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:To assess differences in cardiovascular risk profiles among rural-to-urban migrants and non-migrant groups.Cross-sectional study in Ayacucho and Lima, Peru. Participants were: rural (n=201); rural-to-urban migrants (n=589); and urban (n=199). Cardiovascular risk factors were assessed according to migrant status (migrants vs non-migrants), age at first migration, length of residency in an urban area and lifetime exposure to an urban area.For most risk factors, the migrant group had intermediate levels of risk between those observed for the rural and urban groups. Prevalence for rural, migrant and urban groups was 3%, 20% and 33%, respectively, for obesity, and 0.8%, 3% and 6% for type-2 diabetes. This gradient of risk was not observed uniformly across all risk factors. Blood pressure did not show a clear gradient of difference between groups. The migrant group had similar systolic blood pressure but lower diastolic blood pressure than the rural group. The urban group had higher systolic blood pressure but similar diastolic blood pressure than rural group. Hypertension was more prevalent among the urban (29%) than both the rural and migrant groups (11% and 16%, respectively). For HbA(1c), although the urban group had higher levels, the migrant and rural groups were similar to each other. No differences were observed in triglycerides between the three groups. Within migrants, those who migrated when aged older than 12 years had higher odds of diabetes, impaired fasting glucose and metabolic syndrome compared to people who migrated at younger ages. Adjustment for age, sex and socioeconomic indicators had little impact on the patterns observed.The impact of rural-to-urban migration on cardiovascular risk profile is not uniform across different risk factors, and is further influenced by the age at which migration occurs. A gradient in levels was observed for some risk factors across study groups. This observation indicates that urbanisation is indeed detrimental to cardiovascular health.

Project description:BackgroundDyslipidemia is a leading risk factor for atherosclerotic cardiovascular disease. There are few published epidemiological data regarding dyslipidemia in Africa. We determined full lipid and apolipoprotein profiles and investigated factors associated with lipid levels in urban and rural populations of north-western Tanzania and southern Uganda.MethodsWe conducted a cross-sectional survey of randomly-selected, community-dwelling adults (≥18yrs) including five strata per country: one municipality, two district towns and two rural areas. Participants were interviewed and examined using the World Health Organization STEPwise survey questionnaire. Serum levels of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, and apolipoproteins were measured. Factors associated with mean lipid levels were assessed by multivariable linear regression. Framingham 10-year cardiovascular risk scores were calculated with and without lipids.ResultsOne-third of adults in the study population had dyslipidemia. Low high-density lipoprotein cholesterol affected 32-45% of rural adults. High total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B were found in <15% of adult population in all strata, but were more common in urban adults. Factors independently associated with higher mean low-density lipoprotein cholesterol and apolipoprotein B were female gender, older age, higher education, higher income, obesity, and hypertension. Framingham cardiovascular risk scores with and without lipids yielded similar results and 90% of study subjects in all strata were classified as "low risk". Among older adults (>55 years), 30% were classified as "high" or "very high" risk.ConclusionsDyslipidemias are common among adults in north-western Tanzania and southern Uganda affecting one third of adult population. Overall, cardiovascular risk scores are low but high risk scores are common with older adults. Health services designed and equipped to diagnose and treat dyslipidemia are urgently needed.

Project description:BackgroundBoth hypertension and grip strength (GS) are predictors of mortality and cardiovascular disease (CVD), but whether these risk factors interact to affect CVD and all-cause mortality is unknown. This study sought to investigate the associations of GS with the risk of major CVD incidence, CVD mortality, and all-cause mortality in patients with hypertension.MethodsGS was measured using a Jamar dynamometer (Sammons Preston, Bolingbrook, IL, USA) in participants aged 35-70 years from 12 provinces included in the Prospective Urban Rural Epidemiology China Study. Cox frailty proportional hazards models were used to examine the associations of GS and hypertension and the outcomes of all-cause mortality and CVD incidence/mortality.ResultsAmong 39,862 participants included in this study, 15,964 reported having hypertension, and 9095 had high GS at baseline. After a median follow-up of 8.9 years (interquartile range, 6.7-9.9 years), 1822 participants developed major CVD, and 1250 deaths occurred (388 as a result of CVD). Compared with normotensive participants with high GS, hypertensive patients with high GS had a higher risk of major CVD incidence (hazard ratio (HR) = 2.39; 95% confidence interval (95%CI): 1.86-3.06; p < 0.001) or CVD mortality (HR = 3.11; 95%CI: 1.59-6.06; p < 0.001) but did not have a significantly increased risk of all-cause mortality (HR = 1.24; 95%CI: 0.92-1.68; p = 0.159). These risks were further increased if hypertensive participants whose GS level was low (major CVD incidence, HR = 3.31, 95%CI: 2.60-4.22, p < 0.001; CVD mortality, HR = 4.99, 95%CI: 2.64-9.43, p < 0.001; and all-cause mortality, HR = 1.93, 95%CI: 1.47-2.53, p < 0.001).ConclusionThe present study demonstrates that low GS is associated with the highest risk of major CVD incidence, CVD mortality, and all-cause mortality among hypertensive patients. High levels of GS appear to mitigate long-term mortality risk among hypertensive patients.

Dataset Information

The Prevalence and Awareness of Cardiovascular Diseases Risk Factors among the Lebanese Population: A Prospective Study Comparing Urban to Rural Populations.

Publications

The Prevalence and Awareness of Cardiovascular Diseases Risk Factors among the Lebanese Population: A Prospective Study Comparing Urban to Rural Populations.

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