Mostrando recursos 1 - 20 de 9.794

  1. Adverse obstetric outcomes during delivery hospitalizations complicated by suicidal behavior among US pregnant women

    Zhong, Qiu-Yue; Gelaye, Bizu; Smoller, Jordan W.; Avillach, Paul; Cai, Tianxi; Williams, Michelle A.
    Objective: The effects of suicidal behavior on obstetric outcomes remain dangerously unquantified. We sought to report on the risk of adverse obstetric outcomes for US women with suicidal behavior at the time of delivery. Methods: We performed a cross-sectional analysis of delivery hospitalizations from 2007–2012 National (Nationwide) Inpatient Sample. From the same hospitalization record, International Classification of Diseases codes were used to identify suicidal behavior and adverse obstetric outcomes. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were obtained using logistic regression. Results: Of the 23,507,597 delivery hospitalizations, 2,180 were complicated by suicidal behavior. Women with suicidal behavior were...

  2. Personal Care Product Use in Men and Urinary Concentrations of Select Phthalate Metabolites and Parabens: Results from the Environment And Reproductive Health (EARTH) Study

    Nassan, Feiby L.; Coull, Brent A.; Gaskins, Audrey J.; Williams, Michelle A.; Skakkebaek, Niels E.; Ford, Jennifer B.; Ye, Xiaoyun; Calafat, Antonia M.; Braun, Joseph M.; Hauser, Russ
    Background: Personal care products (PCPs) are exposure sources to phthalates and parabens; however, their contribution to men’s exposure is understudied. Objectives: We examined the association between PCP use and urinary concentrations of phthalate metabolites and parabens in men. Methods: In a prospective cohort, at multiple study visits, men self-reported their use of 14 PCPs and provided a urine sample (2004–2015, Boston, MA). We measured urinary concentrations of 9 phthalate metabolites and methylparaben, propylparaben, and butylparaben. We estimated the covariate-adjusted percent change in urinary concentrations associated with PCP use using linear mixed and Tobit mixed regressions. We also estimated weights for...


    Carter, R. Colin; Kupka, Roland; Manji, Karim; McDonald, Christine M.; Aboud, Said; Erhardt, Juergen G.; Gosselin, Kerri; Kisenge, Rodrick; Liu, Enju; Fawzi, Wafaie; Duggan, Christopher
    BACKGROUND Zinc supplementation adversely affects iron status in animal and adult human studies but few, trials have included young infants. OBJECTIVE To determine the effects of zinc and multivitamin supplementation on infant hematologic and iron status. METHODS In a double-blind RCT, Tanzanian infants were randomized to daily, oral zinc (Zn), multivitamins (MV), Zn and MV, or placebo treatment arms at age 6 wk. Hemoglobin concentration (Hb) and red blood cell indices were measured at baseline and at 6, 12, and 18 mo of age. Plasma samples from 589 infants were examined for iron deficiency (ID) at 6 mo. RESULTS In...

  4. Does early vitamin B12 supplementation improve neurodevelopment and cognitive function in childhood and into school age: a study protocol for extended follow-ups from randomised controlled trials in India and Tanzania

    Winje, Brita Askeland; Kvestad, Ingrid; Krishnamachari, Srinivasan; Manji, Karim; Taneja, Sunita; Bellinger, David C; Bhandari, Nita; Bisht, Shruti; Darling, Anne Marie; Duggan, Christopher P; Fawzi, Wafaie; Hysing, Mari; Kumar, Tivendra; Kurpad, Anura V; Sudfeld, Christopher R; Svensen, Erling; Thomas, Susan; Strand, Tor A
    Introduction: As many as 250 million children under the age of 5 may not be reaching their full developmental potential partly due to poor nutrition during pregnancy and the first 2 years of life. Micronutrients, including vitamin B12, are important for the development of brain structure and function; however, the timing, duration and severity of deficiencies may alter the impact on functional development outcomes. Consequently, to fully explore the effect of vitamin B12 on cognitive function, it is crucial to measure neurodevelopment at different ages, in different populations and with vitamin B12 supplementation at different times during the critical periods...

