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Nonalcoholic steatohepatitis (NASH) is associated with caspase activation. However, a role for pro-inflammatory caspases or inflammasomes has not been explored in diet-induced liver injury. Our aims were to examine the role of caspase-1 in high fat-induced NASH. C57BL/6 wild-type and caspase 1-knockout (Casp1(-/-)) mice were placed on a 12-week high fat diet. Wild-type mice on the high fat diet increased hepatic expression of pro-caspase-1 and IL-1β. Both wild-type and Casp1(-/-) mice on the high fat diet gained more weight than mice on a control diet. Hepatic steatosis and TG levels were increased in wild-type mice on high fat diet, but were attenuated in the absence of caspase-1. Plasma cholesterol and free fatty acids were elevated in wild-type, but not Casp1(-/-) mice, on high fat diet. ALT levels were elevated in both wild-type and Casp1(-/-) mice on high fat diet compared to control. Hepatic mRNA expression for genes associated with lipogenesis was lower in Casp1(-/-) mice on high fat diet compared to wild-type mice on high fat diet, while genes associated with fatty acid oxidation were not affected by diet or genotype. Hepatic Tnfα and Mcp-1 mRNA expression was increased in wild-type mice on high fat diet, but not in Casp1(-/-) mice on high fat diet. αSMA positive cells, Sirius red staining, and Col1α1 mRNA were increased in wild-type mice on high fat diet compared to control. Deficiency of caspase-1 prevented those increases. In summary, the absence of caspase-1 ameliorates the injurious effects of high fat diet-induced obesity on the liver. Specifically, mice deficient in caspase-1 are protected from high fat-induced hepatic steatosis, inflammation and early fibrogenesis. These data point to the inflammasome as an important therapeutic target for NASH.

Misophonia was initially described in 2001 as a specific sensitivity to certain sounds (e.g., chewing, pen clicking). Despite greater recognition of misophonia over the last two decades, the extent of awareness of misophonia in the general public is unknown. Extensive research emphasizes the importance of public awareness in recognition and treatment of mental disorders and medical conditions. Awareness of misophonia is important for the continued advancement of misophonia research and identification of individuals with misophonia. As an important first step, this study investigated the general public’s understanding of misophonia. Data were collected through Ipsos KnowledgePanel, which maintains a large, probability-based web panel designed to be representative of the United States. Panel members were invited to complete a brief survey, and the final sample was comprised of 4,005 participants (51.5% female). A small portion of individuals (11.3%, n  = 451) recognized misophonia. A multivariate binary logistic regression model revealed that individuals who were female, younger, White/non-Hispanic, had a Bachelor’s degree or higher, or reported an annual income between $75,000 - $99,000 were significantly more likely to endorse misophonia recognition. Most participants who were familiar with misophonia reported an accurate understanding about misophonia; yet, low level of knowledge. The internet was most commonly identified as the primary information source. Findings highlight the low level of misophonia awareness among laypersons and emphasize the need to increase public knowledge of misophonia.

In the latter half of the 20th century, societal and technological changes led to a shift in the composition of the American diet to include a greater proportion of processed, pre-packaged foods high in fat and carbohydrates, and low in dietary fiber (a \"Western diet\"). Over the same time period, there have been parallel increases in Salmonella gastroenteritis cases and a broad range of chronic inflammatory diseases associated with intestinal dysbiosis. Several polysaccharide food additives are linked to bacterially-driven intestinal inflammation and may contribute to the pathogenic effects of a Western diet. Therefore, we examined the effect of a ubiquitous polysaccharide food additive, maltodextrin (MDX), on clearance of the enteric pathogen Salmonella using both in vitro and in vivo infection models. When examined in vitro, murine bone marrow-derived macrophages exposed to MDX had altered vesicular trafficking, suppressed NAPDH oxidase expression, and reduced recruitment of NADPH oxidase to Salmonella-containing vesicles, which resulted in persistence of Salmonella in enlarged Rab7+ late endosomal vesicles. In vivo, mice consuming MDX-supplemented water had a breakdown of the anti-microbial mucous layer separating gut bacteria from the intestinal epithelium surface. Additionally, oral infection of these mice with Salmonella resulted in increased cecal bacterial loads and enrichment of lamina propria cells harboring large Rab7+ vesicles. These findings indicate that consumption of processed foods containing the polysaccharide MDX contributes to suppression of intestinal anti-microbial defense mechanisms and may be an environmental priming factor for the development of chronic inflammatory disease.

