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Sample records for factors including type

  1. Laser Microdissection Unravels Cell-Type-Specific Transcription in Arbuscular Mycorrhizal Roots, Including CAAT-Box Transcription Factor Gene Expression Correlating with Fungal Contact and Spread1[W

    PubMed Central

    Hogekamp, Claudia; Arndt, Damaris; Pereira, Patrícia A.; Becker, Jörg D.; Hohnjec, Natalija; Küster, Helge

    2011-01-01

    Arbuscular mycorrhizae (AM) are the most widespread symbioses on Earth, promoting nutrient supply of most terrestrial plant species. To unravel gene expression in defined stages of Medicago truncatula root colonization by AM fungi, we here combined genome-wide transcriptome profiling based on whole mycorrhizal roots with real-time reverse transcription-PCR experiments that relied on characteristic cell types obtained via laser microdissection. Our genome-wide approach delivered a core set of 512 genes significantly activated by the two mycorrhizal fungi Glomus intraradices and Glomus mossae. Focusing on 62 of these genes being related to membrane transport, signaling, and transcriptional regulation, we distinguished whether they are activated in arbuscule-containing or the neighboring cortical cells harboring fungal hyphae. In addition, cortical cells from nonmycorrhizal roots served as a reference for gene expression under noncolonized conditions. Our analysis identified 25 novel arbuscule-specific genes and 37 genes expressed both in the arbuscule-containing and the adjacent cortical cells colonized by fungal hyphae. Among the AM-induced genes specifying transcriptional regulators were two members encoding CAAT-box binding transcription factors (CBFs), designated MtCbf1 and MtCbf2. Promoter analyses demonstrated that both genes were already activated by the first physical contact between the symbionts. Subsequently, and corresponding to our cell-type expression patterns, they were progressively up-regulated in those cortical areas colonized by fungal hyphae, including the arbuscule-containing cells. The encoded CBFs thus represent excellent candidates for regulators that mediate a sequential reprogramming of root tissues during the establishment of an AM symbiosis. PMID:22034628

  2. Prime type III factors

    PubMed Central

    Shlyakhtenko, Dimitri

    2000-01-01

    It is shown that for each 0 < ? < 1, the free ArakiWoods factor of type III? cannot be written as a tensor product of two diffuse von Neumann algebras (i.e., is prime) and does not contain a Cartan subalgebra. PMID:11058159

  3. Risk Factors for Breast Cancer, Including Occupational Exposures

    PubMed Central

    Meo, Margrethe; Vainio, Harri

    2011-01-01

    The knowledge on the etiology of breast cancer has advanced substantially in recent years, and several etiological factors are now firmly established. However, very few new discoveries have been made in relation to occupational risk factors. The International Agency for Research on Cancer has evaluated over 900 different exposures or agents to-date to determine whether they are carcinogenic to humans. These evaluations are published as a series of Monographs (www.iarc.fr). For breast cancer the following substances have been classified as "carcinogenic to humans" (Group 1): alcoholic beverages, exposure to diethylstilbestrol, estrogen-progestogen contraceptives, estrogen-progestogen hormone replacement therapy and exposure to X-radiation and gamma-radiation (in special populations such as atomic bomb survivors, medical patients, and in-utero exposure). Ethylene oxide is also classified as a Group 1 carcinogen, although the evidence for carcinogenicity in epidemiologic studies, and specifically for the human breast, is limited. The classification "probably carcinogenic to humans" (Group 2A) includes estrogen hormone replacement therapy, tobacco smoking, and shift work involving circadian disruption, including work as a flight attendant. If the association between shift work and breast cancer, the most common female cancer, is confirmed, shift work could become the leading cause of occupational cancer in women. PMID:22953181

  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. Proprotein conversion is determined by a multiplicity of factors including convertase processing, substrate specificity, and intracellular environment. Cell type-specific processing of human prorenin by the convertase PC1.

    PubMed

    Benjannet, S; Reudelhuber, T; Mercure, C; Rondeau, N; Chrtien, M; Seidah, N G

    1992-06-01

    Proprotein and prohormone processing at pairs of basic residues is generally thought to be both tissue- and precursor-specific and to be developmentally regulated. Furin, PC1 (also called PC3), and PC2 represent three recently discovered subtilisin-like proteinases which cleave a number of precursors at the same pairs of basic residues normally processed in vivo. Using human prorenin as a model, we show that PC1 can process it to active renin in cells containing secretory granules, such as the somatomammotroph cell line GH4, but not in cells which lack granules, such as the Chinese hamster ovary or African green monkey kidney epithelial (BSC-40) cell lines. In contrast, in both cell types, human prorenin is not activated by either PC2 or furin. Using the vaccinia virus expression system, biosynthetic labeling experiments demonstrated that PC1 and PC2 are themselves cleaved intracellularly at pairs of basic residues and that these two proenzymes are processed to different extents independent of whether the cell line contains dense core secretory granules. Furthermore, we also show that the cells mostly secrete the cleaved forms of PC1 and PC2, and that intracellularly the pro- form of PC2 predominates. Our data demonstrate that propeptide removal from these enzymes, possibly leading to their activation, is not the only criterion which governs precursor processing. PMID:1597471

  6. 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.

  7. Nuclear actin activates human transcription factor genes including the OCT4 gene.

    PubMed

    Yamazaki, Shota; Yamamoto, Koji; Tokunaga, Makio; Sakata-Sogawa, Kumiko; Harata, Masahiko

    2015-01-01

    RNA microarray analyses revealed that nuclear actin activated many human transcription factor genes including OCT4, which is required for gene reprogramming. Oct4 is known to be activated by nuclear actin in Xenopus oocytes. Our findings imply that this process of OCT4 activation is conserved in vertebrates and among cell types and could be used for gene reprogramming of human cells. PMID:25355676

  8. Factor structure of English-language personality type-nouns.

    PubMed

    Saucier, Gerard

    2003-10-01

    Although type-nouns (e.g., idiot, hero) are important in person description, lexical studies of personality have concentrated on adjectives. This study tested structural hypotheses using 372 highly familiar English-language type-nouns and descriptions by 607 participants of either themselves, a liked, or a disliked target person. One- and 2-factor structures were most robust, and replicated similar structures found in previous adjectival studies. Additionally, the structure with 8 orthogonal factors had good replicability and applicability within single-gender subsamples; as in previous studies of type-nouns, it included factors corresponding directly to Extraversion and Intellect/Openness, but also to Attractiveness and Masculinity (or Ruggedness). The Big Five was only weakly replicated. Personality taxonomies based on adjectives are unlikely to be comprehensive, because type-nouns have different content emphases. PMID:14561123

  9. [Immunogenetic factors associated with type 1 diabetes mellitus].

    PubMed

    Fernandes, Ana Paula Morais; Pace, Ana Emilia; Zanetti, Maria Lcia; Foss, Milton Cesar; Donadi, Eduardo Antonio

    2005-01-01

    Type 1 diabetes mellitus has been considered an organ-specific autoimmune disease derived from the selective destruction of pancreatic beta cells. It presents a complex pathogenesis, involving the participation of several factors, including the immunogenetic susceptibility with strong association to histocompatibility genes (HLA), environmental events and autoimmune response with the presence of autoantibodies and/or autoreactive lymphocytes, culminating in metabolic abnormalities. In this study, the literature review describes mechanisms through which some factors cause susceptibility to its appearance and, additionally, prediction innovations regarding this disorder, which will certainly contribute to nursing care for patients with type 1 diabetes. PMID:16308633

  10. Hematopoietic growth factors including keratinocyte growth factor in allogeneic and autologous stem cell transplantation.

    PubMed

    Seggewiss, Ruth; Einsele, Hermann

    2007-07-01

    The aim of hematopoietic stem cell transplantation (HSCT) is to cure patients of malignancies, autoimmune diseases, and immunodeficiency disorders by redirecting the immune system: the often described graft-versus-leukemia (GVL) or graft-versus-tumor (GVT) effects. Unfortunately, fulfillment of this goal is often hampered by relapse of the underlying disease, graft-versus-host disease (GVHD), or severe opportunistic infections, which account for the majority of post-transplantation deaths. Moreover, studies of long-term survivors of transplantation indicate an accelerated immune aging due to the transplantation procedure itself, preceding chemo- or radiotherapy, and acute and chronic GVHD. Significant advances have been made towards overcoming these obstacles by enhancing immune reconstitution with hematopoietic growth factors (HGFs) such as granulocyte colony-stimulating factor (G-CSF) or erythropoietin (EPO) or through the application of cytokines. In addition, there are approaches to promote the thymic-dependent development of naive T cells, which are prepared for the interaction with a multitude of pathogens. Examples are the application of keratinocyte growth factor (KGF), neuroendocrine hormones such as growth hormone or prolactin, sex hormone ablation, or the invention of a three-dimensional artificial thymus based on a cytomatrix. Might these measures result in a higher rate of healthy and fully recovered patients? Here we review progress in each of these areas. PMID:17631184

  11. 78 FR 26847 - Including Specific Pavement Types in Federal-aid Highway Traffic Noise Analyses

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-08

    ... Federal Highway Administration Including Specific Pavement Types in Federal-aid Highway Traffic Noise...: The FHWA requests input from stakeholders and interested parties on expanding the specific pavement... data from three pavement types: dense-graded asphaltic concrete (DGAC), open-graded asphaltic...

  12. 48 CFR 16.104 - Factors in selecting contract types.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 1 2014-10-01 2014-10-01 false Factors in selecting contract types. 16.104 Section 16.104 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION CONTRACTING METHODS AND CONTRACT TYPES TYPES OF CONTRACTS Selecting Contract Types 16.104 Factors in selecting contract types. There are...

  13. Amplification of progenitors in the mammalian telencephalon includes a new radial glial cell type

    PubMed Central

    Pilz, Gregor-Alexander; Shitamukai, Atsunori; Reillo, Isabel; Pacary, Emilie; Schwausch, Julia; Stahl, Ronny; Ninkovic, Jovica; Snippert, Hugo J.; Clevers, Hans; Godinho, Leanne; Guillemot, Francois; Borrell, Victor; Matsuzaki, Fumio; Gtz, Magdalena

    2013-01-01

    The mechanisms governing the expansion of neuron number in specific brain regions are still poorly understood. Enlarged neuron numbers in different species are often anticipated by increased numbers of progenitors dividing in the subventricular zone. Here we present live imaging analysis of radial glial cells and their progeny in the ventral telencephalon, the region with the largest subventricular zone in the murine brain during neurogenesis. We observe lineage amplification by a new type of progenitor, including bipolar radial glial cells dividing at subapical positions and generating further proliferating progeny. The frequency of this new type of progenitor is increased not only in larger clones of the mouse lateral ganglionic eminence but also in cerebral cortices of gyrated species, and upon inducing gyrification in the murine cerebral cortex. This implies key roles of this new type of radial glia in ontogeny and phylogeny. PMID:23839311

  14. 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.

  15. 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-up (thermalization transient) within the detector cannot be ignored. Another example where signal build-up might be observed is when a {sup 3}He based system is used to track the evolution of the time correlated signal created by a higher multiplying item within a reflective configuration such as the measurement of a spent fuel assembly. In this work we develop expressions for the GUFs which include signal build-up.

  16. Humanized mouse models for type 1 diabetes including pancreatic islet transplantation.

    PubMed

    Rahmig, S; Bornstein, S R; Chavakis, T; Jaeckel, E; Waskow, C

    2015-01-01

    We comment here on the suitability of available mouse models for type 1 diabetes research including research on therapeutic pancreatic islet transplantation. The major emphasis will be laid on models that require minimal invasive procedures. Most biological processes are too complex for a complete recapitulation in a test tube. The study of innate or even adaptive immune responses involves a number of different cell types and organs making in vitro studies unreliable but also providing extreme challenges for the use of surrogate model organisms. Studying these processes directly in humans is impossible due to ethical and technical constraints. To resolve this problem small animal models such as mice or rats are frequently used to study mechanisms of complex diseases. This has brought much insight into hematopoiesis and immune cell function including type 1 diabetes (T1D); however, 65 million years of evolution introduced striking differences between mice and humans 1. In fact, none of the many suggested therapies arising from studies using mice 2 3 that have promised prevention or even reversion of T1D made it into the clinic yet 4 5 6. The reason for this are major species-specific differences between rodents and humans regarding the immune system and beta cells. PMID:25369071

  17. 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.

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

    PubMed

    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

  19. 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

  20. 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

  1. 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

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

    PubMed

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

    2015-06-16

    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

  3. 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,

  4. Environmental factors and primary prevention in type 1 diabetes

    PubMed Central

    Ilonen, Jorma; Vaarala, Outi; kerblom, 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

  5. Early Life Factors and Type 2 Diabetes Mellitus

    PubMed Central

    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

  6. Behavioral factors to include in guidelines for lifelong oral healthiness: an observational study in Japanese adults

    PubMed Central

    Morita, Ichizo; Nakagaki, Haruo; Toyama, Atsushi; Hayashi, Matsumi; Shimozato, Miho; Watanabe, Tsuyoshi; Tohmatsu, Shimpei; Igo, Junko; Sheiham, Aubrey

    2006-01-01

    Background The aim of this study was to determine which behavioral factors to include in guidelines for the Japanese public to achieve an acceptable level of oral healthiness. The objective was to determine the relationship between oral health related behaviors and symptoms related to oral disease and tooth loss in a Japanese adult community. Methods Oral health status and lifestyle were investigated in 777 people aged 20 years and older (390 men and 387 women). Subjects were asked to complete a postal questionnaire concerning past diet and lifestyle. The completed questionnaires were collected when they had health examinations. The 15 questions included their preference for sweets, how many between-meal snacks they usually had per day, smoking and drinking habits, presence of oral symptoms, and attitudes towards dental visits. Participants were asked about their behaviors at different stages of their life. The oral health examinations included examination of the oral cavity and teeth performed by dentists using WHO criteria. Odds ratios were calculated for all subjects, all 10 year age groups, and for subjects 30 years or older, 40 years or older, 50 years or older, and 60 years or older. Results Frequency of tooth brushing (OR = 3.98), having your own toothbrush (OR = 2.11), smoking (OR = 2.71) and bleeding gums (OR = 2.03) were significantly associated with number of retained teeth in males. Frequency of between-meal snacks was strongly associated with number of retained teeth in females (OR = 4.67). Having some hobbies (OR = 2.97), having a family dentist (OR = 2.34) and consulting a dentist as soon as symptoms occurred (OR = 1.74) were significantly associated with number of retained teeth in females. Factors that were significantly associated with tooth loss in both males and females included alcohol consumption (OR = 11.96, males, OR = 3.83, females), swollen gums (OR = 1.93, males, OR = 3.04, females) and toothache (OR = 3.39, males, OR = 3.52, females). Conclusion Behavioral factors that were associated with tooth retention were frequency of eating snacks between meals, tooth brushing frequency, having one's own toothbrush, smoking and drinking habits, having hobbies, having a family dentist and when they had dental treatment. Clinical factors included bleeding gums, swollen gums, and toothache. PMID:17181853

  7. Quantitative Differences in the Urinary Proteome of Siblings Discordant for Type 1 Diabetes Include Lysosomal Enzymes.

    PubMed

    Suh, Moo-Jin; Tovchigrechko, Andrey; Thovarai, Vishal; Rolfe, Melanie A; Torralba, Manolito G; Wang, Junmin; Adkins, Joshua N; Webb-Robertson, Bobbie-Jo M; Osborne, Whitney; Cogen, Fran R; Kaplowitz, Paul B; Metz, Thomas O; Nelson, Karen E; Madupu, Ramana; Pieper, Rembert

    2015-08-01

    Individuals with type 1 diabetes (T1D) often have higher than normal blood glucose levels, causing advanced glycation end product formation and inflammation and increasing the risk of vascular complications years or decades later. To examine the urinary proteome in juveniles with T1D for signatures indicative of inflammatory consequences of hyperglycemia, we profiled the proteome of 40 T1D patients with an average of 6.3 years after disease onset and normal or elevated HbA1C levels, in comparison with a cohort of 41 healthy siblings. Using shotgun proteomics, 1036 proteins were identified, on average, per experiment, and 50 proteins showed significant abundance differences using a Wilcoxon signed-rank test (FDR q-value ? 0.05). Thirteen lysosomal proteins were increased in abundance in the T1D versus control cohort. Fifteen proteins with functional roles in vascular permeability and adhesion were quantitatively changed, including CD166 antigen and angiotensin-converting enzyme 2. ?-N-Acetyl-galactosaminidase and ?-fucosidase 2, two differentially abundant lysosomal enzymes, were detected in western blots with often elevated quantities in the T1D versus control cohort. Increased release of proteins derived from lysosomes and vascular epithelium into urine may result from hyperglycemia-associated inflammation in the kidney vasculature. PMID:26143644

  8. 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.

  9. ‘Lonesome Town’? Is Loneliness Associated with the Residential Environment, including Housing and Neighbourhood Factors?

    PubMed Central

    2015-01-01

    This article considers whether feelings of loneliness are associated with aspects of the home and neighbourhood 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 neighbourhood 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 behaviour problems, who had a weak perception of collective efficacy, and who felt unsafe walking alone at night-time 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 neighbourhood physical, service and social environment, including aspects of both quality and trust, in protecting against or reducing loneliness in deprived areas. PMID:26740728

  10. 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 each professional role. As an application, we present the simulation of the discussed error, e.g. the unchecked extraction of the control rods during a power variation maneuver and we show how the effect of human errors can affect the performance function, giving rise to different countermeasures which could call different operator figures into play, potentially not envisaged in the standard procedure. (authors)

  11. The Cognitive Phenotype in Klinefelter Syndrome: A Review of the Literature Including Genetic and Hormonal Factors

    PubMed Central

    Boada, Richard; Janusz, Jennifer; Hutaff-Lee, Christa; Tartaglia, Nicole

    2011-01-01

    Klinefelter syndrome (KS) or 47,XXY occurs in ?1 in 650 males. Individuals with KS often present with physical characteristics including tall stature, hypogonadism, and fertility problems. In addition to medical findings, the presence of the extra X chromosome can lead to characteristic cognitive and language deficits of varying severity. While a small, but significant downward shift in mean overall IQ has been reported, the general cognitive abilities of patients with KS are not typically in the intellectual disability range. Most studies support that males with KS have an increased risk of language disorders and reading disabilities. Results of other studies investigating the relationship between verbal and nonverbal/spatial cognitive abilities have been mixed, with differing results based on the age and ascertainment method of the cohort studied. Executive function deficits have been identified in children and adults with KS, however, the research in this area is limited and further investigation of the neuropsychological profile is needed. In this article, we review the strengths and weaknesses of previous cognitive and neuropsychological studies in males with KS in childhood and adulthood, provide historical perspective of these studies, and review what is known about how hormonal and genetic factors influence cognitive features in 47,XXY/KS. PMID:20014369

  12. Factors underlying parental decisions about combination childhood vaccinations including MMR: a systematic review.

    PubMed

    Brown, Katrina F; Kroll, J Simon; Hudson, Michael J; Ramsay, Mary; Green, John; Long, Susannah J; Vincent, Charles A; Fraser, Graham; Sevdalis, Nick

    2010-06-11

    Suboptimal childhood vaccination uptake results in disease outbreaks, and in developed countries is largely attributable to parental choice. To inform evidence-based interventions, we conducted a systematic review of factors underlying parental vaccination decisions. Thirty-one studies were reviewed. Outcomes and methods are disparate, which limits synthesis; however parents are consistently shown to act in line with their attitudes to combination childhood vaccinations. Vaccine-declining parents believe that vaccines are unsafe and ineffective and that the diseases they are given to prevent are mild and uncommon; they mistrust their health professionals, Government and officially-endorsed vaccine research but trust media and non-official information sources and resent perceived pressure to risk their own child's safety for public health benefit. Interventions should focus on detailed decision mechanisms including disease-related anticipated regret and perception of anecdotal information as statistically representative. Self-reported vaccine uptake, retrospective attitude assessment and unrepresentative samples limit the reliability of reviewed data - methodological improvements are required in this area. PMID:20438879

  13. 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}ȯ )\\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}ȯ )\\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.

  14. Autologous stem cell transplantation for AL amyloidosis: adjustment of melphalan dose by factors including BNP.

    PubMed

    Hayashi, Toshiaki; Ikeda, Hiroshi; Igarashi, Tetsuyuki; Maruyama, Yumiko; Aoki, Yuka; Nojima, Masanori; Ishida, Tadao; Shinomura, Yasuhisa

    2014-12-01

    High-dose melphalan with autologous stem cell transplantation (HDM/ASCT) is a promising treatment option for eligible patients with systemic immunoglobulin light chain (AL) amyloidosis. We present the results of ASCT following risk-adapted melphalan conditioning on the basis of criteria proposed by our group, including B-type natriuretic peptide (BNP). Ten patients with primary systemic AL amyloidosis treated at our institute were evaluated. A full dose of melphalan (200 mg/m(2)) was administered to patients who met all the following: performance status, 0 or 1; number of organs involved, 2 or less; serum creatinine, 1.5 mg/dL or less; EF 50 % or more and BNP 200 pg/mL or less; otherwise 140 mg/m(2). The hematologic complete response was achieved in four and organ response was seen in two patients. The median event-free survival (EFS) of all patients was 21.5 months, and median overall survival (OS) was 47.0 months. EFS and OS were significantly longer for patients who received 200 mg/m(2) of melphalan than for those who received lower dose (EFS: not reached vs. 13.9 months, P = 0.0217; OS: not reached vs. 13.8 months, P = 0.0186). No treatment-related mortality within 100 days from ASCT was observed. Evaluation of cardiac diastolic function may contribute to safer HDM/ASCT and improve outcome of AL amyloidosis. PMID:25281404

  15. 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, Michle; 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 provide clues on the degree of aqueous alteration vs. thermal metamorphism and on the timing of both processes. In particular, Mokoia experienced significant aqueous alteration after the metamorphism peak, whereas Grosnaja, which has similar metamorphism grade, did not.

  16. Abeta species, including IsoAsp23 Abeta, in Iowa-type familial cerebral amyloid angiopathy.

    PubMed

    Shin, Youngah; Cho, Hyun Soon; Fukumoto, Hiroaki; Shimizu, Takahiko; Shirasawa, Takuji; Greenberg, Steven M; Rebeck, G William

    2003-03-01

    Mutations within the Abeta sequence of the AbetaPP gene are associated with familial forms of cerebral amyloid angiopathy (CAA). One mutation, Abeta D23N, was identified in a family in Iowa with a clinical history of early-onset dementia. We analyzed the pattern of Abeta deposition in the hippocampus of an individual with Iowa CAA. In addition to strong amyloid angiopathy, we found unusual diffuse Abeta deposits in the CA4, and in the parenchyma near amyloid-laden vessels. ELISA of cortical brain extracts showed that Abeta40 was nearly 20-fold higher than Abeta42, in both soluble and insoluble fractions. We identified an Abeta antibody that recognized wild-type Abeta but not Iowa Abeta. With this antibody, we found that wild-type Abeta was present in the Abeta deposits, but limited to the strongest deposits in the cerebrovasculature. Previous in vitro studies suggested that the presence of an asparagine at position 23 of Abeta favored formation of an isoAsp residue, which was associated with increased Abeta fibrillogenesis. Using isoAsp-specific antibodies in immunohistochemical studies, we examined the distribution of isoAsp Abeta in the Iowa brain. IsoAsp7 Abeta was present in both the parenchymal and vascular deposits, whereas isoAsp23 Abeta was present only in vascular deposits. These data suggest that alteration of Abeta Asn23 to isoAsp may be an important determinant in the deposition of Abeta in cerebral blood vessels. PMID:12557012

  17. 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

    ... 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 MANAGEMENT REQUIREMENTS General Provisions 719.6 Are there any types of legal matters not included in the coverage of this part? Matters not covered by this...

  18. 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

  19. ABO Genotype, Blood-Type Diet and Cardiometabolic Risk Factors

    PubMed Central

    Wang, Jingzhou; Garca-Bailo, Bibiana; Nielsen, Daiva E.; El-Sohemy, Ahmed

    2014-01-01

    Background The Blood-Type diet advises individuals to eat according to their ABO blood group to improve their health and decrease risk of chronic diseases such as cardiovascular disease. However, the association between blood type-based dietary patterns and health outcomes has not been examined. The objective of this study was to determine the association between blood-type diets and biomarkers of cardiometabolic health and whether an individual's ABO genotype modifies any associations. Methods Subjects (n?=?1,455) were participants of the Toronto Nutrigenomics and Health study. Dietary intake was assessed using a one-month, 196-item food frequency questionnaire and a diet score was calculated to determine relative adherence to each of the four Blood-Type diets. ABO blood group was determined by genotyping rs8176719 and rs8176746 in the ABO gene. ANCOVA, with age, sex, ethnicity, and energy intake as covariates, was used to compare cardiometabolic biomarkers across tertiles of each Blood-Type diet score. Results Adherence to the Type-A diet was associated with lower BMI, waist circumference, blood pressure, serum cholesterol, triglycerides, insulin, HOMA-IR and HOMA-Beta (P<0.05). Adherence to the Type-AB diet was also associated with lower levels of these biomarkers (P<0.05), except for BMI and waist circumference. Adherence to the Type-O diet was associated with lower triglycerides (P<0.0001). Matching the Blood-Type diets with the corresponding blood group did not change the effect size of any of these associations. No significant association was found for the Type-B diet. Conclusions Adherence to certain Blood-Type diets is associated with favorable effects on some cardiometabolic risk factors, but these associations were independent of an individual's ABO genotype, so the findings do not support the Blood-Type diet hypothesis. PMID:24454746

  20. Cerebellar neurochemical alterations in spinocerebellar ataxia type 14 appear to include glutathione deficiency.

    PubMed

    Doss, Sarah; Rinnenthal, Jan Leo; Schmitz-Hbsch, Tanja; Brandt, Alexander U; Papazoglou, Sebastian; Lux, Silke; Maul, Stephan; Wrfel, Jens; Endres, Matthias; Klockgether, Thomas; Minnerop, Martina; Paul, Friedemann

    2015-08-01

    Autosomal dominant ataxia type 14 (SCA14) is a rare usually adult-onset progressive disorder with cerebellar neurodegeneration caused by mutations in protein kinase C gamma. We set out to examine cerebellar and extracerebellar neurochemical changes in SCA14 by MR spectroscopy. In 13 SCA14 patients and 13 healthy sex- and age-matched controls, 3-T single-voxel brain proton MR spectroscopy was performed in a cerebellar voxel of interest (VOI) at TE=30ms to obtain a neurochemical profile of metabolites with short relaxation times. In the cerebellum and in additional VOIs in the prefrontal cortex, motor cortex, and somatosensory cortex, a second measurement was performed at TE=144ms to mainly extract the total N-acetyl-aspartate (tNAA) signal besides the signals for total creatine (tCr) and total choline (tCho). The cerebellar neurochemical profile revealed a decrease in glutathione (6.12E-062.50E-06 versus 8.91E-063.03E-06; p=0028) and tNAA (3.78E-055.67E-06 versus 4.25E-055.15E-06; p=0023) and a trend for reduced glutamate (2.63E-056.48E-06 versus 3.15E-057.61E-06; p=0062) in SCA14 compared to controls. In the tNAA-focused measurement, cerebellar tNAA (296.642.6 versus 351.716.5; p=0004) and tCr (272.125.2 versus 303.231.4; p=0004) were reduced, while the prefrontal, somatosensory and motor cortex remained unaffected compared to controls. Neuronal pathology in SCA14 detected by MR spectroscopy was restricted to the cerebellum and did not comprise cortical regions. In the cerebellum, we found in addition to signs of neurodegeneration a glutathione reduction, which has been associated with cellular damage by oxidative stress in other neurodegenerative diseases such as Parkinson's disease and Friedreich's ataxia. PMID:26041613

  1. 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.

  2. Precipitating and relieving factors of migraine versus tension type headache

    PubMed Central

    2012-01-01

    Background To determine the differences of precipitating and relieving factors between migraine and tension type headache. Methods This is a cross sectional study. We retrospectively reviewed the records of 250 migraine patients and 250 patients diagnosed as tension type headache from the specialized headache clinic in Dept. of Neurology, Dhaka Medical College Hospital. Data were collected through a predesigned questionnaire containing information on age, sex, social status and a predetermined list of precipitating and relieving factors. Results In this study, the female patients predominated (67%). Most of the patients were within 2130?years age group (58.6%). About 58% of them belonged to middle class families. The common precipitating factors like stress, anxiety, activity, journey, reading, cold and warm were well distributed among both the migraine and tension type headache (TTH) patients. But significant difference was demonstrated for fatigue (p?factors of pain, different maneuvers were commonly tried by migraineurs and significant difference were observed for both analgesic drug and massage (p?factors for headache appear to be identical for both migraine and TTH patients. Even though some factors like fatigue, sleep deprivation, sunlight and food significantly precipitate migraine and drug, massage are effective maneuver for relieving pain among migrianeurs. PMID:22920541

  3. 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

  4. Multivariable modeling of radiotherapy outcomes, including dose-volume and clinical factors

    SciTech Connect

    El Naqa, Issam; Bradley, Jeffrey; Blanco, Angel I.; Lindsay, Patricia E.; Vicic, Milos; Hope, Andrew; Deasy, Joseph O. . E-mail: deasy@wustl.edu

    2006-03-15

    Purpose: The probability of a specific radiotherapy outcome is typically a complex, unknown function of dosimetric and clinical factors. Current models are usually oversimplified. We describe alternative methods for building multivariable dose-response models. Methods: Representative data sets of esophagitis and xerostomia are used. We use a logistic regression framework to approximate the treatment-response function. Bootstrap replications are performed to explore variable selection stability. To guard against under/overfitting, we compare several analytical and data-driven methods for model-order estimation. Spearman's coefficient is used to evaluate performance robustness. Novel graphical displays of variable cross correlations and bootstrap selection are demonstrated. Results: Bootstrap variable selection techniques improve model building by reducing sample size effects and unveiling variable cross correlations. Inference by resampling and Bayesian approaches produced generally consistent guidance for model order estimation. The optimal esophagitis model consisted of 5 dosimetric/clinical variables. Although the xerostomia model could be improved by combining clinical and dose-volume factors, the improvement would be small. Conclusions: Prediction of treatment response can be improved by mixing clinical and dose-volume factors. Graphical tools can mitigate the inherent complexity of multivariable modeling. Bootstrap-based variable selection analysis increases the reliability of reported models. Statistical inference methods combined with Spearman's coefficient provide an efficient approach to estimating optimal model order.

  5. Including transcription factor information in the superparamagnetic clustering of microarray data

    NASA Astrophysics Data System (ADS)

    Monsivis-Alonso, M. P.; Navarro-Muoz, J. C.; Riego-Ruiz, L.; Lpez-Sandoval, R.; Rosu, H. C.

    2010-12-01

    In this work, we modify the superparamagnetic clustering algorithm (SPC) by adding an extra weight to the interaction formula that considers which genes are regulated by the same transcription factor. With this modified algorithm which we call SPCTF, we analyze the Spellman et al. microarray data for cell cycle genes in yeast, and find clusters with a higher number of elements compared with those obtained with the SPC algorithm. Some of the incorporated genes by using SPCFT were not detected at first by Spellman et al. but were later identified by other studies, whereas several genes still remain unclassified. The clusters composed by unidentified genes were analyzed with MUSA, the motif finding using an unsupervised approach algorithm, and this allow us to select the clusters whose elements contain cell cycle transcription factor binding sites as clusters worthy of further experimental studies because they would probably lead to new cell cycle genes. Finally, our idea of introducing the available information about transcription factors to optimize the gene classification could be implemented for other distance-based clustering algorithms.

  6. Preoperative Serum Interleukin-6 Is a Potential Prognostic Factor for Colorectal Cancer, including Stage II Patients

    PubMed Central

    Shiga, Kazuyoshi; Hara, Masayasu; Nagasaki, Takaya; Sato, Takafumi; Takahashi, Hiroki; Sato, Mikinori; Takeyama, Hiromitsu

    2016-01-01

    Aims. To evaluate the prognostic significance of serum interleukin-6 (IL-6) in colorectal cancer (CRC). Patients and Methods. Preoperative serum IL-6 was measured in 233 CRC patients and 13 healthy controls. Relationships between IL-6 and various clinicopathological factors were evaluated, and the overall survival (OS) and disease-free survival (DFS) rates according to IL-6 status were calculated for all patients and according to disease stage. Results. The mean IL-6 level was 6.6?pg/mL in CRC patients and 2.6?pg/mL in healthy controls. Using a cutoff of 6.3?pg/mL, obtained using receiver operating characteristic curve analysis, 57 patients had a high IL-6 level. The mean value was higher for stage II disease than for stage III disease. IL-6 status correlated with C-reactive protein (CRP) and carcinoembryonic antigen levels, obstruction, and pT4 disease. The OS differed according to the IL-6 status for all patients, whereas the DFS differed for all patients and for those with stage II disease. The Cox proportional hazards model showed that pT4 disease was an independent risk factor for recurrence in all CRC patients; IL-6, CRP, and pT4 were significant risk factors in stage II patients. Conclusions. The preoperative IL-6 level influences the risk of CRC recurrence. PMID:26858756

  7. Impact of Outliers Arising from Unintended and Unknowingly Included Subpopulations on the Decisions about the Number of Factors in Exploratory Factor Analysis

    ERIC Educational Resources Information Center

    Liu, Yan; Zumbo, Bruno D.

    2012-01-01

    There is a lack of research on the effects of outliers on the decisions about the number of factors to retain in an exploratory factor analysis, especially for outliers arising from unintended and unknowingly included subpopulations. The purpose of the present research was to investigate how outliers from an unintended and unknowingly included

  8. Compilation of air pollutant emission factors, third edition (including supplements 1-7) supplement 10

    SciTech Connect

    Not Available

    1980-02-01

    In this Supplement to AP-42, new, revised and updated emissions data are presented for mobile sources; aircraft; transportation and marketing of petroleum liquids; waste solvent reclamation; tank and drum cleaning; hydrofluoric acid; phosphoric acid; sulfur recovery; wine making; harvesting of grain; primary lead smelting; coal cleaning; glass fiber manufacturing; phosphate rock processing; coal conversion; taconite ore processing; plywood veneer and layout operations; woodworking waste collection operations; and explosives detonation. There is also an expansion and revision of the Appendix A, miscellaneous data and conversion factors.

  9. Alterations in plasma transforming growth factor beta in normoalbuminuric type 1 and type 2 diabetic patients.

    PubMed

    Azar, S T; Salti, I; Zantout, M S; Major, S

    2000-12-01

    Transforming growth factor ss (TGF-ss) is an immunosuppressor. It plays a role in regulating cell proliferation, and deletion of its gene in transgenic mice leads to an autoimmune-like disorder. A role of this cytokine has been proposed in the pathogenesis of type 1 diabetes and probably type 2 diabetes. Previous studies had shown an elevated serum level in type 2 diabetes and a reduced serum level in type 1 diabetes; however, these studies did not address the onset of the alterations of TGF-ss with regard to the duration of diabetes. In this study, we compared the levels of TGF-ss in the serum of groups of patients with type 1 and type 2 diabetes mellitus divided according to the duration of their disease. Twenty-six normoalbuminuric patients with type 1 diabetes and 25 normoalbuminuric patients with type 2 diabetes were divided into three groups according to the onset of their diabetes and were compared with 27 and 15 age-matched normal subjects, respectively. We conclude that in normoalbuminuric patients serum TGF-ss levels increased at the onset of type 2 diabetes and remained elevated throughout the disease; they did not change at the onset of type1 diabetes, however, they started to decrease around 2 yr after the onset of the disease. PMID:11134127

  10. 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 spectrum. PMID:25072324

  11. Cellular factors regulate transactivation of human immunodeficiency virus type 1.

    PubMed Central

    Barry, P A; Pratt-Lowe, E; Unger, R E; Luciw, P A

    1991-01-01

    It is hypothesized that the immediate-early (IE) gene products of human cytomegalovirus (CMV) and the transactivator (TAT) of human immunodeficiency virus type 1 (HIV-1) regulate HIV-1 gene expression through mechanisms involving host cell factors. By using transient transfection assays with the gene for chloramphenicol acetyltransferase (CAT) under the transcriptional control of the HIV-1 long terminal repeat (LTR), we examined transactivation of the LTR by plasmids that express either the HIV-1 gene for TAT or human CMV IE. The ratio of the level of transactivation by CMV IE to the level of transactivation by TAT varied up to 1,000-fold between cell types. The difference in the activities of these transactivators in various cell types was not a consequence of differential expression of the transactivator gene. Analysis of RNA species initiated in the HIV-1 LTR supports the conclusion that cellular factors regulate the level of elongation of the transcription complex on the LTR. Furthermore, evidence that in some cell types the predominant mechanism of transactivation by HIV-1 TAT involves posttranscriptional processes is presented. Images PMID:1995949

  12. Targets of the StBEL5 Transcription Factor Include the FT Ortholog StSP6A.

    PubMed

    Sharma, Pooja; Lin, Tian; Hannapel, David J

    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

  13. 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

  14. Meson electro-magnetic form factors in an extended NambuJona-Lasinio model including heavy quark flavors

    NASA Astrophysics Data System (ADS)

    Luan, Yi-Long; Chen, Xiao-Lin; Deng, Wei-Zhen

    2015-11-01

    Based on an extended NJL model including heavy quark flavors, we calculate the form factors of pseudo-scalar and vector mesons. After taking into account the vector-meson-dominance effect, which introduces a form factor correction to the quark vector coupling vertices, the form factors and electric radii of ?+ and K+ pseudo-scalar mesons in the light flavor sector fit the experimental data well. The magnetic moments of the light vector mesons ?+ and K*+ are comparable with other theoretical calculations. The form factors in the light-heavy flavor sector are presented to compare with future experiments or other theoretical calculations.

  15. 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

  16. 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...

  17. 10 CFR 719.6 - Are there any types of legal matters not included in the coverage of this part?

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... insurance carrier; (b) Routine intellectual property law support services; (c) Routine workers and... 10 Energy 4 2013-01-01 2013-01-01 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...

  18. 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...

  19. 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...

  20. 36 CFR 1290.4 - Types of materials included in scope of assassination record and additional records and information.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 36 Parks, Forests, and Public Property 3 2014-07-01 2014-07-01 false Types of materials included in scope of assassination record and additional records and information. 1290.4 Section 1290.4 Parks, Forests, and Public Property NATIONAL ARCHIVES AND RECORDS ADMINISTRATION JFK ASSASSINATION RECORDS GUIDANCE FOR INTERPRETATION AND IMPLEMENTATION...

  1. 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

    ... water conservation, groundwater recovery, and water reuse and recycling; (g) Associated features to... 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...

  2. 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

    ... water conservation, groundwater recovery, and water reuse and recycling; (g) Associated features to... 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...

  3. 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

    ... water conservation, groundwater recovery, and water reuse and recycling; (g) Associated features to... 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...

  4. 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 §...

  5. 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

    ... 40 Protection of Environment 28 2013-07-01 2013-07-01 false Factors for petitions to include other 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 ...

  6. Inactivation of specific ? cell transcription factors in type 2 diabetes

    PubMed Central

    Guo, Shuangli; Dai, Chunhua; Guo, Min; Taylor, Brandon; Harmon, Jamie S.; Sander, Maike; Robertson, R. Paul; Powers, Alvin C.; Stein, Roland

    2013-01-01

    Type 2 diabetes (T2DM) commonly arises from islet ? cell failure and insulin resistance. Here, we examined the sensitivity of key islet-enriched transcription factors to oxidative stress, a condition associated with ? cell dysfunction in both type 1 diabetes (T1DM) and T2DM. Hydrogen peroxide treatment of ? cell lines induced cytoplasmic translocation of MAFA and NKX6.1. In parallel, the ability of nuclear PDX1 to bind endogenous target gene promoters was also dramatically reduced, whereas the activity of other key ? cell transcriptional regulators was unaffected. MAFA levels were reduced, followed by a reduction in NKX6.1 upon development of hyperglycemia in db/db mice, a T2DM model. Transgenic expression of the glutathione peroxidase-1 antioxidant enzyme (GPX1) in db/db islet ? cells restored nuclear MAFA, nuclear NKX6.1, and ? cell function in vivo. Notably, the selective decrease in MAFA, NKX6.1, and PDX1 expression was found in human T2DM islets. MAFB, a MAFA-related transcription factor expressed in human ? cells, was also severely compromised. We propose that MAFA, MAFB, NKX6.1, and PDX1 activity provides a gauge of islet ? cell function, with loss of MAFA (and/or MAFB) representing an early indicator of ? cell inactivity and the subsequent deficit of more impactful NKX6.1 (and/or PDX1) resulting in overt dysfunction associated with T2DM. PMID:23863625

  7. Psychological Factors, Including Alexithymia, in the Prediction of Cardiovascular Risk in HIV Infected Patients: Results of a Cohort Study

    PubMed Central

    Sozio, Federica; Mazzott, Elena; Ursini, Tamara; Polill, Ennio; Di Stefano, Paola; Tontodonati, Monica; Verrocchio, Maria C.; Fulcheri, Mario; Calella, Giulio; Santilli, Francesca; Manzoli, Lamberto

    2013-01-01

    Background Psychological factors are known predictors of cardiovascular disease in many clinical settings, but data are lacking for HIV infection. We carried out a prospective cohort study to evaluate potential psychological predictors of preclinical and clinical vascular disease in HIV patients. Methodology/Principal Findings HIV patients were consecutively enrolled. Demographics, viral and immune parameters and traditional cardiovascular predictors were considered; Intima-Media Thickness (c-IMT, continuous measure) and Carotid Plaques (CPs, focal thickening ≥1.5 mm) were investigated by B-mode ultrasonography; depressive symptoms by the Beck Depression Inventory (BDI-II), Type D personality (Distressed Personality or Type D) by the DS14, alexithymia by the Toronto Alexithymia Scale (TAS-20). Vascular outcomes included transient ischemic attacks or stroke, acute coronary syndrome, myocardial or other organ infarction. We enrolled 232 HIV subjects, 73.9% males, aged 44.5±9.9 y, 38.2% with AIDS diagnosis, 18.3% untreated. Mean Nadir CD4 T-cell counts were 237.5±186.2/mmc. Of them, 224 (96.5%) attended IMT measurements; 201 (86.6%) attended both IMT assessment and psychological profiling. Mean follow-up was 782±308 days. Fifty-nine patients (29.4%) had CPs at baseline. Nineteen patients (9.5%) had ≥1 vascular event; 12 (6.0%) died due to such events (n = 4) or any cause. At baseline cross-sectional multivariate analysis, increasing age, total cholesterol, current smoking and Alexithymia score≥50 were significantly associated with both increased cIMT (linear regression) and CPs (logistic regression). At follow-up analysis, log-rank tests and Cox’s regression revealed that only older age (p = 0.001), current smoking (p = 0.019) and alexithymia score≥50 (p = 0.013) were independently associated with vascular events. Conclusions/Significance In HIV-infected subjects, the Alexithymic trait emerges as a strong predictor of increased IMT, presence of CPs and vascular events. Such results are preliminary and require confirmation from studies with larger sample size and longer follow-up. PMID:23349927

  8. 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.

  9. 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...

  10. 40 CFR 273.81 - Factors for petitions to include other wastes under 40 CFR part 273.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 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...

  11. 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... requirements appropriate to be added to 40 CFR 273.13, 273.33, and 273.52; and/or applicable Department...

  12. 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...

  13. 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.

  14. 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.

  15. Risk factors and primary prevention trials for type 1 diabetes.

    TOXLINE Toxicology Bibliographic Information

    Wu YL; Ding YP; Gao J; Tanaka Y; Zhang W

    2013-01-01

    Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease resulting in the designated immune destruction of insulin producing ?-cells, usually diagnosed in youth, and associated with important psychological, familial, and social disorders. Once diagnosed, patients need lifelong insulin treatment and will experience multiple disease-associated complications. There is no cure for T1DM currently. The last decade has witnessed great progress in elucidating the causes and treatment of the disease based on numerous researches both in rodent models of spontaneous diabetes and in humans. This article summarises our current understanding of the pathogenesis of T1DM, the roles of the immune system, genes, environment and other factors in the continuing and rapid increase in T1DM incidence at younger ages in humans. In addition, we discuss the strategies for primary and secondary prevention trials of T1DM. The purpose of this review is to provide an overview of this disorder's pathogenesis, risk factors that cause the disease, as well as to bring forward an ideal approach to prevent and cure the disorder.

  16. Risk Factors and Primary Prevention Trials for Type 1 Diabetes

    PubMed Central

    Wu, Yan-Ling; Ding, Yan-Ping; Gao, Jian; Tanaka, Yoshimasa; Zhang, Wen

    2013-01-01

    Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease resulting in the designated immune destruction of insulin producing β-cells, usually diagnosed in youth, and associated with important psychological, familial, and social disorders. Once diagnosed, patients need lifelong insulin treatment and will experience multiple disease-associated complications. There is no cure for T1DM currently. The last decade has witnessed great progress in elucidating the causes and treatment of the disease based on numerous researches both in rodent models of spontaneous diabetes and in humans. This article summarises our current understanding of the pathogenesis of T1DM, the roles of the immune system, genes, environment and other factors in the continuing and rapid increase in T1DM incidence at younger ages in humans. In addition, we discuss the strategies for primary and secondary prevention trials of T1DM. The purpose of this review is to provide an overview of this disorder's pathogenesis, risk factors that cause the disease, as well as to bring forward an ideal approach to prevent and cure the disorder. PMID:23904791

  17. 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.

  18. An assessment of the risk factors for type 2 diabetes among women in rural Jamaica.

    PubMed

    Bryan, G C; Johnson, J A; Dawes, L; Samuel, C

    2012-11-01

    This project examined risk factors (lifestyle, socio-economic and cultural) for Type 2 diabetes among 890 women in rural Jamaica in comparison to national and international trends via the Behavioural Risk Factor Surveillance System (BRFSS) and further analysis via the Kruskal Wallis and Mann-Whitney U tests. Nonparametric tests explored the relationship of body mass index (BMI) and risk factors. Women above age 36 years, sedentary women and women with health insurance showed a significant increase in BMI. Seventh Day Adventists had significantly lower BMIs compared to Protestants. Prevalence of Type 2 diabetes in rural Jamaica is complicated by the lack of adequate health insurance, health practitioners (including dieticians and social workers), and vigorous public awareness campaigns, as well as high healthcare costs. Recommendations include the establishment of a comprehensive plan targeting women to reduce their risk factors for Type 2 diabetes, including early diagnoses, continuing education for healthcare providers and community mobilization among churches, schools, banks, pharmacies and other entities. PMID:23757902

  19. Factor analysis for genetic evaluation of linear type traits in dual-purpose autochthonous breeds.

    PubMed

    Mazza, S; Guzzo, N; Sartori, C; Mantovani, R

    2016-03-01

    Factor analysis was applied to individual type traits (TT) scored in primiparous cows belonging to two dual purpose Italian breeds, Rendena (REN; 20 individual type traits evaluated on 11 399 first parity cows), and Aosta Red Pied (ARP; 22 individual type traits evaluated on 36 168 primiparous cows). Six common latent factors (F1 to F6; eigenvalues ?1) which explained 63% (REN) and 58% (ARP) of the total variance were obtained. F1 included TT mainly related to muscularity, and F2 to body size. The F3 and F4 accounted for udder size and conformation, respectively. F5 included rear legs and feet. Biological significance for F6 was not readily obtained. Moderate to low heritability were estimated through REML single-trait analysis from factor scores (from 0.22 to 0.52 in REN, and from 0.08 to 0.37 in ARP). The greatest heritability values were estimated for body size and muscularity (0.52 and 0.37 for body size; and 0.40 and 0.32 for muscularity in REN and ARP, respectively). As expected, rank correlations, obtained considering estimated breeding values derived from best linear unbiased prediction analysis on the individual TT and factor score, showed similar coefficients to those observed in the factor analysis following loading of TT within each latent factor. These results suggest the possibility to implement the factor analysis in the morphological evaluation, simplifying the information given by the type traits into new variables useful for the genetic improvement of dual purpose cattle. PMID:26358225

  20. Immunohistochemical expression of Type IV Collagen and Autocrine Motility Factor Receptor in Odontogenic Tumours

    PubMed Central

    Sethi, Sneha

    2014-01-01

    Background: Autocrine motility factor receptor (AMFR) is a tumour motility stimulating protein secreted by tumour cells. The protein encoded by this gene is a glycosylated transmembrane protein and a receptor for autocrine motility factor. It has been known to play a role in progression of neoplastic lesions. Basement membranes are specialized extracellular matrices that serve as structural barriers as well as substrates for cellular interactions. The network of type IV collagen is thought to define the scaffold integrating other components such as laminins and perlecan into highly organized supramolecular architecture. The aim of this study was to determine and evaluate the immunohistochemical expression of Type IV Collagen and Autocrine motility factor receptor in odontogenic lesions. Materials and Methods: Immunohistochemical expression of Type IV Collagen and Autocrine motility factor receptor was evaluated in 31 odontogenic lesions, including unicystic ameloblastoma, multicystic ameloblastoma, keratocystic odontogenic tumour and ameloblastic carcinoma. Normal follicular tissue formed the control. Results: Maximum expression for Type IV Collagen was seen in multicystic ameloblastoma and minimum expression in keratocystic odontogenic tumour. The maximum expression of AMFR was seen in ameloblastic carcinoma and minimum expression in multicystic ameloblastoma. Conclusion: The results of this study suggested an association of loss of expression of type IV Collagen with progression of lesion. AMFR expression was found to be associated with the aggressive potential of tumours. PMID:25478440

  1. 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 prediction models were obtained with LKB, RS, and logistic NTCP models. Including clinical factors improved the predictive power of all models significantly.

