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PubMed | Brown University, Wayne State University, University of Cincinnati, University of Texas Medical Branch and 10 more.
Type: Journal Article | Journal: American journal of perinatology | Year: 2016

ObjectiveThe objective of this study was to examine whether there is an association between insulin resistance and subsequent development of puerperal infection by measuring insulin resistance in the mid-trimester using the homeostasis model assessment (HOMA:IR). MethodsSecondary analysis of low-risk nulliparas enrolled in a multicenter preeclampsia prevention trial. HOMA:IR was measured on fasting plasma glucose and insulin concentrations among low-risk nulliparas between 22 and 26 weeks gestation. Median HOMA:IR was compared between women who did and did not develop puerperal infection using Wilcoxon rank sum test. Logistic regression was used to control for potential confounders. ResultsOf 1,180 women with fasting glucose and insulin available, 121 (10.3%) had a puerperal infection. Median HOMA:IR was higher among those with subsequent puerperal infection (4.3 [interquartile, IQR: 2.2-20.5] vs. 2.6 [IQR: 1.5-6.7], p<0.0001). After controlling for potentially confounding variables HOMA:IR was only marginally associated with an increased risk of development of puerperal infection, adjusted odds ratio: 1.01 (95% confidence interval: 1.00-1.02; p=0.04) per unit increase. Elevated HOMA:IR performed poorly as a predictor of puerperal infection, with a positive predictive value of 15% and a negative predictive value of 92%. ConclusionThough associated with an increased risk of puerperal infection, insulin resistance, measured by HOMA:IR, is not a clinically useful predictor of puerperal infection.


PubMed | New York University, University of California at Los Angeles, Georgetown University, The Eunice Kennedy Shriver National Institute of Child Health and Human Development and 4 more.
Type: Journal Article | Journal: The Journal of infectious diseases | Year: 2015

Human immunodeficiency virus (HIV) infectivity increases as receptor/coreceptor expression levels increase. We determined peripheral CD4, CCR5, and CXCR4 expression levels in HIV-uninfected women who used depot medroxyprogesterone acetate (DMPA; n = 32), the levonorgestrel-releasing intrauterine device (LNG-IUD; n = 27), oral contraceptive pills (n = 32), or no hormonal contraception (n = 33). The use of LNG-IUD increased the proportion of CD4(+) and CD8(+) T cells that expressed CCR5; increases in the magnitude of T-cell subset CCR5 expression were observed with DMPA and LNG-IUD use (P < .01 for all comparisons). LNG-IUD and, to a lesser extent, DMPA use were associated with increased peripheral T-cell CCR5 expression.


PubMed | University of Cincinnati, University of Texas Medical Branch, The Eunice Kennedy Shriver National Institute of Child Health and Human Development, University of Alabama at Birmingham and 3 more.
Type: Journal Article | Journal: American journal of perinatology | Year: 2016

ObjectiveIn nonpregnant populations the waist-to-hip ratio (WHR) is a better predictor of obesity-related outcomes than body mass index (BMI). Our objective was to determine, in pregnancy, the relationship between these measures of obesity, and large-for-gestational age (LGA) and cesarean delivery (CD). MethodsThis is a secondary analysis of data from the Combined Antioxidant and Preeclampsia Prediction Study. Women with a WHR of0.85 and 0.80 to 0.84 at 9 to 16 weeks gestation were compared with those with a WHR<0.80. Women with early pregnancy BMI30.0 kg/m(2) (obese) and 25.0 to 29.9 kg/m(2) (overweight) were compared with those<25.0 kg/m(2). LGA was defined as>90% by Alexander nomogram. Univariable analysis, logistic regression, and receiver operating characteristic curves were used. ResultsData from 2,276 women were analyzed. After correcting for potential confounders, only BMI30 was significantly associated with LGA (adjusted odds ratio [aOR]: 2.07, 1.35-3.16) while BMI 25.0-29.9 (aOR: 1.5, 0.98-2.28), WHR 0.8-0.84 (aOR: 1.33, 0.83-2.13), and WHR0.85 (aOR: 1.05, 0.67-1.65) were not. Risk for CD was increased for women with elevated WHR and with higher BMI compared with normal. ConclusionWHR is not associated with LGA. While BMI performed better than WHR, neither was a strong predictor of LGA or need for CD in low-risk nulliparous women.


