Motivating High School Students From Rural Areas to Attend College and Pursue Careers as Osteopathic Physicians.

CONTEXT: One potential way to address critical current and future projected health care workforce shortages is through comprehensive programs that could potentially inspire high school students to pursue osteopathic medical careers in underserved areas. OBJECTIVE: To determine whether a comprehensive, 5-week enrichment program could promote interest among rural high-school students in careers osteopathic medicine. METHODS: In May 2018, 116 high school students with a grade point average of 2.8 or higher from rural areas, including New Mexico and its surrounding rural areas in the US-Mexico border region, enrolled in а 5-week program offering American College Testing (ACT) preparation and biomedical sciences enrichment at Burrell College of Osteopathic Medicine (BCOM). During the program, students were offered more than 150 hours of interactive in-class lectures and hands-on activities with laboratories focusing on college preparedness, health sciences, and motivating students to pursue osteopathic medical career and practice medicine in rural areas. Clinically-oriented sessions covering osteopathic philosophy and osteopathic manipulative medicine were included. After completion, a voluntary and anonymous survey was sent to students who completed the program students through QualtricsXM©. Blinded ACT scores were collected from participants' schools, along with college enrollment status information. RESULTS: Of 116 enrolled students, 106 (91.4%) completed the program successfully. In their postcompletion survey responses, students reported that they had gained a realistic perception of the field of medicine and were motivated to attend college (mean [standard error, SE] score on 5-point Likert scale over 2 questions, 4.8 [0.06]) and osteopathic medical school (mean [SE], 4.7 [0.1]). Participants also felt more informed about physician shortage in rural areas (mean [SE], 4.7 [0.07]) and appeared to be inspired to practice medicine in rural areas (mean [SE], 4.6 [0.09]). Students also reported feeling better prepared to take the ACT after finishing this program (mean [SE], 4.9 [0.04]). Finally, we were able to collect the ACT scores of 51 participants (48.1%) who completed the program; the mean ACT score was 24.3, compared with a reported national mean of 20.7 on a scoring scale of 1-36. We also performed a follow-up inquiry showing that 78 of the 81 participating students (96%) who had graduated from high school were enrolled in college or university and 59 (73%) had elected in science, technology, engineering, mathematics, or health majors. CONCLUSION: Rural high school pipeline programs could be a tool to motivate high school students to attend college and ultimately to develop physicians who are interested to practice in medically underserved areas.

Chronic stress alters adrenal clock function in a sexually dimorphic manner.

Glucocorticoid production is gated at the molecular level by the circadian clock in the adrenal gland. Stress influences daily rhythms in behavior and physiology, but it remains unclear how stress affects the function of the adrenal clock itself. Here, we examine the influence of stress on adrenal clock function by tracking PERIOD2::LUCIFERASE (PER2::LUC) rhythms in vitro Relative to non-stressed controls, adrenals from stressed mice displayed marked changes in PER2::LUC rhythms. Interestingly, the effect of stress on adrenal rhythms varied by sex and the type of stress experienced in vivo To investigate the basis of sex differences in the adrenal response to stress, we next stimulated male and female adrenals in vitro with adrenocorticotropic hormone (ACTH). ACTH shifted phase and increased amplitude of adrenal PER2::LUC rhythms. Both phase and amplitude responses were larger in female adrenals than in male adrenals, an observation consistent with previously described sex differences in the physiological response to stress. Lastly, we reversed the sex difference in adrenal clock function using stress and sex hormone manipulations to test its role in driving adrenal responses to ACTH. We find that adrenal responsiveness to ACTH is inversely proportional to the amplitude of adrenal PER2::LUC rhythms. This suggests that larger ACTH responses from female adrenals may be driven by their lower amplitude molecular rhythms. Collectively, these results indicate a reciprocal relationship between stress and the adrenal clock, with stress influencing adrenal clock function and the state of the adrenal clock gating the response to stress in a sexually dimorphic manner.

An IRF5 Decoy Peptide Reduces Myocardial Inflammation and Fibrosis and Improves Endothelial Cell Function in Tight-Skin Mice.

Interferon regulatory factor 5 (IRF5) has been called a "master switch" for its ability to determine whether cells mount proinflammatory or anti-inflammatory responses. Accordingly, IRF5 should be an attractive target for therapeutic drug development. Here we report on the development of a novel decoy peptide inhibitor of IRF5 that decreases myocardial inflammation and improves vascular endothelial cell (EC) function in tight-skin (Tsk/+) mice. Biolayer interferometry studies showed the Kd of IRF5D for recombinant IRF5 to be 3.72 ± 0.74x10-6M. Increasing concentrations of IRF5D (0-100 µg/mL, 24h) had no significant effect on EC proliferation or apoptosis. Treatment of Tsk/+ mice with IRF5D (1mg/kg/d subcutaneously, 21d) reduced IRF5 and ICAM-1 expression and monocyte/macrophage and neutrophil counts in Tsk/+ hearts compared to expression in hearts from PBS-treated Tsk/+ mice (p<0.05). EC-dependent vasodilatation of facialis arteries isolated from PBS-treated Tsk/+ mice was reduced (~15%). IRF5D treatments (1mg/kg/d, 21d) improved vasodilatation in arteries isolated from Tsk/+ mice nearly 3-fold (~45%, p<0.05), representing nearly 83% of the vasodilatation in arteries isolated from C57Bl/6J mice (~55%). IRF5D (50µg/mL, 24h) reduced nuclear translocation of IRF5 in myocytes cultured on both Tsk/+ cardiac matrix and C57Bl/6J cardiac matrix (p<0.05). These data suggest that IRF5 plays a causal role in inflammation, fibrosis and impaired vascular EC function in Tsk/+ mice and that treatment with IRF5D effectively counters IRF5-dependent mechanisms of inflammation and fibrosis in the myocardium in these mice.

Sexual Differentiation of Circadian Clock Function in the Adrenal Gland.

Sex differences in glucocorticoid production are associated with increased responsiveness of the adrenal gland in females. However, the adrenal-intrinsic mechanisms that establish sexual dimorphic function remain ill defined. Glucocorticoid production is gated at the molecular level by the circadian clock, which may contribute to sexual dimorphic adrenal function. Here we examine sex differences in the adrenal gland using an optical reporter of circadian clock function. Adrenal glands were cultured from male and female Period2::Luciferase (PER2::LUC) mice to assess clock function in vitro in real time. We confirm that there is a pronounced sex difference in the intrinsic capacity to sustain PER2::LUC rhythms in vitro, with higher amplitude rhythms in adrenal glands collected from males than from females. Changes in adrenal PER2::LUC rhythms over the reproductive life span implicate T as an important factor in driving sex differences in adrenal clock function. By directly manipulating hormone levels in adult mice in vivo, we demonstrate that T increases the amplitude of PER2::LUC rhythms in adrenal glands of both male and female mice. In contrast, we find little evidence that ovarian hormones modify adrenal clock function. Lastly, we find that T in vitro can increase the amplitude of PER2::LUC rhythms in male adrenals but not female adrenals, which suggests the existence of sex differences in the mechanisms of T action in vivo. Collectively these results reveal that activational effects of T alter circadian timekeeping in the adrenal gland, which may have implications for sex differences in stress reactivity and stress-related disorders.