Randomised controlled trial of population screening for atrial fibrillation in people aged 70 years and over to reduce stroke: protocol for the SAFER trial.

Introduction: There is a lack of evidence that the benefits of screening for atrial fibrillation (AF) outweigh the harms. Following the completion of the Screening for Atrial Fibrillation with ECG to Reduce stroke (SAFER) pilot trial, the aim of the main SAFER trial is to establish whether population screening for AF reduces incidence of stroke risk.

Methods And Analysis: Approximately 82 000 people aged 70 years and over and not on oral anticoagulation are being recruited from general practices in England.

A medium-chain fatty acid analogue prevents hepatosteatosis and decreases inflammatory lipid metabolites in a murine model of parenteral nutrition-induced hepatosteatosis.

Background: Parenteral (intravenous) nutrition is lifesaving for patients with intestinal failure, but long-term use of parenteral nutrition often leads to liver disease. SEFA-6179 is a synthetic medium-chain fatty acid analogue designed to target multiple fatty acid receptors regulating metabolic and inflammatory pathways. We hypothesized that SEFA-6179 would prevent hepatosteatosis and lipotoxicity in a murine model of parenteral nutrition-induced hepatosteatosis.

Human HDL subclasses modulate energy metabolism in skeletal muscle cells.

In addition to its antiatherogenic role, HDL reportedly modulates energy metabolism at the whole-body level. HDL functionality is associated with its structure and composition, and functional activities can differ between HDL subclasses. Therefore, we studied if HDL and HDL, the two major HDL subclasses, are able to modulate energy metabolism of skeletal muscle cells.

The roles of DGAT1 and DGAT2 in human myotubes are dependent on donor patho-physiological background.

The roles of DGAT1 and DGAT2 in lipid metabolism and insulin responsiveness of human skeletal muscle were studied using cryosections and myotubes prepared from muscle biopsies from control, athlete, and impaired glucose regulation (IGR) cohorts of men. The previously observed increases in intramuscular triacylglycerol (IMTG) in athletes and IGR were shown to be related to an increase in lipid droplet (LD) area in type I fibers in athletes but, conversely, in type II fibers in IGR subjects. Specific inhibition of both diacylglycerol acyltransferase (DGAT) 1 and 2 decreased fatty acid (FA) uptake by myotubes, whereas only DGAT2 inhibition also decreased fatty acid oxidation.

Progression of stroke risk in patients aged <65 years diagnosed with atrial fibrillation: a cohort study in general practice.

Background: As a result of new technologies, atrial fibrillation (AF) is more likely to be diagnosed in people aged <65 years.

Aim: To investigate the risk of someone diagnosed with AF aged <65 years developing an indication for anticoagulation before they reach 65 years.

Design And Setting: Population-based cohort study of patients from English practices using the Clinical Practice Research Datalink, a primary care database of electronic medical records.

SENP2 knockdown in human adipocytes reduces glucose metabolism and lipid accumulation, while increases lipid oxidation.

Adipose tissue is one of the main regulative sites for energy metabolism. Excess lipid storage and expansion of white adipose tissue (WAT) is the primary contributor to obesity, a strong predisposing factor for development of insulin resistance. Sentrin-specific protease (SENP) 2 has been shown to play a role in metabolism in murine fat and skeletal muscle cells, and we have previously demonstrated its role in energy metabolism of human skeletal muscle cells.

General practitioners' perceptions on opportunistic single-time point screening for atrial fibrillation: A European quantitative survey.

Background: There is no clear guidance on how to implement opportunistic atrial fibrillation (AF) screening in daily clinical practice.

Objectives: This study evaluated the perception of general practitioners (GPs) about value and practicalities of implementing screening for AF, focusing on opportunistic single-time point screening with a single-lead electrocardiogram (ECG) device.

Methods: A descriptive cross-sectional study was conducted with a survey developed to assess overall perception concerning AF screening, feasibility of opportunistic single-lead ECG screening and implementation requirements and barriers.

Demographic characteristics, long-term health conditions and healthcare experiences of 6333 trans and non-binary adults in England: nationally representative evidence from the 2021 GP Patient Survey.

Objective: In order to address the lack of data on the health and healthcare needs of trans and non-binary adults, NHS England includes questions asking about both gender and trans status in its surveys to support quality improvement programmes.We used self-reported data from the GP Patient Survey to answer the research question: what are the demographic characteristics, health conditions and healthcare experiences of trans and non-binary adults in England?

