mean age: 59 years, ∼60% male), 20% continued to use basal insulin, 62% had ≥1 interruption, and 18% discontinued therapy in the year after initiation. Older age, multiple antihyperglycemic drug use, and injectable antihyperglycemic use during baseline were associated with significantly higher likelihoods of continuing basal insulin. Relative to interrupters and discontinuers, continuers had fewer emergency department visits, shorter hospital stays, and lower medical costs (continuers: $10,890, interrupters: $13,674, discontinuers: $13,021), but higher pharmacy costs (continuers: $7449, interrupters: $5239, discontinuers: $4857) in the first year post-index (p < 0.05 for all comparisons). Total healthcare costs were similar across the three cohorts. Findings for the second year post-index were similar. Conclusions The majority of people in this study interrupted or discontinued basal insulin

  15. Evaluation of Factors Influencing Efficacy of Vaccine Strain CVI988 Against Marek's Disease in Meat-Type Chickens.

    PubMed

    Gimeno, Isabel M; Cortes, Aneg L; Faiz, Nik M; Barbosa, Taylor; Villalobos, Tarsicio

    2015-09-01

    Marek's disease (MD) strain CVI988 is the most-protective commercially available vaccine against very virulent plus (vv+) Marek's disease virus (MDV). However, its use in meat-type chickens has been controversial. While several countries have been using CVI988 for more than 40 yr, others do not authorize its use or it is restricted mainly to layers. The use of CVI988 in meat-type chickens will be necessary in the future in areas where other vaccine protocols fail. The objective of this study was to evaluate factors (vaccine dose, vaccine origin, chicken genetics, age and route of vaccination, and combination with other MD vaccines) influencing the efficacy of CVI988 against MD in meat-type chickens. Three animal experiments were conducted in which various vaccine protocols using CVI988 were tested for their protection against challenge with vv+ strain 648A by contact at day of age. Experiments 1 and 2 were to compare the efficacy of CVI988 vaccines from three different origins (CVI988-A, CVI988-B, and CVI988-C) and evaluate the effect of vaccine dose and chicken genetics. Experiment 3 was to evaluate the effect of adding CVI988 vaccine to various vaccine protocols using other MD vaccines of serotypes 2 (SB-1) and 3 (rHVT). Our results show that, regardless of the origin of the vaccine, protection against early challenge with 648A was good when vaccines were administered at a high dose (>3000 plaque-forming units [PFU]). Differences among vaccines, however, were detected even when using a high dose in experiment 2 (vaccine CVI988-B conferred higher protection than did CVI988-C) but not in Experiment 1 (CVI988-B was compared to CVI988-A). The use of a fixed low dose (2000 PFU) of vaccine resulted in reduction in protection, and such reduction was more remarkable when using CV1988-A. No statistically significant differences were found when we compared the efficacy of CVI988 in two different genetic lines of broiler chickens (G1 and G2). Vaccination protocols that

  16. Association of vascular endothelial growth factor, transforming growth factor beta, and interferon gamma gene polymorphisms with proliferative diabetic retinopathy in patients with type 2 diabetes

    PubMed Central

    Paine, Suman Kalyan; Basu, Analabha; Mondal, Lakshmi Kanta; Sen, Aditi; Choudhuri, Subhadip; Chowdhury, Imran Hussain; Saha, Avijit; Bhadhuri, Gautam; Mukherjee, Ankur

