Context Neuropeptide Y (NPY) is important to countering stress and is involved in neuroadaptations that drive escalated alcohol drinking following repeated alcohol exposure in rodents. In humans, haplotype-driven diminution in NPY expression is predictive of amygdala response and emotional reactivity to stress. Genetic variation that affects the NPY system could impact resilience to stress and to developing addiction with continued alcohol use. Objective To determine whether functional NPY variation influences CSF NPY, behavioral adaptation to stress, and alcohol consumption in a nonhuman primate model of early adversity (peer rearing). Design We sequenced the rhesus macaque NPY locus (rhNPY) and performed in silico analysis to identify functional variants. We performed gel shift assays for a −1002 T>G using nuclear extract from testes, brain and hypothalamus. Levels of NPY in CSF were measured by RIA, and mRNA levels were assessed in amygdala using RT-PCR. During infancy, animals were exposed to repeated social separation stress, and tested for individual differences in alcohol consumption as young adults. Animals were genotyped for −1002 T>G, and the effects of this variant on mRNA expression, CSF NPY, behavior arousal during stress, and ethanol consumption were assessed by ANOVA. Results The G allele altered binding of regulatory proteins in all nuclear extracts tested, and −1002 T>G resulted in lower levels of NPY expression in amygdala. Macaques exposed to adversity had lower CSF NPY and exhibited higher levels of arousal during stress, but only as a function of the G allele. We also found that stress-exposed G allele carriers consumed more alcohol and exhibited an escalation in intake over cycles of alcohol availability and deprivation. Conclusions Our results suggest a role for NPY promoter variation in the susceptibility to alcohol use disorders and point to NPY as a candidate for examining GxE interactions in humans.

Background: Fournier's gangrene (FG) is a rapidly progressing necrotizing fasciitis that carries a significant morbidity and mortality. The present study sought to identify the predisposing factors related to FG and validate the Fournier's Gangrene Severity Index (FGSI) score as a prognostic tool in the care of the Fournier's patient.Methods: Medstar Washington Hospital Center records were searched from January 2003 to February 2015 for all patients with a diagnosis code of FG, n=42. Epidemiologic data was collected for patients and used to calculate an FGSI score. Results:The average age was 53.45 yrs and M/F ratio was 39:1. Patients presented with an average 2.675 predisposing factors; the most common was diabetes mellitus (n=21) followed by hypertension (n=18). The most common etiology was periscrotal (n=25) next to perirectal (n=9). Streptococcus was the most common source of infection (n=14). Patients on average required three surgical interventions. The average and median hospitalization period was 19.625 and 11.5 days respectively. Eleven patients developed sepsis. Twentyfour (60%) patients experienced a complication. The overall mortality was 5% (n=2). The average FGSI on admission was 5.368. Multivariate analysis showed FGSI score correlates with more surgical intervention, longer hospitalization, sepsis, complication and mortality. Conclusions:The FGSI score predicts a greater likelihood of more surgical interventions, longer hospitalization period, sepsis, complications and mortality within this patient population. Diabetes mellitus continues to be the most common predisposing factors in FG patients. The mortality rate of 5% is much less than the historically reported 20-30% and may reflect improved understanding and care of this aggressive disease.