Animal-related factors associated with moderate-to-severe diarrhea in children younger than five years in western Kenya: A matched case-control study

Background Diarrheal disease remains among the leading causes of global mortality in children younger than 5 years. Exposure to domestic animals may be a risk factor for diarrheal disease. The objectives of this study were to identify animal-related exposures associated with cases of moderate-to-severe diarrhea (MSD) in children in rural western Kenya, and to identify the major zoonotic enteric pathogens present in domestic animals residing in the homesteads of case and control children. Methodology/Principal findings We characterized animal-related exposures in a subset of case and control children (n = 73 pairs matched on age, sex and location) with reported animal presence at home enrolled in the Global Enteric Multicenter Study in western Kenya, and analysed these for an association with MSD. We identified potentially zoonotic enteric pathogens in pooled fecal specimens collected from domestic animals resident at children’s homesteads. Variables that were associated with decreased risk of MSD were washing hands after animal contact (matched odds ratio [MOR] = 0.2; 95% CI 0.08–0.7), and presence of adult sheep that were not confined in a pen overnight (MOR = 0.1; 0.02–0.5). Variables that were associated with increased risk of MSD were increasing number of sheep owned (MOR = 1.2; 1.0–1.5), frequent observation of fresh rodent excreta (feces/urine) outside the house (MOR = 7.5; 1.5–37.2), and participation of the child in providing water to chickens (MOR = 3.8; 1.2–12.2). Of 691 pooled specimens collected from 2,174 domestic animals, 159 pools (23%) tested positive for one or more potentially zoonotic enteric pathogens (Campylobacter jejuni, C. coli, non-typhoidal Salmonella, diarrheagenic E. coli, Giardia, Cryptosporidium, or rotavirus). We did not find any association between the presence of particular pathogens in household animals, and MSD in children. Conclusions and significance Public health agencies should continue to promote frequent hand washing, including after animal contact, to reduce the risk of MSD. Future studies should address specific causal relations of MSD with sheep and chicken husbandry practices, and with the presence of rodents

Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways

Identification of Phosphorylation Sites within the Herpes Simplex Virus Tegument Protein VP22

The herpes simplex virus protein VP22 is a major phosphoprotein of infected cells. In this study, we identify two serine phosphorylation sites within VP22 and show that the N-terminal site is a substrate for casein kinase II, while the extreme C-terminal site is a substrate for another, as yet unidentified, cellular kinase. Furthermore, we show that a mutant of VP22 which has both sites altered is unable to incorporate phosphate in vivo, confirming that there are no other phosphorylation sites within VP22

Non-Targeted Analysis of Petroleum Metabolites in Groundwater Using GC×GC–TOFMS

Groundwater at fuel release sites often contains nonpolar hydrocarbons that originate from both the fuel release and other environmental sources, as well as polar metabolites of petroleum biodegradation. These compounds, along with other polar artifacts, can be quantified as “total petroleum hydrocarbons” using USEPA Methods 3510/8015B, unless a silica gel cleanup step is used to separate nonpolar hydrocarbons from polar compounds prior to analysis. Only a limited number of these metabolites have been identified by traditional GC–MS methods, because they are difficult to resolve using single-column configurations. Additionally, the targeted use of derivatization limits the detection of many potential metabolites of interest. The objective of this research was to develop a nontargeted GC×GC–TOFMS approach to characterize petroleum metabolites in environmental samples gathered from fuel release sites. The method tentatively identified more than 760 unique polar compounds, including acids/esters, alcohols, phenols, ketones, and aldehydes, from 22 groundwater samples collected at five sites. Standards for 28 polar compounds indicate that effective limits of quantitation for most of these compounds in the groundwater samples range from 1 to 11 μg/L

Mitochondrial inhibitor atovaquone increases tumor oxygenation and inhibits hypoxic gene expression in patients with non-small cell lung cancer

Clinical trial with omics and imaging data to study response to treatment

Flow diagram showing selection and enrollment of case and control children into the GEMS-ZED study of moderate-to-severe diarrhea in children in western Kenya.

<p>Flow diagram showing selection and enrollment of case and control children into the GEMS-ZED study of moderate-to-severe diarrhea in children in western Kenya.</p

Results of the final multivariable conditional logistic regression model of animal-related factors associated with moderate-to-severe diarrhea in children younger than 5 years in western Kenya (Akaike information criterion: 76.02).

<p>Results of the final multivariable conditional logistic regression model of animal-related factors associated with moderate-to-severe diarrhea in children younger than 5 years in western Kenya (Akaike information criterion: 76.02).</p

Test results for potential zoonotic enteric pathogens in pooled fecal samples collected from domestic animals resident in the homesteads of case and control children enrolled in the GEMS-ZED study of moderate-to-severe diarrhea in children in western Kenya.

<p>Test results for potential zoonotic enteric pathogens in pooled fecal samples collected from domestic animals resident in the homesteads of case and control children enrolled in the GEMS-ZED study of moderate-to-severe diarrhea in children in western Kenya.</p

Ownership of domestic animals by the 73 matched pairs of case-control households enrolled in the GEMS-ZED study of moderate-to-severe diarrhea in children in western Kenya.

<p>Ownership of domestic animals by the 73 matched pairs of case-control households enrolled in the GEMS-ZED study of moderate-to-severe diarrhea in children in western Kenya.</p

Univariable conditional logistic regression results of pathogens identified in domestic animals resident in compounds of children with and without moderate-to-severe diarrhea enrolled in the GEMS-ZED study.

<p>Univariable conditional logistic regression results of pathogens identified in domestic animals resident in compounds of children with and without moderate-to-severe diarrhea enrolled in the GEMS-ZED study.</p