Ethnic Differences in Disability Prevalence and Their Determinants Studied over a 20-Year Period: A Cohort Study.

BACKGROUND: To compare disability prevalence rates in the major ethnic groups in the UK and understand the risk factors contributing to differences identified. It was hypothesised that Indian Asian and African Caribbean people would experience higher rates of disability compared with Europeans. METHODS: Data was collected from 888 European, 636 Indian Asian and 265 African Caribbean men and women, aged 58-88 years at 20-year follow-up of community-based cohort study, based in West London. Disability was measured using a performance-based locomotor function test and self-reported questionnaires on functional limitation, and instrumental (IADL) and basic activities of daily living (ADL). RESULTS: The mean (SD) age of participants at follow-up was 69.6 (6.2) years. Compared with Europeans, Indian Asian people were significantly more likely to experience all of the disability outcomes than Europeans; this persisted after adjustment for socioeconomic, behavioural, adiposity and chronic disease risk factors measured at baseline (locomotor dysfunction: adjusted odds ratio (OR) 2.20, 95% CI 1.56-3.11; functional limitation: OR 2.77, 2.01-3.81; IADL impairment: OR 3.12, 2.20-4.41; ADL impairment: OR 1.58, 1.11-2.24). In contrast, a modest excess risk of disability was observed in African Caribbeans, which was abolished after adjustment (e.g. locomotor dysfunction: OR 1.37, 0.90-1.91); indeed a reduced risk of ADL impairment appeared after multivariable adjustment (OR from 0.99, 0.68-1.45 to 0.59, 0.38-0.93), compared with Europeans. CONCLUSIONS: Substantially elevated risk of disability was observed among Indian Asian participants, unexplained by known factors. A greater understanding of determinants of disability and normative functional beliefs of healthy aging is required in this population to inform intervention efforts to prevent disability

Shuttling components of nuclear import machinery involved in nuclear translocation of steroid receptors exit nucleus via exportin-1/CRM-1* independent pathway

AbstractThe nucleocytoplasmic transport processes are mediated by soluble transport factors constantly navigating between nuclear and cytoplasmic compartments. Our understanding about nuclear export of general ‘nuclear import factors’ that deliver the cargo to the nucleus is still fragmentary. Utilizing green fluorescent protein tagged glucocorticoid receptor (GR) and relA as our working model and with judicious use of LMB, we show in living cells that all the soluble components of the nuclear import machinery exit nucleus via exportin1/CRM1 independent pathway(s)

Bayesian dynamic network modelling: an application to metabolic associations in cardiovascular diseases

We propose a novel approach to the estimation of multiple Graphical Models to analyse temporal patterns of association among a set of metabolites over different groups of patients. Our motivating application is the Southall And Brent REvisited (SABRE) study, a tri-ethnic cohort study conducted in the UK. We are interested in identifying potential ethnic differences in metabolite levels and associations as well as their evolution over time, with the aim of gaining a better understanding of different risk of cardio-metabolic disorders across ethnicities. Within a Bayesian framework, we employ a nodewise regression approach to infer the structure of the graphs, borrowing information across time as well as across ethnicities. The response variables of interest are metabolite levels measured at two time points and for two ethnic groups, Europeans and South-Asians. We use nodewise regression to estimate the high-dimensional precision matrices of the metabolites, imposing sparsity on the regression coefficients through the dynamic horseshoe prior, thus favouring sparser graphs. We provide the code to fit the proposed model using the software Stan, which performs posterior inference using Hamiltonian Monte Carlo sampling, as well as a detailed description of a block Gibbs sampling scheme

Skeletal Muscle Tissue Saturation Changes Measured Using Near Infrared Spectroscopy During Exercise Are Associated With Post-Occlusive Reactive Hyperaemia

