Project description:People of South Asian descent have an increased risk of cardiovascular disease (CVD) and diabetes, but little is known about the microcirculation in South Asian people despite evidence that this plays an important role in the aetiology of CVD. We compared the retinal microcirculation in a population-based sample of 287 middle-aged adults (144 European 143 South Asian) matched for age and sex. Retinal photographs were taken and analysed using a validated semi-automated program and microvascular measures were compared. Blood pressure, anthropometry and fasting bloods were also measured. South Asians had significantly fewer arteriolar and venular vessels and bifurcations. Arterioles and venules were longer and venules were also more tortuous in South Asians. These differences were not explained by adjustment for traditional risk factors including blood pressure, body mass index, diabetes or measures of insulin resistance. People of South Asian descent have rarefaction of the retinal microcirculation compared to age-sex matched individuals of European descent. Reduced microvascular density could contribute to the elevated risk of CVD and impaired glucose tolerance in South Asian people.
Project description:BackgroundSouth Asians represent about 3% of the Canadian population and have a higher burden of certain cardiovascular risk factors and cardiovascular disease (CVD) compared with white people. The objective of this study was to review the literature to compare cardiovascular risk factors and disease management practices among adult South Asian and white Canadians.MethodsWe searched MEDLINE, Embase, Cochrane and Cumulative Index to Nursing and Allied Health Literature databases from their inception through Feb. 17, 2014 and the reference lists of the selected articles. English-language studies of interventions and observational studies of biological mechanisms underlying CVD risk in South Asians conducted in Canada were eligible for inclusion. Where appropriate, we used random-effects meta-analyses to integrate results comparing the CVD risk profiles of South Asian and white Canadians.ResultsWe included 50 articles (n = 5 805 313 individuals) in this review. Compared with white Canadians, South Asian Canadians had a higher prevalence and incidence of CVD, an increased prevalence of diabetes (odds ratio [OR] 2.25, 95% confidence interval [CI] 1.81 to 2.80, p < 0.001) and hypertension (OR 1.11, 95% CI 1.02 to 1.22, p = 0.02), lower high-density lipoprotein cholesterol levels (mean difference -0.19 mmol/L, 95% CI -0.25 to -0.13 mmol/L, p < 0.001) and a higher percentage of body fat (men: absolute mean difference 3.23%, 95% CI 0.83% to 5.62%, p = 0.008; women: absolute mean difference 4.09%, 95% CI 3.46% to 4.72%, p < 0.001). South Asian people are also more sedentary, consume higher levels of carbohydrates and are less likely to smoke tobacco (OR 0.38, 95% CI 0.24 to 0.60, p < 0.001]) than white Canadians. No differences in access to diagnostic tests, outcomes following cardiovascular surgery or use of cardiac rehabilitation programs were apparent.InterpretationCompared with white people, South Asian people living in Canada have a higher prevalence and incidence of CVD and possess a unique cardiovascular risk profile.
Project description:We computed the network of channels of the 3A4 isoform of the cytochrome P450 (CYP) on the basis of 16 crystal structures extracted from the Protein Data Bank (PDB). The calculations were performed with version 2 of the CCCPP software that we developed for this research project. We identified the minimal cost paths (MCPs) output by CCCPP as probable ways to access to the buried active site. The algorithm of calculation of the MCPs is presented in this paper, with its original method of visualization of the channels. We found that these MCPs constitute four major channels in CYP3A4. Among the many channels proposed by Cojocaru et al. in 2007, we found that only four of them open in 3A4. We provide a refined description of these channels together with associated quantitative data.
