Psychological effects of rapid weight loss and attitudes towards eating among professional jockeys

We examined the psychological effects of rapid weight loss among a sample of 41 professional jockeys (mean age 30.9 years, s¼7.0). Participants completed the Brunel Mood Scale (BRUMS) and the Eating Attitudes Test-26 (EAT-26) to establish the relationships between rapid weight loss, mood, and attitudes towards eating. These instruments were administered on three occasions: at the jockeys’ minimal weight (achieved through rapid weight loss), their optimal riding weight (when they were not excessively restricting their weight and felt healthy), and their relaxed weight (when there were no forthcoming light rides or no rides at all). It was hypothesized that when riding at minimal weight, jockeys would record a more negative mood profile compared with scores recorded at optimal or relaxed weights. The same trend was expected for eating attitudes. These hypotheses were supported as jockeys reported significantly more negative mood profiles and eating attitudes at minimal weight. The EAT-26 scores indicated the presence of disordered attitudes towards eating at this weight. These results suggest that jockeys’ endeavours to reach the minimum weight limit stipulated by governing bodies are likely to jeopardize their psychological well-being. Dialogue surrounding the appropriateness of current weight regulations is therefore encouraged

Hypertension genomics and cardiovascular prevention.

Hypertension continues to be a major risk factor for global mortality, and recent genome-wide association studies (GWAS) have expanded in size, leading to the identification of further genetic loci influencing blood pressure. In light of the new knowledge from the largest cardiovascular GWAS to date, we review the potential impact of genomics on discovering potential drug targets, risk stratification with genetic risk scores, drug selection with pharmacogenetics, and exploring insights provided by gene-environment interactions

Increased NBCn1 expression, Na+/HCO3- co-transport and intracellular pH in human vascular smooth muscle cells with a risk allele for hypertension.

Genome-wide association studies have revealed an association between variation at the SLC4A7 locus and blood pressure. SLC4A7 encodes the electroneutral Na+/HCO3- co-transporter NBCn1 which regulates intracellular pH (pHi). We conducted a functional study of variants at this locus in primary cultures of vascular smooth muscle and endothelial cells. In both cell types, we found genotype-dependent differences for rs13082711 in DNA-nuclear protein interactions, where the risk allele is associated with increased SLC4A7 expression level, NBCn1 availability and function as reflected in elevated steady-state pHi and accelerated recovery from intracellular acidosis. However, in the presence of Na+/H+ exchange activity, the SLC4A7 genotypic effect on net base uptake and steady-state pHi persisted only in vascular smooth muscle cells but not endothelial cells. We found no discernable effect of the missense polymorphism resulting in the amino acid substitution Glu326Lys. The finding of a genotypic influence on SLC4A7 expression and pHi regulation in vascular smooth muscle cells provides an insight into the molecular mechanism underlying the association of variation at the SLC4A7 locus with blood pressure

British South Asian ancestry participants views of pharmacogenomics clinical implementation and research: a thematic analysis.

BACKGROUND: South Asian ancestry populations are underrepresented in genomic studies and therapeutics trials. British South Asians suffer from multi-morbidity leading to polypharmacy. Our objective was to elucidate British South Asian ancestry community perspectives on pharmacogenomic implementation and sharing pharmacogenomic clinical data for research. METHODS: Four focus groups were conducted (9-12 participants in each). Two groups were mixed gender, while one group was male only and one was female only. Simultaneous interpretation was available to participants in Urdu and Bengali. Focus groups were recorded and abridged transcription and thematic analysis were undertaken. RESULTS: There were 42 participants, 64% female. 26% were born in the UK or Europe. 52% were born in Bangladesh and 17% in Pakistan. 36% reported university level education. Implementation of pharmacogenomics was perceived to be beneficial to individuals but pose a risk of overburdening resource limited systems. Pharmacogenomic research was perceived to be beneficial to the community, with concerns about data privacy and misuse. Data sharing was desirable if the researchers did not have a financial stake, and benefits would be shared. Trust was the key condition for the acceptability of both clinical implementation and research. Trust was linked with medication compliance. Education, outreach, and communication facilitate trust. CONCLUSIONS (SIGNIFICANCE AND IMPACT OF THE STUDY): Pharmacogenomics implementation with appropriate education and communication has the potential to enhance trust and contribute to increased medication compliance. Trust drives data sharing, which would enable enhanced representation in research. Representation in scientific evidence base could cyclically enhance trust and compliance

Greater risk of severe COVID-19 in Black, Asian and Minority Ethnic populations is not explained by cardiometabolic, socioeconomic or behavioural factors, or by 25(OH)-vitamin D status: study of 1326 cases from the UK Biobank.

