ObjectiveHyperglycemia and systemic inflammation, hallmarks of Type 2 Diabetes (T2D), can induce the production of the inflammatory signaling molecule Prostaglandin E2 (PGE2) in islets. The effects of PGE2 are mediated by its four receptors, E-Prostanoid Receptors 1-4 (EP1-4). EP3 and EP4 play opposing roles in many cell types due to signaling through different G proteins, Gi and GS, respectively. We previously found that EP3 and EP4 expression are reciprocally regulated by activation of the FoxM1 transcription factor, which promotes β-cell proliferation and survival. Our goal was to determine if EP3 and EP4 regulate β-cell proliferation and survival and, if so, to elucidate the downstream signaling mechanisms.Methodsβ-cell proliferation was assessed in mouse and human islets ex vivo treated with selective agonists and antagonists for EP3 (sulprostone and DG-041, respectively) and EP4 (CAY10598 and L-161,982, respectively). β-cell survival was measured in mouse and human islets treated with the EP3- and EP4-selective ligands in conjunction with a cytokine cocktail to induce cell death. Changes in gene expression and protein phosphorylation were analyzed in response to modulation of EP3 and EP4 activity in mouse islets.ResultsBlockade of EP3 enhanced β-cell proliferation in young, but not old, mouse islets in part through phospholipase C (PLC)-γ1 activity. Blocking EP3 also increased human β-cell proliferation. EP4 modulation had no effect on ex vivo proliferation alone. However, blockade of EP3 in combination with activation of EP4 enhanced human, but not mouse, β-cell proliferation. In both mouse and human islets, EP3 blockade or EP4 activation enhanced β-cell survival in the presence of cytokines. EP4 acts in a protein kinase A (PKA)-dependent manner to increase mouse β-cell survival. In addition, the positive effects of FoxM1 activation on β-cell survival are inhibited by EP3 and dependent on EP4 signaling.ConclusionsOur results identify EP3 and EP4 as novel regulators of β-cell proliferation and survival in mouse and human islets ex vivo.

In busy emergency departments (EDs), it can be difficult for faculty to teach students amid pressure to provide patient care and conduct research. As a result, medical student teaching may be an afterthought rather than a priority, and there is a lack of focus on how students spend their time during clinical shifts in the ED. Students want to contribute to departmental workflow, but can be hampered by systems limitations and lack of clinical knowledge. One solution is for faculty and medical students to partner to add value to patient care in the ED. However, faculty and students must be wary of the distinction between activities that add value and "scutwork," tasks that involve little learning and do not require medical expertise.In this perspective, the student, resident, and faculty authors discuss learner and educator perspectives for how medical students can be productive contributors to patient care in the ED without being subjected to scutwork. They also recommend ideas for productive student activities that promote learning, contrasted with examples of scutwork to avoid. Definitions of value-added activities and scutwork depend on the learner's experience level and interests and are subject to debate. However, if medical students can be engaged in learning while also providing meaningful contributions to patient care, students, educators, and patients stand to benefit.

In our health system with multiple campuses, a universal admissions order (UAO) was introduced to further improve patient flow. We hypothesized that the UAO would more evenly distribute health system capacity, with an increase in admissions to the community affiliate sites. Inpatient and emergency department (ED) metrics were evaluated, and included total admissions, admissions to each clinical site from each ED, the time to the inpatient bed being ready to receive the ED patient, boarding times, and the left without being seen rate. After implementation of the UAO, the average time to inpatient beds being ready to accept ED patients decreased at all three clinical sites by an average of 25 minutes. Admissions were more evenly distributed amongst the three clinical sites, with 3% of all admissions admitted to a new campus. While there were likely other variables at play, there was system-wide reduction in the time to inpatient beds being ready to accept ED patients, and an improvement in boarding at the main clinical site. Our work suggests that a UAO could be a useful adjunct to central capacity management in a health system with multiple clinical campuses.