No abstract

X-linked myotubular myopathy is a congenital myopathy caused by deficiency of myotubularin. Patients often present with severe perinatal weakness, requiring mechanical ventilation to prevent death from respiratory failure. We recently reported that an activin receptor type IIB inhibitor produced hypertrophy of type 2b myofibers and modest increases of strength and life span in the severely myopathic Mtm1δ4 mouse model of X-linked myotubular myopathy. We have now performed a similar study in the less severely symptomatic Mtm1 p.R69C mouse in hopes of finding greater treatment efficacy. Activin receptor type IIB inhibitor treatment of Mtm1 p.R69C animals produced behavioral and histological evidence of hypertrophy in gastrocnemius muscles but not in quadriceps or triceps. The ability of the muscles to respond to activin receptor type IIB inhibitor treatment correlated with treatment-induced increases in satellite cell number and several muscle-specific abnormalities of hypertrophic signaling. Treatment-responsive Mtm1 p.R69C gastrocnemius muscles displayed lower levels of phosphorylated ribosomal protein S6 and higher levels of phosphorylated eukaryotic elongation factor 2 kinase than were observed in Mtm1 p.R69C quadriceps muscle or in muscles from wild-type littermates. Hypertrophy in the Mtm1 p.R69C gastrocnemius muscle was associated with increased levels of phosphorylated ribosomal protein S6. Our findings indicate that muscle-, fiber type-, and mutation-specific factors affect the response to hypertrophic therapies that will be important to assess in future therapeutic trials.

In the United States, the Centers for Disease Control and Prevention estimates that 1.6-to-3.8 million concussions occur annually in sports. This quantitative meta-analysis of one hundred and twenty-one sports-related concussion studies, across fourteen youth sports, investigated the contributions of statistical constructs, and diagnostic methods, considering the impact of nationwide laws and education, as well as distinguished injury surveillance techniques, in this widely diverse literature. Concussion study research designs were found to have differing diagnostic, statistical, and methodological techniques. Among less frequently studied, non-high-contact, sports, a meta-analysis investigated relative rates of concussion and sex differences. Findings indicated considerable variation in reported concussion incidence rates due to the sport played, but also due to the number of study authors listed and the proportion of female athletes represented. Such factors likely influence the reported incidence of sports-related concussions, especially in sports not typically associated with a high risk of head injuries. To better capture the incidence of sports-related head injuries and concussion, a universal data repository for youth concussions might be established to provide an ongoing, comprehensive, and accurate picture of concussions in youth and collegiate athletics.