Inflammatory bowel disease (IBD) encompasses a group of disorders affecting the gastrointestinal tract characterized by acute and chronic inflammation. These are complex and multifactorial disorders that arise in part from a genetic predisposition. However, the increasing incidence of IBD in developing countries suggests that environmental factors, such as diet, are also critical components of disease susceptibility. Evidence suggests that consumption of a Western diet, enriched with saturated fat, refined carbohydrates, and food additives, is associated with increased IBD risk. Dietary components, such as omega-6 fatty acids, long-chain fatty acids, protein, and digestible carbohydrates, may contribute to IBD pathogenesis through altering intestinal microbiota, increasing intestinal permeability, and promoting inflammation; whereas omega-3 fatty acids, medium chain triglycerides, and nondigestible carbohydrates improve these parameters and intestinal health. However, the limited amount of prospective studies, small sample sizes, and the heterogeneity of disease subtype result in inconsistencies between studies and difficulty in conclusively determining the specific effects of diet on intestinal homeostasis. There are no standard clinical dietary recommendations for patients with IBD. However, exclusionary diet interventions have shown some efficacy in relieving symptoms or inducing remission, suggesting more research is needed to fully understand how diet influences disease behavior or combines with other IBD risk factors to promote disease. This review focuses on the associations of various dietary components and IBD risk in clinical studies and genetically susceptible IBD models.

Non-alcoholic steatohepatitis (NASH) is typically associated with pro-apoptotic caspase activation. A potential role for pro-inflammatory caspases remains incompletely understood. Our aims were to examine a potential role of caspase-1 in the development of liver damage and fibrosis in NASH. C57BL/6 wild type (WT) developed marked steatohepatitis, activation, fibrosis and increased hepatic caspase-1 and interleukin-1β expression when placed on the methionine- and choline-deficient (MCD) diet. Marked caspase-1 activation was detected in the liver of MCD-fed mice. Hepatocyte and non-parenchymal fractionation of the livers further demonstrated that caspase-1 activation after MCD feeding was mainly localized to non-parenchymal cells. Caspase-1-knockout (Casp1−/−) mice on the MCD diet showed marked reduction in mRNA expression of genes involved in inflammation and fibrogenesis (tumor necrosis factor-α was 7.6-fold greater in WT vs Casp1−/− MCD-fed mice; F4/80 was 1.5-fold greater in WT vs Casp1−/− MCD-fed mice; α-smooth muscle actin was 3.2-fold greater in WT vs Casp1−/− MCD-fed mice; collagen 1-α was 7.6-fold greater in WT vs Casp1−/− MCD-fed mice; transforming growth factor-β was 2.4-fold greater in WT vs Casp1−/− MCD-fed mice; cysteine- and glycine-rich protein 2 was 3.2-fold greater in WT vs Casp1−/− MCD-fed mice). Furthermore, Sirius red staining for hepatic collagen deposition was significantly reduced in Casp1−/− MCD-fed mice compared with WT MCD-fed animals. However, serum alanine aminotransferase levels, caspase-3 activity and terminal deoxynucleotidyl transferase dUTP nick-end labeling-positive cells were similar in Casp1−/− and WT mice on the MCD diet. Selective Kupffer cell depletion by clodronate injection markedly suppressed MCD-induced caspase-1 activation and protected mice from fibrogenesis and fibrosis associated with this diet. The conclusion of this study is that it uncovers a novel role for caspase-1 in inflammation and fibrosis during NASH development.

The connection between stress and skin disease has been extensively documented; however, there are no empirical studies investigating the incidence of traumatic event exposure and posttraumatic stress (PTS) symptoms among dermatology patients. To address this gap in the literature and begin to understand the associations between PTS symptoms and skin disease symptoms, this study used a sample of adults with self-reported skin disease symptoms to examine: (1) rates of potentially traumatic event (PTE) exposure and PTS symptoms; and (2) the association between PTS symptoms and skin-related quality of life, controlling for relevant covariates. Data were collected online through Cloud Research, and participants completed a battery of self-report measures. The sample included 310 participants (68.4% female) who endorsed current skin disease symptoms. Results indicated that 47.1% of participants endorsed clinical levels of PTS symptoms. Consistent with hypotheses, greater levels of PTS symptoms were associated with worse skin-related quality of life, and this association was particularly robust for arousal-related symptoms. Results shed light on the occurrence of trauma-related experiences among individuals with self-reported skin disease and indicate a link between PTS symptoms and the perceived burden of skin disease symptoms on daily living. However, this study was cross-sectional and relied on self-report measures; therefore, findings should be interpreted with caution, particularly since diagnoses could not be verified. Replication of this work in dermatology patients is needed to further understand these connections.