  2. 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, 573-602] classification scheme. To fully investigate the E-type population, we enlarged our sample including 6 E-type asteroids spectra available in literature, resulting in a total sample of 21 objects. The analysis of the spectral slope for the 3 different E-type subgroups versus the orbital elements show that E[III] members have the lowest mean spectral slope value inside the whole sample, and that they are located between 2.2-2.7 AU in low inclination orbits. E[II] members has the highest spectral slope inside the sample, half of them are located in the Hungaria region, 2 are NEA and 2 (64 Angelina and 2867 Steins), are in the main belt. A similar distribution is found for the 5 featureless E[I] members, located mainly in the Hungaria region (3 members), one in the middle main belt while one is a NEA (2004 VD17). Finally, for the five E-type asteroids observed both in the visible and near infrared range, plus 2867 Steins, we attempt to model their surface composition using linear geographical mixtures of no more than 3 components, selected from aubrite meteorites and correlated minerals. In particular we suggest that the aubrite Peña Blanca might have the E[III] Asteroid 317 Roxane as parent body, and that the aubrite ALH78113 might be related to the E[II] subgroup asteroids.

  3. [Environmental factors in the development of type 1 diabetes -- a new insight].

    PubMed

    P?aczkiewicz-Jankowska, Ewa; Szybi?ski, Zbigniew; Huszno, Bohdan

    2007-01-01

    According to the traditional model of pathogenesis of type 1 diabetes - it develops in genetically susceptible individuals in whom environmental factors trigger an autoimmune process of beta-cell destruction. Although susceptibility may be inherited, there is a growing body of evidence showing the role of environmental factors that might not only trigger but also perpetuate the chronic autoimmune process. These factors may exert their action long before the disease manifests itself clinically, which significantly hampers their identification. Three groups of environmental factors that were most widely studied include of viral infections, feeding patterns in infancy and toxic compounds (especially nitrites). Other factors possibly playing a role in modifying the development of the disease are vaccinations, psychological stress and climatological factors. The authors summarize the data supporting the role of environmental factors in the development of the disease and show a more recent model of type 1 diabetes pathogenesis. It may partly explain why the disease incidence increased has so much in the last three decades despite markedly improved hygiene and health care standards. PMID:17941471

  4. Factors affecting surgical results of Wassel type IV thumb duplications.

    PubMed

    Patel, A U C; Tonkin, M A; Smith, B J; Alshehri, A H; Lawson, R D

    2014-11-01

    The aim of this study is to review the outcomes of Wassel type IV thumb duplications with a minimum of one year follow-up, and to identify any factors that may compromise the quality of results. Forty one patients (42 thumbs) returned for assessment of thumb alignment, metacarpophalangeal joint and interphalangeal joint stability and motion; carpometacarpal joint motion; pinch and grip strengths; and thumb size. The subjective assessment considered thumb shape and contour, scarring, nail deformity and examiner and patient/parent satisfaction. The mean age at surgery was 16 months and the mean follow-up time was 79 months. Metacarpophalangeal joint and interphalangeal joint mal-alignment was present in 56% and 38% of cases, respectively. Interphalangeal ulnar collateral ligament laxity was significant. Metacarpophalangeal joint and interphalangeal joint motion was significantly decreased. Pinch and grip strength measurements were normal. A novel and comprehensive assessment scale is introduced, which revealed results of one (2.5%) excellent, 23 (59%) good, 14 (36%) fair and one (2.5%) poor. We consider that greater attention should be directed to the avoidance of mal-alignment and instability to improve these results. PMID:24309550

  5. Oxytocin and Psychological Factors Affecting Type 2 Diabetes Mellitus

    PubMed Central

    Kontoangelos, K.; Raptis, A. E.; Papageorgiou, C. C.; Tsiotra, P. C.; Papadimitriou, G. N.; Rabavilas, A. D.; Dimitriadis, G.; Raptis, S. A.

    2012-01-01

    Background. The aim of this study was to investigate the association of oxytocin with trait and state psychological factors in type 2 diabetic patients. Methods. OXT and psychological variables were analyzed from 86 controlled diabetic patients (glycosylated haemoglobin A1c (HbA1c) < 7%) from 45 uncontrolled diabetic patients (HbA1c ≥ 7). Psychological characteristics were assessed with the Eysenck Personality Questionnaire (EPQ), while state psychological characteristics were measured with the Symptom Checklist 90-R (SCL 90-R). Blood samples were taken for measuring oxytocin in both subgroups during the initial phase of the study. One year later, the uncontrolled diabetic patients were reevaluated with the use of the same psychometric instruments. Results. During the first evaluation of the uncontrolled diabetic patients, a statistically significant positive relationship between the levels of OXT and psychoticism in EPQ rating scale (P < 0.013) was observed. For controlled diabetic patients, a statistically significant negative relationship between oxytocin and somatization (P < 0.030), as well as obsessive-compulsive scores (P < 0.047) in SCL-90 rating scale, was observed. During the second assessment, the values of OXT decreased when the patients managed to control their metabolic profile. Conclusions. The OXT is in association with psychoticism, somatization, and obsessionality may be implicated in T2DM. PMID:22997507

  6. Paroxysmal Autonomic Instability With Dystonia Managed Using Chemodenervation Including Alcohol Neurolysis and Botulinum Toxin Type A Injection: A Case Report

    PubMed Central

    Lee, Hye-Sun; Oh, Hyun-Seung

    2015-01-01

    Paroxysmal autonomic instability with dystonia (PAID) is a rare complication of brain injury. Symptoms of PAID include diaphoresis, hyperthermia, hypertension, tachycardia, and tachypnea accompanied by hypertonic movement. Herein, we present the case of a 44-year-old female patient, who was diagnosed with paraneoplastic limbic encephalopathy caused by thyroid papillary cancer. The patient exhibited all the symptoms of PAID. On the basis that the symptoms were unresponsive to antispastic medication and her liver function test was elevated, we performed alcohol neurolysis of the musculocutaneous nerve followed by botulinum toxin type A (BNT-A) injection into the biceps brachii and brachialis. Unstable vital signs and hypertonia were relieved after chemodenervation. Accordingly, alcohol neurolysis and BNT-A injection are proposed as a treatment option for intractable PAID. PMID:25932429

  7. 8q12 microduplication including CHD7: clinical report on a new patient with Duane retraction syndrome type 3

    PubMed Central

    2013-01-01

    Background A novel multiple congenital anomalies syndrome has been recently identified in four patients carrying a 8q12 microduplication sharing the smallest region of overlap (SRO, size 1.6Mb) including five genes CA8, ASPH, RAB2B, CLVS1 and CDH7. The phenotype is mainly characterized by neurodevelopmental delay, heart defects, facial features and Type 1 Duane anomaly. Increasing dosage of CDH7 was proposed to be responsible for the recurrent pattern of MCA. Results High resolution array-CGH analysis identified a 4.2Mb de novo interstitial duplication of the 8q12.1-q12.3 chromosome region in a boy with developmental delay, dysmorphic features, type 3 Duane anomaly. This duplication includes several genes and spans the SRO. Discussion The present case represents a further patient with an interstitial duplication of chromosome 8q12 and several shared clinical features. Although more cases are needed to delineate the full-blown phenotype of 8q12 duplication syndrome, published data and present observations suggest that it results in a clinically recognizable phenotype. The presence of Duane anomaly in four out of five described patients with a 8q12 duplication definitely rules against the possibility of its being a chance finding unrelated to the imbalance and points toward a pathogenic role. Gene content analysis of the duplicated region and review of the literature suggest that gain-of-dosage of the CHD7 gene may be a good candidate for the main clinical features of the syndrome. PMID:24206642

  8. Keratinocyte growth factor is a growth factor for type II pneumocytes in vivo.

    PubMed Central

    Ulich, T R; Yi, E S; Longmuir, K; Yin, S; Biltz, R; Morris, C F; Housley, R M; Pierce, G F

    1994-01-01

    Keratinocyte growth factor (KGF) administered as a single intratracheal injection causes a prominent dose-dependent proliferation of type II alveolar epithelial cells in the lungs of adult rats. The increase in mitotically active alveolar cells histologically appears as a micropapillary epithelial cell hyperplasia after 2 d and peaks after 3 d in the form of monolayers of cuboidal epithelial cells lining alveolar septae. Proliferating cell nuclear antigen immunohistochemistry confirmed the profound proliferative response induced by KGF. The hyperplastic alveolar lining cells contain immunoreactive surfactant protein B and are ultrastructurally noted to contain lamellar inclusions characteristic of surfactant-producing type II pneumocytes. Mild focal bronchiolar epithelial hyperplasia is noted but is much less striking than the proliferation of type II pneumocytes. Large airways are unaffected by KGF. Daily intravenous injection of KGF is also able to cause pneumocyte proliferation. The normal adult rat lung constitutively expresses both KGF and KGF receptor mRNA, suggesting that endogenous KGF may be implicated in the paracrine regulation of the growth of pneumocytes. In conclusion, KGF rapidly and specifically induces proliferation and differentiation of type II pneumocytes in the normal adult lung. Images PMID:8132770

  9. Importance of genetic factors in the occurrence of epilepsy syndrome type: A twin study

    PubMed Central

    Corey, Linda A.; Pellock, John M.; Kjeldsen, Marianne J.; Nakken, Karl Otto

    2011-01-01

    Summary Although there is strong evidence that genetic factors contribute to risk for epilepsy, their role in the determination of syndrome type is less clear. This study was undertaken to address this question. Information related to epilepsy was obtained from twins included in 455 monozygotic and 868 dizygotic pairs ascertained from population-based twin registries in Denmark, Norway and the United States. Syndrome type was determined based on medical record information and detailed clinical interviews and classified using the International Classification Systems for the Epilepsies and Epileptic Syndromes. Concordance rates were significantly increased in monozygotic versus dizygotic pairs for all major syndrome groups except localization-related cryptogenic epilepsy. Among generalized epilepsies, genetic factors were found to play an important role in the determination of childhood absence, juvenile absence, juvenile myoclonic, and idiopathic generalized epilepsy; and to a lesser degree for epilepsies with grand mal seizures on awakening. Among localization-related epilepsies, genetic factors contributed to risk for localization-related idiopathic and symptomatic syndromes overall, but did not appear to play an important role in determining risk for frontal, occipital or temporal lobe epilepsy. These results suggest that, while genetic factors contribute to risk for major syndrome types, determined when possible, their contribution to risk for localization-related syndrome sub-types, as defined by specific focality, may be modest. PMID:21885256

  10. Tumor necrosis factor-? receptor type 1, not type 2, mediates its acute responses in the kidney.

    PubMed

    Castillo, Alexander; Islam, M Toriqul; Prieto, Minolfa C; Majid, Dewan S A

    2012-06-15

    Acute administration of tumor necrosis factor-? (TNF-?) resulted in decreases in renal blood flow (RBF) and glomerular filtration rate (GFR) but induced diuretic and natriuretic responses in mice. To define the receptor subtypes involved in these renal responses, experiments were conducted to assess the responses to human recombinant TNF-? (0.3 ngmin(-1)g body wt(-1) iv infusion for 75 min) in gene knockout (KO) mice for TNF-? receptor type 1 (TNF?R1 KO, n = 5) or type 2 (TNF?R2 KO, n = 6), and the results were compared with those obtained in corresponding wild-type [WT (C57BL/6), n = 6] mice. Basal levels of RBF (PAH clearance) and GFR (inulin clearance) were similar in TNF?R1 KO, but were lower in TNF?R2 KO, than WT mice. TNF-? infusion in WT mice decreased RBF and GFR but caused a natriuretic response, as reported previously. In TNF?R1 KO mice, TNF-? infusion failed to cause such vasoconstrictor or natriuretic responses; rather, there was an increase in RBF and a decrease in renal vascular resistance. Similar responses were also observed with infusion of murine recombinant TNF-? in TNF?R1 KO mice (n = 5). However, TNF-? infusion in TNF?R2 KO mice caused changes in renal parameters qualitatively similar to those observed in WT mice. Immunohistochemical analysis in kidney slices from WT mice demonstrated that while both receptor types were generally located in the renal vascular and tubular cells, only TNF?R1 was located in vascular smooth muscle cells. There was an increase in TNF?R1 immunoreactivity in TNF?R2 KO mice, and vice versa, compared with WT mice. Collectively, these functional and immunohistological findings in the present study demonstrate that the activation of TNF?R1, not TNF?R2, is mainly involved in mediating the acute renal vasoconstrictor and natriuretic actions of TNF-?. PMID:22461305

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

    PubMed Central

    Kern, Elisandra Lurdes; Cobuci, Jaime Arajo; Costa, Cludio 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

  12. The Cellulosome System of Acetivibrio cellulolyticus Includes a Novel Type of Adaptor Protein and a Cell Surface Anchoring Protein

    PubMed Central

    Xu, Qi; Gao, Wenchen; Ding, Shi-You; Kenig, Rina; Shoham, Yuval; Bayer, Edward A.; Lamed, Raphael

    2003-01-01

    A scaffoldin gene cluster was identified in the mesophilic cellulolytic anaerobe Acetivibrio cellulolyticus. The previously described scaffoldin gene, cipV, encodes an N-terminal family 9 glycoside hydrolase, a family 3b cellulose-binding domain, seven cohesin domains, and a C-terminal dockerin. The gene immediately downstream of cipV was sequenced and designated scaB. The protein encoded by this gene has 942 amino acid residues and a calculated molecular weight of 100,358 and includes an N-terminal signal peptide, four type II cohesions, and a C-terminal dockerin. ScaB cohesins 1 and 2 are very closely linked. Similar, but not identical, 39-residue Thr-rich linker segments separate cohesin 2 from cohesin 3 and cohesin 3 from cohesin 4, and an 84-residue Thr-rich linker connects the fourth cohesin to a C-terminal dockerin. The scaC gene downstream of scaB codes for a 1,237-residue polypeptide that includes a signal peptide, three cohesins, and a C-terminal S-layer homology (SLH) module. A long, ca. 550-residue linker separates the third cohesin and the SLH module of ScaC and is characterized by an 18-residue Pro-Thr-Ala-Ser-rich segment that is repeated 27 times. The calculated molecular weight of the mature ScaC polypeptide (excluding the signal peptide) is 124,162. The presence of the cohesins and the conserved SLH module implies that ScaC acts as an anchoring protein. The ScaC cohesins are on a separate branch of the phylogenetic tree that is close to, but distinct from, the type I cohesins. Affinity blotting with representative recombinant probes revealed the following specific intermodular interactions: (i) an expressed CipV cohesin binds selectively to an enzyme-borne dockerin, (ii) a representative ScaB cohesin binds to the CipV band of the cell-free supernatant fraction, and (iii) a ScaC cohesin binds to the ScaB dockerin. The experimental evidence thus indicates that CipV acts as a primary (enzyme-recognizing) scaffoldin, and the protein was also designated ScaA. In addition, ScaB is thought to assume the role of an adaptor protein, which connects the primary scaffoldin (ScaA) to the cohesin-containing anchoring scaffoldin (ScaC). The cellulosome system of A. cellulolyticus thus appears to exhibit a special type of organization that reflects the function of the ScaB adaptor protein. The intercalation of three multiple cohesin-containing scaffoldins results in marked amplification of the number of enzyme subunits per cellulosome unit. At least 96 enzymes can apparently be incorporated into an individual A. cellulolyticus cellulosome. The role of such amplified enzyme incorporation and the resultant proximity of the enzymes within the cellulosome complex presumably contribute to the enhanced synergistic action and overall efficient digestion of recalcitrant forms of cellulose. Comparison of the emerging organization of the A. cellulolyticus cellulosome with the organizations in other cellulolytic bacteria revealed the diversity of the supramolecular architecture. PMID:12867464

  13. 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

  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. Factors Associated with Types of Mathematics Anxiety in College Students.

    ERIC Educational Resources Information Center

    Bessant, Kenneth C.

    1995-01-01

    Factor analysis of a version of the Mathematics Anxiety Rating Scale (MARS) and the Study Process Questionnaire (SPQ) given to (n=173) introductory statistics students found 6 factors: general evaluation anxiety, everyday numerical anxiety, passive observation anxiety, performance anxiety, mathematics test anxiety, and problem-solving anxiety. (39

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

    PubMed

    Martnez-Salazar, Martha; Lpez-Urrutia, Eduardo; Arechaga-Ocampo, Elena; Bonilla-Moreno, Raul; Martnez-Castillo, Macario; Daz-Hernndez, Job; Del Moral-Hernndez, Oscar; Cedillo-Barrn, Leticia; Martines-Juarez, Vctor; De Nova-Ocampo, Monica; Valdes, Jess; Berumen, Jaime; Villegas-Seplveda, Nicols

    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

  17. 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

  18. Reducing cardiovascular complications of type 2 diabetes by targeting multiple risk factors.

    PubMed

    Reasner, Charles A

    2008-08-01

    Insulin resistance syndrome is characterized by hyperglycemia, atherogenic dyslipidemia, hypertension, and abdominal obesity. Hyperglycemia is the major risk factor for microvascular complications in type 2 diabetes. However, 70% to 80% of patients with type 2 diabetes will die of macrovascular disease. Atherogenic dyslipidemia-characterized by elevated triglyceride levels, low high-density lipoprotein cholesterol (HDL-c) levels, and a preponderance of small, dense, low-density lipoprotein (LDL) particles-is the major cause of atherosclerosis in individuals with type 2 diabetes. Therefore, treatment of type 2 diabetes must address hyperglycemia to prevent microvascular disease (retinopathy, neuropathy, and nephropathy) and atherogenic dyslipidemia to prevent macrovascular complications. Emerging evidence indicates lipid and glucose homeostasis are interrelated via bile acid-activated nuclear hormone receptor signaling pathways. Agents that act on these pathways could simultaneously address hyperglycemia and dyslipidemia in patients with type 2 diabetes. Recent studies have shown that bile acid sequestrants, including cholestyramine, colestimide, and colesevelam HCl, significantly improve glycemic control and reduce LDL cholesterol levels in patients with type 2 diabetes. This paper will review the effects of bile acid sequestrants on both glucose and lipid metabolism in patients with type 2 diabetes. PMID:18670366

  19. 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

  20. Cardiovascular Risk Factors Are Associated With Increased Arterial Stiffness in Youth With Type 1 Diabetes

    PubMed Central

    Dabelea, Dana; Talton, Jennifer W.; D’Agostino, Ralph; Wadwa, R. Paul; Urbina, Elaine M.; Dolan, Lawrence M.; Daniels, Stephen R.; Marcovina, Santica M.; Hamman, Richard F.

    2013-01-01

    OBJECTIVE To evaluate if presence of cardiovascular (CV) risk factors and their clustering as metabolic syndrome (MetS) is associated with increased arterial stiffness and accelerated progression over time among youth with type 1 diabetes. RESEARCH DESIGN AND METHODS Longitudinal study of 298 youth with type 1 diabetes (age 14.5 years; 46.3% female; duration 4.8 years), with two research visits conducted 5 years apart. CV factors included: waist circumference, blood pressure (BP), fasting lipids (HDL cholesterol, LDL cholesterol [LDL-c], triglycerides), albumin/creatinine ratio, and HbA1c. MetS was based on Adult Treatment Panel III criteria modified for youth. Pulse wave velocity (PWV) in the carotid–femoral segment was measured by tonometry. Mixed models were used to assess the rate of progression in PWV and the association between CV factors and PWV over time. RESULTS PWV increased significantly over time (0.145 m/s/year; P < 0.0001). MetS (P = 0.0035), large waist (P < 0.0001), and elevated BP (P = 0.0003) at baseline were each associated with worse PWV over time. These baseline factors, however, did not significantly influence the rate of progression. Increases in waist circumference (P < 0.0001), LDL-c levels (P = 0.0156), and declining glucose control (HbA1c; P = 0.0419) were independently associated with higher PWV over time. CONCLUSIONS Presence, clustering, and worsening of CV risk factors are associated with increased arterial stiffness over time in youth with type 1 diabetes. Whether improvement in CV risk factors early in life will slow the progression of arterial stiffness and reduce the burden of CV disease in this population requires further study. PMID:24101697

  1. 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

    ... 25 Indians 1 2012-04-01 2011-04-01 true What types of activities can a recreation, tourism, and... Eligibility Recreation, Tourism and Trails 170.137 What types of activities can a recreation, tourism, and... may perform under a recreation, tourism, and trails program: (1) Transportation planning for...

  2. 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

    ... 25 Indians 1 2013-04-01 2013-04-01 false What types of activities can a recreation, tourism, and... Eligibility Recreation, Tourism and Trails 170.137 What types of activities can a recreation, tourism, and... may perform under a recreation, tourism, and trails program: (1) Transportation planning for...

  3. 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... Eligibility Recreation, Tourism and Trails 170.137 What types of activities can a recreation, tourism, and... may perform under a recreation, tourism, and trails program: (1) Transportation planning for...

  4. 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…

  5. Evidence Gap on the Prevalence of Non-conventional Risk Factors for Type 2 Diabetes in Iran

    PubMed Central

    Shaghaghi, Abdolreza; Ahmadi, Ali

    2014-01-01

    Objectives Robust scientific evidence exists about the role of non-conventional risk factors in type 2 diabetes worldwide. The current epidemiological pattern of the disease in Iran suggests a precipitating role for these non-conventional risk factors. This review was performed to examine the research evidence suggesting a higher prevalence of non-conventional type 2 diabetes risk factors in Iran. Methods MeSH keywords were applied to search several databases, including PUBMED, MEDLINE, AMED, EMBASE, Iran DOC, and the Scientific Information Database without a time limit from inception to September 2011. The quality of the non-interventional and population-based studies on Iranians included in these databases was assessed by the authors and any disagreement was resolved with consensus. Results The literature search yielded 1847 publications, of which 62 were included in this study after eliminating non-relevant and overlapping papers. No study was found that verified a higher prevalence of the non-conventional type 2 diabetes risk factors in the Iranian population. Conclusion The identified evidence gap about the role of prominent non-conventional risk factors of type 2 diabetes in the Iranian population could be a major caveat in the application of an evidence-based approach to endorse or reject existing hypothesis about these risk factors. Studies on the prevalence of non-conventional biomarkers of type 2 diabetes among Iranians could be a promising area of research. PMID:25389516

  6. Activation of a serine/threonine kinase signaling pathway by transforming growth factor type beta.

    PubMed Central

    Atfi, A; Lepage, K; Allard, P; Chapdelaine, A; Chevalier, S

    1995-01-01

    Transforming growth factor type beta (TGF-beta) is a multifunctional factor that regulates proliferation and differentiation of many cell types. TGF-beta mediates its effects by binding to and activating cell surface receptors that possess serine/threonine kinase activity. However, the intracellular signaling pathways through which TGF-beta receptors act remain largely unknown. Here we show that TGF-beta activates a 78-kDa protein (p78) serine/threonine kinase as evidenced by an in-gel kinase assay. Ligand-induced activation of the kinase was near-maximal 5 min after TGF-beta addition to the cells and occurred exclusively on serine and threonine residues. This kinase is distinct from TGF-beta receptor type II, as well as several cytoplasmic serine/threonine kinases of similar size, including protein kinase C, Raf, mitogen-activated protein kinase kinase kinase, and ribosomal S6 kinase. Indeed, these kinases can be separated almost completely from p78 kinase by immunoprecipitation with specific antibodies. Furthermore, using different cell lines, we demonstrate that p78 kinase is activated only in cells for which TGF-beta can act as a growth inhibitory factor. These data raise the interesting possibility that protein serine/threonine kinases contribute to the intracellular relay of biological signals originating from receptor serine/threonine kinases such as the TGF-beta receptors. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:8618854

  7. Analysis of factors inducing different type of landslide in apparently similar environmental contexts

    NASA Astrophysics Data System (ADS)

    Busnardo, Enrico; Secco, Michele; Salbego, Giorgio; Toaldo, Miriam; Lampo, Chiara; Artioli, Gilberto; Floris, Mario

    2014-05-01

    Landslides frequently hit the hilly region of the Vicenza province (North-Eastern Italian Alps) exposing human activities to damage. The region includes Lessini Mountains and Marostica hills. These two areas are separated by a portion of the upper Vicenza plain. They have the same lithological framework, with the predominance of Tertiary volcanic rocks (Basalts and Tuffs) and most of landslides are earth slides and earth flows which affect the altered volcanic bedrock. At first glance, only considering these two type of movements, it seems that the predisposing conditions, as well as triggering factors (i.e. rainfall) are the same. The aim of this work is to find the factors that determine earth slides rather than earth flows. In other words, we checked if there are any anomalies due to particular lithological and morphological constraints attributable to a type of movement. The research was performed both at large and small scale. At large scale, we decide to perform spatial analysis of four numerical and seven categorical factors. Numerical factors are elevation, provided by the Veneto Region, slope gradient, slope aspect and surface curvature, derived from elevation. Categorical data are: soils map and land-use map, both provided by the Veneto Region; lithological map provided by the Vicenza province; IFFI (Inventory of Landslide Phenomena in Italy) project data. We also consider factors such as roads, rivers network and civil buildings. Spatial analysis was performed using a simple probabilistic method that compares spatial distribution of landslides with numerical and categorical factors. At small-scale, we performed mineralogical and geotechnical analyses of samples collected from an earth slide and an earth flow. In order to define the mineralogical phases we use x-ray powder diffraction (XRD) of whole sample and of thin portion. Geotechnical indexes were obtained by Atterber Limits and sieve analyses. We also determined the rheological and swelling properties of the materials. In particular we investigated the variation of those properties as a function of water content. At large-scale, we identified which are the main factors (morphological, lithological and anthropic factors) that determine the different types of landslides. At small-scale, we found significant differences in geotechnical and mineralogical properties of materials involved in the two type of landslide.

  8. 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

  9. THE FURTHER SEPARATION OF TYPES AMONG THE PNEUMOCOCCI HITHERTO INCLUDED IN GROUP IV AND THE DEVELOPMENT OF THERAPEUTIC ANTISERA FOR THESE TYPES.

    PubMed

    Cooper, G; Rosenstein, C; Walter, A; Peizer, L

    1932-03-31

    The unclassified strains known as Group IV have been separated into twenty-nine types which are designated by the Roman numerals IV and XXXII. Only a small percentage of the pneumococcus strains isolated in New York City for this study were left unclassified. The majority of the types gave very slight cross-reactions, the exceptions being Types II and V, III and VIII, VII and XVIII and XV and XXX. In the series of cases studied, Types IV, V, VII and VIII were found more prevalent in the lobar pneumonia of adults and Types V, VI a and XIV in children. The majority of the types were also found in normal individuals and in persons having respiratory infections other than pneumonia. Types VI a and XIX were most prevalent in the limited number of strains studied by us. Fourteen of the types were found in pneumococcus meningitis; Type XVIII was found most often. Antisera suitable for clinical trial have been prepared for fourteen types. From the majority of the horses inoculated for more than a year, antisera having 500 to 1000 units per cc. were obtained. Antisera of lower potency were concentrated and preparations obtained equal to or stronger than high grade unconcentrated serum. Potent bivalent antisera have been prepared for types which were found to give marked cross-agglutination reactions. The results with each type as to prevalence, severity of cases, presence in normal individuals, and in spinal meningitis, potency of antisera produced for therapeutic trial and virulence of strains for mice have been considered under the different type headings. PMID:19870011

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

    PubMed

    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 nave, memory, and regulatory CD4+ T cells as well as nave and memory CD8+ T cells and nave 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. Prevalence, types, and RNA concentrations of human parechoviruses, including a sixth parechovirus type, in stool samples from patients with acute enteritis.

    PubMed

    Baumgarte, Sigrid; de Souza Luna, Luciano Kleber; Grywna, Klaus; Panning, Marcus; Drexler, Jan Felix; Karsten, Claudia; Huppertz, Hans Iko; Drosten, Christian

    2008-01-01

    Parechovirus epidemiology and disease association are not fully understood. Real-time reverse transcriptase PCR (RT-PCR) for all human parechoviruses (HPeV) was applied on stool samples from two groups of patients. Both groups contained patients with acute enteritis of all age groups, seen during one full year. Patients with norovirus, adenovirus, enterovirus, astrovirus, or rotavirus infections were excluded. In 118 patients from outbreak and hospital settings, no HPeV was detected. In a prospective study group of 499 nonhospitalized patients, the detection rate was 1.6%. One virus-positive patient was detected from 39 control patients. Positive samples occurred only in summer and autumn. Only one patient had accompanying respiratory symptoms. An association with travel or animal contact was not found. All positive patients except one were <2 years of age, with a neutral gender ratio. In children <2 years of age, the detection rate was 11.6% (7 of 60 children). The range of viral loads was 3,170 to 503,377,290 copies per gram or milliliter of stool. One of the highest viral loads occurred in a control child without symptoms at the time of testing. Phylogenetic analysis showed mainly contemporary HPeV1 strains in our patients but also showed a separate new lineage of HPeV1 in evolutionary transition from the historical prototype strain. Moreover, a novel sixth HPeV type was identified. Full genome analysis of the two viruses revealed recombination between HPeV1 and -3 in one and HPeV6 and -1 in another. HPeV seems relevant in children <2 years and specific RT-PCR for HPeV should be included in enteritis screening. PMID:18057123

  12. 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

  13. 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

  14. 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

  15. 48 CFR 16.104 - Factors in selecting contract types.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... interest. (b) Price analysis. Price analysis with or without competition, may provide a basis for selecting the contract type. The degree to which price analysis can provide a realistic pricing standard should be carefully considered. (See 15.404-1(b).) (c) Cost analysis. In the absence of effective...

  16. 48 CFR 16.104 - Factors in selecting contract types.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... interest. (b) Price analysis. Price analysis with or without competition, may provide a basis for selecting the contract type. The degree to which price analysis can provide a realistic pricing standard should be carefully considered. (See 15.404-1(b).) (c) Cost analysis. In the absence of effective...

  17. 48 CFR 16.104 - Factors in selecting contract types.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... interest. (b) Price analysis. Price analysis with or without competition, may provide a basis for selecting the contract type. The degree to which price analysis can provide a realistic pricing standard should be carefully considered. (See 15.404-1(b).) (c) Cost analysis. In the absence of effective...

  18. 48 CFR 16.104 - Factors in selecting contract types.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... interest. (b) Price analysis. Price analysis with or without competition, may provide a basis for selecting the contract type. The degree to which price analysis can provide a realistic pricing standard should be carefully considered. (See 15.404-1(b).) (c) Cost analysis. In the absence of effective...

  19. 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

  20. 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.

  1. Type II1 factors satisfying the spatial isomorphism conjecture

    PubMed Central

    Cameron, Jan; Christensen, Erik; Sinclair, Allan M.; Smith, Roger R.; White, Stuart A.; Wiggins, Alan D.

    2012-01-01

    This paper addresses a conjecture in the work by Kadison and Kastler [Kadison RV, Kastler D (1972) Am J Math 94:3854] that a von Neumann algebra M on a Hilbert space should be unitarily equivalent to each sufficiently close von Neumann algebra N, and, moreover, the implementing unitary can be chosen to be close to the identity operator. This conjecture is known to be true for amenable von Neumann algebras, and in this paper, we describe classes of nonamenable factors for which the conjecture is valid. These classes are based on tensor products of the hyperfinite II1 factor with crossed products of abelian algebras by suitably chosen discrete groups. PMID:23184993

  2. Risk Factors for Type 1 Diabetes Recurrence in Immunosuppressed Recipients of Simultaneous Pancreas-Kidney Transplants.

    PubMed

    Vendrame, F; Hopfner, Y-Y; Diamantopoulos, S; Virdi, S K; Allende, G; Snowhite, I V; Reijonen, H K; Chen, L; Ruiz, P; Ciancio, G; Hutton, J C; Messinger, S; Burke, G W; Pugliese, A

    2016-01-01

    Patients with type 1 diabetes (T1D) who are recipients of pancreas transplants are believed to rarely develop T1D recurrence in the allograft if effectively immunosuppressed. We evaluated a cohort of 223 recipients of simultaneous pancreas-kidney allografts for T1D recurrence and its risk factors. With long-term follow-up, recurrence was observed in approximately 7% of patients. Comparing the therapeutic regimens employed in this cohort over time, lack of induction therapy was associated with recurrence, but this occurs even with the current regimen, which includes induction; there was no influence of maintenance regimens. Longitudinal testing for T1D-associated autoantibodies identified autoantibody positivity, number of autoantibodies, and autoantibody conversion after transplantation as critical risk factors. Autoantibodies to the zinc transporter 8 had the strongest and closest temporal association with recurrence, which was not explained by genetically encoded amino acid sequence donor-recipient mismatches for this autoantigen. Genetic risk factors included the presence of the T1D-predisposing HLA-DR3/DR4 genotype in the recipient and donor-recipient sharing of HLA-DR alleles, especially HLA-DR3. Thus, T1D recurrence is not uncommon and is developing in patients treated with current immunosuppression. The risk factors identified in this study can be assessed in the transplant clinic to identify recurrent T1D and may lead to therapeutic advances. PMID:26317167

  3. 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.

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

    PubMed Central

    Gamero, Joaqun J; Romero, Jose?Luis; Peralta, Juan?Luis; Carvalho, Mnica; 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

  5. Longitudinal Study of Finnish Campylobacter jejuni and C. coli Isolates from Humans, Using Multilocus Sequence Typing, Including Comparison with Epidemiological Data and Isolates from Poultry and Cattle?

    PubMed Central

    Krenlampi, Rauni; Rautelin, Hilpi; Schnberg-Norio, Daniela; Paulin, Lars; Hnninen, Marja-Liisa

    2007-01-01

    We describe a study on the application of multilocus sequence typing for the analysis of Campylobacter jejuni and C. coli isolates from human domestically acquired infections in the Helsinki-Uusimaa area of Finland in 1996, 2002, and 2003. In addition, isolates from poultry meat and fecal samples of cattle from the seasonal peak (July to September) in 2003 were included in the study. In total, 361 Finnish C. jejuni and C. coli strains were typed. Sequence type 45 (ST-45) (45%), ST-21 (21%), and ST-677 (11%) clonal complexes were the most prevalent. The ST-45 and ST-677 complexes were overrepresented in comparison with previous studies. The longitudinal study revealed an association between C. coli (ST-828 complex) infection and elderly patients (?60 years). Analysis of exposure factors, determined by a previous case-control study conducted during the seasonal peak in 2002, revealed that the ST-48 complex was significantly (P < 0.05) associated with the tasting or eating of raw minced meat. New and unassigned STs were associated with swimming in natural bodies of water, whereas the ST-677 complex was related to drinking nonchlorinated water from a small water plant or water from natural sources. The ST-45 complex was associated with contact with pet cats and dogs. In 2003, ST-45 occurrence was significantly associated with poultry whereas ST-50 was associated with isolates from humans. In contrast, ST-53, ST-58, ST-61, and ST-883 were significantly associated with isolates from cattle. Further studies are needed to reveal the significance of the observed associations. PMID:17085689

  6. 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

  7. Predictive Factors for a Kyphosis Recurrence Following Short-Segment Pedicle Screw Fixation Including Fractured Vertebral Body in Unstable Thoracolumbar Burst Fractures

    PubMed Central

    Kim, Gun-Woo; Hur, Hyuk; Lee, Jung-Kil; Kim, Jae-Hyoo; Kim, Soo-Han

    2014-01-01

    Objective The technique of short segment pedicle screw fixation (SSPSF) has been widely used for stabilization in thoracolumbar burst fractures (TLBFs), but some studies reported high rate of kyphosis recurrence or hardware failure. This study was to evaluate the results of SSPSF including fractured level and to find the risk factors concerned with the kyphosis recurrence in TLBFs. Methods This study included 42 patients, including 25 males and 17 females, who underwent SSPSF for stabilization of TLBFs between January 2003 and December 2010. For radiologic assessments, Cobb angle (CA), vertebral wedge angle (VWA), vertebral body compression ratio (VBCR), and difference between VWA and Cobb angle (DbVC) were measured. The relationships between kyphosis recurrence and radiologic parameters or demographic features were investigated. Frankel classification and low back outcome score (LBOS) were used for assessment of clinical outcomes. Results The mean follow-up period was 38.6 months. CA, VWA, and VBCR were improved after SSPSF, and these parameters were well maintained at the final follow-up with minimal degree of correction loss. Kyphosis recurrence showed a significant increase in patients with Denis burst type A, load-sharing classification (LSC) score >6 or DbVC >6 (p<0.05). There were no patients who worsened to clinical outcome, and there was no significant correlation between kyphosis recurrence and clinical outcome in this series. Conclusion SSPSF including the fractured vertebra is an effective surgical method for restoration and maintenance of vertebral column stability in TLBFs. However, kyphosis recurrence was significantly associated with Denis burst type A fracture, LSC score >6, or DbVC >6. PMID:25368766

  8. 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…

  9. Factors That Influence Parental Attitudes toward Enrollment in Type 1 Diabetes Trials

    PubMed Central

    Buscariollo, Daniela L.; Davidson, Mario A.; Black, Margo; Russell, William E.; Rothman, Russell L.; Moore, Daniel J.

    2012-01-01

    Aims To assess parental attitudes towards type 1 diabetes clinical trials (T1DCTs) and factors that impact willingness to enroll their children with and without diabetes. Methods A cross-sectional survey of parents of children with type 1 diabetes was administered at an academic clinic and a diabetes educational event. Results Survey response rate was 36%. Of 166 participating parents, 76% were aware of T1DCTs. More parents reported willingness to enroll children with diabetes (47%) than unaffected children (36%). Only 18% recalled being asked to enroll their children, and of these, 60% agreed to enroll at least some of those times. Less than 30% were comfortable with placebos. Factors predicting willingness to enroll children with diabetes included healthcare provider trust, comfort with consent by proxy, low fear of child being a “guinea pig,” and comfort with placebo. Factors predicting willingness to enroll unaffected children were provider trust, comfort with consent by proxy, comfort with placebo, and perceived ease of understanding T1DCT information. Conclusions Parents report moderate willingness to enroll children in T1DCTs. Willingness is diminished by common trial methodologies. Although most parents recalled receiving trial-related information, significantly fewer recalled being asked to participate. Efforts to optimize effective communication around identified areas of parental concern may increase T1DCT participation. PMID:22937171

  10. 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: 1.24.1). 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

  11. 13 CFR 123.401 - What types of mitigation measures can your business include in an application for a pre-disaster...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... can your business include in an application for a pre-disaster mitigation loan? 123.401 Section 123... Mitigation Loans 123.401 What types of mitigation measures can your business include in an application for a pre-disaster mitigation loan? To be included in a pre-disaster mitigation loan application,...

  12. 13 CFR 123.401 - What types of mitigation measures can your business include in an application for a pre-disaster...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... can your business include in an application for a pre-disaster mitigation loan? 123.401 Section 123... Mitigation Loans § 123.401 What types of mitigation measures can your business include in an application for a pre-disaster mitigation loan? To be included in a pre-disaster mitigation loan application,...

  13. 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

  14. Effect of Neighborhood Factors on Diabetes Self-Care Behaviors in Adults with Type 2 Diabetes

    PubMed Central

    Smalls, Brittany L.; Gregory, Chris M.; Zoller, James S.; Egede, Leonard E.

    2014-01-01

    Objective The objective of this study was to identify latent variables for neighborhood factors and diabetes self-care and examine the effect of neighborhood factors on diabetes self-care in adults with type 2 diabetes. Research Design and Methods 615 subjects were recruited from an academic medical center and a Veterans affairs medical center in the southeastern United States. Validated scales were used to assess neighborhood factors and diabetes-related self-care. Confirmatory factor analysis (CFA) was used to determine the latent constructs. Structural equation modeling (SEM) was then used to assess the relationship between neighborhood factors and diabetes self-care. Results Based on a theoretical framework, CFA yielded four latent variables for neighborhood factors (neighborhood violence, access to healthy food, social support, and neighborhood aesthetics) and one latent variable diabetes self-care ( including diet, exercise, foot care, blood sugar testing and medication adherence). SEM showed that social support (r=0.28, p<0.001) and access to healthy foods (r=-0.16, p=0.003) were significantly associated with self-care behaviors, while neighborhood violence (r= -0.06, p<0.001) and aesthetics (r=-0.07, p=0.278) were not ?2 (180, N=611)=192, p=0.26, RMSEA=0.01, CFI=0.999). In the final trimmed model, social support (r=0.31, p<0.001) and access to healthy foods (r=-0.20, p<0.001) remained significantly associated with self-care behaviors ?2 (76, N=611)=60, p=0.91, RMSEA=0.00, CFI=1.0). Conclusion This study developed latent factors for neighborhood characteristics and diabetes self-care and found that social support and access to healthy foods were significantly associated with diabetes self-care and should be considered as targets for future interventions. PMID:25451904

  15. Characterization of Transcription Factor Binding to Human Papillomavirus Type 16 DNA during Cellular Differentiation

    PubMed Central

    Carson, Andrew; Khan, Saleem A.

    2006-01-01

    Human papillomaviruses (HPVs) require terminal differentiation of the host cell to produce infectious virions. The process of viral maturation involves a variety of changes in the expression/activity of host proteins that lead to high-level replication of the viral genome and expression of the late viral genes. Although the late promoter regions of HPV type 16 (HPV-16) are still not fully characterized, differentiation-dependent regulation of viral genes is thought to involve changes in the binding of host cell transcription factors to the viral promoter and regulatory regions. Currently, very little is known about specific cellular transcription factors involved in this process. We used the Panomics TransSignal protein/DNA array to identify changes in the levels of cellular transcription factors during methylcellulose-induced differentiation of W12 (20863) cells containing HPV-16. We then identified the differentially expressed transcription factors that specifically bind to HPV-16 DNA, including the known promoter and regulatory regions. We have validated the results obtained from the Panomics array by Western blot analysis. Furthermore, by chromatin immunoprecipitation assays, we have shown that many of the transcription factors identified in the above screen bind to the HPV-16 promoter/regulatory sequences in vivo and that the level of this binding is increased during differentiation. This approach identified approximately 30 transcription factors that specifically bind to HPV-16 sequences and may be involved in regulating HPV-16 transcription during differentiation. Although some of these transcription factors have previously been suggested to be involved in HPV-16 transcription, a number of them represent novel viral DNA-host protein interactions. PMID:16611894

  16. Retinal image quality with the different types of intraocular lenses including new idea of the hybrid IOLs

    NASA Astrophysics Data System (ADS)

    Siedlecki, D.; Zaj?c, M.; Nowak, J.

    2007-07-01

    Cataract is one of the most frequent reasons of blindness all around the world. Its treatment relies on removing the pathologically altered crystalline lens and replacing it with an artificial intraocular lens (IOL). There exists plenty of types of such implants, which differ in the optical materials and designs (shapes). However one of the important features, which is rather overlooked in the development of the intraocular implants is the chromatic aberration and its influence on the retinal image quality. In this study authors try to estimate the influence of the design and optical material of the implant on the retinal image quality in the polychromatic light, taking into consideration several exemplary types of IOLs which are commercially available. Authors also propose the partially achromatized hybrid IOLs, the longitudinal chromatic aberration (LCA)of which reduces the total LCA of the phakic eye to the level of a healthy eye's LCA. Several image characteristics, as the polychromatic Point Spread Function (PSF) and the Modulation Transfer Function (MTF) and the polychromatic encircled energy are estimated. The results of the simulations show the significance of the partial chromatic aberration correction.

  17. Genetic defects at the UGT1 locus associated with Crigler-Najjar type I disease, including a prenatal diagnosis

    SciTech Connect

    Ciotti, M.; Obaray, R.; Owens, I.S.; Martin, M.G.

    1997-01-20

    Characterization of the UGT1 gene complex locus encoding both multiple bilirubin and phenol UDP-glucuronosyltransferases (transferases) has been critical in identifying mutations in the bilirubin isoforms. This study utilizes this information to identify the bases of deficient bilirubin UDP-glucuronosyltransferase activity encoded by the UGT1A gene for the major bilirubin isozyme, HUG-Br1, in 3 Crigler-Najjar type I individuals and the genotype of an at-risk unborn sibling of one patient. A homozygous and heterozygous two-base mutation (CCC to CGT) created the HUG-Br1P387R mutant of the major bilirubin transferase in 2 different Crigler-Najjar type I patients, B.G. and G.D., respectively. Both parents of B.G. and his unborn sibling, J.G., were determined to be carriers of the P387R mutation. G.D. also contains the CAA to TAA nonsense mutation (G1n357st). Y.A. has a homozygous CT deletion in codons 40/41. The HUG-Br1P387R mutant protein was totally inactive at the major pH optimum, but retained 26% normal activity at the minor pH optimum (7.6), which was 5.4% of the combined activities measured at the two pH values. 27 refs., 5 figs.

  18. 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

    ... conservation, groundwater recovery, and water reuse and recycling; (g) Associated features to mitigate adverse... 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...

  19. Evaluation of a multiplex PCR assay (Bruce-ladder) for molecular typing of all Brucella species, including the vaccine strains.