PubMed | University of Pittsburgh, Thomas Jefferson University, University of Miami, Wayne State University and 12 more.
Type: Journal Article | Journal: American journal of perinatology | Year: 2015

This study aims to evaluate whether magnesium sulfate administration for neuroprotection prolongs latency in women with preterm premature rupture of membranes (PPROM) between 24 and 31(6/7) weeks gestation.This is a secondary analysis of a randomized controlled trial of magnesium sulfate for prevention of cerebral palsy. Gravid women with a singleton pregnancy between 24 and 31(6/7) weeks gestation with PPROM without evidence of labor were randomized to receive magnesium sulfate, administered intravenously as a 6-g bolus followed by a constant infusion of 2 g per hour up to 12 hours, or placebo. Maternal outcomes for this analysis were delivery in less than 48 hours and in less than 7 days from randomization. Neonatal outcomes included a composite of respiratory distress syndrome, interventricular hemorrhage grades 3 or 4, periventricular leukomalacia, sepsis, necrotizing enterocolitis, retinopathy of prematurity, or death.A total of 1,259 women were included. The rate of delivery < 48 hours was not different in the magnesium sulfate and the placebo groups (22.2 and 20.7%, p = 0.51). Delivery < 7 days was similar between groups (55.4 and 51.4%, p = 0.16). Median latency was also similar between groups (median [interquartile range], 6.0 days [range, 2.4-13.8 days] and 6.6 days [range, 2.4-15.1 days], p = 0.29). Composite neonatal outcomes did not differ between groups.Magnesium sulfate administration given for neuroprotection in women with a singleton gestation with PPROM and without labor before 32 weeks does not impact latency.


PubMed | Health-U, National Center for Complementary and Integrative Health, The Eunice Kennedy Shriver National Institute of Child Health and Human Development and U.S. Department of Agriculture
Type: Journal Article | Journal: The Journal of nutrition | Year: 2015

Homo sapiens harbor trillions of microbes, whose microbial metagenome (collective genome of a microbial community) using omic validation interrogation tools is estimated to be at least 100-fold that of human cells, which comprise 23,000 genes. This article highlights some of the current progress and open questions in nutrition-related areas of microbiome research. It also underscores the metabolic capabilities of microbial fermentation on nutritional substrates that require further mechanistic understanding and systems biology approaches of studying functional interactions between diet composition, gut microbiota, and host metabolism. Questions surrounding bacterial fermentation and degradation of dietary constituents (particularly by Firmicutes and Bacteroidetes) and deciphering how microbial encoding of enzymes and derived metabolites affect recovery of dietary energy by the host are more complex than previously thought. Moreover, it is essential to understand to what extent the intestinal microbiota is subject to dietary control and to integrate these data with functional metabolic signatures and biomarkers. Many lines of research have demonstrated the significant role of the gut microbiota in human physiology and disease. Probiotic and prebiotic products are proliferating in the market in response to consumer demand, and the science and technology around these products are progressing rapidly. With high-throughput molecular technologies driving the science, studying the bidirectional interactions of host-microbial cometabolism, epithelial cell maturation, shaping of innate immune development, normal vs. dysfunctional nutrient absorption and processing, and the complex signaling pathways involved is now possible. Substantiating the safety and mechanisms of action of probiotic/prebiotic formulations is critical. Beneficial modulation of the human microbiota by using these nutritional and biotherapeutic strategies holds considerable promise as next-generation drugs, vaccinomics, and metabolic agents and in novel food discovery.


Morissette R.,U.S. National Institute on Aging | Morissette R.,U.S. National Institutes of Health | Merke D.P.,U.S. National Institutes of Health | Merke D.P.,The Eunice Kennedy Shriver National Institute of Child Health and Human Development | McDonnell N.B.,U.S. National Institute on Aging
European Journal of Medical Genetics | Year: 2014

Patients with congenital adrenal hyperplasia (CAH) with tenascin-X deficiency (CAH-X syndrome) have both endocrine imbalances and characteristic Ehlers Danlos syndrome phenotypes. Unlike other subtypes, tenascin-X-related Ehlers Danlos syndrome is caused by an extracellular matrix protein deficiency rather than a defect in fibrillar collagen or a collagen-modifying enzyme, and the understanding of the disease mechanisms is limited. We hypothesized that transforming growth factor-β pathway dysregulation may, in part, be responsible for connective tissue phenotypes observed in CAH-X, due to this pathway's known role in connective tissue disorders.Fibroblasts and direct tissue from human skin biopsies from CAH-X probands and age- and sex-matched controls were screened for transforming growth factor-β biomarkers known to be dysregulated in other hereditary disorders of connective tissue. In CAH-X fibroblast lines and dermal tissue, pSmad1/5/8 was significantly upregulated compared to controls, suggesting involvement of the bone morphogenetic protein pathway. Additionally, CAH-X samples compared to controls exhibited significant increases in fibroblast-secreted TGF-β3, a cytokine important in secondary palatal development, and in plasma TGF-β2, a cytokine involved in cardiac function and development, as well as palatogenesis. Finally, MMP-13, a matrix metalloproteinase important in secondary palate formation and tissue remodeling, had significantly increased mRNA and protein expression in CAH-X fibroblasts and direct tissue.Collectively, these results demonstrate that patients with CAH-X syndrome exhibit increased expression of several transforming growth factor-β biomarkers and provide a novel link between this signaling pathway and the connective tissue dysplasia phenotypes associated with tenascin-X deficiency. © 2013.


