Cigarette smoking is an important risk factor for diabetes, cardiovascular disease and non-alcoholic fatty liver disease. The health risk associated with smoking can be aggravated by obesity. Smoking might also trigger cardiomyocyte (CM) apoptosis. Given that CM apoptosis has been implicated as a potential mechanism in the development of cardiomyopathy and heart failure, we characterize the key signaling pathways in nicotine plus high-fat diet (HFD)-induced CM apoptosis. Adult C57BL6 male mice were fed a normal diet (ND) or HFD and received twice-daily intraperitoneal (IP) injections of nicotine (0.75 mg/kg body weight [BW]) or saline for 16 weeks. An additional group of nicotine-treated mice on HFD received twice-daily IP injections of mecamylamine (1 mg/kg BW), a non-selective nicotinic acetylcholine receptor antagonist, for 16 weeks. Nicotine when combined with HFD led to a massive increase in CM apoptosis that was fully prevented by mecamylamine treatment. Induction of CM apoptosis was associated with increased oxidative stress and activation of caspase-2-mediated intrinsic pathway signaling coupled with inactivation of AMP-activated protein kinase (AMPK). Furthermore, nicotine treatment significantly (P < 0.05) attenuated the HFD-induced decrease in fibroblast growth factor 21 (FGF21) and silent information regulator 1 (SIRT1). We conclude that nicotine, when combined with HFD, triggers CM apoptosis through the generation of oxidative stress and inactivation of AMPK together with the activation of caspase-2-mediated intrinsic apoptotic signaling independently of FGF21 and SIRT1.

α7-Nicotinic acetylcholine receptor (α7nAChR) agonists confer protection against a wide variety of cytotoxic insults and suppress oxidative stress and apoptosis in various cell systems, including hepatocytes. We recently demonstrated that nicotine, when combined with a high-fat diet (HFD), triggers oxidative stress, activates hepatocyte apoptosis, and exacerbates HFD-induced hepatic steatosis in male mice. This study evaluates whether PNU-282987 (PNU), a specific α7nAChR agonist, is effective in preventing nicotine plus HFD-induced hepatic steatosis. Adult C57BL6 male mice were fed a normal chow diet or HFD with 60% of calories derived from fat and received twice-daily intraperitoneal injections of 0.75 mg/kg body weight (BW) of nicotine, PNU (0.26 mg/kg BW), PNU plus nicotine, or saline for 10 weeks. PNU treatment was effective in attenuating nicotine plus HFD-induced increase in hepatic triglyceride levels, hepatocyte apoptosis, and hepatic steatosis. The preventive effects of PNU on nicotine plus HFD-induced hepatic steatosis were mediated by suppression of oxidative stress and activation of adenosine 5'-monophosphate-activated protein kinase (AMPK) together with inhibition of its downstream target sterol regulatory element binding protein 1c (SREBP1c), fatty acid synthase (FAS), and acetyl-coenzyme A-carboxylase (ACC). We conclude that the α7nAChR agonist PNU protects against nicotine plus HFD-induced hepatic steatosis in obese mice. PNU appears to work at various steps of signaling pathways involving suppression of oxidative stress, activation of AMPK, and inhibition of SREBP1c, FAS, and ACC. α7nAChR agonists may be an effective therapeutic strategy for ameliorating fatty liver disease, especially in obese smokers.

Purpose: The Geriatric Nutritional Risk Index (GNRI) is a simple screening tool to predict nutrition-related risk of morbidity and mortality in older patients. We assessed whether preoperative GNRI was associated with 30-day complications after radical cystectomy (RC). Materials and Methods: Using the American College of Surgeons National Surgical Quality Improvement Program database, we identified patients 65 years or older who underwent RC for the treatment of bladder cancer between 2007 and 2019. Patients were dichotomized into at-risk (GNRI 98) or no-risk (GNRI >98) groups. Using propensity score matching, the 2 groups were compared for baseline differences and 30-day outcomes. We evaluated GNRI as an independent predictor of postoperative complications using multivariable logistic regression analysis. Results: We identified 2,926 patients eligible for analysis. After propensity score matching, patients in the at-risk GNRI group had higher rates of any complication (p[0.017), blood transfusion (p[0.002), extended length of stay (p[0.004) and nonhome discharge (p <0.001). Multivariable logistic regression analysis revealed that a decreasing GNRI is an independent prognostic factor for mortality (OR 1.05, 95% CI 1.01e1.08, p[0.009), blood transfusion (OR 1.03, 95% CI 1.02e1.04, p <0.001), pneumonia (OR 1.04, 95% CI 1.01e1.07, p[0.013), extended length of stay (OR 1.03, 95% CI 1.02e1.05, p <0.001) and nonhome discharge (OR 1.04, 95% CI 1.03e1.06, p <0.001). Conclusions: We demonstrate that nutritional status evaluated by GNRI predicts 30-day complications after RC.