  5. Change in alcohol intake in relation to weight change in a cohort of United States men with 24 years of follow-up

    Downer, Mary Kathryn; Bertoia, Monica L; Mukamal, Ken J; Rimm, Eric B; Stampfer, Meir J
    Objective: We sought to prospectively investigate potential effects of alcohol by subtype on reported long-term weight change. Methods: We examined change in alcohol intake (total, wine, light beer, regular beer, liquor) and simultaneous change in reported body weight within four-year periods from 1986 to 2010 from U.S. men in the Health Professionals Follow-Up Study. We adjusted for age, change in lifestyle and dietary covariates and cardiovascular risk factors. Results: We observed 44,603 four-year periods from 14,971 men. Total alcohol, total beer, regular beer, and liquor, modeled as the increase in weight per increase in drink/day, were each directly associated with...

  6. Calcium-Dependent Protein Kinase 5 Is Required for Release of Egress-Specific Organelles in Plasmodium falciparum

    Absalon, Sabrina; Blomqvist, Karin; Rudlaff, Rachel M.; DeLano, Travis J.; Pollastri, Michael P.; Dvorin, Jeffrey D.
    ABSTRACT The human malaria parasite Plasmodium falciparum requires efficient egress out of an infected red blood cell for pathogenesis. This egress event is highly coordinated and is mediated by several signaling proteins, including the plant-like P. falciparum calcium-dependent protein kinase 5 (PfCDPK5). Knockdown of PfCDPK5 results in an egress block where parasites are trapped inside their host cells. The mechanism of this PfCDPK5-dependent block, however, remains unknown. Here, we show that PfCDPK5 colocalizes with a specialized set of parasite organelles known as micronemes and is required for their discharge, implicating failure of this step as the cause of the egress...

  7. Serum anti-flagellin and anti-lipopolysaccharide immunoglobulins as predictors of linear growth faltering in Pakistani infants at risk for environmental enteric dysfunction

    Syed, Sana; Iqbal, Najeeha T.; Sadiq, Kamran; Ma, Jennie Z.; Akhund, Tauseef; Xin, Wenjun; Moore, Sean R.; Liu, Enju; Qureshi, Shahida; Gosselin, Kerri; Gewirtz, Andrew; Duggan, Christopher P.; Ali, S. Asad
    Background: Environmental Enteric Dysfunction (EED) in children from low-income countries has been linked to linear growth declines. There is a critical need to identify sensitive and early EED biomarkers. Objective: Determine whether levels of antibodies against bacterial components flagellin (flic) and lipopolysaccharide (LPS) predict poor growth. Design/Methods In a prospective birth cohort of 380 children in rural Pakistan blood and stool samples were obtained at ages 6 and 9 months. Linear mixed effects models were used to examine longitudinal associations between quartiles of anti-flic and anti-LPS antibodies and changes in LAZ, WAZ and WLZ scores. Spearman’s correlations were measured between...

  8. PD-L1 up-regulation restrains Th17 cell differentiation in STAT3 loss- and STAT1 gain-of-function patients

    Zhang, Yuan; Ma, Chi A.; Lawrence, Monica G.; Break, Timothy J.; O’Connell, Michael P.; Lyons, Jonathan J.; López, Diego B.; Barber, John S.; Zhao, Yongge; Barber, Daniel L.; Freeman, Alexandra F.; Holland, Steven M.; Lionakis, Michail S.; Milner, Joshua D.
    Patients with hypomorphic mutations in STAT3 and patients with hypermorphic mutations in STAT1 share several clinical and cellular phenotypes suggesting overlapping pathophysiologic mechanisms. We, therefore, examined cytokine signaling and CD4+ T cell differentiation in these cohorts to characterize common pathways. As expected, differentiation of Th17 cells was impaired in both cohorts. We found that STAT1 was hyperphosphorylated in response to cytokine stimulation in both cohorts and that STAT1-dependent PD-L1 up-regulation—known to inhibit Th17 differentiation in mouse models—was markedly enhanced as well. Overexpression of SOCS3 strongly inhibited phosphorylation of STAT1 and PD-L1 up-regulation, suggesting that diminished SOCS3 expression may lead to...

