Childhood motor performance is increased by participation in organized sport: the CHAMPS Study-DK

Evidence suggests that motor performance in children is declining globally. We tested whether participation in organized sport is associated with motor performance, and estimate the effect of 30 months participation in organized sport on motor performance. Study participants were 1067 primary school students, enrolled in the Danish Childhood Health, Activity, and Motor Performance School study. Participation in organized sport was reported via text messaging. Coordination-related motor performance composite, fitness-related motor performance composite, and total motor performance composite were calculated. Data were analyzed using Generalized Estimating Equations. Participation in organized sport was positively associated with motor performance (all composites) in models that did and did not control for baseline motor performance. For models that did not control for baseline motor performance, this equated to 2–6% increases in motor performance per weekly sport session; for models that did control for baseline motor performance, this equated to 1–5% increases in motor performance per weekly sport session. Positive associations between participation in organized sport and motor performance identify participation in organized sport as a way to improve motor performance in children. These results might provide the basis to determine whether participation in organized sport could be beneficial for children with developmental movement disorders

Overuse and traumatic extremity injuries in schoolchildren surveyed with weekly text messages over 2.5 years

The objectives of this prospective cohort study were to report the incidence, prevalence, and duration of traumatic and overuse injuries during a period of 2.5 years and to estimate the odds of injury types. In all, 1259 schoolchildren, aged 6-12, were surveyed each week with an automated mobile phone text message asking questions on the presence of any musculo-skeletal problems and participation in leisure-time sport. Children were examined and injuries classified as overuse or traumatic. The overall injury incidence and prevalence were 1.2% and 4.6% per week, with 2.5 times more overuse than traumatic injuries in lower extremities, and mean injury duration of 5.3 and 4.8 weeks, respectively. A reverse pattern was found for upper extremities, with 3.1 times more traumatic than overuse injuries and mean durations of 3.3 and 5.2 weeks, respectively. Grade level, school type, leisure-time sport, and seasonal variation were associated with the risk of sustaining lower extremity injuries. Only grade level was associated with upper extremity injuries. The magnitude of overuse and traumatic limb injuries emphasizes the need for health professionals, coaches, and parents to pay special attention in relation to the growing and physically active child

Receptor structure-based discovery of non-metabolite agonists for the succinate receptor GPR91

Besides functioning as an intracellular metabolite, succinate acts as a stress-induced extracellular signal through activation of GPR91 (SUCNR1) for which we lack suitable pharmacological tools.Here we first determined that the cis conformation of the succinate backbone is preferred and that certain backbone modifications are allowed for GPR91 activation. Through receptor modeling over the X-ray structure of the closely related P2Y1 receptor, we discovered that the binding pocket is partly occupied by a segment of an extracellular loop and that succinate therefore binds in a very different mode than generally believed. Importantly, an empty side-pocket is identified next to the succinate binding site. All this information formed the basis for a substructure-based search query, which, combined with molecular docking, was used in virtual screening of the ZINC database to pick two serial mini-libraries of a total of only 245 compounds from which sub-micromolar, selective GPR91 agonists of unique structures were identified. The best compounds were backbone-modified succinate analogs in which an amide-linked hydrophobic moiety docked into the side-pocket next to succinate as shown by both loss- and gain-of-function mutagenesis. These compounds displayed GPR91-dependent activity in altering cytokine expression in human M2 macrophages similar to succinate, and importantly were devoid of any effect on the major intracellular target, succinate dehydrogenase.These novel, synthetic non-metabolite GPR91 agonists will be valuable both as pharmacological tools to delineate the GPR91-mediated functions of succinate and as leads for the development of GPR91-targeted drugs to potentially treat low grade metabolic inflammation and diabetic complications such as retinopathy and nephropathy