Sleep, circadian biology and skeletal muscle interactions : Implications for metabolic health

There currently exists a modern epidemic of sleep loss, triggered by the changing demands of our 21st century lifestyle that embrace ‘round-the-clock’ remote working hours, access to energy-dense food, prolonged periods of inactivity, and on-line social activities. Disturbances to sleep patterns impart widespread and adverse effects on numerous cells, tissues, and organs. Insufficient sleep causes circadian misalignment in humans, including perturbed peripheral clocks, leading to disrupted skeletal muscle and liver metabolism, and whole-body energy homeostasis. Fragmented or insufficient sleep also perturbs the hormonal milieu, shifting it towards a catabolic state, resulting in reduced rates of skeletal muscle protein synthesis. The interaction between disrupted sleep and skeletal muscle metabolic health is complex, with the mechanisms underpinning sleep-related disturbances on this tissue often multifaceted. Strategies to promote sufficient sleep duration combined with the appropriate timing of meals and physical activity to maintain circadian rhythmicity are important to mitigate the adverse effects of inadequate sleep on whole-body and skeletal muscle metabolic health. This review summarises the complex relationship between sleep, circadian biology, and skeletal muscle, and discusses the effectiveness of several strategies to mitigate the negative effects of disturbed sleep or circadian rhythms on skeletal muscle health

Addressing domestic abuse within the police – exploring Welsh police forces’ response to victims and offenders as employees

This small project was instigated in response to the current crisis of police legitimacy, particularly regarding Violence Against Women and Girls (VAWG). Violence against women committed by serving police officers e.g., David Carrick and Wayne Cousins has shaken trust in the police and called into question their organisational integrity. One of the key challenges levelled at the police is the need to effectively manage internal issues regarding misogyny, harassment and domestic abuse (HMICFRS, 2021). As the senior panel response to the ‘super complaint’ on Police Perpetrated Domestic Abuse (PPDA) acknowledged, ‘the police response to PPDA is a feature of policing that is significantly harming the interests of the public’ (Gov.uk, 2022)

A systematic review on fitness testing in adult male basketball players : tests adopted, characteristics reported and recommendations for practice

Background: As basketball match-play requires players to possess a wide range of physical characteristics, many tests have been introduced in the literature to identify talent and quantify fitness in various samples of players. However, a synthesis of the literature to identify the most frequently used tests, outcome variables, and normative values for basketball-related physical characteristics in adult male basketball players is yet to be conducted. Objective: The primary objectives of this systematic review are to (1) identify tests and outcome variables used to assess physical characteristics in adult male basketball players across all competition levels, (2) report a summary of anthropometric, muscular power, linear speed, change-of-direction speed, agility, strength, anaerobic capacity, and aerobic capacity in adult male basketball players based on playing position and competition level, and (3) introduce a framework outlining recommended testing approaches to quantify physical characteristics in adult male basketball players. Methods: A systematic review of MEDLINE, PubMed, SPORTDiscus, Scopus, and Web of Science was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify relevant studies. To be eligible for inclusion, studies were required to: (1) be original research articles; (2) be published in a peer-reviewed journal; (3) have full-text versions available in the English language; and (4) include the primary aim of reporting tests used and/or the physical characteristics of adult (i.e., ≥ 18 years of age) male basketball players. Additionally, data from the top 10 draft picks who participated in the National Basketball Association combined from 2011–12 to 2020–21 were extracted from the official league website to highlight the physical characteristics of elite 19- to 24-year-old basketball players. Results: A total of 1684 studies were identified, with 375 being duplicates. Consequently, the titles and abstracts of 1309 studies were screened and 231 studies were eligible for full-text review. The reference list of each study was searched, with a further 59 studies identified as eligible for review. After full-text screening, 137 studies identified tests, while 114 studies reported physical characteristics in adult male basketball players. Conclusions: Physical characteristics reported indicate a wide range of abilities are present across playing competitions. The tests and outcome variables reported in the literature highlight the multitude of tests currently being used. Because there are no accepted international standards for physical assessment of basketball players, establishing normative data is challenging. Therefore, future testing should involve repeatable protocols that are standardised and provide outcomes that can be monitored across time. Recommendations for testing batteries in adult male basketball players are provided so improved interpretation of data can occur. Clinical Trial Registration: This review was registered with the International Prospective Register of Systematic Reviews and allocated registration number CRD42020187151 on 28 April, 2020. © 2022, The Author(s)

