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Selection bias, regression to the mean, the placebo effect, and the simultaneous behavioural changes that often accompany a clinic visit (renewed attention to diet, restored adherence to protocols, increased motivation) all confound the interpretation of clinical-observation reports of this kind

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In further embodiments, the invention encompasses a method of providing muscular therapy by contacting a cell expressing NNMT with a NNMT inhibitor (such as a cation of Formula I or IA, or otherwise disclosed herein) and one or more chemical entities (e.g., nicotinamide riboside, nicotinamide mononucleotide) that modulates intracellular NAD+ levels to provide muscular therapy

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