Association Between Acute Kidney Injury Hospital Visits and Environmental Heat Stress at a Nicaraguan Sugarcane Plantation

Background: Mesoamerican sugarcane cutters are at a high risk of chronic kidney disease of non-traditional origin, a disease likely linked to heat-related acute kidney injury (AKI). Studies in general populations have described a positive association between high environmental temperatures and clinically assessed kidney outcomes, but there are no studies in occupational settings. Method: We accessed routine records of clinically diagnosed AKI (AKI-CD) and wet bulb globe temperatures (WBGT) at a large Nicaraguan sugarcane plantation and modeled the relationship between these using negative binomial regression. A rest-shade-hydration intervention was gradually enhanced during the study period, and efforts were made to increase the referral of workers with suspected AKI to healthcare. Results: Each 1°C WBGT was associated with an 18% (95% confidence interval [CI]: [4, 33%]) higher AKI-CD rate on the same day and a 14% (95% CI [−5, 37%]) higher rate over a week. AKI-CD rates and severity, and time between symptoms onset and diagnosis decreased during the study period, that is, with increasing rest-shade-hydration intervention. Symptoms and biochemical signs of systemic inflammation were common among AKI-CD cases. Discussion: Occupational heat stress, resulting from heavy work in environmental heat, was associated with a higher rate of clinically diagnosed AKI in a population at risk of CKDnt. Promoting rest-shade-hydration may have contributed to reducing AKI rates during the study period. Occupational health and safety personnel have key roles to play in enforcing rest, shade, and hydration practices, referring workers with suspected AKI to healthcare as well as collecting and analyzing the data needed to support workplace heat stress interventions

Plasma cytokines in women with chronic fatigue syndrome

© 2009 Fletcher et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Wolbachia Infections Are Virulent and Inhibit the Human Malaria Parasite Plasmodium Falciparum in Anopheles Gambiae

Endosymbiotic Wolbachia bacteria are potent modulators of pathogen infection and transmission in multiple naturally and artificially infected insect species, including important vectors of human pathogens. Anopheles mosquitoes are naturally uninfected with Wolbachia, and stable artificial infections have not yet succeeded in this genus. Recent techniques have enabled establishment of somatic Wolbachia infections in Anopheles. Here, we characterize somatic infections of two diverse Wolbachia strains (wMelPop and wAlbB) in Anopheles gambiae, the major vector of human malaria. After infection, wMelPop disseminates widely in the mosquito, infecting the fat body, head, sensory organs and other tissues but is notably absent from the midgut and ovaries. Wolbachia initially induces the mosquito immune system, coincident with initial clearing of the infection, but then suppresses expression of immune genes, coincident with Wolbachia replication in the mosquito. Both wMelPop and wAlbB significantly inhibit Plasmodium falciparum oocyst levels in the mosquito midgut. Although not virulent in non-bloodfed mosquitoes, wMelPop exhibits a novel phenotype and is extremely virulent for approximately 12–24 hours post-bloodmeal, after which surviving mosquitoes exhibit similar mortality trajectories to control mosquitoes. The data suggest that if stable transinfections act in a similar manner to somatic infections, Wolbachia could potentially be used as part of a strategy to control the Anopheles mosquitoes that transmit malaria

Loss-of-function mutations in SLC30A8 protect against type 2 diabetes.