Project description:Helicases are a ubiquitous class of enzymes involved in nearly all aspects of DNA and RNA metabolism. Despite recent progress in understanding their mechanism of action, limited resolution has left inaccessible the detailed mechanisms by which these enzymes couple the rearrangement of nucleic acid structures to the binding and hydrolysis of ATP. Observing individual mechanistic cycles of these motor proteins is central to understanding their cellular functions. Here we follow in real time, at a resolution of two base pairs and 20 ms, the RNA translocation and unwinding cycles of a hepatitis C virus helicase (NS3) monomer. NS3 is a representative superfamily-2 helicase essential for viral replication, and therefore a potentially important drug target. We show that the cyclic movement of NS3 is coordinated by ATP in discrete steps of 11 +/- 3 base pairs, and that actual unwinding occurs in rapid smaller substeps of 3.6 +/- 1.3 base pairs, also triggered by ATP binding, indicating that NS3 might move like an inchworm. This ATP-coupling mechanism is likely to be applicable to other non-hexameric helicases involved in many essential cellular functions. The assay developed here should be useful in investigating a broad range of nucleic acid translocation motors.
Project description:BackgroundThe cardiovascular disease (CVD) burden among South Asians is high. Lifestyle interventions have been effective in the primary prevention of CVD, but this has not been replicated, through a synthesis of randomised trials, in South Asians.MethodsFour electronic databases (MEDLINE, Embase, CENTRAL and CINAHL), two clinical trial registries and references of included articles were searched through June 2022 (featuring ≥90% South Asian participants). Random-effects pairwise meta-analyses were performed, and heterogeneity was quantified with the I2 statistic. The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) framework was used to report on the quality of evidence (International Prospective Register of Systematic Reviews registration (PROSPERO).ResultsThirty-five studies were included. Twelve tested diet and physical activity interventions; 18 tested diet alone; and 5 tested physical activity alone. All reported effects of the intervention(s) on at least one established risk factor for CVD, including blood pressure (systolic blood pressure (SBP), diastolic blood pressure (DBP) and blood lipids (high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc) or triglycerides). No trials reported clinical CVD. There is moderate-quality evidence that diet and physical activity interventions improve SBP (mean difference (MD) -2.72 mm Hg, 95% CI -4.11 to -1.33) and DBP (MD -1.53 mm Hg, 95% CI -2.57 to -0.48); high-quality to moderate-quality evidence that diet-only interventions improve DBP (MD -2.05 mm Hg, 95% CI -2.93 to -1.16) and blood lipids (triglycerides (MD -0.10 mmol/L, 95% CI -0.14 to -0.06) and LDLc (MD -0.19 mmol/L, 95% CI -0.32 to -0.06)); and moderate-quality evidence that physical activity-only interventions improve SBP (MD -9.7 mm Hg, 95% CI -11.05 to -8.35), DBP (MD -7.29 mm Hg, 95% CI -8.42 to -6.16) and HDLc (MD 0.08 mmol/L, 95% CI 0.04 to 0.11) compared with usual care.ConclusionsLifestyle interventions improve blood pressure and blood lipid profiles in adult South Asians at risk of CVD. Tailored interventions should be used to modify cardiovascular risk factors in this at-risk group.Prospero registration numberCRD42018090419.
Project description:South Asians (SAs), people from the Indian subcontinent (e.g., India, Pakistan, Bangladesh, Sri Lanka, and Nepal) have a higher prevalence of cardiovascular disease (CVD) and suffer from a greater risk of CVD-associated mortality compared to other global populations. These problems are compounded by the alterations in lifestyles due to urbanization and changing cultural, social, economic, and political environments. Current methods of CV risk prediction are based on white populations that under-estimate the CVD risk in SAs. Prospective studies are required to obtain actual CVD morbidity/mortality rates so that comparisons between predicted CVD risk can be made with actual events. Overwhelming data support a strong influence of genetic factors. Genome-Wide Association Studies (GWAS) serve as a starting point for future genetic and functional studies since the mechanisms of action by which these associated loci influence CVD is still unclear. It is difficult to predict the potential implication of these findings in clinical settings. This review provides a systematic assessment of the risk factors, genetics, and environmental causes of CV health disparity in SAs, and highlights progress made in clinical and genomics discoveries in the rapidly evolving field, which has the potential to show clinical relevance in the near future.
