Clostridium perfringens epsilon toxin (ETX) is responsible for causing the economically devastating disease, enterotoxaemia, in livestock. It is well accepted that ETX causes blood brain barrier (BBB) permeability, however the mechanisms involved in this process are not well understood. Using in vivo and in vitro methods, we determined that ETX causes BBB permeability in mice by increasing caveolae-dependent transcytosis in brain endothelial cells. When mice are intravenously injected with ETX, robust ETX binding is observed in the microvasculature of the central nervous system (CNS) with limited to no binding observed in the vasculature of peripheral organs, indicating that ETX specifically targets CNS endothelial cells. ETX binding to CNS microvasculature is dependent on MAL expression, as ETX binding to CNS microvasculature of MAL-deficient mice was not detected. ETX treatment also induces extravasation of molecular tracers including 376Da fluorescein salt, 60kDA serum albumin, 70kDa dextran, and 155kDA IgG. Importantly, ETX-induced BBB permeability requires expression of both MAL and caveolin-1, as mice deficient in MAL or caveolin-1 did not exhibit ETX-induced BBB permeability. Examination of primary murine brain endothelial cells revealed an increase in caveolae in ETX-treated cells, resulting in dynamin and lipid raft-dependent vacuolation without cell death. ETX-treatment also results in a rapid loss of EEA1 positive early endosomes and accumulation of large, RAB7-positive late endosomes and multivesicular bodies. Based on these results, we hypothesize that ETX binds to MAL on the apical surface of brain endothelial cells, causing recruitment of caveolin-1, triggering caveolae formation and internalization. Internalized caveolae fuse with early endosomes which traffic to late endosomes and multivesicular bodies. We believe that these multivesicular bodies fuse basally, releasing their contents into the brain parenchyma.

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Background: Interest in firearm injuries (FAIs), from medical and public health perspectives continues to grow. Few studies have analyzed the relationship of FAIs, craniofacial fractures, and traumatic brain injuries (TBIs). Methods: FAIs were isolated from national data from the American College of Surgeons (ACS) Trauma Quality Improvement Program (TQIP) 2014 to 2016 using external cause encodings. Pertinent demographic, injury, and hospital characteristics were extracted to characterize trends and statistically significant outcomes. Results: Thirty-two thousand eight hundred ninety-three (out of 829 805 cases) FAIs were captured, with a majority of patients being male and non-Hispanic/Latino Black. Multivariate linear regression revealed that race/ethnicity, age, hospital size, hospital region, intent of injury, and ISS significantly contributed to risk of mortality, increased hospital length of stay (LOS), and intensive care unit (ICU) duration. Five thousand nine hundred ten (18.0%) FAIs had at least 1 craniofacial fracture, and among these 75.1% (4441) incurred a traumatic brain injury (TBI). Mortality rate among patients with craniofacial FAI was 43.8% (2586/5910), compared to 9.7% (2618/26 983) without. Delayed surgical repair significantly increased hospital LOS ( P < .01), but not mortality ( P = .09). Conclusion: FAIs with craniofacial injury have significantly higher mortality rates than those without craniofacial injury. FAI-associated craniofacial injuries are frequently associated with TBI which is associated with significant morbidity and mortality. Such findings pose important public health and economic implications.

Background: Obesity and metabolic syndrome (MS) are prevalent and associated with negative health outcomes in the elderly. There is a need to identify risk factors for these diseases in this population. Methodology: The 2013-14 National Health and Nutrition Examination Survey was used in this study. Adults aged 60 or under were categorized into normosmia, hyposmia, anosmia, and combined anosmia + hyposmia using the Pocket Sniff Test. Taste was evaluated using quinine and NaCl solutions. Multivariate logistic regression models were used to characterize associations between smell and taste status and obesity and MS. Results: In univariate obesity analysis, normosmia, combined anosmia + hyposmia, and 0.32M NaCl taste dysfunction were significant. 0.32M NaCl taste dysfunction remained significant in multivariate analysis. MS was significantly associated with only tongue tip quinine dysfunction in univariate and multivariate analyses. Conclusions: Salty taste dysfunction was found to be negatively associated with obesity while bitter taste dysfunction was found to be positively associated with MS.