Neðst á síðunni er hægt að nálgast greinina í heild sinni með því að smella á hlekkinn View/OpenLoss-of-function mutations protective against human disease provide in vivo validation of therapeutic targets, but none have yet been described for type 2 diabetes (T2D). Through sequencing or genotyping of ~150,000 individuals across 5 ancestry groups, we identified 12 rare protein-truncating variants in SLC30A8, which encodes an islet zinc transporter (ZnT8) and harbors a common variant (p.Trp325Arg) associated with T2D risk and glucose and proinsulin levels. Collectively, carriers of protein-truncating variants had 65% reduced T2D risk (P = 1.7 × 10(-6)), and non-diabetic Icelandic carriers of a frameshift variant (p.Lys34Serfs*50) demonstrated reduced glucose levels (-0.17 s.d., P = 4.6 × 10(-4)). The two most common protein-truncating variants (p.Arg138* and p.Lys34Serfs*50) individually associate with T2D protection and encode unstable ZnT8 proteins. Previous functional study of SLC30A8 suggested that reduced zinc transport increases T2D risk, and phenotypic heterogeneity was observed in mouse Slc30a8 knockouts. In contrast, loss-of-function mutations in humans provide strong evidence that SLC30A8 haploinsufficiency protects against T2D, suggesting ZnT8 inhibition as a therapeutic strategy in T2D prevention.US National Institutes of Health (NIH) Training 5-T32-GM007748-33 Doris Duke Charitable Foundation 2006087 Fulbright Diabetes UK Fellowship BDA 11/0004348 Broad Institute from Pfizer, Inc. NIH U01 DK085501 U01 DK085524 U01 DK085545 U01 DK085584 Swedish Research Council Dnr 521-2010-3490 Dnr 349-2006-237 European Research Council (ERC) GENETARGET T2D GA269045 ENGAGE 2007-201413 CEED3 2008-223211 Sigrid Juselius Foundation Folkh lsan Research Foundation ERC AdG 293574 Research Council of Norway 197064/V50 KG Jebsen Foundation University of Bergen Western Norway Health Authority Lundbeck Foundation Novo Nordisk Foundation Wellcome Trust WT098017 WT064890 WT090532 WT090367 WT098381 Uppsala University Swedish Research Council and the Swedish Heart- Lung Foundation Academy of Finland 124243 102318 123885 139635 Finnish Heart Foundation Finnish Diabetes Foundation, Tekes 1510/31/06 Commission of the European Community HEALTH-F2-2007-201681 Ministry of Education and Culture of Finland European Commission Framework Programme 6 Integrated Project LSHM-CT-2004-005272 City of Kuopio and Social Insurance Institution of Finland Finnish Foundation for Cardiovascular Disease NIH/NIDDK U01-DK085545 National Heart, Lung, and Blood Institute (NHLBI) National Institute on Minority Health and Health Disparities N01 HC-95170 N01 HC-95171 N01 HC-95172 European Union Seventh Framework Programme, DIAPREPP Swedish Child Diabetes Foundation (Barndiabetesfonden) 5U01DK085526 DK088389 U54HG003067 R01DK072193 R01DK062370 Z01HG000024info:eu-repo/grantAgreement/EC/FP7/20201

A new strategy for enhancing imputation quality of rare variants from next-generation sequencing data via combining SNP and exome chip data

Background: Rare variants have gathered increasing attention as a possible alternative source of missing heritability. Since next generation sequencing technology is not yet cost-effective for large-scale genomic studies, a widely used alternative approach is imputation. However, the imputation approach may be limited by the low accuracy of the imputed rare variants. To improve imputation accuracy of rare variants, various approaches have been suggested, including increasing the sample size of the reference panel, using sequencing data from study-specific samples (i.e., specific populations), and using local reference panels by genotyping or sequencing a subset of study samples. While these approaches mainly utilize reference panels, imputation accuracy of rare variants can also be increased by using exome chips containing rare variants. The exome chip contains 250 K rare variants selected from the discovered variants of about 12,000 sequenced samples. If exome chip data are available for previously genotyped samples, the combined approach using a genotype panel of merged data, including exome chips and SNP chips, should increase the imputation accuracy of rare variants. Results: In this study, we describe a combined imputation which uses both exome chip and SNP chip data simultaneously as a genotype panel. The effectiveness and performance of the combined approach was demonstrated using a reference panel of 848 samples constructed using exome sequencing data from the T2D-GENES consortium and 5,349 sample genotype panels consisting of an exome chip and SNP chip. As a result, the combined approach increased imputation quality up to 11 %, and genomic coverage for rare variants up to 117.7 % (MAF < 1 %), compared to imputation using the SNP chip alone. Also, we investigated the systematic effect of reference panels on imputation quality using five reference panels and three genotype panels. The best performing approach was the combination of the study specific reference panel and the genotype panel of combined data. Conclusions: Our study demonstrates that combined datasets, including SNP chips and exome chips, enhances both the imputation quality and genomic coverage of rare variants