Physical exertion exacerbates decline in the musculature of an animal model of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a genetic disorder caused by loss of the protein dystrophin. In humans, DMD has early onset, causes developmental delays, muscle necrosis, loss of ambulation, and death. Current animal models have been challenged by their inability to model the early onset and severity of the disease. It remains unresolved whether increased sarcoplasmic calcium observed in dystrophic muscles follows or leads the mechanical insults caused by the muscle's disrupted contractile machinery. This knowledge has important implications for patients, as potential physiotherapeutic treatments may either help or exacerbate symptoms, depending on how dystrophic muscles differ from healthy ones. Recently we showed how burrowing dystrophic (dys-1) C. elegans recapitulate many salient phenotypes of DMD, including loss of mobility and muscle necrosis. Here, we report that dys-1 worms display early pathogenesis, including dysregulated sarcoplasmic calcium and increased lethality. Sarcoplasmic calcium dysregulation in dys-1 worms precedes overt structural phenotypes (e.g., mitochondrial, and contractile machinery damage) and can be mitigated by reducing calmodulin expression. To learn how dystrophic musculature responds to altered physical activity, we cultivated dys-1 animals in environments requiring high intensity or high frequency of muscle exertion during locomotion. We find that several muscular parameters (e.g., size) improve with increased activity. However, longevity in dystrophic animals was negatively associated with muscular exertion, regardless of effort duration. The high degree of phenotypic conservation between dystrophic worms and humans provides a unique opportunity to gain insight into the pathology of the disease as well as the initial assessment of potential treatment strategies.

A study of porcine liver motion during respiration for improving targeting in image-guided needle placements.

PURPOSE: Liver motion due to respiration restricts targeting and needle placement accuracy during image-guided interventional procedures. Breath holds, imaging techniques, and navigation systems are used to improve targeting accuracy. Data of in-vivo liver behavior under respiration can enhance these approaches. METHODS: An experimental study was performed using the swine model to capture the dynamics of liver motion during respiration using needles tipped with electromagnetic sensors. The swine liver was segmented into four lobes (right lateral, right medial, left medial and left lateral), and two sensor-tipped needles were placed in each location to acquire representative displacement data. RESULTS: Maximum displacement was found to occur in the left medial and left lateral lobes, in the anterior-posterior direction. Significant lobe-dependent variation in motion behavior was recorded, but a variation within a lobe was minimal and independent of needle approach. Magnitude of displacement in all lobes was found to be monotonically correlated to breathing volume. Displacement of liver was found to be out of phase with breathing by approximately 2 Hz. The positioning of the animal was also found to influence direction and magnitude of liver displacement in different lobes. CONCLUSIONS: We have presented previously unavailable data and insight into the role of easily controllable parameters such as breathing volume, patient positioning, and lobe-specific heterogeneity in the displacement of liver due to respiration.