Hyperglycemia Has a Greater Impact on Left Ventricle Function in South Asians Than in Europeans

OBJECTIVE Diabetes is associated with left ventricular (LV) diastolic and systolic dysfunction. South Asians may be at particular risk of developing LV dysfunction owing to a high prevalence of diabetes. We investigated the role of diabetes and hyperglycemia in LV dysfunction in a community-based cohort of older South Asians and white Europeans. RESEARCH DESIGN AND METHODS Conventional and Doppler echocardiography was performed in 999 participants (542 Europeans and 457 South Asians aged 58–86 years) in a population-based study. Anthropometry, fasting bloods, coronary artery calcification scoring, blood pressure, and renal function were measured. RESULTS Diabetes and hyperglycemia across the spectrum of HbA1c had a greater adverse effect on LV function in South Asians than Europeans (N-terminal-probrain natriuretic peptide β ± SE 0.09 ± 0.04, P = 0.01, vs. −0.04 ± 0.05, P = 0.4, P for HbA1c/ethnicity interaction 0.02), diastolic function (E/e′ 0.69 ± 0.12, P < 0.0001, vs. 0.09 ± 0.2, P = 0.6, P for interaction 0.005), and systolic function (s′ −0.11 ± 0.06, P = 0.04, vs. 0.14 ± 0.09, P = 0.1, P for interaction 0.2). Multivariable adjustment for hypertension, microvascular disease, LV mass, coronary disease, and dyslipidemia only partially accounted for the ethnic differences. Adverse LV function in diabetic South Asians could not be accounted for by poorer glycemic control or longer diabetes duration. CONCLUSIONS Diabetes and hyperglycemia have a greater adverse effect on LV function in South Asians than Europeans, incompletely explained by adverse risk factors. South Asians may require earlier and more aggressive treatment of their cardiometabolic risk factors to reduce risks of LV dysfunction

Accumulation and dissemination of prion protein in experimental sheep scrapie in the natural host

<p>Abstract</p> <p>Background</p> <p>In order to study the sites of uptake and mechanisms of dissemination of scrapie prions in the natural host under controlled conditions, lambs aged 14 days and homozygous for the VRQ allele of the PrP gene were infected by the oral route. Infection occurred in all lambs with a remarkably short and highly consistent incubation period of approximately 6 months. Challenge of lambs at approximately eight months of age resulted in disease in all animals, but with more variable incubation periods averaging significantly longer than those challenged at 14 days.</p> <p>This model provides an excellent system in which to study the disease in the natural host by virtue of the relatively short incubation period and close resemblance to natural infection.</p> <p>Results</p> <p>Multiple sites of prion uptake were identified, of which the most important was the Peyer's patch of the distal ileum.</p> <p>Neuroinvasion was detected initially in the enteric nervous system prior to infection of the central nervous system. At end stage disease prion accumulation was widespread throughout the entire neuraxis, but vacuolar pathology was absent in most animals that developed disease at 6–7 months of age.</p> <p>Conclusion</p> <p>Initial spread of detectable PrP was consistent with drainage in afferent lymph to dependent lymph nodes. Subsequent accumulation of prions in lymphoid tissue not associated with the gut is consistent with haematogenous spread. In addition to macrophages and follicular dendritic cells, prion containing cells consistent with afferent lymph dendritic cells were identified and are suggested as a likely vehicle for carriage of prions from initial site of uptake to the lymphoreticular system, and as potential carriers of prion protein in blood. It is apparent that spongiform change, the characteristic lesion of scrapie and other prion diseases, is not responsible for the clinical signs in sheep, but may develop in an age dependent manner.</p

Microtubules Regulate Migratory Polarity through Rho/ROCK Signaling in T Cells

Background: Migrating leukocytes normally have a polarized morphology with an actin-rich lamellipodium at the front and a uropod at the rear. Microtubules (MTs) are required for persistent migration and chemotaxis, but how they affect cell polarity is not known.Methodology/Principal Findings: Here we report that T cells treated with nocodazole to disrupt MTs are unable to form a stable uropod or lamellipodium, and instead often move by membrane blebbing with reduced migratory persistence. However, uropod-localized receptors and ezrin/radixin/moesin proteins still cluster in nocodazole-treated cells, indicating that MTs are required specifically for uropod stability. Nocodazole stimulates RhoA activity, and inhibition of the RhoA target ROCK allows nocodazole-treated cells to re-establish lamellipodia and uropods and persistent migratory polarity. ROCK inhibition decreases nocodazole-induced membrane blebbing and stabilizes MTs. The myosin inhibitor blebbistatin also stabilizes MTs, indicating that RhoA/ROCK act through myosin II to destabilize MTs.Conclusions/Significance: Our results indicate that RhoA/ROCK signaling normally contributes to migration by affecting both actomyosin contractility and MT stability. We propose that regulation of MT stability and RhoA/ROCK activity is a mechanism to alter T-cell migratory behavior from lamellipodium-based persistent migration to bleb-based migration with frequent turning

Characterising lower-body musculoskeletal morphology and whole-body composition of elite female and male Australian Football players

Background: Physical demands and injury rates differ between elite female and male Australian Football (AF) players. To improve understanding of contributing physical factors to these differences, the purpose of this study was to investigate lower-body morphology and whole-body composition of elite footballers competing in the Australian Football League (AFL) and Australian Football League Women’s (AFLW). Methods: Lower-body morphology and whole-body composition of 23 AFL players and 23 AFLW players were assessed using peripheral Quantitative Computed Tomography and Dual-energy X-ray Absorptiometry at the beginning of pre-season. Differences between cohorts, with sub-analyses of kicking vs. support limbs, and experienced vs. inexperienced player status were assessed using two-sample independent t-tests. Magnitude of differences were assessed using Cohen’s d effect sizes. Results: AFL players had greater absolute (p \u3c 0.001; ES = 3.28) and relative (p \u3c 0.001; ES = 2.29) whole body lean soft-tissue mass, with less absolute (p = 0.004; ES = 0.91) and relative (p \u3c 0.001; ES = 2.29) fat mass than AFLW players. For AFLW players, no significant differences existed between kicking and support limbs with few differences observed between experienced and inexperienced players. Conclusions: Greater emphasis on physical development in AFLW players may be required to enable increases in muscle mass and skeletal robustness, to ensure they can tolerate the loads of elite competition

