Three weeks of interrupting sitting lowers fasting glucose and glycemic variability, but not glucose tolerance, in free-living women and men with obesity

Funding This work was supported by grants from the Novo Nordisk Foundation (NNF14OC0011493, NNF14OC0009941, NNF18CC0034900), Swedish Diabetes Foundation (DIA2018-357), Diabetes Wellness Sverige (1849-PG), Swedish Research Council (2015-00165, 2018-02389), the Strategic Research Programme in Diabetes at Karolinska Institutet (2009-1068), the Knut and Alice Wallenberg Foundation (2018-0094), and the Stockholm County Council (SLL20170159). D.D. is supported by the National Health and Medical Research Council and the Victorian Government’s OIS scheme. Acknowledgements We thank the Swedish Metabolomics Centre (Umeå University) for assisting with the lipidomic analysis and Mariam Nordstrand for efforts in the recruitment and screening of participants, and in muscle biopsy procedure. The current addresses for S.P. and B.M.G. are the School of Life Sciences, University of Nottingham, Nottingham, UK, and The Rowett Institute, University of Aberdeen, Aberdeen, UK, respectively.Peer reviewedPostprin

Cell selectivity in succinate receptor SUCNR1/GPR91 signaling in skeletal muscle

Succinate is released by skeletal muscle during exercise and activates SUCNR1/GPR91. Signaling of SUCNR1 is involved in metabolite-sensing paracrine communication in skeletal muscle during exercise. However, the specific cell types responding to succinate and the directionality of communication are unclear. We aim to characterize the expression of SUCNR1 in human skeletal muscle. De novo analysis of transcriptomic datasets demonstrated that SUCNR1 mRNA is expressed in immune, adipose, and liver tissues, but scarce in skeletal muscle. In human tissues, SUCNR1 mRNA was associated with macrophage markers. Single-cell RNA sequencing and fluorescent RNAscope demonstrated that in human skeletal muscle, SUCNR1 mRNA is not expressed in muscle fibers but coincided with macrophage populations. Human M2-polarized macrophages exhibit high levels of SUCNR1 mRNA and stimulation with selective agonists of SUCNR1 triggered Gq- and Gi-coupled signaling. Primary human skeletal muscle cells were unresponsive to SUCNR1 agonists. In conclusion, SUCNR1 is not expressed in muscle cells and its role in the adaptive response of skeletal muscle to exercise is most likely mediated via paracrine mechanisms involving M2-like macrophages within the muscle. NEW & NOTEWORTHY Macrophages but not skeletal muscle cells respond to extracellular succinate via SUCNR1/GPR91

Tests examining skill outcomes in sport: A systematic review of measurement properties and feasibility

BackgroundA high level of participant skill is influential in determining the outcome of many sports. Thus, tests assessing skill outcomes in sport are commonly used by coaches and researchers to estimate an athlete&rsquo;s ability level, to evaluate the effectiveness of interventions or for the purpose of talent identification.ObjectiveThe objective of this systematic review was to examine the methodological quality, measurement properties and feasibility characteristics of sporting skill outcome tests reported in the peer-reviewed literature.Data SourcesA search of both SPORTDiscus and MEDLINE databases was undertaken.Study SelectionStudies that examined tests of sporting skill outcomes were reviewed. Only studies that investigated measurement properties of the test (reliability or validity) were included. A total of 22 studies met the inclusion/exclusion criteria.Study Appraisal and Synthesis MethodsA customised checklist of assessment criteria, based on previous research, was utilised for the purpose of this review.ResultsA range of sports were the subject of the 22 studies included in this review, with considerations relating to methodological quality being generally well addressed by authors. A range of methods and statistical procedures were used by researchers to determine the measurement properties of their skill outcome tests. The majority (95 %) of the reviewed studies investigated test&ndash;retest reliability, and where relevant, inter and intra-rater reliability was also determined. Content validity was examined in 68 % of the studies, with most tests investigating multiple skill domains relevant to the sport. Only 18 % of studies assessed all three reviewed forms of validity (content, construct and criterion), with just 14 % investigating the predictive validity of the test. Test responsiveness was reported in only 9 % of studies, whilst feasibility received varying levels of attention.LimitationsIn organised sport, further tests may exist which have not been investigated in this review. This could be due to such tests firstly not being published in the peer-review literature and secondly, not having their measurement properties (i.e., reliability or validity) examined formally.ConclusionsOf the 22 studies included in this review, items relating to test methodological quality were, on the whole, well addressed. Test&ndash;retest reliability was determined in all but one of the reviewed studies, whilst most studies investigated at least two aspects of validity (i.e., content, construct or criterion-related validity). Few studies examined predictive validity or responsiveness. While feasibility was addressed in over half of the studies, practicality and test limitations were rarely addressed. Consideration of study quality, measurement properties and feasibility components assessed in this review can assist future researchers when developing or modifying tests of sporting skill outcomes.<br /

Thrombotic and hemorrhagic complications of COVID-19 in adults hospitalized in high-income countries compared with those in adults hospitalized in low- and middle-income countries in an international registry

Background: COVID-19 has been associated with a broad range of thromboembolic, ischemic, and hemorrhagic complications (coagulopathy complications). Most studies have focused on patients with severe disease from high-income countries (HICs). Objectives: The main aims were to compare the frequency of coagulopathy complications in developing countries (low- and middle-income countries [LMICs]) with those in HICs, delineate the frequency across a range of treatment levels, and determine associations with in-hospital mortality. Methods: Adult patients enrolled in an observational, multinational registry, the International Severe Acute Respiratory and Emerging Infections COVID-19 study, between January 1, 2020, and September 15, 2021, met inclusion criteria, including admission to a hospital for laboratory-confirmed, acute COVID-19 and data on complications and survival. The advanced-treatment cohort received care, such as admission to the intensive care unit, mechanical ventilation, or inotropes or vasopressors; the basic-treatment cohort did not receive any of these interventions. Results: The study population included 495,682 patients from 52 countries, with 63% from LMICs and 85% in the basic treatment cohort. The frequency of coagulopathy complications was higher in HICs (0.76%-3.4%) than in LMICs (0.09%-1.22%). Complications were more frequent in the advanced-treatment cohort than in the basic-treatment cohort. Coagulopathy complications were associated with increased in-hospital mortality (odds ratio, 1.58; 95% CI, 1.52-1.64). The increased mortality associated with these complications was higher in LMICs (58.5%) than in HICs (35.4%). After controlling for coagulopathy complications, treatment intensity, and multiple other factors, the mortality was higher among patients in LMICs than among patients in HICs (odds ratio, 1.45; 95% CI, 1.39-1.51). Conclusion: In a large, international registry of patients hospitalized for COVID-19, coagulopathy complications were more frequent in HICs than in LMICs (developing countries). Increased mortality associated with coagulopathy complications was of a greater magnitude among patients in LMICs. Additional research is needed regarding timely diagnosis of and intervention for coagulation derangements associated with COVID-19, particularly for limited-resource settings