Measuring local haemodynamics in skeletal muscle has the potential to provide valuable insight into the oxygen delivery to tissue, especially during high demand situations such as exercise. The aim of this study was to compare the skeletal muscle microvascular response during post-occlusive reactive hyperaemia (PORH) with the response to exercise, each measured using near-infrared spectroscopy (NIRS) and to establish if associations exist between muscle measures and exercise capacity or sex. Participants were from a population-based cohort study, the Southall and Brent Revisited (SABRE) study. Skeletal muscle measures included changes in tissue saturation index at the onset of exercise (∆TSIBL-INC) and across the whole of exercise (∆TSIBL-EE), time to 50%, 95% and 100% PORH, rate of PORH recovery, area under the curve (AUC) and total oxygenated Haemoglobin (oxy-Hb) change during PORH. Exercise capacity was measured using a 6-min stepper test (6MST). Analysis was by multiple linear regression. In total, 558 participants completed the 6MST with NIRS measures of TSI (mean age±SD: 73 ± 7years, 59% male). A sub-set of 149 participants also undertook the arterial occlusion. Time to 100% PORH, recovery rate, AUC and ∆oxy-Hb were all associated with ∆TSIBL-EE (β-coefficient (95%CI): 0.05 (0.01, 0.09), p = 0.012; -47 (-85, -9.9), p = 0.014; 1.7 (0.62, 2.8), p = 0.002; 0.04 (0.002.0.108), p = 0.041, respectively). Time to 95% & 100% PORH, AUC and ∆oxy-Hb were all associated with ∆TSIBL-INC (β-coefficient (95%CI): -0.07 (-0.12,-0.02), p = 0.02; -0.03 (-0.05, -0.003), p = 0.028; 0.85 (0.18, 1.5), p = 0.013 & 0.05 (0.02, 0.09), p = 0.001, respectively). AUC and ∆Oxy-Hb were associated with steps achieved (β-coefficient (95%CI): 18.0 (2.3, 33.7), p = 0.025; 0.86 (0.10, 1.6), p = 0.027). ∆TSIBL-EE was associated with steps and highest VO2 (1.7 (0.49, 2.9), p = 0.006; 7.7 (3.2, 12.3), p = 0.001). ∆TSIBL-INC was associated with steps and VO2 but this difference was attenuated towards the null after adjustment for age, sex and ethnicity. ∆TSIBL-EE was greater in women (3.4 (0.4, 8.9) versus 2.1 (0.3, 7.4), p = 0.017) and ∆TSIBL-INC was lower in women versus men (2.4 (0.2, 10.2) versus 3.2 (0.2, 18.2), p = 0.016). These Local microvascular NIRS-measures are associated with exercise capacity in older adults and several measures can detect differences in microvascular reactivity between a community-based sample of men and women

Declining Levels and Bioavailability of IGF-I in Cardiovascular Aging Associate With QT Prolongation-Results From the 1946 British Birth Cohort

BACKGROUND: As people age, circulating levels of insulin-like growth factors (IGFs) and IGF binding protein 3 (IGFBP-3) decline. In rat cardiomyocytes, IGF-I has been shown to regulate sarcolemmal potassium channel activity and late sodium current thus impacting cardiac repolarization and the heart rate-corrected QT (QTc). However, the relationship between IGFs and IGFBP-3 with the QTc interval in humans, is unknown. OBJECTIVES: To examine the association of IGFs and IGFBP-3 with QTc interval in an older age population-based cohort. METHODS: Participants were from the 1946 Medical Research Council (MRC) National Survey of Health and Development (NSHD) British birth cohort. Biomarkers from blood samples at age 53 and 60–64 years (y, exposures) included IGF-I/II, IGFBP-3, IGF-I/IGFBP-3 ratio and the change (Δ) in marker levels between the 60–64 and 53y sampled timepoints. QTc (outcome) was recorded from electrocardiograms at the 60–64y timepoint. Generalized linear multivariable models with adjustments for relevant demographic and clinical factors, were used for complete-cases and repeated after multiple imputation. RESULTS: One thousand four hundred forty-eight participants were included (48.3% men; QTc mean 414 ms interquartile range 26 ms). Univariate analysis revealed an association between low IGF-I and IGF-I/IGFBP-3 ratio at 60–64y with QTc prolongation [respectively: β −0.30 ms/nmol/L, (95% confidence intervals −0.44, −0.17), p < 0.001; β−28.9 ms/unit (-41.93, −15.50), p < 0.001], but not with IGF-II or IGFBP-3. No association with QTc was found for IGF biomarkers sampled at 53y, however both ΔIGF-I and ΔIGF-I/IGFBP-3 ratio were negatively associated with QTc [β −0.04 ms/nmol/L (−0.08, −0.008), p = 0.019; β −2.44 ms/unit (-4.17, −0.67), p = 0.007] while ΔIGF-II and ΔIGFBP-3 showed no association. In fully adjusted complete case and imputed models (reporting latter) low IGF-I and IGF-I/IGFBP-3 ratio at 60–64y [β −0.21 ms/nmol/L (−0.39, −0.04), p = 0.017; β −20.14 ms/unit (−36.28, −3.99), p = 0.015], steeper decline in ΔIGF-I [β −0.05 ms/nmol/L/10 years (−0.10, −0.002), p = 0.042] and shallower rise in ΔIGF-I/IGFBP-3 ratio over a decade [β −2.16 ms/unit/10 years (−4.23, −0.09), p = 0.041], were all independently associated with QTc prolongation. Independent associations with QTc were also confirmed for other previously known covariates: female sex [β 9.65 ms (6.65, 12.65), p < 0.001], increased left ventricular mass [β 0.04 ms/g (0.02, 0.06), p < 0.001] and blood potassium levels [β −5.70 ms/mmol/L (−10.23, −1.18) p = 0.014]. CONCLUSIONS: Over a decade, in an older age population-based cohort, declining levels and bioavailability of IGF-I associate with prolongation of the QTc interval. As QTc prolongation associates with increased risk for sudden death even in apparently healthy people, further research into the antiarrhythmic effects of IGF-I on cardiomyocytes is warranted