    PubMed

    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

    2008-10-01

    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

  20. Blood pressure and lipid management fall far short in persons with type 2 diabetes: results from the DIAB-CORE Consortium including six German population-based studies

    PubMed Central

    2012-01-01

    Background Although most deaths among patients with type 2 diabetes (T2D) are attributable to cardiovascular disease, modifiable cardiovascular risk factors appear to be inadequately treated in medical practice. The aim of this study was to describe hypertension, dyslipidemia and medical treatment of these conditions in a large population-based sample. Methods The present analysis was based on the DIAB-CORE project, in which data from five regional population-based studies and one nationwide German study were pooled. All studies were conducted between 1997 and 2006. We assessed the frequencies of risk factors and co-morbidities, especially hypertension and dyslipidemia, in participants with and without T2D. The odds of no or insufficient treatment and the odds of pharmacotherapy were computed using multivariable logistic regression models. Types of medication regimens were described. Results The pooled data set comprised individual data of 15, 071 participants aged 45–74 years, including 1287 (8.5%) participants with T2D. Subjects with T2D were significantly more likely to have untreated or insufficiently treated hypertension, i.e. blood pressure of > = 140/90 mmHg (OR = 1.43, 95% CI 1.26-1.61) and dyslipidemia i.e. a total cholesterol/HDL-cholesterol ratio > = 5 (OR = 1.80, 95% CI 1.59-2.04) than participants without T2D. Untreated or insufficiently treated blood pressure was observed in 48.9% of participants without T2D and in 63.6% of participants with T2D. In this latter group, 28.0% did not receive anti-hypertensive medication and 72.0% were insufficiently treated. In non-T2D participants, 28.8% had untreated or insufficiently treated dyslipidemia. Of all participants with T2D 42.5% had currently elevated lipids, 80.3% of these were untreated and 19.7% were insufficiently treated. Conclusions Blood pressure and lipid management fall short especially in persons with T2D across Germany. The importance of sufficient risk factor control besides blood glucose monitoring in diabetes care needs to be emphasized in order to prevent cardiovascular sequelae and premature death. PMID:22569118

  1. 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 Depressional (Open, Semiclosed, and Closed), 231 were Riverine (Upper Perennial and Nonperennial), 210 were Soil Flat (Mineral and Organic), 68 were Lacustrine Fringe, 51 were Tidal Fringe, 22 were Hilltop/Upper Hillslope, and another 35 were small open water bodies. Most small, isolated wetlands classified on the island are Slope wetlands. The least common, Hilltop/Upper Hillslope wetlands, only occur on a few hilltops and shoulders of hills and mountains. Large wetland complexes generally consist of groups of Depressional wetlands and Mineral Soil Flat or Organic Soil Flat wetlands, often with fringing Slope wetlands at their edges and Riverine wetlands near streams flowing through them. The two analyses of wetland hydrologic susceptibility on Mt. Desert Island were applied to 186 wetlands located partially or entirely within ANP. These analyses were conducted using individually mapped catchments for each wetland. The 186 wetlands were aggregated from the original 1,202 mapped wetland polygons on the basis of their HGM classes. Landscape-level hydrologic, geomorphic, and soil variables were defined for the catchments of the wetlands, and transformed into scaled scores from 0 to 10 for each variable. The variables included area of the wetland, area of the catchment, area of the wetland divided by the area of the catchment, the average topographic slope of the catchment, the amount of the catchment where bedrock crops out with no soil cover or excessively thin soil cover, the amount of storage (in lakes and wetlands) in the catchment, the topographic relief of the catchment, the amount of clay-rich soil in the catchment, the amount of manmade impervious surface, whether the wetland had a stream inflow, and whether the wetland had a hydraulic connection to a lake or estuary. These data were determined using a GIS and data layers mapped at a scale of 1:24,000 or larger. These landscape variables were combined in different ways for the two hydrologic susceptibility fact

  2. 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 60C 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

  3. 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

  4. 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...

  5. 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...

  6. 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...

  7. 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...

  8. 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...

  9. Risk factors for type 2 diabetes mellitus among patients attending a rural Kenyan hospital

    PubMed Central

    2010-01-01

    ABSTRACT Background The Diabetes Management and Information Center in Nairobi has conducted population surveys among rural and urban Kenyans during the last decade. They have reported a rise in the prevalence of diabetes among rural Kenyans from 3% in 2003 to 7% in 2007. Our study was undertaken to investigate rural factors for type 2 diabetes and determine those that could be responsible for this rise in prevalence. Objectives To describe the risk factors for type 2 diabetes mellitus among patients attending the outpatient clinics in a rural mission hospital in Kenya. Method Forty-five diabetics and forty-five non-diabetics, resident in this rural hospital's catchment area for at least 10 years, were randomly selected from patients attending outpatient clinics. Diabetics in a stable condition (not requiring hospitalisation), whose fasting blood sugars were below 6.1 mmol/L, were matched for age and gender with the non-diabetics who came to the hospital for outpatient services. A pilot-tested questionnaire on demography, current and past dietary habits, social habits, and family history was used to collect data. Waist circumference, height and weight were measured and BMI calculated. Data was analysed using SPSS for Windows. The KruskalWallis test was used to compare the medians for the continuous variables, while the chi-squared test was used for the categorical variables. The z-test was used to calculate the relative risk. Results Ninety participants (26 males, 64 females). The mean age was 61.8 for diabetics and 61.4 for non-diabetics. Childhood starvation (relative risk 2.08, p = 0.0090) and use of cassava for sustenance during childhood starvation (relative risk 3.12, p = 0.0090) were identified as risk factors. Diabetes in close relatives, another risk factor for this population (relative risk 2.2, p = 0.0131). Abdominal obesity was a risk factor for this population (in females relative risk 2.0, p = 0.0010). Conclusion The risk factors for type 2 diabetes mellitus described in this rural population include advancing age, diabetes in a first-degree relative and abdominal obesity. This is similar to what has been cited in other studies. At variance, we found that more than 50% of the diabetics reported having suffered malnutrition/starvation in childhood, with more than half of them reporting their dependence on cassava as the only food source during starvation.

  10. The major transcriptional regulatory protein of herpes simplex virus type 1 includes a protease resistant DNA binding domain.

    PubMed Central

    Everett, R D; Paterson, T; Elliott, M

    1990-01-01

    Herpes simplex virus type 1 expresses five immediate-early (IE) polypeptides. In the absence of functional Vmw175 (the product of IE gene 3) activation of transcription of later classes of viral genes and repression of IE gene expression does not occur. The recognition of specific DNA sequences by Vmw175 requires, as determined by sensitivity to mutation, a part of the protein highly conserved in the corresponding proteins of related herpes viruses. However, mutations in other parts of the protein can also disrupt specific DNA binding. This paper shows that the DNA binding domain of Vmw175 can be liberated as a functional unit by digestion with proteinase K. Analysis of mutant Vmw175 proteins showed that the proteinase K resistant domain has an amino terminus between amino acid residues 229 and 292, while its carboxy terminus is between residues 495 and 518. Mutations outside this region which affect DNA binding by the intact protein do not eliminate binding of the proteinase K resistant domain. This implies that direct DNA binding by Vmw175 involves a linear subsection of the polypeptide, and that mutations in other parts of the polypeptide which affect DNA binding of the whole protein do so by indirect means. Images PMID:2167472

  11. Improvement of Surface Functionalities, Including Allergenicity Attenuation, of Whole Buckwheat Protein Fraction by Maillard-Type Glycation with Dextran

    PubMed Central

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

    2014-01-01

    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

  12. 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 ?-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 similar for the two methods. However, appreciably different concentrations were calculated for the individual primary organic matter contributions, although for most source categories the CMB and AMS-PMF results were highly correlated (r2 = 0.69-0.91). In comparison with the CMB model, the AMS appears to overestimate the biomass burning/coal and food cooking sources by a factor of around 1.5 to 2 while estimates of the traffic source are rather similar for each model. The largest divergence is in the primary/secondary organic matter split, with the AMS estimating an appreciably smaller secondary component. Possible reasons for these discrepancies are discussed, but despite these substantial divergences, the strong correlation of the two methods gives some confidence in their application.

  13. 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 ?-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 rather similar for the two methods. However, appreciably different concentrations were calculated for the individual primary organic matter contributions, although for most source categories the CMB and AMS-PMF results were highly correlated (r2 = 0.69-0.91). In comparison with the CMB model, the AMS appears to over-estimate the biomass burning/coal and food cooking sources by a factor of around 1.5 to 2 while estimates of the traffic source are rather similar for each model. The largest divergence is in the primary/secondary organic matter split, with the AMS estimating an appreciably smaller secondary component. Possible reasons for these discrepancies are discussed, but despite these substantial divergences, the strong correlation of the two methods gives some confidence in their application.

  14. 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.

  15. 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

  16. 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

    ... and facilities that may not be included in a rural water supply project? 404.10 Section 404.10 Public... RECLAMATION RURAL WATER SUPPLY PROGRAM Overview § 404.10 Are there certain types of infrastructure and facilities that may not be included in a rural water supply project? Yes. A rural water supply project...

  17. 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 ?-lactamase (ESBL) and metallo-?-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 Fishers 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 infections, from surgical wards, high resistance levels to cephalosporins, fluoroquinolones, monobactam, but low levels to carbapenems, among males isolated from pus in age group >0-28 days and >28 days -1 year and among females from urine in >20-30 years, no significant difference when correlated with risk factors. MBL (NDM-1) producing isolates were mainly from females with age range 0 days to 70 years, mainly admitted to ICU/postoperative wards with urinary catheter in-situ, ventilatory support, surgery, diabetes mellitus, haematological and neurological disease. Conclusion Risk factors for infections due to ESBL and MBL producing Gram Negative Bacteria (GNB) should be clearly identified to reduce their spread and to optimise antibiotic use. PMID:26675893

  18. 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

  19. Postnatal visual deprivation in rats regulates several retinal genes and proteins, including differentiation-associated fibroblast growth factor-2.

    PubMed

    Prokosch-Willing, Verena; Meyer zu Hoerste, Melissa; Mertsch, Sonja; Stupp, Tobias; Thanos, Solon

    2015-01-01

    Little is known about the retinal cellular basis of amblyopia, which is a developmental disease characterized by impaired visual acuity. This study examined the retinal transcripts associated with experimentally induced unilateral amblyopia in rats. Surgical tarsorrhaphy of the eyelids on one side was performed in pups prior to eye opening at postnatal day 14, thereby preventing any visual experience. This condition was maintained for over 2 months, after which electroretinograms (ERGs) were recorded, the retinal ganglion cell (RGC) arrangement and number were determined using neuroanatomical tracing, the retinal transcripts were studied using microarray analysis, regulated mRNAs were confirmed with quantitative reverse-transcriptase PCR, and proteins were stained using Western blotting and immunohistochemistry. An attenuated ERG was found in eyes that were deprived of visual experience. Retrograde neuroanatomical staining disclosed a larger number of RGCs within the retina on the visually deprived side compared to the non-deprived, control side, and a multilayered distribution of RGCs. At the retinomic level, several transcripts associated with retinal differentiation, such as fibroblast growth factor 2 (FGF-2), were either up- or downregulated. Most of the transcripts could be verified at the mRNA level. To unravel the role of a differentiation-associated protein, we tested FGF-2 in dissociated postnatal retinal cell cultures and found that FGF-2 is a potent factor triggering ganglion cell differentiation. The data suggest that visual experience shapes the postnatal retinal differentiation, whereas visual deprivation induces changes at the functional, cellular and molecular levels within the retina. PMID:25402196

  20. Dextran sulfate included in factor Xa assay reagent overestimates heparin activity in patients after heparin reversal by protamine.

    PubMed

    Mouton, Christine; Calderon, Joachim; Janvier, Grard; Vergnes, Marie-Christine

    2003-01-01

    A lack of correlation between activated partial thromboplastin time (aPTT), thrombin time (TT) and anti-factor Xa (AXa) activity was observed in patients after cardiac surgery with cardiopulmonary bypass (CBP). Indeed, AXa activity measured by the chromogenic assay, Coamatic Heparin, was higher than expected with regard to results obtained in coagulation assays. To account for this discrepancy, another AXa chromogenic assay was tested. First, AXa activity was measured with two chromogenic assays (Coamatic Heparin and Rotachrom Heparin) in plasma samples of 25 patients undergoing cardiac surgery at two time points after heparin reversal by protamine. AXa activity was significantly higher when measured with Coamatic Heparin than with Rotachrom Heparin in samples collected just after protamine infusion (p<0.01). Next, since Coamatic( Heparin contains dextran sulfate (DXS) to reduce the influence of heparin antagonists such as platelet factor 4 (PF4), whereas Rotachrom Heparin does not, we hypothesized that the dextran sulfate contained in the reagent might explain this discrepancy. We therefore performed in vitro studies consisting in neutralizing unfractionated heparin (UFH) with protamine and measuring AXa activity with the two chromogenic assays. An AXa activity was still measurable with Coamatic Heparin after neutralization, thus strongly suggesting that dextran sulfate dissociates protamine/heparin complexes. We conclude that Coamatic Heparin assays should be avoided when measuring AXa activity in plasma samples immediately after protamine infusion, as inaccurate results may lead to inadequate management of heparin reversal. PMID:14693175

  1. The Opportunistic Pathogen Propionibacterium acnes: Insights into Typing, Human Disease, Clonal Diversification and CAMP Factor Evolution

    PubMed Central

    McDowell, Andrew; Nagy, István; Magyari, Márta; Barnard, Emma; Patrick, Sheila

    2013-01-01

    We previously described a Multilocus Sequence Typing (MLST) scheme based on eight genes that facilitates population genetic and evolutionary analysis of P. acnes. While MLST is a portable method for unambiguous typing of bacteria, it is expensive and labour intensive. Against this background, we now describe a refined version of this scheme based on two housekeeping (aroE; guaA) and two putative virulence (tly; camp2) genes (MLST4) that correctly predicted the phylogroup (IA1, IA2, IB, IC, II, III), clonal complex (CC) and sequence type (ST) (novel or described) status for 91% isolates (n = 372) via cross-referencing of the four gene allelic profiles to the full eight gene versions available in the MLST database (http://pubmlst.org/pacnes/). Even in the small number of cases where specific STs were not completely resolved, the MLST4 method still correctly determined phylogroup and CC membership. Examination of nucleotide changes within all the MLST loci provides evidence that point mutations generate new alleles approximately 1.5 times as frequently as recombination; although the latter still plays an important role in the bacterium's evolution. The secreted/cell-associated ‘virulence’ factors tly and camp2 show no clear evidence of episodic or pervasive positive selection and have diversified at a rate similar to housekeeping loci. The co-evolution of these genes with the core genome might also indicate a role in commensal/normal existence constraining their diversity and preventing their loss from the P. acnes population. The possibility that members of the expanded CAMP factor protein family, including camp2, may have been lost from other propionibacteria, but not P. acnes, would further argue for a possible role in niche/host adaption leading to their retention within the genome. These evolutionary insights may prove important for discussions surrounding camp2 as an immunotherapy target for acne, and the effect such treatments may have on commensal lineages. PMID:24058439

  2. Factors associated with non-adherence to insulin in patients with type 1 diabetes

    PubMed Central

    Riaz, Musarrat; Basit, Abdul; Fawwad, Asher; Yakoob Ahmedani, Muhammad; Ali Rizvi, Zahara

    2014-01-01

    Objectives: To find out the various factors associated with non-adherence to diet, physical activity and insulin among patients with type 1 diabetes. (T1DM). Methods: This cross sectional study was conducted among T1DM subjects attending the Baqai Institute of Diabetology & Endocrinology (BIDE) and Diabetic Association of Pakistan (DAP), from July 2011 to June 2012.Clinical characteristics, anthropometric measurements, knowledge regarding type 1 diabetes along with adherence to dietary advice, physical activity and insulin were noted on a predesigned questionnaire and score was assigned to each question. Patients were categorized as adherent or non-adherent on the basis of scores obtained. Statistical Package for Social Sciences (SPSS) for windows version 17.0 was used to analyze the data. Results: A total of 194 patients (Male 94, Female 100), with mean age of 17.9 6.4 years, mean duration of diabetes 5.374.96 years (38.1% >5 yrs, 61.9% <5 yrs) were included in the study. One hundred and fourteen (58.5%) patients were non adherent to dietary advice, 82(42.3%) non adherent to physical activity while 88.1% respondents were non adherent to their prescribed insulin regimen. Factors associated with non-compliance were family type, occupation & educational level of respondents parents, duration of T1DM, family history of diabetes, frequency of visits to diabetic clinic, knowledge regarding diabetes, lack of family support and fear of hypoglycemia. Conclusion: Non adherence to prescribed treatment regimen in patient with TIDM is quite high. There is need to design strategies to help patients and their family members understand their treatment regimen in order to improve their adherence. PMID:24772118

  3. Metabolic Risk Factors and Type 2 Diabetes Incidence in American Indian Children.

    PubMed

    Wheelock, Kevin M; Sinha, Madhumita; Knowler, William C; Nelson, Robert G; Fufaa, Gudeta D; Hanson, Robert L

    2016-04-01

    Four childhood metabolic risk factors were assessed as predictors of future type 2 diabetes; obesity and impaired glucose tolerance were strong predictors, hypertension and dyslipidemia were not. PMID:26913636

  4. 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 22C, these fungi grow as mold that produce conidia or infectious particles, whereas at 37C 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 22C, and biosynthesis of siderophores under iron-replete conditions. Insertional and null mutants fail to convert to mold, do not accumulate significant biomass at 22C, 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

  5. 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

  6. Prevalence of and Risk Factors for Type 2 Diabetes Mellitus in Hyperlipidemia in China

    PubMed Central

    Chen, Guang-Yu; Li, Lui; Dai, Fei; Li, Xing-Jian; Xu, Xiao-Xin; Fan, Jian-Gao

    2015-01-01

    Background We explored the prevalence of and risk factors for type 2 diabetes in the adult population of Shanghai (China) with and without dyslipidemia. Material/Methods We conducted a cross-sectional survey including 14 385 adults (aged 16 to 88 years) in Shanghai using a stratified, multistage cluster sampling approach. Results Type 2 diabetes and hyperlipidemia were found in 1456 (10.1%) and 4583 (31.9%) subjects, respectively. Type 2 diabetes was more common in males (11.4%) than in females (9.2%, P<0.01), in the elderly (> or =65 years, 22.5%) than in younger (<55 years, <10%, P<0.01) individuals, and in urban (12.8%) than in rural populations (5.2%, P<0.01). Diabetes incidence was higher among patients with hyperlipidemia than in controls (16.9% vs. 7.0%, P<0.01; OR=2.72, 95% CI 2.44–3.03). Compared with controls, the risk for diabetes in subjects with isolated hypertriglyceridemia, isolated hypercholesterolemia, and mixed hyperlipidemia increased 1.75-fold (95% CI 1.53–1.99), 1.53-fold (95% CI 1.17–2.01), and 2.93-fold (95% CI 2.37–3.63), respectively. The fasting plasma glucose (FPG) and 2h-postprandial plasma glucose (2h-PG) increased with age in both sexes. The age- and sex-adjusted FPG and 2h-PG levels in hyperlipidemia were significantly higher than in controls (P<0.01). Conclusions A high prevalence of type 2 diabetes in hyperlipidemia patients exists in Shanghai. Hyperlipidemia is associated with elevated blood glucose levels and therefore requires prompt intervention for prevention and treatment of diabetes in patients with dyslipidemia. PMID:26297334

  7. 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

  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, 2011 CFR

    2011-10-01

    ... 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 PROGRAM Overview 404.10 Are there certain types of infrastructure...

  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, 2013 CFR

    2013-10-01

    ... 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 PROGRAM Overview 404.10 Are there certain types of infrastructure...

  10. 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

    ... 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 PROGRAM Overview 404.10 Are there certain types of infrastructure...

  11. 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...

  12. Myeloid expression of the AP-1 transcription factor JUNB modulates outcomes of type 1 and type 2 parasitic infections.

    PubMed

    Fontana, M F; Baccarella, A; Kellar, D; Oniskey, T K; Terinate, P; Rosenberg, S D; Huang, E J; Herbert, D R; Kim, C C

    2015-09-01

    Activation of macrophages is a key step in the initiation of immune responses, but the transcriptional mechanisms governing macrophage activation during infection are not fully understood. It was recently shown that the AP-1 family transcription factor JUNB positively regulates macrophage activation in response to Toll-like receptor agonists that promote classical or M1 polarization, as well as to the cytokine interleukin-4 (IL-4), which elicits an alternatively activated or M2 phenotype. However, a role for JUNB in macrophage activation has never been demonstrated invivo. Here, to dissect the role of JUNB in macrophage activation in a physiological setting, mice lacking JUNB specifically in myeloid cells were tested in two infection models: experimental cerebral malaria, which elicits a pathological type 1 immune response, and helminth infection, in which type 2 responses are protective. Myeloid-restricted deletion of Junb reduced type 1 immune activation, which was associated with reduced cerebral pathology and improved survival during infection with Plasmodium berghei. Myeloid JUNB deficiency also compromised type 2 activation during infection with the hookworm Nippostrongylus brasiliensis, leading to diminished cytokine production and eosinophil recruitment and increased parasite burden. These results demonstrate that JUNB in myeloid cells shapes host responses and outcomes during type 1 and type 2 infections. PMID:26178310

  13. Angiogenic Type I Collagen Extracellular Matrix Integrated with Recombinant Bacteriophages Displaying Vascular Endothelial Growth Factors.

    PubMed

    Yoon, Junghyo; Korkmaz Zirpel, Nuriye; Park, Hyun-Ji; Han, Sewoon; Hwang, Kyung Hoon; Shin, Jisoo; Cho, Seung-Woo; Nam, Chang-Hoon; Chung, Seok

    2016-01-01

    Here, a growth-factor-integrated natural extracellular matrix of type I collagen is presented that induces angiogenesis. The developed matrix adapts type I collagen nanofibers integrated with synthetic colloidal particles of recombinant bacteriophages that display vascular endothelial growth factor (VEGF). The integration is achieved during or after gelation of the type I collagen and the matrix enables spatial delivery of VEGF into a desired region. Endothelial cells that contact the VEGF are found to invade into the matrix to form tube-like structures both in vitro and in vivo, proving the angiogenic potential of the matrix. PMID:26638984

  14. 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

  15. Physician and patient management of type 2 diabetes and factors related to glycemic control in Spain

    PubMed Central

    Yurgin, Nicole Rae; Boye, Kristina Secnik; Dilla, Tatiana; Suriach, Nria Lara; Llach, Xavier Badia

    2008-01-01

    The objective of this study was to assess current treatment patterns, blood glucose test strip usage, and treatment compliance in patients with type 2 diabetes mellitus (T2DM) in primary care centers in Spain, and to assess factors related to glycemic control. We conducted a retrospective chart review of patients with T2DM and measured treatment compliance using the Morisky-Green questionnaire. 294 patients were included in the study from a population of patients attending 30 primary care centers throughout Spain. Results showed that the majority of patients were treated with oral monotherapy (36%) and oral combination therapy (35%). Less than half of the patients had good glycemic control (HbA1c ? 6.5%). Half of the patients treated pharmacologically reported good compliance with treatment. Logistic regression analyses performed to identify factors associated with glycemic control showed that high body mass index (BMI) and poor compliance were the strongest predictors of poor HbA1c control (OR: 2.198 and 1.789, respectively, p < 0.05). In conclusion, in the course of managing diabetes, physicians and patients should attempt to improve compliance and lower BMI, which could lead to better glycemic control. PMID:19920948

  16. 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.

  17. A3 Domain Region 18031818 Contributes to the Stability of Activated Factor VIII and Includes a Binding Site for Activated Factor IX

    PubMed Central

    Bloem, Esther; Meems, Henriet; van den Biggelaar, Maartje; Mertens, Koen; Meijer, Alexander B.

    2013-01-01

    A recent chemical footprinting study in our laboratory suggested that region 18031818 might contribute to A2 domain retention in activated factor VIII (FVIIIa). This site has also been implicated to interact with activated factor IX (FIXa). Asn-1810 further comprises an N-linked glycan, which seems incompatible with a role of the amino acids 18031818 for FIXa or A2 domain binding. In the present study, FVIIIa stability and FIXa binding were evaluated in a FVIII-N1810C variant, and two FVIII variants in which residues 18031810 and 18111818 are replaced by the corresponding residues of factor V (FV). Enzyme kinetic studies showed that only FVIII/FV 18111818 has a decreased apparent binding affinity for FIXa. Flow cytometry analysis indicated that fluorescent FIXa exhibits impaired complex formation with only FVIII/FV 18111818 on lipospheres. Site-directed mutagenesis revealed that Phe-1816 contributes to the interaction with FIXa. To evaluate FVIIIa stability, the FVIII/FV chimeras were activated by thrombin, and the decline in cofactor function was followed over time. FVIII/FV 18031810 and FVIII/FV 18111818 but not FVIII-N1810C showed a decreased FVIIIa half-life. However, when the FVIII variants were activated in presence of FIXa, only FVIII/FV 18111818 demonstrated an enhanced decline in cofactor function. Surface plasmon resonance analysis revealed that the FVIII variants K1813A/K1818A, E1811A, and F1816A exhibit enhanced dissociation after activation. The results together demonstrate that the glycan at 1810 is not involved in FVIII cofactor function, and that Phe-1816 of region 18111818 contributes to FIXa binding. Both regions 18031810 and 18111818 contribute to FVIIIa stability. PMID:23884417

  18. Differential Regulation of Type I Interferon and Epidermal Growth Factor Pathways by a Human Respirovirus Virulence Factor

    PubMed Central

    Caignard, Grgory; Komarova, Anastassia V.; Boura, Mehdi; Mourez, Thomas; Jacob, Yves; Jones, Louis M.; Rozenberg, Flore; Vabret, Astrid; Freymuth, Franois; Tangy, Frdric; Vidalain, Pierre-Olivier

    2009-01-01

    A number of paramyxoviruses are responsible for acute respiratory infections in children, elderly and immuno-compromised individuals, resulting in airway inflammation and exacerbation of chronic diseases like asthma. To understand the molecular pathogenesis of these infections, we searched for cellular targets of the virulence protein C of human parainfluenza virus type 3 (hPIV3-C). We found that hPIV3-C interacts directly through its C-terminal domain with STAT1 and GRB2, whereas C proteins from measles or Nipah viruses failed to do so. Binding to STAT1 explains the previously reported capacity of hPIV3-C to block type I interferon signaling, but the interaction with GRB2 was unexpected. This adaptor protein bridges Epidermal Growth Factor (EGF) receptor to MAPK/ERK pathway, a signaling cascade recently found to be involved in airway inflammatory response. We report that either hPIV3 infection or transient expression of hPIV3-C both increase cellular response to EGF, as assessed by Elk1 transactivation and phosphorylation levels of ERK1/2, 40S ribosomal subunit protein S6 and translation initiation factor 4E (eIF4E). Furthermore, inhibition of MAPK/ERK pathway with U0126 prevented viral protein expression in infected cells. Altogether, our data provide molecular basis to explain the role of hPIV3-C as a virulence factor and determinant of pathogenesis and demonstrate that Paramyxoviridae have evolved a single virulence factor to block type I interferon signaling and to boost simultaneous cellular response to growth factors. PMID:19806178

  19. 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 and HCl to more than 99%.

  20. 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

  1. 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 diabetes on, and involving them in, the management of their condition. PMID:23476735

  2. Factors associated with consumption of diabetic diet among type 2 diabetic subjects from Ahmedabad, Western India.

    PubMed

    Patel, Mayur; Patel, Ina M; Patel, Yash M; Rathi, Suresh K

    2012-12-01

    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

  3. 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.

  4. 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

  5. Vasopressin increases type IV collagen production through the induction of transforming growth factor-beta secretion in rat mesangial cells.

    PubMed

    Tahara, Atsuo; Tsukada, Junko; Tomura, Yuichi; Yatsu, Takeyuki; Shibasaki, Masayuki

    2008-02-01

    Production of extracellular matrix proteins, such as type IV collagen, by mesangial cells contributes to progressive glomerulosclerosis. Transforming growth factor-beta (TGF-beta) modulates mesangial cell growth and stimulates extracellular matrix synthesis by mesangial cells. In this study, the ability of vasopressin (AVP), which causes mesangial cell proliferation and hypertrophy, to stimulate type IV collagen production and correlation with TGF-beta secretion by cultured rat mesangial cells was examined. AVP induced a time- and concentration-dependent increase in TGF-beta secretion and mitogenic effect in rat mesangial cells. This AVP-induced increase in TGF-beta secretion was potently inhibited by AVP V(1A) receptor-selective antagonist. AVP also induced a concentration-dependent increase in the production of type IV collagen and this effect was inhibited by V(1A) receptor-selective antagonist. Furthermore, TGF-beta also induced an increase in the production of type IV collagen; the AVP-enhanced production of type IV collagen was inhibited by an anti-TGF-beta antibody. These results demonstrate that AVP stimulates synthesis of type IV collagen by cultured rat mesangial cells through the induction of TGF-beta synthesis mediated by V(1A) receptors. Therefore, AVP-induced TGF-beta secretion by proliferating mesangial cells might act as an autocrine factor to regulate synthesis of extracellular matrix; this mechanism may contribute to glomerulosclerosis in renal diseases including diabetic nephropathy. PMID:18299204

  6. Does the photon beam quality factor depend on the type of ionization chamber?

    PubMed

    Christ, G; Major, J; Nüsslin, F

    1995-08-01

    The photon beam quality factor Q of 6- and 15-MV photon beams has been measured using different types of thimble ionization chambers with various wall, electrode and insulator materials. Some types of chambers seem to overestimate the corresponding Q-value by 0.4% (6 MV) and 0.7% (15 MV), respectively. The effect on the stopping power ratio water to air and on the pertubation correction will be discussed. PMID:7501813

  7. 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.

  8. Cardiovascular Autonomic Neuropathy Is Associated With Macrovascular Risk Factors in Type 2 Diabetes

    PubMed Central

    Yderstraede, Knud; Gulichsen, Elisabeth; Jakobsen, Poul Erik; Lervang, Hans Henrik; Eldrup, Ebbe; Nygaard, Hans; Tarnow, Lise; Ejskjaer, Niels

    2014-01-01

    Background: The objective was to identify the presence of cardiovascular autonomic neuropathy (CAN) in a cohort of individuals with diabetes in outpatient clinics from 4 different parts of Denmark and to explore the difference between type 1 and type 2 diabetes in relation to CAN. Methods: The DAN-Study is a Danish multicenter study focusing on diabetic autonomic neuropathy. Over a period of 12 months, 382 type 1 and 271 type 2 individuals with diabetes were tested for CAN. Patients were randomly recruited and tested during normal visits to outpatient clinics at 4 Danish hospitals. The presence of CAN was quantified by performing 3 cardiovascular reflex tests (response to standing, deep breathing, and valsalva). To describe possible associations, multivariate analysis with CAN as the dependent variable was performed. Results: The prevalence of CAN was higher among patients with type 2 diabetes (35%) compared to patients with type 1 diabetes (25%). Multivariate analysis revealed significant associations between CAN and different risk markers in the 2 populations. In type 1 diabetes patients CAN was associated with microalbuminuria (P < .001), macroalbuminuria (P = .011), simplex retinopathy (P < .001), proliferative retinopathy (P < .001), and peripheral neuropathy (P = .041). Among type 2 diabetes patients CAN was independently associated with high pulse pressure (P < .01), BMI (P = .006), and smoking (P = .025). Conclusion: In this cross-sectional observational study CAN was independently associated with microvascular complication in type 1, whereas in type 2 CAN was associated with macrovascular risk factors. PMID:24876410

  9. Heel bone strength is related to lifestyle factors in Okinawan men with type 2 diabetes mellitus

    PubMed Central

    Gushiken, Michiko; Komiya, Ichiro; Ueda, Shinichiro; Kobayashi, Jun

    2015-01-01

    Aims/Introduction Although male diabetic patients have an increased risk of fracture, there is little information about this in the literature. The association between heel bone stiffness and the lifestyle of male patients with diabetes was evaluated. Materials and Methods The study included 108 participants with type 2 diabetes mellitus patients and 168 age-adjusted, healthy male volunteers. None of the participants had a history of osteoporosis or other severe diseases. Heel bone stiffness was examined by quantitative ultrasound, and each participant completed a health interview survey questionnaire. Bone stiffness was taken as an indicator of bone strength. Stepwise regression analysis was used to investigate associations between bone stiffness and lifestyle-related factors, such as sunlight exposure, intake of milk or small fish, regular exercise, cigarette smoking, consumption of alcohol, and number of remaining teeth. Results Bone stiffness showed a significant negative association with cigarette smoking [standardized coefficient (SC) = −0.297, F-value (F) = 10.059] and age (SC = −0.207, F = 7.565) in diabetic patients. Bone stiffness showed a significant negative association with age (SC = −0.371, F = 12.076) and height (SC = −0.193, F = 7.898), as well as a significant positive association with sunlight exposure (SC = 0.182, F = 9.589) and intake of small fish (SC = 0.170, F = 7.393) in controls. Conclusions These findings suggest that cigarette smoking and age are negatively associated with bone stiffness in Okinawan male patients with type 2 diabetes mellitus. PMID:25802722

  10. Hypertension is an independent risk factor for type 2 diabetes: the Korean genome and epidemiology study

    PubMed Central

    Kim, Min-Ju; Lim, Nam-Kyoo; Choi, Sun-Ja; Park, Hyun-Young

    2015-01-01

    Hypertension and diabetes share common risk factors and frequently co-occur. Although high blood pressure (BP) was reported as a significant predictor of type 2 diabetes, little is known about this association in Korea. This study investigated the relationship of prehypertension and hypertension with type 2 diabetes in 7150 middle-aged Koreans, as well as the effect of BP control on diabetes development over 8 years. At 8 years, 1049 (14.7%) of the 7150 participants had newly developed diabetes, including 11.2, 16.7 and 21.5% of baseline normotensive, prehypertensive and hypertensive subjects, respectively. The overall incidence rate of diabetes was 22.3 events per 1000 person-years. Subjects with baseline prehypertension (hazard ratio (HR), 1.27; 95% confidence interval (CI), 1.091.48) and hypertension (HR 1.51; 95% CI, 1.291.76) were at higher risk of diabetes than normotensive subjects after controlling for potential confounders (P-value for trend <0.001). These associations persisted even when subjects were stratified by baseline glucose status, sex and body mass index (BMI). The risk of diabetes was significantly higher in subjects who had normal BP at baseline and progressed to prehypertention or hypertension at 8 years (HR, 1.48; 95% CI, 1.201.83) than those with controlled BP, but these associations were not observed in subjects with baseline prehypertension and hypertension. These findings showed that prehypertension and hypertension are significantly associated with the development of diabetes, independent of baseline glucose status, sex and BMI. Active BP control reduced incident diabetes only in normotensive individuals, suggesting the need for early BP management. PMID:26178151

  11. Two Domains of Cytotoxic Necrotizing Factor Type 1 Bind the Cellular Receptor, Laminin Receptor Precursor Protein▿

    PubMed Central

    McNichol, Beth A.; Rasmussen, Susan B.; Carvalho, Humberto M.; Meysick, Karen C.; O'Brien, Alison D.

    2007-01-01

    Cytotoxic necrotizing factor type 1 (CNF1) and CNF2 are highly homologous toxins that are produced by certain pathogenic strains of Escherichia coli. These 1,014-amino-acid toxins catalyze the deamidation of a specific glutamine residue in RhoA, Rac1, and Cdc42 and consist of a putative N-terminal binding domain, a transmembrane region, and a C-terminal catalytic domain. To define the regions of CNF1 that are responsible for binding of the toxin to its cellular receptor, the laminin receptor precursor protein (LRP), a series of CNF1 truncated toxins were characterized and assessed for toxin binding. In particular, three truncated toxins, ΔN63, ΔN545, and ΔC469, retained conformational integrity and in vitro enzymatic activity and were immunologically reactive against a panel of anti-CNF1 monoclonal antibodies (MAbs). Based on a comparison of these truncated toxins with wild-type CNF1 and CNF2 in LRP and HEp-2 cell binding assays and in MAb and LRP competitive binding inhibition assays and based on the results of confocal microscopy, we concluded that CNF1 contains two major binding regions: one located within the N terminus, which contained amino acids 135 to 164, and one which resided in the C terminus and included amino acids 683 to 730. The data further indicate that CNF1 can bind to an additional receptor(s) on HEp-2 cells and that LRP can also serve as a cellular receptor for CNF2. PMID:17709415

  12. 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,…

  13. 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

  14. 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...

  15. 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…

  16. 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

  17. 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,

  18. 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…

  19. Investigating Factors Associated with Depression of Type 2 Diabetic Retinopathy Patients in China

    PubMed Central

    Qian, Duo; Dong, Qing; Gu, Zhifeng

    2015-01-01

    Aims and objectives To assess the depression status of type 2 diabetic retinopathy patients in Nantong China and to identify factors associated with depression. Methods Two hundred and ninety-four patients with type 2 diabetic retinopathy were recruited from the Affiliated Hospital of Nantong University. The severity of DR was measured in the worse eye. Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression Scale (CES-D); the quality of life was measured with the Medical Outcomes Study Short Form 36 (SF-36). The logistic regression analyses were used to identify the independent factors of depression. Results The mean age of the study subjects was 57.77 years (SD: 9.64). Approximately 35.7% of subjects reported depressive symptoms (n = 105).Multiple logistic regression analyses showed that female gender (p = 0.014), low monthly income (p = 0.01), poor vision in the better eye (P = 0.002), laser treatment history (p = 0.01) were significant risk factors for depression. The quality of life of individuals with CES-D score<16 was significantly better compared with individuals with CES-D score?16. Conclusion The reported depressive symptoms among type 2 diabetic retinopathy population is higher in Nantong China. Gender, salary, vision acuity and treatment history were important risk factors linked to this disorder in the Chinese type 2 diabetic retinopathy population from Nantong. More attention by medical care personnel needs to be paid to the psychological health of this population. PMID:26151365

  20. Pleiotropic effects of type 2 diabetes management strategies on renal risk factors.

    PubMed

    Muskiet, Marcel H A; Tonneijck, Lennart; Smits, Mark M; Kramer, Mark H H; Heerspink, Hiddo J Lambers; van Raalte, Daniël H

    2015-05-01

    In parallel with the type 2 diabetes pandemic, diabetic kidney disease has become the leading cause of end-stage renal disease worldwide, and is associated with high cardiovascular morbidity and mortality. As established in landmark randomised trials and recommended in clinical guidelines, prevention and treatment of diabetic kidney disease focuses on control of the two main renal risk factors, hyperglycaemia and systemic hypertension. Treatment of systemic hypertension with angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers is advocated because these drugs seem to exert specific renoprotective effects beyond blood pressure lowering. Emerging evidence shows that obesity, glomerular hyperfiltration, albuminuria, and dyslipidaemia might also adversely affect the kidney in diabetes. Control of these risk factors could have additional benefits on renal outcome in patients with type 2 diabetes. However, despite multifactorial treatment approaches, residual risk for the development and progression of diabetic kidney disease in patients with type 2 diabetes remains, and novel strategies or therapies to treat the disease are urgently needed. Several drugs used in the treatment of type 2 diabetes are associated with pleiotropic effects that could favourably or unfavourably change patients' renal risk profile. We review the risk factors and treatment of diabetic kidney disease, and describe the pleiotropic effects of widely used drugs in type 2 diabetes management on renal outcomes, with special emphasis on antihyperglycaemic drugs. PMID:25943756

  1. Adiponectin levels and cardiovascular risk factors in Japanese men with type 2 diabetes.

    PubMed

    Sakuta, Hidenari; Suzuki, Takashi; Yasuda, Hiroko; Ito, Teizo

    2005-04-01

    Several cardiovascular risk factors correlate with adiponectin levels. It is not known whether total homocysteine, folate and gamma-glutamyl transferase levels correlate with adiponectin. We cross-sectionally analyzed the association between adiponectin and these cardiovascular risk factors in diabetic patients. One hundred and two male inpatients with type 2 diabetes without overt nephropathy or insulin use were studied. In a regression analysis of the quartiles of adiponectin, plasma levels of adiponectin were associated positively with HDL-cholesterol and age, and inversely with body mass index and HbA1c, but not with total homocysteine, folate or gamma-glutamyl transferase. Non-traditional cardiovascular risk factors such as homocysteine and folate levels were not associated with adiponectin levels in male type 2 diabetic patients who are not subject to insulin therapy. PMID:15863955

  2. 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 literature series, the main causes of MEN1-related deaths were due to the malignant nature of the PETs, followed by the malignant nature of thymic carcinoid tumors. These results differ from the results of a number of the literature series, especially those reported before the 1990s. The causes of non-MEN1-related death for the 2 series, in decreasing frequency, were cardiovascular disease, other nonendocrine tumors > lung diseases, cerebrovascular diseases. The most frequent non-MEN1-related tumor deaths were colorectal, renal > lung > breast, oropharyngeal. Although both overall and disease-related survival are better than in the past (30-yr survival of NIH series: 82% overall, 88% disease-related), the mean age at death was 55 years, which is younger than expected for the general population. Detailed analysis of causes of death correlated with clinical, laboratory, and tumor characteristics of patients in the 2 series allowed identification of a number of prognostic factors. Poor prognostic factors included higher fasting gastrin levels, presence of other functional hormonal syndromes, need for >3 parathyroidectomies, presence of liver metastases or distant metastases, aggressive PET growth, large PETs, or the development of new lesions. The results of this study have helped define the causes of death of MEN1 patients at present, and have enabled us to identify a number of prognostic factors that should be helpful in tailoring treatment for these patients for both short- and long-term management, as well as in directing research efforts to better define the natural history of the disease and the most important factors determining long-term survival at present. PMID:23645327

  3. 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.

  4. 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

  5. Mother, Infant, and Household Factors Associated with the Type of Food Infants Receive in Developing Countries

    PubMed Central

    Yarnoff, Benjamin; Allaire, Benjamin; Detzel, Patrick

    2014-01-01

    Objectives: We explore the complex factors associated with infant feeding by analyzing what mother, infant, and household factors are associated with the types of food given to infants. We seek to quantify associations in order to inform public health policy about the importance of target populations for infant feeding programs. Methods: We used data from the Demographic Health Survey in 20 developing countries for multiple years to examine mother, infant, and household factors associated with six types of food given to infants (exclusive breastfeeding, non-exclusive breastfeeding, infant formula, milk liquids, non-milk liquids, and solid foods). We performed a seemingly unrelated regressions analysis with community-year fixed effects to account for correlation between food types and control for confounding factors associated with community resources, culture, time period, and geography in the pooled analysis. Results: We found that several mother, infant, and household characteristics were associated with each of the feeding types. Most notably, mothers education, working status, and weight are significantly associated with the type of food given to infants. We provide quantified estimates of the association of each of these variables with six types of food given to infants. Conclusion: By identifying maternal characteristics associated with infant feeding and quantifying those associations, we help public health policymakers generate priorities for targeting infant feeding programs to specific populations that are at greatest risk. Higher educated, working mothers are best to target with exclusive breastfeeding programs for young infants. Mothers with lower education are best to target with complementary feeding programs in infants older than 1?year. Finally, while maternal weight is associated with higher levels of exclusive breastfeeding the association is too weak to merit targeting of breastfeeding programs to low-weight mothers. PMID:24616887

  6. Why you need to include human factors in clinical and empirical studies of in vitro point of care devices? Review and future perspectives.

    PubMed

    Borsci, Simone; Buckle, Peter; Hanna, George B

    2016-04-01

    Use of in-vitro point of care devices - intended as tests performed out of laboratories and near patient - is increasing in clinical environments. International standards indicate that interaction assessment should not end after the product release, yet human factors methods are frequently not included in clinical and empirical studies of these devices. Whilst the literature confirms some advantages of bed-side tests compared to those in laboratories there is a lack of knowledge of the risks associated with their use. This article provides a review of approaches applied by clinical researchers to model the use of in-vitro testing. Results suggest that only a few studies have explored human factor approaches. Furthermore, when researchers investigated people-device interaction these were predominantly limited to qualitative and not standardised approaches. The methodological failings and limitations of these studies, identified by us, demonstrate the growing need to integrate human factors methods in the medical field. PMID:26878393

  7. 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 secondary processes during daily threshold exceedances. Finally, apparent discrepancies that could be generally observed between filter-based studies (such as the present one) and Aerosol Mass Spectrometer-based PMF analyses (organic fractions) are also discussed here.

  8. 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 further underlines the major influence of secondary processes during daily threshold exceedances. Finally, apparent discrepancies that could be generally observed between filter-based studies (such as the present one) and aerosol mass spectrometer-based PMF analyses (organic fractions) are also discussed.

  9. What Preoperative Factors, Including a Bone Bruise, are Associated with Knee Pain/Symptoms at Index ACLR? A MOON Cohort Study

    PubMed Central

    Dunn, Warren R.; Spindler, Kurt P.; Amendola, Annunziato; Andrish, Jack T.; Brophy, Robert H.; Flanigan, David C.; Jones, Morgan H.; Kaeding, Christopher C.; Marx, Robert G.; Matava, Matthew J.; McCarty, Eric C.; Parker, Richard D.; Wolcott, Michelle L.; Vidal, Armando F.; Wolf, Brian R.; Huston, Laura J.; Harrell, Frank E.; An, Angel Qi; Wright, Rick W.

    2013-01-01

    BACKGROUND Increased knee pain at the time of ACL reconstruction may potentially predict more difficult rehabilitation, prolonged recovery, and/or be predictive of increased knee pain at two years. HYPOTHESIS We hypothesize that a bone bruise and/or other preoperative factors are associated with more knee pain/symptoms at the time of index ACL reconstruction, and the presence of a bone bruise would be associated with specific demographic and injury-related factors. STUDY DESIGN Prospective cohort. METHODS In 2007, the Multicenter Orthopaedic Outcomes Network (MOON) database began to prospectively collect surgeon-reported MRI bone bruise status. A multivariable analysis was performed to: 1) determine if a bone bruise, among other preoperative factors, is associated with more knee symptoms/pain, and 2) examine the association of factors related to bone bruise. To evaluate the association of a bone bruise with knee pain/symptoms, linear multiple regression models were fit using the continuous scores of the KOOS symptoms and pain subscales and the SF-36 bodily pain subscale as dependent variables. To examine the association between a bone bruise and risk factors, a logistic regression model was used in which the dependent variable was the presence or absence of a bone bruise. RESULTS Baseline data for 525 subjects was used for analysis, and a bone bruise was present in 419 (80%). The cohort is 58% male, median age 23 yrs. Median Marx activity level was 13. Factors associated with more pain were higher body mass index (p< 0.0001), female sex (p= 0.001), lateral collateral ligament injury (p=0.012), and older age (p= 0.038). Factors associated with more symptoms were a concomitant lateral collateral ligament injury (p=0.014), higher body mass index (p< 0.0001), and female sex (p< 0.0001). Bone bruise is not associated with symptoms/pain at the time of index ACL reconstruction. None of the factors included in the SF-36 bodily pain model were found to be significant. After controlling for other baseline factors, the following factors were associated with a bone bruise: younger age (p=0.034) and not jumping at the time of injury (p=0.006). CONCLUSION Following ACL injury, risk factors associated with a bone bruise are younger age and not jumping at the time of injury. Bone bruise is not associated with symptoms/pain at the time of index ACL reconstruction. PMID:20595556

  10. Microbiological characteristics of clinical isolates of Cryptococcus neoformans in Taiwan: serotypes, mating types, molecular types, virulence factors, and antifungal susceptibility.