Mitochondrial dysfunction has divergent, cell type-dependent effects on insulin action

The contribution of mitochondrial dysfunction to insulin resistance is a contentious issue in metabolic research. Recent evidence implicates mitochondrial dysfunction as contributing to multiple forms of insulin resistance. However, some models of mitochondrial dysfunction fail to induce insulin resistance, suggesting greater complexity describes mitochondrial regulation of insulin action. We report that mitochondrial dysfunction is not necessary for cellular models of insulin resistance. However, impairment of mitochondrial function is sufficient for insulin resistance in a cell type-dependent manner, with impaired mitochondrial function inducing insulin resistance in adipocytes, but having no effect, or insulin sensitising effects in hepatocytes. The mechanism of mitochondrial impairment was important in determining the impact on insulin action, but was independent of mitochondrial ROS production. These data can account for opposing findings on this issue and highlight the complexity of mitochondrial regulation of cell type-specific insulin action, which is not described by current reductionist paradigms

Do health behaviours change after colonoscopy? A prospective cohort study on diet, alcohol, physical activity and smoking among patients and their partners

Objectives: To describe diet, alcohol, physical activity and tobacco use prospectively, that is, before and 10 months after colonoscopy for patients and their partners. Design: Prospective cohort study of health behaviour change in patients and partners. Comparison groups are patients receiving a normal result notification (NRN) versus patients receiving an abnormal result notification (ARN). Patients and partners (controls) are also compared. Setting: 5 Scottish hospitals. Participants: Of 5798 colonoscopy registrations, 2577 (44%) patients met the eligibility criteria of whom 565 (22%) were recruited; 460 partners were also recruited. Measures: International Physical Activity Questionnaire, Scottish Collaborative Group Food Frequency Questionnaire (includes alcohol), smoking status, sociodemographic characteristics, body mass index, medical conditions, colonoscopy result, Multidimensional Health Locus of Control Scale, behaviour-specific self-efficacy scales. Results: 57% of patients were men, with a mean age of 60.8 years (SE 0.5) and 43% were from more affluent areas. 72% (n=387) of patients received an ARN and 28% (n=149) received an NRN. Response rate of the second questionnaire was 68.9%. Overall, 27% of patients consumed < 5 measures of fruit and vegetables/day, 20% exceeded alcohol limits, 50% had low levels of physical activity and 21% were obese. At 10-month follow-up, a 5% reduction in excessive alcohol consumption and an 8% increase in low levels of physical activity were observed among patients; no significant changes occurred in partners. Baseline high alcohol consumption and low physical activity were the strongest predictors of these behaviours at follow-up. Low alcohol self-efficacy and increasing age were associated with poorer health-related behaviours at follow-up for alcohol consumption and physical activity, respectively. Conclusions: Colonoscopy is associated with marginal beneficial changes in some behaviours but not others. Further work is needed to explore how services can optimise increases in beneficial behaviours and mitigate increases in harmful ones

Do health behaviours change after colonoscopy?:A prospective cohort study on diet, alcohol, physical activity and smoking among patients and their partners

