Well-being at a Military Medical School and Implications for Military Retention.

INTRODUCTION: Physical and psychological well-being play a critical role in the academic and professional development of medical students and can alter the trajectory of a student\u27s quality of personal and professional life. Military medical students, given their dual role as officer and student, experience unique stressors and issues that may play a role in their future intentions to continue military service, as well as practice medicine. As such, this study explores well-being across the 4 years of medical school at Uniformed Services University (USU) and how well-being relates to a student\u27s likelihood to continue serving in the military and practicing medicine. METHODS: In September 2019, 678 USU medical students were invited to complete a survey consisting of three sections-the Medical Student Well-being Index (MSWBI), a single-item burnout measure, and six questions regarding their likelihood of staying in the military and medical practice. Survey responses were analyzed using descriptive statistics, analysis of variance (ANOVA), and contingency table analysis. Additionally, thematic analysis was conducted on open-ended responses included as part of the likelihood questions. RESULTS: Our MSWBI and burnout scores suggest that the overall state of well-being among medical students at USU is comparable to other studies of the medical student population. ANOVA revealed class differences among the four cohorts, highlighted by improved well-being scores as students transitioned from clerkships to their fourth-year curriculum. Fewer clinical students (MS3s and MS4s), compared to pre-clerkship students, indicated a desire to stay in the military. In contrast, a higher percentage of clinical students seemed to reconsider their medical career choice compared to their pre-clerkship student counterparts. Medicine-oriented likelihood questions were associated with four unique MSWBI items, whereas military-oriented likelihood questions were associated with one unique MSWBI item. CONCLUSION: The present study found that the overall state of well-being in USU medical students is satisfactory, but opportunities for improvement exist. Medical student well-being seemed to have a stronger association with medicine-oriented likelihood items than with military-oriented likelihood items. To obtain and refine best practices for strengthening engagement and commitment, future research should examine if and how military and medical contexts converge and diverge throughout training. This may enhance the medical school and training experience and, ultimately, reinforce, or strengthen, the desire and commitment to practice and serve in military medicine

Metabolic acetate therapy improves phenotype in the tremor rat model of Canavan disease

Genetic mutations that severely diminish the activity of aspartoacylase (ASPA) result in the fatal brain dysmyelinating disorder, Canavan disease. There is no effective treatment. ASPA produces free acetate from the concentrated brain metabolite, N-acetylaspartate (NAA). Because acetyl coenzyme A is a key building block for lipid synthesis, we postulated that the inability to catabolize NAA leads to a brain acetate deficiency during a critical period of CNS development, impairing myelination and possibly other aspects of brain development. We tested the hypothesis that acetate supplementation during postnatal myelination would ameliorate the severe phenotype associated with ASPA deficiency using the tremor rat model of Canavan disease. Glyceryltriacetate (GTA) was administered orally to tremor rats starting 7 days after birth, and was continued in food and water after weaning. Motor function, myelin lipids, and brain vacuolation were analyzed in GTA-treated and untreated tremor rats. Significant improvements were observed in motor performance and myelin galactocerebroside content in tremor rats treated with GTA. Further, brain vacuolation was modestly reduced, and these reductions were positively correlated with improved motor performance. We also examined the expression of the acetyl coenzyme A synthesizing enzyme acetyl coenzyme A synthase 1 and found upregulation of expression in tremor rats, with a return to near normal expression levels in GTA-treated tremor rats. These results confirm the critical role played by NAA-derived acetate in brain myelination and development, and demonstrate the potential usefulness of acetate therapy for the treatment of Canavan disease

Alternating Hemiplegia of Childhood-Related Neural and Behavioural Phenotypes in Na+,K+-ATPase α3 Missense Mutant Mice

Missense mutations in ATP1A3 encoding Na(+),K(+)-ATPase α3 have been identified as the primary cause of alternating hemiplegia of childhood (AHC), a motor disorder with onset typically before the age of 6 months. Affected children tend to be of short stature and can also have epilepsy, ataxia and learning disability. The Na(+),K(+)-ATPase has a well-known role in maintaining electrochemical gradients across cell membranes, but our understanding of how the mutations cause AHC is limited. Myshkin mutant mice carry an amino acid change (I810N) that affects the same position in Na(+),K(+)-ATPase α3 as I810S found in AHC. Using molecular modelling, we show that the Myshkin and AHC mutations display similarly severe structural impacts on Na(+),K(+)-ATPase α3, including upon the K(+) pore and predicted K(+) binding sites. Behavioural analysis of Myshkin mice revealed phenotypic abnormalities similar to symptoms of AHC, including motor dysfunction and cognitive impairment. 2-DG imaging of Myshkin mice identified compromised thalamocortical functioning that includes a deficit in frontal cortex functioning (hypofrontality), directly mirroring that reported in AHC, along with reduced thalamocortical functional connectivity. Our results thus provide validation for missense mutations in Na(+),K(+)-ATPase α3 as a cause of AHC, and highlight Myshkin mice as a starting point for the exploration of disease mechanisms and novel treatments in AHC

Management of patients receiving long-term treatment with mifepristone

Objective: To determine clinical side effects and biochemical and hematological abnormalities in patients with nonresectable meningioma on long-term mifepristone (RU 486) therapy. Design: Long-term mifepristone administration in patients with meningioma. Setting: Outpatient clinic of a university hospital. Patient(s): Sixteen women and 9 men aged 22–80 years with nonresectable meningioma. Intervention(s): Mifepristone (200 mg daily). One patient received treatment for more than 13 years; six received treatment for 10–12 years; five received treatment for 4-9 years; eight received treatment for 1–4 years; and the remainder received treatment for 4-10 months. Main Outcome Measure(s): Evaluation of side effects and of hematological and biochemical abnormalities. Result(s): Fatigue was observed in 22 of 25 patients. Endometrial hyperplasia occurred in one premenopausal woman and one postmenopausal woman. Another two women had endometrial thickening without hyperplasia. There were no consistent abnormalities in liver or renal function or in any other biochemical or hematological parameters. One subject (on long-term dexamethasone) developed hypoadrenalism, which responded to treatment. Conclusion(s): Mifepristone can be administered for prolonged periods. Ultrasound should be performed if irregular vaginal bleeding occurs. In asymptomatic women, it should be performed annually. If endometrial thickening is observed, then endometrial biopsy is recommended. Because biochemical hypothyroidism has been reported during long-term mifepristone therapy, thyroid function tests should be performed annually