Duffy L.C.,National Center for Complementary and Integrative Health | Raiten D.J.,The Eunice Kennedy Shriver National Institute of Child Health and Human Development | Hubbard V.S.,U.S. National Institutes of Health | Hubbard V.S.,U.S. National Institute of Diabetes and Digestive and Kidney Diseases | And 2 more authors.
Journal of Nutrition | Year: 2015

Homo sapiens harbor trillions of microbes, whose microbial metagenome (collective genome of a microbial community) using omic validation interrogation tools is estimated to be at least 100-fold that of human cells, which comprise 23,000 genes. This article highlights some of the current progress and open questions in nutrition-related areas of microbiome research. It also underscores the metabolic capabilities of microbial fermentation on nutritional substrates that require further mechanistic understanding and systems biology approaches of studying functional interactions between diet composition, gut microbiota, and host metabolism. Questions surrounding bacterial fermentation and degradation of dietary constituents (particularly by Firmicutes and Bacteroidetes) and deciphering howmicrobial encoding of enzymes and derived metabolites affect recovery of dietary energy by the host are more complex than previously thought. Moreover, it is essential to understand to what extent the intestinal microbiota is subject to dietary control and to integrate these data with functional metabolic signatures and biomarkers. Many lines of research have demonstrated the significant role of the gut microbiota in human physiology and disease. Probiotic and prebiotic products are proliferating in themarket in response to consumer demand, and the science and technology around these products are progressing rapidly. With high-throughput molecular technologies driving the science, studying the bidirectional interactions of host-microbial cometabolism, epithelial cell maturation, shaping of innate immune development, normal vs. dysfunctional nutrient absorption and processing, and the complex signaling pathways involved is now possible. Substantiating the safety and mechanisms of action of probiotic/prebiotic formulations is critical. Beneficial modulation of the human microbiota by using these nutritional and biotherapeutic strategies holds considerable promise as next-generation drugs, vaccinomics, and metabolic agents and in novel food discovery. © 2015 American Society for Nutrition.


PubMed | The Eunice Kennedy Shriver National Institute of Child Health and Human Development and Ra Pharmaceuticals
Type: | Journal: RNA biology | Year: 2016

In vitro studies of translation provide critical mechanistic details, yet purification of large amounts of highly active eukaryotic ribosomes remains a challenge for biochemists and structural biologists. Here, we present an optimized method for preparation of highly active yeast ribosomes that could easily be adapted for purification of ribosomes from other species. The use of a nitrogen mill for cell lysis coupled with chromatographic purification of the ribosomes results in 10-fold-increased yield and less variability compared with the traditional approach, which relies on sedimentation through sucrose cushions. We demonstrate that these ribosomes are equivalent to those made using the traditional method in a host of in vitro assays, and that utilization of this new method will consistently produce high yields of active yeast ribosomes.


Fields R.D.,The Eunice Kennedy Shriver National Institute of Child Health and Human Development | Woo D.H.,The Eunice Kennedy Shriver National Institute of Child Health and Human Development | Basser P.J.,U.S. National Institutes of Health
Neuron | Year: 2015

If "the connectome" represents a complete map of anatomical and functional connectivity in the brain, it should also include glia. Glia define and regulate both the brain's anatomical and functional connectivity over a broad range of length scales, spanning the whole brain to subcellular domains of synaptic interactions. This Perspective article examines glial interactions with the neuronal connectome (including long-range networks, local circuits, and individual synaptic connections) and highlights opportunities for future research. Our understanding of the structure and function of the neuronal connectome would be incomplete without an understanding of how all types of glia contribute to neuronal connectivity and function, from single synapses to circuits. © 2015 Elsevier Inc.

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