Project description:Atmospheric particulate matter (PM) is a recognized risk factor for the global burden of disease in human populations. We are presenting here the application of toxicogenomics in the evaluation of the toxic effects of organic content of atmospheric particle matter (PM), from urban and rural environments (city of Barcelona and village of La Pobla, NE Spain), using the developing zebrafish embryo. The main goal is to identify the metabolic pathways involved in the adverse effects observed in zebrafish embryos exposed to PM organic content from urban and rural environments, also allowing the selection of genes of interest that are differentially expressed. The relevance of particle size to the PM toxicity is also addressed. Indeed, the zebrafish embryos were exposed to PM of aerodynamic diameter larger than 7.2 μm and smaller than 0.5 μm (PM10 and PM0.5, respectively). PM0.5 concentrated biological and toxic activities linked to organic substances. Transcriptomic analyses showed strong induction of the AhR signalling pathway (a.k.a. dioxin-like activity) for embryos exposed to both rural and urban extracts, correlating with the concentrations of PAHs. Urban extracts, with strong contribution of traffic emissions, specifically de-regulated oxidative stress-related genes, as well as pancreatic and eye-lens specific genes, two organs known to be affected by air pollution in humans. Exposure to rural extracts, with high contribution of wood burning emissions, affected genes implicated in basic cellular functions, in agreement with their strong embryotoxicity. Extracts from rural and urban samples elicited both common and specific transcriptome responses, suggesting different potentially adverse outcomes depending on PM source and composition. The authors thank the financial support of the Spanish Ministry (project TEA-PARTICLE, grant number CGL2011-29621) and the Portuguese Foundation for Science and Technology for the doctoral grant of Sofia R. Mesquita (SFRH/BD/80710/2011) funded by the Program POPH-QREN through the Portuguese Ministry of Education and Science and the European Social Fund, and support through project PEst-C/MAR/LA0015/2013.

Project description:Atmospheric particulate matter (PM) is a recognized risk factor for the global burden of disease in human populations. We are presenting here the application of toxicogenomics in the evaluation of the toxic effects of organic content of atmospheric particle matter (PM), from urban and rural environments (city of Barcelona and village of La Pobla, NE Spain), using the developing zebrafish embryo. The main goal is to identify the metabolic pathways involved in the adverse effects observed in zebrafish embryos exposed to PM organic content from urban and rural environments, also allowing the selection of genes of interest that are differentially expressed. The relevance of particle size to the PM toxicity is also addressed. Indeed, the zebrafish embryos were exposed to PM of aerodynamic diameter larger than 7.2 Î¼m and smaller than 0.5 Î¼m (PM10 and PM0.5, respectively). PM0.5 concentrated biological and toxic activities linked to organic substances. Transcriptomic analyses showed strong induction of the AhR signalling pathway (a.k.a. dioxin-like activity) for embryos exposed to both rural and urban extracts, correlating with the concentrations of PAHs. Urban extracts, with strong contribution of traffic emissions, specifically de-regulated oxidative stress-related genes, as well as pancreatic and eye-lens specific genes, two organs known to be affected by air pollution in humans. Exposure to rural extracts, with high contribution of wood burning emissions, affected genes implicated in basic cellular functions, in agreement with their strong embryotoxicity. Extracts from rural and urban samples elicited both common and specific transcriptome responses, suggesting different potentially adverse outcomes depending on PM source and composition. The authors thank the financial support of the Spanish Ministry (project TEA-PARTICLE, grant number CGL2011-29621) and the Portuguese Foundation for Science and Technology for the doctoral grant of Sofia R. Mesquita (SFRH/BD/80710/2011) funded by the Program POPH-QREN through the Portuguese Ministry of Education and Science and the European Social Fund, and support through project PEst-C/MAR/LA0015/2013. The PM filter samples used in the present study were PM10 and PM0.5 from the urban site - total of 4 samples from 2 sampling months; and PM0.5 from the rural site - total of 2 samples from 2 sampling months (PM10 samples from the rural site were not tested due to their very low concentration in organic compounds, and insignificant biological activity, previously measured). Sampling occurred during the cold periods of the year 2012/2013. The organic fraction of PM samples was extracted by sonication using a mixture of dichloromethane:methanol. Then, the extracts were filtered, evaporated and re-dissolved in Dimethyl sulfoxide (DMSO). Zebrafish fertilized eggs were exposed to PM organic extracts (0.2% DMSO) from the urban and rural sites from 24 to 120h post-fertilization. Total RNA was isolated from whole embryos (pools of 20 individuals), using Trizol reagent protocol (Invitrogen Life Technologies, Carlsberg, CA). The microarray study was performed using the Agilent Two-colour D. rerio Oligo Microarray v3 platform, following the Agilent Microarray â?? Based Gene Expression Analysis protocol. Three biological replicates were performed for each PM sample and controls. Biological replicates, a technical replicate and a self-to-self, were simultaneously amplified and labelled using Cyanine 3 (Cy3) and Cyanine 5 (Cy5) dye. After cRNA purification (RNeasy Kit, Quiagen GmbH, Hilden, Germany), the cRNA concentration and labelling were quantified in the NanoDrop spectrophotometer, obtaining incorporation rates in the range of 15-20pmol of cyanide dye/Âµl cRNA and yield values > 0.825ug, as recommended. cRNA was fragmented and hybridized in 4x44K arrays, for 17h at 65oC. After the hybridization the array slides were washed, and immediately scanned using Microarray Scanner Agilent G2505C system. Data was extracted using Agilent Feature Extraction Software v10.5.1.1, and the quality of microarray data was evaluated using the Quality Control report provided by Agilent Software. Based on the microarray data analysis, 22 primers were selected and designed using Primer Express 2.0 software (Applied Biosystems, Foster City, CA). Genes were quantified by real-time PCR to validate the microarray data, and a subset of 13 genes were further selected by their robust behaviour in the validation assays, allowing to differentiate the toxic potential of PM from urban and rural sources.

