The dystrophin protein protects cardiac and skeletal muscle from damage during normal contraction and relaxation by acting as a shock absorber in the cell. Mutations in the dystrophin gene lead to Duchenne muscular dystrophy (DMD), an X-linked recessive disease. Boys suffering from the disease become ventilator dependent at a young age and usually succumb to cardiac failure in their thirties. Other symptoms of DMD include muscle wasting, cardiomyopathy and respiratory failure. Currently there is no cure for DMD and while gene therapy has shown great promise, it still needs to be complemented with additional therapeutic interventions in order to fully address the symptoms of DMD. Previous work by our lab identified several drugs that blocked a certain type of calcium channel in cardiac muscle and protected the cells from damage following injury by correcting calcium movement into and out of the cell during muscle contraction. In this study, the leading drugs will be tested further using a cross-platform approach. The drugs will initially be tested in cardiac and skeletal muscle differentiated from healthy and DMD patient-derived induced pluripotent stem cells (iPSCs). The top three drugs that restore normal contraction and relaxation kinetics in vitro will then be tested in the DMDmdx rat. This novel, small animal model has a similar progression of DMD symptoms to human patients. The rats will be fed the drugs in their chow. Skeletal and cardiac muscle performance will be evaluated to determine whether correcting muscle contraction kinetics ameliorates the symptoms of DMD. Furthermore, we will show whether the same drug is equally effective in treating both cardiac and skeletal muscle. The cross-platform approach may help to better predict drug efficacy, leading to a reduced rate of failure in clinical trials. Moreover, this approach may serve as a benchmark for drug discovery in other neuromuscular diseases.

Pain catastrophizing (PC) and pain-related self-efficacy (PSE) have both been shown to be associated with patient function in individuals with chronic pain, but the extent to which they may contribute independent variance to the prediction of pain and pain interference has been rarely examined. We conducted a secondary analysis of baseline data from a randomized controlled clinical trial with 177 individuals with chronic low back pain and/ or chronic pain associated with multiple sclerosis, muscular dystrophy, acquired amputation, and/ or spinal cord injury. We hypothesized PSE and PC would each be associated with pain interference (BPI), over and above the variance they share with each other and with a measure of pain intensity (0-10 NRS). Linear regression analyses revealed PC and PSE were each uniquely associated with BPI, after accounting for their shared variance and NRS. PC and PSE together accounted for substantial variance in BPI, over and above pain intensity, ΔR² = .20, F(1,170) = 59.74, p < .001, PC (B = 0.35, p < .001) and PSE (B = -0.20, p < .01). The findings indicate PSE and PC may play unique roles in adjustment to chronic pain, although PC may have larger effects. Conclusions regarding the causal role of PSE and PC on patient function cannot be determined from this cross-section study. However, future research should evaluate temporal and possible causal associations between PC, PSE, and subsequent changes in BPI and other important pain-related domains. Findings from such research would inform the potential importance of targeting these variables to maximize treatment benefits in individuals with chronic pain.

 The number of older adults ≥65 years with bothersome pain has increased in the past decade due to an increase in population size and life expectancy of older adults. Amongst several factors studied that may contribute to pain prevalence, socioeconomic status(SES) has been concluded in most studies to be more directly associated with pain prevalence rather than race/ethnicity. The objective of this project was to determine how physical function, due to pain, varies by race/ethnicity. We conducted a retrospective secondary analysis on the National Health & Trends Study(NHATS) to determine how Short Physical Performance Battery (SPPB) scores and secondary pain outcomes differed by race/ethnicity amongst participants who reported bothersome pain in 2011. Baseline race/ethnicity characteristics were gathered to characterize cohort. SPPB score and secondary outcomes for white(NH), black(NH), and hispanics were described for Rounds 1&2. Weighted, regression analysis were performed on SPPB scores to adjust for covariates using survey features. Results show a meaningful difference of SPPB scores among racial/ethnic groups that prompts for more research as to what factors may play a role in differences on the impact of pain on physical function by race/ethnicity.