Background: Therapeutic exercise is a central component in the management of many common conditions. It is imperative, therefore, that clinicians monitor and correct patient performance to facilitate the use of proper form both in the clinic and during home exercise programs. Although clinicians are trained to prescribe exercise and analyze form, there are many subtleties that may be missed by relying on visual assessment. This study investigated the accuracy and precision of a novel, exercise-training smartphone application (app), running on an iPhone^® (Apple, Cupertino, CA) 4 and using its LIS331DLH accelerometer to dynamically measure and record movement during exercise. Materials and Methods: The iPhone, running the app, was mounted to the movement arm of a Biodex™ isokinetic dynamometer System 4 (Biodex Corp., Shirley, NY). Angle and time measurements taken by the app were compared with the dynamometer (gold standard) while rotating at 30°/s, 60°/s, 90°/s, 120°/s, and 150°/s. Accuracy was assessed using limits of agreement and fast Fourier transform analyses. Precision was assessed using the coefficient of variation. Results: The mean difference between the app and the Biodex recordings was less than 1°/s for all test velocities. The coefficient of variation was less than 3% at velocities from 30°/s to 120°/s and less than 7% at 150°/s. Conclusions: The app was highly accurate and precise. The validation of apps designed for motion tracking is a vital prerequisite to clinical implementation. The app described in this article is clinically identical to the Biodex dynamometer in its ability to accurately and precisely read angular movement over time.

Deficits in plasma membrane repair have been identified in dysferlinopathy and Duchenne Muscular Dystrophy, and contribute to progressive myopathy. Although Facioscapulohumeral Muscular Dystrophy (FSHD) shares clinicopathological features with these muscular dystrophies, it is unknown if FSHD is characterized by plasma membrane repair deficits. Therefore, we exposed immortalized human FSHD myoblasts, immortalized myoblasts from unaffected siblings, and myofibers from a murine model of FSHD (FLExDUX4) to focal, pulsed laser ablation of the sarcolemma. Repair kinetics and success were determined from the accumulation of intracellular FM1-43 dye post-injury. We subsequently treated FSHD myoblasts with a DUX4-targeting antisense oligonucleotide (AON) to reduce DUX4 expression, and with the antioxidant Trolox to determine the role of DUX4 expression and oxidative stress in membrane repair. Compared to unaffected myoblasts, FSHD myoblasts demonstrate poor repair and a greater percentage of cells that failed to repair, which was mitigated by AON and Trolox treatments. Similar repair deficits were identified in FLExDUX4 myofibers. This is the first study to identify plasma membrane repair deficits in myoblasts from individuals with FSHD, and in myofibers from a murine model of FSHD. Our results suggest that DUX4 expression and oxidative stress may be important targets for future membrane-repair therapies.

Proteomic studies in facioscapulohumeral muscular dystrophy (FSHD) could offer new insight into disease mechanisms underpinned by post-transcriptional processes. We used stable isotope (deuterium oxide; D₂O) labeling and peptide mass spectrometry to investigate the abundance and turnover rates of proteins in cultured muscle cells from two individuals affected by FSHD and their unaffected siblings (UASb). We measured the abundance of 4420 proteins and the turnover rate of 2324 proteins in each (n = 4) myoblast sample. FSHD myoblasts exhibited a greater abundance but slower turnover rate of subunits of mitochondrial respiratory complexes and mitochondrial ribosomal proteins, which may indicate an accumulation of "older" less viable mitochondrial proteins in myoblasts from individuals affected by FSHD. Treatment with a 2'-O-methoxyethyl modified antisense oligonucleotide targeting exon 3 of the double homeobox 4 (DUX4) transcript tended to reverse mitochondrial protein dysregulation in FSHD myoblasts, indicating the effect on mitochondrial proteins may be a DUX4-dependent mechanism. Our results highlight the importance of post-transcriptional processes and protein turnover in FSHD pathology and provide a resource for the FSHD research community to explore this burgeoning aspect of FSHD.