    2012-01-01

    Purpose Chronic hyperglycemia and hypoxemia are believed to be causal factors in the development of proliferative diabetic retinopathy (PDR) among individuals with type 2 diabetes. It is hypothesized that formation of new blood vessels in the retina due to prolonged hypoxia is associated with increased expression of several growth factors and angiogenic cytokines. In the present study, we investigated the association of genetic polymorphisms in vascular endothelial growth factor (VEGF), transforming growth factor beta (TGF-β), and interferon γ (IFN-γ) genes, which may be responsible for the hypoxia-induced VEGF-mediated neovascularization pathway for the pathogenesis of PDR. Methods Our case-control association study composed of 493 ethnically matched volunteers (253 with PDR [cases] and 240 diabetic controls [DC]). Gene polymorphisms were determined with Taqman-based real-time PCR and amplification refractory mutation analysis system PCR. Results The VEGF-460C (rs833061C; p=0.0043) and IFN-γ +874T (rs2430561T; p=0.0011) alleles were significantly associated with PDR. Conclusions Genetic variations at VEGF-460C and IFN-γ +874T might accelerate the pathogenesis of retinal neovascularization in PDR. PMID:23213275

  17. Effect of centrifugation time on growth factor and MMP release of an experimental platelet-rich fibrin-type product.

    PubMed

    Eren, Gülnihal; Gürkan, Ali; Atmaca, Harika; Dönmez, Ayhan; Atilla, Gül

    2016-07-01

    Platelet-rich fibrin (PRF) has a controlled release of growth factors due to the fibrin matrix structure. Different centrifugation protocols were suggested for PRF preparation. Since the derivation method of PRF can alter its contents, in the present study it is aimed to investigate the cell contents and transforming growth factor beta-1 (TGF-β1), platelet-derived growth factor (PDGF-AB), vascular endothelial growth factor (VEGF), matrix metalloproteinase (MMP)-1 and-8 release from experimental PRF-type membranes obtained with different centrifugation times at 400 gravity. Three blood samples were collected from 20 healthy non-smoker volunteers. One tube was used for whole blood analyses. The other two tubes were centrifuged at 400 g for 10 minutes (group A) or 12 minutes (group B). Each experimental PRF-type membrane was placed in Dulbecco's Modified Eagle's Medium (DMEM)and at 1, 24 and 72 hours, TGF-β1, PDGF-AB, VEGF, MMP-1 and -8 release amounts were analysed by enzyme-linked immunosorbent assay (ELISA). The blood cell count of membranes was determined by subtracting plasma supernatant and red blood cell (RBC) mixture from the whole blood cell counts. At 72 hours, the VEGF level of group B was statistically higher than that of group A (p = 0.040). The centrifugation time was not found to influence the release of other growth factors, enzymes and cell counts. Within the limits of the present study, it might be suggested that centrifugation time at a constant gravity has a significant effect on the VEGF levels released from experimental PRF-type membrane. It can be concluded that due to the importance of VEGF in the tissue healing process, membranes obtained at 12-minute centrifugation time may show a superior potential in wound healing. PMID:26830681

  18. Effects of metformin plus gliclazide versus metformin plus glimepiride on cardiovascular risk factors in patients with type 2 diabetes mellitus.

    PubMed

    Hassan, Memy Hegazy; Abd-Allah, Gamil Mohamed

    2015-09-01

    High blood glucose level, lipid profile disturbances and plasma homocysteine (Hcy) are important risk factors for cardiovascular diseases in patients with type 2 diabetes. This study was conducted to evaluate and compare effects of glimepiride/metformin combination versus gliclazide/metformin combination on cardiovascular risk factors in type-2 diabetes mellitus (T2DM) patients. One hundred and eighty T2DM patients were randomly allocated for treatment with placebo (control), metformin (500 mg twice daily), glimepiride (3mg once daily), gliclazide (80 mg once daily), metformin plus glimepiride or metformin plus gliclazide for 3 months. We evaluated plasma levels of glucose (PG), glycated hemoglobin (HbA1C), Hcy, vitamin B12, folic acid and lipid profile before treatment and 3 months post treatment. Compared to metformin treated patients, glimepiride plus metformin induced significant reductions in: fasting plasma glucose, postprandial PG level, HbA1C % and Hcy level. Conversely, plasma folic acid and vitamin B12 were significantly increased. The levels of total cholesterol and triglyceride were significantly decreased; low-density lipoprotein was markedly decreased, whereas high-density lipoprotein was significantly increased and hence risk ratio was significantly decreased. Similar results but with lower values were obtained using combination of metformin plus gliclazide on glycemic control only. Combination of glimepiride with metformin was superior to gliclazide plus metformin in alleviating the cardiovascular risk factors in type 2 diabetes mellitus patients. PMID:26408873

