652 research outputs found

    Maternal and Newborn Polymorphisms in Phase I/II Metabolic Genes Contribute to Risk of Adverse Reproductive Outcomes

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    Maternal cigarette smoke exposure during pregnancy has been identified as a risk factor for adverse reproductive outcomes, a major public health concern. However, little is known about genetic susceptibility and possible interactions with environmental factors to increase risk of these events. This study was designed to investigate relative contributions of genetic and maternal environmental risk factor interactions to adverse reproductive outcomes. Maternal peripheral and umbilical cord blood samples from 1148 healthy mother/newborn pairs were genotyped for a panel of polymorphisms associated with the metabolic enzymes CYP1A1, CYP2E1, GSTM1, GSTT1 and NAT2* for several subgroups; low birthweight (<2500g, n=86), preterm delivery (<37th gestational week, n=93), premature birth (<2500g & <37th gestational week, n=53) and small for gestational age (SGA) at term („d37th gestational week, n=948) in comparison to the average for gestational age (AGA) group (n=948). Maternal cigarette smoking during the last trimester was significantly associated with birthweight reduction (ƒÝ=101.4g, SE=32, p=0.002). Maternal GSTT1 null genotype was significantly associated with low birthweight (OR=1.97, 95% CI: 1.24-3.12, p=0.004), preterm delivery (OR=1.91, 95% CI: 1.22-2.98, p=0.004) and premature birth (OR=2.42, 95% CI: 1.38-4.26, p=0.002). The mean reduction of birthweight observed among the maternal GSTT1 null genotype group was 89.6g (SE=37, p=0.018) and the mean reduction in gestational age was 0.25 weeks (SE=0.1, p=0.049). In addition, African American women were more likely to have a smaller baby; the mean reduction of birthweight was 230g (SE=34.5, p<0.001) compared with Caucasians. An additive interaction between smoking, African American ethnicity and GSTT1 null genotype was observed (OR=7.81, 95% CI: 2.49-24.43, p<0.001). The mean birthweight reduction observed in this group was 570.0g (SE=117, p<0.001) and the mean gestational age reduction was 1.10 weeks (SE=0.4, p=0.007). A similar risk was observed for newborn GSTT1 null genotype in the presence of maternal smoking (426.7g,SE=111, p<0.001) and (1.0 weeks, SE=0.4, p=0.012). These results demonstrated a clear overrepresentation of maternal and newborn GSTT1 null genotype among adverse reproductive outcome cases. Furthermore, a gene-gene-environment interaction was observed where the combination of maternal and newborn GSTT1 null genotype in the presence of maternal cigarette smoke during pregnancy significantly increased risk of adverse reproductive outcomes

    Glomerular expression profiling and novel proteins in normal mouse kidney and adriamycin-induced nephrosis

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    Kidney glomeruli function as high-capacity molecular sieves through which plasma is filtered into the Bowman s space as primary urine. The glomerular filtration barrier is composed of glomerular endothelial cells, the glomerulus basement membrane and the podocyte cell layer. Dysfunction of the glomerulus is a central component of renal complications leading to end-stage renal disease. However, the molecular composition of the glomerulus and how it changes during disease are still mostly unknown. To elucidate the picture of molecules involved in the biology and pathology of the glomerulus, large-scale approaches including two-dimensional gel electrophoresis (2-DE) coupled with mass spectrometry analysis and microarray profiling were applied to normal and diseased glomeruli. A proteome analysis of healthy glomeruli in mouse was performed using 2-DE with two different staining methods and subsequent mass spectrometric identifications. Altogether, 414 protein spots were identified, revealing 232 different proteins representing a wide spectrum of activities. Only 53 of the proteins identified here were detected in another proteome study, showing the value of analysis utilizing different methodologies. 80 of the proteins were not identified in a separate transcriptome analysis, while ten of the present proteins were identified as genes implicated in glomerulus development and function, allowing direct correlation with expression data. Characterization of five glomerulus-upregulated transcripts/proteins, ehd3, dendrin, sh2d4a, plekhh2, and 2310066E14Rik was performed. The expression pattern of these novel glomerular transcripts in various mouse tissues was studied, and the distribution of corresponding proteins was examined. All five transcripts/proteins were expressed in the kidney exclusively by glomerular cells. Ehd3 was expressed only by glomerular endothelial cells. Importantly, ehd3 is the first gene ever shown to be expressed exclusively by glomerular endothelial cells and not by other endothelial cells in the kidney. Dendrin, sh2d4a, plekhh2, and 2310066E14Rik were transcribed specifically in podocytes within the glomerulus. With the use of polyclonal antibodies, dendrin, sh2d4a, and plekhh2 proteins were localized to the slit diaphragm and the foot process, whereas 2310066E14Rik protein was localized to the podocyte major processes and cell body. Comparison of the normal glomerular transcriptome with its changes during progression of glomerular disease can yield information about molecular pathomechanisms. The adriamycin (ADR)-induced proteinuric mouse model allows the precise timing of the onset of proteinuria and of morphological changes in glomerulus. Overt proteinuria was observed from four days after ADR injection, and reached maximum at seven days. Blood urea nitrogen (BUN) gradually elevated indicating the failure of renal function. TUNEL staining of kidney section revealed an increase in apoptotic positive cells in glomeruli. Transcriptional profiling of kidney glomeruli revealed that nine p53 target genes were up-regulated probably due to DNA damage caused by ADR at four days and several glomerular enriched genes were differentially expressed indicating glomerular injury at seven days. These studies provide fresh insights into glomerular biology and reveal new possibilities to explore the role of glomerular specific proteins in renal physiology and pathophysiology. Furthermore, these studies shed light on the pathomechanisms of proteinuria, which eventually results in end-stage kidney disease as a result of progressive glomerular damage

