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By contrast, MTLE patients showed higher behavioral costs of response conflict resolution and reduced conflict-related HC activation. In patients with left MTLE, left HC activation was predictive of faster conflict-related response times (RT). By contrast, right HC activation was related to RT slowing, suggestive of a maladaptive compensation attempt in MTLE patients. Our results provide evidence that left hippocampal activation is required for the successful resolution of response conflicts. OBJECTIVE The present study was designed to investigate the roles and mechanism of mafenide (MAF) in targeted inhibition of Gasdermin D (GSDMD) cleavage and in suppressing pyroptosis. METHODS Lipopolysaccharide (LPS) and Nigericin were used to induce pyroptosis in mouse bone marrow-derived macrophages (iBMDM) and mouse microglia (BV2). Lactate dehydrogenase (LDH) release rate and Propidium Iodide (PI) uptake rate were used to detect cytotoxicity, Western blot was used to detect the protein expression, and Enzyme-linked immunosorbent assay (ELISA) was utilized to detect the expression of inflammatory factors from culture medium. MAF was labeled with biotin and subsequently subjected to Pull-down assay to detect its binding to GSDMD. GSDMD-Asp275 site was further mutated to validate the binding of MAF to GSDMD. Finally, the effects of MAF on inflammatory factor release and microglial activation were confirmed in the APP/PS12 animal model. RESULTS MAF could inhibit pyroptosis in iBMDM and microglia BV2, and decrease the release of inflammatory factors. MAF could inhibit GSDMD cleavage by directly binding to the GSDMD-Asp275 site, while the expression of p30-GSDMD was simultaneously down-regulated and the release of inflammatory factors was decreased. MAF could reduce the levels of inflammatory factors in cerebrospinal fluid and peripheral blood of APP/PS1 mice, and suppress the activation of microglia. CONCLUSION The mechanism underlying the regulation of MAF on inflammatory response was correlated with the inhibition of pyroptosis. MAF could inhibit GSDMD cleavage by directly binding to GSDMD. V.BACKGROUND Short-term survival after orthotopic liver transplantation (OLT) has improved over the past decades, but long-term survival remains impaired. The effects of obesity on long-term survival after OLT are controversial. Because pre-transplant body mass index (BMI) can be confounded by ascites, we hypothesized that post-transplant BMI at 1 year could predict long-term survival. METHODS A post-hoc analysis was performed of an observational cohort study consisting of adult recipients of a first OLT between 1993-2010. Baseline BMI was measured at 1-year post-transplantation to represent a stable condition. Recipients were stratified into normal weight (BMI30kg/m2). Kaplan-Meier survival analyses were performed with log-rank testing, followed by multivariable Cox proportional hazards regression analysis. RESULTS Out of 370 included recipients, 184 had normal weight, 136 were overweight, and 50 were obese at 1-year post-transplantation. After median follow-up for 12.3 years, 107 recipients had died, of whom 46 (25%) had normal weight, 39 (29%) were overweight, and 22 (44%) were obese (log-rank P=0.020). Obese recipients had a significantly increased mortality risk compared to normal weight recipients (HR 2.00, 95% CI 1.08-3.68, P=0.027). BMI was inversely associated with 15 years patient survival (HR 1.08, 95% CI 1.03-1.14, P=0.001 per kg/m2), independent of age, gender, muscle mass, transplant characteristics, cardiovascular risk factors, kidney- and liver function. CONCLUSION Obesity at 1-year post-transplantation conveys a 2-fold increased mortality risk, which may offer potential for interventional strategies (i.e. dietary advice, lifestyle modification, or bariatric surgery) to improve long-term survival after OLT. see more Melanopsin, a G family coupled receptor, found within the ganglion cell layer in the retina, plays an important role in non-image-forming visual functions, including hormone secretion, entrainment of circadian rhythms, cognitive and affective processes. Diffuse projections of melanopsin-containing cells to many brain areas suggest that different responses may involve different neural projections, thus different melanopsin cells. Considering the complexity of the melanopsin system, its contribution to so many different biological functions is not surprising. In this review, we summarize the current knowledge about melanopsin in terms of its photophysics, photochemistry, mechanisms of activation, cell signaling, morphology, and physiology. In the last part, the role of melanopsin in image and non-image forming processes and cognitive and affective functioning of animals and humans, are discussed. Although in recent years considerable insight has been gained into the melanopsin system, it still remains an open question of how one protein expressed by several thousand cells in the retina, could be responsible for so many diverse functions and what activation mechanism(s) it uses. Clinical and preclinical research have identified sex differences in substance use and addiction-related behaviors. Historically, substance use disorders are more prevalent in men than women, though this gap is closing. Despite this difference, women appear to be more susceptible to the effects of many drugs and progress to substance abuse treatment more quickly than men. While the glutamate system is a key regulator of addiction-related behaviors, much of the work implicating glutamate signaling and glutamatergic circuits has been conducted in men and male rodents. An increasing number of studies have identified sex differences in drug-induced glutamate alterations as well as sex and estrous cycle differences in drug seeking behaviors. This review will describe sex differences in the glutamate system with an emphasis on implications for substance use disorders, highlighting the gaps in our current understanding of how innate and drug-induced alterations in the glutamate system may contribute to sex differences in addiction-related behaviors. INTRODUCTION Fine needle aspiration biopsies (FNABs) have become increasingly important in the assessment of infectious diseases. We assess the ability of cytopathology to predict the presence of a pathogen and review how often neoplasia occurs concurrently with infection. MATERIALS AND METHODS A 3-year retrospective review of FNABs with concurrent culture results was performed at the Zuckerberg San Francisco General Hospital and Trauma Center. Rapid onsite evaluation was performed for all cases by a pathologist. The results of the special and immunohistochemical stains and polymerase chain reaction testing were correlated, when available. RESULTS A total of 231 samples from 11 different tissue sites were submitted for microbial culture, of which 49 (21%) were positive for pathogenic organisms. Only 2 false-negative cases by cytology were found in immunosuppressed patients. A total of 38 patients had a diagnosis of neoplasia, with 2 (5%) having concurrent infection. Overall, the sensitivity and specificity of cytology in predicting the presence of infection was 96% (95% confidence interval, 86%-100%) and 42% (95% confidence interval, 34%-50%), respectively.