Background: Healthy development of children is under pressure. While governments, schools and organizations are trying to stimulate physical activity in children, reduce overweight and improve motor skills, they are facing challenges in finding effective strategies. The model proposed by Stodden et al. (2008) is an interesting framework for studying healthy development of children, as it encompasses the physical aspect (motor skill competence, physical fitness, weight status), the mental aspect (perceived competence) and a behavioral component (physical activity). Importantly, it acknowledges the developmental stages of children by including age. Therefore, this model serves as the basis for this study in which we are looking for insights to effectively influence healthy development of children. Methods and Results: We measured these five variables in a large sample (N > 1000) of children in the Netherlands (age: 4-12, 50% girls). Through structural equation modeling we searched for cross-sectional as well as 1-year longitudinal relationships. Our results showed concurrent relationships between all variables and a tipping point at which relationships emerged or strengthened. The results indicated that targeting motor competence at a young age might be a feasible way to ensure continued participation in physical activities. However, longitudinal analyses revealed no effect of motor skill competence (T1) on physical activity (T2). Physical fitness appeared to be more important as a potential mediator than perceived motor competence. As a follow-up study, the five variables will be analyzed via a person-centered approach (latent profile analyses). This will guide us towards tailoring future interventions to the specific needs of subgroups of children. Analyses of this study are ongoing and will be presented at the conference. Conclusions: Our multiple analyses have shed additional light on the complexity of healthy development of children. In the upcoming presentation we will unite our study findings and delineate implications for developing effective strategies.
MULTIFILE
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.