Impact of kidney function on cardiovascular risk and mortality: a comparison of South Asian and European cohorts

Evidence is limited on ethnic differences in associations between kidney function markers and mortality or cardiovascular disease (CVD). Baseline cross-sectional analysis and longitudinal follow-up study of a UK population-based cohort of 1,116 Europeans and 1,104 South Asians of predominantly Indian descent, age 52 ± 7 years at baseline (1988-1991). Kidney function was estimated using Cystatin C and creatinine-based chronic kidney disease (CKD) Epidemiology Collaboration estimated glomerular filtration rate (eGFR) equations, and urinary albumin-creatinine ratio (ACR). Mortality was captured at 27 years, and incident CVD at 22 years, from death certification, medical records and participant report. Longitudinal associations between eGFR/ACR and mortality/incident CVD were examined using Cox models. eGFRcys was lower and ACR higher in South Asians than Europeans. eGFRcys and -eGFRcreat were more strongly associated with outcomes in Europeans than South Asians. Conversely, associations between ACR and outcomes were greater in South Asians than Europeans, for example, for CVD mortality: HRs (95% CI) adjusted for CVD risk factors and ACR/eGFRcys as appropriate, p for ethnicity interaction: eGFRcys: Europeans: 0.76 (0.62-0.92), South Asians: 0.92 (0.78-1.07), p = 0.05, eGFRcreat: Europeans 0.81 (0.67-0.99), South Asians 1.18 (0.97-1.41), p = 0.002, ACR: -Europeans: 1.24 (1.08-1.42), South Asians: 1.39 (1.25-1.57), p= 0.23. Addition of all CKD measures to a standard CVD risk factor model modestly improved prediction capability in -Europeans; in South Asians only ACR contributed to improvement. Strong associations between ACR and outcomes in South Asians of predominantly Indian origin, and null associations for eGFRcys and eGFRcreat, suggest that ACR may have greater utility in CVD risk prediction in South Asians. Further work is needed to validate these -findings. [Abstract copyright: © 2019 S. Karger AG, Basel.

Adverse childhood experiences and the development of multimorbidity across adulthood—a national 70-year cohort study

AIM: To examine impact of adverse childhood experiences (ACE) on rates and development of multimorbidity across three decades in adulthood. METHODS: Sample: Participants from the 1946 National Survey of Health and Development, who attended the age 36 assessment in 1982 and follow-up assessments (ages 43, 53, 63, 69; N = 3,264, 51% males). Prospectively collected data on nine ACEs was grouped into (i) psychosocial, (ii) parental health and (iii) childhood health. For each group, we calculated cumulative ACE scores, categorised into 0, 1 and ≥2 ACEs. Multimorbidity was estimated as the total score of 18 health disorders.Serial cross-sectional linear regression was used to estimate associations between grouped ACEs and multimorbidity during follow-up. Longitudinal analysis of ACE-associated changes in multimorbidity trajectories across follow-up was estimated using linear mixed-effects modelling for ACE groups (adjusted for sex and childhood socioeconomic circumstances). FINDINGS: Accumulation of psychosocial and childhood health ACEs were associated with progressively higher multimorbidity scores throughout follow-up. For example, those with ≥2 psychosocial ACEs experienced 0.20(95% CI 0.07, 0.34) more disorders at age 36 than those with none, rising to 0.61(0.18, 1.04) disorders at age 69.All three grouped ACEs were associated with greater rates of accumulation and higher multimorbidity trajectories across adulthood. For example, individuals with ≥2 psychosocial ACEs developed 0.13(-0.09, 0.34) more disorders between ages 36 and 43, 0.29(0.06, 0.52) disorders between ages 53 and 63, and 0.30(0.09, 0.52) disorders between ages 63 and 69 compared with no psychosocial ACEs. INTERPRETATIONS: ACEs are associated with widening inequalities in multimorbidity development in adulthood and early old age. Public health policies should aim to reduce these disparities through individual and population-level interventions