Design/setting: Nationally representative, population-based cross-sectional survey in England with survey data collection from January to March 2021.

Participants: 840 691 survey respondents including 6333 trans and non-binary adults.

Cluster randomised controlled trial of screening for atrial fibrillation in people aged 70 years and over to reduce stroke: protocol for the pilot study for the SAFER trial.

Introduction: Atrial fibrillation (AF) is a common arrhythmia associated with 30% of strokes, as well as other cardiovascular disease, dementia and death. AF meets many criteria for screening, but there is limited evidence that AF screening reduces stroke. Consequently, no countries recommend national screening programmes for AF.

Pancreatic Cancer Cell-Conditioned, Human-Derived Primary Myotubes Display Increased Leucine Turnover, Increased Lipid Accumulation, and Reduced Glucose Uptake.

Metabolic alterations occurring in cancer cells have been seen to also occur in other tissues than cancerous tissue. For instance, cachexia, peripheral insulin resistance, or both are commonly seen in patients with cancer. We explored differences in substrate use in myotubes conditioned with the medium from a pancreatic cancer cell line, PANC-1, or primary human pancreatic cells, hPECs.

Knockdown of sarcolipin (SLN) impairs substrate utilization in human skeletal muscle cells.

Background: Recent studies have highlighted that uncoupling of sarco-/endoplasmic reticulum Ca-ATPase (SERCA) by sarcolipin (SLN) increases ATP consumption and contributes to heat liberation. Exploiting this thermogenic mechanism in skeletal muscle may provide an attractive strategy to counteract obesity and associated metabolic disorders. In the present study, we have investigated the role of SLN on substrate metabolism in human skeletal muscle cells.

A structurally engineered fatty acid, icosabutate, suppresses liver inflammation and fibrosis in NASH.

Background & Aims: Although long-chain omega-3 fatty acids (LCn-3FAs) regulate inflammatory pathways of relevance to non-alcoholic steatohepatitis (NASH), their susceptibility to peroxidation may limit their therapeutic potential. We compared the metabolism of eicosapentaenoic acid (EPA) with an engineered EPA derivative (icosabutate) in human hepatocytes in vitro and their effects on hepatic glutathione metabolism, oxidised lipids, inflammation, and fibrosis in a dietary mouse model of NASH, and in patients prone to fatty liver disease.

Methods: Oxidation rates and cellular partitioning of EPA and icosabutate were compared in primary human hepatocytes.

SENP2 is vital for optimal insulin signaling and insulin-stimulated glycogen synthesis in human skeletal muscle cells.

Sentrin-specific protease (SENP) 2 has been suggested as a possible novel drug target for the treatment of obesity and type 2 diabetes mellitus after observations of a palmitate-induced increase in SENP2 that lead to increased fatty acid oxidation and improved insulin sensitivity in skeletal muscle cells from mice. However, no precedent research has examined the role of SENP2 in human skeletal muscle cells. In the present work, we have investigated the impact of SENP2 on fatty acid and glucose metabolism as well as insulin sensitivity in human skeletal muscle using cultured primary human myotubes.

The small molecule SERCA activator CDN1163 increases energy metabolism in human skeletal muscle cells.

Background And Objective: A number of studies have highlighted muscle-specific mechanisms of thermogenesis involving futile cycling of Ca driven by sarco (endo)plasmic reticulum Ca-ATPase (SERCA) and generating heat from ATP hydrolysis to be a promising strategy to counteract obesity and metabolic dysfunction. However, to the best of our knowledge, no experimental studies concerning the metabolic effects of pharmacologically targeting SERCA in human skeletal muscle cells have been reported. Thus, in the present study, we aimed to explore the effects of SERCA-activating compound, CDN1163, on energy metabolism in differentiated human skeletal muscle cells (myotubes).

Skeletal muscle energy metabolism in obesity.

Comparing energy metabolism in human skeletal muscle and primary skeletal muscle cells in obesity, while focusing on glucose and fatty acid metabolism, shows many common changes. Insulin-mediated glucose uptake in skeletal muscle and primary myotubes is decreased by obesity, whereas differences in basal glucose metabolism are inconsistent among studies. With respect to fatty acid metabolism, there is an increased uptake and storage of fatty acids and a reduced complete lipolysis, suggesting alterations in lipid turnover.

