The purpose of this proposal is to further the candidate's scientific development in translational and clinical research and to make possible his transition to become an independent translational scientist in rehabilitation. The University of Texas Medical Branch at Galveston provides an outstanding academic and research environment and infrastructure to facilitate the candidate's education and training in the conduct of translational research. Career Goals: This award will support the candidate's successful transition from a junior researcher into a mid level independent investigator by providing an array of formal and informal career development activities, and a research project for hands-on learning and acquisition of essential preliminary data under the supervision of an exceptional mentoring team. The specific short-term career goals will include training in muscle metabolism, stable isotope techniques and rehabilitation research;training in the responsible conduct of research and other standard scientific skills;performance of a research study for the acquisition of practical clinical research skills and of preliminary data for future research applications in rehabilitation science. The long term scientific goal is for the candidate to become an expert in skeletal muscle metabolism and rehabilitation with continuous funding for medical research. Research Plan: The general hypothesis is that in older adults muscle regrowth after an acute musculoskeletal stress will be positively influenced by traditional physical rehabilitation, and further enhanced by nutritional supplementation. Using state-of-the-art stable isotope methodologies for the study of muscle metabolism and methodologies for the measurement of cell signaling, the candidate will test the following specific hypotheses: (1) Total knee arthroplasty (TKA) induces an acute net protein catabolism mainly by reducing muscle protein synthesis;(2) TKA induced catabolism is attenuated by the ingestion of essential amino acids (EAA);(3) EAA supplementation in combination with physical therapy (PT) will stimulate muscle protein synthesis and mTOR signaling to a greater extent than PT with placebo;and (4) EAA supplementation during TKA PT rehabilitation will improve muscle strength, muscle volume and functional outcomes to a greater extent than PT with placebo. Public Benefit: This research will focus rehabilitation efforts on specific and currently unresolved mechanisms responsible for muscle loss following total knee replacement in older adults. While knee pain due to bone arthritis is often alleviated after knee replacement, complete return of physical function and independence is difficult to achieve. This research will help to restore physical function and independence in the rapidly growing population of older adults with knee arthritis.
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