Introduction: Chronic liver disease (CLD) is a term used to describe a wide spectrum of disorders, including idiopathic, infectious, genetic, drug-induced, toxin-induced, and autoimmune disorders. The common consequence of chronic damage to the liver is cirrhosis. Cirrhotic patients are further classified by their severity based on the Child-Pugh scoring system. Currently, Child-Pugh scoring consists of ascites, hepatic encephalopathy (HE), prothrombin time, serum albumin level, and total bilirubin level. Lipid panel in CLD is a great marker in determining the severity of CLD. Method and methodology: It was a descriptive cross-sectional study conducted at a tertiary care hospital. A sample size of 122 was calculated by using a RaoSoft Digital Sample Size Calculator (RaoSoft, Inc., Seattle, WA) in which we used 5% as a margin of error, 95% as confidence interval (CI), 178 as population size, and response distribution as 50%. Non-complicated CLD patients having age in between 15 and 80 years with no cirrhotic complications including HE, spontaneous bacterial peritonitis, hepato-pumonary, or hepato-renal syndrome were included in our study; the rest of the CLD patients were excluded from our study. Results: The mean age of the study population was 47.09 ± 12.30 years with more than half of the patients lying among the age group 25-50 years. The study population included 76% of males (n=93) and 24% of females (n=29), with a mean age of females higher than the males. Diabetes mellitus (58.19%) was the most frequent comorbidity associated with CLD in subjects included in our study. Parameters of lipid panel were decreased exponentially as the severity of CLD increases from Child score A to C. Total cholesterol, lowdensity lipoprotein (LDL), very-low-density lipoprotein (VLDL), high-density lipoprotein (HDL), and triglyceride (TG) level decreased as the severity increases in our study. The mean model for end-stage liver disease (MELD) score increased as per hypothesized as the severity increases from Child score A to Child score C, respectively. Conclusion: Our study concluded that as the severity of CLD increases from Child class A to Child class C, the lipid panel profile decreases exponentially which proved the idea that had been hypothesized at the beginning of our study.

The Ritualization of Violence in The Magic Toyshop by Victor Chalfant This dissertation will explore the way Philip treats puppets and masks as pseudosacred objects in order to maintain control in Angela Carter's work The Magic Toyshop. To show the implications of the pseudo-sacred, I will use Violence and the Sacred by Rene Girard that examines the way primitive cultures are able to maintain order through particular religious beliefs and collective violence against a scapegoat. My critical reading of the text will look closely at how Philip uses the pseudo-sacred to build up the community. When the pseudo-sacred is finally called into question the community is threatened. Although Philip attempts to deflect blame onto the scapegoat Melanie, he fails as there is no social buy-in, leading to the destruction of the community. While the house is burned down destroying the puppets and masks, presumably along with Philip, the pseudo-sacred still has the chance of being perpetuated through Finn's own obsession with power and control. v TABLE OF CONTENTS

Background To stratify 10‐year survival outcomes by degree of social disparities in pediatric Wilms' tumor patients. We applied the Social Deprivation Index (SDI) to survival outcomes from the national SEER database to elucidate the effects of lower socioeconomics on cancer survival. Methods A retrospective cohort study was performed using the national Surveillance, Epidemiology, and End Results (SEER) oncology registry from 1975 to 2016 based on county‐level data. Pediatric patients (<18 years old) with a diagnosis of WT (C64.9) and confirmed based on histology codes (8960/8963) were included. SDI scores were calculated for each patient and initially divided into quintiles. Patients were delineated into high‐risk (>60th percentile/more deprived) or low‐risk (<60th percentile/less deprived) groups. Statistics were assessed using Fisher's exact test, Student's t ‐test, and Kaplan–Meier assessed survival differences with log‐rank test for trend. Results A total of 3406 patients were included with 1366 patients reported in the high‐risk group and 2040 patients in the low‐risk group. Quintile data demonstrated a stratification in survival based on socioeconomic status. Patients in more socially deprived counties were significantly ( p = 0.035) more likely to have worse overall survival compared with those living in less deprived areas at 10‐year (87.3% vs 89.3%) follow‐up. Conclusions 10‐year overall and cancer‐specific survival data for patients with Wilms' tumor stratify by socioeconomic lines. This represents an area that needs to be addressed in this pediatric oncologic population. Patients from more socially deprived areas have significantly worse 10‐year overall survival rates and noticeably different 10‐year cancer‐specific survival rates.

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