    PubMed

    Liaw, S-J; Wu, H-C; Hsueh, P-R

    2010-06-01

    This study investigated the microbiological characteristics of 100 clinical isolates of Cryptococcus neoformans species complex, including serotypes, mating types, molecular types, antifungal susceptibility and virulence. The isolates were collected at National Taiwan University Hospital from 1999 to 2004. Eight isolates of C. neoformans from pigeon droppings were also evaluated. Among these isolates, 99 were C. neoformans var. grubii serotype A and one was C. neoformans var. gattii serotype B. All of these isolates were alpha mating types. PCR fingerprinting, generated by primers M13 and (GACA)(4), and URA5 gene restriction fragment length polymorphism analysis revealed that C. neoformans var. grubii isolates belonged to the VNI (98 isolates) and the VNII (one isolate) types, and the single C. neoformans var. gattii was VGI type. The similar profiles of clinical and environmental isolates suggest that patients might acquire these yeasts from the environment. The MIC(90) for fluconazole, itraconazole, 5-flucytosine, voriconazole and amphotericin B against all C. neoformans isolates were 8, 0.5, 4, 0.125 and 0.5 mg/L, respectively. All clinical isolates produced urease, phospholipase, capsule and melanin, but these activities varied with individual isolates. Analysis of six clinical and two environmental isolates with various levels of phospholipase activity indicated a correlation between phospholipase activity and the ability to adhere to the lung epithelial cell line, A549. The extent of cell damage, as indicated by lactate dehydrogenase release, also paralleled the phospholipase activity of these isolates. In addition, production of melanin contributed significant protection against amphotericin B killing of the isolates tested. PMID:19694765

  11. Loss of striatal type 1 cannabinoid receptors is a key pathogenic factor in Huntington's disease.

    PubMed

    Blzquez, Cristina; Chiarlone, Anna; Sagredo, Onintza; Aguado, Tania; Pazos, M Ruth; Resel, Eva; Palazuelos, Javier; Julien, Boris; Salazar, Mara; Brner, Christine; Benito, Cristina; Carrasco, Carolina; Diez-Zaera, Mara; Paoletti, Paola; Daz-Hernndez, Miguel; Ruiz, Carolina; Sendtner, Michael; Lucas, Jos J; de Ybenes, Justo G; Marsicano, Giovanni; Monory, Krisztina; Lutz, Beat; Romero, Julin; Alberch, Jordi; Gins, Silvia; Kraus, Jrgen; Fernndez-Ruiz, Javier; Galve-Roperh, Ismael; Guzmn, Manuel

    2011-01-01

    Endocannabinoids act as neuromodulatory and neuroprotective cues by engaging type 1 cannabinoid receptors. These receptors are highly abundant in the basal ganglia and play a pivotal role in the control of motor behaviour. An early downregulation of type 1 cannabinoid receptors has been documented in the basal ganglia of patients with Huntington's disease and animal models. However, the pathophysiological impact of this loss of receptors in Huntington's disease is as yet unknown. Here, we generated a double-mutant mouse model that expresses human mutant huntingtin exon 1 in a type 1 cannabinoid receptor-null background, and found that receptor deletion aggravates the symptoms, neuropathology and molecular pathology of the disease. Moreover, pharmacological administration of the cannabinoid ?(9)-tetrahydrocannabinol to mice expressing human mutant huntingtin exon 1 exerted a therapeutic effect and ameliorated those parameters. Experiments conducted in striatal cells show that the mutant huntingtin-dependent downregulation of the receptors involves the control of the type 1 cannabinoid receptor gene promoter by repressor element 1 silencing transcription factor and sensitizes cells to excitotoxic damage. We also provide in vitro and in vivo evidence that supports type 1 cannabinoid receptor control of striatal brain-derived neurotrophic factor expression and the decrease in brain-derived neurotrophic factor levels concomitant with type 1 cannabinoid receptor loss, which may contribute significantly to striatal damage in Huntington's disease. Altogether, these results support the notion that downregulation of type 1 cannabinoid receptors is a key pathogenic event in Huntington's disease, and suggest that activation of these receptors in patients with Huntington's disease may attenuate disease progression. PMID:20929960

  12. Migraine and tension-type headache in Croatia: a population-based survey of precipitating factors.

    PubMed

    Zivadinov, R; Willheim, K; Sepic-Grahovac, D; Jurjevic, A; Bucuk, M; Brnabic-Razmilic, O; Relja, G; Zorzon, M

    2003-06-01

    The careful monitoring of the trigger factors of headache could be an important step in treatment, because their avoidance may lessen the frequency and severity of attacks. Furthermore, they may provide a clue to the aetiology of headache. The aim of the present study was to estimate the prevalence of tension-type headache (TTH) and to establish the frequency of precipitating factors in subjects with migraine and TTH in the adult population of Bakar, County of the Coast and Gorski Kotar, Croatia. Another important purpose of the study was to examine the relationship of the precipitating factors with migraine and TTH, and with migraine subtypes: migraine with aura (MA) and migraine without aura (MO). We performed a population-based survey using a 'face-to-face door-to-door' interview method. The surveyed population consisted of 5173 residents aged between 15 and 65 years. The 3794 participants (73.3%) were screened for headache history according to the International Headache Society (IHS) criteria. Headache screen-positive responders, 2475 (65.2%), were interviewed by trained medical students with a structured detailed interview focused on the precipitating factors. The following precipitating factors in lifetime migraineurs and tension-type headachers have been assessed: stress, sleep disturbances, eating habits, menstrual cycle, oral contraceptives, food items, afferent stimulation, changes in weather conditions and temperature, frequent travelling and physical activity. A total of 720 lifetime migraineurs and 1319 tension-type headachers have been identified. The most common precipitants for both migraine and TTH were stress and frequent travelling. Stress (odds ratio (OR) 1.4, 95% confidence interval (CI) 1.17, 1.69) was associated with migraine, whereas physical activity (OR 0.72, 95% CI 0.59, 0.87) was related to TTH. Considering MA and MO, frequent travelling (OR 2.2, 95% CI 1.59, 2.99), food items (OR 2.2, 95% CI 1.35, 3.51) and changes in weather conditions and temperature (OR 1.75, 95% CI 1.27, 2.41) exhibited a significant positive association with MA. The present study demonstrated that precipitant-dependent attacks are frequent among both migraineurs and tension-type headachers. Lifetime migraineurs experienced headache attacks preceded by triggering factors more frequently than tension-type headachers. MA was more frequently associated with precipitating factors than MO. We suggest that some triggering factors may contribute to the higher occurrence of precipitant-dependent headache attacks in susceptible individuals. PMID:12780762

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

    PubMed Central

    Lima, Adman Cmara Soares; Arajo, Mrcio Flvio Moura; de Freitas, Roberto Wagner Jnior Freire; Zanetti, Maria Lcia; de Almeida, Paulo Csar; 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

  14. Ec sub. gamma. receptor type III (CD16) is included in the. zeta. NK receptor complex expressed by human natural killer cells

    SciTech Connect

    Anderson, P.; Caligiuri, M.; O'Brien, C.; Manley, T.; Ritz, J.; Schlossman, S.F. )

    1990-03-01

    The authors recently reported that CD3{sup {minus}} natural killer (NK) cells express the {zeta} chain of the T-cell receptor complex ({zeta} NK) in association with higher molecular weight structures whose expression differs between individual NK cell clones. Because NK cell cytolytic activity is known to be triggered by perturbation of the type III Fc{sub {gamma}} receptor (CD16), they sought to determine whether this activating molecule is included in the {zeta}NK molecular complex. Biochemical evidence for a physical association between CD16 and {zeta}NK was obtained by comparing immunoprecipitates formed using monoclonal antibodies reactive with each of these molecules by SDS/polyacrylamide gel electrophoresis, immunoblotting, and peptide mapping. In both clonal and polyclonal populations of CD3{sup {minus}}NK cells, CD16 and {zeta}NK specifically associated with one another. Functional evidence for a specific association between CD16 and {zeta}NK in intact cells was obtained by demonstrating a coordinate down-modulation of both of these molecules induced by either phorbol 12-myristate 13-acetate or monoclonal antibodies reactive with CD16. The results suggest that Fc{sub {gamma}} receptor type III (CD16) is included in the {zeta}NK complex and that this complex is likely to play an important role in NK cell activation.

  15. ABO non-O type as a risk factor for thrombosis in patients with pancreatic cancer.

    PubMed

    Li, Donghui; Pise, Mayurika N; Overman, Michael J; Liu, Chang; Tang, Hongwei; Vadhan-Raj, Saroj; Abbruzzese, James L

    2015-11-01

    ABO blood type has previously been identified as a risk factor for thrombosis and pancreatic cancer (PC). The aim of the study is to demonstrate the associations between ABO blood type and other clinical factors with the risk of thromboembolism (TE) in patients with PC. We conducted a retrospective study in 670 patients with pathologically confirmed pancreatic adenocarcinoma at the University of Texas MD Anderson Cancer Center. Clinical information was retrieved from medical records. ABO blood type was determined serologically and/or genetically. Logistic regression models, Kaplan-Meier plot, log-rank test, and Cox proportional hazard regression models were employed in data analysis. The incidence of TE was 35.2% in 670 patients who did not have TE prior to cancer diagnosis. Pulmonary embolism (PE) and deep vein thrombosis (DVT) consisted 44.1% of the TE events. Non-O blood type, pancreatic body/tail tumors, previous use of antithrombotic medication, and obesity (body mass index >30 kg/m(2) ) were significant predictors for TE in general. Blood type A and AB, low hemoglobin level (≤ 10 g/dL), obesity, metastatic tumor, and pancreatic body/tail tumors were significant predictors for PE and DVT. Patients with metastatic tumor or pancreatic body/tail tumors had a much higher frequency of early TE events (≤ 3 months after cancer diagnosis); and early TE occurrence was a significant independent predictor for increased risk of death. These observations suggest that ABO non-O blood type is an independent predictor for TE in PC. A better understanding of the risk factors for TE in PC may help to identify patients who are most likely to benefit from prophylactic anticoagulation therapy. PMID:26275671

  16. ABO non-O type as a risk factor for thrombosis in patients with pancreatic cancer

    PubMed Central

    Li, Donghui; Pise, Mayurika N; Overman, Michael J; Liu, Chang; Tang, Hongwei; Vadhan-Raj, Saroj; Abbruzzese, James L

    2015-01-01

    ABO blood type has previously been identified as a risk factor for thrombosis and pancreatic cancer (PC). The aim of the study is to demonstrate the associations between ABO blood type and other clinical factors with the risk of thromboembolism (TE) in patients with PC. We conducted a retrospective study in 670 patients with pathologically confirmed pancreatic adenocarcinoma at the University of Texas MD Anderson Cancer Center. Clinical information was retrieved from medical records. ABO blood type was determined serologically and/or genetically. Logistic regression models, Kaplan–Meier plot, log-rank test, and Cox proportional hazard regression models were employed in data analysis. The incidence of TE was 35.2% in 670 patients who did not have TE prior to cancer diagnosis. Pulmonary embolism (PE) and deep vein thrombosis (DVT) consisted 44.1% of the TE events. Non-O blood type, pancreatic body/tail tumors, previous use of antithrombotic medication, and obesity (body mass index >30 kg/m2) were significant predictors for TE in general. Blood type A and AB, low hemoglobin level (≤10 g/dL), obesity, metastatic tumor, and pancreatic body/tail tumors were significant predictors for PE and DVT. Patients with metastatic tumor or pancreatic body/tail tumors had a much higher frequency of early TE events (≤3 months after cancer diagnosis); and early TE occurrence was a significant independent predictor for increased risk of death. These observations suggest that ABO non-O blood type is an independent predictor for TE in PC. A better understanding of the risk factors for TE in PC may help to identify patients who are most likely to benefit from prophylactic anticoagulation therapy. PMID:26275671

  17. 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

  18. Cross-Sectional Associations of Blood Elements, Clotting Factors, Nephropathy, and Retinal Outcomes in Long Duration Type 1 Diabetes

    PubMed Central

    Klein, Barbara E. K.; Klein, Ronald; Howard, Kerri P.; Lee, Kristine E.

    2012-01-01

    Purpose To determine the association of blood elements, selected clotting factors, and nephropathy with proliferative diabetic retinopathy (PDR) and macular edema (ME) in those with long duration type 1 diabetes. Methods Participants (n=442) were seen in 20052007 at the 25-year follow-up of a population-based study of diabetic retinopathy, and were eligible for this analysis. Fundus photographs were graded using a standard retinopathy severity scheme. Laboratory measures included hematocrit, white blood cell and platelet counts, serum fibrinogen, interleukin-6, and von Willebrand factor. Results In models including duration of diabetes, hypertension, and diabetic nephropathy, only hematocrit was marginally associated (odds ratio; 95% confidence interval; P value for trend per quintile) with decreased odds of PDR (0.87; 0.741.01; P=0.06). Stratifying by nephropathy status, in those with and without nephropathy, there were no significant associations of any laboratory measures with PDR or ME. None of the variables we examined were associated with ME in individuals with or without nephropathy. Conclusion In persons with long duration type 1 diabetes, none of the blood elements or clotting factors was associated with increased odds of PDR or ME. Investigation of common pathways that lead to diabetic nephropathy and diabetic retinal outcomes should be a research priority in efforts to prevent vision-threatening complications of diabetes and nephropathy. PMID:22568424

  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. Cell type-specific interactions of transcription factors with a housekeeping promoter in vivo.

    PubMed Central

    Stapleton, G; Somma, M P; Lavia, P

    1993-01-01

    Mammalian housekeeping promoters represent a class of regulatory elements different from those of tissues-specific genes, lacking a TATA box and associated with CG-rich DNA. We have compared the organization of the housekeeping Htf9 promoter in different cell types by genomic footprinting. The sites of in vivo occupancy clearly reflected local combinations of tissue-specific and ubiquitous binding factors. The flexibility of the Htf9 promoter in acting as the target of cell-specific combinations of factors may ensure ubiquitous expression of the Htf9-associated genes. Images PMID:8389443

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

    PubMed Central

    Sonestedt, Emily; verby, 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 20002011 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 to draw conclusions. PMID:22855643

  2. Transforming growth factor beta 1-responsive element: closely associated binding sites for USF and CCAAT-binding transcription factor-nuclear factor I in the type 1 plasminogen activator inhibitor gene.

    PubMed Central

    Riccio, A; Pedone, P V; Lund, L R; Olesen, T; Olsen, H S; Andreasen, P A

    1992-01-01

    Transforming growth factor beta (TGF-beta) is the name of a group of closely related polypeptides characterized by a multiplicity of effects, including regulation of extracellular proteolysis and turnover of the extracellular matrix. Its cellular mechanism of action is largely unknown. TGF-beta 1 is a strong and fast inducer of type 1 plasminogen activator inhibitor gene transcription. We have identified a TGF-beta 1-responsive element in the 5'-flanking region of the human type 1 plasminogen activator inhibitor gene and shown that it is functional both in its natural context and when fused to a heterologous nonresponsive promoter. Footprinting and gel retardation experiments showed that two different nuclear factors, present in extracts from both TGF-beta 1-treated and nontreated cells, bind to adjacent sequences contained in the responsive unit. A palindromic sequence binds a trans-acting factor(s) of the CCAAT-binding transcription factor-nuclear factor I family. A partially overlapping dyad symmetry interacts with a second protein that much evidence indicates to be USF. USF is a transactivator belonging to the basic helix-loop-helix family of transcription factors. Mutations which abolish the binding of either CCAAT-binding transcription factor-nuclear factor I or USF result in reduction of transcriptional activation upon exposure to TGF-beta 1, thus showing that both elements of the unit are necessary for the TGF-beta 1 response. We discuss the possible relationship of these findings to the complexity of the TGF-beta action. Images PMID:1549130

  3. Differential regulation of mesodermal gene expression by Drosophila cell type-specific Forkhead transcription factors

    PubMed Central

    Zhu, Xianmin; Ahmad, Shaad M.; Aboukhalil, Anton; Busser, Brian W.; Kim, Yongsok; Tansey, Terese R.; Haimovich, Adrian; Jeffries, Neal; Bulyk, Martha L.; Michelson, Alan M.

    2012-01-01

    A common theme in developmental biology is the repeated use of the same gene in diverse spatial and temporal domains, a process that generally involves transcriptional regulation mediated by multiple separate enhancers, each with its own arrangement of transcription factor (TF)-binding sites and associated activities. Here, by contrast, we show that the expression of the Drosophila Nidogen (Ndg) gene at different embryonic stages and in four mesodermal cell types is governed by the binding of multiple cell-specific Forkhead (Fkh) TFs including Biniou (Bin), Checkpoint suppressor homologue (CHES-1-like) and Jumeau (Jumu) to three functionally distinguishable Fkh-binding sites in the same enhancer. Whereas Bin activates the Ndg enhancer in the late visceral musculature, CHES-1-like cooperates with Jumu to repress this enhancer in the heart. CHES-1-like also represses the Ndg enhancer in a subset of somatic myoblasts prior to their fusion to form multinucleated myotubes. Moreover, different combinations of Fkh sites, corresponding to two different sequence specificities, mediate the particular functions of each TF. A genome-wide scan for the occurrence of both classes of Fkh domain recognition sites in association with binding sites for known cardiac TFs showed an enrichment of combinations containing the two Fkh motifs in putative enhancers found within the noncoding regions of genes having heart expression. Collectively, our results establish that different cell-specific members of a TF family regulate the activity of a single enhancer in distinct spatiotemporal domains, and demonstrate how individual binding motifs for a TF class can differentially influence gene expression. PMID:22378636

  4. 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 513 years, 60.9% for those aged 1429 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 3039 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

  5. 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

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

    PubMed

    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

  7. 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

  8. Early risk factors for nonadherence in pediatric type 1 diabetes: a review of the recent literature.

    PubMed

    Schwartz, David D; Cline, Virginia Depp; Hansen, J A; Axelrad, Marni E; Anderson, Barbara J

    2010-05-01

    Nonadherence to different aspects of the diabetes regimen is common. Problems early in the course of illness predict later difficulties with nonadherence; conversely, good management early on protects against later complications. Screening for early risk factors at the time of diabetes diagnosis is therefore critical for promoting the health of children with type 1 diabetes. The purpose of this paper is to review and synthesize the recent empirical literature on early risk factors for nonadherence in type 1 diabetes, with a focus on three specific adherence behaviors: insulin administration, blood glucose monitoring, and clinic attendance. Risk factors are considered within several broad categories: sociodemographic barriers that limit access to care; child and parent factors that affect adherence both directly and indirectly via their impact on the development of family teamwork; and family interactions with their health-care providers. We integrate the different findings into a "simple model" that can be used to develop efficient screening protocols that can in turn guide efforts at preventive intervention. PMID:20380630

  9. Factors Associated with Glycemic Variability in Patients with Type 2 Diabetes: Focus on Oral Hypoglycemic Agents and Cardiovascular Risk Factors

    PubMed Central

    Yoo, Soyeon; Chin, Sang-Ouk; Lee, Sang-Ah

    2015-01-01

    Background The role of glycemic variability (GV) in development of cardiovascular diseases remains controversial, and factors that determine glucose fluctuation in patients with diabetes are unknown. We investigated relationships between GV indices, kinds of oral hypoglycemic agents (OHAs), and cardiovascular risk factors in patients with type 2 diabetes mellitus (T2DM). Methods We analyzed 209 patients with T2DM. The GV index (standard deviation [SD] and mean absolute glucose change [MAG]) were calculated from 7-point self-monitoring of blood glucose profiles. The patients were classified into four groups according to whether they take OHAs known as GV-lowering (A) and GV-increasing (B): 1 (A only), 2 (neither), 3 (both A and B), and 4 (B only). The 10-year risk for atherosclerotic cardiovascular disease (ASCVD) was calculated using the Pooled Cohort Equations. Results GV indices were significantly higher in patients taking sulfonylureas (SUs), but lower in those taking dipeptidyl peptidase-4 inhibitors. In hierarchical regression analysis, the use of SUs remained independent correlates of the SD (?=0.209, P=0.009) and MAG (?=0.214, P=0.011). In four OHA groups, GV indices increased progressively from group 1 to group 4. However, these did not differ according to quartiles of 10-year ASCVD risk. Conclusion GV indices correlated significantly with the use of OHAs, particularly SU, and differed significantly according to combination of OHAs. However, cardiovascular risk factors and 10-year ASCVD risk were not related to GV indices. These findings suggest that GV is largely determined by properties of OHAs and not to cardiovascular complications in patients with T2DM. PMID:26248860

  10. 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

  11. 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

  12. 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

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

    NASA Astrophysics Data System (ADS)

    Duarte, Mrcio; Vicente, Estela; Calvo, Ana; Nunes, Teresa; Tarelho, Luis; Alves, Clia

    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.

  14. 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

  15. 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]: 0.010.66, 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

  16. 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; Milln, 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

  17. Fibroblast Growth Factor 23 and Incident CKD in Type 2 Diabetes

    PubMed Central

    Craven, Timothy E.; Lee, Jungwha; Scialla, Julia J.; Xie, Huiliang; Wahl, Patricia; Marcovina, Santica M.; Byington, Robert P.; Wolf, Myles

    2015-01-01

    Background and objectives High levels of fibroblast growth factor 23 are associated with accelerated progression of CKD. Whether high fibroblast growth factor 23 levels also predict incident CKD is uncertain. Design, setting, participants, & measurements A prospective case-cohort study was conducted within the Action to Control Cardiovascular Risk in Diabetes Trial. The analytic sample consisted of a random subcohort of 590 patients with type 2 diabetes without prevalent CKD at baseline, 124 of whom developed incident CKD during follow-up, and 520 additional patients with incident CKD outside the random subcohort. The association between serum intact fibroblast growth factor 23 and incident CKD, defined as the new onset of eGFR<60 ml/min per 1.73 m2 that represented a ?25% decrease from baseline in an individual with eGFR?60 ml/min per 1.73 m2 and no microalbuminuria (<30 mg/g creatinine) at baseline, was tested. Results The mean baseline eGFR in the random subcohort was 90.922.7 ml/min per 1.73 m2. During a median follow-up of 4.7 years, there was a total of 644 patients with incident CKD. The median baseline fibroblast growth factor 23 level was modestly higher among patients with incident CKD versus controls (43.5, interquartile range=34.755.1 versus 39.8, interquartile range=31.949.5 pg/ml; P<0.001). Higher baseline fibroblast growth factor 23 levels were associated with higher risk of incident CKD in unadjusted and demographics-adjusted models, but the effect was attenuated after additional adjustment for clinical risk factors and baseline eGFR (hazard ratio per SD of natural log fibroblast growth factor 23, 1.09; 95% confidence interval, 0.94 to 1.27), which was the strongest predictor of incident CKD. Consistent with the results of primary analyses, baseline fibroblast growth factor 23 was not associated with eGFR slope. Conclusions Higher fibroblast growth factor 23 levels are not independently associated with higher risk of incident CKD in patients with type 2 diabetes. PMID:25343949

  18. Predominant factor determining wear properties of ?-type and (?+?)-type titanium alloys in metal-to-metal contact for biomedical applications.

    PubMed

    Lee, Yoon-Seok; Niinomi, Mitsuo; Nakai, Masaaki; Narita, Kengo; Cho, Ken

    2015-01-01

    The predominant factor determining the wear properties of a new titanium alloy, Ti-29Nb-13Ta-4.6Zr (TNTZ) and a conventional titanium alloy, Ti-6Al-4V extra-low interstitial (Ti64) was investigated for TNTZ and Ti64 combinations in metal-to-metal contacting bio-implant applications. The worn surfaces, wear debris, and subsurface damages were analyzed using a scanning electron microscopy combined with energy-dispersive spectroscopy and electron-back scattered diffraction analysis. The volume loss of TNTZ is found to be larger than that of Ti64, regardless of the mating material. The wear track of TNTZ exhibits the galled regions and severe plastic deformation with large flake-like debris, indicative of delamination wear, which strongly suggests the occurrence of adhesive wear. Whereas, the wear track of Ti64 have a large number of regular grooves and microcuttings with cutting chip-like wear debris and microfragmentation of fine oxide debris, indicative of abrasive wear combined with oxidative wear. This difference in the wear type is caused by severe and mild subsurface deformations of TNTZ and Ti64, respectively. The lower resistance to plastic shearing for TNTZ compared to that of Ti64 induces delamination, resulting in a higher wear rate. PMID:25460417

  19. Risk factors for migraine and tension-type headache in 11year old children

    PubMed Central

    2014-01-01

    Background Though migraine and tension type headache are both commonly diagnosed in childhood, little is known about their determinants when diagnosed prior to puberty onset. Our aim was to determine psychosocial- and health-related risk factors of migraine and tension-type headache in 11year old children. Methods 871 New Zealand European children were enrolled in a longitudinal study at birth and data were collected at birth, 1, 3.5, 7, and 11years of age. Primary headache was determined at age 11years based on the International Headache Society. Perinatal factors assessed were small for gestational age status, sex, maternal smoking during pregnancy, maternal perceived stress, and maternal school leaving age. Childhood factors assessed were sleep duration, percent body fat, television watching, parent and self-reported total problem behaviour, being bullied, and depression. Results Prevalence of migraine and tension-type headache was 10.5% and 18.6%, respectively. Both migraine and TTH were significantly associated with self-reported problem behaviour in univariable logistic regression analyses. Additionally, migraine was associated with reduced sleep duration, and both sleep and behaviour problems remained significant after multivariable analyses. TTH was also significantly associated with antenatal maternal smoking, higher body fat, and being bullied. For TTH, problem behaviour measured at ages 3.5 and 11years both remained significant after multivariable analysis. Being born small for gestational age was not associated with either headache group. Conclusions Although they share some commonality, migraine and tension-type headache are separate entities in childhood with different developmental characteristics. The association between primary headache and problem behaviour requires further investigation. PMID:25205384

  20. Racial Disparities in the Control Status of Cardiovascular Risk Factors in an Underinsured Population with Type 2 Diabetes

    PubMed Central

    Wang, Y.; Katzmarzyk, P.T.; Horswell, R.; Zhao, W.; Li, W.; Johnson, J.; Ryan, D.H.; Hu, G

    2014-01-01

    Aims To investigate the race-specific trend in attainment of the American Diabetes Association (ADA) cardiovascular risk factors control goals of patients with type 2 diabetes (HbA1c <53 mmol/mol [7.0%], blood pressure <130/80 mmHg, and low-density lipoprotein [LDL] cholesterol <2.6 mmol/L). Methods The study sample included 14,946 African American and 12,758 White patients who were newly diagnosed with type 2 diabetes between 2001 and 2009 in the Louisiana State University Hospital System. The race-specific percentages of patients attainment of ADA goals were calculated using the baseline and follow-up measurements of HbA1c, blood pressure, and LDL-cholesterol levels. Logistic regression was used to test the difference between African American and White patients. Results The percentage of patients who met all three ADA goals increased from 8.2% in 2001 to 10.2% in 2009 (increased by 24.4%) in this cohort. Compared with African American patients, White patients had better attainment of the following ADA goals: HbA1c goal (61.4 vs. 55.1%), blood pressure goal (25.8 vs. 20.4%), LDL-cholesterol goal (40.1 vs. 37.7%), and all three goals (7.3 vs. 5.1%). African American and White patients generally had improved CVD risk factors profile during follow-up when we assessed attainment of the ADA goals by using means of HbA1c, blood pressure and LDL cholesterol. Conclusions During 20012009, this low income cohort with type 2 diabetes generally experienced improved control of CVD risk factors. White patients had better attainment of the ADA cardiovascular risk factors control goals than their African American counterparts. PMID:24750373

  1. Functional roles and clinical values of insulin-like growth factor-binding protein-5 in different types of cancers

    PubMed Central

    Gll, Gke; Karabulut, Sevgi; Akkiprik, Mustafa

    2012-01-01

    Insulin-like growth factor-binding proteins (IGFBPs) are critical regulators of the mitogenic activity of insulin-like growth factors (IGFs). IGFBP5, one of these IGFBPs, has special structural features, including a nuclear transport domain, heparin-binding motif, and IGF/extracellular matrix/acid-labile subunit-binding sites. Furthermore, IGFBP5 has several functional effects on carcinogenesis and even normal cell processes, such as cell growth, death, motility, and tissue remodeling. These biological effects are sometimes related with IGF (IGF-dependent effects) and sometimes not (IGF-independent effects). The functional role of IGFBP5 is most likely determined in a cell-type and tissue-type specific manner but also depends on cell context, especially in terms of the diversity of interacting proteins and the potential for nuclear localization. Clinical findings show that IGFBP5 has the potential to be a useful clinical biomarker for predicting response to therapy and clinical outcome of cancer patients. In this review, we summarize the functional diversity and clinical importance of IGFBP5 in different types of cancers. PMID:22313597

  2. 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 area if more data on drought impacts become available.

  3. A mammary cell-specific enhancer in mouse mammary tumor virus DNA is composed of multiple regulatory elements including binding sites for CTF/NFI and a novel transcription factor, mammary cell-activating factor.

    PubMed Central

    Mink, S; Härtig, E; Jennewein, P; Doppler, W; Cato, A C

    1992-01-01

    Mouse mammary tumor virus (MMTV) is a milk-transmitted retrovirus involved in the neoplastic transformation of mouse mammary gland cells. The expression of this virus is regulated by mammary cell type-specific factors, steroid hormones, and polypeptide growth factors. Sequences for mammary cell-specific expression are located in an enhancer element in the extreme 5' end of the long terminal repeat region of this virus. This enhancer, when cloned in front of the herpes simplex thymidine kinase promoter, endows the promoter with mammary cell-specific response. Using functional and DNA-protein-binding studies with constructs mutated in the MMTV long terminal repeat enhancer, we have identified two main regulatory elements necessary for the mammary cell-specific response. These elements consist of binding sites for a transcription factor in the family of CTF/NFI proteins and the transcription factor mammary cell-activating factor (MAF) that recognizes the sequence G Pu Pu G C/G A A G G/T. Combinations of CTF/NFI- and MAF-binding sites or multiple copies of either one of these binding sites but not solitary binding sites mediate mammary cell-specific expression. The functional activities of these two regulatory elements are enhanced by another factor that binds to the core sequence ACAAAG. Interdigitated binding sites for CTF/NFI, MAF, and/or the ACAAAG factor are also found in the 5' upstream regions of genes encoding whey milk proteins from different species. These findings suggest that mammary cell-specific regulation is achieved by a concerted action of factors binding to multiple regulatory sites. Images PMID:1328867

  4. Nodular histogenetic type -- the most significant factor for thick melanoma: implications for prevention.

    PubMed

    Bergenmar, M; Ringborg, U; Mnsson Brahme, E; Brandberg, Y

    1998-10-01

    Tumour thickness is the most important prognostic factor in malignant melanoma. To reduce the melanoma-related mortality, factors related to the presentation of thick melanoma have to be identified. Three samples of melanoma patients (n=694) were studied for this purpose. Histogenetic type was the only factor which differentiated between 'thin' (< or = 0.8 mm) and 'thick' (> 2.0 mm) lesions. During a 10-year period only 3% of the nodular lesions were 'thin' at diagnosis. Differences in knowledge about melanoma or the location of the lesion (either 'easy' or 'difficult' for the patient to observe) did not explain differences in tumour thickness. The most common tumour site irrespective of histogenetic type and gender was 'back of the trunk'. 'Increase in diameter' and 'bleeding' were the symptoms most frequently reported by patients with 'thick' melanoma. 'Thick' lesions were diagnosed in older age groups and in men to a greater extent. Considering these results, melanoma prevention should also be targeted to older age groups and attention should be paid to symptoms such as 'increase in diameter' even in the absence of other characteristic symptoms of melanoma. An increased proportion of nodular melanoma diagnosed as 'thin' lesions can be interpreted as a step forward in secondary prevention. PMID:9835453

  5. 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 Networks 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

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

    PubMed

    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, and leptin/adiponectin). PMID:26132231

  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, and leptin/adiponectin). PMID:26132231

  8. Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2.

    PubMed

    Rost, Simone; Fregin, Andreas; Ivaskevicius, Vytautas; Conzelmann, Ernst; Hrtnagel, Konstanze; Pelz, Hans-Joachim; Lappegard, Knut; Seifried, Erhard; Scharrer, Inge; Tuddenham, Edward G D; Mller, Clemens R; Strom, Tim M; Oldenburg, Johannes

    2004-02-01

    Coumarin derivatives such as warfarin represent the therapy of choice for the long-term treatment and prevention of thromboembolic events. Coumarins target blood coagulation by inhibiting the vitamin K epoxide reductase multiprotein complex (VKOR). This complex recycles vitamin K 2,3-epoxide to vitamin K hydroquinone, a cofactor that is essential for the post-translational gamma-carboxylation of several blood coagulation factors. Despite extensive efforts, the components of the VKOR complex have not been identified. The complex has been proposed to be involved in two heritable human diseases: combined deficiency of vitamin-K-dependent clotting factors type 2 (VKCFD2; Online Mendelian Inheritance in Man (OMIM) 607473), and resistance to coumarin-type anticoagulant drugs (warfarin resistance, WR; OMIM 122700). Here we identify, by using linkage information from three species, the gene vitamin K epoxide reductase complex subunit 1 (VKORC1), which encodes a small transmembrane protein of the endoplasmic reticulum. VKORC1 contains missense mutations in both human disorders and in a warfarin-resistant rat strain. Overexpression of wild-type VKORC1, but not VKORC1 carrying the VKCFD2 mutation, leads to a marked increase in VKOR activity, which is sensitive to warfarin inhibition. PMID:14765194

  9. Tumor necrosis factor alpha inhibits type I collagen synthesis through repressive CCAAT/enhancer-binding proteins.

    TOXLINE Toxicology Bibliographic Information

    Greenwel P; Tanaka S; Penkov D; Zhang W; Olive M; Moll J; Vinson C; Di Liberto M; Ramirez F

    2000-02-01

    Extracellular matrix (ECM) formation and remodeling are critical processes for proper morphogenesis, organogenesis, and tissue repair. The proinflammatory cytokine tumor necrosis factor alpha (TNF-alpha) inhibits ECM accumulation by stimulating the expression of matrix proteolytic enzymes and by downregulating the deposition of structural macromolecules such as type I collagen. Stimulation of ECM degradation has been linked to prolonged activation of jun gene expression by the cytokine. Here we demonstrate that TNF-alpha inhibits transcription of the gene coding for the alpha2 chain of type I collagen [alpha2(I) collagen] in cultured fibroblasts by stimulating the synthesis and binding of repressive CCAAT/enhancer proteins (C/EBPs) to a previously identified TNF-alpha-responsive element. This conclusion was based on the concomitant identification of C/EBPbeta and C/EBPdelta as TNF-alpha-induced factors by biochemical purification and expression library screening. It was further supported by the ability of the C/EBP-specific dominant-negative (DN) protein to block TNF-alpha inhibition of alpha2(I) collagen but not TNF-alpha stimulation of the MMP-13 protease. The DN protein also blocked TNF-alpha downregulation of the gene coding for the alpha1 chain of type I collagen. The study therefore implicates repressive C/EBPs in the TNF-alpha-induced signaling pathway that controls ECM formation and remodeling.

  10. Tumor Necrosis Factor Alpha Inhibits Type I Collagen Synthesis through Repressive CCAAT/Enhancer-Binding Proteins

    PubMed Central

    Greenwel, Patricia; Tanaka, Shizuko; Penkov, Dmitri; Zhang, Wen; Olive, Michelle; Moll, Jonathan; Vinson, Charles; Di Liberto, Maurizio; Ramirez, Francesco

    2000-01-01

    Extracellular matrix (ECM) formation and remodeling are critical processes for proper morphogenesis, organogenesis, and tissue repair. The proinflammatory cytokine tumor necrosis factor alpha (TNF-?) inhibits ECM accumulation by stimulating the expression of matrix proteolytic enzymes and by downregulating the deposition of structural macromolecules such as type I collagen. Stimulation of ECM degradation has been linked to prolonged activation of jun gene expression by the cytokine. Here we demonstrate that TNF-? inhibits transcription of the gene coding for the ?2 chain of type I collagen [?2(I) collagen] in cultured fibroblasts by stimulating the synthesis and binding of repressive CCAAT/enhancer proteins (C/EBPs) to a previously identified TNF-?-responsive element. This conclusion was based on the concomitant identification of C/EBP? and C/EBP? as TNF-?-induced factors by biochemical purification and expression library screening. It was further supported by the ability of the C/EBP-specific dominant-negative (DN) protein to block TNF-? inhibition of ?2(I) collagen but not TNF-? stimulation of the MMP-13 protease. The DN protein also blocked TNF-? downregulation of the gene coding for the ?1 chain of type I collagen. The study therefore implicates repressive C/EBPs in the TNF-?-induced signaling pathway that controls ECM formation and remodeling. PMID:10629048

  11. Tumor necrosis factor alpha inhibits type I collagen synthesis through repressive CCAAT/enhancer-binding proteins.

    PubMed

    Greenwel, P; Tanaka, S; Penkov, D; Zhang, W; Olive, M; Moll, J; Vinson, C; Di Liberto, M; Ramirez, F

    2000-02-01

    Extracellular matrix (ECM) formation and remodeling are critical processes for proper morphogenesis, organogenesis, and tissue repair. The proinflammatory cytokine tumor necrosis factor alpha (TNF-alpha) inhibits ECM accumulation by stimulating the expression of matrix proteolytic enzymes and by downregulating the deposition of structural macromolecules such as type I collagen. Stimulation of ECM degradation has been linked to prolonged activation of jun gene expression by the cytokine. Here we demonstrate that TNF-alpha inhibits transcription of the gene coding for the alpha2 chain of type I collagen [alpha2(I) collagen] in cultured fibroblasts by stimulating the synthesis and binding of repressive CCAAT/enhancer proteins (C/EBPs) to a previously identified TNF-alpha-responsive element. This conclusion was based on the concomitant identification of C/EBPbeta and C/EBPdelta as TNF-alpha-induced factors by biochemical purification and expression library screening. It was further supported by the ability of the C/EBP-specific dominant-negative (DN) protein to block TNF-alpha inhibition of alpha2(I) collagen but not TNF-alpha stimulation of the MMP-13 protease. The DN protein also blocked TNF-alpha downregulation of the gene coding for the alpha1 chain of type I collagen. The study therefore implicates repressive C/EBPs in the TNF-alpha-induced signaling pathway that controls ECM formation and remodeling. PMID:10629048

  12. AP2-type transcription factors determine stem cell identity in the moss Physcomitrella patens.

    PubMed

    Aoyama, Tsuyoshi; Hiwatashi, Yuji; Shigyo, Mikao; Kofuji, Rumiko; Kubo, Minoru; Ito, Motomi; Hasebe, Mitsuyasu

    2012-09-01

    Stem cells are formed at particular times and positions during the development of multicellular organisms. Whereas flowering plants form stem cells only in the sporophyte generation, non-seed plants form stem cells in both the sporophyte and gametophyte generations. Although the molecular mechanisms underlying stem cell formation in the sporophyte generation have been extensively studied, only a few transcription factors involved in the regulation of gametophyte stem cell formation have been reported. The moss Physcomitrella patens forms a hypha-like body (protonema) and a shoot-like body (gametophore) from a protonema apical cell and a gametophore apical cell, respectively. These apical cells have stem cell characteristics and are formed as side branches of differentiated protonema cells. Here, we show that four AP2-type transcription factors orthologous to Arabidopsis thaliana AINTEGUMENTA, PLETHORA and BABY BOOM (APB) are indispensable for the formation of gametophore apical cells from protonema cells. Quadruple disruption of all APB genes blocked gametophore formation, even in the presence of cytokinin, which enhances gametophore apical cell formation in the wild type. All APB genes were expressed in emerging gametophore apical cells, but not in protonema apical cells. Heat-shock induction of an APB4 transgene driven by a heat-shock promoter increased the number of gametophores. Expression of all APB genes was induced by auxin but not by cytokinin. Thus, the APB genes function synergistically with cytokinin signaling to determine the identity of the two types of stem cells. PMID:22833122

  13. 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

  14. 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…

  15. 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

  16. Survival Outcomes According to Adjuvant Treatment and Prognostic Factors Including Host Immune Markers in Patients with Curatively Resected Ampulla of Vater Cancer

    PubMed Central

    Ha, Hye rim; Oh, Do-Youn; Kim, Tae-Yong; Lee, KyoungBun; Kim, Kyubo; Lee, Kyung-Hun; Han, Sae-Won; Chie, Eui Kyu; Jang, Jin-Young; Im, Seock-Ah; Kim, Tae-You; Kim, Sun-Whe; Bang, Yung-Jue

    2016-01-01

    Background Ampulla of Vater cancer (AoV Ca) is a rare tumor, and its adjuvant treatment has not been established. The purpose of this study was to find out prognostic factors including host immunity and role of adjuvant treatment in AoV Ca. Methods and Findings We reviewed 227 AoV Ca patients with curative resection. Clinical characteristics, adjuvant treatment, disease-free survival (DFS) and overall survival (OS) were analyzed. Among all patients, 63.9, 36.1 and 33.9% had T1/T2, T3/T4 stage and lymph node-positive disease (LN+), respectively. OS of all patients was 90.9 months (95% CI: 52.9–129.0). OS was different according to neutrophil-to-lymphocyte ratio (HR 1.651, 95% CI: 1.11–2.47), platelet-to-lymphocyte ratio (HR 1.488, 95% CI: 1.00–2.21) and systemic inflammatory index (HR 1.669, 95% CI: 1.13–2.47). In multivariate analysis, adverse prognostic factors for OS included vascular invasion (HR 2.571, 95% CI: 1.20–5.53) and elevated CA 19–9 (HR 1.794, 95% CI: 1.07–3.05). A total of 104 patients (46.3%) received adjuvant treatment (25 out of 111of T1/T2 & LN (-), 79 out of 116 of T3/T4 or LN (+)). In T3/T4 or LN (+) stage, adjuvant CCRT with maintenance chemotherapy provided the longest OS (5-year OS rate: 47.0 vs. 41.4%). Conclusions Vascular invasion and elevated CA 19–9 were adverse prognostic factors in resected AoV Ca. In T3/T4 or LN (+) stage, adjuvant CCRT with maintenance chemotherapy provided the best survival outcome. Adjuvant treatment should be further defined in AoV Ca, especially with poor prognostic factors. PMID:26974670

  17. Identification of Rep-Associated Factors in Herpes Simplex Virus Type 1-Induced Adeno-Associated Virus Type 2 Replication Compartments?

    PubMed Central

    Nicolas, Armel; Alazard-Dany, Nathalie; Biollay, Coline; Arata, Loredana; Jolinon, Nelly; Kuhn, Lauriane; Ferro, Myriam; Weller, Sandra K.; Epstein, Alberto L.; Salvetti, Anna; Greco, Anna

    2010-01-01

    Adeno-associated virus (AAV) is a human parvovirus that replicates only in cells coinfected with a helper virus, such as adenovirus or herpes simplex virus type 1 (HSV-1). We previously showed that nine HSV-1 factors are able to support AAV rep gene expression and genome replication. To elucidate the strategy of AAV replication in the presence of HSV-1, we undertook a proteomic analysis of cellular and HSV-1 factors associated with Rep proteins and thus potentially recruited within AAV replication compartments (AAV RCs). This study resulted in the identification of approximately 60 cellular proteins, among which factors involved in DNA and RNA metabolism represented the largest functional categories. Validation analyses indicated that the cellular DNA replication enzymes RPA, RFC, and PCNA were recruited within HSV-1-induced AAV RCs. Polymerase ? was not identified but subsequently was shown to colocalize with Rep within AAV RCs even in the presence of the HSV-1 polymerase complex. In addition, we found that AAV replication is associated with the recruitment of components of the Mre11/Rad50/Nbs1 complex, Ku70 and -86, and the mismatch repair proteins MSH2, -3, and -6. Finally, several HSV-1 factors were also found to be associated with Rep, including UL12. We demonstrated for the first time that this protein plays a role during AAV replication by enhancing the resolution of AAV replicative forms and AAV particle production. Altogether, these analyses provide the basis to understand how AAV adapts its replication strategy to the nuclear environment induced by the helper virus. PMID:20573815

  18. Over-expression of Dof-type transcription factor increases lipid production in Chlamydomonas reinhardtii.

    PubMed

    Ibáñez-Salazar, Alejandro; Rosales-Mendoza, Sergio; Rocha-Uribe, Alejandro; Ramírez-Alonso, Jocelín Itzel; Lara-Hernández, Ignacio; Hernández-Torres, Araceli; Paz-Maldonado, Luz María Teresita; Silva-Ramírez, Ana Sonia; Bañuelos-Hernández, Bernardo; Martínez-Salgado, José Luis; Soria-Guerra, Ruth Elena

    2014-08-20

    The high demand for less polluting, newer, and cheaper fuel resources has increased the search of the most innovative options for the production of the so-called biofuels. Chlamydomonas reinhardtii is a photosynthetic unicellular algae with multiple biotechnological advantages such as easy handling in the laboratory, a simple scale-up to industrial levels, as well as a feasible genetic modification at nuclear and chloroplast levels. Besides, its fatty acids can be used to produce biofuels. Previous studies in plants have found that the over expression of DOF-type transcription factor genes increases the synthesis and the accumulation of total lipids in seeds. In this context, the over-expression of a DOF-type transcription factor in C. reinhardtii was applied as approach to increase the amount of lipids. The results indicate higher amounts (around 2-fold) of total lipids, which are mainly fatty acids, in the genetically C. reinhardtii modified strains when compared with the non-genetically modified strain. In order to elucidate the possible function of the introduced Dof-type transcription factor, we performed a transcription profile of 8 genes involved in fatty acid biosynthesis and 6 genes involved in glycerolipid biosynthesis, by quantitative real time (qRT-PCR). Differential expression profile was observed, which can explain the increase in lipid accumulation. However, these strains did not show notable changes in the fatty acid profile. This work represents an early effort in generating a strategy to increase fatty acids production in C. reinhardtii and their use in biofuel synthesis. PMID:24844864

  19. 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 was a high proportion of individuals with T2DM, who failed to adhere to the national dietary guidelines. The importance of taking a well-balanced diet in accordance with the guidelines should be emphasized, especially among those with lower educational level through a simple and easy-to-understand approach. PMID:25895200

  20. Attenuation of fibroblast growth factor signaling by poly-N-acatyllactosamine type glycans

    PubMed Central

    Sugihara, Kazuhiro; Shibata, Toshiaki K.; Takata, Kayoko; Kimura, Takako; Kanayama, Naohiro; Williams, Roy; Hatakeyama, Shingo; Akama, Tomoya O.; Kuo, Chu-Wei; Khoo, Kay-Hooi; Fukuda, Michiko N.

    2014-01-01

    Fibroblast growth factors (FGFs) and their receptors are expressed in a variety of mammalian tissues, playing a role in development and cell proliferation. While analyzing human sperm motility, we found that sperm treated with endo-?-galactosidase (EBG), which specifically hydrolyzes poly-N-acetyllactosamine type glycans (polyLacs), enhanced motility. Mass spectrometry analysis revealed that sperm-associated polyLacs are heavily fucosylated, consistent with Lewis Y antigen. Immunohistochemistry of epididymis using an anti-Lewis Y antibody before and after EBG treatment suggested that polyLacs carrying the Lewis Y epitope are synthesized in epididymal epithelia and secreted to seminal fluid. EBG-treated sperm elevated cAMP levels and calcium influx, indicating activation of fibroblast growth factor signaling. Seminal fluid polyLacs bound to FGFs in vitro, and impaired FGF-mediated signaling in HEK293T cells. PMID:23968720

  1. [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

  2. Early onset type 2 diabetes: risk factors, clinical impact and management

    PubMed Central

    Idris, Iskandar

    2014-01-01

    Early onset type 2 diabetes mellitus (T2DM) is increasingly prevalent with a significant impact on the individual, healthcare service delivery and planning. The individuals are likely to be obese, lead a sedentary lifestyle, have a strong family history of T2DM, be of black and minority ethnic (BME) origin and come from a less affluent socioeconomic group. They have a heightened risk of developing microvascular and macrovascular complications, often at an earlier stage and with greater frequency than seen in type 1 diabetes. As such, early and aggressive risk factor management is warranted. Early onset T2DM is complex and impacts on service delivery with a need for multidisciplinary care of complications and comorbidities’, in addition to adequate educational and psychological support. This review on the impact of early onset T2DM provides the latest insights into this emerging epidemic. PMID:25364491

  3. Expression and secretion of type beta transforming growth factor by activated human macrophages.

    PubMed Central

    Assoian, R K; Fleurdelys, B E; Stevenson, H C; Miller, P J; Madtes, D K; Raines, E W; Ross, R; Sporn, M B

    1987-01-01

    Alveolar macrophages activated with concanavalin A and peripheral blood monocytes activated with lipopolysaccharide secrete type beta transforming growth factor (TGF-beta). There is minimal TGF-beta secretion in unactivated monocytes, even though TGF-beta mRNA is expressed in these cells at a level similar to that in activated, lipopolysaccharide-treated cultures. U937 lymphoma cells, which have monocytic characteristics, also express mRNA for TGF-beta. Freshly isolated monocytes, both control and lipopolysaccharide-treated, secrete an acid-labile binding protein that inhibits TGF-beta action. We conclude the following: (i) that expression of TGF-beta mRNA is unrelated to monocyte activation, (ii) that secretion of TGF-beta is induced by monocyte activation, and (iii) that cosecretion of TGF-beta and its monocyte/macrophage-derived binding protein may modulate growth factor action. In contrast, monocytic expression of other growth factor genes, such as the B chain of platelet-derived growth factor, is not constitutive and requires activation. Images PMID:2888109

  4. Expression and secretion of type. beta. transforming growth factor by activated human macrophages

    SciTech Connect

    Assoian, R.K.; Fleurdelys, B.E.; Stevenson, H.C.; Miller, P.J.; Madtes, D.K.; Raines, E.W.; Ross, R.; Sporn, M.B.