  19. Type 1 Diabetes in the Spanish Population: additional factors to Class II HLA-DR3 and -DR4

    PubMed Central

    Urcelay, Elena; Santiago, José L; de la Calle, Hermenegildo; Martínez, Alfonso; Méndez, Julián; Ibarra, José M; Maluenda, Carlos; Fernández-Arquero, Miguel; de la Concha, Emilio G

    2005-01-01

    Background The Major Histocompatibility Complex is the main genetic contributor to susceptibility to type 1 diabetes (T1D); genome-wide scans have consistently mapped increased predisposition to this region. The highest disease risk has been associated with HLA-DR3 and HLA-DR4. In particular, the DR3-positive ancestral haplotype 18.2 was reported as highly diabetogenic. We aimed to corroborate whether this haplotype increases the susceptibility conferred by the DQ2-DR3 alleles in a Mediterranean population. We also searched for additional susceptibility factors to the classic DQ2-DR3 and DQ8-DR4. Results Genetic MHC markers were analysed in a case-control study with 302 T1D patients and 529 ethnically matched controls. DR3-TNFa1b5 carrier rate was significantly higher in DR3-positive heterozygous T1D patients than in DR3-positive heterozygous controls (p = 0.0019; odds ratio OR [95% confidence interval CI] = 2.26 [1.3–3.93]). This data was confirmed analysing the allelic frequency, which includes the information corresponding to the DR3-homozygous individuals (p = 0.001; OR = 2.09) and by using the Arlequin software to check the DR3-positive haplotypes (p = 0.004;OR = 1.93). The present results provide strong evidence of a second susceptibility region in the ancestral haplotype 18.2 in the Spanish population. Moreover, we searched for T1D susceptibility factors in addition to the MHC classical ones, within the DR2-DQ6/DR3-DQ2/DR4-DQ8 negative population. Several genetic markers in both MHC class II (DQA1*0101-DQB1*0501 [p = 0.007;OR = 2.81], DQA1*0201-DQB1*0202 [p = 0.03; OR = 2.35]) and III (TNFa2b1 [p = 0.01 OR = 2.74], BAT-2*2 [p = 0.004; OR = 3.19]) were found. These different alleles associated with T1D were not independent and we observed linkage disequilibrium among them leading us to describe two new risk haplotypes (DQA1*0101-DQB1*0501-TNFa2b1 and DQA1*0201-DQB1*0202- BAT-2*2). Finally, we studied a T1D susceptibility/protection marker located in

  20. Type 2 diabetes and edentulism as chronic co-morbid factors affecting Indian elderly: an overview.

    PubMed

    Ladha, Komal; Tiwari, Bhawana

    2013-12-01

    In past 50 years, type 2 diabetes has emerged as one of the major public health problem. India leads the world with the largest number of diabetic patients and has a huge elderly population. The present article discusses the effect of diabetes and edentulism on the overall general health of elderly. The prevalence of type 2 diabetes and edentulism in Indian elderly and their inter-relationship has been discussed. Dentists must provide optimum oral care with special attention towards comprehensive periodontal management and oral hygiene awareness among diabetics to prevent tooth loss. Dental and medical professionals can improve patient management of the oral and overall effects of diabetes by implementing various awareness programs; organizing camps; distributing informative pamphlets and dietary counseling. Dentists can detect undiagnosed cases of diabetes and refer patients to physicians for further evaluation and management. PMID:24431769

  1. [Factors limiting glycaemic control in insulin-treated type 2 diabetes].

