Limited neuromuscular input results in muscle weakness in neuromuscular disease either because of a reduction in the density of muscle innervation, the rate of neuromuscular junction activation or the efficiency of synaptic transmission1. We developed a small molecule fast skeletal troponin activator, CK-2017357, as a means to increase muscle strength by amplifying the response of muscle when neuromuscular input is diminished secondary to a neuromuscular disease. Binding selectively to the fast skeletal troponin complex, CK-2017357 slows the rate of calcium release from troponin C and sensitizes muscle to calcium. As a consequence, the force-calcium relationship of muscle fibers shifts leftwards as does the force-frequency relationship of a nerve-muscle pair. In vitro and in vivo, CK-2017357 increases the production of force at sub-maximal stimulation rates. Importantly, we show that sensitization of the fast skeletal troponin complex to calcium improves muscle force and grip strength immediately after single doses of CK-2017357 in a model of neuromuscular disease, myasthenia gravis. Troponin activation may provide a new therapeutic approach to improve physical activity in diseases where neuromuscular function is compromised.

Although communication is an essential part of the nursing process, nurses have little to no formal education in how to best communicate patient safety event (PSE) information to nursing home (NH) residents and their family members. The current mixed-methods study tested an intervention aimed at educating nurses on how to communicate a PSE to residents/family members using a structured communication tool. Nurse participants improved their knowledge of PSE communication, especially about the cause of the event, what they would say to the resident/family member, and future prevention of the PSE. Through qualitative subgroup analysis, an increased number of empathic statements were noted post-intervention. The tool tested in this study provides structure to an important care process that is necessary for improving the culture of safety in NH settings. [Journal of Gerontological Nursing, 44(2), 25-32.].

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Myasthenia gravis is a chronic autoimmune disease wherein the body produces antibodies that inhibit transmission at the neuromuscular junction, causing skeletal muscle weakness and fatigue. CK‐2017357 (CK‐357) is a small molecule activator of fast skeletal muscle that sensitizes the sarcomere to calcium and increases sub‐maximal force production. The objective of this study was to determine if administration of CK‐357 could increase muscle strength and improve functional capacity in a rodent model of myasthenia gravis. Female, Sprague‐Dawley rats injected with a single intra‐peritoneal dose of inhibitory acetylcholine receptor antibody displayed decreased tension‐generating capacity of intact, fast twitch muscle in situ and decreased conscious functional capacity assessed by forelimb grip strength. Single doses of CK‐357 improved conscious grip function in a dose‐dependent manner. In addition, CK‐357 increased force‐generating capacity and decreased tension decline during repeated stimulation of intact muscle in situ. Together these data suggest CK‐357 may ameliorate muscle weakness and fatigue associated with myasthenia gravis to provide a novel therapeutic approach for treatment of these patients. Supported, in part, by NIH Award 1RC3NS070670. Content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.