Objectives To describe diet, alcohol, physical activity and tobacco use prospectively, that is, before and 10 months after colonoscopy for patients and their partners.Design Prospective cohort study of health behaviour change in patients and partners. Comparison groups are patients receiving a normal result notification (NRN) versus patients receiving an abnormal result notification (ARN). Patients and partners (controls) are also compared.Setting 5 Scottish hospitals.Participants Of 5798 colonoscopy registrations, 2577 (44%) patients met the eligibility criteria of whom 565 (22%) were recruited; 460 partners were also recruited.Measures International Physical Activity Questionnaire, Scottish Collaborative Group Food Frequency Questionnaire (includes alcohol), smoking status, sociodemographic characteristics, body mass index, medical conditions, colonoscopy result, Multidimensional Health Locus of Control Scale, behaviour-specific self-efficacy scales.Results 57% of patients were men, with a mean age of 60.8 years (SE 0.5) and 43% were from more affluent areas. 72% (n=387) of patients received an ARN and 28% (n=149) received an NRN. Response rate of the second questionnaire was 68.9%. Overall, 27% of patients consumed &lt;5 measures of fruit and vegetables/day, 20% exceeded alcohol limits, 50% had low levels of physical activity and 21% were obese. At 10-month follow-up, a 5% reduction in excessive alcohol consumption and an 8% increase in low levels of physical activity were observed among patients; no significant changes occurred in partners. Baseline high alcohol consumption and low physical activity were the strongest predictors of these behaviours at follow-up. Low alcohol self-efficacy and increasing age were associated with poorer health-related behaviours at follow-up for alcohol consumption and physical activity, respectively.Conclusions Colonoscopy is associated with marginal beneficial changes in some behaviours but not others. Further work is needed to explore how services can optimise increases in beneficial behaviours and mitigate increases in harmful ones

Putting the squeeze on compression garments: current evidence and recommendations for future research: a systematic scoping review

Background: Compression garments are regularly worn during exercise to improve physical performance, mitigate fatigue responses, and enhance recovery. However, evidence for their efficacy is varied and the methodological approaches and outcome measures used within the scientific literature are diverse. Objectives: The aim of this scoping review is to provide a comprehensive overview of the effects of compression garments on commonly assessed outcome measures in response to exercise, including: performance, biomechanical, neuromuscular, cardiovascular, cardiorespiratory, muscle damage, thermoregulatory, and perceptual responses. Methods: A systematic search of electronic databases (PubMed, SPORTDiscus, Web of Science and CINAHL Complete) was performed from the earliest record to 27 December, 2020. Results: In total, 183 studies were identified for qualitative analysis with the following breakdown: performance and muscle function outcomes: 115 studies (63%), biomechanical and neuromuscular: 59 (32%), blood and saliva markers: 85 (46%), cardiovascular: 76 (42%), cardiorespiratory: 39 (21%), thermoregulatory: 19 (10%) and perceptual: 98 (54%). Approximately 85% (n = 156) of studies were published between 2010 and 2020. Conclusions: Evidence is equivocal as to whether garments improve physical performance, with little evidence supporting improvements in kinetic or kinematic outcomes. Compression likely reduces muscle oscillatory properties and has a positive effect on sensorimotor systems. Findings suggest potential increases in arterial blood flow; however, it is unlikely that compression garments meaningfully change metabolic responses, blood pressure, heart rate, and cardiorespiratory measures. Compression garments increase localised skin temperature and may reduce perceptions of muscle soreness and pain following exercise; however, rating of perceived exertion during exercise is likely unchanged. It is unlikely that compression garments negatively influence exercise-related outcomes. Future research should assess wearer belief in compression garments, report pressure ranges at multiple sites as well as garment material, and finally examine individual responses and varying compression coverage areas

Rapid development of non-alcoholic steatohepatitis in Psammomys obesus (Israeli sand rat)

