AimsGenetic hypertrophic cardiomyopathy (HCM) is caused by mutations in sarcomere protein-encoding genes (i.e. genotype-positive HCM). In an increasing number of patients, HCM occurs in the absence of a mutation (i.e. genotype-negative HCM). Mitochondrial dysfunction is thought to be a key driver of pathological remodelling in HCM. Reports of mitochondrial respiratory function and specific disease-modifying treatment options in patients with HCM are scarce.Methods and resultsRespirometry was performed on septal myectomy tissue from patients with HCM (n = 59) to evaluate oxidative phosphorylation and fatty acid oxidation. Mitochondrial dysfunction was most notably reflected by impaired NADH-linked respiration. In genotype-negative patients, but not genotype-positive patients, NADH-linked respiration was markedly depressed in patients with an indexed septal thickness ≥10 compared with <10. Mitochondrial dysfunction was not explained by reduced abundance or fragmentation of mitochondria, as evaluated by transmission electron microscopy. Rather, improper organization of mitochondria relative to myofibrils (expressed as a percentage of disorganized mitochondria) was strongly associated with mitochondrial dysfunction. Pre-incubation with the cardiolipin-stabilizing drug elamipretide and raising mitochondrial NAD+ levels both boosted NADH-linked respiration.ConclusionMitochondrial dysfunction is explained by cardiomyocyte architecture disruption and is linked to septal hypertrophy in genotype-negative HCM. Despite severe myocardial remodelling mitochondria were responsive to treatments aimed at restoring respiratory function, eliciting the mitochondria as a drug target to prevent and ameliorate cardiac disease in HCM. Mitochondria-targeting therapy may particularly benefit genotype-negative patients with HCM, given the tight link between mitochondrial impairment and septal thickening in this subpopulation.
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OBJECTIVE: Juvenile dermatomyositis (DM) is an inflammatory myopathy in which the immune system targets the microvasculature of the skeletal muscle and skin, leading to significant muscle weakness and exercise intolerance, although the precise etiology is unknown. The goal of this study was to investigate the changes in exercise capacity in children with myositis during active and inactive disease periods and to study the responsiveness of exercise parameters.METHODS: Thirteen children with juvenile DM (mean+/-SD age 11.2+/-2.6 years) participated in this study. Patients performed a maximal exercise test using an electronically braked cycle ergometer and respiratory gas analysis system. Exercise parameters were analyzed, including peak oxygen uptake (VO2peak), peak work rate (Wpeak), and ventilatory anaerobic threshold (VAT). All children were tested during an active period of the disease and during a remission period. From these data, 4 different response statistics were calculated.RESULTS: The children performed significantly better during a remission period compared with a period of active disease. Most exercise parameters showed a very large response. The 5 most responsive parameters were Wpeak, Wpeak (percent predicted), oxygen pulse, VO2peak, and power at the VAT.CONCLUSION: We found in our longitudinal study that children with active juvenile DM had significantly reduced exercise parameters compared with a remission period. Moreover, we found that several parameters had very good responsiveness. With previously established validity and reliability, exercise testing has been demonstrated to be an excellent noninvasive instrument for the longitudinal followup of children with myositis.
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Mechanical power output is a key performance-determining variable in many cyclic sports. In rowing, instantaneous power output is commonly determined as the dot product of handle force moment and oar angular velocity. The aim of this study was to show that this commonly used proxy is theoretically flawed and to provide an indication of the magnitude of the error. To obtain a consistent dataset, simulations were performed using a previously proposed forward dynamical model. Inputs were previously recorded rower kinematics and horizontal oar angle, at 20 and 32 strokes∙min−1. From simulation outputs, true power output and power output according to the common proxy were calculated. The error when using the common proxy was quantified as the difference between the average power output according to the proxy and the true average power output (P̅residual), and as the ratio of this difference to the true average power output (ratiores./rower). At stroke rate 20, P̅residual was 27.4 W and ratiores./rower was 0.143; at stroke rate 32, P̅residual was 44.3 W and ratiores./rower was 0.142. Power output in rowing appears to be underestimated when calculated according to the common proxy. Simulations suggest this error to be at least 10% of the true power output.