    PubMed

    Ferencz, Viktória; Domján, Beatrix; Gerő, László; Tänczer, Tímea; Tabák, Gy Ádám

    2015-09-01

    Insulin therapy is the most effective treatment of diabetes. It is proven to prevent microvascular disease and likely to decrease the risk of cardiovascular complications. However, these benefits are associated with a 2-3 times increased risk of hypoglycaemia and a faster weight gain compared to other antidiabetic medications. In addition, one study found elevated all-cause mortality among patients on intensive therapy (requiring more frequent insulinisation). Insulin has growth factor properties that may translate to increased mitogenicity. These factors could prevent the medical team or the patient from initiation or intensification of insulin therapy. The authors describe evidence on long-term remission related to transient intensified insulin therapy at diabetes diagnosis. The currently recommended method of insulin initiation is once daily basal insulin treatment that offers different schedules for intensification. The authors review the pharmacokinetics of analogue insulins that translate to similar efficacy to human insulins with a 20-30% lower risk of hypoglycaemia. PMID:26320598

  2. Fibroblast Growth Factor 21 As an Emerging Therapeutic Target for Type 2 Diabetes Mellitus.

    PubMed

    So, Wing Yan; Leung, Po Sing

    2016-07-01

    Fibroblast growth factor (FGF) 21 is a distinctive member of the FGF family that functions as an endocrine factor. It is expressed predominantly in the liver, but is also found in adipose tissue and the pancreas. Pharmacological studies have shown that FGF21 normalizes glucose and lipid homeostasis, thereby preventing the development of metabolic disorders, such as obesity and diabetes. Despite growing evidence for the therapeutic potential of FGF21, paradoxical increases of FGF21 in different disease conditions point to the existence of FGF21 resistance. In this review, we give a critical appraisal of recent advances in the understanding of the regulation of FGF21 production under various physiological conditions, its antidiabetic actions, and the clinical implications. We also discuss recent preclinical and clinical trials using engineered FGF21 analogs in the management of diabetes, as well as the potential side effects of FGF21 therapy. PMID:27031294

  3. Factors associated with diet barriers in patients with poorly controlled type 2 diabetes

    PubMed Central

    Cheng, Li; Leung, Doris Yin-ping; Sit, Janet Wing-hung; Li, Xiao-mei; Wu, Yu-ning; Yang, Miao-yan; Gao, Cui-xia; Hui, Rong

    2016-01-01

    Background The study was conducted to investigate the diet barriers perceived by patients with poorly controlled type 2 diabetes and examine the associations between diet barriers and sociodemographic characteristics, medical condition, and patient-centered variables. Methods Secondary subgroup analyses were conducted based on the responses of 246 adults with poorly controlled type 2 diabetes from a multicenter, cross-sectional study. Diet barriers were captured by the Diet Barriers subscale of the Personal Diabetes Questionnaire. Participants also completed validated measures of diet knowledge, empowerment level, and appraisal of diabetes. Multiple regression techniques were used for model building, with a hierarchical block design to determine the separate contribution of sociodemographic characteristics, medical condition, and patient-centered variables to diet barriers. Results Diet barriers were moderately evident (2.23±0.86) among Chinese patients with poorly controlled type 2 diabetes. The feeling of deprivation as a result of complying with a diet was the most recognized diet barrier (3.24±1.98), followed by “eating away from home” (2.79±1.82). Significantly higher levels of diet barriers were observed among those with lower levels of diet knowledge (β=−0.282, P<0.001) and empowerment (β=−0.190, P=0.015), and more negative appraisal (β=0.225, P=0.003). Conclusion Culturally tailored, patient-centered intervention programs that acknowledge individuals’ preferences and allow for flexibility in diet management should be launched. Interventions programs that could enhance diet knowledge, promote positive appraisal, and improve empowerment level might effectively address diet barriers perceived by patients with poorly controlled type 2 diabetes. PMID:26834464

  4. Quality Factor Measurements of Various Types of Quartz Crystal Resonators Operating Near 4 K.

    PubMed

    Galliou, Serge; Goryachev, Maxim; Abbe, Philippe; Vacheret, Xavier; Tobar, Michael E; Bourquin, Roger

