Should physical activity recommendations be ethnicity-specific? Evidence from a cross-sectional study of south Asian and European men

Background Expert bodies and health organisations recommend that adults undertake at least 150 min.week−1 of moderate-intensity physical activity (MPA). However, the underpinning data largely emanate from studies of populations of European descent. It is unclear whether this level of activity is appropriate for other ethnic groups, particularly South Asians, who have increased cardio-metabolic disease risk compared to Europeans. The aim of this study was to explore the level of MPA required in South Asians to confer a similar cardio-metabolic risk profile to that observed in Europeans undertaking the currently recommended MPA level of 150 min.week−1.<p></p> Methods Seventy-five South Asian and 83 European men, aged 40–70, without cardiovascular disease or diabetes had fasted blood taken, blood pressure measured, physical activity assessed objectively (using accelerometry), and anthropometric measures made. Factor analysis was used to summarise measured risk biomarkers into underlying latent ‘factors’ for glycaemia, insulin resistance, lipid metabolism, blood pressure, and overall cardio-metabolic risk. Age-adjusted regression models were used to determine the equivalent level of MPA (in bouts of ≥10 minutes) in South Asians needed to elicit the same value in each factor as Europeans undertaking 150 min.week−1 MPA.<p></p> Findings For all factors, except blood pressure, equivalent MPA values in South Asians were significantly higher than 150 min.week−1; the equivalent MPA value for the overall cardio-metabolic risk factor was 266 (95% CI 185-347) min.week−1.<p></p> Conclusions South Asian men may need to undertake greater levels of MPA than Europeans to exhibit a similar cardio-metabolic risk profile, suggesting that a conceptual case can be made for ethnicity-specific physical activity guidance. Further study is needed to extend these findings to women and to replicate them prospectively in a larger cohort.<p></p&gt

Mice lacking ataxin-1 display learning deficits and decreased hippocampal paired-pulse facilitation.

Spinocerebellar ataxia type 1 (SCA1) is a neurodegenerative disorder characterized by ataxia, progressive motor deterioration, and loss of cerebellar Purkinje cells. To investigate SCA1 pathogenesis and to gain insight into the function of the SCA1 gene product ataxin-1, a novel protein without homology to previously described proteins, we generated mice with a targeted deletion in the murine Sca1 gene. Mice lacking ataxin-1 are viable, fertile, and do not show any evidence of ataxia or neurodegeneration. However, Sca1 null mice demonstrate decreased exploratory behavior, pronounced deficits in the spatial version of the Morris water maze test, and impaired performance on the rotating rod apparatus. Furthermore, neurophysiological studies performed in area CA1 of the hippocampus reveal decreased paired-pulse facilitation in Sca1 null mice, whereas long-term and post-tetanic potentiations are normal. These findings demonstrate that SCA1 is not caused by loss of function of ataxin-1 and point to the possible role of ataxin-1 in learning and memory

A procedure for the change point problem in parametric models based on phi-divergence test-statistics

This paper studies the change point problem for a general parametric, univariate or multivariate family of distributions. An information theoretic procedure is developed which is based on general divergence measures for testing the hypothesis of the existence of a change. For comparing the accuracy of the new test-statistic a simulation study is performed for the special case of a univariate discrete model. Finally, the procedure proposed in this paper is illustrated through a classical change-point example

Recovery of renal function in dialysis patients

BACKGROUND: Although recovery of renal functions in dialysis dependent patients is estimated to be greater than 1%, there are no indicators that actually suggest such revival of renal function. Residual renal function in dialysis patients is unreliable and seldom followed. Therefore renal recovery (RR) in dialysis dependent patients may remain unnoticed. We present a group of dialysis dependent patients who regained their renal functions. The aim of this project is to determine any indicators that may identify the recovery of renal functions in dialysis dependent patients. METHODS: All the discharges from the chronic dialysis facilities were identified. Among these discharges deaths, transplants, voluntary withdrawals and transfers either to another modality or another dialysis facility were excluded in order to isolate the patients with RR. The dialysis flow sheets and medical records of these patients were subsequently reviewed. RESULTS: Eight patients with a mean age of 53.8 ± 6.7 years (± SEM) were found to have RR. Dialysis was initiated due to uremic symptoms in 6 patients and fluid overload in the remaining two. The patients remained dialysis dependent for 11.1 ± 4.2 months. All these patients had good urine output and 7 had symptoms related to dialysis. Their mean pre-initiation creatinine and BUN levels were 5.21 ± 0.6 mg/dl and 72.12 ± 11.12 mg/dl, respectively. Upon discontinuation, they remained dialysis free for 19.75 ± 5.97 months. The mean creatinine and BUN levels after cessation of dialysis were 2.85 ± 0.57 mg/dl and 29.62 ± 5.26 mg/dl, respectively, while the mean creatinine clearance calculated by 24-hour urine collection was 29.75 ± 4.78 ml/min. One patient died due to HIV complications. One patient resumed dialysis after nine months. Remaining continue to enjoy a dialysis free life. CONCLUSION: RR must be considered in patients with good urine output and unresolved acute renal failure. Dialysis intolerance may be an indicator of RR among such patients