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Physical activity (PA) is important for healthy ageing. Better insight into objectively measured PA levels in older adults is needed, since most previous studies employed self-report measures for PA assessment, which are associated with overestimation of PA. This study aimed to provide insight in objectively measured indoor and outdoor PA of older adults, and in PA differences by frailty levels. Data were collected among non-frail (N = 74) and frail (N = 10) subjects, aged 65 to 89 years. PA, measured for seven days with accelerometers and GPS-devices, was categorized into three levels of intensity (sedentary, light, and moderate-to-vigorous PA). Older adults spent most time in sedentary and light PA. Subjects spent 84.7%, 15.1% and 0.2%per day in sedentary, light and moderate-to-vigorous PA respectively. On average, older adults spent 9.8 (SD 23.7) minutes per week in moderate-to-vigorous activity, and 747.0 (SD 389.6) minutes per week in light activity. None of the subjects met the WHO recommendations of 150 weekly minutes of moderate-to-vigorous PA. Age-, sex- and health status-adjusted results revealed no differences in PA between non-frail and frail older adults. Subjects spent significantly more sedentary time at home, than not at home. Non-frail subjects spent significantly more time not at home during moderate-to-vigorous activities, than at home. Objective assessment of PA in older adults revealed that most PA was of light intensity, and time spent in moderate-to-vigorous PA was very low. None of the older adults met the World Health Organization recommendations for PA. These levels of MVPA are much lower than generally reported based on self-reported PA. Future studies should employ objective methods, and age specific thresholds for healthy PA levels in older adults are needed. These results emphasize the need for effective strategies for healthy PA levels for the growing proportion of older adults. https://doi.org/10.1371/journal.pone.0123168
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Background: The aims of this systematic review were to study the effectiveness of primary school-based physical activity, sedentary behavior and nutrition interventions with direct parental involvement on children’s BMI or BMI z-score, physical activity, sedentary behavior and nutrition behavior and categorize intervention components into targeted socio-cognitive determinants and environmental types using the Environmental Research framework for weight Gain prevention. Methods: In March 2018, a systematic search was conducted in four electronic literature databases. Articles written in English about effectiveness studies on school-based interventions with direct parental involvement targeting 4–12 year olds were included. Interventions with indirect parental involvement, interventions not targeting the school environment, and pilot studies were excluded. Study and intervention characteristics were extracted. Study quality and study effectiveness were assessed and effect sizes (Cohen’s d) were calculated for the outcome measures. Types of socio-cognitive factors and environmental types targeted were distinguished. Results: In total, 25 studies were included. Most studies on BMI or BMI z-score, physical activity and sedentary behavior found favorable results: 61.1%, 81.1% and 75%, respectively. Results regarding nutrition behavior were inconclusive. Methodological study quality varied. All interventions targeted multiple environmental types in the school and family environment. Five targeted socio-cognitive determinants (knowledge, awareness, attitude, self-efficacy and intrinsic motivation) of the children were identified. No consistent pattern was found between either type of environment targeted, number of type of environment targeted, or the child’s targeted socio-cognitive determinants and intervention effectiveness. Discussion: School-based interventions with direct parental involvement have the potential to improve children’s weight status, physical activity and sedentary behavior. Based on the results, it is recommended that school-based interventions with direct parental involvement target more than one EBRB, last at least one year, and focus particularly on the physical and social environment within both the school and the family environment
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AbstractThis study assessed the efficacy of a co-designed, school-based intervention meant to promote physical activityand fitness among Dutch prevocational secondary students. In a two-year clustered randomized controlled trial,students’ physical activity and fitness was measured by indirect and direct methods. In the intervention group,we used the triple-I procedure, a participatory action research method, to co-design the intervention together withthe students and schools. This procedure involved focus group discussions by interviewing and imagingtechniques, followed by a co-design process to align the intervention content and implementation processes withstudents’ preferences. The study involved 22 Dutch schools, with a total of 2685 13-to-14-year-old prevocationalsecondary students. Schools were randomly assigned to either intervention (11 schools, 1446 students) or controlgroup (11 schools, 1239 students).There were no significant intervention differences between students’ overallphysical activity behavior on intervention versus control schools. However, with regards to various specificphysical fitness indicators, such as the long jump, handgrip strength, shuttle run test, and the sum of skinfolds,intervention school students performed significantly better than the control group students. Furthermore, whentaking into account student participation, i.e. the success of the co-design process, schools with higher levels ofstudent participation showed higher shuttle run scores. However, such graded effects were not similarly apparentwith regards to students’ physical fitness indicators. This study showed that co-designing a comprehensivephysical activity intervention on numerous Dutch high schools via the Triple-I Interactive Method was feasible.Moreover, results showed that certain aspects of physical fitness were improved after two years of intervention,although taken together with the lack of effects on physical activity, results were mixed.
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As the two prime examples of sport light, running and walking have become very popular sports activities in the past decades. There are references in the literature of similarities between both sports, however these parallels have never been studied. In addition, the current digitalisation of society can have important influences on the further diversification of profiles. Data of a large-scale population survey among runners and walkers (n = 4913) in Flanders (Belgium) were used to study their sociodemographic, sports related and attitudinal characteristics, and wearable usage. The results showed that walkers are more often female, older, lower educated, and less often use wearables. To predict wearable usage, sports-related and attitudinal characteristics are important among runners but not among walkers. Motivational variables to use wearables are important to predict wearable usage among both runners and walkers. Additionally, whether or not the runner or walker registers the heart rate is the most important predictor. The present study highlights similarities and differences between runners and walkers. By adding attitudinal characteristics and including walkers this article provides new insights to the literature, which can be used by policymakers and professionals in the field of sport, exercise and health, and technology developers to shape their services accordingly.
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Muscle fiber-type specific expression of UCP3-protein is reported here for the firts time, using immunofluorescence microscopy
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Skeletal muscle-related symptoms are common in both acute coronavirus disease (Covid)-19 and post-acute sequelae of Covid-19 (PASC). In this narrative review, we discuss cellular and molecular pathways that are affected and consider these in regard to skeletal muscle involvement in other conditions, such as acute respiratory distress syndrome, critical illness myopathy, and post-viral fatigue syndrome. Patients with severe Covid-19 and PASC suffer from skeletal muscle weakness and exercise intolerance. Histological sections present muscle fibre atrophy, metabolic alterations, and immune cell infiltration. Contributing factors to weakness and fatigue in patients with severe Covid-19 include systemic inflammation, disuse, hypoxaemia, and malnutrition. These factors also contribute to post-intensive care unit (ICU) syndrome and ICU-acquired weakness and likely explain a substantial part of Covid-19-acquired weakness. The skeletal muscle weakness and exercise intolerance associated with PASC are more obscure. Direct severe acute respiratory syndrome coronavirus (SARS-CoV)-2 viral infiltration into skeletal muscle or an aberrant immune system likely contribute. Similarities between skeletal muscle alterations in PASC and chronic fatigue syndrome deserve further study. Both SARS-CoV-2-specific factors and generic consequences of acute disease likely underlie the observed skeletal muscle alterations in both acute Covid-19 and PASC.
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