    1987-09-01

    Alveolar macrophages activated with concanavalin A and peripheral blood monocytes activated with lipopolysaccharide secrete type ..beta.. transforming growth factor (TGF-..beta..). There is minimal TGF-..beta.. secretion in unactivated monocytes, even though TGF-..beta.. mRNA is expressed in these cells at a level similar to that in activated, lipopolysaccharide-treated cultures. U937 lymphoma cells, which have momocytic characteristics, also express mRNA for TGF-..beta... Freshly isolated monocytes, both control and lipopolysaccharide-treated, secrete an acid-labile binding protein that inhibits TGF-..beta.. action. They conclude the following: (i) that expression of TGF-..beta.. mRNA is unrelated to monocyte activation, (ii) that secretion of TGF-..beta.. is induced by monocyte activation, and (iii) that cosecretion of TGF-..beta.. and its monocyte/macrophage-derived binding protein may modulate growth factor action. In contrast, monocytic expression of other growth factor genes, such as the B chain of platelet-derived growth factor, is not constitutive and requires activation.

  5. Noninvasive screening for risk factors of type 2 diabetes in young, rural, caucasian children.

    PubMed

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

    2010-08-01

    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, racial/ethnic background, hypertension, and acanthosis nigricans. Two thirds of those screened (n = 299) had at least one of the five risk factors for T2DM. Seventeen students (5.6% of those screened) had three or more of the five risk factors and were considered at risk for T2DM. Fifteen percent (n = 43) had hypertension or prehypertension, and 18% (n = 53) were morbidly obese. Hypertension and acanthosis nigricans were significantly associated with being at risk in morbidly obese students. School nurses play an important role as frontline health professionals who are aware that risk factors for T2DM exist in all schools, regardless of students' age, size of community, or ethnic background. PMID:20335231

  6. Characterization of coagulation factor synthesis in nine human primary cell types

    PubMed Central

    Dashty, Monireh; Akbarkhanzadeh, Vishtaseb; Zeebregts, Clark J.; Spek, C. Arnold; Sijbrands, Eric J.; Peppelenbosch, Maikel P.; Rezaee, Farhad

    2012-01-01

    The coagulation/fibrinolysis system is essential for wound healing after vascular injury. According to the standard paradigm, the synthesis of most coagulation factors is restricted to liver, platelets and endothelium. We challenged this interpretation by measuring coagulation factors in nine human primary cell types. FX mRNA was expressed by fibroblasts, visceral preadipocytes/adipocytes and hepatocytes, but not in macrophages or other cells. All cells expressed FVIII except endothelial cells. Fibroblasts, endothelial cells and macrophages produced thrombomodulin but not FV. Interestingly, vascular-related cells (platelets/monocytes) that expressed FV did not express FX and vice versa. Monocytes expressed FV, FVIII and FXIIIA, which are positive regulators of clot formation, but these cells also contained thrombomodulin, a negative regulator of coagulation. Our data show that the expression of coagulation factors is much more complex than previously thought, and we speculate that this intricate regulation of coagulation factor expression is necessary for correct fine-tuning of fibrinogenesis versus fibrinolysis. PMID:23145311

  7. Calibration factor for LR-115 type II track detectors for environmental radon measurements

    NASA Astrophysics Data System (ADS)

    Srivastava, D. S.; Singh, P.; Rana, N. P. S.; Naqvi, A. H.; Azam, A.; Ramachandran, T. V.; Subba Ramu, M. C.

    1995-10-01

    This paper presents the experimental calibration of LR-115 type II plastic track detectors for monitoring environmental radon. The detectors were calibrated using a standard radon chamber and simulating the environmental conditions as normally found in dwellings. The value of the calibration factor was found to be 625 tracks cm-2 d-1 per WL in the BARE mode and 0.116 tracks cm-2 d-1 per Bq m-3 for cup with membrane mode. Results of measurements of radon and its daughters in Bijnor (India) are also presented.

  8. Maternal Enterovirus Infection as a Risk Factor for Type 1 Diabetes in the Exposed Offspring

    PubMed Central

    Viskari, Hanna; Knip, Mikael; Tauriainen, Sisko; Huhtala, Heini; Veijola, Riitta; Ilonen, Jorma; Simell, Olli; Surcel, Helj-Marja; Hyty, Heikki

    2012-01-01

    OBJECTIVE Maternal enterovirus infections during pregnancy have been linked to an increased risk of type 1 diabetes in the offspring. The aim of this study was to evaluate this association in a unique series of pregnant mothers whose child progressed to clinical type 1 diabetes. RESEARCH DESIGN AND METHODS Maternal and in utero enterovirus infections were studied in 171 offspring who presented with type 1 diabetes before the age of 11 years and in 316 control subjects matched for date and place of birth, sex, and HLA-DQ risk alleles for diabetes. Acute enterovirus infections were diagnosed by increases in enterovirus IgG and IgM in samples taken from the mother at the end of the first trimester of pregnancy and cord blood samples taken at delivery. RESULTS Signs of maternal enterovirus infection were observed in altogether 19.3% of the mothers of affected children and in 12.0% of the mothers of control children (P = 0.038). This difference was seen in different HLA risk groups and in both sexes of the offspring, and it was unrelated to the age of the child at the diagnosis of diabetes or the age of the mother at delivery. CONCLUSIONS These results suggest that an enterovirus infection during pregnancy is not a major risk factor for type 1 diabetes in childhood but may play a role in some susceptible subjects. PMID:22432113

  9. Nordihydroguaiaretic acid inhibits transforming growth factor beta type 1 receptor activity and downstream signaling.

    PubMed

    Li, Fusheng; Pham, Johnny D; Anderson, Marc O; Youngren, Jack F

    2009-08-15

    It has been well documented that nordihydroguaiaretic acid (NDGA), a phenolic lignan isolated from the creosote bush, Larrea tridentate, has anti-cancer activity in vitro and in vivo. Several mechanisms have been identified that could contribute to these actions, as NDGA directly inhibits metabolic enzymes and receptor tyrosine kinases that are established anti-cancer targets. In the present study, we show that NDGA inhibits the transforming growth factor beta (TGF-beta) type I receptor, a serine threonine kinase receptor. In cultured cells, NDGA treatment repressed Smad2 phosphorylation induced by TGF-beta treatment and by a constitutively active mutant of TGF-beta type I receptor (T202D). NDGA also inhibited downstream transcriptional activation mediated by both TGF-beta treatment and the constitutively active mutant receptor. In vitro, NDGA inhibited TGF-beta type I receptor mediated Smad2 phosphorylation in crude cell lysates and in a purified preparation. Importantly, screening select analogs demonstrated that modification of NDGA's structure resulted in altered potency against the receptor. These results indicated that the structure of NDGA can be modified to achieve increased potency. Together our data provide a novel mechanism for NDGA activity which could help explain its anti-cancer activity, and suggest that NDGA could serve as a structural motif for developing serine/threonine kinase inhibitors with selectivity for TGF-beta type I receptor. PMID:19540220

  10. Nordihydroguaiaretic acid inhibits transforming growth factor β type 1 receptor activity and downstream signaling

    PubMed Central

    Li, Fusheng; Anderson, Marc O.; Youngren, Jack F.

    2009-01-01

    It has been well documented that nordihydroguaiaretic acid (NDGA), a phenolic lignan isolated from the creosote bush, Larrea tridentate, has anti-cancer activity in vitro and in vivo. Several mechanisms have been identified that could contribute to these actions, as NDGA directly inhibits metabolic enzymes and receptor tyrosine kinases that are established anti-cancer targets. In the present study, we show that NDGA inhibits the transforming growth factor β (TGF-β) type I receptor, a serine threonine kinase receptor. In cultured cells, NDGA treatment repressed Smad2 phosphorylation induced by TGF-β treatment and by a constitutively active mutant of TGF-β type I receptor (T202D). NDGA also inhibited downstream transcriptional activation mediated by both TGF-β treatment and the constitutively active mutant receptor. In vitro, NDGA inhibited TGF-β type I receptor mediated Smad2 phosphorylation in crude cell lysates and in a purified preparation. Importantly, screening select analogs demonstrated that modification of NDGA’s structure resulted in altered potency against the receptor. These results indicated that the structure of NDGA can be modified to achieve increased potency. Together our data provide a novel mechanism for NDGA activity which could help explain its anti-cancer activity, and suggest that NDGA could serve as a structural motif for developing serine/threonine kinase inhibitors with selectivity for TGF-β type I receptor. PMID:19540220

  11. Factors affecting pharyngeal Haemophilus influenzae type b colonization rates in children.

    PubMed Central

    Michaels, R H; Poziviak, C S; Stonebraker, F E; Norden, C W

    1976-01-01

    Over 1,300 children were studied in an analysis of factors that might affect pharyngeal colonization with Haemophilus influenzae type b. Our semiquantitative methods for the culture of H. influenzae type b, consisting of inoculation of 0.001 ml of throat swab fluid on antiserum agar plates and division of the results into three grades of intensity, showed agreement as to intensity of colonization in over 80% of repeat throat cultures. Our data also suggest that throat swabs are more efficient than nasopharyngeal swabs for detecting colonization, particularly for older children. All 17 H. influenzae type b carriers found with either method were detected with throat swabs, but six had negative nasopharyngeal cultures; four of these six were lightly colonized older children. Furthermore, colony counts were apt to be higher on plates inoculated with throat swab fluids. The frequency of pharyngeal H. influenzae type b colonization in children visiting health department clinics and pediatricians' offices was low during the first 6 months of life (0.7%) but averaged 3 to 5% throughout the rest of childhood. Approximately two-thirds of the carriers were colonized at an intensity too low to be detected by standard laboratory techniques. No influence on colonization rates was found for sex, race, season, economic status, or common childhood infectious diseases such as coryza or otitis media. PMID:1086855

  12. Diffusible factors are responsible for differences in nuclease sensitivity among chromatins originating from different cell types.

    PubMed

    Chambers, S A; Cognetti, G; Shaw, B R

    1984-09-01

    We have examined the kinetics of nuclease digestion of chromatin from committed and uncommitted cells in experiments where the nuclei are mixed and co-digested. Cultures of the sea urchin, Arbacia punctulata, were grown to the 16-cell stage in either [3H]thymidine or [14C]thymidine and the macromere, mesomere, and micromere cell types separated. After isolation, sets of nuclei with two different blastomere types (each having different radionucleotide tagging) were mixed and co-digested with micrococcal nuclease or DNase. I. The extent of digestion was monitored by solubility in 5% perchloric acid (PCA). We find no significant differences in initial digestion rates or limit digests among the different cell types when co-digested with either nuclease. Differences in nuclease sensitivity observed when nuclei are digested separately are abolished when nuclei are probed in a mixing experiment. The results support the hypothesis that phenotypic differences in digestibility among different cell types in vitro reflect differences in chromatin-condensing factors which can diffuse between nuclei. PMID:6236093

  13. Socio-economic factors and diabetes consequences among patients with type 2 diabetes

    PubMed Central

    Tol, Azar; Sharifirad, Gholamreza; Shojaezadeh, Davoud; Tavasoli, Elahe; Azadbakht, Leila

    2013-01-01

    Background: Considering the effect of socio-economic factors on the emergence of chronic diseases and the importance of this aspect of diseases for policy makers and authorities of health care organizations, this study tried to investigate the role of these factors in type 2 diabetes and its consequences, which can be used in health policy making for preventing from this disease. Materials and Methods: This descriptive-analytical study was conducted on 384 diabetic patients who were admitted to a diabetes center in the city of Isfahan. The participants were selected using simple random sampling. A questionnaire with 42 questions was used for gathering the data which were analyzed using chi-square and Fisher's statistical tests. Results: The studied population consisted of 52.1% male and 47.9% female participants. There was a statistically significant relationship between diabetes complications, age group, educational level, job status, relationship with family members, number of family visits and the reassurance provided by the family, type of leisure time activities, health status, years with diabetes, smoking, type of treatment, fried food consumption and income (P < 0.001), sense of security and communication in living environment (P < 0.002) and daily intake of vegetables (P < 0.02). Conclusion: It seems that the application of supportive resources and secondary strategies is an essential issue in the patients with chronic diseases, particularly diabetes. Empowering strategies can induce basic changes in order to increase positive expectations, hope, self-esteem and self- confidence in patients; this is the exact strategy which must be used to efficiently control diabetes and its different types of complications among patients. PMID:24083262

  14. 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

  15. An Empirical Study of the Type I Error Rates of Five Multivariate Tests for the Single-Factor Repeated Measures Model.

    ERIC Educational Resources Information Center

    Harwell, Michael; Serlin, Ronald

    A Monte Carlo study was used to examine the Type I error rates of five multivariate tests for the single-factor repeated measures model. The performance of Hotelling's T-squared and four nonparametric tests, including a chi-square and an "F" test version of a rank-transform procedure, was investigated for different distributions, sample sizes, and

  16. Contribution of modifiable risk factors for hypertension and type-2 diabetes in Peruvian resource-limited settings

    PubMed Central

    Carrillo-Larco, Rodrigo M; Gilman, Robert H; Checkley, William; Smeeth, Liam

    2016-01-01

    Background It is important to understand the local burden of non-communicable diseases including within-country heterogeneity. The aim of this study was to characterise hypertension and type-2 diabetes profiles across different Peruvian geographical settings emphasising the assessment of modifiable risk factors. Methods Analysis of the CRONICAS Cohort Study baseline assessment was conducted. Cardiometabolic outcomes were blood pressure categories (hypertension, prehypertension, normal) and glucose metabolism disorder status (diabetes, prediabetes, normal). Exposures were study setting and six modifiable factors (smoking, alcohol drinking, leisure time and transport-related physical activity levels, TV watching, fruit/vegetables intake and obesity). Poisson regression models were used to report prevalence ratios (PR). Population attributable risks (PAR) were also estimated. Results Data from 3238 participants, 48.3% male, mean age 45.3?years, were analysed. Age-standardised (WHO population) prevalence of prehypertension and hypertension was 24% and 16%, whereas for prediabetes and type-2 diabetes it was 18% and 6%, respectively. Outcomes varied according to study setting (p<0.001). In multivariable model, hypertension was higher among daily smokers (PR 1.76), heavy alcohol drinkers (PR 1.61) and the obese (PR 2.06); whereas only obesity (PR 2.26) increased the prevalence of diabetes. PAR showed that obesity was an important determinant for hypertension (15.7%) and type-2 diabetes (23.9%). Conclusions There is an evident heterogeneity in the prevalence of and risk factors for hypertension and diabetes within Peru. Prehypertension and prediabetes are highly prevalent across settings. Our results emphasise the need of understanding the epidemiology of cardiometabolic conditions to appropriately implement interventions to tackle the burden of non-communicable diseases. PMID:26248550

  17. 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

  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. Constitutively Active MAVS Inhibits HIV-1 Replication via Type I Interferon Secretion and Induction of HIV-1 Restriction Factors.

    PubMed

    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 (?LMP1). Supernatant from ?LMP1-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 ?LMP1-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 ?LMP1-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, ?LMP1-MAVS markedly enhanced secretion of IFN-? and IL-12p70 by dendritic cells and the activation and maturation of dendritic cells. Based on this immunostimulatory activity, an adenoviral vector (Ad5) expressing ?LMP1-MAVS was tested as a molecular adjuvant in an HIV vaccine mouse model. Ad5-Gag antigen combined with Ad5-?LMP1-MAVS enhanced control of vaccinia-gag replication in a mouse challenge model, with 4/5 animals showing undetectable virus following challenge. Overall, ?LMP1-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

  20. 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

  1. Klebsiella spp. as Nosocomial Pathogens: Epidemiology, Taxonomy, Typing Methods, and Pathogenicity Factors

    PubMed Central

    Podschun, R.; Ullmann, U.

    1998-01-01

    Bacteria belonging to the genus Klebsiella frequently cause human nosocomial infections. In particular, the medically most important Klebsiella species, Klebsiella pneumoniae, accounts for a significant proportion of hospital-acquired urinary tract infections, pneumonia, septicemias, and soft tissue infections. The principal pathogenic reservoirs for transmission of Klebsiella are the gastrointestinal tract and the hands of hospital personnel. Because of their ability to spread rapidly in the hospital environment, these bacteria tend to cause nosocomial outbreaks. Hospital outbreaks of multidrug-resistant Klebsiella spp., especially those in neonatal wards, are often caused by new types of strains, the so-called extended-spectrum-β-lactamase (ESBL) producers. The incidence of ESBL-producing strains among clinical Klebsiella isolates has been steadily increasing over the past years. The resulting limitations on the therapeutic options demand new measures for the management of Klebsiella hospital infections. While the different typing methods are useful epidemiological tools for infection control, recent findings about Klebsiella virulence factors have provided new insights into the pathogenic strategies of these bacteria. Klebsiella pathogenicity factors such as capsules or lipopolysaccharides are presently considered to be promising candidates for vaccination efforts that may serve as immunological infection control measures. PMID:9767057

  2. 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

  3. Factors influencing psoriasis: an analysis based upon the extent of involvement and clinical type.

    PubMed

    Park, B S; Youn, J I

    1998-02-01

    A variety of external stimuli are accepted as important in modifying the severity of psoriasis. We sought to determine whether there is any difference in the influence of external factors on psoriasis in relation to extent of involvement or clinical type. A total of 870 psoriasis patients seen between 1982 and 1995 were categorized as mild, moderate, or severe on the basis of extent of the disease, and as guttate, nummular/plaque, or exfoliative/generalized pustular according to clinical type. We then performed a questionnaire survey concerning the influence of external factors such as seasonal changes, sunlight, stress, and pregnancy. These data sets were combined and analysed. The majority of patients stated favorable effects of summer, sunlight, and pregnancy and adverse effects of winter and stress. A statistically significant correlation was noted between the extent of psoriasis and the proportion of patients stating that their disease worsened at times of psychological stress (p < 0.01). We confirmed that psoriasis patients with more extensive involvement experience greater fluctuations in their condition, notice these changes, and therefore relate them to psychological stress. PMID:9563276

  4. 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.

  5. Nuclear factor I and epithelial cell-specific transcription of human papillomavirus type 16.

    PubMed Central

    Apt, D; Chong, T; Liu, Y; Bernard, H U

    1993-01-01

    The transcription of human papillomavirus type 16 (HPV-16) is mediated by the viral enhancer. Epithelial cell-specific activation is achieved by the cooperative interaction of apparently ubiquitous transcriptional factors. One of them, nuclear factor I (NFI), binds seven sites within the HPV-16 enhancer. Point mutations on enhancer fragments, which retain epithelial cell specificity, verify the functional contribution of NFI. In band shift experiments, the epithelial cell-derived NFI proteins CTF-1, CTF-2, and CTF-3 form a characteristic pattern of heterodimeric complexes which are observed in all epithelial cells tested. Divergence from this pattern in fibroblasts, liver cells, and lymphoid cells correlates with the lack of HPV-16 enhancer activation. The HPV-16 enhancer can be activated by CTF-1 in SL-2 cells, which lack NFI-like proteins. However, exogenous CTF-1 fails to overcome the inactivity of the viral enhancer in fibroblasts. Western immunoblot and supershift analysis shows that exogenously introduced CTF-1 proteins form different heterodimer complexes with the given subset of endogenous NFI proteins in epithelial or fibroblast cells. Polymerase chain reaction analysis and cDNA library screens identified the endogenous fibroblast type NFI as NFI-X, an NFI family member originally cloned from hamster liver cells. The strict correlation between the activation or lack of activation of the HPV-16 enhancer and cell-specific subsets of NFI proteins argues for the pivotal role of NFI binding sites in the epithelial cell-specific function of the viral enhancer. Images PMID:8392590

  6. Corticotropin releasing factor acting on corticotropin releasing factor receptor type 1 is critical for binge alcohol drinking in mice

    PubMed Central

    Kaur, Simranjit; Li, Ju; Stenzel-Poore, Mary P.; Ryabinin, Andrey E.

    2011-01-01

    Background The corticotropin releasing factor (CRF) system has been implicated in the regulation of alcohol consumption. However, previous mouse knockout (KO) studies using continuous ethanol access have failed to conclusively confirm this. Recent studies have shown that CRF receptor 1 (CRFR1) antagonists attenuate alcohol intake in the limited access “drinking in the dark” (DID) model of binge drinking. To avoid the potential non-specific effects of antagonists, in the present study we tested alcohol drinking in CRFR1, CRFR2, CRF and Ucn1 KO and corresponding wild-type (WT) littermates using the DID paradigm. Methods On days 1–3, the CRFR1, CRFR2, Ucn1 and CRF KO mice and their respective wildtype (WT) littermates were provided with 20% ethanol or 10% sucrose for 2 hours with water available at all other times. On day 4, access to ethanol or sucrose was increased to 4 hours. At the end of each drinking session, the volume of ethanol consumed was recorded and at the conclusion of the last session, blood was also collected for blood ethanol concentration (BEC) analysis. Results CRFR1 KO mice had lower alcohol intakes and BECs and higher intakes of sucrose compared to WTs. In contrast, CRFR2 KO mice, while having reduced intakes initially, had similar alcohol intakes on days 2–4 and similar BECs as the WTs. In order to determine the ligand responsible, Ucn1 and CRF KO and WT mice were tested next. While Ucn1 KOs had similar alcohol intakes and BECs to their WTs, CRF KO mice showed reduced alcohol consumption and lower BECs compared to WTs. Conclusions Our results confirm that CRFR1 plays a key role in binge drinking and identify CRF as the ligand critically involved in excessive alcohol consumption. PMID:21895713

  7. Association of insulin-related serum factors with colorectal polyp number and type in adult males

    PubMed Central

    Comstock, Sarah S.; Xu, Diana; Hortos, Kari; Kovan, Bruce; McCaskey, Sarah; Pathak, Dorothy R.; Fenton, Jenifer I.

    2014-01-01

    Background Dysregulated insulin signaling is thought to contribute to cancer risk. Methods To determine if insulin-related serum factors are associated with colon polyps, 126 asymptomatic men (4865yr) were recruited at colonoscopy. Blood was collected. Odds ratios were determined using polytomous logistic regression for polyp number and type. Results Males with serum C-peptide concentration >3.3 ng/ml were 3.8 times more likely to have an adenoma relative to no polyp than those with C-peptide ?1.8 ng/ml. As C-peptide tertile increased, an individual was 2 times more likely to have an adenoma (p=0.01) than no polyp. There were no associations between insulin-like growth factor or its binding proteins with polyp number or type. Males with soluble receptor for advanced glycation end products (sRAGE) concentration >120.4 pg/ml were 0.25 times less likely to have ?3 polyps relative to no polyps compared to males with sRAGE ?94.5 pg/ml. For each increase in sRAGE tertile, a man was 0.5 times less likely to have ?3 polyps than no polyps (p=0.03). Compared to males with a serum vascular endothelial growth factor (VEGF) concentration ?104.7 pg/ml, males with a serum VEGF concentration >184.2 pg/ml were 3.4 times more likely to have ?3 polyps relative to no polyps. As the VEGF tertile increased, a man was 1.9 times more likely to have ?3 polyps than no polyps (p=0.049). Conclusions Serum concentrations of C-peptide, sRAGE, and VEGF may indicate which men could benefit most from colonoscopy. Impact Identification of biomarkers could reduce medical costs through the elimination of colonoscopies on low-risk individuals. PMID:24962837

  8. Recurrent subthreshold depression in type 2 diabetes: an important risk factor for poor health outcomes.

    PubMed

    Schmitz, Norbert; Garipy, Genevive; Smith, Kimberley J; Clyde, Matthew; Malla, Ashok; Boyer, Richard; Strychar, Irene; Lesage, Alain; Wang, Jianli

    2014-04-01

    OBJECTIVE To evaluate the association between recurrent subthreshold depressive episodes and functioning in a prospective community sample of people with type 2 diabetes. RESEARCH DESIGN AND METHODS A prospective community study in Quebec, Canada, was carried out between 2008 and 2013 (n = 1,064). Five yearly follow-up assessments (telephone interviews) were conducted. Baseline and the first three follow-up assessments were used to identify recurrent subthreshold depressive episodes (Patient Health Questionnaire [PHQ]-9). Functioning (World Health Organization Disability Assessment Schedule II [WHODAS-II]) and health-related quality of life (Centers for Disease Control and Prevention [CDC] unhealthy days) at 4- and 5-year follow-up assessments were the outcome measures. RESULTS Nearly half of the participants suffered from at least one episode of subthreshold depressive symptoms. After adjusting for potentially confounding factors, the risk of poor functioning/impaired health-related quality of life was nearly three times higher (relative risk = 2.86) for participants with four subthreshold depressive episodes compared with participants with no/minimal depression. Results suggest a dose-response relationship: the risk of poor functioning/impaired health-related quality of life increased with the number of recurrent subthreshold depressive episodes even after controlling for potentially confounding variables (significant linear trend, P < 0.001). CONCLUSIONS Recurrent subthreshold depressive symptoms might be an important risk factor for poor health outcomes in type 2 diabetes. Early identification, monitoring, and treatment of recurrent subthreshold depressive symptoms might improve functioning and quality of life in people with type 2 diabetes. PMID:24198303

  9. 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

  10. Chemokine Receptor-5?32 Mutation is No Risk Factor for Ischemic-Type Biliary Lesion in Liver Transplantation

    PubMed Central

    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-5?32 (CCR-5?32) was strongly associated with the incidence of ITBL in adult liver transplantation. This study re-evaluates the association of CCR-5?32 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-5?32 mutation. There were no major differences in donor or recipients demographics. No association was found between CCR-5?32 mutation and the development of ITBL. We conclude that CCR-5?32 is no risk factor for the development of ITBL in our patient cohort. PMID:20107582

  11. Impact of Walking on Glycemic Control and Other Cardiovascular Risk Factors in Type 2 Diabetes: A Meta-Analysis

    PubMed Central

    Qiu, Shanhu; Cai, Xue; Schumann, Uwe; Velders, Martina; Sun, Zilin; Steinacker, Jürgen Michael

    2014-01-01

    Background Walking is the most popular and most preferred exercise among type 2 diabetes patients, yet compelling evidence regarding its beneficial effects on cardiovascular risk factors is still lacking. The aim of this meta-analysis of randomized controlled trials (RCTs) was to evaluate the association between walking and glycemic control and other cardiovascular risk factors in type 2 diabetes patients. Methods Three databases were searched up to August 2014. English-language RCTs were eligible for inclusion if they had assessed the walking effects (duration ≥8 weeks) on glycemic control or other cardiovascular risk factors among type 2 diabetes patients. Data were pooled using a random-effects model. Subgroup analyses based on supervision status and meta-regression analyses of variables regarding characteristics of participants and walking were performed to investigate their association with glycemic control. Results Eighteen studies involving 20 RCTs (866 participants) were included. Walking significantly decreased glycosylated haemoglobin A1c (HbA1c) by 0.50% (95% confidence intervals [CI]: −0.78% to −0.21%). Supervised walking was associated with a pronounced decrease in HbA1c (WMD −0.58%, 95% CI: −0.93% to −0.23%), whereas non-supervised walking was not. Further subgroup analysis suggested non-supervised walking using motivational strategies is also effective in decreasing HbA1c (WMD −0.53%, 95% CI: −1.05% to −0.02%). Effects of covariates on HbA1c change were generally unclear. For other cardiovascular risk factors, walking significantly reduced body mass index (BMI) and lowered diastolic blood pressure (DBP), but non-significantly lowered systolic blood pressure (SBP), or changed high-density or low-density lipoprotein cholesterol levels. Conclusions This meta-analysis supports that walking decreases HbA1c among type 2 diabetes patients. Supervision or the use of motivational strategies should be suggested when prescribed walking to ensure optimal glycemic control. Walking also reduces BMI and lowers DBP, however, it remains insufficient regarding the association of walking with lowered SBP or improved lipoprotein profiles. Trial Registration PROSPERO CRD42014009515 PMID:25329391

  12. Suicide, schizophrenia, and schizoid-type psychosis: role of life events and childhood factors.

    PubMed

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

    2011-02-01

    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 psychosis. Thirty-three cases of suicide with a diagnosis of schizophrenia or schizoid-type psychosis were compared with 34 living patients with a similar diagnosis. The psychological autopsy method was used. The assessments were made with the Structured Clinical Interview for the Diagnostic and Statistical Manual for Axis I mental disorders, the Life Events and Difficulties Schedule, and the Child Experiences and Child Abuse Interview. The suicide group (SG) experienced more often a recent severe event, usually of a humiliation nature, than the control group (CG). It also experienced more severe events associated with aggressive behavior or with psychiatric impairment. Contrary to expectations, the CG had worse scores than the SG for quality of care during childhood. In conclusion, suicide in schizophrenia is related both to environmental stress and to psychiatric impairment. PMID:21309825

  13. Blood Viscosity and Hematocrit as Risk Factors for Type 2 Diabetes Mellitus

    PubMed Central

    Tamariz, Leonardo J.; Pankow, James S.; Yeh, Hsin-Chieh; Schmidt, Maria Ines; Astor, Brad; Brancati, Frederick L.

    2008-01-01

    Several lines of evidence support the notion that elevated blood viscosity may predispose to insulin resistance and type 2 diabetes mellitus by limiting delivery of glucose, insulin, and oxygen to metabolically active tissues. To test this hypothesis, the authors analyzed longitudinal data on 12,881 initially nondiabetic adults, aged 4564 years, who were participants in the Atherosclerosis Risk in Communities (ARIC) Study (19871998). Whole blood viscosity was estimated by using a validated formula based on hematocrit and total plasma proteins at baseline. At baseline, estimated blood viscosity was independently associated with several features of the metabolic syndrome. In models adjusted simultaneously for known predictors of diabetes, estimated whole blood viscosity and hematocrit predicted incident type 2 diabetes mellitus in a graded fashion (Ptrend (linear) < 0.001): Compared with their counterparts in the lowest quartiles, adults in the highest quartile of blood viscosity (hazard ratio = 1.68, 95% confidence interval: 1.53, 1.84) and hematocrit (hazard ratio = 1.63, 95% confidence interval: 1.49, 1.79) were over 60% more likely to develop diabetes. Therefore, elevated blood viscosity and hematocrit deserve attention as emerging risk factors for insulin resistance and type 2 diabetes mellitus. PMID:18931370

  14. Hypoxia-Inducible Factor-1 Facilitates Cervical Cancer Progression in Human Papillomavirus Type 16 Transgenic Mice

    PubMed Central

    Lu, Zhi Hong; Wright, Jason D.; Belt, Brian; Cardiff, Robert D.; Arbeit, Jeffrey M.

    2007-01-01

    Advanced cervical cancer remains a vexing clinical challenge despite screening programs. Many of these cancers are hypoxic, and expression of the ? subunit of the major regulator of the hypoxic cellular response, the transcription factor hypoxia-inducible factor-1 (HIF-1), is correlated with poor prognosis. Here, we tested a functional role for HIF-1? in pathogenesis of cervical cancer in estrogen-treated transgenic mice. Double-transgenic (DTG) mice developed locally invasive cervical cancers 70 times larger than K14-HPV16 mice. In vivo bromodeoxyuridine incorporation was elevated in DTG cancers without a significant increase in apoptosis. HIF-1? gain of function did not up-regulate canonical HIF-1 targets in premalignant DTG cervices, in contrast to elevation of these targets in K14-HIF-1? transgenic cervices. The DTG transcriptional signature included up-regulation of mRNAs encoding cytokines and chemokines, immune signaling molecules, extracellular proteases, and cell motility factors, as well as reduced expression of cell adhesion and epithelial differentiation genes. Importantly, a set of gene markers derived from the DTG transcriptome predicted cervical cancer progression in patients. This study suggests a novel paradigm for HIF-1 function evident in multistage carcinogenesis as opposed to established malignancies, including interaction with viral oncogenes to induce multiple genomic networks in premalignancy that fosters the development of advanced cervical cancer. PMID:17600126

  15. Is affluence a risk factor for bronchial asthma and type 1 diabetes?

    PubMed

    Tedeschi, Alberto; Airaghi, Lorena

    2006-11-01

    In the last decades, an increase in bronchial asthma and type 1 diabetes occurrence has been observed in affluent countries, and a positive association between the two disorders has been demonstrated at the population level. This association could be explained by common risk factors predisposing to both disorders. Altered environmental and lifestyle conditions, possibly related to socio-economic status, might account for the rising trend of the two disorders. To test this hypothesis, we calculated the correlation between the occurrence of type 1 diabetes and asthma, the gross national product (GNP) and the infant mortality rate, in several European and extra-European countries. GNP was positively correlated with the incidence of type 1 diabetes and with symptoms of asthma in European (r(sp): 0.53 and 0.69; p = 0.001 and p < 0.0001, respectively) and extra-European countries (r(sp): 0.44 and 0.46; p = 0.04 for both diseases). Infant mortality rate was inversely correlated with GNP and with the occurrences of the two diseases in Europe (r(sp): -0.66, p < 0.0001 for type 1 diabetes; r(sp):- 0.51, p = 0.01 for asthma). In extra-European countries, a significant relationship was found between infant mortality and asthma (r(sp): -0.46; p = 0.03); a trend towards a negative correlation between infant mortality and type 1 diabetes was also found, although no statistical significance was reached (r(sp): -0.21; p = 0.31). This analysis indicates that type 1 diabetes and asthma are positively associated with the GNP at the population level. Similarly, countries with low infant mortality rates tend to have a higher incidence of these immune-mediated diseases. Although GNP reflects many societal and lifestyle differences, it is notable that a high socio-economic status implies a reduced or delayed exposure to infectious agents. The reduced pressure of infectious agents on the immune system throughout life might contribute to increase the susceptibility to bronchial asthma and type 1 diabetes. PMID:17014630

  16. 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.

  17. MTHFR C677T genotype as a risk factor for epilepsy including post-traumatic epilepsy in a representative military cohort.

    PubMed

    Scher, Ann I; Wu, Holly; Tsao, Jack W; Blom, Henk J; Feit, Preethy; Nevin, Remington L; Schwab, Karen A

    2011-09-01

    The well-studied C677T variant in the methylenetetrahydrofolate reductase (MTHFR) enzyme is a biologically plausible genetic risk factor for seizures or epilepsy. First, plasma/serum levels of homocysteine, a pro-convulsant, are moderately elevated in individuals with the homozygote TT genotype. Furthermore, the TT genotype has been previously linked with migraine with aura-a comorbid condition-and with alcohol withdrawal seizures. Finally, several small studies have suggested that the TT genotype may be overrepresented in epilepsy patients. In this study, we consider whether the MTHFR C677T or A1298C variants are associated with risk of epilepsy including post-traumatic epilepsy (PTE) in a representative military cohort. Study subjects were selected from the cohort of military personnel on active duty during the years 2003 through 2007 who had archived serum samples at the DoD Serum Repository, essentially all active duty personnel during this time frame. We randomly selected 800 epilepsy patients and 800 matched controls based on ICD-9-CM diagnostic codes. We were able to isolate sufficient genetic material from the archived sera to genotype approximately 85% of our study subjects. The odds of epilepsy were increased in subjects with the TT versus CC genotype (crude OR=1.52 [1.04-2.22], p=0.031; adjusted OR=1.57 [1.07-2.32], p=0.023). In our sensitivity analysis, risk was most evident for patients with repeated rather than single medical encounters for epilepsy (crude OR=1.85 [1.14-2.97], p=0.011, adjusted OR=1.95 [1.19-3.19], p=0.008), and particularly for PTE (crude OR=3.14 [1.41-6.99], p=0.005; adjusted OR=2.55 [1.12-5.80], p=0.026). Our early results suggest a role for the common MTHFR C677T variant as a predisposing factors for epilepsy including PTE. Further exploration of baseline homocysteine and folate levels as predictors of seizure risk following traumatic brain injury is warranted. PMID:21787169

  18. Genome-wide identification of target genes of a mating-type ?-domain transcription factor reveals functions beyond sexual development.

    PubMed

    Becker, Kordula; Beer, Christina; Freitag, Michael; Kck, Ulrich

    2015-06-01

    Penicillium chrysogenum is the main industrial producer of the ?-lactam antibiotic penicillin, the most commonly used drug in the treatment of bacterial infections. Recently, a functional MAT1-1 locus encoding the ?-box transcription factor MAT1-1-1 was discovered to control sexual development in P. chrysogenum. As only little was known from any organism about the regulatory functions mediated by MAT1-1-1, we applied chromatin immunoprecipitation combined with next-generation sequencing (ChIP-seq) to gain new insights into the factors that influence MAT1-1-1 functions on a molecular level and its role in genome-wide transcriptional regulatory networks. Most importantly, our data provide evidence for mating-type transcription factor functions that reach far beyond their previously understood role in sexual development. These new roles include regulation of hyphal morphology, asexual development, as well as amino acid, iron, and secondary metabolism. Furthermore, in vitro DNA-protein binding studies and downstream analysis in yeast and P. chrysogenum enabled the identification of a MAT1-1-1 DNA-binding motif, which is highly conserved among euascomycetes. Our studies pave the way to a more general understanding of these master switches for development and metabolism in all fungi, and open up new options for optimization of fungal high production strains. PMID:25728030

  19. 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

  20. Modifiable lifestyle and social factors affect chronic kidney disease in high-risk individuals with type 2 diabetes mellitus.

    PubMed

    Dunkler, Daniela; Kohl, Maria; Heinze, Georg; Teo, Koon K; Rosengren, Annika; Pogue, Janice; Gao, Peggy; Gerstein, Hertzel; Yusuf, Salim; Oberbauer, Rainer; Mann, Johannes F E

    2015-04-01

    This observational study examined the association between modifiable lifestyle and social factors on the incidence and progression of early chronic kidney disease (CKD) among those with type 2 diabetes. All 6972 people from the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) with diabetes but without macroalbuminuria were studied. CKD progression was defined as decline in GFR of more than 5% per year, progression to end-stage renal disease, microalbuminuria, or macroalbuminuria at 5.5 years. Lifestyle/social factors included tobacco and alcohol use, physical activity, stress, financial worries, the size of the social network and education. Adjustments were made for known risks such as age, diabetes duration, GFR, albuminuria, gender, body mass index, blood pressure, fasting plasma glucose, and angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers use. Competing risk of death was considered. At study end, 31% developed CKD and 15% had died. The social network score (SNS) was a significant independent risk factor of CKD and death, reducing the risk by 11 and 22% when comparing the third to the first tertile of the SNS (odds ratios of CKD 0.89 and death 0.78). Education showed a significant association with CKD but stress and financial worries did not. Those with moderate alcohol consumption had a significantly decreased CKD risk compared with nonusers. Regular physical activity significantly decreased the risk of CKD. Thus, lifestyle is a determinant of kidney health in people at high cardiovascular risk with diabetes. PMID:25493953

  1. Risk factors for acute kidney injury in overweight patients with acute type A aortic dissection: a retrospective study

    PubMed Central

    Zhao, Honglei; Pan, Xudong; Gong, Zhizhong; Zheng, Jun; Liu, Yongmin; Zhu, Junming

    2015-01-01

    Background To identify risk factors for acute kidney injury (AKI) in overweight patients who underwent surgery for acute type A aortic dissection (TAAD). Methods A retrospective study including 108 consecutive overweight patients [body mass index (BMI) ?24] between December 2009 and April 2013 in Beijing Anzhen Hospital has been performed. AKI was defined by Acute Kidney Injury Network (AKIN) criteria, which is based on serum creatinine (sCr) or urine output. Results The mean age of the patients was 43.699.66 years. Seventy-two patients (66.7%) developed AKI during the postoperative period. A logistic regression analysis was performed to identify two independent risk factors for AKI: elevated preoperative sCr level and 72-h drainage volume. Renal replacement therapy (RRT) was required in 15 patients (13.9%). The overall postoperative mortality rate was 7.4%, 8.3% in AKI group and 5.6% in non-AKI group. There is no statistically significant difference between the two groups (P=0.32). Conclusions A higher incidence of AKI (66.7%) in overweight patients with acute TAAD was confirmed. The logistic regression model identified elevated preoperative sCr level and 72-h drainage volume as independent risk factors for AKI in overweight patients. We should pay more attention to prevent AKI in overweight patients with TAAD. PMID:26380764

  2. Incidence, risk factors, and implemented prophylaxis of varicella zoster virus infection, including complicated varicella zoster virus and herpes simplex virus infections, in lenalidomide-treated multiple myeloma patients.

    PubMed

    Knig, C; Kleber, M; Reinhardt, H; Knop, S; Wsch, R; Engelhardt, M

    2014-03-01

    In the era of high-dose chemotherapy and novel antimyeloma agents, the survival of multiple myeloma (MM) patients has substantially improved. Adverse effects, including infections, may however arise in the era of combination antimyeloma therapies. In general, MM patients have shown a risk of varicella zoster virus (VZV) infection of 1-4 %, increasing with bortezomib treatment or transplants, but whether immunomodulatory drugs also bear a risk of VZV/complicated herpes simplex virus (HSV) (e.g., VZV-encephalitis [VZV-E], disseminated VZV-infection [d-VZV-i], or conus-cauda syndrome [CCS]) has not been elucidated. We here assessed VZV, VZV-E, d-VZV-i, and CCS in 93 lenalidomide-treated MM patients, consecutively seen and treated in our department. Patients' data were analyzed via electronic medical record retrieval within our research data warehouse as described previously. Of the 93 MM patients receiving lenalidomide, 10 showed VZV or other complicated VZV/HSV infections. These VZV patients showed defined risk factors as meticulously assessed, including suppressed lymphocyte subsets, substantial cell-mediated immune defects, and compromised humoral immune response. Due to our findings-and in line with an aciclovir prophylaxis in bortezomib and stem cell transplant protocols-we introduced a routine aciclovir prophylaxis in our lenalidomide protocols in May 2012 to minimize adverse events and to avoid discontinuation of lenalidomide treatment. Since then, we have observed no case of VZV/complicated HSV infection. Based on our data, we encourage other centers to also focus on these observations, assess viral infections, and-in those centers facilitating a research data warehouse-advocate an analogue data review as an appropriate multicenter approach. PMID:24318541

  3. 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

  4. Microvascular Complications and Their Associated Risk Factors in Newly Diagnosed Type 2 Diabetes Mellitus Patients

    PubMed Central

    Bansal, Dipika; Gudala, Kapil; Esam, Hari Prasad; Nayakallu, Ramya; Vyamusani, Raja Vikram; Bhansali, Anil

    2014-01-01

    The study was aimed at assessing the prevalence of microvascular complications and associated risk factors in newly diagnosed type 2 diabetes mellitus patients. A cross-sectional study was conducted in a public tertiary care hospital. All the recruited patients underwent extensive examination for the presence of microvascular complications like neuropathy, retinopathy, and nephropathy. Prevalence of any complication was 18.04%. Prevalence of neuropathy, retinopathy, and nephropathy was found to be 8.2%, 9.5%, and 2.8%, respectively. Triglycerides (OR, 1.01; P = 0.011) and old age (OR, 1.06; P ≤ 0.01) were significantly associated with any complication. Triglycerides were significantly associated with neuropathy (OR, 1.01; P = 0.05) and retinopathy (OR, 1.01; P = 0.02). Being male posed high risk for nephropathy (OR, 0.06; P = 0.01). These results are suggesting need of regular screening for microvascular complications. PMID:26464850

  5. 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

  6. Type B Aortic Dissection: A Review of Prognostic Factors and Meta-analysis of Treatment Options

    PubMed Central

    Luebke, Thomas; Brunkwall, Jan

    2014-01-01

    According to international guidelines, stable patients with uncomplicated Type B aortic dissection (TBAD) should receive optimal medical treatment. Despite adequate antihypertensive therapy, the long-term prognosis of these patients is characterized by a significant aortic aneurysm formation in 25-30% within four years, and survival rates from 50 to 80% at five years and 30 to 60% at 10 years. In a prospective randomized trial, preemptive thoracic endovascular aortic repair (TEVAR) in patients with chronic uncomplicated TBAD was associated with an excess early mortality (due to periprocedural hazards), but the procedure showed its benefit in prevention of aortic-specific mortality at five years of follow-up. However, preemptive TEVAR may not be the treatment of choice in all patients with uncomplicated TBAD because of the inherent periprocedural complications like stroke, paraparesis, and death, as well as stent graft-induced complications (i.e., retrograde dissection or endoleaks). Thus, the TEVAR-related deaths and complications (especially paraplegia and stroke) raise concerns that moderate the better survival with TEVAR at five years. By timely identification of those patients prone for developing complications, early intervention, preferably in the subacute or early chronic phase, may improve the overall long-term outcome for these patients. Therefore, early detectable and reliable prognostic factors for adverse events are essential to stratify patients who can be treated medically and those who will benefit from rigorous follow-up and, in the long-term, from timely, or even prophylactic, TEVAR. Several studies have identified prognostic factors in TBAD such as aortic diameter, partial false lumen thrombosis, false lumen thickness, and location of the primary entry tear. Combining these clinical and radiological predictors may be essential to implement a patient-specific approach designed to intervene only in those patients who are at high risk of developing complications to improve the long-term outcomes of patients with uncomplicated Type B aortic dissection. PMID:26798745

  7. Predictive Factors for Efficacy of Dipeptidyl Peptidase-4 Inhibitors in Patients with Type 2 Diabetes Mellitus

    PubMed Central

    Aihara, Ken-ichi; Akaike, Masashi; Fukuda, Daiju; Salim, Hotimah Masdan; Ishida, Masayoshi; Matsuura, Tomomi; Ise, Takayuki; Yamaguchi, Koji; Iwase, Takashi; Yamada, Hirotsugu; Soeki, Takeshi; Wakatsuki, Tetsuzo; Shimabukuro, Michio; Matsumoto, Toshio; Sata, Masataka

    2015-01-01

    Background Predictive factors for the efficacy of dipeptidyl peptidase-4 (DPP-4) inhibitors for lowering glycosylated hemoglobin (HbA1c) remain unclear in patients with type 2 diabetes mellitus. The aim of this study is therefore to clarify predictive factors of the efficacy of DPP-4 inhibitors for lowering HbA1c after 12 months of treatment. Methods A total of 191 consecutive type 2 diabetic patients (male sex 55%, mean age, 68.335.8 years), who had been treated with DPP-4 inhibitors for 12 months, were enrolled in this study and evaluated retrospectively. Results After 12 months of DPP-4 inhibitor treatment, random blood glucose level, and HbA1c level, decreased from 16763 to 15149 mg/dL (P<0.01), and from 7.5%1.3% to 6.9%0.9% (P<0.01) respectively, without severe side effects. Multiple regression analysis showed that predictors of DPP-4 inhibitor treatment efficacy in lowering HbA1c level after 12 months were a decrease in HbA1c level after 3 months of treatment, a high baseline HbA1c level, a low baseline body mass index, and the absence of coronary artery disease. Conclusion Most suitable candidates for treatment with DPP-4 inhibitors are diabetics who are not obese and do not have coronary artery disease. In addition, long-term efficacy of DPP-4 inhibitors can be predicted by decrement of HbA1c after 3 months of treatment. PMID:26301197

  8. Racial/ethnic Differences in Clinical and Biochemical Type 2 Diabetes Mellitus Risk Factors in Children

    PubMed Central

    Rosenbaum, Michael; Fennoy, Ilene; Accacha, Siham; Altshuler, Lisa; Carey, Dennis E.; Holleran, Steven; Rapaport, Robert; Shelov, Steven P.; Speiser, Phyllis W.; Ten, S.; Bhangoo, Amrit; Boucher-Berry, Claudia; Espinal, Yomery; Gupta, Rishi; Hassoun, Abeer A.; Iazetti, Loretta.; Jacques, Fabien J.; Jean, Amy M.; Klein, Michelle. L.; Levine, Robert; Lowell, Barbara; Michel, Lesley; Rosenfeld, Warren

    2013-01-01

    Objective To examine whether peri-adolescent children demonstrate the significant racial/ethnic differences in body fatness relative to BMI and in the prevalence and relationship of body composition to risk factors for type 2 diabetes (T2DM) as in adults. Design and Methods We examined family history of obesity and T2DM, anthropometry, insulin sensitivity and secretory capacity, lipids, and cytokines (IL-6, CRP, TNF-α, and adiponectin) in a cohort of 994 middle school students (47% male, 53%, female; 12% African American, 14% East Asian, 13% South Asian, 9% Caucasian, 44% Hispanic, and 8% other). Results Fractional body fat content was significantly greater at any BMI among South Asians. There were racial/ethnic specific differences in lipid profiles, insulin secretory capacity, insulin sensitivity, and inflammatory markers corrected for body fatness that are similar to those seen in adults. Family history of T2DM was associated with lower insulin secretory capacity while family history of obesity was more associated with insulin resistance. Conclusion Children show some of the same racial/ethnic differences in risk factors for adiposity-related co-morbidities as adults. BMI and waist circumference cutoffs to identify children at-risk for adiposity-related co-morbidities should be adjusted by racial/ethnic group as well as other variables such as birthweight and family history. PMID:23596082

  9. The Complex Interplay of Genetic and Lifestyle Risk Factors in Type 2 Diabetes: An Overview

    PubMed Central

    Franks, Paul W.

