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A genetic variant in the SAND domain of autoimmune regulator (AIRE), R247C, was identified in a patient with type I diabetes mellitus (T1DM) and his mother with rheumatoid arthritis. In vitro, the variant dominantly inhibited AIRE; however, typical features of Autoimmune Polyendocrinopathy Candidiasis and Ectodermal Dysplasia (APECED) were not seen in the subjects. Rather, early manifestation of autoimmunity appeared to be dependent on additional genetic factors. On a population level, diverse variants were identified in this region. Surprisingly, many likely pathogenic variants were seen disproportionately in Africans when compared to Europeans, reinforcing the importance of these variants in altering the immune repertoire. In light of these findings, we propose that R247C and other variants within the SAND-domain alter protein function in a dominant fashion and hold potential as drivers of autoimmunity.

Abstract In this clinical trial, the safety and effectiveness of Lactobacillus paracasei N1115 (LP N1115) were investigated as a potential probiotic to enhance gut development in young children born by caesarean section. Infants and young children between the ages of 6 months and 3 years were administered with a probiotic consisting of LP N1115 strain (n = 30) or placebo supplement (n = 30) over an 8 weeks intervention. And the stool consistency, bowel habits, salivary cortisol, fecal microbiota, and short‐chain fatty acid metabolism were investigated. Efficacy data were obtained from 58 participants who completed the study. Overall, the placebo functioned similarly to LP N1115 group in relation to stool consistency, gastrointestinal symptoms, salivary cortisol, and short‐chain fatty acids. However, the scoring data relating to the 6–18 months subgroup receiving LP N1115 remained stable over 8 weeks in comparison to placebo. Analysis of the fecal microbiota using 16S rRNA amplicon sequencing revealed that the phyla Firmicutes represented 62% of the microbial relative abundance in the feces of the subjects during the intervening period. No significant changes in alpha‐ or beta‐diversity were noted between the placebo and LP N1115 groups overtime and at each time point. Differential abundance analysis indicated an increase in Lactobacillus in LP N1115 group at weeks 4 (p

This study aimed to investigate the dose–response effect of Bifidobacterium breve CCFM683 on relieving psoriasis and its underlying patterns. Specifically, the expression of keratin 16, keratin 17, and involucrin were substantially decreased by administration of 109 CFU and 1010 CFU per day. Moreover, interleukin (IL)-17 and TNF-α levels were substantially decreased by 109 and 1010 CFU/day. Furthermore, the gut microbiota in mice treated with 109 or 1010 CFU/day was rebalanced by improving the diversity, regulating microbe interactions, increasing Lachnoclostridium, and decreasing Oscillibacter. Moreover, the concentrations of colonic bile acids were positively correlated with the effectiveness of the strain in relieving psoriasis. The gavage dose should be more than 108.42 CFU/day to improve psoriasis according to the dose–effect curve. In conclusion, CCFM683 supplementation alleviated psoriasis in a dose-dependent manner by recovering microbiota, promoting bile acid production, regulating the FXR/NF-κB pathway, diminishing proinflammatory cytokines, regulating keratinocytes, and maintaining the epidermal barrier function. These results may help guide probiotic product development and clinical trials in psoriasis.

Educators have struggled to incorporate authentic team-based learning (TBL) into the business curriculum despite increasing evidence that collaborative learning can enhance learning outcomes. We investigate the use of online business simulations as a platform for fostering authentic TBL for undergraduate and postgraduate business students studying at seven institutions in Australia and Hong Kong. Quantitative analysis of 365 surveys is supported by focus groups with 14 students. Structural equation modeling (SEM) is used to model the relationships between teamwork, learning outcomes, and satisfaction. Qualitative results support the statistical modeling and are presented to add further insights and conceptual richness. The findings support our proposition that online business simulations provide an authentic TBL environment, which contributes to learner satisfaction by supporting the development of management-related learning outcomes through socially constructed meaning. This conceptual contribution highlights further avenues for research and leads to some practical implications for educators using simulation-based pedagogies.

The global rise in type 2 diabetes (T2D) and obesity necessitates innovative dietary interventions. This study investigates the effects of allulose, a rare sugar shown to reduce blood glucose, in a rat model of diet-induced obesity and T2D. Over 12 weeks, we hypothesized that allulose supplementation would improve body weight, insulin sensitivity, and glycemic control. Our results showed that allulose mitigated the adverse effects of high-fat, high-sugar diets, including reduced body weight gain and improved insulin resistance. The allulose group exhibited lower food consumption and increased levels of glucagon-like peptide-1 (GLP-1), enhancing glucose regulation and appetite control. Additionally, allulose prevented liver triglyceride accumulation and promoted mitochondrial uncoupling in adipose tissue. These findings suggest that allulose supplementation can improve metabolic health markers, making it a promising dietary component for managing obesity and T2D. Further research is needed to explore the long-term benefits and mechanisms of allulose in metabolic disease prevention and management. This study supports the potential of allulose as a safe and effective intervention for improving metabolic health in the context of dietary excess. [ABSTRACT FROM AUTHOR]

