Skeletal muscle TFEB signaling promotes central nervous system function and reduces neuroinflammation during aging and neurodegenerative disease.

Skeletal muscle has recently arisen as a regulator of central nervous system (CNS) function and aging, secreting bioactive molecules known as myokines with metabolism-modifying functions in targeted tissues, including the CNS. Here, we report the generation of a transgenic mouse with enhanced skeletal muscle lysosomal and mitochondrial function via targeted overexpression of transcription factor E-B (TFEB). We discovered that the resulting geroprotective effects in skeletal muscle reduce neuroinflammation and the accumulation of tau-associated pathological hallmarks in a mouse model of tauopathy. Muscle-specific TFEB overexpression significantly ameliorates proteotoxicity, reduces neuroinflammation, and promotes transcriptional remodeling of the aged CNS, preserving cognition and memory in aged mice. Our results implicate the maintenance of skeletal muscle function throughout aging in direct regulation of CNS health and disease and suggest that skeletal muscle originating factors may act as therapeutic targets against age-associated neurodegenerative disorders.

Impact of educational intervention on management of periprocedural anticoagulation.

PURPOSE: The effect of education regarding new evidence in periprocedural anticoagulation, with a focus on reducing use in patients at only moderate thromboembolic risk, is presented. METHODS: A retrospective cohort analysis and quasiexperimental design were used. The initial review identified the current state of practice regarding bridging anticoagulation. Education was then provided to primary care providers and pharmacists on recent evidence. A subsequent review was completed to assess the impact of this education on clinical decision-making. Inclusion criteria were adults taking warfarin for an indication of mechanical heart valve, atrial fibrillation (AF), or history of venous thromboembolism (VTE) and required interruption of warfarin therapy to undergo a planned procedure. Patients were excluded if their anticoagulation was managed outside of the Minneapolis Veterans Affairs Anticoagulation Clinic. RESULTS: The overall rate of bridging decreased from 38.8% to 24.8% (14% decrease; 95% confidence interval [CI], 2-26%; p = 0.028) confidence interval [CI], 0.02-0.26; p = 0.026) after educational intervention. This decrease occurred in the moderate thromboembolic risk group, in which the bridging rate decreased from 63.8% to 30.2% (33.6% decrease; 95% CI, 14-53%; p = 0.001). Bleeding complications occurred more frequently in patients who received bridging. There were no thromboembolic complications. CONCLUSION: The majority of patients at moderate thromboembolic risk were previously receiving bridging until new evidence was released indicating that the risks may outweigh any benefits. The provision of education to primary care physicians and pharmacy staff regarding this new evidence in the area of periprocedural anticoagulation management significantly reduced the amount of bridging used for patients on warfarin for AF or a history of VTE who were at moderate thromboembolic risk.