    2016-07-01

    Quartz crystal resonators can exhibit huge quality factors (in excess of 1 billion) at liquid-helium temperature. However, they must satisfy a set of conditions to meet this high level of performance. With the help of experimentation, the main conditions are identified, such as the material quality, the energy trapping due to the vibrational mode structure, as well as the corresponding influence of the support mechanism and the effects of the electrodes. PMID:26701342

  5. Borna disease virus nucleoprotein inhibits type I interferon induction through the interferon regulatory factor 7 pathway

    SciTech Connect

    Song, Wuqi; Kao, Wenping; Zhai, Aixia; Qian, Jun; Li, Yujun; Zhang, Qingmeng; Zhao, Hong; Hu, Yunlong; Li, Hui; Zhang, Fengmin

    2013-09-06

    Highlights: •IRF7 nuclear localisation was inhibited by BDV persistently infected. •BDV N protein resistant to IFN induction both in BDV infected OL cell and N protein plasmid transfected OL cell. •BDV N protein is related to the inhibition of IRF7 nuclear localisation. -- Abstract: The expression of type I interferon (IFN) is one of the most potent innate defences against viral infection in higher vertebrates. Borna disease virus (BDV) establishes persistent, noncytolytic infections in animals and in cultured cells. Early studies have shown that the BDV phosphoprotein can inhibit the activation of type I IFN through the TBK1–IRF3 pathway. The function of the BDV nucleoprotein in the inhibition of IFN activity is not yet clear. In this study, we demonstrated IRF7 activation and increased IFN-α/β expression in a BDV-persistently infected human oligodendroglia cell line following RNA interference-mediated BDV nucleoprotein silencing. Furthermore, we showed that BDV nucleoprotein prevented the nuclear localisation of IRF7 and inhibited endogenous IFN induction by poly(I:C), coxsackie virus B3 and IFN-β. Our findings provide evidence for a previously undescribed mechanism by which the BDV nucleoprotein inhibits type I IFN expression by interfering with the IRF7 pathway.

  6. So-Eum Type as an Independent Risk Factor for Irritable Bowel Syndrome: A Population-Based Study in Korea

    PubMed Central

    Lee, Seung Ku; Yoon, Dae Wui; Yi, Hyeryeon; Lee, Si Woo; Kim, Jong Yeol; Kim, Jin Kwan; Hong, Jeong Hwa

    2014-01-01

    Abstract Objectives: It has been hypothesized that Sasang constitutional types (SCTs) have a specific hypoactive organ, which can account for vulnerability to related diseases or symptoms. This study examined the relationship between SCTs and irritable bowel syndrome (IBS). Design: Cross-sectional study in a population-based cohort study in Korea. Participants: 1362 individuals (705 men and 657 women) who participated in the Korean Genome and Epidemiology Study. Outcome measures: The participants were classified into SCTs by the integrated diagnostic model and asked about symptoms related to IBS using the Rome II criteria. Results: The prevalence of IBS differed significantly among the SCTs, with 33 (18.3%) of the So-eum (SE) type, 74 (9.9%) of the Tae-eum (TE) type, and 57 (13.2%) of the So-yang (SY) type having IBS. Even after adjustment for possible confounders, the SE type for both sexes continued to show 1.82-fold (95% confidence interval [CI], 1.05–3.16) excess odds of having IBS. Men with SE type had a 2.97 times (95% CI, 1.34–6.58) and a 2.50 times (95% CI, 1.15–5.47) significantly higher odds of having IBS than the TE and SY types, respectively. In analysis for the joint effect of SCT and psychological stress, the multivariate odds ratio of IBS was 3.21 (95% CI, 1.33–7.75) for the SE type and Psychological Well-Being Index-Short Form (PWI-SF) score (<27), and 5.83 (95% CI, 1.80–18.88) for the SE type and PWI-SF (≥27) compared with the TE type and PWI-SF score (<27). Conclusions: The SE type of SCT is an independent risk factor for IBS. The findings support the hypothesis that persons with SE type are vulnerable to gastrointestinal diseases. PMID:25148474

  7. Ciliary transcription factors in cancer--how understanding ciliogenesis can promote the detection and prognosis of cancer types.