Anticoagulation trends in adults aged 65 years and over with atrial fibrillation: a cohort study.

Objective: To describe patterns of anticoagulation prescription and persistence for those aged ≥65 years with atrial fibrillation (AF).

Methods: Descriptive cohort study using electronic general practice records of patients in England, who attended an influenza vaccination aged ≥65 years and were diagnosed with AF between 2008 and 2018. Patients were stratified by 10-year age group and year of diagnosis.

Mitochondrial DNA from osteoarthritic patients drives functional impairment of mitochondrial activity: a study on transmitochondrial cybrids.

With the redefinition of osteoarthritis (OA) and the understanding that the joint behaves as an organ, OA is now considered a systemic illness with a low grade of chronic inflammation. Mitochondrial dysfunction is well documented in OA and has the capacity to alter chondrocyte and synoviocyte function. Transmitochondrial cybrids are suggested as a useful cellular model to study mitochondrial biology in vitro, as they carry different mitochondrial variants with the same nuclear background.

Temporal trends in incidence of atrial fibrillation in primary care records: a population-based cohort study.

Objectives: Atrial fibrillation (AF) is a heart condition associated with a fivefold increased risk of stroke. The condition can be detected in primary care and treatment can greatly reduce the risk of stroke. In recent years, a number of policy initiatives have tried to improve diagnosis and treatment of AF, including local National Health Service schemes and the Quality and Outcomes Framework.

Substrate oxidation in primary human skeletal muscle cells is influenced by donor age.

Primary human myotubes represent an alternative system to intact skeletal muscle for the study of human diseases related to changes in muscle energy metabolism. This work aimed to study if fatty acid and glucose metabolism in human myotubes in vitro were related to muscle of origin, donor gender, age, or body mass index (BMI). Myotubes from a total of 82 donors were established from three different skeletal muscles, i.

Pancreatic cancer cells show lower oleic acid oxidation and their conditioned medium inhibits oleic acid oxidation in human myotubes.

Background: /Objectives: We aimed to metabolically compare healthy primary human pancreatic epithelial cells (hPEC) to a pancreatic cancer cell line (PANC-1) and explore the effect on energy metabolism of exposing primary human myotubes to conditioned medium from hPEC and PANC-1 cells.

Methods: Differences in metabolism were examined with radiolabeled glucose, oleic acid and lactic acid, and by qPCR. Mass spectrometry-based proteomics was used to study global protein secretion from the two cell types.

Impaired Metabolic Flexibility in the Osteoarthritis Process: A Study on Transmitochondrial Cybrids.

Osteoarthritis (OA) is the most frequent joint disease; however, the etiopathogenesis is still unclear. Chondrocytes rely primarily on glycolysis to meet cellular energy demand, but studies implicate impaired mitochondrial function in OA pathogenesis. The relationship between mitochondrial dysfunction and OA has been established.

Treatment of human skeletal muscle cells with inhibitors of diacylglycerol acyltransferases 1 and 2 to explore isozyme-specific roles on lipid metabolism.

Diacylglycerol acyltransferases (DGAT) 1 and 2 catalyse the final step in triacylglycerol (TAG) synthesis, the esterification of fatty acyl-CoA to diacylglycerol. Despite catalysing the same reaction and being present in the same cell types, they exhibit different functions on lipid metabolism in various tissues. Yet, their roles in skeletal muscle remain poorly defined.

Increased Glycolysis and Higher Lactate Production in Hyperglycemic Myotubes.

Previous studies have shown that chronic hyperglycemia impairs glucose and fatty acid oxidation in cultured human myotubes. To further study the hyperglycemia-induced suppression of oxidation, lactate oxidation, mitochondrial function and glycolytic rate were evaluated. Further, we examined the intracellular content of reactive oxygen species (ROS), production of lactate and conducted pathway-ANOVA analysis on microarray data.

Higher lipid turnover and oxidation in cultured human myotubes from athletic versus sedentary young male subjects.

In this study we compared fatty acid (FA) metabolism in myotubes established from athletic and sedentary young subjects. Six healthy sedentary (maximal oxygen uptake (VO) ≤ 46 ml/kg/min) and six healthy athletic (VO > 60 ml/kg/min) young men were included. Myoblasts were cultured and differentiated to myotubes from satellite cells isolated from biopsy of musculus vastus lateralis.