The selectivity, voltage-dependence and acid sensitivity of the tandem pore potassium channel TASK-1 : contributions of the pore domains

We have investigated the contribution to ionic selectivity of residues in the selectivity filter and pore helices of the P1 and P2 domains in the acid sensitive potassium channel TASK-1. We used site directed mutagenesis and electrophysiological studies, assisted by structural models built through computational methods. We have measured selectivity in channels expressed in Xenopus oocytes, using voltage clamp to measure shifts in reversal potential and current amplitudes when Rb+ or Na+ replaced extracellular K+. Both P1 and P2 contribute to selectivity, and most mutations, including mutation of residues in the triplets GYG and GFG in P1 and P2, made channels nonselective. We interpret the effects of these—and of other mutations—in terms of the way the pore is likely to be stabilised structurally. We show also that residues in the outer pore mouth contribute to selectivity in TASK-1. Mutations resulting in loss of selectivity (e.g. I94S, G95A) were associated with slowing of the response of channels to depolarisation. More important physiologically, pH sensitivity is also lost or altered by such mutations. Mutations that retained selectivity (e.g. I94L, I94V) also retained their response to acidification. It is likely that responses both to voltage and pH changes involve gating at the selectivity filter

Evidence of a Clear Atmosphere for WASP-62b: The Only Known Transiting Gas Giant in the JWST Continuous Viewing Zone

Exoplanets with cloud-free, haze-free atmospheres at the pressures probed by transmission spectroscopy represent a valuable opportunity for detailed atmospheric characterization and precise chemical abundance constraints. We present the first optical to infrared (0.3−5 μm) transmission spectrum of the hot Jupiter WASP-62b, measured with Hubble/STIS and Spitzer/IRAC. The spectrum is characterized by a 5.1σ detection of Na I absorption at 0.59 μm, in which the pressurebroadened wings of the Na D-lines are observed from space for the first time. A spectral feature at 0.4 μm is tentatively attributed to SiH at 2.1σ confidence. Our retrieval analyses are consistent with a cloud-free atmosphere without significant contamination from stellar heterogeneities. We simulate James Webb Space Telescope (JWST) observations, for a combination of instrument modes, to assess the atmospheric characterization potential of WASP-62b. We demonstrate that JWST can conclusively detect Na, H2O, FeH, NH3, CO, CO2, CH4, and SiH within the scope of its Early Release Science (ERS) program. As the only transiting giant planet currently known in the JWST Continuous Viewing Zone, WASP-62b could prove a benchmark giant exoplanet for detailed atmospheric characterization in the James Webb era

Teaching tools in Evidence Based Practice: evaluation of reusable learning objects (RLOs) for learning about Meta-analysis

<p>Abstract</p> <p>Background</p> <p>All healthcare students are taught the principles of evidence based practice on their courses. The ability to understand the procedures used in systematically reviewing evidence reported in studies, such as meta-analysis, are an important element of evidence based practice. Meta-analysis is a difficult statistical concept for healthcare students to understand yet it is an important technique used in systematic reviews to pool data from studies to look at combined effectiveness of treatments. In other areas of the healthcare curricula, by supplementing lectures, workbooks and workshops with pedagogically designed, multimedia learning objects (known as reusable learning objects or RLOs) we have shown an improvement in students' perceived understanding in subjects they found difficult. In this study we describe the development and evaluation of two RLOs on meta-analysis. The RLOs supplement associated lectures and aim to improve students' understanding of meta-analysis in healthcare students.</p> <p>Methods</p> <p>Following a quality controlled design process two RLOs were developed and delivered to two cohorts of students, a Master in Public Health course and Postgraduate diploma in nursing course. Students' understanding of five key concepts of Meta-analysis were measured before and after a lecture and again after RLO use. RLOs were also evaluated for their educational value, learning support, media attributes and usability using closed and open questions.</p> <p>Results</p> <p>Students rated their understanding of meta-analysis as improved after a lecture and further improved after completing the RLOs (Wilcoxon paired test, p < 0.01 in all cases) Whilst the media components of the RLOs such as animations helped most students (86%) understand concepts including for example Forest plots, 93% of students rated usability and control as important to their learning. A small number of students stated they needed the support of a lecturer alongside the RLOs (7% 'Agreed' and 21% 'Neutral').</p> <p>Conclusions</p> <p>Meta-analysis RLOs that are openly accessible and unrestricted by usernames and passwords provide flexible support for students who find the process of meta-analysis difficult.</p

Assessing the causal role of epigenetic clocks in the development of multiple cancers: a Mendelian randomization study