    PubMed

    Walentek, Peter

    2016-05-01

    Cilia play a plethora of roles in normal development and homeostasis as well as in disease. Their involvement in cell signalling processes and ability to inhibit cell cycle progression make them especially interesting subjects of investigation in the context of tumour formation and malignancy. Several key transcription factors regulate the transcriptional programme in cilia formation and some of these, eg RFX factors and FOXJ1, are implicated in cancer formation. Furthermore, RFX factors and FOXJ1 are increasingly being explored for their potential as markers to diagnose, classify and predict the outcome of cancers in patients, including recent work published in this journal on aggressive ependymoma and choroid plexus tumours. Here, some of the key findings and concepts on the roles of ciliary transcription factors in tumourigenesis are highlighted, and a brief perspective is given on how the investigation of ciliogenesis could contribute valuable tools for the diagnosis and prognosis of cancers. PMID:26880325

  8. GSK3 protein positively regulates type I insulin-like growth factor receptor through forkhead transcription factors FOXO1/3/4.

    PubMed

    Huo, Xiaodong; Liu, Shu; Shao, Ting; Hua, Hui; Kong, Qingbin; Wang, Jiao; Luo, Ting; Jiang, Yangfu

    2014-09-01

    Glycogen synthase kinase-3 (GSK3) has either tumor-suppressive roles or pro-tumor roles in different types of human tumors. A number of GSK3 targets in diverse signaling pathways have been uncovered, such as tuberous sclerosis complex subunit 2 and β-catenin. The O subfamily of forkhead/winged helix transcription factors (FOXO) is known as tumor suppressors that induce apoptosis. In this study, we find that FOXO binds to type I insulin-like growth factor receptor (IGF-IR) promoter and stimulates its transcription. GSK3 positively regulates the transactivation activity of FOXO and stimulates IGF-IR expression. Although kinase-dead GSK3β cannot up-regulate IGF-IR, the constitutively active GSK3β induces IGF-IR expression in a FOXO-dependent manner. Serum starvation or Akt inhibition leads to an increase in IGF-IR expression, which could be blunted by GSK3 inhibition. GSK3β knockdown or GSK3 inhibitor suppresses IGF-I-induced IGF-IR, Akt, and ERK1/2 phosphorylation. Moreover, knockdown of GSK3β or FOXO1/3/4 leads to a decrease in cellular proliferation and abrogates IGF-I-induced hepatoma cell proliferation. These results suggest that GSK3 and FOXO may positively regulate IGF-I signaling and hepatoma cell proliferation. PMID:25053419

  9. GSK3 Protein Positively Regulates Type I Insulin-like Growth Factor Receptor through Forkhead Transcription Factors FOXO1/3/4

    PubMed Central

    Huo, Xiaodong; Liu, Shu; Shao, Ting; Hua, Hui; Kong, Qingbin; Wang, Jiao; Luo, Ting; Jiang, Yangfu

    2014-01-01

    Glycogen synthase kinase-3 (GSK3) has either tumor-suppressive roles or pro-tumor roles in different types of human tumors. A number of GSK3 targets in diverse signaling pathways have been uncovered, such as tuberous sclerosis complex subunit 2 and β-catenin. The O subfamily of forkhead/winged helix transcription factors (FOXO) is known as tumor suppressors that induce apoptosis. In this study, we find that FOXO binds to type I insulin-like growth factor receptor (IGF-IR) promoter and stimulates its transcription. GSK3 positively regulates the transactivation activity of FOXO and stimulates IGF-IR expression. Although kinase-dead GSK3β cannot up-regulate IGF-IR, the constitutively active GSK3β induces IGF-IR expression in a FOXO-dependent manner. Serum starvation or Akt inhibition leads to an increase in IGF-IR expression, which could be blunted by GSK3 inhibition. GSK3β knockdown or GSK3 inhibitor suppresses IGF-I-induced IGF-IR, Akt, and ERK1/2 phosphorylation. Moreover, knockdown of GSK3β or FOXO1/3/4 leads to a decrease in cellular proliferation and abrogates IGF-I-induced hepatoma cell proliferation. These results suggest that GSK3 and FOXO may positively regulate IGF-I signaling and hepatoma cell proliferation. PMID:25053419