Nonalcoholic fatty liver disease (NAFLD) is currently the most common form of chronic liver disease affecting both adults and children in the USA and many other parts of the world. NAFLD encompasses a wide spectrum of conditions associated with the overaccumulation of lipids in the liver, ranging from steatosis to nonalcoholic steatohepatitis, to cirrhosis and its feared complications of portal hypertension, liver failure and hepatocellular carcinoma. In this article, we will focus on the growing evidence linking changes in hepatic lipid metabolism and accumulation of specific lipid types in the liver with hepatocellular damage, inflammation and apoptosis, resulting in disease progression to the more serious forms of this condition.

COPD is one of the leading causes of death in the United States and results in increased healthcare costs and disability. Smoking is the main determinant of COPD development and continued use increases mortality as compared to those who have stopped smoking. Research has indicated that cigarette smoking may play a role in attempts to regulate distressing emotional experiences and thus, may be an important transdiagnostic process underlying continued smoking behavior among adults with COPD. The current study investigated the role of ER difficulties in relation to smoking status and cigarettes smoked per day among adults with COPD. This cross-sectional study included a sample was adults with COPD (N = 320). Participants self-reported current smoking status, daily smoking, and the Difficulties in Emotion Regulation Scale. All analyses were adjusted for age, sex, probable depression, probable anxiety, and dyspnea severity. DERS total scores were associated with greater odds of current smoking. With the exception of impulsivity, all other dimensions of emotion regulation were significantly associated with current smoking. Greater difficulties in emotional awareness were associated with greater cigarettes smoked per day. However, neither the DERS total score nor any other dimensions of emotional regulation were significantly associated with cigarettes smoked per day. The present study provides preliminary data linking ER difficulties to smoking behavior among adults with COPD. If corroborated by future research, these findings suggest that ER might be a potential target for smoking cessation programs among adults with COPD.

Approximately one-third of adults with chronic respiratory disease (CRD) have comorbid depressive and anxiety disorders; yet these disorders are often unrecognized in this patient population. Transdiagnostic processes such as anxiety sensitivity (AS) are useful for identifying mechanisms underlying psychological and heath conditions. The Short-Scale AS Index (SSASI) is a brief self-report measure of AS which has potential clinical utility among CRD populations to evaluate psychological distress and inform comprehensive care. The present study investigated the psychometric properties of the SSASI among adults with CRDs. Participants were recruited from a web-based panel of adults with CRDs ( n  = 768; 49.3% female; 57.8% White) including adults with asthma only ( n  = 230), COPD only ( n  = 321), or co-occurring asthma and COPD ( n  = 217). Participants completed a battery of self-report questionnaires assessing psychological and medical symptoms. Analyses were conducted to examine the factor structure and measurement invariance across CRD groups. Convergent validity and criterion validity of the SSASI were assessed within each group. Results supported partial measurement invariance across CRD groups. The SSASI demonstrated high reliability, convergent validity, and criterion validity with each CRD group. Findings from this study and existing work indicate that the SSASI is an effective and economical assessment tool for identifying patients CRD who may benefit from psychological interventions to reduce AS.

Emerging research suggests social anxiety, health anxiety, and generalized anxiety disorder symptoms are particularly relevant for dermatology patients. Unfortunately, very few studies have investigated how these anxieties affect quality of life among individuals with skin disease. The aims of the present study were to characterize the rates of these anxiety syndromes among adults with active skin disease symptoms, examine correlations between anxiety and skin disease symptoms, and test the mediating role of anxiety sensitivity in skin-related impairment. A considerable number of participants (N = 237) screened positive for social anxiety disorder (62.9%), health anxiety (18.1%), and generalized anxiety disorder (32.5%). Consistent with hypothesis, each anxiety syndrome was indirectly related to skin-related impairment through anxiety sensitivity. Overall, the findings emphasize the importance of anxiety symptoms in dermatological outcomes.