    2012-01-01

    Type 2 diabetes (T2D) is one of the scourges of modern times, with many millions of people affected by the disease. Diabetes occurs most frequently in those who are overweight or obese. However, not all overweight and obese persons develop diabetes, and there are those who develop the disease who are lean and physically active. Certain ethnicities, especially indigenous populations, are at considerably higher risk of obesity and diabetes than those of white European ancestry. The patterns and distributions of diabetes have led some to speculate that the disease is caused by interactions between genetic and obesogenic lifestyle factors. Whilst to many this is a plausible explanation, remarkably little reliable evidence exists to support it. In this review, an overview of published literature relating to genetic and lifestyle risk factors for T2D is provided. The review also describes the concepts and rationale that have motivated the view that gene-lifestyle interactions cause diabetes and overviews the empirical evidence published to date to support this hypothesis. PMID:24278702

  10. Influence of Cardiovascular Risk Factors on Aortic Wall Motion After Repair of Type A Aortic Dissection

    PubMed Central

    Croccia, Mariagrazia; Levantino, Maurizio; Marraccini, Paolo; Franchi, Federico; Bortolotti, Uberto

    2013-01-01

    Background: We aimed to evaluate size changes of the thoracic aorta during the cardiac cycle with dynamic computed tomographic angiography (CTA) at specific anatomic landmarks in patients who previously underwent ascending aorta repair because of type A dissection, and to correlate aortic wall motion with several cardiovascular risk factors. Methods: From December 2008 to December 2010, 18 patients (14 men and 4 women, mean age 64 12 years) with previous aortic repair underwent electrocardiography-gated CTA follow-up. Aortic systolic and diastolic diameter and cross-sectional area were measured at 4 levels: 1 cm proximal (level A) and 1 (B), 3 (C), and 10 cm (D) distal to the origin of the left subclavian artery. Results were assessed according to age and presence of diabetes, hypertension, and smoking. Results: This morpho-functional evaluation of aortic wall motion demonstrated a significant influence (P < 0.05) of hypertension at level A and D and diabetes at level D. Smoking had a borderline significance at level C and D. No significant correlation with age was evident, with results not significantly different in patients ? 55 and > 55 years. Conclusions: Smoking, diabetes, and hypertension play a role in impairing aortic size variations. These variations might predict wall structural alterations due to cardiovascular risk factors before they become morphologically evident. This might influence timing of surveillance following repair of acute dissection, allowing it to be specifically tailored for any single subject.

  11. A new type of protein lysine methyltransferase trimethylates Lys-79 of elongation factor 1A

    PubMed Central

    Dzialo, Maria C.; Travaglini, Kyle J.; Shen, Sean; Loo, Joseph A.; Clarke, Steven G.

    2014-01-01

    The elongation factors of Saccharomyces cerevisiae are extensively methylated, containing a total of ten methyllysine residues. Elongation factor methyltransferases (Efm1, Efm2, Efm3, and Efm4) catalyze at least four of these modifications. Here we report the identification of a new type of protein lysine methyltransferase, Efm5 (Ygr001c), which was initially classified as N6-adenine DNA methyltransferase-like. Efm5 is required for trimethylation of Lys-79 on EF1A. We directly show the loss of this modification in efm5Δ strains by both mass spectrometry and amino acid analysis. Close homologs of Efm5 are found in vertebrates, invertebrates, and plants, although some fungal species apparently lack this enzyme. This suggests possible unique functions of this modification in S. cerevisiae and higher eukaryotes. The misannotation of Efm5 was due to the presence of a DPPF sequence in post-Motif II, typically associated with DNA methylation. Further analysis of this motif and others like it demonstrates a potential consensus sequence for N-methyltransferases. PMID:25446118

  12. 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

  13. Mutations in Niemann Pick type C gene are risk factor for Alzheimer's disease.

    PubMed

    Kresojevi?, Nikola; Dobri?i?, Valerija; Svetel, Marina; Kosti?, Vladimir

    2014-11-01

    Alzheimer's disease (AD) is the most common form of dementia characterized by deterioration of memory and other cognitive domains which leads to death in 3-9years after diagnosis. In addition to mutations in APP, PSEN1 and PSEN2 genes, that cause early onset autosomal dominant AD, several genetic risk factors for late onset AD are now known. There is another distinctive neurodegenerative lysosomal storage disorder - Niemann-Pick type C (NPC) that is sometimes referred to as "Childhood Alzheimer's". NPC is autosomal recessive disease caused by mutations in the NPC1 or NPC2 genes. NPC and AD share some biochemical and pathological similarities which are discussed in this paper. On the other hand, there is a well documented connection between other autosomal recessive lysosomal storage disorder - Gaucher's disease (GD) and neurodegenerative disorder - Parkinson's disease (PD). It has been shown that GD patients have 20-fold increased life-time risk of developing PD. Surprisingly, even heterozygous carriers of mutations in glucocerebrosidase gene (GBA) have increased risk for developing PD. Having in mind above mentioned correlations, we hypothesized that heterozygous mutations in the NPC gene may act as an independent risk factor for Alzheimer's disease. If true, this would expand link between lysosomal disorders and neurodegenerative diseases. Also, if heterozygous NPC1/2 mutation carriers develop AD we assume it would be worth trying with miglustat-specific therapy recommended for NPC disease. PMID:25220527

  14. 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

  15. 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

  16. Non-adherence to life-style modification and its factors among type 2 diabetic patients.

    PubMed

    Mumu, Shirin Jahan; Saleh, Farzana; Ara, Ferdous; Afnan, Fadia; Ali, Liaquat

    2014-01-01

    Non-adherence to preventive and therapeutic life-style recommendations among patients with diabetes is special challenge in the management of these patients. This study aimed to measure the proportion of non-adherence to life-style modification and factors associated with these among a group of Bangladeshi type 2 diabetic patients. Under an analytical cross-sectional design 374 type 2 diabetic patients (age >20 years), diagnosed for at least 1 year, were selected from different health care centers operated by the Diabetic Association of Bangladesh. Non-adherence rate were assessed for: Diet (88%), exercise (25%), routine blood glucose testing (32%), foot care (70%), smoking (6%) and betel quid chewing habit (25%). Binary logistic regression suggests that higher education group (P = 0.013), rural area (P = 0.013) and attendance to diabetes education classes (P = 0.043) showed good adherence to diet and non-attendance to diabetes education class (P = 0.014), older age (P = 0.037) are associated to non-adherence to exercise. Unemployed patients showed more non-adherence to blood glucose testing (P = 0.045) than others. Non-attendance to diabetes education class (P = 0.037) and business occupation group (P = 0.039) showed significant association to smoking and betel quid intake habit respectively. PMID:24748356

  17. Interest in different types of patients. What factors influence new-to-practice family physicians?

    PubMed Central

    Cohen, M.; Woodward, C. A.; Ferrier, B.; Williams, A. P.

    1996-01-01

    OBJECTIVE: To identify factors that influence new-to-practice family physicians to be particularly interested in certain types of patients. DESIGN: Qualitative study and cross-sectional survey. SETTING: Ontario family practices. PARTICIPANTS: Seven focus groups involved a volunteer sample of 34 physicians who completed family medicine residency training between 1984 and 1989. A convenience sample of 43 physicians who had completed their residencies between 1990 and 1992 were interviewed. All certificates of the College of Family Physicians of Canada currently practising in Ontario who received certification between 1989 and 1991 were surveyed. MAIN OUTCOME MEASURES: Physician interest as determined by scores on two scales: one labeled "Chronic/Older Patient," designed to assess special interest in geriatric patients, chronic pain patients, palliative care patients, and chronically ill patients, and one labeled "Young Patient," designed to assess special interest in young families and adolescents. RESULTS: In general, new-to-practice physicians had little interest in caring for older or chronic patients; older physicians and male physicians had greater interest in caring for chronic or older patients. Women physicians, physicians rating higher on the "empathy" and "interest in counseling" scale, and physicians receiving primarily fee-for-service remuneration showed greater interest in caring for young families and adolescents than other physicians. CONCLUSIONS: Physicians' age, sex, attitudes to patient care, method of remuneration, undergraduate and postgraduate schools of medical training, and the age and sex composition of their practices all influenced their interest in caring for different types of patients. PMID:8939318

  18. 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...

  19. 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...

  20. Prevalence and Risk Factors of Type 2 Diabetes in the Adults in Haikou City, Hainan Island, China

    PubMed Central

    XIA, Zhenfang; WANG, Zhuansuo; CAI, Qunfang; YANG, Jianjun; ZHANG, Xuan; YANG, Tubao

    2013-01-01

    Background: Type 2 diabetes mellitus (T2DM) occurs around the world with high prevalence and causes serious physical harm and economic burden to the afflicted. Haikou City is Chinas southernmost tropical island city, which has not been previously studied for its T2DM prevalence. The objective of the study in employing a cross-sectional survey is to discuss the epidemiologic status of T2DM in Haikou City and to analyze the possible determinants. Methods: A total of 12,000 community residents over 18 years old from four districts in Haikou City were stratified-randomly sampled. A questionnaire survey and physical examination were conducted. Data entry and statistical analysis were performed using SPSS17.0 software. Results: The prevalence of T2DM in Haikou City was 5.3% (5.15% for males and 5.46% for females). According to the multivariate analysis, the positive factors mainly associated with T2DM in the city included family history, Waist-to-Hip Ratio (WHR), triglycerides, low high-density lipoproteins (HDL), and blood pressure. For both men and women, family history was the highest independent risk factor associated with T2DM (OR= 47.128). The T2DM risk increased with increasing metabolic aggregate. Conclusion: The prevalence of T2DM for the community population of Haikou City was low. The possible risk factors included age, occupation, BMI, waist circumference, WHR, overweight, systemic obesity, central obesity, systolic blood pressure, diastolic blood pressure, total cholesterol, triglycerides, low-density lipoproteins, family history, and HDL. PMID:23641399

  1. 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 factors avoid the use of gradient correction factors as used in the TG-51 protocol although a chamber dependent optimal shift in the EPOM is required when using plane-parallel chambers while no shift is needed with cylindrical chambers. The sensitivity of these results to parameters used to model the ion chambers is discussed and the uncertainty related to the practical use of these results is evaluated. Conclusions: These results will prove useful as electron beam reference dosimetry protocols are being updated. The analysis of this work indicates that cylindrical ion chambers may be appropriate for use in low-energy electron beams but measurements are required to characterize their use in these beams.

  2. Effect of Atorvastatin on Growth Differentiation Factor-15 in Patients with Type 2 Diabetes Mellitus and Dyslipidemia

    PubMed Central

    Kim, Ji Min; Back, Min Kyung; Yi, Hyon-Seung; Joung, Kyong Hye

    2016-01-01

    Background Elevated serum levels of growth differentiation factor-15 (GDF-15) are associated with type 2 diabetes. Therefore, the effects of atorvastatin on metabolic parameters and GDF-15 levels in patients with type 2 diabetes and dyslipidemia were evaluated. Methods In this prospective randomized trial from February 2013 to March 2014, 50 consecutive type 2 diabetic patients with a low density lipoprotein cholesterol (LDL-C) levels ≥100 mg/dL were enrolled. The patients were divided into two groups based on the amount of atorvastatin prescribed, 10 mg/day (n=23) or 40 mg/day (n=27). The effect of atorvastatin on metabolic parameters, including lipid profiles and GDF-15 levels, at baseline and after 8 weeks of treatment were compared. Results The baseline metabolic parameters and GDF-15 levels were not significantly different between the two groups. After 8 weeks of treatment, the total cholesterol (TC) and LDL-C levels were significantly decreased in both groups. The mean changes in TC and LDL-C levels were more significant in the 40 mg atorvastatin group. The GDF-15 level was decreased in the 10 mg atorvastatin group, from 1,460.6±874.8 to 1,451.0±770.8 pg/mL, and was increased in the 40 mg atorvastatin group, from 1,271.6±801.0 to 1,341.4±855.2 pg/mL. However, the change in the GDF-15 level was not statistically significant in the 10 or 40 mg atorvastatin group (P=0.665 and P=0.745, respectively). Conclusion The GDF-15 levels were not significantly changed after an 8-week treatment with atorvastatin in type 2 diabetic patients. PMID:26616597

  3. 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...

  4. Comparing Factor, Class, and Mixture Models of Cannabis Initiation and DSM Cannabis Use Disorder Criteria, Including Craving, in the Brisbane Longitudinal Twin Study

    PubMed Central

    Kubarych, Thomas S.; Kendler, Kenneth S.; Aggen, Steven H.; Estabrook, Ryne; Edwards, Alexis C.; Clark, Shaunna L.; Martin, Nicholas G.; Hickie, Ian B.; Neale, Michael C.; Gillespie, Nathan A.

    2014-01-01

    Accumulating evidence suggests that the Diagnostic and Statistical Manual of Mental Disorders (DSM) diagnostic criteria for cannabis abuse and dependence are best represented by a single underlying factor. However, it remains possible that models with additional factors, or latent class models or hybrid models, may better explain the data. Using structured interviews, 626 adult male and female twins provided complete data on symptoms of cannabis abuse and dependence, plus a craving criterion. We compared latent factor analysis, latent class analysis, and factor mixture modeling using normal theory marginal maximum likelihood for ordinal data. Our aim was to derive a parsimonious, best-fitting cannabis use disorder (CUD) phenotype based on DSM-IV criteria and determine whether DSM-5 craving loads onto a general factor. When compared with latent class and mixture models, factor models provided a better fit to the data. When conditioned on initiation and cannabis use, the association between criteria for abuse, dependence, withdrawal, and craving were best explained by two correlated latent factors for males and females: a general risk factor to CUD and a factor capturing the symptoms of social and occupational impairment as a consequence of frequent use. Secondary analyses revealed a modest increase in the prevalence of DSM-5 CUD compared with DSM-IV cannabis abuse or dependence. It is concluded that, in addition to a general factor with loadings on cannabis use and symptoms of abuse, dependence, withdrawal, and craving, a second clinically relevant factor defined by features of social and occupational impairment was also found for frequent cannabis use. PMID:24588857

  5. 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...

  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. 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

  8. The photometric variability of solar-type stars. III - Results from 1981-82, including parallel observations of thirty-six Hyades stars

    NASA Technical Reports Server (NTRS)

    Radick, R. R.; Mihalas, D.; Lockwood, G. W.; Thompson, D. T.; Warnock, A., III; Hartmann, L. W.; Worden, S. P.; Henry, G. W.; Sherlin, J. M.

    1983-01-01

    A photometric survey of main-sequence stars in the Pleiades, Hyades, and Malmquist Field, to investigate variability among solar-type stars, had been continued at Cloudcroft Observatory for a second season. Possibly six of 40 Pleiades stars, two (possibly six) of 49 Hyades stars and possibly four of 42 stars in the Malmquist Field are found to be variable. Parallel observations of Hyades stars were obtained also at Lowell Observatory. These measurements, which achieved better precision, reveal significiant variations in eleven (possibly 16) of 36 Hyades stars, all of spectral type F7 V-K2 V. Agreement between the two surveys is acceptable. The two seasons of the Cloudcroft survey show that changes in the mean annual brightness of the Hyades stars accompany changes in the amplitude of their short-term variability, in the sense that a star tends to become fainter as its variability increases and vice versa. Color effects are absent.

  9. 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

  10. 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

  11. 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 669years) and 100 (90% men, age 6513years) age-matched non-diabetic volunteers were enrolled. 25(OH)D assay and the main cardiovascular risk factors were explored. 25(OH)D concentration was 2210ng/ml in control subjects and 18.2310ng/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

  12. 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

  13. Etiopathogenesis of type 1 diabetes mellitus: prognostic factors for the evolution of residual ? 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

  14. Assessment of the Common Risk Factors Associated with Type 2 Diabetes Mellitus in Jeddah

    PubMed Central

    Murad, Manal A.; Abdulmageed, Samia S.; Iftikhar, Rahila; Sagga, Bayan Khaled

    2014-01-01

    Risk factor management is important in avoiding life-threatening complications and preventing new-onset diabetes. We performed a case-control study in 2013 at ten primary health care centers in Jeddah, Saudi Arabia to determine the common risk factors of diabetes mellitus type 2 (DM2) and the demographic background of adult Saudi patients with DM2. Known diabetic patients were recruited as cases, while nondiabetic attendants were selected as controls. A pretested designed questionnaire was used to collect data from 159 cases and 128 controls. Cases were more likely than controls to be men (P < 0.0001), less educated (P < 0.0001), natives of eastern Saudi Arabia (P < 0.0001), retired (P < 0.0001), lower-salaried (P < 0.0001), or married or divorced (P < 0.0001). By univariate analysis cases were likely to be current smokers (P < 0.0001), hypertensive (P < 0.0001), or overweight/obese (P < 0.0001). Cases were also more likely to have a history of DM in a first-degree relative (P = 0.020). By multivariate analysis, cases were more likely to be older than 40 years (P < 0.0001), less educated (P = 0.05), married or divorced (P = 0.04), jobless/housewives (P < 0.0001), or current smokers (P = 0.002). They were also more likely to have salaries <7000 Saudi riyals (P = 0.01). Overall, prediabetic and high risk groups should be identified and counseled early before the occurrence of diabetes. PMID:25548563

  15. Wild Type p53 Transcriptionally Represses the SALL2 Transcription Factor under Genotoxic Stress

    PubMed Central

    Farkas, Carlos; Martins, Carla P.; Escobar, David; Hepp, Matias I.; Donner, David B.; Castro, Ariel F.; Evan, Gerard; Gutirrez, Jos L.; Warren, Robert; Pincheira, Roxana

    2013-01-01

    SALL2- a member of the Spalt gene family- is a poorly characterized transcription factor found deregulated in various cancers, which suggests it plays a role in the disease. We previously identified SALL2 as a novel interacting protein of neurotrophin receptors and showed that it plays a role in neuronal function, which does not necessarily explain why or how SALL2 is deregulated in cancer. Previous evidences indicate that SALL2 gene is regulated by the WT1 and AP4 transcription factors. Here, we identified SALL2 as a novel downstream target of the p53 tumor suppressor protein. Bioinformatic analysis of the SALL2 gene revealed several putative p53 half sites along the promoter region. Either overexpression of wild-type p53 or induction of the endogenous p53 by the genotoxic agent doxorubicin repressed SALL2 promoter activity in various cell lines. However R175H, R249S, and R248W p53 mutants, frequently found in the tumors of cancer patients, were unable to repress SALL2 promoter activity, suggesting that p53 specific binding to DNA is important for the regulation of SALL2. Electrophoretic mobility shift assay demonstrated binding of p53 to one of the identified p53 half sites in the Sall2 promoter, and chromatin immunoprecipitation analysis confirmed in vivo interaction of p53 with the promoter region of Sall2 containing this half site. Importantly, by using a p53ERTAM knockin model expressing a variant of p53 that is completely dependent on 4-hydroxy-tamoxifen for its activity, we show that p53 activation diminished SALL2 RNA and protein levels during genotoxic cellular stress in primary mouse embryo fibroblasts (MEFs) and radiosensitive tissues in vivo. Thus, our finding indicates that p53 represses SALL2 expression in a context-specific manner, adding knowledge to the understanding of SALL2 gene regulation, and to a potential mechanism for its deregulation in cancer. PMID:24040083

  16. In vitro and in vivo binding of human immunodeficiency virus type 1 Tat protein and Sp1 transcription factor.

    PubMed Central

    Jeang, K T; Chun, R; Lin, N H; Gatignol, A; Glabe, C G; Fan, H

    1993-01-01

    Recent genetic experiments have suggested that tat transactivation of the human immunodeficiency virus type 1 (HIV-1) long terminal repeat requires functional upstream enhancer sequences--Sp1 sites, in particular. In these experiments, HeLa cell nuclear extracts were passed over affinity matrices containing chemically synthesized or bacterially expressed HIV-1 Tat. Assay of material that bound to and eluted from the Tat matrices revealed the presence of the Sp1 transcription factor. Other transcription factors (Oct and NF-kappa B) also bound to Tat matrices but with less efficiency--in parallel with the lower capacities of these binding motifs to confer Tat responsiveness on a basal HIV-1 promoter compared with Sp1 sites. Passage of nuclear extracts over matrices containing other neutral proteins, including bovine serum albumin, ovalbumin, and lysozyme, revealed no or reduced binding. Cross-linking experiments indicated that the purified Sp1 and Tat proteins can form multimeric complexes in the absence of other proteins. The region of Tat responsible for Sp1 binding was localized to a region encompassing residues 30 to 62. Immunoprecipitation experiments with HIV-1-infected T lymphocytes indicated coimmunoprecipitation of Tat and Sp1. These experiments extend previous genetic experiments and suggest a direct interaction between Tat and Sp1 during transactivation. Images PMID:7690421

  17. Hepatocyte growth factor activator inhibitor type 1 suppresses metastatic pulmonary colonization of pancreatic carcinoma cells.

    PubMed

    Fukushima, Tsuyoshi; Kawaguchi, Makiko; Yamasaki, Masatoshi; Tanaka, Hiroyuki; Yorita, Kenji; Kataoka, Hiroaki

    2011-02-01

    Hepatocyte growth factor activator inhibitor type 1 (HAI-1) is a transmembrane protease inhibitor that regulates the activities of membrane-bound and extracellular serine proteases. HAI-1 has two Kunitz-type inhibitor domains with the N-terminal Kunitz domain (KD1) responsible for inhibiting known target proteases. Previously, we reported that knockdown of HAI-1 in the human pancreatic carcinoma cell line SUIT-2 resulted in epithelial to mesenchymal transition. To evaluate the role of HAI-1 in metastasis, we examined the metastatic capability of SUIT-2 cells that did or did not stably express HAI-1 short-hairpin RNA in an experimental pulmonary metastasis assay using nude mice. The extent of pulmonary metastasis was verified by histological examination and direct measurement of human cytokeratin 19 mRNA levels. One week after injecting SUIT-2 cells into mouse tail veins, apparent metastatic colonization was observed in 36% (4/11) of mice injected with HAI-1-knockdown SUIT-2, whereas none (0/11) of the control mice were positive for metastasis. After 2 weeks the metastasis positive ratios were 80% (4/5) and 40% (2/5), and after 4 weeks the ratios were 82% (9/11) and 45% (5/11) for HAI-1-knockdown and control SUIT-2 cells, respectively. Thus, loss of HAI-1 promoted pulmonary metastasis. Co-injection of recombinant KD1 abolished metastasis produced by HAI-1-knockdown SUIT-2 cells after 1 week. Moreover, recombinant KD1 restored E-cadherin levels in HAI-1 knockdown SUIT-2 cells and reduced their invasiveness in vitro. These data indicate that HAI-1 regulates pulmonary metastasis of SUIT-2, and KD1 may have therapeutic application for inhibiting metastatic cancer cell spreading. PMID:21166957

  18. Perturbations of Fibroblast Growth Factors 19 and 21 in Type 2 Diabetes

    PubMed Central

    Roesch, Stephen L.; Styer, Amanda M.; Wood, G. Craig; Kosak, Zachary; Seiler, Jamie; Benotti, Peter; Petrick, Anthony T.; Gabrielsen, Jon; Strodel, William E.; Gerhard, Glenn S.; Still, Christopher D.; Argyropoulos, George

    2015-01-01

    Fibroblast growth factors 19 and 21 (FGF19 and FGF21) have been implicated, independently, in type 2 diabetes (T2D) but it is not known if their circulating levels correlate with each other or whether the associated hepatic signaling mechanisms that play a role in glucose metabolism are dysregulated in diabetes. We used a cross-sectional, case/control, experimental design involving Class III obese patients undergoing Roux-en-Y bariatric surgery (RYGB), and measured FGF19 and FGF21 serum levels and hepatic gene expression (mRNA) in perioperative liver wedge biopsies. We found that T2D patients had lower FGF19 and higher FGF21 serum levels. The latter was corroborated transcriptionally, whereby, FGF21, as well as CYP7A1, β-Klotho, FGFR4, HNF4α, and glycogen synthase, but not of SHP or FXR mRNA levels in liver biopsies were higher in T2D patients that did not remit diabetes after RYGB surgery, compared to T2D patients that remitted diabetes after RYGB surgery or did not have diabetes. In a Phenome-wide association analysis using 205 clinical variables, higher FGF21 serum levels were associated with higher glucose levels and various cardiometabolic disease phenotypes. When serum levels of FGF19 were < 200 mg/mL and FGF21 > 500 mg/mL, 91% of patients had diabetes. These data suggest that FGF19/FGF21 circulating levels and hepatic gene expression of the associated signaling pathway are significantly dysregulated in type 2 diabetes. PMID:25664662

  19. Vitamin D as a risk factor for premature atherosclerosis in patients with type 2 diabetes

    PubMed Central

    Hamdy Al-Said, Nehal; Abd El Ghaffar Mohamed, Nagwa; Salam, Randa F.; Fawzy, Mary Wadie

    2015-01-01

    Background: Several cardiovascular risk factors have been recognized in patients with diabetes and vitamin D deficiency is emerging as a new risk. The aim of this study was to determine the effect of vitamin D deficiency on the incidence of premature atherosclerosis in patients with type 2 diabetes. Methods: A total of 78 patients with type 2 diabetes were subjected to history taking, physical examination, fasting glucose level, homeostasis model assessment of insulin resistance, lipid profile, 25(OH) vitamin D measurement, and carotid Doppler. Results: Patients with normal carotid intima-media thickness (CIMT) had sufficient vitamin D. Of those with increased CIMT 23.1% had insufficient vitamin D while 76.9% had sufficient vitamin D (six patients had plaques, one of them had vitamin D insufficiency, and the other five patients had sufficient vitamin D). There was a statistically significant difference in the serum level of vitamin D between patients with increased CIMT, and those with normal intima, with a decreased level in the first group. There was a significant negative correlation between vitamin D and fasting blood glucose. There was a statistically significant correlation in left CIMT between the vitamin D sufficiency group and the vitamin D insufficiency group, with higher values in the second group. There was no statistically significant difference in serum cholesterol, triglycerides, HDL cholesterol, and LDL cholesterol in patients with increased CIMT and those with normal intima. Conclusions: Decreased vitamin D levels in patients with diabetes lead to increased CIMT. The absence of a statistically significance difference in lipid profile between increased and normal CIMT groups raises the possibility of underlying causes for atherosclerosis in patients with diabetes other than dyslipidemia. PMID:26623002

  20. 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 mol m-2 s-1) and the lowest values in algae-crusted soil (0.73 0.31 mol 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

  1. Islet amyloid: a complication of islet dysfunction or an aetiological factor in Type 2 diabetes?

    PubMed

    Clark, A; Nilsson, M R

    2004-02-01

    The role of islet amyloidosis in the onset and progression of Type 2 diabetes remains obscure. Islet amyloid polypeptide is a 37 amino-acid, beta-cell peptide which is co-stored and co-released with insulin. Human islet amyloid polypeptide refolds to a beta-conformation and oligomerises to form insoluble fibrils; proline substitutions in rodent islet amyloid polypeptide prevent this molecular transition. Pro-islet amyloid polypeptide (67 amino acids in man) is processed in secretory granules. Refolding of islet amyloid polypeptide may be prevented by intragranular heterodimer formation with insulin (but not proinsulin). Diabetes-associated abnormal proinsulin processing could contribute to de-stabilisation of granular islet amyloid polypeptide. Increased pro-islet amyloid polypeptide secretion as a consequence of islet dysfunction could promote fibrillogenesis; the propeptide forms fibrils and binds to basement membrane glycosamino-glycans. Islet amyloid polypeptide gene polymorphisms are not universally associated with Type 2 diabetes. Transgenic mice expressing human islet amyloid polypeptide gene have increased islet amyloid polypeptide concentrations but develop islet amyloid only against a background of obesity and/or high fat diet. In transgenic mice, obese monkeys and cats, initially small perivascular deposits progressively increase to occupy 80% islet mass; the severity of amyloidosis in animal models is related to the onset of hyperglycaemia, suggesting that islet amyloid and the associated destruction of islet cells cause diabetes. In human diabetes, islet amyloid can affect less than 1% or up to 80% of islets indicating that islet amyloidosis largely results from diabetes-related pathologies and is not an aetiological factor for hyperglycaemia. However, the associated progressive beta-cell destruction leads to severe islet dysfunction and insulin requirement. PMID:14722650

  2. Impact of Environmental Factors and Biological Soil Crust Types on Soil Respiration in a Desert Ecosystem

    PubMed Central

    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 (0.930.43 mol m?2 s?1) and the lowest values in algae-crusted soil (0.730.31 mol 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

  3. Type 1 Fimbriae, a Colonization Factor of Uropathogenic Escherichia coli, Are Controlled by the Metabolic Sensor CRP-cAMP

    PubMed Central

    Müller, Claudia M.; Åberg, Anna; Straseviçiene, Jurate; Emődy, Levente; Uhlin, Bernt Eric; Balsalobre, Carlos

    2009-01-01

    Type 1 fimbriae are a crucial factor for the virulence of uropathogenic Escherichia coli during the first steps of infection by mediating adhesion to epithelial cells. They are also required for the consequent colonization of the tissues and for invasion of the uroepithelium. Here, we studied the role of the specialized signal transduction system CRP-cAMP in the regulation of type 1 fimbriation. Although initially discovered by regulating carbohydrate metabolism, the CRP-cAMP complex controls a major regulatory network in Gram-negative bacteria, including a broad subset of genes spread into different functional categories of the cell. Our results indicate that CRP-cAMP plays a dual role in type 1 fimbriation, affecting both the phase variation process and fimA promoter activity, with an overall repressive outcome on fimbriation. The dissection of the regulatory pathway let us conclude that CRP-cAMP negatively affects FimB-mediated recombination by an indirect mechanism that requires DNA gyrase activity. Moreover, the underlying studies revealed that CRP-cAMP controls the expression of another global regulator in Gram-negative bacteria, the leucine-responsive protein Lrp. CRP-cAMP-mediated repression is limiting the switch from the non-fimbriated to the fimbriated state. Consistently, a drop in the intracellular concentration of cAMP due to altered physiological conditions (e.g. growth in presence of glucose) increases the percentage of fimbriated cells in the bacterial population. We also provide evidence that the repression of type 1 fimbriae by CRP-cAMP occurs during fast growth conditions (logarithmic phase) and is alleviated during slow growth (stationary phase), which is consistent with an involvement of type 1 fimbriae in the adaptation to stress conditions by promoting biofilm growth or entry into host cells. Our work suggests that the metabolic sensor CRP-cAMP plays a role in coupling the expression of type 1 fimbriae to environmental conditions, thereby also affecting subsequent attachment and colonization of host tissues. PMID:19229313

  4. 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

  5. Herpes Simplex Virus Type 1 and Other Pathogens are Key Causative Factors in Sporadic Alzheimer's Disease.

    PubMed

    Harris, Steven A; Harris, Elizabeth A

    2015-01-01

    This review focuses on research in epidemiology, neuropathology, molecular biology, and genetics regarding the hypothesis that pathogens interact with susceptibility genes and are causative in sporadic Alzheimer's disease (AD). Sporadic AD is a complex multifactorial neurodegenerative disease with evidence indicating coexisting multi-pathogen and inflammatory etiologies. There are significant associations between AD and various pathogens, including Herpes simplex virus type 1 (HSV-1), Cytomegalovirus, and other Herpesviridae, Chlamydophila pneumoniae, spirochetes, Helicobacter pylori, and various periodontal pathogens. These pathogens are able to evade destruction by the host immune system, leading to persistent infection. Bacterial and viral DNA and RNA and bacterial ligands increase the expression of pro-inflammatory molecules and activate the innate and adaptive immune systems. Evidence demonstrates that pathogens directly and indirectly induce AD pathology, including amyloid-? (A?) accumulation, phosphorylation of tau protein, neuronal injury, and apoptosis. Chronic brain infection with HSV-1, Chlamydophila pneumoniae, and spirochetes results in complex processes that interact to cause a vicious cycle of uncontrolled neuroinflammation and neurodegeneration. Infections such as Cytomegalovirus, Helicobacter pylori, and periodontal pathogens induce production of systemic pro-inflammatory cytokines that may cross the blood-brain barrier to promote neurodegeneration. Pathogen-induced inflammation and central nervous system accumulation of A? damages the blood-brain barrier, which contributes to the pathophysiology of AD. Apolipoprotein E4 (ApoE4) enhances brain infiltration by pathogens including HSV-1 and Chlamydophila pneumoniae. ApoE4 is also associated with an increased pro-inflammatory response by the immune system. Potential antimicrobial treatments for AD are discussed, including the rationale for antiviral and antibiotic clinical trials. PMID:26401998

  6. Impact of Plasmids, Including Those EncodingVirB4/D4 Type IV Secretion Systems, on Salmonella enterica serovar Heidelberg Virulence in Macrophages and Epithelial Cells

    PubMed Central

    Gokulan, Kuppan; Khare, Sangeeta; Rooney, Anthony W.; Han, Jing; Lynne, Aaron M.; Foley, Steven L.

    2013-01-01

    Salmonella enterica serovar Heidelberg (S. Heidelberg) can cause foodborne illness in humans following the consumption of contaminated meat and poultry products. Recent studies from our laboratory have demonstrated that certain S. Heidelberg isolated from food-animal sources harbor multiple transmissible plasmids with genes that encode antimicrobial resistance, virulence and a VirB4/D4 type-IV secretion system. This study examines the potential role of these transmissible plasmids in bacterial uptake and survival in intestinal epithelial cells and macrophages, and the molecular basis of host immune system modulation that may be associated with disease progression. A series of transconjugant and transformant strains were developed with different combinations of the plasmids to determine the roles of the individual and combinations of plasmids on virulence. Overall the Salmonella strains containing the VirB/D4 T4SS plasmids entered and survived in epithelial cells and macrophages to a greater degree than those without the plasmid, even though they carried other plasmid types. During entry in macrophages, the VirB/D4 T4SS encoding genes are up-regulated in a time-dependent fashion. When the potential mechanisms for increased virulence were examined using an antibacterial Response PCR Array, the strain containing the T4SS down regulated several host innate immune response genes which likely contributed to the increased uptake and survival within macrophages and epithelial cells. PMID:24098597

  7. Herpesvirus saimiri small RNA and interleukin-4 mRNA AUUUA repeats compete for sequence-specific factors including a novel 70K protein.

    PubMed

    Geck, P; Medveczky, M M; Chou, C S; Brown, A; Cus, J; Medveczky, P G

    1994-09-01

    A highly oncogenic strain of the lymphotropic tumour virus herpesvirus saimiri (HVS; strain 484-77) expresses four small RNAs (HSUR1 to 4) in high copy numbers in transformed T cells. In HSUR1 and HSUR2 the 5' terminal regions contain conserved AUUUA sequence repeats. The same AUUUA repeats occur in the 3' non-coding regions of growth factor, lymphokine and protooncogene mRNAs, and the sequence is involved in rapid mRNA degradation. We report here that by using a highly specific u.v. cross-linking method we identified a novel 70K binding factor with AUUUA sequence specificity. Non-radiolabelled competition and V8 protease analysis show that the protein can form a complex with the 3' non-coding region of interleukin-4 mRNA and bind the AUUUA repeats of a HVS small RNA. We also detected an AUUUA-specific minor 32K human protein with the same electrophoretic mobility as a marmoset factor implicated in growth factor mRNA destabilization. The findings are consistent with the hypothesis that the viral small RNAs can compete for factors involved in rapid degradation of growth factor mRNAs and may contribute to viral oncogenesis. PMID:8077927

  8. 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

  9. Individual factors associated with L- and H-type Bovine Spongiform Encephalopathy in France

    PubMed Central

    2012-01-01

    Background Cattle with L-type (L-BSE) and H-type (H-BSE) atypical Bovine Spongiform encephalopathy (BSE) were identified in 2003 in Italy and France respectively before being identified in other countries worldwide. As of December 2011, around 60 atypical BSE cases have currently been reported in 13 countries, with over one third in France. While the epidemiology of classical BSE (C-BSE) has been widely described, atypical BSEs are still poorly documented, but appear to differ from C-BSE. We analysed the epidemiological characteristics of the 12 cases of L-BSE and 11 cases of H-BSE detected in France from January 2001 to late 2009 and looked for individual risk factors. As L-BSE cases did not appear to be homogeneously distributed throughout the country, two complementary methods were used: spatial analysis and regression modelling. L-BSE and H-BSE were studied separately as both the biochemical properties of their pathological prion protein and their features differ in animal models. Results The median age at detection for L-BSE and H-BSE cases was 12.4 (range 8.4-18.7) and 12.5 (8.3-18.2) years respectively, with no significant difference between the two distributions. However, this median age differed significantly from that of classical BSE (7.0 (range 3.5-15.4) years). A significant geographical cluster was detected for L-BSE. Among animals over eight years of age, we showed that the risk of being detected as a L-BSE case increased with age at death. This was not the case for H-BSE. Conclusion To the best of our knowledge this is the first study to describe the epidemiology of the two types of atypical BSE. The geographical cluster detected for L-BSE could be partly due to the age structure of the background-tested bovine population. Our regression analyses, which adjusted for the effect of age and birth cohort showed an age effect for L-BSE and the descriptive analysis showed a particular age structure in the area where the cluster was detected. No birth cohort effect was evident. The relatively small number of cases of atypical BSE and the few individual data available for the tested population limited our analysis to the investigation of age and cohort effect only. We conclude that it is essential to maintain BSE surveillance to further elucidate our findings. PMID:22647660

  10. Tumor Necrosis Factor ReceptorAssociated Factor (Traf)2 Represses the T Helper Cell Type 2 Response through Interaction with Nfat-Interacting Protein (Nip45)

    PubMed Central

    Lieberson, Rebecca; Mowen, Kerri A.; McBride, Kathryn D.; Leautaud, Veronica; Zhang, Xiankui; Suh, Woong-Kyung; Wu, Lin; Glimcher, Laurie H.

    2001-01-01

    Recently we have identified a novel protein NIP45 (nuclear factor of activated T cells [NFAT]-interacting protein) which substantially augments interleukin (IL)-4 gene transcription. The provision of NIP45 together with NFAT and the T helper cell type 2 (Th2)-specific transcription factor c-Maf to cells normally refractory to IL-4 production, such as B cells or Th1 clones, results in substantial IL-4 secretion to levels that approximate those produced by primary Th2 cells. In studies designed to further our understanding of NIP45 activity, we have uncovered a novel facet of IL-4 gene regulation. We present evidence that members of the tumor necrosis factor receptorassociated factor (TRAF) family of proteins, generally known to function as adapter proteins that transduce signals from the tumor necrosis factor receptor superfamily, contribute to the repression of IL-4 gene transcription and that this effect is mediated through their interaction with NIP45. PMID:11435475

  11. Steroid hormone synthesis by a vaccinia enzyme: a new type of virus virulence factor.

    PubMed Central

    Moore, J B; Smith, G L

    1992-01-01

    Vaccinia virus open reading frame (ORF) SalF7L has 31% amino acid identity to human 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase (3 beta-HSD). Here we show that SalF7L encodes an active 3 beta-HSD, by the conversion of pregnenolone to the steroid hormone progesterone. The gene is transcribed early during infection into a 1.4 kb mRNA from an initiation site 12 bp upstream of the ORF. An antiserum raised against bacterially expressed SalF7L immunoprecipitated a 38 kDa polypeptide from infected cells, but not from mock infected cells or from cells infected with a mutant virus from which the SalF7L ORF had been removed. Deletion of the gene had no effect on virus replication in CV-1 cells in culture, yet the deletion mutant was attenuated when intranasally inoculated into mice. This steroid hormone synthesizing enzyme is a novel type of virus virulence factor. Images PMID:1582424

  12. Type 2 diabetes as a risk factor for cognitive impairment: current insights

    PubMed Central

    Umegaki, Hiroyuki

    2014-01-01

    Type 2 diabetes mellitus (T2DM) is a risk factor for cognitive dysfunction and dementia in the elderly. T2DM has been thought to be associated with vascular diseases, eventually leading to vascular dementia, but recent studies have established that T2DM is also associated with Alzheimers disease (AD). With the increase in the number of elderly individuals with T2DM, the number of diabetic patients with cognitive dysfunction has been increasing. T2DM may accelerate AD-associated pathologies through insulin resistance. Vascular pathologies may also be associated with cognitive dysfunction and dementia in T2DM subjects. Several other mechanisms also seem to be involved in T2DM-related cognitive dysfunction. More investigations to clarify the association of T2DM with cognitive impairment are warranted. These investigations may help to increase our understanding of AD and open a new door to the development of therapeutics. Recent pharmaceutical advancement in T2DM treatment has resulted in the availability of a wide range of antidiabetics. Some evidence has suggested that antidiabetic therapies help to prevent cognitive dysfunction. At present, however, the optimal level of blood glucose control and the best combination of medications to achieve it in terms of cognitive preservation have not been established. More investigation is warranted. Cognitive dysfunction is an emerging new complication of T2DM that requires further study. PMID:25061284

  13. Effect of Fenugreek Seeds on Serum Metabolic Factors and Adiponectin Levels in Type 2 Diabetic Patients.

    PubMed

    Rafraf, Maryam; Malekiyan, Mina; Asghari-Jafarabadi, Mohammad; Aliasgarzadeh, Akbar

    2014-01-01

    This triple-blind randomized controlled clinical trial was conducted on 88 type 2 diabetic (T2DM) patients (males and females). Subjects in the fenugreek seed (n=44) and placebo (n=44) groups consumed 10 g/d of powdered whole fenugreek seeds or 5 g/d of wheat starch for 8 weeks. Fasting blood samples, anthropometric measurements and dietary records were collected at the baseline and at the end of the trial. Fenugreek seeds significantly decreased fasting blood glucose (P=0.007) and HbA1c (P=0.0001), serum levels of insulin (P=0.03), homeostatic model assessment for insulin resistance (P=0.004), total cholesterol (P=0.005) and triglycerides (P=0.0001) and increased serum levels of adiponectin (P=0.001) compared with placebo. No significant changes were shown in serum low-density lipoprotein cholesterol and high-density lipoprotein cholesterol in both groups. In conclusion, fenugreek seeds improved glucose metabolism, serum lipid profile and adiponectin levels in studied subjects, and may be useful in the control of diabetes risk factors in TD2M patients. PMID:26098483

  14. Cytotoxic Necrotizing Factor Type 1 Production by Uropathogenic Escherichia coli Modulates Polymorphonuclear Leukocyte Function

    PubMed Central

    Davis, Jon M.; Rasmussen, Susan B.; O'Brien, Alison D.

    2005-01-01

    Many strains of uropathogenic Escherichia coli (UPEC) produce cytotoxic necrotizing factor type 1 (CNF1), a toxin that constitutively activates the Rho GTPases RhoA, Rac1, and Cdc42. We previously showed that CNF1 contributes to the virulence of UPEC in a mouse model of ascending urinary tract infection and a rat model of acute prostatitis and that a striking feature of the histopathology of the mouse bladders and rat prostates infected with CNF1-positive strains is an elevation in levels of polymorphonuclear leukocytes (PMNs). We also found that CNF1 synthesis leads to prolonged survival of UPEC in association with human neutrophils. Here, we tested the hypothesis that CNF1 production by UPEC diminishes the antimicrobial capacity of mouse PMNs by affecting phagocyte function through targeting Rho family GTPases that are critical to phagocytosis and the generation of reactive oxygen species. We found that, as with human neutrophils, CNF1 synthesis provided a survival advantage to UPEC incubated with mouse PMNs. We also observed that CNF1-positive UPEC down-regulated phagocytosis, altered the distribution of the complement receptor CR3 (CD11b/CD18), enhanced the intracellular respiratory burst, and increased levels of Rac2 activation in PMNs. From these results, we conclude that modulation of PMN function by CNF1 facilitates UPEC survival during the acute inflammatory response. PMID:16113245

  15. 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.

  16. Residence place as a risk factor in different types of fatal car accidents.

    PubMed

    Leveau, Carlos M; Vacchino, Marta N

    2015-01-01

    The association between place of residence, population density, relief and type of event (collision or non-collision of the vehicle) has not been evaluated in developing countries. The main objective of this study is to determine the differential factors associated with the occurrence of deaths of collision and non-collision automobile users in Patagonia, Argentina. A multiple logistic regression analysis was performed using as the dependent variable death by car accident (collision or non-collision of the vehicle) and sex, age, place of residence of the victim, relief and population density as the independent variables. Collision fatalities were related to areas of high population density, while non-collision fatalities were related to areas of low population density, mountainous landscape and place of residence of the victims outside the Patagonian region. The results obtained in this study indicate the need to develop differential primary prevention policies by place of residence of car occupants, focusing on Patagonia non-resident drivers and by emphasising non-collision accidents. PMID:24134389

  17. 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

  18. Evolutionary trends of European bat lyssavirus type 2 including genetic characterization of Finnish strains of human and bat origin 24 years apart.

    PubMed

    Jakava-Viljanen, Miia; Miia, Jakava-Viljanen; Nokireki, Tiina; Tiina, Nokireki; Sironen, Tarja; Tarja, Sironen; Vapalahti, Olli; Olli, Vapalahti; Sihvonen, Liisa; Liisa, Sihvonen; Huovilainen, Anita; Anita, Huovilainen

    2015-06-01

    Among other Lyssaviruses, Daubenton's and pond-bat-related European bat lyssavirus type 2 (EBLV-2) can cause human rabies. To investigate the diversity and evolutionary trends of EBLV-2, complete genome sequences of two Finnish isolates were analysed. One originated from a human case in 1985, and the other originated from a bat in 2009. The overall nucleotide and deduced amino acid sequence identity of the two Finnish isolates were high, as well as the similarity to fully sequenced EBLV-2 strains originating from the UK and the Netherlands. In phylogenetic analysis, the EBLV-2 strains formed a monophyletic group that was separate from other bat-type lyssaviruses, with significant support. EBLV-2 shared the most recent common ancestry with Bokeloh bat lyssavirus (BBLV) and Khujan virus (KHUV). EBLV-2 showed limited diversity compared to RABV and appears to be well adapted to its host bat species. The slow tempo of viral evolution was evident in the estimations of divergence times for EBLV-2: the current diversity was estimated to have built up during the last 2000 years, and EBLV-2 diverged from KHUV about 8000 years ago. In a phylogenetic tree of partial N gene sequences, the Finnish EBLV-2 strains clustered with strains from Central Europe, supporting the hypothesis that EBLV-2 circulating in Finland might have a Central European origin. The Finnish EBLV-2 strains and a Swiss strain were estimated to have diverged from other EBLV-2 strains during the last 1000 years, and the two Finnish strains appear to have evolved from a common ancestor during the last 200 years. PMID:25877913

  19. Type I IFN induces binding of STAT1 to Bcl6: divergent roles of STAT family transcription factors in the T follicular helper cell genetic program.

