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Introduction: Adverse childhood experiences (ACEs) are associated with higher mental and physical illness and substance use disorders in adulthood. However, little is known about the prevalence of ACEs among student pharmacists and the factors associated with exposure. Our objective was to determine the prevalence of ACEs, resilience, and maladaptive coping strategies among student pharmacists in California. Methods: Student pharmacists from 14 California pharmacy schools completed a 24-item online survey in 2020. This survey instrument comprised the ACEs questionnaire and collected data on the students' demographic characteristics, coping strategies, and resilience. Results: Most respondents were Asian/Pacific Islander (n = 186, 61.0%), female (n = 216, 70.8%), and aged between 25 and 31 years (n = 154, 50.7%). Many (n = 137, 44.9%) students had more than 1 ACE exposure; 66 students (21.6%) had more than 3 ACEs. Many students indicated that they were diagnosed or suspected to be diagnosed with a mental health condition (n = 105, 34.4%) and agreed/strongly agreed that they struggled to manage the workload of pharmacy school (n = 119, 39.9%). Respondents with higher ACE scores (> 3) were more likely to report struggling with managing the workload of pharmacy school, have or suspect having a mental health condition, drink alcohol in the last 12 months, and/or have multiple sexual partners than students with lower ACE scores. Discussion: More than 1 in 5 student pharmacists in this study were exposed to more than 3 ACEs. The student pharmacists' ACE exposure was associated with higher likelihood of mental health conditions and high-risk health behaviors. Further studies are needed to investigate this topic among student pharmacists.
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Insulin resistance (IR) is one of the hallmarks of heart failure (HF). Abnormalities in skeletal muscle (SM) metabolism have been identified in patients with HF. However, the underlying mechanisms of IR development in SM in HF are poorly understood. Herein, we hypothesize that HF upregulates miR-133b in SM and in turn alters glucose metabolism and the propensity toward IR. Mitochondria isolated from SM of mice with HF induced by transverse aortic constriction (TAC) showed lower respiration and downregulation of muscle-specific components of the tricarboxylic acid (TCA) cycle, AMP deaminase 1 (AMPD1), and fumarate compared with those from control animals. RNA-Seq and subsequent qPCR validation confirmed upregulation of SM-specific microRNA (miRNA), miR-133b, in TAC versus sham animals. miR-133b overexpression alone resulted in significantly lower mitochondrial respiration, cellular glucose uptake, and glycolysis along with lower ATP production and cellular energy reserve compared with the scramble (Scr) in C2C12 cells. miR-133b binds to the 3'-untranslated region (UTR) of KLF15, the transcription factor for the insulin-sensitive glucose transporter, GLUT4. Overexpression of miR-133b lowers GLUT4 and lowers pAkt in presence of insulin in C2C12 cells. Finally, lowering miR-133b in primary skeletal myocytes isolated from TAC mice using antagomir-133b reversed the changes in KLF15, GLUT4, and AMPD1 compared with the scramble-transfected myocytes. Taken together, these data demonstrate a role for SM miR-133b in altered glucose metabolism in HF and suggest the therapeutic potential in HF to improve glucose uptake and glycolysis by restoring GLUT4 abundance. The data uncover a novel mechanism for IR and ultimately SM metabolic abnormalities in patients with HF.NEW & NOTEWORTHY Heart failure is associated with systemic insulin resistance and abnormalities in glucose metabolism but the underlying mechanisms are poorly understood. In the skeletal muscle, the major peripheral site of glucose utilization, we observe an increase in miR-133b in heart failure mice, which reduces the insulin-sensitive glucose transporter (GLUT4), glucose uptake, and metabolism in C2C12 and in myocytes. The antagomir for miR-133b restores GLUT4 protein and markers of metabolism in skeletal myocytes from heart failure mice demonstrating that miR-133b is an exciting target for systemic insulin resistance in heart failure and an important player in the cross talk between the heart and the periphery in the heart failure syndrome.