Background and Aims: A major impediment to establishing new treatments for non-alcoholic steatohepatitis is the lack of suitable animal models that accurately mimic the biochemical and metabolic characteristics of the disease. The aim of this study was to explore a unique polygenic animal model of metabolic disease as a model of non-alcoholic steatohepatitis by determining the effects of 2% dietary cholesterol supplementation on metabolic and liver endpoints in Psammomys obesus (Israeli sand rat). Methods: P. obesus were provided ad libitum access to either a standard rodent diet (20% kcal/fat) or a standard rodent diet supplemented with 2% cholesterol (w/w) for 4 weeks. Histological sections of liver from animals on both diets were examined for key features of non-alcoholic steatohepatitis. The expression levels of key genes involved in hepatic lipid metabolism were measured by real-time PCR. Results: P. obesus fed a cholesterol-supplemented diet exhibited profound hepatomegaly and steatosis, and higher plasma transaminase levels. Histological analysis identified extensive steatosis, inflammation, hepatocyte injury and fibrosis. Hepatic gene expression profiling revealed decreased expression of genes involved in delivery and uptake of lipids, and fatty acid and triglyceride synthesis, and increased expression of genes involved in very low density lipoprotein cholesterol synthesis, triglyceride and cholesterol export. Conclusions: P. obesus rapidly develop non-alcoholic steatohepatitis when fed a cholesterol-supplemented diet that appears to be histologically and mechanistically similar to patients. © 2014 Spolding et al

Zinc Finger Nuclease mediated knockout of ADP dependent Glucokinase in Cancer cell lines: Effects on cell survival and Mitochondrial Oxidative Metabolism

<div><p>Zinc finger nucleases (ZFN) are powerful tools for editing genes in cells. Here we use ZFNs to interrogate the biological function of <i>ADPGK</i>, which encodes an ADP-dependent glucokinase (ADPGK), in human tumour cell lines. The hypothesis we tested is that ADPGK utilises ADP to phosphorylate glucose under conditions where ATP becomes limiting, such as hypoxia. We characterised two ZFN knockout clones in each of two lines (H460 and HCT116). All four clones had frameshift mutations in all alleles at the target site in exon 1 of <i>ADPGK,</i> and were ADPGK-null by immunoblotting. <i>ADPGK</i> knockout had little or no effect on cell proliferation, but compromised the ability of H460 cells to survive siRNA silencing of hexokinase-2 under oxic conditions, with clonogenic survival falling from 21±3% for the parental line to 6.4±0.8% (p = 0.002) and 4.3±0.8% (p = 0.001) for the two knockouts. A similar increased sensitivity to clonogenic cell killing was observed under anoxia. No such changes were found when <i>ADPGK</i> was knocked out in HCT116 cells, for which the parental line was less sensitive than H460 to anoxia and to hexokinase-2 silencing. While knockout of <i>ADPGK</i> in HCT116 cells caused few changes in global gene expression, knockout of <i>ADPGK</i> in H460 cells caused notable up-regulation of mRNAs encoding cell adhesion proteins. Surprisingly, we could discern no consistent effect on glycolysis as measured by glucose consumption or lactate formation under anoxia, or extracellular acidification rate (Seahorse XF analyser) under oxic conditions in a variety of media. However, oxygen consumption rates were generally lower in the <i>ADPGK</i> knockouts, in some cases markedly so. Collectively, the results demonstrate that <i>ADPGK</i> can contribute to tumour cell survival under conditions of high glycolytic dependence, but the phenotype resulting from knockout of <i>ADPGK</i> is cell line dependent and appears to be unrelated to priming of glycolysis in these lines.</p></div

Author Correction: Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk

Correction to: Nature Geneticshttps://doi.org/10.1038/s41588-023-01314-0, published online 13 March 2023. In the version of the article initially published, the sample sizes in the main text and Supplementary Tables 1 and 2 were incorrect. In the abstract, the last paragraph of the Introduction, the first paragraph of the Results, the top box in Figure 1a and the Supplementary Information, the total sample size has been corrected from 580,869 to 588,452 participants and the size of the European cohort from 468,062 to 475,645. Some of the effect sizes in Supplementary Table 14 (columns W, Z, AC, AF) had the wrong sign. There was also an error in Supplementary Table 3 where the sample size instead of the variant count was shown for EXCEED. The errors do not affect the conclusions of the study. Additionally, two acknowledgments for use of INTERVAL pQTL and Lung eQTL consortium data were omitted from the Supplementary Information. These errors have been corrected in the Supplementary Information and HTML and PDF versions of the article