    PubMed

    Nakayamada, Shingo; Poholek, Amanda C; Lu, Kristina T; Takahashi, Hayato; Kato, Masanari; Iwata, Shigeru; Hirahara, Kiyoshi; Cannons, Jennifer L; Schwartzberg, Pamela L; Vahedi, Golnaz; Sun, Hong-Wei; Kanno, Yuka; O'Shea, John J

    2014-03-01

    CD4(+) T follicular helper cells (TFH) are critical for the formation and function of B cell responses to infection or immunization, but also play an important role in autoimmunity. The factors that contribute to the differentiation of this helper cell subset are incompletely understood, although several cytokines including IL-6, IL-21, and IL-12 can promote TFH cell formation. Yet, none of these factors, nor their downstream cognate STATs, have emerged as nonredundant, essential drivers of TFH cells. This suggests a model in which multiple factors can contribute to the phenotypic characteristics of TFH cells. Because type I IFNs are often generated in immune responses, we set out to investigate whether these factors are relevant to TFH cell differentiation. Type I IFNs promote Th1 responses, thus one possibility was these factors antagonized TFH-expressed genes. However, we show that type I IFNs (IFN-α/β) induced B cell lymphoma 6 (Bcl6) expression, the master regulator transcription factor for TFH cells, and CXCR5 and programmed cell death-1 (encoded by Pdcd1), key surface molecules expressed by TFH cells. In contrast, type I IFNs failed to induce IL-21, the signature cytokine for TFH cells. The induction of Bcl6 was regulated directly by STAT1, which bound to the Bcl6, Cxcr5, and Pdcd1 loci. These data suggest that type I IFNs (IFN-α/β) and STAT1 can contribute to some features of TFH cells but are inadequate in inducing complete programming of this subset. PMID:24489092

  20. Frequency and associated risk factors of recurrent diabetic ketoacidosis among Saudi adolescents with type 1 diabetes mellitus

    PubMed Central

    Al-Hayek, Ayman A.; Robert, Asirvatham A.; Braham, Rim B.; Turki, Anoud S.; Al-Sabaan, Fahad S.

    2015-01-01

    Objectives: To explore the frequency and associated risk factors of recurrent diabetic ketoacidosis (RDKA) among Saudi adolescents with type 1 diabetes mellitus (T1DM). Methods: A cross-sectional study was conducted among 103 T1DM adolescents (aged 13-18 years, 57 males) who were hospitalized for diabetic ketoacidosis (DKA) between January 2013 and May 2014 at Prince Sultan Military Medical City (PSMMC), Riyadh, Kingdom of Saudi Arabia. The respondents were purposively, conveniently selected, and interviewed using a structured Arabic questionnaire including clinical information and demographics. Results: Fifty-six participants had experienced one episode of DKA, 41 had 2 episodes, and 6 had ≥3 episodes. Compared with adolescents who had hemoglobin A1c (HbA1c) ≤9, mean difference in RDKA was found among adolescents with >9 HbA1c. Similarly, adolescents who stopped insulin and those with lipodystrophy at the injection site had a higher frequency of RDKA. Discontinuing insulin (67%) was the major reason for RDKA followed by infection (31%). Among adolescents who discontinued insulin treatment, 31 (46.3%) gave no reason for stopping, 25 (37.3%) reported feeling sick, 7 (10.4%) gave a combination of reasons, and 4 (6%) reported a lack of supplies or other reasons. Regression analysis revealed that a higher HbA1c level and the presence of lipodystrophy were independent risk factors for RDKA. Conclusion: The frequency of RDKA was significantly greater in the T1DM adolescents with a higher HbA1c level, lipodystrophy, and those who had discontinued insulin treatment. Comprehensive multidisciplinary diabetes education should be offered to control modifiable risk factors in these patients. PMID:25719588

  1. Changes in Fundus Autofluorescence after Anti-vascular Endothelial Growth Factor According to the Type of Choroidal Neovascularization in Age-related Macular Degeneration

    PubMed Central

    Lee, Ji Young; Chung, Hyewon

    2016-01-01

    Purpose To describe the changes of fundus autofluorescence (FAF) in patients with age-related macular degeneration before and after intravitreal injection of anti-vascular endothelial growth factor according to the type of choroidal neovascularization (CNV) and to evaluate the correlation of FAF with spectral domain optical coherence tomography (SD-OCT) parameters and vision. Methods This was a retrospective study. Twenty-one treatment-naïve patients with neovascular age-related macular degeneration were included. Study eyes were divided into two groups according to the type of CNV. Fourteen eyes were type 1 CNV and seven eyes were type 2 CNV. All eyes underwent a complete ophthalmologic examination, including an assessment of best-corrected visual acuity, SD-OCT, fluorescein angiography, and FAF imaging, before and 3 months after intravitreal anti-vascular endothelial growth factor injection. Gray scales of FAF image for CNV areas, delineated as in fluorescein angiography, were analyzed using the ImageJ program, which were adjusted by comparison with normal background areas. Correlation of changes in FAF with changes in SD-OCT parameters, including CNV thickness, photoreceptor inner and outer segment junction disruption length, external limiting membrane disruption length, central macular thickness, subretinal fluid, and intraretinal fluid were analyzed. Results Eyes with both type 1 and type 2 CNV showed reduced FAF before treatment. The mean gray scales (%) of type 1 and type 2 CNV were 52.20% and 42.55%, respectively. The background values were 106.72 and 96.86. After treatment, the mean gray scales (%) of type 1 CNV and type 2 CNV were changed to 57.61% (p = 0.005) and 57.93% (p = 0.008), respectively. After treatment, CNV thickness, central macular thickness, and inner and outer segment junction disruption length were decreased while FAF increased. Conclusions FAF was noted to be reduced in eyes with newly diagnosed wet age-related macular degeneration, but increased after anti-vascular endothelial growth factor therapy regardless of CNV lesion type. PMID:26865799

  2. 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.

  3. Epidemiological characteristics and risk factors of diabetic retinopathy in type 2 diabetes mellitus in Shandong Peninsula of China

    PubMed Central

    Du, Zhao-Dong; Hu, Li-Ting; Zhao, Gui-Qiu; Ma, Yan; Zhou, Zhan-Yu; Jiang, Tao

    2011-01-01

    AIM To determine the epidemiological characteristics and estimate the risk factors of diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM) in Shandong Peninsula of China. METHODS The cases of T2DM admitted to Affiliated Hospital of Medical College of Qingdao University, Shandong Province, China, from January 2006 to December 2010 were retrospectively reviewed. The epidemiological characteristics of DR were estimated. The cases were divided into two groups according to degrees of retinopathy: non-DR group and DR group. Logistic regression analysis was used to study the related risk factors of DR. RESULTS The prevalence of DR in patients with T2DM was 25.08% (834/3326). There was significant difference between the average age for men (59.08±15.43 years) and for women (62.92±18.19 years, P=0.0021). The majority of DR occurred in women (female: male ratio=1.76:1, P<0.0001). The incidence rate of DR in urban (489/834) was higher than that in rural area (345/834, P<0.0001). In 834 DR patients, the mean duration of T2DM was 8.90±4.15 years (range: 0-16 years); 440 people (52.76%) had received varying degrees of health education about prevention and primary care of DM; and 473 people (56.71%) suffered from other DM complications confirmed at the same time. In addition, the incidence rate of monocular (551/3326) and binocular retinopathy (283/3326) were statistically different (P<0.0001). Factors associated (P<0.05) with the presence of DR included old age, lower health educational level, intraocular surgery history, longer duration of T2DM, accompanying with other DM complications, no standard treatment procedure, lower body mass index (BMI) and higher fasting plasma glucose (FPG), glycated hemoglobin A1C (HbA1C), urine albumin (UA), total cholesterol (TC), low-density-lipoprotein cholesterol (LDL-C). The risk factors (P<0.05) independently associated with the presence of DR were: longer duration of T2DM, lower health educational level, higher FPG, higher UA, lower BMI and higher TC. CONCLUSION DR is highly prevalent in the patients with T2DM in Shandong Peninsula of China. Besides blood glucose, many factors are associated with the present and development of DR. PMID:22553643

  4. Redescription of Philometra globiceps (Rudolphi, 1819) (Nematoda: Philometridae), the type species of Philometra Costa, 1845, including the first data obtained by SEM.

    PubMed

    Moravec, Frantiek; 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

  5. Prevalence of HIV, human papillomavirus type 16 and herpes simplex virus type 2 among female sex workers in Guinea and associated factors.

    PubMed

    Aho, Joséphine; Koushik, Anita; Coutlée, François; Diakité, Soumaïla Laye; Rashed, Sélim

    2014-03-01

    Female sex workers are at high risk for HIV infection. Sexually transmitted infections are known to be co-factors for HIV infection. Our aims were (1) to assess the prevalence of HIV and other sexually transmitted infections in this population; (2) to determine the association between sociodemographic characteristics, behavioural variables, and variables related to HIV prevention and HIV infection. A cross-sectional study was conducted in Conakry, Guinea, among a convenience sample of 223 female sex workers. A questionnaire on sociodemographic characteristics, risk factors, and exposure to prevention was administered. Screening for HIV, herpes simplex virus type 2, human papillomavirus type 16, Neisseria gonorrhoeae, and Chlamydia trachomatis was performed. Prevalences of HIV, herpes simplex virus type 2, human papillomavirus type 16, N. gonorrhoeae, and C. trachomatis were 35.3%, 84.1%, 12.2%, 9.0%, and 13.6%, respectively. Having a child, lubricant use, and human papillomavirus type 16 infection were associated with HIV infection. Interventions that promote screening and treatment of sexually transmitted infections are needed in order to achieve successful interventions to prevent HIV among female sex workers in resource-limited settings. PMID:24216036

  6. 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

  7. Association between vascular endothelial growth factor and hypertension in children and adolescents type I diabetes mellitus

    PubMed Central

    Zorena, K; Myśliwska, J; Myśliwiec, M; Rybarczyk-Kapturska, K; Malinowska, E; Wiśniewski, P; Raczyńska, K

    2010-01-01

    The aim of the study was to analyse the relationship between the serum level of vascular endothelial growth factor (VEGF) and the incidence of hypertension (HT) in children and adolescents with type I diabetes mellitus (T1DM). One hundred and five patients with T1DM were enrolled in the study. The control group consisted of 30 healthy controls. All the T1DM patients were subjected to biochemical analyses, ophthalmologic examination and 24-h blood pressure monitoring. Besides, all the patients and healthy controls had serum VEGF levels measured with the use of the ELISA methodology. The essence of our research is that patients with T1DM and HT and with microalbuminuria (MA) and diabetic retinopathy (DR) (MA/DR) are characterized by a significantly higher level of VEGF (340.23±93.22 pg ml–1) in blood serum in comparison with the group of T1DM patients without HT and MA/DR (183.6±96.6 pg ml–1) and with healthy controls (145.32±75.58 pg ml–1). In addition, the VEGF level was significantly higher in T1DM patients, who presented all three complications, that is HT, retinopathy and MA in comparison with T1DM patients without HT, but with MA/DR (P=0.036). On the other hand, no statistically significant differences (P=0.19) were noted in the level of VEGF in serum between T1DM patients without HT and MA/DR and the healthy control group. At a further stage of analysis, using the method of multiple regression, it was shown that systolic pressure, HbA1c and duration of disease are independent factors influencing the concentration of VEGF. Summarizing, the measurement of VEGF serum levels allows for the identification of groups of patients who have the highest risk of HT and, subsequently, progression of vascular complications. PMID:20164848

  8. 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.

  9. Genetic and environmental factors affecting mating type frequency in natural isolates of Tetrahymena thermophila.

    PubMed

    Arslanyolu, M; Doerder, F P

    2000-01-01

    In Tetrahymena thermophila mating type alleles specify temperature sensitive frequency distributions of multiple mating types. A-like alleles specify mating types I, II, III, V and VI, whereas B-like alleles specify mating types II through VII. We have characterized the mating type distributions specified by several A- and B-like genotypes segregated by genomic exclusion from cells isolated from a pond in northwestern Pennsylvania. The B-like genotypes are alike in specifying very low frequencies of mating type III, but differ with respect to the frequencies of other mating types, particularly II and VII. An A-like genotype specifies a high frequency of mating type III and is unstable in successive generations for the expression of mating type II, suggesting a possible modifier. Inter se crosses performed at 18 degrees C, 28 degrees C and 34 degrees C showed that each genotype specifies a frequency distribution that is uniquely affected by temperature. No mating type was affected the same way by temperature in all genotypes. In A/B heterozygotes, the B-like genotype exhibited partial dominance. The genotypes described here differ significantly from previously described genotypes from the same pond, indicating that there are numerous mating type alleles. For frequency-dependent selection to equalize mating type frequencies, it must act not only on complex multiple alleles but also on the response of mating type alleles to temperature. PMID:11140456

  10. 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

  11. 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-points. PMID:25186015

  12. Replacement of the replication factors of porcine circovirus (PCV) type 2 with those of PCV type 1 greatly enhances viral replication in vitro.

    PubMed

    Beach, N M; Juhan, N M; Cordoba, L; Meng, X J

    2010-09-01

    Porcine circovirus type 1 (PCV1), originally isolated as a contaminant of PK-15 cells, is nonpathogenic, whereas porcine circovirus type 2 (PCV2) causes an economically important disease in pigs. To determine the factors affecting virus replication, we constructed chimeric viruses by swapping open reading frame 1 (ORF1) (rep) or the origin of replication (Ori) between PCV1 and PCV2 and compared the replication efficiencies of the chimeric viruses in PK-15 cells. The results showed that the replication factors of PCV1 and PCV2 are fully exchangeable and, most importantly, that both the Ori and rep of PCV1 enhance the virus replication efficiencies of the chimeric viruses with the PCV2 backbone. PMID:20573809

  13. Replacement of the Replication Factors of Porcine Circovirus (PCV) Type 2 with Those of PCV Type 1 Greatly Enhances Viral Replication In Vitro?

    PubMed Central

    Beach, N. M.; Juhan, N. M.; Cordoba, L.; Meng, X. J.

    2010-01-01

    Porcine circovirus type 1 (PCV1), originally isolated as a contaminant of PK-15 cells, is nonpathogenic, whereas porcine circovirus type 2 (PCV2) causes an economically important disease in pigs. To determine the factors affecting virus replication, we constructed chimeric viruses by swapping open reading frame 1 (ORF1) (rep) or the origin of replication (Ori) between PCV1 and PCV2 and compared the replication efficiencies of the chimeric viruses in PK-15 cells. The results showed that the replication factors of PCV1 and PCV2 are fully exchangeable and, most importantly, that both the Ori and rep of PCV1 enhance the virus replication efficiencies of the chimeric viruses with the PCV2 backbone. PMID:20573809

  14. 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.

  15. 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

  16. Risk factors of herpes simplex virus type 2 among STD clinic attenders in Delhi, India.

    PubMed

    Kaur, Ravinder; Mittal, Nalini; Bhalla, P; Reddy, B N S; Baveja, Usha K

    2006-12-01

    The present study was conducted to determine the seroprevalence and risk factors associated with HSV-2 infection among sexually transmitted diseases (STD) clinic attenders of Delhi in India. Out of 128 patients included, 76 were males and 52 were females. Antibodies to HSV 1 and 2 and HIV infection were determined by ELISA. Syphilis seropositivity was determined by VDRL test and confirm by TPHA test. Ulcer scrapping were stained by Giemsa for Herpes progenitalis and Donovan bodies and Grams for Haemophilus decreyi infection. The HSV-2 and HSV-I seroprevalence was found to be 85.2% and 77.3% respectively. 87.3% of HSV-2 seropositive patients were asymptomic. 10.7% of patients had coinfection of HSV-2 and HIV. STDs like syphilis, chancroid, gonococcal and non-gonococcal urethritis were significantly associated in HSV-2 infection. Thus the study demonstrates high prevalence of HSV-2 infection in Delhi city. Significant association of HSV-2 infection with previous history of STD (p < 0.02) and multiple sexual partners in males was found (p < 0.002). PMID:17913210

  17. Eye color, hair color, blood type, and the rhesus factor: exploring possible genetic links to sexual orientation.

    PubMed

    Ellis, Lee; Ficek, Christopher; Burke, Donald; Das, Shyamal

    2008-02-01

    The present study sought to expand the limited evidence that sexual orientation is influenced by genetic factors. This was accomplished by seeking statistical differences between heterosexuals and homosexuals for four traits that are known to be genetically determined: eye color, natural hair color, blood type, and the Rhesus factor. Using a sample of over 7,000 U.S. and Canadian college students supplemented with additional homosexual subjects obtained through internet contacts, we found no significant differences between heterosexuals and homosexuals regarding eye color or hair color. In the case of blood type and the Rh factor, however, interesting patterns emerged. Heterosexual males and females exhibited statistically identical frequencies of the A blood type, while gay men exhibited a relatively low incidence and lesbians had a relatively high incidence (p < .05). In the case of the Rh factor, unusually high proportions of homosexuals of both sexes were Rh- when compared to heterosexuals (p < .06). The findings suggest that a connection may exist between sexual orientation and genes both on chromosome 9 (where blood type is determined) and on chromosome 1 (where the Rh factor is regulated). PMID:18074215

  18. [Hypoglycemia as a limiting factor in the management of type 1 diabetes].

    PubMed

    Nery, Mrcia

    2008-03-01

    Type 1 diabetic patients frequently present hypoglycemic episodes during their insulinotherapy, which, besides the discomfort and constrains does not allow the ideal glycemic control. Further, hypoglycemic events lead to the deficiency of the counter-regulation mechanisms in the subsequent episode, with a decrease in the release of epinephrine and the symptoms of warming, with great risk of severe hypoglycemia. The occurrence of hypoglycemia during some risky activities, specially driving, could result in accidents with the patient and /or third parts including property damage, stressing here the need to advise diabetics against having the necessary caution while driving. Generally the connective recovery is total after correcting a hypoglycemic coma. However when these episodes are repetitive, particularly in children, they could result in definitive cognitive disturbances. Hypoglycemic events without a warning signal (hypoglycemic unawareness) are difficult to reverse, thus it is necessary to prevent their occurrence, adjusting the treatment with glycemic targets, using continuous glucose monitoring at home and teaching them how to have an early recognition of hypoglycemia. PMID:18438539

  19. Extended-spectrum beta-lactamase-producing Escherichia coli in Spain belong to a large variety of multilocus sequence typing types, including ST10 complex/A, ST23 complex/A and ST131/B2.

    PubMed

    Oteo, Jesús; Diestra, Karol; Juan, Carlos; Bautista, Verónica; Novais, Angela; Pérez-Vázquez, María; Moyá, Bartolome; Miró, Elisenda; Coque, Teresa M; Oliver, Antonio; Cantón, Rafael; Navarro, Ferran; Campos, José

    2009-08-01

    In this study, we investigated the population structure of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli in Spain and determined possible associations between specific multilocus sequence typing (MLST) types and ESBL types. Ninety-two ESBL-producing E. coli isolates from 11 Spanish hospitals were studied. The predominant ESBLs in this collection were CTX-M-14 (45.7%), SHV-12 (21.7%) and CTX-M-9 (20.6%). Phylogenetic groups and MLST types were studied. Thirty-seven isolates (40.2%) belonged to phylogroup A, 26 (28.3%) to group B1, 13 (14.1%) to group B2 and 16 (17.4%) to group D. Fifty-six sequence types (STs) were identified, but ST131 (eight isolates) and ST167 (five isolates) were the most prevalent. The most common ST complexes were ST10 (13 isolates; 14.3%) and ST23 (10 isolates; 11%). Escherichia coli ST131 carried six different ESBLs (CTX-M-1, CTX-M-9, CTX-M-10, CTX-M-14, CTX-M-15 and SHV-12), E. coli ST10 complex carried five ESBLs and E. coli ST23 complex carried four ESBLs. A great diversity of MLST types was observed among Spanish ESBL-producing E. coli isolates. PMID:19464856

  20. Orientation factor and number of fibers at failure plane in ring-type steel fiber reinforced concrete

    SciTech Connect

    Lee, C.; Kim, H.

    2010-05-15

    Considering the probabilistic distributions of fibers in ring-type steel fiber reinforced concrete, the orientation factor and the number of ring-type steel fibers crossing the failure plane were theoretically derived as a function of fiber geometry, specimen dimensions, and fiber volume fraction. A total number of 24 specimens were tested incorporating different fiber types, specimen geometry, and fiber volume fractions of 0.2% and 0.4%: 5 beams and 5 panels containing straight steel fibers; and 6 beams and 8 panels containing ring-type steel fibers. Measurements were made to assess the number of fibers at fractured surfaces of steel fiber reinforced concrete. The developed theoretical expressions reasonably predicted the orientation factor and the number of ring-type steel fibers at failure plane: the average and the standard deviation for the ratios of the test to theory were 1.03 and 0.26, respectively. Theoretical investigations and comparisons were made for the values of orientation factor and the number of fibers at failure plane for straight steel fibers and ring-type steel fibers.

  1. Secretion of nerve growth factor, brain-derived neurotrophic factor, and glial cell-line derived neurotrophic factor in co-culture of four cell types in cerebrospinal fluid-containing medium.

    PubMed

    Feng, Sanjiang; Zhuang, Minghua; Wu, Rui

    2012-12-25

    The present study co-cultured human embryonic olfactory ensheathing cells, human Schwann cells, human amniotic epithelial cells and human vascular endothelial cells in complete culture medium-containing cerebrospinal fluid. Enzyme linked immunosorbent assay was used to detect nerve growth factor, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor secretion in the supernatant of co-cultured cells. Results showed that the number of all cell types reached a peak at 7-10 days, and the expression of nerve growth factor, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor peaked at 9 days. Levels of secreted nerve growth factor were four-fold higher than brain-derived neurotrophic factor, which was three-fold higher than glial cell line-derived neurotrophic factor. Increasing concentrations of cerebrospinal fluid (10%, 20% and 30%) in the growth medium caused a decrease of neurotrophic factor secretion. Results indicated co-culture of human embryonic olfactory ensheathing cells, human Schwann cells, human amniotic epithelial cells and human vascular endothelial cells improved the expression of nerve growth factor, brain-derived neurotrophic factor, and glial cell line-derived neurotrophic factor. The reduction of cerebrospinal fluid extravasation at the transplant site after spinal cord injury is beneficial for the survival and secretion of neurotrophic factors from transplanted cells. PMID:25317143

  2. UV-B-Responsive Association of the Arabidopsis bZIP Transcription Factor ELONGATED HYPOCOTYL5 with Target Genes, Including Its Own Promoter[W][OPEN

    PubMed Central

    Binkert, Melanie; Kozma-Bognr, Lszl; Terecskei, Kata; De Veylder, Lieven; Nagy, Ferenc; Ulm, Roman

    2014-01-01

    In plants subjected to UV-B radiation, responses are activated that minimize damage caused by UV-B. The bZIP transcription factor ELONGATED HYPOCOTYL5 (HY5) acts downstream of the UV-B photoreceptor UV RESISTANCE LOCUS8 (UVR8) and promotes UV-B-induced photomorphogenesis and acclimation. Expression of HY5 is induced by UV-B; however, the transcription factor(s) that regulate HY5 transcription in response to UV-B and the impact of UV-B on the association of HY5 with its target promoters are currently unclear. Here, we show that HY5 binding to the promoters of UV-B-responsive genes is enhanced by UV-B in a UVR8-dependent manner in Arabidopsis thaliana. In agreement, overexpression of REPRESSOR OF UV-B PHOTOMORPHOGENESIS2, a negative regulator of UVR8 function, blocks UV-B-responsive HY5 enrichment at target promoters. Moreover, we have identified a T/G-box in the HY5 promoter that is required for its UV-B responsiveness. We show that HY5 and its homolog HYH bind to the T/GHY5-box cis-acting element and that they act redundantly in the induction of HY5 expression upon UV-B exposure. Therefore, HY5 is enriched at target promoters in response to UV-B in a UVR8 photoreceptor-dependent manner, and HY5 and HYH interact directly with a T/G-box cis-acting element of the HY5 promoter, mediating the transcriptional activation of HY5 in response to UV-B. PMID:25351492

  3. Human Campylobacteriosis in Luxembourg, 2010-2013: A Case-Control Study Combined with Multilocus Sequence Typing for Source Attribution and Risk Factor Analysis.

    PubMed

    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

  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. CDK13, a New Potential Human Immunodeficiency Virus Type 1 Inhibitory Factor Regulating Viral mRNA Splicing?

    PubMed Central

    Berro, Reem; Pedati, Caitlin; Kehn-Hall, Kylene; Wu, Weilin; Klase, Zachary; Even, Yasmine; Genevire, Anne-Marie; Ammosova, Tatiana; Nekhai, Sergei; Kashanchi, Fatah

    2008-01-01

    The human immunodeficiency virus type 1 (HIV-1) Tat is a 14-kDa viral protein that acts as a potent transactivator by binding to the transactivation-responsive region, a structured RNA element located at the 5? end of all HIV-1 transcripts. Tat transactivates viral gene expression by inducing the phosphorylation of the C-terminal domain of RNA polymerase II through several Tat-activated kinases and by recruiting chromatin-remodeling complexes and histone-modifying enzymes to the HIV-1 long terminal repeat. Histone acetyltransferases, including p300 and hGCN5, not only acetylate histones but also acetylate Tat at lysine positions 50 and 51 in the arginine-rich motif. Acetylated Tat at positions 50 and 51 interacts with a specialized protein module, the bromodomain, and recruits novel factors having this particular domain, such as P/CAF and SWI/SNF. In addition to having its effect on transcription, Tat has been shown to be involved in splicing. In this study, we demonstrate that Tat interacts with cyclin-dependent kinase 13 (CDK13) both in vivo and in vitro. We also found that CDK13 increases HIV-1 mRNA splicing and favors the production of the doubly spliced protein Nef. In addition, we demonstrate that CDK13 acts as a possible restriction factor, in that its overexpression decreases the production of the viral proteins Gag and Env and subsequently suppresses virus production. Using small interfering RNA against CDK13, we show that silencing of CDK13 leads to a significant increase in virus production. Finally, we demonstrate that CDK13 mediates its effect on splicing through the phosphorylation of ASF/SF2. PMID:18480452

  6. Differential regulation of type III secretion and virulence genes in Bordetella pertussis and Bordetella bronchiseptica by a secreted anti-? factor.

    PubMed

    Ahuja, Umesh; Shokeen, Bhumika; Cheng, Ning; Cho, Yeonjoo; Blum, Charles; Coppola, Giovanni; Miller, Jeff F

    2016-03-01

    The BvgAS phosphorelay regulates ?10% of the annotated genomes of Bordetella pertussis and Bordetella bronchiseptica and controls their infectious cycles. The hierarchical organization of the regulatory network allows the integration of contextual signals to control all or specific subsets of BvgAS-regulated genes. Here, we characterize a regulatory node involving a type III secretion system (T3SS)-exported protein, BtrA, and demonstrate its role in determining fundamental differences in T3SS phenotypes among Bordetella species. We show that BtrA binds and antagonizes BtrS, a BvgAS-regulated extracytoplasmic function (ECF) sigma factor, to couple the secretory activity of the T3SS apparatus to gene expression. In B. bronchiseptica, a remarkable spectrum of expression states can be resolved by manipulating btrA, encompassing over 80 BtrA-activated loci that include genes encoding toxins, adhesins, and other cell surface proteins, and over 200 BtrA-repressed genes that encode T3SS apparatus components, secretion substrates, the BteA effector, and numerous additional factors. In B. pertussis, BtrA retains activity as a BtrS antagonist and exerts tight negative control over T3SS genes. Most importantly, deletion of btrA in B. pertussis revealed T3SS-mediated, BteA-dependent cytotoxicity, which had previously eluded detection. This effect was observed in laboratory strains and in clinical isolates from a recent California pertussis epidemic. We propose that the BtrA-BtrS regulatory node determines subspecies-specific differences in T3SS expression among Bordetella species and that B. pertussis is capable of expressing a full range of T3SS-dependent phenotypes in the presence of appropriate contextual cues. PMID:26884180

  7. The yeast BDF1 gene encodes a transcription factor involved in the expression of a broad class of genes including snRNAs.

    PubMed Central

    Lygerou, Z; Conesa, C; Lesage, P; Swanson, R N; Ruet, A; Carlson, M; Sentenac, A; Sraphin, B

    1994-01-01

    While screening for genes that affect the synthesis of yeast snRNPs, we identified a thermosensitive mutant that abolishes the production of a reporter snRNA at the non-permissive temperature. This mutant defines a new gene, named BDF1. In a bdf1-1 strain, the reporter snRNA synthesized before the temperature shift remains stable at the non-permissive temperature. This demonstrates that the BDF1 gene affects the synthesis rather than the stability of the reporter snRNA and suggests that the BDF1 gene encodes a transcription factor. BDF1 is present in single copy on yeast chromosome XII, and is important for normal vegetative growth but not essential for cell viability. bdf1 null mutants share common phenotypes with several mutants affecting general transcription and are defective in snRNA production. BDF1 encodes a protein of 687 amino-acids containing two copies of the bromodomain, a motif also present in other transcription factors as well as a new conserved domain, the ET domain, also present in Drosophila and human proteins. Images PMID:7816623

  8. Identification and characterization of multiple corticotropin-releasing factor type 2 receptor isoforms in the rat esophagus.

    PubMed

    Wu, S Vincent; Yuan, Pu-qing; Wang, Lixin; Peng, Yen L; Chen, Chih-Yen; Taché, Yvette

    2007-04-01

    The rat esophagus shares some cellular features with skin squamous epithelium and striated muscle that express high levels of corticotropin-releasing factor type 2 (CRF2) receptors or their cognate ligand urocortin (Ucn) 1, 2, and 3. We investigated the expression and cell signaling of CRF2 receptors and ligands in the rat esophagus and lower esophageal sphincter (LES) by RT-PCR and quantitative PCR in normal and corticosterone-treated whole esophageal tissue, laser capture microdissected layers, and isolated esophageal cells. The expression of CRF2 receptor protein and intracellular cAMP and ERK1/2 responses to CRF agonists and CRF2 antagonist were determined in cultured esophageal cells and HEK-293 cells transfected with CRF2b receptors. CRF2 was abundantly expressed in the mucosa and longitudinal muscle layers of the esophagus and LES, whereas CRF1 expression was scarce. CRF2b wild-type transcript was predominantly expressed in the esophagus, and in addition, several new CRF2 splice variants including six CRF2a isoforms were identified. Expression of Ucn 1, Ucn 2, and to a smaller extent Ucn 3, but not CRF mRNA, was detected in the esophagus and LES. Ucn 1 and Ucn 2 stimulated dose-dependent cAMP production and ERK1/2 phosphorylation in the esophageal cells, whereas CRF and CRF1 agonist, cortagine, had less potent effects. In addition, Ucn 2-stimulated cAMP and ERK responses were blocked by the CRF2 antagonist, astressin2-B. These data established the presence of a prominent CRF2 signaling system in the esophagus and LES-encompassing multiple CRF2 receptor variants and Ucn, suggesting a functional role in secretomotor activity and epithelial and muscle cell proliferation. PMID:17218420

  9. Evaluation of dietary habits and related factors among type 2 diabetic patients: An innovative study in Iran

    PubMed Central

    Tol, Azar; Mohebbi, Bahram; Sadeghi, Roya

    2014-01-01

    Introduction: The aim of this study was to assess dietary habits and related factors among type 2 diabetic mellitus patients for designing an effective nutrition intervention. Materials and Methods: A descriptive–analytical study was performed on 480 diabetic patients referred to four selected teaching hospitals affiliated to the Tehran University of Medical Sciences (TUMS) in Tehran for a period of nine months in 2012. Patients’ dietary habits were measured by a 51-item self-report instrument with four general questions about dietary habits and four subscales reflecting domains including general diabetes information (12 items), planning, shopping for, and preparing meals (6 items), eating meals (17 items), and family influence on dietary habits (12 items). The collected data was analyzed by using SPSS software version 11.5. Results were considered significant at a conventional P < 0.05 level. Results: Mean age of the participants was 59.96 ± 11.53 years. Mean scores in the domains were (53.72 ± 19.83), (57.31 ± 23.82), (52.27 ± 12.13), and (64.72 ± 14.3), respectively. Family influence on dietary habits was highlighted as the most important domain in the dietary habits instrument. Study results revealed that there was a significant association between the four domains and socioeconomic and some variables related to dietary habits such as dietary self-management, planned healthy lifestyle and attending diabetes educational programs. Discussion: The important role of family on dietary habits among type 2 diabetic patients highlighted the role of perceived social support from the family. The results of the sociodemographic variables stressed the necessity of tailoring specific intervention programs accordingly. PMID:24741644

  10. 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

  11. Relationship between Levels of Brain-Derived Neurotrophic Factor and Metabolic Parameters in Patients with Type 2 Diabetes Mellitus

    PubMed Central

    Boyuk, Banu; Degirmencioglu, Serife; Atalay, Hande; Guzel, Savas; Acar, Ayse; Celebi, Aslan; Ekizoglu, Ismail; Simsek, Caglar

    2014-01-01

    Background and Aim. Studies have suggested that brain-derived neurotrophic factor (BDNF) plays a role in glucose and lipid metabolism and inflammation. The aim of this study was to evaluate the relationship between serum BDNF levels and various metabolic parameters and inflammatory markers in patients with type 2 diabetes mellitus (T2DM). Materials and Methods. The study included 88 T2DM patients and 33 healthy controls. Fasting blood samples were obtained from the patients and the control group. The serum levels of BDNF were measured with an ELISA kit. The current paper introduces a receiver-operating characteristic (ROC) generalization curve to identify cut-off for the BDNF values in type 2 diabetes patients. Results. The serum levels of BDNF were significantly higher in T2DM patients than in the healthy controls (206.81??107.32?pg/mL versus 130.84??59.81?pg/mL; P < 0.001). They showed a positive correlation with the homeostasis model assessment of insulin resistance (HOMA-IR) (r = 0.28; P < 0.05), the triglyceride level (r = 0.265; P < 0.05), and white blood cell (WBC) count (r = 0.35; P < 0.001). In logistic regression analysis, age (P < 0.05), body mass index (BMI) (P < 0.05), C-reactive protein (CRP) (P < 0.05), and BDNF (P < 0.01) were independently associated with T2DM. In ROC curve analysis, BDNF cut-off was 137. Conclusion. The serum BDNF level was higher in patients with T2DM. The BDNF had a cut-off value of 137. The findings suggest that BDNF may contribute to glucose and lipid metabolism and inflammation. PMID:25587547

  12. Selective Inhibition of Membrane Type 1 Matrix Metalloproteinase Abrogates Progression of Experimental Inflammatory Arthritis: Synergy With Tumor Necrosis Factor Blockade

    PubMed Central

    Kaneko, Kazuyo; Williams, Richard O.; Dransfield, Daniel T.; Nixon, Andrew E.; Sandison, Ann

    2016-01-01

    Objective In rheumatoid arthritis (RA), destruction of articular cartilage by the inflamed synovium is considered to be driven by increased activities of proteolytic enzymes, including matrix metalloproteinases (MMPs). The purpose of this study was to investigate the therapeutic potential of selective inhibition of membrane type 1 MMP (MT1‐MMP) and its combination with tumor necrosis factor (TNF) blockage in mice with collagen‐induced arthritis (CIA). Methods CIA was induced in DBA/1 mice by immunization with bovine type II collagen. From the onset of clinical arthritis, mice were treated with MT1‐MMP selective inhibitory antibody DX‐2400 and/or TNFR‐Fc fusion protein. Disease progression was monitored daily, and serum, lymph nodes, and affected paws were collected at the end of the study for cytokine and histologic analyses. For in vitro analysis, bone marrow–derived macrophages were stimulated with lipopolysaccharide for 24 hours in the presence of DX‐2400 and/or TNFR‐Fc to analyze cytokine production and phenotype. Results DX‐2400 treatment significantly reduced cartilage degradation and disease progression in mice with CIA. Importantly, when combined with TNF blockade, DX‐2400 acted synergistically, inducing long‐term benefit. DX‐2400 also inhibited the up‐regulation of interleukin‐12 (IL‐12)/IL‐23 p40 via polarization toward an M2 phenotype in bone marrow–derived macrophages. Increased production of IL‐17 induced by anti‐TNF, which correlated with an incomplete response to anti‐TNF, was abrogated by combined treatment with DX‐2400 in CIA. Conclusion Targeting MT1‐MMP provides a potential strategy for joint protection, and its combination with TNF blockade may be particularly beneficial in RA patients with an inadequate response to anti‐TNF therapy. PMID:26315469

  13. An investigation of three patients with Christmas disease due to an abnormal type of factor ix

    PubMed Central

    Denson, K. W. E.; Biggs, Rosemary; Mannucci, P. M.

    1968-01-01

    Three patients with Christmas disease whose plasma was shown to have a prolonged one-stage prothrombin time with ox brain thromboplastin have been investigated. These patients have an inhibitor for the reaction between factor X, factor VII, and ox brain extract. The abnormal constituent responsible for this inhibitor appears to be factor IX whuch is functionally inactive but antigenically indistinguishable from normal factor IX. It is proposed that patients might be classified into haemophilia B+ for patients with this defect (Christmas disease+) and haemophilia B? (Christmas disease?) for patients who have classical Christmas disease. Images PMID:4972271

  14. 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

  15. Drugs, including alcohol, that act as risk factors for cataract, and possible protection against cataract by aspirin-like analgesics and cyclopenthiazide.

    PubMed Central

    Harding, J J; van Heyningen, R

    1988-01-01

    A case-control study of cataract in Oxfordshire explored the risks and benefits associated with a variety of drugs. Steroids including the diuretic spironolactone, nifedipine, heavy smoking, and beer drinking were associated with a raised risk. On the other hand aspirin-like analgesics (paracetamol, ibuprofen, aspirin, etc. appeared to protect against cataract. Cyclopenthiazide appeared to provide a similar protection. PMID:3207655

  16. Patterns of Circulating Fibroblast Growth Factor 21 in Subjects with and without Type 2 Diabetes

    PubMed Central

    Ma, Xiaojing; Hao, Yaping; Lu, Wei; Li, Huating; Bao, Yuqian; Zhou, Jian; Jia, Weiping

    2015-01-01

    Background Fibroblast growth factor 21 (FGF21) exerts wide-range effects on carbohydrate and lipid metabolism. However, its perturbation in type 2 diabetes mellitus (T2DM) remains elusive. Besides, previous human studies in T2DM simply investigated fasting or stimulated levels of FGF21. The current study sought to evaluate the temporal changes of circulating FGF21 in subjects with and without T2DM. Methods Ten patients with T2DM and 16 normal controls (NC) were recruited. Participants were categorized as obese (BMI≥25 kg/m2) or lean (BMI<25 kg/m2). Blood samples were drawn every 30 min within 7 hours (8 a.m.-3 p.m.). Serum FGF21, blood glucose, insulin, free fatty acids (FFAs) and adiponectin were measured in all subjects. Results The peak levels of FGF21 were observed in the fasting state (8 a.m.) both in T2DM and NC groups (267.35 ±158.72 ng/L vs. 178.93±121.37 ng/L, P = 0.096). FGF21 AUC did not differ significantly between the two groups (T2DM: 949.4±471.47 ng/L; NC: 883.13±561.40 ng/L, P = 0.770). Obese subjects had higher FGF21 levels than lean ones in patients either with or without T2DM. The pattern of FFAs closely resembled that of FGF21. Correlation analysis showed that temporal levels of FGF21 were significantly related to FFAs (r = 0.749, P = 0.002),but not blood glucose, insulin or adiponectin (all P> 0.05). Conclusions These findings suggest that the pattern of circulating FGF21 does not differ significantly between T2DM and NC,although T2DM patients showed a trend toward higher fasting FGF21 than healthy subjects. The pattern of circulating FFAs is significantly associated with that of FGF21. PMID:26540514

  17. 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.

  18. T-helper cell type-1 transcription factor T-bet is upregulated in pulmonary sarcoidosis.

    PubMed

    Kriegova, E; Fillerova, R; Tomankova, T; Hutyrova, B; Mrazek, F; Tichy, T; Kolek, V; du Bois, R M; Petrek, M

    2011-11-01

    Upregulation of genes for interferon (IFN)-γ and CXC chemokine receptor (CXCR)3 expression, two crucial molecules in sarcoid inflammation and granuloma formation, is directly controlled by the T-helper (Th)1 transcription factor T-bet (T-box, expressed in T-cells). However, there is no information on T-bet expression in sarcoidosis or its relationship with "sarcoidosis-associated" genes. Therefore, we investigated expression of T-bet mRNA and, in parallel, a spectrum of genes known to be involved in sarcoidosis pathogenesis. Transcripts were determined in bronchoalveolar lavage (BAL) cells from 62 sarcoidosis patients and 25 controls by quantitative RT-PCR; T-bet protein was localised by immunohistochemistry. Patient's BAL cells expressed higher mRNA T-bet levels than those of controls (mean ± sd fold change 3.64 ± 1.72; p = 0.00006). T-bet mRNA expression did not vary between clinical phenotypes as assessed by chest radiography stage, presence/absence of Löfgren's syndrome, extrapulmonary/pulmonary involvement or progressing/remitting disease (p > 0.05). T-bet mRNA expression correlated with expression of IFN-γ, CC chemokine ligand 5, CXC chemokine ligand (CXC)10, interleukin (IL)-2 receptor/IL-15 receptor β, CXCR3 and CXCR6 (p < 0.01). T-bet protein was localised to alveolar macrophages and lymphocytes, tissue multinucleated giant cells, macrophages and lymphocytes. In pulmonary sarcoidosis, T-bet upregulation is associated with changes in expression of IFN-γ, CXCR3 and chemokines/receptors involved in the pathogenesis of sarcoidosis, which suggests a role for T-bet in this Th1 disease, including modulation of some sarcoidosis-associated genes. PMID:21540308

  19. 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 (? = -0.277, P = 0.01) and self-efficacy (? = -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

  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. 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

  2. Development of Rotary-Type Voice Coil Motor Actuator for Small-Form-Factor Optical Disk Drive

    NASA Astrophysics Data System (ADS)

    Lee, Dong?Ju; Park, Se?June; Oh, Jeseung; Park, No?Cheol; Park, Young?Pil; Jung, Ho?Seop

    2006-02-01

    We propose the miniaturized rotary-type voice coil motor (VCM) actuator that has an effective focusing mechanism and a sufficient bandwidth for a small-form-factor (SFF) optical disk drive (ODD) based on Blu-ray disk (BD) 1 specifications.

  3. 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 ...

  4. 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...

  5. Arg578Gln mutations in the von Willebrand factor gene in three unrelated cases of type IIB von Willebrand disease.

    PubMed

    Piao, Y C; Lavergne, J M; Boyer-Neumann, C; Schandelong, A; Alessi, M C; Meyer, D

    1993-10-01

    A recurrent heterozygous CGG-->CAG (Arg578Gln) mutation was detected in exon 28 of the von Willebrand factor gene in three additional unrelated families with inherited type IIB von Willebrand disease. This identical mutation showed a differential phenotypic expression in each family. PMID:8292729

  6. 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.

  7. 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

  8. 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

  9. Biosynthesis of Dictyostelium Discoideum Differentation-Inducing Factor by a Hybrid Type I Fatty Acid A-Type III polyketide synthase

    SciTech Connect

    Austin,M.; Saito, T.; Bowman, M.; Haydock, S.; Kato, A.; Moore, B.; Kay, R.; Noel, J.

    2006-01-01

    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 {approx}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.

  10. The role of insulin-like growth factor-I and its binding proteins in glucose homeostasis and type 2 diabetes

    PubMed Central

    Rajpathak, Swapnil N.; Gunter, Marc J.; Wylie-Rosett, Judith; Ho, Gloria Y. F.; Kaplan, Robert C.; Muzumdar, Radhika; Rohan, Thomas E.; Strickler, Howard D.

    2014-01-01

    Summary This review addresses the possible role of the insulin-like growth factor (IGF)-axis in normal glucose homoeostasis and in the etiopathogenesis of type 2 diabetes. IGF-I, a peptide hormone, shares amino acid sequence homology with insulin and has insulin-like activity; most notably, the promotion of glucose uptake by peripheral tissues. Type 2 diabetes as well as pre-diabetic states, including impaired fasting glucose and impaired glucose tolerance, are associated cross-sectionally with altered circulating levels of IGF-I and its binding proteins (IGFBPs). Administration of recombinant human IGF-I has been reported to improve insulin sensitivity in healthy individuals as well as in patients with insulin resistance and type 2 diabetes. Further, IGF-I may have beneficial effects on systemic inflammation, a risk factor for type 2 diabetes, and on pancreatic β-cell mass and function. There is considerable inter-individual heterogeneity in endogenous levels of IGF-I and its binding proteins; however, the relationship between these variations and the risk of developing type 2 diabetes has not been extensively investigated. Large prospective studies are required to evaluate this association. PMID:19145587

  11. Correlation between electrophoretic types B1 and B2 of carboxylesterase B and host-dependent factors in Escherichia coli septicaemia.

    PubMed Central

    Picard, B.; Goullet, P.

