ProblemPhysicians are playing a growing role as clinician-innovators. Academic physicians are well positioned to contribute to the medical device innovation process, yet few medical school curricula provide students opportunities to learn the conceptual framework for clinical needs finding, needs screening, concept generation and iterative prototyping, and intellectual property management. This framework supports innovation and encourages the development of valuable interdisciplinary communication skills and collaborative learning strategies. ApproachOur university offers a novel 3-yearlong medical student Longitudinal Interdisciplinary Elective in Biodesign (MSLIEB) that teaches medical device innovation in 4 stages: (1) seminars and small-group work, (2) shared clinical experiences for needs finding, (3) concept generation and product development by serving as consultants for biomedical engineering capstone projects, and (4) reflection and mentorship. The MSLIEB objectives are to: create a longitudinal interdisciplinary peer mentorship relationship between undergraduate biomedical engineering students and medical students, and encourage codevelopment of professional identities in relation to medical device innovation.

Introduction: The TANGO2 gene encodes a transport and Golgi organization protein of unclear function; mutations should be considered in patients presenting with acute metabolic crisis, hypoglycemic episodes, cardiac arrhythmias, and other endocrinopathies. We report the novel use of a continuous glucose monitor (CGM) to help predict and prevent significant hypoglycemic episodes in a patient with TANGO2 mutation. Clinical Case: A 14-month old previously healthy, developmentally normal female who presented with unresponsive hypoglycemia (glucose 26 mg/dL) was demonstrated by Next Generation Sequencing to have a pathogenic 31.8 kb deletion of exon 3 to 9 in the TANGO-2 gene and a suspected pathogenic hemizygous c.569_592dup, p.Ile190_Leu197dup in TANGO-2. Her hospital course was notable for MRI showing hypoxic ischemic encephalopathy and both physical and electrical cardiac dysfunction. Continuous intravenous dextrose corrected the hypoglycemia, and transient hyperglycemia followed after several days of a glucose infusion rate between 3.2 to 5.8 mg/kg/min. After transitioning to ad lib oral feeds without restrictions, she was discharged. A second admission for acute unresponsive hypoglycemia and metabolic acidosis (glucose 30 mg/dL) occurred at 17 months of age with no clear inciting cause. Continuous IV dextrose at 9.9 mg/kg/min corrected the hypoglycemia and again resulted in transient hyperglycemia up to 271 mg/dl. Levothyroxine was also started for a TSH of 27 mIU/mL and a T4 of 4.6 ug/dL. Immediately after discharge, a DexCom G6 CGM was placed. Data over 2 weeks shows an average glucose of 104 ng/dL with 99% of the BS in target range. Parents report that CGM predictive low alerts have allowed intervention to abort fasting-related metabolic crises. Conclusion: In TANGO-2 deficiency, the liver may not adequately store and/or release glycogen in response to glucagon due to abnormal endoplasmic reticulum, Golgi apparatus, and mitochondrial functioning in states of stress or illness. Recent reports are conflicting with some showing reduced mitochondrial respiration in TANGO-2 patients in steady state with others finding normal values, opening the possibility that a combination of factors in the setting of stress may precipitate a metabolic crisis. Our patient quickly returns to near-normal physiological functioning; consequently, we suggest that use of a CGM can help prevent fasting related metabolic crisis in TANGO2 patients and can help guide feeding schedule and food choices to limit hyper- and hypoglycemia. In addition, CGM data can help further investigate if any beta cell dysregulation exists in non-acute states. References: Bérat CM, ... & de Lonlay P. (2020). Clinical and biological characterization of 20 patients with TANGO2 deficiency indicates novel triggers of metabolic crises.... J Inherit Metab Dis. 2020 Sep 14. doi: 10.1002/jimd.12314.

Bcr-abl1 oncogene causes a shift in the transcription start site of the SMS1 gene (SGMS1) encoding the sphingomyelin (SM) synthesizing enzyme, sphingomyelin synthase 1 (SMS1). This results in an mRNA with a significantly shorter 5 0-UTR, called 7-SGMS1, which is translated more efficiently than another transcript (IIb-SGMS1) with a longer 5 0 UTR in Bcr-abl1-positive cells. Here, we determine the effects of these alternative 5 0 UTRs on SMS1 translation and investigate the key features underlying such regulation. First, the presence of the longer IIb 5 0 UTR is sufficient to greatly impair translation of a reporter gene. Deletion of the upstream open reading frame (À164 nt) or of the predicted stem-loops in the 5 0 UTR of IIb-SGMS1 has minimal effects on SGMS1 translation. Conversely, deletion of nucleotides À310 to À132 enhanced transcription of IIb-SGMS1 to reach that of 7-SGMS1. We thus suggest that regulatory features within nucleotides À310 and À132 modulate IIb-SGMS1 translation efficiency.

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