Developing a core outcome set for periodontal trials

Acknowledgments The authors wish to thank all patients and professionals who took part in the Delphi process and face-to-face consensus meeting. We wish to thank Jillian Sutherland, Shirley Bell, Margaret Mooney and Lorna Barnsley for helping to organise the face-to-face consensus meeting. Patient participant recruitment to this study was facilitated by SHARE–the Scottish Health Research Register. SHARE is supported by NHS Research Scotland and the Chief Scientists Office Funding: TL received research funding for the core outcome set development for the prevention and management of periodontal diseases which was provided by the Tattershall fund, Dundee Dental School. This grant provided funds for the e-Delphi software, SHARE services and the face-to-face consensus meeting travel and catering costs. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscriptPeer reviewedPublisher PD

Pre-season body composition has minimal influence on in-season match availability, and match performance in female Australian Football League (AFLW) players

This study examined the relationship between pre-season body composition, in-season match performance, and match availability in female players competing in the Australian Football League Women\u27s (AFLW) competition. With the outlawing of body composition assessments as part of pre-draft player evaluations in the AFLW, this study seeks to examine whether this is justified. Twenty-two (n = 22) players had body composition assessed with dual-energy x-ray absorptiometry at the beginning of the 2021 AFLW pre-season (whole-body and regional fat mass and lean soft-tissue mass [LSTM]). In-season match availability and match performance data (Coaches Score [CS], Champion Data Player Rank, average disposals, disposal and kicking efficiency) were collected throughout the 2021 competition. Pearson correlations were performed to assess if associations existed between body composition and in-season match performance and availability. A median split was performed to divide players into higher and lower performing groups for match performance variables. Two-sample independent t-tests were then used to assess differences between groups. No body composition characteristics could differentiate between in-season match availability groups (100 % availability vs. \u3c 100 % availability) or higher and lower performing groups for all match performance variables. Total leg LSTM asymmetry shared a moderate negative association with CS. Body composition may not be important for determining in-season match availability and performance in female AFLW players. Thus, the repercussions following the removal of pre-draft body composition assessments across the league may not be as significant as is currently perceived. Other physiological, biomechanical, or performance qualities are more variable and may mask the effect of body composition in these players. AFLW practitioners should prioritize the development of other important attributes, such as aerobic fitness, muscular strength and power, and technical skill

Ethnic differences in cross-sectional associations between impaired glucose regulation, identified by oral glucose tolerance test or HbA1c values, and cardiovascular disease in a cohort of European and South Asian origin

Aims We contrasted impaired glucose regulation (prediabetes) prevalence, defined according to oral glucose tolerance test or HbA1c values, and studied cross-sectional associations between prediabetes and subclinical/clinical cardiovascular disease (CVD) in a cohort of European and South Asian origin. Methods For 682 European and 520 South Asian men and women, aged 58–85 years, glycaemic status was determined by oral glucose tolerance test or HbA1c thresholds. Questionnaires, record review, coronary artery calcification scores and cerebral magnetic resonance imaging established clinical plus subclinical coronary heart and cerebrovascular disease. Results Prediabetes was more prevalent in South Asian participants when defined by HbA1c rather than by oral glucose tolerance test criteria. Accounting for age, sex, smoking, systolic blood pressure, triglycerides and waist–hip ratio, prediabetes was associated with coronary heart disease and cerebrovascular disease in European participants, most obviously when defined by HbA1c rather than by oral glucose tolerance test [odds ratios for HbA1c-defined prediabetes 1.60 (95% CI 1.07, 2.39) for coronary heart disease and 1.57 (95% CI 1.00, 2.51) for cerebrovascular disease]. By contrast, non-significant associations were present between oral glucose tolerance test-defined prediabetes only and coronary heart disease [odds ratio 1.41 (95% CI 0.84, 2.36)] and HbA1c-defined prediabetes only and cerebrovascular disease [odds ratio 1.39 (95% CI 0.69, 2.78)] in South Asian participants. Prediabetes defined by HbA1c or oral glucose tolerance test criteria was associated with cardiovascular disease (defined as coronary heart and/or cerebrovascular disease) in Europeans [odds ratio 1.95 (95% CI 1.31, 2.91) for HbA1c prediabetes criteria] but not in South Asian participants [odds ratio 1.00 (95% CI 0.62, 2.66); ethnicity interaction P = 0.04]. Conclusions Prediabetes appeared to be less associated with cardiovascular disease in the South Asian than in the European group. These findings have implications for screening, and early cardiovascular prevention strategies in South Asian populations

Double Empathy: Why Autistic People Are Often Misunderstood

Autism affects how someone makes sense of the world around them. About 1–2% of people are autistic. You might have an autistic classmate or family member, or maybe you are autistic. Autistic people might communicate differently than people who are not autistic. This means that it can be difficult for other people to understand what autistic people are trying to say or what they mean. We tend to think that people who are not autistic might be more successful at understanding other people, but in fact, autistic people may be better understood by other autistic people. We will examine and explain some research that has explored how autistic and non-autistic people communicate with each other and explore how this research fits with a theory called the double empathy problem. Understanding what makes interaction comfortable and easy for different people can help us all understand each other better