  10. Technology-Delivered Dating Aggression: Risk and Promotive Factors and Patterns of Associations Across Violence Types Among High-Risk Youth

    PubMed Central

    Roche, Jessica S.; Walton, Maureen A.; Zimmerman, Marc A.; Chermack, Stephen T.; Cunningham, Rebecca M.

    2014-01-01

    Abstract Increasingly, technology (text, e-mail, and social media) is being used in dating relationships to stalk, control, threaten, and harass dating partners. This study examines risk and promotive factors associated with technology-delivered dating aggression (TDA) and relations between types of violence (physical dating/nondating, community violence, and TDA). Participants (14–20 years old) self-administered a computerized survey as part of a larger study at an urban emergency department. The study includes 210 youth who reported having a dating partner in the past 2 months. About 48.1% of participants reported TDA in the past 2 months. Mindfulness was negatively associated with TDA. Youth reporting TDA were more likely to report physical dating violence and community violence exposure. TDA is not an isolated occurrence and is positively associated with in-person violence among adolescents. Associations between TDA, risk and promotive factors, and other forms of violence can help identify avenues for targeting interventions.

  11. Association of Heart-Type Fatty Acid-Binding Protein with Cardiovascular Risk Factors and All-Cause Mortality in the General Population: The Takahata Study

    PubMed Central

    Otaki, Yoichiro; Watanabe, Tetsu; Takahashi, Hiroki; Hirayama, Atushi; Narumi, Taro; Kadowaki, Shinpei; Honda, Yuki; Arimoto, Takanori; Shishido, Tetsuro; Miyamoto, Takuya; Konta, Tsuneo; Shibata, Yoko; Fukao, Akira; Daimon, Makoto; Ueno, Yoshiyuki; Kato, Takeo; Kayama, Takamasa; Kubota, Isao

    2014-01-01

    Background Despite many recent advances in medicine, preventing the development of cardiovascular diseases remains a challenge. Heart-type fatty acid-binding protein (H-FABP) is a marker of ongoing myocardial damage and has been reported to be a useful indicator for future cardiovascular events. However, it remains to be determined whether H-FABP can predict all-cause and cardiovascular deaths in the general population. Methods and Results This longitudinal cohort study included 3,503 subjects who participated in a community-based health checkup with a 7-year follow-up. Serum H-FABP was measured in registered subjects. The results demonstrated that higher H-FABP levels were associated with increasing numbers of cardiovascular risk factors, including hypertension, diabetes mellitus, obesity, and metabolic syndrome. There were 158 deaths during the follow-up period, including 50 cardiovascular deaths. Deceased subjects had higher H-FABP levels compared to surviving subjects. Multivariate Cox proportional hazard regression analysis revealed that H-FABP is an independent predictor of all-cause and cardiovascular deaths after adjustments for confounding factors. Subjects were divided into four quartiles according to H-FABP level, and Kaplan-Meier analysis demonstrated that the highest H-FABP quartile was associated with the greatest risks for all-cause and cardiovascular deaths. Net reclassification index and integrated discrimination index were significantly increased by addition of H-FABP to cardiovascular risk factors. Conclusions H-FABP level was increased in association with greater numbers of cardiovascular risk factors and was an independent risk factor for all-cause and cardiovascular deaths. H-FABP could be a useful indicator for the early identification of high-risk subjects in the general population. PMID:24847804

