TFEB/3 govern repair Schwann cell generation and function following peripheral nerve injury.

TFEB and TFE3 (TFEB/3), key regulators of lysosomal biogenesis and autophagy, play diverse roles depending on cell type. This study highlights a hitherto unrecognized role of TFEB/3 crucial for peripheral nerve repair. Specifically, they promote the generation of progenitor-like repair Schwann cells after axonal injury. In Schwann cell-specific TFEB/3 double knock-out mice of either sex, the TFEB/3 loss disrupts the transcriptomic reprogramming that is essential for the formation of repair Schwann cells. Consequently, mutant mice fail to populate the injured nerve with repair Schwann cells and exhibit defects in axon-regrowth, target reinnervation, and functional recovery. TFEB/3 deficiency inhibits the expression of injury-responsive repair Schwann cell genes, despite the continued expression of c-Jun, a previously identified regulator of repair Schwann cell function. TFEB/3 binding motifs are enriched in the enhancer regions of injury-responsive genes, suggesting their role in repair gene activation. Autophagy-dependent myelin breakdown is not impaired despite TFEB/3 deficiency. These findings underscore a unique role of TFEB/3 in adult Schwann cells that is required for proper peripheral nerve regeneration.Significance Statement Peripheral nerves have been recognized for their efficient regenerative capabilities compared to the central nervous system neurons. This is due to the remarkable ability of Schwann cells to undergo a reprogramming process, transforming into progenitor-like repair Schwann cells that actively contribute to axon regeneration and overall nerve repair. However, the specific transcriptional regulators responsible for initiating this transformation in the adult peripheral nerve have remained elusive. Our study elucidates a previously undescribed, injury-responsive function of TFEB/3 in adult Schwann cells, showcasing its ability to promote tissue repair. Our findings hold important implications for enhancing nerve regeneration by bolstering the regenerative capacity of glial cells, thereby contributing to advancements in the field of neural tissue repair.

Estimates of Direct Medical and Indirect Costs Associated With COVID-19 Among U.S. Active Duty Army Soldiers.

INTRODUCTION: This study estimated the direct medical and indirect costs associated with coronavirus disease 2019 (COVID-19) diagnoses among U.S. active duty (AD) Army service members (SMs). These cost estimates provide the U.S. Military with a better understanding of the financial burden of COVID-19 and provide a foundation for cost-effectiveness estimates. MATERIALS AND METHODS: The study was approved as Public Health Practice (#17-605) by the U.S. Army Public Health Center, Public Health Review Board. U.S. AD Army SMs with COVID-19 were identified using an Army COVID-19 testing and surveillance database. Encounters for these SMs were captured from medical record where International Classification of Disease Tenth Revision, Clinical Modification code U07.1 was in the first or second diagnostic position. Analyses were conducted on SMs with COVID-19 who either had no healthcare encounters in the Military Health System (MHS); at least one MHS COVID-19 inpatient hospitalization; or at least one MHS outpatient COVID-19 encounter. Coronavirus disease 2019 (COVID-19) costs captured from the encounters were used to develop direct medical cost estimates. Literature on COVID-19 recovery post-hospitalization, along with the number of COVID-19 hospitalizations and outpatient visits from encounters were used to describe the intensity of COVID-19 care. Estimates of the indirect cost of lost duty were based on SMs salary information, along with recovery time, bed days, or outpatient visit time. The indirect cost of limited duty was estimated using the time associated with the Department of Defense (DoD) COVID-19 pandemic mitigation strategies in place when these SMs were identified as positive for COVID-19. RESULTS: Coronavirus disease 2019 (COVID-19) cost estimates were developed for the Army using data from 19,086 SMs identified as positive for COVID-19 between June 1, 2020, and December 31, 2020. Direct medical costs, or the amount paid by the DoD to facilities for COVID-19 care, averaged $606 per SM with an encounter. Indirect costs for lost duty or the cost for recovery and the time taken to seek care for COVID-19 averaged $319 per SM, while indirect costs for limited duty or isolation associated with COVID-19 averaged $4,111 per SM or $411 per day. Service members (SMs) with an inpatient hospitalization averaged 4.8 bed days (range 1-43) and 266 recovery hours while SMs who sought outpatient care for COVID-19 averaged two outpatient visits (range 1-60 visits). CONCLUSIONS: The direct medical costs of a COVID-19 encounter in the MHS ($606) are a small portion of the costs for a SM with COVID-19. Indirect costs of lost and limited duty associated with COVID-19 averaged seven times higher ($4,331) and accounted for the vast majority of costs. Recognition of these costs is important especially given that soldiers in the hospital or in quarters being quarantined are complete losses of manpower to the Army. While the COVID-19 pandemic is ongoing and prevention, treatment, and mitigation efforts continue to evolve, having reliable estimates of direct medical and indirect costs from this study allows the U.S. Army and MHS to better account for the cost of this pandemic for its population.

Integration of Multiple Surveillance Systems to Track COVID-19 in the U.S. Army Population.

INTRODUCTION: The coronavirus disease (COVID-19) pandemic presented unique challenges for surveillance of the military population, which include active component service members and their family members. Through integrating multiple Department of Defense surveillance systems, the Army Public Health Center can provide near real-time case counts to Army leadership on a daily basis. MATERIALS AND METHODS: The incidence of COVID-19 was tracked by incorporating data from the Disease Reporting System Internet, laboratory test results, Commanders' Critical Incidence Reports, reports from the Centers for Disease Control and Prevention military liaison, and media reports. Cases were validated via a medical record review for all Army beneficiaries. Descriptive analyses were performed using Microsoft Excel and SAS 9.4 to measure demographic frequencies. RESULTS: In the first year of the pandemic from February 1, 2020 to February 28, 2021, a total of 96,315 COVID-19 cases were reported to the Disease Reporting System internet, the Army's passive surveillance system, of which 95,429 (99%) were confirmed and 886 (1%) were probable. A total of 76 outbreak reports were submitted from 14 Army installations. The proportion of Army beneficiaries with severe illness was low: 2,271 (2.4%) individuals required hospitalization and 269 (0.3%) died. Installations in Texas reported the highest proportion of confirmed-not hospitalized cases (n = 19,246, 20.7%), confirmed-hospitalized cases (n = 1,037, 45.7%), and deaths (n = 137, 50.9%) as compared to other states with Army installations. CONCLUSIONS: The pandemic has demonstrated the need for a robust public health enterprise with a focus on data collection, validation, and analysis, allowing leaders to make informed decisions that may impact the health of the Army.