  9. Assessment of the cPAS-based BGISEQ-500 platform for metagenomic sequencing

    Fang, Chao; Zhong, Huanzi; Lin, Yuxiang; Chen, Bing; Han, Mo; Ren, Huahui; Lu, Haorong; Luber, Jacob M; Xia, Min; Li, Wangsheng; Stein, Shayna; Xu, Xun; Zhang, Wenwei; Drmanac, Radoje; Wang, Jian; Yang, Huanming; Hammarström, Lennart; Kostic, Aleksandar D; Kristiansen, Karsten; Li, Junhua
    Abstract Background: More extensive use of metagenomic shotgun sequencing in microbiome research relies on the development of high-throughput, cost-effective sequencing. Here we present a comprehensive evaluation of the performance of the new high-throughput sequencing platform BGISEQ-500 for metagenomic shotgun sequencing and compare its performance with that of 2 Illumina platforms. Findings: Using fecal samples from 20 healthy individuals, we evaluated the intra-platform reproducibility for metagenomic sequencing on the BGISEQ-500 platform in a setup comprising 8 library replicates and 8 sequencing replicates. Cross-platform consistency was evaluated by comparing 20 pairwise replicates on the BGISEQ-500 platform vs the Illumina HiSeq 2000 platform...

  10. 980Pediatric Patients with Gastrointestinal Conditions and Central Line-Associated Bloodstream Infections

    Klieger, Sarah B.; Raphael, Bram; Potter-Bynoe, Gail; Duggan, Christopher; Sandora, Thomas J.; Zerr, Danielle; Lee, Grace; Cox, Elaine; Coffin, Susan E.

  11. High‐throughput identification of RNA nuclear enrichment sequences

    Shukla, Chinmay J; McCorkindale, Alexandra L; Gerhardinger, Chiara; Korthauer, Keegan D; Cabili, Moran N; Shechner, David M; Irizarry, Rafael A; Maass, Philipp G; Rinn, John L
    Abstract In the post‐genomic era, thousands of putative noncoding regulatory regions have been identified, such as enhancers, promoters, long noncoding RNAs (lncRNAs), and a cadre of small peptides. These ever‐growing catalogs require high‐throughput assays to test their functionality at scale. Massively parallel reporter assays have greatly enhanced the understanding of noncoding DNA elements en masse. Here, we present a massively parallel RNA assay (MPRNA) that can assay 10,000 or more RNA segments for RNA‐based functionality. We applied MPRNA to identify RNA‐based nuclear localization domains harbored in lncRNAs. We examined a pool of 11,969 oligos densely tiling 38 human lncRNAs that...

  12. diffloop: a computational framework for identifying and analyzing differential DNA loops from sequencing data

    Lareau, Caleb A; Aryee, Martin J
    Abstract Summary The 3D architecture of DNA within the nucleus is a key determinant of interactions between genes, regulatory elements, and transcriptional machinery. As a result, differences in DNA looping structure are associated with variation in gene expression and cell state. To systematically assess changes in DNA looping architecture between samples, we introduce diffloop, an R/Bioconductor package that provides a suite of functions for the quality control, statistical testing, annotation, and visualization of DNA loops. We demonstrate this functionality by detecting differences between ENCODE ChIA-PET samples and relate looping to variability in epigenetic state. Availability and implementation Diffloop is implemented...