This is a pre-copyedited, author-produced version of an article accepted for publication in Journal of Public Health, following peer review. The version of record: Zahra Raisi-Estabragh, Celeste McCracken, Mae S Bethell, Jackie Cooper, Cyrus Cooper, Mark J Caulfield, Patricia B Munroe, Nicholas C Harvey, Steffen E Petersen, Greater risk of severe COVID-19 in Black, Asian and Minority Ethnic populations is not explained by cardiometabolic, socioeconomic or behavioural factors, or by 25(OH)-vitamin D status: study of 1326 cases from the UK Biobank, Journal of Public Health, fdaa095, https://doi.org/10.1093/pubmed/fdaa095 is available online at: https://doi.org/10.1093/pubmed/fdaa095BACKGROUND: We examined whether the greater severity of coronavirus disease 2019 (COVID-19) amongst men and Black, Asian and Minority Ethnic (BAME) individuals is explained by cardiometabolic, socio-economic or behavioural factors. METHODS: We studied 4510 UK Biobank participants tested for COVID-19 (positive, n = 1326). Multivariate logistic regression models including age, sex and ethnicity were used to test whether addition of (1) cardiometabolic factors [diabetes, hypertension, high cholesterol, prior myocardial infarction, smoking and body mass index (BMI)]; (2) 25(OH)-vitamin D; (3) poor diet; (4) Townsend deprivation score; (5) housing (home type, overcrowding) or (6) behavioural factors (sociability, risk taking) attenuated sex/ethnicity associations with COVID-19 status. RESULTS: There was over-representation of men and BAME ethnicities in the COVID-19 positive group. BAME individuals had, on average, poorer cardiometabolic profile, lower 25(OH)-vitamin D, greater material deprivation, and were more likely to live in larger households and in flats/apartments. Male sex, BAME ethnicity, higher BMI, higher Townsend deprivation score and household overcrowding were independently associated with significantly greater odds of COVID-19. The pattern of association was consistent for men and women; cardiometabolic, socio-demographic and behavioural factors did not attenuate sex/ethnicity associations. CONCLUSIONS: In this study, sex and ethnicity differential pattern of COVID-19 was not adequately explained by variations in cardiometabolic factors, 25(OH)-vitamin D levels or socio-economic factors. Factors which underlie ethnic differences in COVID-19 may not be easily captured, and so investigation of alternative biological and genetic susceptibilities as well as more comprehensive assessment of the complex economic, social and behavioural differences should be prioritised

CYP2C19 Genotype Prevalence and Association With Recurrent Myocardial Infarction in British–South Asians Treated With Clopidogrel

BACKGROUND: Cytochrome P450 family 2 subfamily C member 19 (CYP2C19) is a hepatic enzyme involved in the metabolism of clopidogrel from a prodrug to its active metabolite. Prior studies of genetic polymorphisms in CYP2C19 and their relationship with clinical efficacy have not included South Asian populations. OBJECTIVES: The objective of this study was to assess prevalence of common CYP2C19 genotype polymorphisms in a British-South Asian population and correlate these with recurrent myocardial infarction risk in participants prescribed clopidogrel. METHODS: The Genes & Health cohort of British Bangladeshi and Pakistani ancestry participants were studied. CYP2C19 diplotypes were assessed using array data. Multivariable logistic regression was used to test for association between genetically inferred CYP2C19 metabolizer status and recurrent myocardial infarction, controlling for known cardiovascular disease risk factors, percutaneous coronary intervention, age, sex, and population stratification. RESULTS: Genes & Health cohort participants (N = 44,396) have a high prevalence (57%) of intermediate or poor CYP2C19 metabolizers, with at least 1 loss-of-function CYP2C19 allele. The prevalence of poor metabolizers carrying 2 CYP2C19 loss-of-function alleles is 13%, which is higher than that in previously studied European (2.4%) and Central/South Asian populations (8.2%). Sixty-nine percent of the cohort who were diagnosed with an acute myocardial infarction were prescribed clopidogrel. Poor metabolizers were significantly more likely to have a recurrent myocardial infarction (OR: 3.1; P = 0.019). CONCLUSIONS: A pharmacogenomic-driven approach to clopidogrel prescribing has the potential to impact significantly on clinical management and outcomes in individuals of Bangladeshi and Pakistani ancestry

Mid-Upper Arm Circumference based Nutrition Programming: evidence for a new approach in regions with high burden of Acute Malnutrition

In therapeutic feeding programs (TFP), mid-upper arm circumference (MUAC) shows advantages over weight-for-height Z score (WHZ) and is recommended by the World Health Organization (WHO) as an independent criterion for screening children 6-59 months old. Here we report outcomes and treatment response from a TFP using MUAC ≤118 mm or oedema as sole admission criteria for severe acute malnutrition (SAM)

Over 1000 genetic loci influencing blood pressure with multiple systems and tissues implicated.

High blood pressure (BP) remains the major heritable and modifiable risk factor for cardiovascular disease. Persistent high BP, or hypertension, is a complex trait with both genetic and environmental interactions. Despite swift advances in genomics, translating new discoveries to further our understanding of the underlying molecular mechanisms remains a challenge. More than 500 loci implicated in the regulation of BP have been revealed by genome-wide association studies (GWAS) in 2018 alone, taking the total number of BP genetic loci to over 1000. Even with the large number of loci now associated to BP, the genetic variance explained by all loci together remains low (~5.7%). These genetic associations have elucidated mechanisms and pathways regulating BP, highlighting potential new therapeutic and drug repurposing targets. A large proportion of the BP loci were discovered and reported simultaneously by multiple research groups, creating a knowledge gap, where the reported loci to date have not been investigated in a harmonious way. Here, we review the BP-associated genetic variants reported across GWAS studies and investigate their potential impact on the biological systems using in silico enrichment analyses for pathways, tissues, gene ontology and genetic pleiotropy

Randomised, double-blind, placebo-controlled study investigating the effects of inorganic nitrate on vascular function, platelet reactivity and restenosis in stable angina: protocol of the NITRATE-OCT study

KSR and this work are funded by an NIHR Doctoral Fellowship (DRF-2014-07-008