  12. Cell Type-Dependent Nonspecific Fibroblast Growth Factor Signaling in Apert Syndrome.

    PubMed

    Yeh, Erika; Atique, Rodrigo; Fanganiello, Roberto Dalto; Sunaga, Daniele Yumi; Ishiy, Felipe Augusto André; Passos-Bueno, Maria Rita

    2016-08-15

    Apert Syndrome (AS) is one of the most severe forms of craniosynostosis. It is caused by gain-of-function mutations in the receptor fibroblast growth factor receptor 2 (FGFR2), which leads to ligand-receptor promiscuity. Here, we aimed to better understand the behavior of mesenchymal stem cells (MSCs) and of fibroblastoid cells, cellular populations that are part of the suture complex, when stimulated with different fibroblast growth factors (FGFs). We also aimed to verify whether FGFR2 specificity loss due to AS mutations would change their signaling behavior. We tested this hypothesis through cell proliferation and differentiation assays and through gene expression profiling. We found that FGF19 and FGF10 increase proliferation of fibroblastoid cells harboring the FGFR2 p.S252W mutation, but not of mutant MSCs. FGF19 and FGF10 were associated with different expression profiles in p.S252W cells. Further, in accordance to our gene expression microarray data, FGF19 decreases bone differentiation rate of mutant fibroblastoid cells and increases bone differentiation rate of MSCs. This effect in osteogenesis appears to be mediated by BMP signaling. The present data indicate that non-natural FGFR2 ligands, such as FGF10 and FGF19, are important factors in the pathophysiology of AS. Further research is needed to determine the role of modulation of MSC proliferation or use of FGF19 or anti-BMP2 as inhibitors of osteogenesis in AS subjects' cells, and whether these findings can be used in the clinical management of AS. PMID:27339175

  13. Risk factors for anal human papillomavirus infection type 16 among HIV-positive men who have sex with men in San Francisco

    PubMed Central

    Hernandez, Alexandra L.; Efird, Jimmy T.; Holly, Elizabeth A.; Berry, J. Michael; Jay, Naomi; Palefsky, Joel M.

    2015-01-01

    Background and Objective HIV-positive men who have sex with men (MSM) are at high risk of anal cancer compared with the general population. Human papillomavirus (HPV) infection, particularly HPV 16, is causally associated with anal cancer. However, risk factors for anal HPV 16 infection are poorly understood. We determined the prevalence and risk factors for anal HPV 16 infection in a population of HIV-positive MSM, most of whom were being treated with antiretroviral therapy. Design Cross-sectional data from the baseline visit of a 4-year prospective cohort study. Methods 348 HIV-positive MSM were recruited in San Francisco and received a detailed sexual behavior risk-factor questionnaire. An anal swab was used to collect specimens for HPV type-specific DNA testing using L1 HPV DNA PCR. We used log-binomial multivariable models to determine risk factors for anal HPV 16 infection. Results 92% of HIV-positive MSM had at least one anal HPV type, 80% had at least one oncogenic HPV type and 42% had HPV 16. Non-Hispanic white race and higher level of education were associated with a decreased risk of HPV 16 infection. A higher number of total male partners was associated with HPV 16 (RR: 1.6, 95%CI 1.1–2.4, p=0.01) for 201–1000 partners compared with 1–200. Injection drug use (IDU) was independently associated with anal HPV 16 infection (RR: 1.5, 95%CI 1.2–1.9, p=0.003). Conclusions The prevalence of anal HPV infection, including HPV 16, is high in HIV-positive MSM. HIV-positive MSM should be counseled about the risk associated with increased partners and IDU. PMID:23614994

  14. Impact of type 2 diabetes on the plasma levels of vascular endothelial growth factor and its soluble receptors type 1 and type 2 in patients with peripheral arterial disease*

    PubMed Central

    Wieczór, Radosław; Gadomska, Grażyna; Ruszkowska-Ciastek, Barbara; Stankowska, Katarzyna; Budzyński, Jacek; Fabisiak, Ja