  13. Effect of Zinc Supplementation on Growth Outcomes in Children under 5 Years of Age

    Liu, Enju; Pimpin, Laura; Shulkin, Masha; Kranz, Sarah; Duggan, Christopher P.; Mozaffarian, Dariush; Fawzi, Wafaie W.
    (1) Background: The effects of zinc supplementation on child growth, and prior reviews of these studies, have shown mixed results. We aim to systematically review and meta-analyze randomized controlled trials evaluating effects of preventive zinc supplementation for 3 months or longer during pregnancy or in children up to age 5 years on pregnancy outcomes and child growth; (2) Methods: We searched PubMed, EMBASE, Cochrane Library, Web of Science, and trial registries for eligible trials up to October 10, 2017. Inclusion selection and data extractions were performed independently and in duplicate. Study quality was evaluated by the Cochrane Risk of Bias...

  14. Exposure to Low Levels of Lead in Utero and Umbilical Cord Blood DNA Methylation in Project Viva: An Epigenome-Wide Association Study

    Wu, Shaowei; Hivert, Marie-France; Cardenas, Andres; Zhong, Jia; Rifas-Shiman, Sheryl L.; Agha, Golareh; Colicino, Elena; Just, Allan C.; Amarasiriwardena, Chitra; Lin, Xihong; Litonjua, Augusto A.; DeMeo, Dawn L.; Gillman, Matthew W.; Wright, Robert O.; Oken, Emily; Baccarelli, Andrea A.
    Background: Early-life exposure to lead is associated with deficits in neurodevelopment and with hematopoietic system toxicity. DNA methylation may be one of the underlying mechanisms for the adverse effects of prenatal lead on the offspring, but epigenome-wide methylation data for low levels of prenatal lead exposure are lacking. Objectives: We investigated the association between prenatal maternal lead exposure and epigenome-wide DNA methylation in umbilical cord blood nucleated cells in Project Viva, a prospective U.S.-based prebirth cohort with relatively low levels of lead exposure. Methods: Among 268 mother–infant pairs, we measured lead concentrations in red blood cells (RBC) from prenatal maternal...

  15. Estimated Effects of Future Atmospheric CO2 Concentrations on Protein Intake and the Risk of Protein Deficiency by Country and Region

    Medek, Danielle E.; Schwartz, Joel; Myers, Samuel S.
    Background: Crops grown under elevated atmospheric CO2 concentrations (eCO2) contain less protein. Crops particularly affected include rice and wheat, which are primary sources of dietary protein for many countries. Objectives: We aimed to estimate global and country-specific risks of protein deficiency attributable to anthropogenic CO2 emissions by 2050. Methods: To model per capita protein intake in countries around the world under eCO2, we first established the effect size of eCO2 on the protein concentration of edible portions of crops by performing a meta-analysis of published literature. We then estimated per-country protein intake under current and anticipated future eCO2 using global...

  16. Rapid Detection of Powassan Virus in a Patient With Encephalitis by Metagenomic Sequencing

    Piantadosi, Anne; Kanjilal, Sanjat; Ganesh, Vijay; Khanna, Arjun; Hyle, Emily P; Rosand, Jonathan; Bold, Tyler; Metsky, Hayden C; Lemieux, Jacob; Leone, Michael J; Freimark, Lisa; Matranga, Christian B; Adams, Gordon; McGrath, Graham; Zamirpour, Siavash; Telford, Sam; Rosenberg, Eric; Cho, Tracey; Frosch, Matthew P; Goldberg, Marcia B; Mukerji, Shibani S; Sabeti, Pardis C
    Abstract We describe a patient with severe and progressive encephalitis of unknown etiology. We performed rapid metagenomic sequencing from cerebrospinal fluid and identified Powassan virus, an emerging tick-borne flavivirus that has been increasingly detected in the United States.