Project description:BackgroundObservational studies have shown that alcohol consumption above the recommended limit is associated with increased cardiovascular disease (CVD), although its association in South Asians is unclear. Less is known regarding the association between alcohol consumption and cardiovascular health (CVH), assessed by the American Heart Association's Life's Simple 7 (LS7) health metrics among those with South Asian ancestry.MethodsThis analysis included 701 participants without CVD from the Mediators of Atherosclerosis in South Asians Living in America (MASALA) cohort (2015 to 2018). Based on a personal history questionnaire, participants were divided into never, former, and current drinkers. The current drinking category was further classified into 1 to 3 drinks/wk, 4 to 7 drinks/wk, and >7 drinks/wk. The consumption of 5 or more drinks on 1 occasion in the past month was defined as binge drinking. Each LS7 component was given a point score of 0, 1, or 2. The total score was categorized into 0 to 6, 7 to 10, and 11 to 14 to represent poor, intermediate, and ideal CVH, respectively. We use multinomial logistic regression to examine the association between alcohol consumption and CVH.ResultsIn the MASALA cohort (mean age = 59 years, 43% female), participants consuming >7 drinks/wk had the lowest mean CVH score. Compared with never drinkers, male participants consuming >7 drinks/wk were less likely to have intermediate CVH (0.44 [0.08, 0.91]) and ideal CVH (0.23 [0.03, 0.96]). Binge drinking was associated with significantly lower odds of ideal CVH compared with never drinkers.ConclusionWe found evidence of an inverse association of moderate to heavy alcohol consumption and ideal CVH in South Asian men. These findings further underscore the important relationship between alcohol consumption and CVH in this unique population of South Asians.
Project description:AimWe investigated the association between acculturation strategies and cardiometabolic risk among South Asian (SA) immigrants in the US.MethodsIn this cross-sectional analysis of data from 849 SA participants in the Mediators of Atherosclerosis in SAs Living in America (MASALA), we performed multidimensional measures of acculturation to categorize the participants into three acculturation classes: separation (preference for SA culture), assimilation (preference for US culture), and integration (similar preference for both cultures). Differences in glycemic indices, blood pressure, lipid parameters and body composition by acculturation strategy were examined.ResultsWomen in the integration class had the lowest prevalence of diabetes (16.4%), prediabetes (29.7%), fasting and 2-h glucose compared to women in the separation class with the highest prevalence of diabetes (29.3%), prediabetes (31.5%), fasting and 2-h glucose and 2-hr insulin (all p < 0.05). Women in the assimilation class had significantly lower triglycerides, BMI, and waist circumference and higher HDL compared to women in the separation class after adjusting for age, study site, and years in the US. After additionally accounting for socioeconomic/lifestyle factors, women in the assimilation class had significantly lower triglyceride and higher HDL levels compared to women in the separation class (p < 0.01). There was no significant association between acculturation strategies and cardiometabolic risk in SA men.ConclusionSA women who employed an assimilation or integration strategy had a more favorable cardiometabolic profile compared to women using a separation strategy. Future research should investigate the behavioral and psychosocial pathways linking acculturation strategies with cardiometabolic health to inform preventive interventions among SAs living in America.
Project description:Few studies have investigated the association between ectopic fat from different depots and cardiovascular risk scores and their components in the same population, and none have investigated these relations in South Asians. In a cross-sectional analysis of 796 participants in the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study who had measurements of visceral, subcutaneous, pericardial, hepatic, and intermuscular fat from abdominal and cardiac computed tomography scans, we used linear regression to determine the associations of 1 standard deviation difference in each ectopic fat depot with pooled cohort risk score and its components. Pericardial and visceral fat were more strongly associated with the pooled cohort risk score (3.1%, 95% confidence interval [CI] 2.5 to 3.7, and 2.7%, 95% CI 2.1 to 3.3, respectively) and components than intermuscular fat (2.3%, 95% CI 1.7 to 3.0); subcutaneous fat was inversely associated with the pooled cohort risk score (-2.6%, 95% CI -3.2 to 1.9) and hepatic fat attenuation was not linearly associated with the pooled cohort risk score when mutually adjusted (-0.3%, 95% CI -0.9 to 0.4). Associations for risk factor components differed by fat depot. In conclusion, subcutaneous and hepatic fat may have different functions than fat stored in other depots in South Asians. Determining whether these relations are heterogeneous by race may help elucidate the mechanisms underlying CVD disparities.