Project description:Importance:In China, diabetes prevalence has increased substantially in recent decades, but there are no reliable estimates of the excess mortality currently associated with diabetes. Objectives:To assess the proportional excess mortality associated with diabetes and estimate the diabetes-related absolute excess mortality in rural and urban areas of China. Design, Setting, and Participants:A 7-year nationwide prospective study of 512?869 adults aged 30 to 79 years from 10 (5 rural and 5 urban) regions in China, who were recruited between June 2004 and July 2008 and were followed up until January 2014. Exposures:Diabetes (previously diagnosed or detected by screening) recorded at baseline. Main Outcomes and Measures:All-cause and cause-specific mortality, collected through established death registries. Cox regression was used to estimate adjusted mortality rate ratio (RR) comparing individuals with diabetes vs those without diabetes at baseline. Results:Among the 512?869 participants, the mean (SD) age was 51.5 (10.7) years, 59% (n?=?302?618) were women, and 5.9% (n?=?30?280) had diabetes (4.1% in rural areas, 8.1% in urban areas, 5.8% of men, 6.1% of women, 3.1% had been previously diagnosed, and 2.8% were detected by screening). During 3.64 million person-years of follow-up, there were 24?909 deaths, including 3384 among individuals with diabetes. Compared with adults without diabetes, individuals with diabetes had a significantly increased risk of all-cause mortality (1373 vs 646 deaths per 100?000; adjusted RR, 2.00 [95% CI, 1.93-2.08]), which was higher in rural areas than in urban areas (rural RR, 2.17 [95% CI, 2.07-2.29]; urban RR, 1.83 [95% CI, 1.73-1.94]). Presence of diabetes was associated with increased mortality from ischemic heart disease (3287 deaths; RR, 2.40 [95% CI, 2.19-2.63]), stroke (4444 deaths; RR, 1.98 [95% CI, 1.81-2.17]), chronic liver disease (481 deaths; RR, 2.32 [95% CI, 1.76-3.06]), infections (425 deaths; RR, 2.29 [95% CI, 1.76-2.99]), and cancer of the liver (1325 deaths; RR, 1.54 [95% CI, 1.28-1.86]), pancreas (357 deaths; RR, 1.84 [95% CI, 1.35-2.51]), female breast (217 deaths; RR, 1.84 [95% CI, 1.24-2.74]), and female reproductive system (210 deaths; RR, 1.81 [95% CI, 1.20-2.74]). For chronic kidney disease (365 deaths), the RR was higher in rural areas (18.69 [95% CI, 14.22-24.57]) than in urban areas (6.83 [95% CI, 4.73-9.88]). Among those with diabetes, 10% of all deaths (16% rural; 4% urban) were due to definite or probable diabetic ketoacidosis or coma (408 deaths). Conclusions and Relevance:Among adults in China, diabetes was associated with increased mortality from a range of cardiovascular and noncardiovascular diseases. Although diabetes was more common in urban areas, it was associated with greater excess mortality in rural areas.

Dataset Information

Relationship between hypertension, diabetes and proteinuria in rural and urban households in Yemen.

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Relationship between hypertension, diabetes and proteinuria in rural and urban households in Yemen.

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