Previous studies involving workers at brick kilns in the Kathmandu Valley of Nepal have investigated chronic exposure to hazardous levels of fine particulate matter (PM2.5) common in ambient and occupational environments. Such exposures are known to cause and/or exacerbate chronic respiratory diseases, including chronic obstructive pulmonary disease (COPD) and asthma. However, there is a paucity of data regarding the status of systemic inflammation observed in exposed workers at brick manufacturing facilities within the country. In the current study, we sought to elucidate systemic inflammatory responses by quantifying the molecular cytokine/chemokine profiles in serum from the study participants. A sample of participants were screened from a kiln in Bhaktapur, Nepal (n = 32; 53% female; mean ± standard deviation: 28.42 ± 11.47 years old) and grouped according to job category. Blood was procured from participants on-site, allowed to clot at room temperature, and centrifuged to obtain total serum. A human cytokine antibody array was used to screen the inflammatory mediators in serum samples from each of the participants. For the current study, four job categories were evaluated with n = 8 for each. Comparisons were generated between a control group of administration workers vs. fire master workers, administration workers vs. green brick hand molders, and administration workers vs. top loaders. We discovered significantly increased concentrations of eotaxin-1, eotaxin-2, GCSF, GM-CSF, IFN-γ, IL-1α, IL-1β, IL-6, IL-8, TGF-β1, TNF-α, and TIMP-2 in serum samples from fire master workers vs. administration workers (p < 0.05). Each of these molecules was also significantly elevated in serum from green brick hand molders compared to administration workers (p < 0.05). Further, each molecule in the inflammatory screening with the exception of TIMP-2 was significantly elevated in serum from top loaders compared to administration workers (p < 0.05). With few exceptions, the fire master workers expressed significantly more systemic inflammatory molecular abundance when compared to all other job categories. These results reveal an association between pulmonary exposure to PM2.5 and systemic inflammatory responses likely mediated by cytokine/chemokine elaboration. The additional characterization of a broader array of inflammatory molecules may provide valuable insight into the susceptibility to lung diseases among this population. [ABSTRACT FROM AUTHOR]

Exposure to respirable dust and crystalline silica (SiO2) has been linked to chronic obstructive pulmonary disease, silicosis, cancer, heart disease, and other respiratory diseases. Relatively few studies have measured respirable dust and SiO2 concentrations among workers at brick kilns in low- and middle-income countries. The purpose of this study was to measure personal breathing zone (PBZ) respirable dust and SiO2 concentrations among workers at one brick kiln in Bhaktapur, Nepal. A cross-sectional study was conducted among 49 workers in five job categories: administration, fire master, green (unfired) brick hand molder, green brick machine molder, and top loader. PBZ air samples were collected from each worker following Methods 0600 (respirable dust) and 7500 (respirable crystalline SiO2: cristobalite, quartz, tridymite) of the U.S. National Institute for Occupational Safety and Health. Eight-hour time-weighted average (TWA) respirable dust and quartz concentrations were also calculated. SiO2 percentage was measured in one bulk sample each of wet clay, the release agent used by green brick hand molders, and top coat soil at the brick kiln. The geometric mean (GM) sample and TWA respirable dust concentrations were 0.20 (95% confidence interval [CI]: 0.16, 0.27) and 0.12 (95% CI: 0.09, 0.16) mg/m3, respectively. GM sample and TWA quartz concentrations were 15.28 (95% CI: 11.11, 21.02) and 8.60 (95% CI: 5.99, 12.34) µg/m3, respectively. Job category was significantly associated with GM sample and TWA respirable dust and quartz concentrations (all p < 0.0001). Top loaders had the highest GM sample and TWA respirable dust concentrations of 1.49 and 0.99 mg/m3, respectively. Top loaders also had the highest GM sample and TWA quartz concentrations of 173.08 and 114.39 µg/m3, respectively. Quartz percentages in bulk samples were 16%-27%. Interventions including using wet methods to reduce dust generation, administrative controls, personal protective equipment, and education and training should be implemented to reduce brick kiln worker exposures to respirable dust and SiO2. [ABSTRACT FROM AUTHOR]

Abstract It is well established that the gut microbiota plays an important role in host health and is perturbed by several factors including antibiotics. Antibiotic‐induced changes in microbial composition can have a negative impact on host health including reduced microbial diversity, changes in functional attributes of the microbiota, formation, and selection of antibiotic‐resistant strains making hosts more susceptible to infection with pathogens such as Clostridioides difficile. Antibiotic resistance is a global crisis and the increased use of antibiotics over time warrants investigation into its effects on microbiota and health. In this review, we discuss the adverse effects of antibiotics on the gut microbiota and thus host health, and suggest alternative approaches to antibiotic use.