  17. Epigenetic restriction of extraembryonic lineages mirrors the somatic transition to cancer

    Smith, Zachary D.; Shi, Jiantao; Gu, Hongcang; Donaghey, Julie; Clement, Kendell; Cacciarelli, Davide; Gnirke, Andreas; Michor, Franziska; Meissner, Alexander
    In mammals, the canonical somatic DNA methylation landscape is established upon specification of the embryo proper and subsequently disrupted within many cancer types1-4. However, the underlying mechanisms that direct this genome-scale transformation remain elusive, with no clear model for its systematic acquisition or potential developmental utility5,6. Here we analyzed global remethylation from the mouse preimplantation embryo into the early epiblast and extraembryonic ectoderm. We show that these two states acquire highly divergent genomic distributions with substantial disruption of bimodal, CpG density-dependent methylation in the placental progenitor7,8. The extraembryonic epigenome includes specific de novo methylation at hundreds of embryonically-protected CpG island...

  18. Naked Mole Rat Cells Have a Stable Epigenome that Resists iPSC Reprogramming

    Tan, Li; Ke, Zhonghe; Tombline, Gregory; Macoretta, Nicholas; Hayes, Kevin; Tian, Xiao; Lv, Ruitu; Ablaeva, Julia; Gilbert, Michael; Bhanu, Natarajan V.; Yuan, Zuo-Fei; Garcia, Benjamin A.; Shi, Yujiang G.; Shi, Yang; Seluanov, Andrei; Gorbunova, Vera
    Summary Naked mole rat (NMR) is a valuable model for aging and cancer research due to its exceptional longevity and cancer resistance. We observed that the reprogramming efficiency of NMR fibroblasts in response to OSKM was drastically lower than that of mouse fibroblasts. Expression of SV40 LargeT antigen (LT) dramatically improved reprogramming of NMR fibroblasts. Inactivation of Rb alone, but not p53, was sufficient to improve reprogramming efficiency, suggesting that NMR chromatin may be refractory to reprogramming. Analysis of the global histone landscape revealed that NMR had higher levels of repressive H3K27 methylation marks and lower levels of activating H3K27...

  19. Generation of a Motor Nerve Organoid with Human Stem Cell-Derived Neurons

    Kawada, Jiro; Kaneda, Shohei; Kirihara, Takaaki; Maroof, Asif; Levi, Timothée; Eggan, Kevin; Fujii, Teruo; Ikeuchi, Yoshiho
    Summary During development, axons spontaneously assemble into a fascicle to form nerves and tracts in the nervous system as they extend within a spatially constrained path. However, understanding of the axonal fascicle has been hampered by lack of an in vitro model system. Here, we report generation of a nerve organoid composed of a robust fascicle of axons extended from a spheroid of human stem cell-derived motor neurons within our custom-designed microdevice. The device is equipped with a narrow channel providing a microenvironment that facilitates the growing axons to spontaneously assemble into a unidirectional fascicle. The fascicle was specifically made...

  20. Haematopoietic stem and progenitor cells from human pluripotent stem cells

    Sugimura, Ryohichi; Jha, Deepak Kumar; Han, Areum; Soria-Valles, Clara; da Rocha, Edroaldo Lummertz; Lu, Yi-Fen; Goettel, Jeremy A.; Serrao, Erik; Rowe, R. Grant; Malleshaiah, Mohan; Wong, Irene; Sousa, Patricia; Zhu, Ted N.; Ditadi, Andrea; Keller, Gordon; Engelman, Alan N.; Snapper, Scott B.; Doulatov, Sergei; Daley, George Q.
    A variety of tissue lineages can be differentiated from pluripotent stem cells by mimicking embryonic development through stepwise exposure to morphogens, or by conversion of one differentiated cell type into another by enforced expression of master transcription factors. Here, to yield functional human haematopoietic stem cells, we perform morphogen-directed differentiation of human pluripotent stem cells into haemogenic endothelium followed by screening of 26 candidate haematopoietic stem-cell-specifying transcription factors for their capacity to promote multi-lineage haematopoietic engraftment in mouse hosts. We recover seven transcription factors (ERG, HOXA5, HOXA9, HOXA10, LCOR, RUNX1 and SPI1) that are sufficient to convert haemogenic endothelium into...

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