Background: Epigenetic clocks have been associated with cancer risk in several observational studies. Nevertheless, it is unclear whether they play a causal role in cancer risk or if they act as a non-causal biomarker. Methods: We conducted a two-sample Mendelian randomization (MR) study to examine the genetically predicted effects of epigenetic age acceleration as measured by HannumAge (nine single-nucleotide polymorphisms (SNPs)), Horvath Intrinsic Age (24 SNPs), PhenoAge (11 SNPs), and GrimAge (4 SNPs) on multiple cancers (i.e. breast, prostate, colorectal, ovarian and lung cancer). We obtained genome-wide association data for biological ageing from a meta-analysis (N = 34,710), and for cancer from the UK Biobank (N cases = 2671-13,879; N controls = 173,493-372,016), FinnGen (N cases = 719-8401; N controls = 74,685-174,006) and several international cancer genetic consortia (N cases = 11,348-122,977; N controls = 15,861-105,974). Main analyses were performed using multiplicative random effects inverse variance weighted (IVW) MR. Individual study estimates were pooled using fixed effect meta-analysis. Sensitivity analyses included MR-Egger, weighted median, weighted mode and Causal Analysis using Summary Effect Estimates (CAUSE) methods, which are robust to some of the assumptions of the IVW approach. Results: Meta-analysed IVW MR findings suggested that higher GrimAge acceleration increased the risk of colorectal cancer (OR = 1.12 per year increase in GrimAge acceleration, 95% CI 1.04-1.20, p = 0.002). The direction of the genetically predicted effects was consistent across main and sensitivity MR analyses. Among subtypes, the genetically predicted effect of GrimAge acceleration was greater for colon cancer (IVW OR = 1.15, 95% CI 1.09-1.21, p = 0.006), than rectal cancer (IVW OR = 1.05, 95% CI 0.97-1.13, p = 0.24). Results were less consistent for associations between other epigenetic clocks and cancers. Conclusions: GrimAge acceleration may increase the risk of colorectal cancer. Findings for other clocks and cancers were inconsistent. Further work is required to investigate the potential mechanisms underlying the results. Funding: FMB was supported by a Wellcome Trust PhD studentship in Molecular, Genetic and Lifecourse Epidemiology (224982/Z/22/Z which is part of grant 218495/Z/19/Z). KKT was supported by a Cancer Research UK (C18281/A29019) programme grant (the Integrative Cancer Epidemiology Programme) and by the Hellenic Republic's Operational Programme 'Competitiveness, Entrepreneurship & Innovation' (OΠΣ 5047228). PH was supported by Cancer Research UK (C18281/A29019). RMM was supported by the NIHR Biomedical Research Centre at University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol and by a Cancer Research UK (C18281/A29019) programme grant (the Integrative Cancer Epidemiology Programme). RMM is a National Institute for Health Research Senior Investigator (NIHR202411). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. GDS and CLR were supported by the Medical Research Council (MC_UU_00011/1 and MC_UU_00011/5, respectively) and by a Cancer Research UK (C18281/A29019) programme grant (the Integrative Cancer Epidemiology Programme). REM was supported by an Alzheimer's Society project grant (AS-PG-19b-010) and NIH grant (U01 AG-18-018, PI: Steve Horvath). RCR is a de Pass Vice Chancellor's Research Fellow at the University of Bristol

Capsular profiling of the Cronobacter genus and the association of specific Cronobacter sakazakii and C. malonaticus capsule types with neonatal meningitis and necrotizing enterocolitis

Background: Cronobacter sakazakii and C. malonaticus can cause serious diseases especially in infants where they are associated with rare but fatal neonatal infections such as meningitis and necrotising enterocolitis. Methods: This study used 104 whole genome sequenced strains, covering all seven species in the genus, to analyse capsule associated clusters of genes involved in the biosynthesis of the O-antigen, colanic acid, bacterial cellulose, enterobacterial common antigen (ECA), and a previously uncharacterised K-antigen. Results: Phylogeny of the gnd and galF genes flanking the O-antigen region enabled the defining of 38 subgroups which are potential serotypes. Two variants of the colanic acid synthesis gene cluster (CA1 and CA2) were found which differed with the absence of galE in CA2. Cellulose (bcs genes) were present in all species, but were absent in C. sakazakii sequence type (ST) 13 and clonal complex (CC) 100 strains. The ECA locus was found in all strains. The K-antigen capsular polysaccharide Region 1 (kpsEDCS) and Region 3 (kpsMT) genes were found in all Cronobacter strains. The highly variable Region 2 genes were assigned to 2 homology groups (K1 and K2). C. sakazakii and C. malonaticus isolates with capsular type [K2:CA2:Cell+] were associated with neonatal meningitis and necrotizing enterocolitis. Other capsular types were less associated with clinical infections. Conclusion: This study proposes a new capsular typing scheme which identifies a possible important virulence trait associated with severe neonatal infections. The various capsular polysaccharide structures warrant further investigation as they could be relevant to macrophage survival, desiccation resistance, environmental survival, and biofilm formation in the hospital environment, including neonatal enteral feeding tubes