    1988-01-01

    Electrophoretic types B1 and B2 of carboxylesterase B produced by strains of Escherichia coli isolated from 100 septicaemia cases were correlated with alpha-haemolysin and mannose resistant haemagglutinin (MRHA) production and with clinical data including eventual underlying diseases, origin of septicaemia and evolution. Electrophoretic type B2 was phenotypically linked with alpha-haemolysin and MRHA production. The proportion of type B2 isolates varied significantly with occurrence of an underlying illness (45% for patients without an underlying disease and 22% for compromised patients) and with the site of origin of the septicaemia (40% for those of urinary origin and 18% for infection of digestive origin). In the former infections, type B2 isolates were obtained in the majority from male patients while type B1 isolates predominated in women. The septicaemias associated with type B1 were characterized by a lower proportion of isolates producing alpha-haemolysin and MRHA and by a greater frequency of septic shock and death than those associated with type B2. These facts emphasize the importance of host-dependent factors in E. coli septicaemia. PMID:3276540

  12. CT Findings of Risk Factors for Persistent Type II Endoleak from Inferior Mesenteric Artery to Determine Indicators of Preoperative IMA Embolization

    PubMed Central

    Matsuda, Hitoshi; Sanda, Yoshihiro; Morita, Yoshiaki; Minatoya, Kenji; Kobayashi, Junjiro; Naito, Hiroaki

    2014-01-01

    Purpose: To identify the computed tomography (CT) findings of persistent type II endoleak from the inferior mesenteric artery (IMA) which indicate the need for preoperative IMA embolization. Materials and Methods: Included were 120 patients (96 males, 4993 years old, mean: 77.7) who underwent endovascular aortic aneurysm repair (EVAR) between June 2007 and October 2010. The relationship between persistent type II endoleak and CT findings of IMA orifice was examined. Results: CT showed no type II endoleak from IMA in 106 patients (89%; Group N), and transient type II endoleak from IMA in 10 patients (8.3%; Group T). CT showed persistent type II endoleak from IMA in 4 patients (3.3%; Group P) and three of them underwent reintervention. Univariate Cox-Mantel test analysis indicated that stenosis (p = 0.0003) and thrombus (p = 0.043) in IMA orifice were significant factors for persistent type II endoleak. The ratios of patients with proximal IMA more than 2.5 mm diameter in Groups N, Y, and P were 26/106 (24%), 5/10 (50%) and 4/4 (100%), respectively. Conclusion: Indicators for embolization of IMA prior to EVAR for the prevention of type II endoleak appear to be: (1) more than 2.5 mm in diameter and (2) no stenosis due to calcification or mural thrombus in IMA orifice. PMID:25298829

  13. 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

  14. Impact of Leisure-Time Physical Activity on Glycemic Control and Cardiovascular Risk Factors in Japanese Patients with Type 2 Diabetes Mellitus: The Fukuoka Diabetes Registry

    PubMed Central

    Kaizu, Shinako; Kishimoto, Hiro; Iwase, Masanori; Fujii, Hiroki; Ohkuma, Toshiaki; Ide, Hitoshi; Jodai, Tamaki; Kikuchi, Yohei; Idewaki, Yasuhiro; Hirakawa, Yoichiro; Nakamura, Udai; Kitazono, Takanari

    2014-01-01

    Aims/hypothesis The effects of leisure-time physical activity (LTPA) on glycemia and cardiovascular risk factors are not fully understood in Asian type 2 diabetic patients, who are typically non-obese. We studied associations between LTPA and glycemia and cardiovascular risk factors in Japanese type 2 diabetic patients. Methods A total of 4,870 Japanese type 2 diabetic patients aged ?20 years were divided into eight groups according to their LTPA. We investigated associations between the amount and intensity levels of physical activity (PA) and glycemic control, insulin sensitivity, cardiovascular risk factors, and low-grade systemic inflammation in a cross-sectional study. Results LTPA was dose-dependently associated with body mass index (BMI), waist circumference, hemoglobin A1c (HbA1c), fasting plasma glucose, homeostasis model assessment of insulin resistance, triglyceride, high density lipoprotein cholesterol, high sensitivity C-reactive protein, and prevalence of metabolic syndrome, but not with blood pressure, low density lipoprotein cholesterol or adiponectin. The amount of PA required to lower HbA1c was greater than that required to improve cardiovascular risk factors. LTPA was inversely associated with HbA1c in non-obese participants but not in obese participants after multivariate adjustments for age, sex, duration of diabetes, current smoking, current drinking, energy intake, cardiovascular diseases, depressive symptoms, and treatment of diabetes. Higher-intensity LTPA, not lower-intensity LTPA was associated with HbA1c after multivariate adjustments with further adjustment including BMI. Conclusions/interpretation LTPA was dose-dependently associated with better glycemic control and amelioration of some cardiovascular risk factors in Japanese type 2 diabetic patients. In addition, increased higher-intensity LTPA may be appropriate for glycemic control. PMID:24897110

  15. 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

  16. Real-world Experience with Sofosbuvir-based Regimens for Chronic Hepatitis C, Including Patients with Factors Previously Associated with Inferior Treatment Response

    PubMed Central

    Wu, Christina J; Roytman, Marina M; Hong, Leena K; Huddleston, Leslie; Trujillo, Ruby; Cheung, Alvin; Poerzgen, Peter

    2015-01-01

    The introduction of sofosbuvir, a direct acting antiviral, has revolutionized the treatment of chronic hepatitis C virus (HCV). Phase 3 clinical trials have demonstrated the efficacy, simplicity, and tolerability of sofosbuvir-based regimens and report high rates of sustained virological response (SVR) rates. The purpose of this study was to assess whether clinical trial findings translate into a real-world setting, particularly with treatment of chronic HCV in our diverse, multiethnic population of Hawaii. Retrospective analysis was performed for 113 patients with genotype 16 HCV infection being treated at the Queen's Liver Center between January 2014 and March 2015. SVR rates for our cohort were slightly lower than the rates published by the clinical trials. Data analysis also suggested that most baseline characteristics previously associated with inferior response might not be as significant for sofosbuvir-based regimens; in our cohort, male gender was the only factor significantly related to increased risk of virologic relapse. Pacific Islanders also had higher rate of relapse compared to other ethnic groups, but the small number of patients treated in this subgroup make it difficult to validate this finding. While newer all-oral treatment regimens have been introduced since this study, we highlight the importance of comparing real-world versus clinical trial results for new treatments, and provide data analyses for treatment of chronic HCV in Hawaii.

  17. 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

  18. Convergent transcripts of the yeast PRP38-SMD1 locus encode two essential splicing factors, including the D1 core polypeptide of small nuclear ribonucleoprotein particles.

    PubMed Central

    Rymond, B C

    1993-01-01

    The PRP38 gene of Saccharomyces cerevisiae is necessary for the excision of intron sequences from pre-mRNA and required for the maintenance of maximal levels of U6 small nuclear RNA (snRNA). This report describes the identification of a gene of related function, SMD1, located immediately 3' to PRP38. The PRP38 and SMD1 transcription units are configured in an unusual "tail-to-tail" arrangement with their respective open reading frames terminating on opposite strands of a common 6-bp region. The predicted SMD1 polypeptide, Smd1p, is 40% identical to the D1 protein of human small nuclear ribonucleoprotein particles. Experimentally induced depletion of Smd1p blocks the first step of splicing and results in growth arrest. In addition, the levels of the trimethylguanosine-capped spliceosomal snRNAs, U1, U2, U4, and U5, but not the Prp38p-sensitive U6 snRNA, decrease in response to Smd1p depletion. The cap structures of snRNAs persisting in the absence of SMD1 expression appear to be peculiar, as they are poorly recognized by an anti-trimethylguanosine antibody. These data establish Smd1p as a required component of the cellular splicing apparatus and a factor in snRNA maturation and stability. Images PMID:8430095

  19. 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 4716 months. Late death occurred in 6 patients. DSINE occurred in 39 patients (6.7%) at mean 2217 months after the initial TEVAR, which was managed with re-TEVAR in 25 and medically in 14. At 3318 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 difference in mobility of the dissected flap. Expedite repeat TEVAR is recommended to improve the clinical prognosis for patients with DSINE. PMID:26716029

  20. 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 early stages. Following a diagnosis of DFU more intensive surveillance and aggressive care may improve outcome. PMID:25573978

  1. SERPINE2 haplotype as a risk factor for panlobular type of emphysema

    PubMed Central

    2011-01-01

    Background SERPINE2 (serpin peptidase inhibitor, clade E, member 2) has previously been identified as a positional candidate gene for chronic obstructive pulmonary disease (COPD) and has subsequently been associated to COPD and emphysema in several populations. We aimed to further examine the role of SERPINE2 polymorphisms in the development of pulmonary emphysema and different emphysema subtypes. Methods Four single nucleotide polymorphisms (SNPs) in SERPINE2 were analyzed from 951 clinically and radiologically examined Finnish construction workers. The genotype and haplotype data was compared to different emphysematous signs confirmed with high-resolution computed tomography (HRCT), forced vital capacity (FVC), forced expiratory volume in one second (FEV1), diffusing capacity (DLCO), and specific diffusing capacity (DLCO/VA). Results Three of the studied SERPINE2 SNPs (rs729631, rs975278, and rs6748795) were found to be in tight linkage disequilibrium. Therefore, only one of these SNPs (rs729631) was included in the subsequent analyses, in addition to the rs840088 SNP which was in moderate linkage with the other three studied SNPs. The rs729631 SNP showed a significant association with panlobular emphysema (p = 0.003). In further analysis, the variant allele of the rs729631 SNP was found to pose over two-fold risk (OR 2.22, 95% CI 1.05-4.72) for overall panlobular changes and over four-fold risk (OR 4.37, 95% CI 1.61-11.86) for pathological panlobular changes. A haplotype consisting of variant alleles of both rs729631 and rs840088 SNPs was found to pose an almost four-fold risk for overall panlobular (OR 3.72, 95% CI 1.56-8.90) and subnormal (OR 3.98, 95% CI 1.55-10.20) emphysema. Conclusions Our results support the previously found association between SERPINE2 polymorphisms and pulmonary emphysema. As a novel finding, our study suggests that the SERPINE2 gene may in particular be involved in the development of panlobular changes, i.e., the same type of changes that are involved in alpha-1-antitrypsin (AAT) -deficiency. PMID:22145704

  2. 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

  3. Dynamic Stress Factor (DySF): A Significant Predictor of Severe Hypoglycemic Events in Children with Type 1 Diabetes

    PubMed Central

    Rawlings, RA; Yuan, L; Shi, H; Brehm, W; Pop-Busui, R; Nelson, PW

    2013-01-01

    Hemoglobin A1c (HbA1c) is the current standard used in the clinical treatment of patients with diabetes. However, it has been shown that patients with similar HbA1c values may have widely different fluctuations in blood glucose values over the same period of time, including time spent in hyper- and/or hypo-glycemia. Hence, there exists a need for quantitative measures that can supplement HbA1c in managing patients with diabetes. We introduce and compare the Dynamic Stress Factor, DySF, a newly developed metric that quantifies glycemic volatility based on patient-specific glucose transition density profiles with HbA1c and with currently used glucose variability metrics in predicting severe hypoglycemia in children with type 1 diabetes. DySF, the daily weighted number of large monotonic glycemic transitions that occur within one hour, was calculated for 441 total subjects with type 1 diabetes (146 children, aged 8-14 yrs) to assess the magnitude and frequency of glucose transitions per day. Severe hypoglycemic episodes (HE) were quantified for all subjects and evaluated against HbA1c and existing measures of glucose variability, including SD, MAGE, MODD, and CONGA using logistic regression models. DySF was found to be a predictor of severe HE in children (p = 0.018) with the likelihood of a child, aged 8-14 yrs, experiencing severe hypoglycemia increasing by up to 20% with decreasing values of up to 60% of DySF. Patients of any age who had one or multiple severe hypoglycemic episodes had on average a lower DySF when compared to those with no HE. Additionally, when considering mean glucose levels, DySF/mean was a preliminary predictor of severe HE in patients with HbA1c ? 6.5% (p = 0.062). DySF is a dynamic, quantitative, measure of daily glucose volatility that separates patients, within the same strata of HbA1c, into visually distinct patient profiles. DySF can be used as a preliminary predictor of clinically severe hypoglycemia in children and well-controlled patients with HbA1c ? 6.5%. PMID:24349871

  4. Transcriptional regulators of the Schizosaccharomyces pombe fbp1 gene include two redundant Tup1p-like corepressors and the CCAAT binding factor activation complex.

    PubMed Central

    Janoo, R T; Neely, L A; Braun, B R; Whitehall, S K; Hoffman, C S

    2001-01-01

    The Schizosaccharomyces pombe fbp1 gene, which encodes fructose-1,6-bis-phosphatase, is transcriptionally repressed by glucose through the activation of the cAMP-dependent protein kinase A (PKA) and transcriptionally activated by glucose starvation through the activation of a mitogen-activated protein kinase (MAPK). To identify transcriptional regulators acting downstream from or in parallel to PKA, we screened an adh-driven cDNA plasmid library for genes that increase fbp1 transcription in a strain with elevated PKA activity. Two such clones express amino-terminally truncated forms of the S. pombe tup12 protein that resembles the Saccharomyces cerevisiae Tup1p global corepressor. These clones appear to act as dominant negative alleles. Deletion of both tup12 and the closely related tup11 gene causes a 100-fold increase in fbp1-lacZ expression, indicating that tup11 and tup12 are redundant negative regulators of fbp1 transcription. In strains lacking tup11 and tup12, the atf1-pcr1 transcriptional activator continues to play a central role in fbp1-lacZ expression; however, spc1 MAPK phosphorylation of atf1 is no longer essential for its activation. We discuss possible models for the role of tup11- and tup12-mediated repression with respect to signaling from the MAPK and PKA pathways. A third clone identified in our screen expresses the php5 protein subunit of the CCAAT-binding factor (CBF). Deletion of php5 reduces fbp1 expression under both repressed and derepressed conditions. The CBF appears to act in parallel to atf1-pcr1, although it is unclear whether or not CBF activity is regulated by PKA. PMID:11238405

  5. Nipple discharge: is its significance as a risk factor for breast cancer fully understood? Observational study including 915 consecutive patients who underwent selective duct excision.

    PubMed

    Montroni, Isacco; Santini, Donatella; Zucchini, Giorgia; Fiacchi, Monica; Zanotti, Simone; Ugolini, Giampaolo; Manaresi, Alessio; Taffurelli, Mario

    2010-10-01

    Nipple discharge (ND) is a common symptom seen in breast cancer clinics. The primary aim of this study was to identify preoperative risk factors for breast cancer in patients with pathologic ND. The secondary aim was to assess the clinical and pathological effectiveness of physical examination, galactography, cytological examination of the discharge, selective duct excision and ductoscopy. All patients operated on between 1975 and 2008 who presented with ND as their only symptom was analyzed. Discharge's characteristics, cytological data and galactography reports were recorded. The relationship between each individual finding and the risk of breast cancer was calculated. For each diagnostic tool, the sensitivity, specificity and complication rates were calculated and compared. Nine-hundred-fifteen patients underwent selective duct excision. Two-hundred-nineteen patients (23.9%) were found to be affected by carcinoma. In 100/330 (30.3%) patients with bloody discharge and in 42/239 (17.6%) patients with serous secretion cancer was detected (P = 0.004, P = 0.013, respectively). Patients with sero-sanguinous or coloured discharge had the same risk of cancer as the population analyzed (23.9%, P = NS). Galactographic finding of irregular stenosis seemed to be associated with a higher risk of cancer (P = 0.0001). Cytological findings C5 and C4 were associated with cancer (P = 0.001). Selective duct excision showed highest sensitivity and specificity. In conclusion, the well established role of bloody secretion is confirmed. The supposed benign aetiology of serous, coloured or sero-sanguinous discharge is questionable. The high specificity of the cytological exam justifies routine examination of the ND. Selective duct excision can be considered as the diagnostic gold-standard. PMID:20354781

  6. 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

  7. 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

  8. A TCP domain transcription factor controls flower type specification along the radial axis of the Gerbera (Asteraceae) inflorescence

    PubMed Central

    Broholm, Suvi K.; Thtiharju, Sari; Laitinen, Roosa A. E.; Albert, Victor A.; Teeri, Teemu H.; Elomaa, Paula

    2008-01-01

    Several key processes in plant development are regulated by TCP transcription factors. CYCLOIDEA-like (CYC-like) TCP domain proteins have been shown to control flower symmetry in distantly related plant lineages. Gerbera hybrida, a member of one of the largest clades of angiosperms, the sunflower family (Asteraceae), is an interesting model for developmental studies because its elaborate inflorescence comprises different types of flowers that have specialized structures and functions. The morphological differentiation of flower types involves gradual changes in flower size and symmetry that follow the radial organization of the densely packed inflorescence. Differences in the degree of petal fusion further define the distinct shapes of the Gerbera flower types. To study the role of TCP transcription factors during specification of this complex inflorescence organization, we characterized the CYC-like homolog GhCYC2 from Gerbera. The expression of GhCYC2 follows a gradient along the radial axis of the inflorescence. GhCYC2 is expressed in the marginal, bilaterally symmetrical ray flowers but not in the centermost disk flowers, which are nearly radially symmetrical and have significantly less fused petals. Overexpression of GhCYC2 causes disk flowers to obtain morphologies similar to ray flowers. Both expression patterns and transgenic phenotypes suggest that GhCYC2 is involved in differentiation among Gerbera flower types, providing the first molecular evidence that CYC-like TCP factors take part in defining the complex inflorescence structure of the Asteraceae, a major determinant of the family's evolutionary success. PMID:18574149

  9. CXCR-4 (Fusin), a co-receptor for the type 1 human immunodeficiency virus (HIV-1), is expressed in the human brain in a variety of cell types, including microglia and neurons.

    PubMed Central

    Lavi, E.; Strizki, J. M.; Ulrich, A. M.; Zhang, W.; Fu, L.; Wang, Q.; O'Connor, M.; Hoxie, J. A.; González-Scarano, F.

    1997-01-01

    Entry of the type 1 human immunodeficiency virus into most cells requires the presence of the CD4 protein in combination with one of several recently described co-receptors. CXCR-4 (fusin) was the first identified, and it serves as co-receptor for T-cell-line tropic (T-tropic) HIV-1 isolates. To determine the expression of CXCR-4 in the brain, a major target of HIV pathology, we used immunohistochemistry and reverse transcriptase polymerase chain reaction with CXCR-4-specific antibodies and probes. We found that CXCR-4 was expressed in several cell types in brain, but notably in neurons and microglia, a finding that was replicated in tissue culture. The study of the expression of CXCR-4 in the brain, which may be one of many chemokine receptors in the central nervous system, may provide further insight into the interactions between brain cells, pathogens, and the immune system, and help understand the pathogenesis of HIV dementia. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:9327737

  10. 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 in these comparisons. There was probable evidence for a moderate direct association between total fat intake and BW. Furthermore, there was convincing evidence that partial replacement of SFA with PUFA decreases the risk of CVD, especially in men. This finding was supported by an association with biomarkers of PUFA intake; the evidence of a beneficial effect of dietary total PUFA, n-6 PUFA, and linoleic acid (LA) on CVD mortality was limited suggestive. Evidence for a direct association between total fat intake and risk of T2DM was inconclusive, whereas there was limited-suggestive evidence from biomarker studies that LA is inversely associated with the risk of T2DM. However, there was limited-suggestive evidence in biomarker studies that odd-chain SFA found in milk fat and fish may be inversely related to T2DM, but these associations have not been supported by controlled studies. The evidence for an association between dietary n-3 PUFA and T2DM was inconclusive. Evidence for effects of fat on major types of cancer was inconclusive regarding both the amount and quality of dietary fat, except for prostate cancer where there was limited-suggestive evidence for an inverse association with intake of ALA and for ovarian cancer for which there was limited-suggestive evidence for a positive association with intake of SFA. This SR reviewed a large number of studies focusing on several different health outcomes. The time period covered by the search may not have allowed obtaining the full picture of the evidence in all areas covered by this SR. However, several SRs and meta-analyses that covered studies published before year 2000 were evaluated, which adds confidence to the results. Many of the investigated questions remain unresolved, mainly because of few studies on certain outcomes, conflicting results from studies, and lack of high quality–controlled studies. There is thus an evident need of highly controlled RCT and PCS with sufficient number of subjects and long enough duration, specifically regarding the effects of the amount and quality of dietary fat on insulin sensitivity, T2DM, low-grade inflammation, and blood pressure. New metabolic and other potential risk markers and utilization of new methodology in the area of lipid metabolism may provide new insight. PMID:25045347

  11. Job Strain as a Risk Factor for Type 2 Diabetes: A Pooled Analysis of 124,808 Men and Women

    PubMed Central

    Fransson, Eleonor I.; Heikkil, 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, Tres; Vnnen, 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 1.061.25) with no difference between men and women (1.19 [1.061.34] and 1.13 [1.001.28], 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 (1.001.23). 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

  12. Cardiorenal Syndrome Type 1: A Defective Regulation of Monocyte Apoptosis Induced by Proinflammatory and Proapoptotic Factors

    PubMed Central

    Pastori, Silvia; Virzì, Grazia Maria; Brocca, Alessandra; de Cal, Massimo; Clementi, Anna; Vescovo, Giorgio; Ronco, Claudio

    2015-01-01

    In this study, we examined the possible immune-mediated mechanisms in cardiorenal syndrome (CRS) type 1 pathogenesis. We enrolled 40 patients with acute heart failure (AHF), 11 patients with CRS type 1 and 15 controls. Plasma from the different groups was incubated with monocytes; subsequently, cell apoptosis was evaluated by DNA fragmentation, caspase activity and cytofluorometric assay. Cytokine quantification in plasma and supernatant was performed by ELISA. Monocytes treated with CRS type 1 plasma showed significantly higher apoptosis compared with those treated with AHF and the controls (p < 0.05). Caspase-3 (CRS type 1: 2.20 ng/ml, IQR 2.06-2.33; AHF: 1.48 ng/ml, IQR 1.31-1.56; controls: 0.71 ng/ml, IQR 0.67-0.81) and caspase-8 levels (CRS type 1: 1.49 ng/ml, IQR 1.42-1.57; AHF: 0.94 ng/ml, IQR 0.84-0.98; controls: 0.56 ng/ml, IQR 0.51-0.58) in cells incubated with plasma from these patients demonstrated a significantly higher concentration. We observed a strong upregulation of plasma IL-6 and IL-18 in CRS type 1 compared with AHF and the controls (p < 0.05). Interestingly, we observed a similar concentration of TNF-α in CRS type 1 and AHF. In CRS type 1 patients, IL-6 (52.13 ng/ml, IQR 47.29-66.83) and IL-18 levels (197.75 ng/ml, IQR 120.80-265.49) in supernatant were significantly higher than in AHF patients (IL-6: 28.79 ng/ml, IQR 19.90-36.10; IL-18: 21.98 ng/ml, IQR 15.98-29.85) and controls (IL-6: 5.02 ng/ml, IQR 4.56-6.44; IL-18: 7.91 ng/ml, IQR 5.57-10.62). These findings suggest the presence of a defective regulation of monocyte apoptosis in CRS type 1 patients and the involvement of an immune-mediated mechanism in the pathophysiology of this syndrome. PMID:25999959

  13. Impact of dietary fiber intake on glycemic control, cardiovascular risk factors and chronic kidney disease in Japanese patients with type 2 diabetes mellitus: the Fukuoka Diabetes Registry

    PubMed Central

    2013-01-01

    Background Dietary fiber is beneficial for the treatment of type 2 diabetes mellitus, although it is consumed differently in ethnic foods around the world. We investigated the association between dietary fiber intake and obesity, glycemic control, cardiovascular risk factors and chronic kidney disease in Japanese type 2 diabetic patients. Methods A total of 4,399 patients were assessed for dietary fiber intake using a brief self-administered diet history questionnaire. The associations between dietary fiber intake and various cardiovascular risk factors were investigated cross-sectionally. Results Body mass index, fasting plasma glucose, HbA1c, triglyceride and high-sensitivity C-reactive protein negatively associated with dietary fiber intake after adjusting for age, sex, duration of diabetes, current smoking, current drinking, total energy intake, fat intake, saturated fatty acid intake, leisure-time physical activity and use of oral hypoglycemic agents or insulin. The homeostasis model assessment insulin sensitivity and HDL cholesterol positively associated with dietary fiber intake. Dietary fiber intake was associated with reduced prevalence of abdominal obesity, hypertension and metabolic syndrome after multivariate adjustments including obesity. Furthermore, dietary fiber intake was associated with lower prevalence of albuminuria, low estimated glomerular filtration rate and chronic kidney disease after multivariate adjustments including protein intake. Additional adjustments for obesity, hypertension or metabolic syndrome did not change these associations. Conclusion We demonstrated that increased dietary fiber intake was associated with better glycemic control and more favorable cardiovascular disease risk factors including chronic kidney disease in Japanese type 2 diabetic patients. Diabetic patients should be encouraged to consume more dietary fiber in daily life. PMID:24330576

  14. Toward a Two-Factor Theory of One Type of Mathematics Disabilities.

    ERIC Educational Resources Information Center

    Robinson, Carol S.; Menchetti, Bruce M.; Torgesen, Joseph K.

    2002-01-01

    This article proposes a two-factor theory of mathematics disabilities based on the premise that weak cognitive representations lead to poorer retrieval of information from long term memory. Comparison of children with math disabilities alone (MD) and those with both math and reading disabilities (MD/RD) suggests that weak phonological processing

  15. 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

  16. 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...

  17. 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

  18. 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…

  19. Exposure to environmental factors in drinking water: risk of islet autoimmunity and type 1 diabetes--the BABYDIAB study.

    PubMed

    Winkler, C; Mollenhauer, U; Hummel, S; Bonifacio, E; Ziegler, A-G

    2008-08-01

    Type 1 diabetes (T1D) is characterized by autoimmunity against pancreatic islets, and autoantibodies may be present for years before diagnosis. Environmental factors during early life, including drinking water, may play a role in pathogenesis of T1D. The German BABYDIAB study is a prospective observational study that followed newborn offspring of mothers or fathers with T1D from birth to 17 years of age. The present study was a nested case-control analysis, where subjects with islet autoimmunity were defined as cases (n=95), those without as controls (n=139). Drinking water quality was obtained from the German Water Supply Authorities for the participating families for the first year of the child's life. There was no significant association between water acidity or drinking water quality (concentration of minerals and elements) and islet autoimmunity risk. Increased progression to diabetes in islet autoantibody-positive children was associated with exposure to water with lower pH values (less than cohort median, 7.62; odds ratio [OR]: 2.5; 95% confidence interval [CI]: 1.1-5.7; p=0.03) but was not significant after correction for multiple comparisons. Concentrations of nitrate, nitrite, iron, aluminum, and manganese were not associated with risk of T1D progression. This is the first prospective study with water quality measured before the onset of islet autoimmunity and T1D. Consistent with a previous cross-sectional case-control study, we found an association between drinking water pH and the rate of T1D development in at-risk children. The association is marginal and requires validation in other prospective cohorts. PMID:18500677

  20. Continuing Disparities in Cardiovascular Risk Factors and Complications Between Aboriginal and Anglo-Celt Australians With Type 2 Diabetes

    PubMed Central

    Davis, Timothy M.E.; Hunt, Kerry; McAullay, Daniel; Chubb, Stephen A.P.; Sillars, Brett A.; Bruce, David G.; Davis, Wendy A.

    2012-01-01

    OBJECTIVE To determine whether disparities in the nature and management of type 2 diabetes persist between Aboriginal and the majority Anglo-Celt patients in an urban Australian community. RESEARCH DESIGN AND METHODS Baseline data from the observational Fremantle Diabetes Study collected from 1993 to 1996 (phase I) and from 2008 to 2011 (phase II) were analyzed. Patients characterized as Aboriginal or Anglo-Celt by self-report and supporting data underwent comprehensive assessment, including questionnaires, examination, and biochemical testing in a single laboratory. Generalized linear modeling with age/sex adjustment was used to examine differences in changes in variables in the two groups between phases I and II. RESULTS The indigenous participants were younger at entry and at diabetes diagnosis than the Anglo-Celt participants in both phases. They were also less likely to be educated beyond primary level and were more likely to be smokers. HbA1c decreased in both groups over time (Aboriginal median 9.6% [interquartile range 7.810.7%] to 8.4% [6.610.6%] vs. Anglo-Celt median 7.1% [6.28.4%] to 6.7% [6.27.5%]), but the gap persisted (P = 0.65 for difference between phases I and II by ethnic group). Aboriginal patients were more likely to have microvascular disease in both phases. The prevalence of peripheral arterial disease (ankle-brachial index ?0.90 or lower-extremity amputation) increased in Aboriginal but decreased in Anglo-Celt participants (15.829.7 vs. 30.721.5%; P = 0.055). CONCLUSIONS Diabetes management has improved for Aboriginal and Anglo-Celt Australian patients, but disparities in cardiovascular risk factors and complications persist. PMID:22815295

  1. R-factor cointegrate formation in Salmonella typhimurium bacteriophage type 201 strains.

    PubMed

    Helmuth, R; Stephan, R; Bulling, E; van Leeuwen, W J; van Embden, J D; Guine, P A; Portnoy, D; Falkow, S

    1981-05-01

    The genetic and molecular properties of the plasmids in Salmonella typhimurium phase type 201 isolated are described. Such strains are resistant to streptomycin, tetracycline, chloramphenicol, ampicillin, kanamycin, and several other antimicrobial drugs, and are highly pathogenic for calves. These strains have been encountered with increasing frequency since 1972 in West Germany and The Netherlands. We show that isolates of this phage type constitute a very homogeneous group with regard to their extrachromosomal elements. These bacteria carry three small plasmids: pRQ3, a 4.2-megadalton (Md) colicinogenic plasmid; pRQ4, 3.4-Md plasmid that interferes with the propagation of phages; and pRQ5, a 3.2-Md cryptic plasmid. Tetracycline resistance resides on a conjugative 120-MD plasmid pRQ1, belonging to the incompatibility class H2. Other antibiotic resistance determinants are encoded by a nonconjugative 108-Md plasmid pRQ2. Transfer of multiple-antibiotic resistance to appropriate recipient strains was associated with the appearance of a 230-Md plasmid, pRQ6. It appears that pRQ6 is a stable cointegrate of pRQ1 and pRQ2. This cointegrate plasmid was transferable with the same efficiency as pRQ1. Other conjugative plasmids could mobilize pRQ2, but stable cointegrates were not detected in the transconjugants. Phase type 201 strains carry a prophage, and we show that phage pattern 201 reflects the interference with propagation of typing phages effected by this prophage and plasmid pRQ4 in strains of phage type 201. PMID:7012128

  2. 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, lvaro; 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

  3. INTERMEDIATE-TERM MORTALITY AND CARDIAC TRANSPLANTATION IN INFANTS WITH SINGLE-VENTRICLE LESIONS: RISK FACTORS AND THEIR INTERACTION WITH SHUNT TYPE

    PubMed Central

    Tweddell, James S.; Sleeper, Lynn A.; Ohye, Richard G.; Williams, Ismee A.; Mahony, Lynn; Pizarro, Christian; Pemberton, Victoria L.; Frommelt, Peter C.; Bradley, Scott M.; Cnota, James F.; Hirsch, Jennifer; Kirshbom, Paul; Li, Jennifer S.; Pike, Nancy; Puchalski, Michael; Ravishankar, Chitra; Jacobs, Jeffrey P.; Laussen, Peter C.; McCrindle, Brian W.

    2012-01-01

    Objectives We sought to identify factors associated with death and cardiac transplantation in infants undergoing the Norwood procedure and to determine differences in associations that might favor either the modified Blalock-Taussig shunt (MBTS) or a right ventricle-to-pulmonary artery shunt (RVPAS). Methods We used competing risks methodology to analyze death without transplantation, cardiac transplantation, and survival without transplantation. Parametric time-to-event modeling and bootstrapping were used to identify independent predictors. Results Data from 549 subjects (follow-up, 2.70.9 years) were analyzed. Mortality risk was characterized by early and constant phases; transplant was characterized by only a constant phase. Early phase factors associated with death included lower socioeconomic status (SES; P=.01), obstructed pulmonary venous return (P<.001), smaller ascending aorta (P=.02), and anatomic subtype. Constant phase factors associated with death included genetic syndrome (P<.001) and lower gestational age (GA, P<.001). The RVPAS had better survival in the 51% who were full term with aortic atresia (P<.001). The MBTS was better among the 4% who were preterm with a patent aortic valve (P =.003). Lower pre-Norwood right ventricular fractional area change, pre-Norwood surgery, and anatomy other than hypoplastic left heart syndrome were independently associated with transplantation (all P<.03); but shunt type was not (P=.43). Conclusions Independent risk factors for intermediate-term mortality include lower SES, anatomy, genetic syndrome, and lower GA. Term infants with aortic atresia benefited from a RVPAS and preterm infants with a patent aortic valve benefited from a MBTS. Right ventricular function and anatomy, but not shunt type, were associated with transplantation. PMID:22341427

  4. 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…

  5. 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 treatment in the year after initiation; and incurred higher medical resource use and costs than continuers. The findings are limited to the commercially insured population in the US. In addition, persistence patterns were assessed using administrative claims as opposed to actual medication-taking behavior and did not account for measures of glycemic control. Further research is needed to understand the reasons behind basal insulin persistence and the implications thereof, to help clinicians manage care for T2DM more effectively. PMID:26703951

  6. 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 imbalance of CHD-type remodeler levels, which consequently may lead to changes of transcriptional programs, may be an underlying mechanism involved in impaired fear extinction learning and its therapeutic rescue. PMID:26635563

  7. 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 imbalance of CHD-type remodeler levels, which consequently may lead to changes of transcriptional programs, may be an underlying mechanism involved in impaired fear extinction learning and its therapeutic rescue. PMID:26635563

  8. 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 differences in the costs of T1D and in the socioeconomic profile and health care provided to the patients with T1D in specialized public centers in Brazil. Both factors influenced directly the costs of T1D and should be considered for discussing future health policies. PMID:24373627

  9. 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

  10. Development of abiotic stress tolerance via bZIP-type transcription factor LIP19 in common wheat.

    PubMed

    Kobayashi, Fuminori; Maeta, Eri; Terashima, Akihiro; Kawaura, Kanako; Ogihara, Yasunari; Takumi, Shigeo

    2008-01-01

    Cereal lip19 genes encoding bZIP-type transcription factors are assumed to play a regulatory role in gene expression during the cold acclimation process. However, no direct evidence shows an association of LIP19-type bZIPs with stress tolerance or activation of stress-responsive Cor/Lea genes. To understand the molecular basis of development of abiotic stress tolerance through the LIP19 transcription factor, a wheat lip19 homologue, Wlip19, was isolated and characterized. Wlip19 expression was activated by low temperature in seedlings and was higher in a freezing-tolerant cultivar than in a freezing-sensitive one. Wlip19 also responded to drought and exogenous ABA treatment. Wlip19-expressing transgenic tobacco showed a significant increase in abiotic stress tolerance, especially freezing tolerance. Expression of a GUS reporter gene under the control of promoter sequences of four wheat Cor/Lea genes, Wdhn13, Wrab17, Wrab18, and Wrab19, was enhanced by Wlip19 expression in wheat callus and tobacco plants. These results indicate that WLIP19 acts as a transcriptional regulator of Cor/Lea genes in the development of abiotic stress tolerance. Moreover, direct protein-protein interaction between WLIP19 and a wheat OBF1 homologue TaOBF1, another bZIP-type transcription factor, was observed, suggesting that this interaction is conserved in cereals. PMID:18326864

  11. Low shear stress can initiate von Willebrand factor-dependent platelet aggregation in patients with type IIB and platelet-type von Willebrand disease.

    PubMed Central

    Murata, M; Fukuyama, M; Satoh, K; Fujimura, Y; Yoshioka, A; Takahashi, H; Handa, M; Kawai, Y; Watanabe, K; Ikeda, Y

    1993-01-01

    Platelets exposed to shear stress aggregate in the absence of exogenously added agonists, utilizing distinct platelet membrane receptors and ligands depending upon the level of shear stress applied. Using a modified cone and plate type viscometer, we previously demonstrated that, under low shear stress (18 dyn/cm2), aggregation is mediated by platelet membrane glycoprotein (GP) IIb-IIIa and fibrinogen, whereas aggregation induced by high shear stress (108 dyn/cm2) requires the binding of von Willebrand factor (vWF) to both GPIb-IX and GPIIb-IIIa (Ikeda, Y., M. Handa, K. Kawano, T. Kamata, M. Murata, Y. Araki, H. Anbo, Y. Kawai, K. Watanabe, I. Itagaki, et al. 1991. J. Clin. Invest. 87:1234-1240). Here we report that vWF-dependent aggregation occurs under low shear stress in citrated platelet-rich plasma (PRP) from two types of congenital bleeding disorders, platelet-type von Willebrand disease (vWD) and type IIB vWD, in both of which ristocetin-induced aggregation is known to be heightened. Aggregation induced by low shear stress was enhanced in both types of disorders compared to normal controls, and the enhancement was completely abolished by anti-vWF monoclonal antibody NMC-4, which blocks the GPIb-binding site on vWF. Under high shear stress, the extent of maximal aggregation was not different between controls and the patient groups although maximal aggregation was reached much more quickly in the latter. When citrated PRP was exposed to a gradient of shear stress (6 to 108 dyn/cm2 over a 5-min period), vWF-dependent aggregation, as judged from the inhibitory effect of NMC-4, first occurred at 14 dyn/cm2 in platelet-type vWD and at 10-12 dyn/cm2 in type IIB vWD, as compared with more than 81 +/- 20.1 dyn/cm2 in control platelets. These results suggest that an abnormality in either vWF or GPIb-IX triggers the aggregation-inducing interaction of the two molecules under low shear stress, which might explain the intravascular platelet clumping, that presumably underlies the thrombocytopenia observed in these bleeding disorders. PMID:8376606

  12. RNA-directed DNA methylation and plant development require an IWR1-type transcription factor

    PubMed Central

    Kanno, Tatsuo; Bucher, Etienne; Daxinger, Lucia; Huettel, Bruno; Kreil, David P; Breinig, Frank; Lind, Marc; Schmitt, Manfred J; Simon, Stacey A; Gurazada, Sai Guna Ranjan; Meyers, Blake C; Lorkovic, Zdravko J; Matzke, Antonius J M; Matzke, Marjori

    2010-01-01

    RNA-directed DNA methylation (RdDM) in plants requires two RNA polymerase (Pol) II-related RNA polymerases, namely Pol IV and Pol V. A genetic screen designed to reveal factors that are important for RdDM in a developmental context in Arabidopsis identified DEFECTIVE IN MERISTEM SILENCING 4 (DMS4). Unlike other mutants defective in RdDM, dms4 mutants have a pleiotropic developmental phenotype. The DMS4 protein is similar to yeast IWR1 (interacts with RNA polymerase II), a conserved putative transcription factor that interacts with Pol II subunits. The DMS4 complementary DNA partly complements the K1 killer toxin hypersensitivity of a yeast iwr1 mutant, suggesting some functional conservation. In the transgenic system studied, mutations in DMS4 directly or indirectly affect Pol IV-dependent secondary short interfering RNAs, Pol V-mediated RdDM, Pol V-dependent synthesis of intergenic non-coding RNA and expression of many Pol II-driven genes. These data suggest that DMS4 might be a regulatory factor for several RNA polymerases, thus explaining its diverse roles in the plant. PMID:20010803

  13. Type 2 diabetes in Asians: prevalence, risk factors, and effectiveness of behavioral intervention at individual and population levels.

    PubMed

    Weber, Mary Beth; Oza-Frank, Reena; Staimez, Lisa R; Ali, Mohammed K; Narayan, K M Venkat

    2012-08-21

    This review summarizes the current data on diabetes risk factors, prevalence, and prevention efforts in Asia and Asian migrant populations. Studies indicate that type 2 diabetes mellitus is a large and growing threat to public health in Asian populations. Furthermore, Asian subgroups (e.g., South Asians/Asian Indians, Chinese) have unique risk factor profiles for developing diabetes, which differ from other populations and between Asian ethnic groups. Lifestyle intervention programs are effective in preventing diabetes in Asians, as with other ethnicities. The strength of these findings is lessened by the lack of systematically collected data using objective measurements. Large epidemiologic studies of diabetes prevalence and risk factor profiles and translational trials identifying sustainable and culturally acceptable lifestyle programs for Asian subgroups are needed. PMID:22524185

  14. 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

  15. Disparity in preoperative patient factors between insurance types in total joint arthroplasty.

    PubMed

    Martin, Christopher T; Callaghan, John J; Liu, Steve S; Gao, Yubo; Johnston, Richard C

    2012-12-01

    Equity in health care has become a focal point of debate. However, the disparity between insurance payer types in total joint arthroplasty is poorly defined. The authors identified 1312 consecutive patients who underwent elective primary total hip or knee arthroplasty with available preoperative Short Form 36 and Western Ontario and McMaster University Osteoarthritis Index surveys and stratified them into groups based on insurance type (Iowa Care [a state-run insurance program for patients who are indigent], Medicare, Medicaid, or private insurance) to compare demographics, access to care, and functional data. Significance was a P value less than .05 after a Turkey-Kramer adjustment for multiple comparisons. A multivariate analysis identified independent predictors of Short Form 36 and Western Ontario and McMaster University Osteoarthritis Index preoperative functional status. Few differences existed between patients with Iowa Care and Medicaid, but both groups had significantly lower Short Form 36 and Western Ontario and McMaster University Osteoarthritis Index scores across every category compared with patients with Medicare or private insurance (P<.05 for each comparison). In addition, patients with Iowa Care and Medicaid had a higher incidence of current smoking and higher mean body mass index and traveled an average of 29 to 30 miles farther for access to care (P<.05 for each comparison). Payer type was an independent predictor of preoperative Short Form 36 and Western Ontario and McMaster University Osteoarthritis Index functional scores in the multivariate analysis (P<.02). Significant differences exist between payer types in total joint arthroplasty. Further research is necessary to better inform health policy decisions. PMID:23218639

  16. Borna disease virus nucleoprotein inhibits type I interferon induction through the interferon regulatory factor 7 pathway.

    PubMed

    Song, Wuqi; Kao, Wenping; Zhai, Aixia; Qian, Jun; Li, Yujun; Zhang, Qingmeng; Zhao, Hong; Hu, Yunlong; Li, Hui; Zhang, Fengmin

    2013-09-01

    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. PMID:23939047

  17. Comparison of virulence factors and capsular types of Streptococcus agalactiae isolated from human and bovine infections.

    PubMed

    Emaneini, Mohammad; Khoramian, Babak; Jabalameli, Fereshteh; Abani, Samira; Dabiri, Hossein; Beigverdi, Reza

    2016-02-01

    Streptococcus agalactiae is a leading cause of human and bovine infections. A total of 194 S. agalactiae isolates, 55 isolates from bovines and 139 from humans, were analyzed for capsular types, virulence genes (scpB, hly, rib, bca and bac) and mobile genetic elements (IS1548 and GBSi1) using polymerase chain reaction (PCR) and multiplex PCR. Capsular type III was predominant (61%), followed by types V, II, Ib, and IV. The scpB, hly, bca and bac virulence genes were only found among human isolates. Twelve and 2 distinct virulence gene profiles were identified among human and bovine isolates respectively. The virulence gene profiles scpB- hly- IS1548- rib-bca (51%) and scpB- hly- IS1548- bca (19%) were only predominant among human isolates. The rib gene was the most common virulence gene in both human and bovine isolates. The study showed a high prevalence of virulence genes in S. agalactiae strains isolated from human infections, these result can support the idea that S. agalactiae isolated from humans and bovines are generally unrelated and probably belonged to separate populations. PMID:26593104

  18. Borna disease virus nucleoprotein inhibits type I interferon induction through the interferon regulatory factor 7 pathway

    SciTech Connect

    Song, Wuqi; Department of Microbiology, Harbin Medical University ; Kao, Wenping; Department of Microbiology, Harbin Medical University ; Zhai, Aixia; Qian, Jun; Li, Yujun; Zhang, Qingmeng; Zhao, Hong; Hu, Yunlong; Li, Hui; Zhang, Fengmin; The Key Laboratory of Pathogenic Biology, Heilongjiang Higher Education Institutions; Department of Microbiology, Harbin Medical University

    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.

  19. The transcription factor GATA3 is essential for the function of human type 2 innate lymphoid cells.

    PubMed

    Mjsberg, Jenny; Bernink, Jochem; Golebski, Korneliusz; Karrich, Julien J; Peters, Charlotte P; Blom, Bianca; te Velde, Anje A; Fokkens, Wytske J; van Drunen, Cornelis M; Spits, Hergen

    2012-10-19

    Type 2 innate lymphoid cells (ILC2s) are part of a large family of ILCs that are important effectors in innate immunity, lymphoid organogenesis, and tissue remodeling. ILC2s mediate parasite expulsion but also contribute to airway inflammation, emphasizing the functional similarity between these cells and Th2 cells. Consistent with this, we report that the transcription factor GATA3 was highly expressed by human ILC2s. CRTH2(+) ILC2s were enriched in nasal polyps of patients with chronic rhinosinusitis, a typical type 2-mediated disease. Nasal polyp epithelial cells expressed TSLP, which enhanced STAT5 activation, GATA3 expression, and type 2 cytokine production in ILC2s. Ectopic expression of GATA3 in Lin(-)CD127(+)CRTH2(-) cells resulted in induction of CRTH2 and the capacity to produce high amounts of type 2 cytokines in response to TSLP plus IL-33. Hence, we identify GATA3, potently regulated by TSLP, as an essential transcription factor for the function of human ILC2s. PMID:23063330

  20. The Effects of 12 Weeks Regular Aerobic Exercise on Brain-derived Neurotrophic Factor and Inflammatory Factors in Juvenile Obesity and Type 2 Diabetes Mellitus

    PubMed Central

    Lee, Sung Soo; Yoo, Jae Ho; Kang, Sung; Woo, Jin Hee; Shin, Ki Ok; Kim, Kwi Beak; Cho, Su Youn; Roh, Hee Tae; Kim, Young Il

    2014-01-01

    [Purpose] The purpose of this study was to investigate the effects of 12 weeks regular aerobic exercise on brain-derived neurotrophic factor (BDNF) and inflammatory factors in juvenile obesity and type 2 diabetes mellitus (T2DM). Obesity and T2DM, typically common among adults, have recently become more prevalent in the Korean juvenile population, affecting not only their lipid profiles and oxidant stress levels, but also their BDNF and inflammatory factor levels. [Subjects] This study enrolled 26 juveniles (boys = 15, girls = 9) who were assigned to a control group (CG, n = 11), obesity group (OG, n = 8), or T2DM group (TG, n = 7). [Methods] The outcome of a 4060-minute aerobic exercise session that took place three times per week for 12 weeks at a maximum oxygen intake (VO2max) of 50~60% was investigated. [Results] The exercise resulted in a significant reduction in the resting serum BDNF and TrkB levels (baseline) among juveniles in the OG and TG as compared to those in the CG. Additionally, the 12 weeks of regular aerobic exercise led to significant reductions in body weight, body fat percentage, and body mass index in the OG and a significant increase of VO2max in the OG and TG. However, no significant differences in serum NGF or inflammatory factors were found among the three groups. There was a significant increase in resting serum BDNF levels following the 12 weeks regular exercise only in the OG. [Conclusion] While 12 weeks of regular aerobic exercise had a positive effect on body composition, and increased BDNF levels of juveniles in the OG, it did not affect the inflammatory factor levels and had no effect on the TG. PMID:25202180

  1. Contribution of modifiable risk factors to social inequalities in type 2 diabetes: prospective Whitehall II cohort study

    PubMed Central

    2012-01-01

    Objective To assess the contribution of modifiable risk factors to social inequalities in the incidence of type 2 diabetes when these factors are measured at study baseline or repeatedly over follow-up and when long term exposure is accounted for. Design Prospective cohort study with risk factors (health behaviours (smoking, alcohol consumption, diet, and physical activity), body mass index, and biological risk markers (systolic blood pressure, triglycerides and high density lipoprotein cholesterol)) measured four times and diabetes status assessed seven times between 1991-93 and 2007-09. Setting Civil service departments in London (Whitehall II study). Participants 7237 adults without diabetes (mean age 49.4 years; 2196 women). Main outcome measures Incidence of type 2 diabetes and contribution of risk factors to its association with socioeconomic status. Results Over a mean follow-up of 14.2 years, 818 incident cases of diabetes were identified. Participants in the lowest occupational category had a 1.86-fold (hazard ratio 1.86, 95% confidence interval 1.48 to 2.32) greater risk of developing diabetes relative to those in the highest occupational category. Health behaviours and body mass index explained 33% (?1% to 78%) of this socioeconomic differential when risk factors were assessed at study baseline (attenuation of hazard ratio from 1.86 to 1.51), 36% (22% to 66%) when they were assessed repeatedly over the follow-up (attenuated hazard ratio 1.48), and 45% (28% to 75%) when long term exposure over the follow-up was accounted for (attenuated hazard ratio 1.41). With additional adjustment for biological risk markers, a total of 53% (29% to 88%) of the socioeconomic differential was explained (attenuated hazard ratio 1.35, 1.05 to 1.72). Conclusions Modifiable risk factors such as health behaviours and obesity, when measured repeatedly over time, explain almost half of the social inequalities in incidence of type 2 diabetes. This is more than was seen in previous studies based on single measurement of risk factors. PMID:22915665

  2. 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

  3. Cardiovascular risk factors in Assyrians/Syrians and native Swedes with type 2 diabetes: a population-based epidemiological study

    PubMed Central

    2009-01-01

    Background A large number of people throughout the world have diabetes and the prevalence is increasing. Persons with diabetes have a twice higher risk of cardiovascular disease than those without diabetes. There is a lack of studies focusing on cardiovascular risk factors in Assyrians/Syrians with type 2 diabetes. The aim of this study is to estimate the prevalence of some cardiovascular risk factors among Assyrians/Syrians and na