    Assessing Community Health Center (CHC) Assets and Capabilities for Recruiting and Retaining Physicians: The CHC Community Apgar Questionnaire

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    Community factors play a key role in the recruitment and retention of physicians. While prior workforce studies often investigated characteristics of the candidate-physician, the initial Critical Access Hospital Community Apgar Questionnaire (CAH CAQ) study identified community factors at critical access hospitals which help determine the success of achieving and maintaining an adequate local physician workforce. The goals of the current study are to identify opportunities for improvement in physician retention and recruitment in Idaho’s Community Health Center (CHC) systems and to develop a better understanding of the community factors in this dynamic process

    Alloying Effect of Nickel–Cobalt Based Binary Metal Catalysts Supported on α-Alumina for Ammonia Decomposition

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    The development of a base metal catalyst which shows high performance for the ammonia (NH3) decomposition have been conducted. For the Ni and Co based catalysts using α-Al2O3 as a support, the performance of the single metal catalysts was lower than that of the γ-Al2O3 supported catalysts. However, its performance was greatly improved by using a binary metal catalyst system. Based on the XRD analysis, it was found that Ni and Co supported on α-Al2O3 were alloyed. TEM observation confirmed that the metal particle size in the α-Al2O3 supported Ni-Co catalyst is smaller than that of the single metal catalysts (Ni/α-Al2O3 or Co/α-Al2O3). Furthermore, in-situ XRD and H2-TPR measurements revealed that the Ni-Co alloy forms during the reduction process. The optimum mixing ratio of Ni and Co components was 1:1, and the optimum pre-reduction temperature before the performance test was 600 °C. Studies on the differences of support oxides proved that the improvement effect by alloying can be similarly obtained with the SiO2 supported catalyst, indicating that the catalyst using the support with less interaction between the active metal and the support is more likely to obtain the performance improvement effect by alloying

    Rural Idaho Family Physicians’ Scope of Practice

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    Context: Scope of practice is an important factor in both training and recruiting rural family physicians. Purpose: To assess rural Idaho family physicians’ scope of practice and to examine variations in scope of practice across variables such as gender, age and employment status. Methods: A survey instrument was developed based on a literature review and was validated by physician educators, practicing family physicians and executives at the state hospital association. This survey was mailed to rural family physicians practicing in Idaho counties with populations of less than 50,000. Descriptive, bivariate and multivariate analyses were employed to describe and compare scope of practice patterns. Results: Responses were obtained from 92 of 248 physicians (37.1% response rate). Idaho rural family physicians reported providing obstetrical services in the areas of prenatal care (57.6%), vaginal delivery (52.2%) and C-sections (37.0%) and other operating room services (43.5%), esophagogastroduodenoscopy (EGD) or colonoscopy services (22.5%), emergency room coverage (48.9%), inpatient admissions (88.9%), mental health services (90.1%), nursing home services (88.0%), and supervision to midlevel care providers (72.5%). Bivariate analyses showed differences in scope of practice patterns across gender, age group and employment status. Binomial logistic regression models indicated that younger physicians were roughly three times more likely to provide prenatal care and perform vaginal deliveries than older physicians in rural areas. Conclusion: Idaho practicing rural family physicians report a broad scope of practice. Younger, employed and female rural family medicine physicians are important subgroups for further study

    4-Chloro-7-hydr­oxy-6-methyl-1,7-naphthyridin-8(7H)-one

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    The title compound, C9H7ClN2O2, was prepared by reaction of methyl 4-chloro-3-(prop-1-yn­yl)picolinate with hydroxy­l­amine in MeOH/KOH solution. The two essentially planar mol­ecules which make up the asymmetric unit have almost identical geometries and and are linked into dimeric aggregates via pairs of O—H⋯O hydrogen bonds. These aggregates have almost perfect inversion symmetry; however, quite unusually, the inversion center of the dimer does not coincide with the crystallographic inversion center

    Sulfonylurea-resistant biotypes of Monochoria vaginalis generate higher ultraweak photon emissions than the susceptible ones

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    All living organisms spontaneously generate ultraweak photon emissions, which originate from biochemical reactions in cells. Current research uses the ultraweak photon emission from organisms as a novel indicator in nondestructive analyses of an organisms living state. This study indicates that ultraweak photon emissions from Monochoria vaginalis are different between resistant biotypes (R) to sulfonylurea (SU) and susceptible biotypes (S). In SU-R biotypes, distinct increases in photon emissions were observed, but there was little increase in SU-S biotypes. In addition, photon emissions from the resistant biotypes of M. vaginalis were suppressed by treatment with P450 inhibitors. This suggests that cytochrome P450 monooxygenase, which plays a crucial role in the metabolic detoxification of SUs, could be associated with the generation of ultraweak photon emissions. Ultraweak photon emissions have a potential use in a novel diagnosis system as an indicator in a nondestructive testing of weeds resistant to SUs
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