An Observation Medicine Curriculum for Emergency Medicine Education.

Audience and type of curriculum: This curriculum, designed and implemented at the Ronald O. Perelman Department of Emergency Medicine at NYU Langone Health, primarily targets third- and fourth-year emergency medicine (EM) residents, and is an immersive observation medicine rotation that can be integrated into existing emergency medicine residency training. Length of curriculum: The curriculum is designed for a dedicated rotation of two weeks for senior residents and can be expanded to 4 weeks. Introduction: Observation medicine is an extension of emergency medicine and is increasingly playing a role in the delivery of acute healthcare, with over half of all observation units (OUs) in the nation being led by emergency medicine.1 Despite this, many emergency medicine residencies have yet to establish a formal observation medicine curriculum. In a 2002 study by Mace and Shah, only 10% of emergency medicine residencies had a dedicated observation medicine rotation, despite 85% of emergency medicine residency directors believing this was an important part of emergency medicine training.2 The first description of a model longitudinal observation medicine curriculum did not appear until 2016.3 In order to prepare our graduates for the evolving demands of the EM workplace, we must provide diverse educational experiences that train and showcase the expanding skill set of future emergency physicians. Educational Goals: The primary goal of this observation medicine curriculum is to train current EM residents in short-term acute care beyond the initial ED visit. This entails caring for patients from the time of their arrival to the OU to the point when a final disposition from the OU is determined, be it inpatient admission or discharge to home. Educational Methods: The educational strategies used in this curriculum include experiential learning through supervised direct patient care, independent learning based on prescribed literature, and didactic teaching. Research Methods: Education content was evaluated by the learners through pre- and post-rotation surveys, as well as written attending evaluations describing the progress of the learners during the rotation. Results: All residents reported increases in the confidence of their abilities to perform observation care. Discussion: Observation medicine is an increasingly vital aspect of emergency medicine, but education in observation medicine has not developed in tandem with its implementation. A lack of observation medicine training represents a missed opportunity for each trainee to gain a robust understanding of the interface between inpatient and outpatient care, and how to arrive at the most appropriate disposition for ED patients. Considering the wide breadth of clinical conditions managed in OUs and the variability of OU management at various learning sites, the curriculum must be tailored to the specific unit to maximize effectiveness of the learning experience. Topics: Observation medicine, curriculum, education, clinical rotation.

The circadian gene Rev-erbα improves cellular bioenergetics and provides preconditioning for protection against oxidative stress.

Diurnal oscillations in the expression of antioxidant genes imply that protection against oxidative stress is circadian-gated. We hypothesized that stabilization of the core circadian gene Rev-erbα (Nr1d1) improves cellular bioenergetics and protects against nutrient deprivation and oxidative stress. Compared to WT, mouse lung fibroblasts (MLG) stably transfected with a degradation resistant Rev-erbα (Ser(55/59) to Asp; hence referred to as SD) had 40% higher protein content, 1.5-fold higher mitochondrial area (confocal microscopy), doubled oxidative phosphorylation by high-resolution respirometry (Oroboros) and were resistant to glucose deprivation for 24h. This resulted from a 4-fold reduction in mitophagy (L3CB co-localized with MitoTracker Red) versus WT. Although PGC1α protein expression was comparable between SD and WT MLG cells, the role of mitochondrial biogenesis in explaining increased mitochondrial mass in SD cells was less clear. Embryonic fibroblasts (MEF) from C57Bl/6-SD transgenic mice, had a 9-fold induction of FoxO1 mRNA and increased mRNA of downstream antioxidant targets heme oxygenase-1 (HO-1), Mn superoxide dismutase and catalase (1.5, 2 fold and 2 fold respectively) versus WT. This allowed the SD cells to survive 1h incubation with 500 µM H2O2 as well as 24h of exposure to 95% O2 and remain attached whereas most WT cells did not. These observations establish a mechanistic link between the metabolic functions of Rev-erbα with mitochondrial homeostasis and protection against oxidative stress.

Oxidative stress and inflammation modulate Rev-erbα signaling in the neonatal lung and affect circadian rhythmicity.

AIMS: The response to oxidative stress and inflammation varies with diurnal rhythms. Nevertheless, it is not known whether circadian genes are regulated by these stimuli. We evaluated whether Rev-erbα, a key circadian gene, was regulated by oxidative stress and/or inflammation in vitro and in a mouse model. RESULTS: A unique sequence consisting of overlapping AP-1 and nuclear factor kappa B (NFκB) consensus sequences was identified on the mouse Rev-erbα promoter. This sequence mediates Rev-erbα promoter activity and transcription in response to oxidative stress and inflammation. This region serves as an NrF2 platform both to receive oxidative stress signals and to activate Rev-erbα, as well as an NFκB-binding site to repress Rev-erbα with inflammatory stimuli. The amplitude of the rhythmicity of Rev-erbα was altered by pre-exposure to hyperoxia or disruption of NFκB in a cell culture model of circadian simulation. Oxidative stress overcame the inhibitory effect of NFκB binding on Rev-erbα transcription. This was confirmed in neonatal mice exposed to hyperoxia, where hyperoxia-induced lung Rev-erbα transcription was further increased with NFκB disruption. Interestingly, this effect was not observed in similarly exposed adult mice. INNOVATION: These data provide novel mechanistic insights into how key circadian genes are regulated by oxidative stress and inflammation in the neonatal lung. CONCLUSION: Rev-erbα transcription and circadian oscillation are susceptible to oxidative stress and inflammation in the neonate. Due to Rev-erbα's role in cellular metabolism, this could contribute to lung cellular function and injury from inflammation and oxidative stress.

Silencing hyperoxia-induced C/EBPα in neonatal mice improves lung architecture via enhanced proliferation of alveolar epithelial cells.

Postnatal lung development requires proliferation and differentiation of specific cell types at precise times to promote proper alveolar formation. Hyperoxic exposure can disrupt alveolarization by inhibiting cell growth; however, it is not fully understood how this is mediated. The transcription factor CCAAT/enhancer binding protein-α (C/EBPα) is highly expressed in the lung and plays a role in cell proliferation and differentiation in many tissues. After 72 h of hyperoxia, C/EBPα expression was significantly enhanced in the lungs of newborn mice. The increased C/EBPα protein was predominantly located in alveolar type II cells. Silencing of C/EBPα with a transpulmonary injection of C/EBPα small interfering RNA (siRNA) prior to hyperoxic exposure reduced expression of markers of type I cell and differentiation typically observed after hyperoxia but did not rescue the altered lung morphology at 72 h. Nevertheless, when C/EBPα hyperoxia-exposed siRNA-injected mice were allowed to recover for 2 wk in room air, lung epithelial cell proliferation was increased and lung morphology was restored compared with hyperoxia-exposed control siRNA-injected mice. These data suggest that C/EBPα is an important regulator of postnatal alveolar epithelial cell proliferation and differentiation during injury and repair.