Impact of the Las Vegas Mass Shooting Event on the Graduate Medical Education Mission: Can There Be Growth from Tragedy?

INTRODUCTION: Our aim was to determine the psychological and educational impact of the 2017 Las Vegas mass shooting on the graduate medical education (GME) mission within two cohorts of resident physicians and attending faculty at two nearby academic trauma centers. METHODS: A cross-sectional survey assessed 55 resident physicians and attending faculty involved in the acute care of the patients from the mass shooting. We measured the psychological impact of the event, post-traumatic growth, team cohesion, social support, and known risk factors for post-traumatic stress disorder (PTSD). Additionally, we assessed the impact of the event on GME-specific tasks. RESULTS: Attending faculty and physicians in training in GME residencies evaluated over 300 penetrating trauma patients in less than 24 hours, and approximately 1 in 3 physicians had a patient die under their care. Despite this potential for psychological trauma, the majority of clinicians reported minimal distress and minimal impact on GME activities. However, 1 in 10 physicians screened positive for possible PTSD. Paradoxically, the minority of physicians who sought psychological counseling after the event (20%) were not those who reported the highest levels of distress. Residents generally assessed the event as having an overall negative impact on their educational goals, while attendings reported a positive impact. Psychological impact correlated inversely with social support and the amount of prior education relating to mass casualty incidents (MCI) but correlated directly with the degree of stress prior to the event. CONCLUSION: Despite the substantial level of exposure, most resident physicians did not report significant psychological trauma or an impact on their GME mission. Some reported post-traumatic growth. However, a minority reported a significant negative impact; institutions should consider broad screening efforts to detect and assist these individuals after a MCI. Social support, stress reduction, and education on MCIs may buffer the effects of future psychologically traumatic events on physicians in training.

Dissecting the kinetics of the NADP(+)-FADH2 charge transfer complex and flavin semiquinones in neuronal nitric oxide synthase.

Electron flow within the neuronal nitric oxide synthase reductase domain (nNOSrd) includes hydride transfer from NADPH to FAD followed by two one-electron transfer reactions from FAD to FMN. We have used stopped flow spectrometry to closely monitor these electron transfer steps for both the wild type and the ΔG810 mutant of nNOSrd using a protocol involving both global analyses of the photodiode array spectral scans and curve fittings of single wavelength kinetic traces. The charge transfer complex and interflavin electron transfer events recorded at 750nm and 600nm, respectively, show the kinetics in different time frames. All electron transfer events are slow enough at 4°C to enable measurements of rate constants even for the fast charge transfer event. To our knowledge this is the first time the rate constants for the charge transfer between NADP(+) and FADH2 have been determined for NOS. These procedures allow us to conclude that (1) binding of the second NADPH is necessary to drive the full reduction of FMN and; (2) charge transfer and the subsequent interflavin electron transfer have distinct spectral features that can be monitored separately with stopped flow spectroscopy. These studies also enable us to conclude that interflavin electron transfer reported at 600nm is not limiting in NOS catalysis.

Binge drinking upregulates accumbens mGluR5-Homer2-PI3K signaling: functional implications for alcoholism.

The glutamate receptor-associated protein Homer2 regulates alcohol-induced neuroplasticity within the nucleus accumbens (NAC), but the precise intracellular signaling cascades involved are not known. This study examined the role for NAC metabotropic glutamate receptor (mGluR)-Homer2-phosphatidylinositol 3-kinase (PI3K) signaling in regulating excessive alcohol consumption within the context of the scheduled high alcohol consumption (SHAC) model of binge alcohol drinking. Repeated bouts of binge drinking ( approximately 1.5 g/kg per 30 min) elevated NAC Homer2a/b expression and increased PI3K activity in this region. Virus-mediated knockdown of NAC Homer2b expression attenuated alcohol intake, as did an intra-NAC infusion of the mGluR5 antagonist MPEP [2-methyl-6-(phenylethynyl)pyridine hydrochloride] (0.1-1 microg/side) and the PI3K antagonist wortmannin (50 ng/side), supporting necessary roles for mGluR5/Homer2/PI3K in binge alcohol drinking. Moreover, when compared with wild-type littermates, transgenic mice with an F1128R point mutation in mGluR5 that markedly reduces Homer binding exhibited a 50% reduction in binge alcohol drinking, which was related to reduced NAC basal PI3K activity. Consistent with the hypothesis that mGluR5-Homer-PI3K signaling may be a mechanism governing excessive alcohol intake, the "anti-binge" effects of MPEP and wortmannin were not additive, nor were they observed in the mGluR5(F1128R) transgenic mice. Finally, mice genetically selected for a high versus low SHAC phenotype differed in NAC mGluR, Homer2, and PI3K activity, consistent with the hypothesis that augmented NAC mGluR5-Homer2-PI3K signaling predisposes a high binge alcohol-drinking phenotype. Together, these data point to an important role for NAC mGluR5-Homer2-PI3K signaling in regulating binge-like alcohol consumption that has relevance for our understanding of the neurobiology of alcoholism and its pharmacotherapy.