Differential Effects of Dietary versus Exercise Intervention on Intrahepatic MAIT Cells and Histological Features of NAFLD

Background: Mucosal-associated invariant T (MAIT) cells promote inflammation in obesity and are implicated in the progression of non-alcoholic fatty liver disease (NAFLD). However, as the intrahepatic MAIT cell response to lifestyle intervention in NAFLD has not been investigated, this work aimed to examine circulating and intrahepatic MAIT cell populations in patients with NAFLD, after either 12 weeks of dietary intervention (DI) or aerobic exercise intervention (EI). Methods: Multicolour flow cytometry was used to immunophenotype circulating and intrahepatic MAIT cells and measure MAIT cell expression (median fluorescence intensity, MFI) of the activation marker CD69 and apoptotic marker CD95. Liver histology, clinical parameters, and MAIT cell populations were assessed at baseline (T0) and following completion (T1) of DI or EI. Results: Forty-five patients completed the study. DI participants showed decreased median (interquartile range) expression of the activation marker CD69 on circulating MAIT cells (T0: 104 (134) versus T1 27 (114) MFI; p = 0.0353) and improvements in histological steatosis grade post-intervention. EI participants showed increased expression of the apoptotic marker CD95, both in circulating (T0: 1549 (888) versus T1: 2563 (1371) MFI; p = 0.0043) and intrahepatic MAIT cells (T0: 2724 (862) versus T1: 3117 (1622) MFI; p = 0.0269). Moreover, the percentage of intrahepatic MAIT cells significantly decreased after EI (T0: 11.1 (14.4) versus T1: 5.3 (9.3)%; p = 0.0029), in conjunction with significant improvements in fibrosis stage and hepatocyte ballooning. Conclusions: These data demonstrate independent benefits from dietary and exercise intervention and suggest a role for intrahepatic MAIT cells in the observed histological improvements in NAFLD.     

SARS CoV-2 (Delta Variant) Infection Kinetics and Immunopathogenesis in Domestic Cats

Continued emergence of SARS-CoV-2 variants highlights the critical need for adaptable and translational animal models for acute COVID-19. Limitations to current animal models for SARS CoV-2 (e.g., transgenic mice, non-human primates, ferrets) include subclinical to mild lower respiratory disease, divergence from clinical COVID-19 disease course, and/or the need for host genetic modifications to permit infection. We therefore established a feline model to study COVID-19 disease progression and utilized this model to evaluate infection kinetics and immunopathology of the rapidly circulating Delta variant (B.1.617.2) of SARS-CoV-2. In this study, specific-pathogen-free domestic cats (n = 24) were inoculated intranasally and/or intratracheally with SARS CoV-2 (B.1.617.2). Infected cats developed severe clinical respiratory disease and pulmonary lesions at 4- and 12-days post-infection (dpi), even at 1/10 the dose of previously studied wild-type SARS-CoV-2. Infectious virus was isolated from nasal secretions of delta-variant infected cats in high amounts at multiple timepoints, and viral antigen was co-localized in ACE2-expressing cells of the lungs (pneumocytes, vascular endothelium, peribronchial glandular epithelium) and strongly associated with severe pulmonary inflammation and vasculitis that were more pronounced than in wild-type SARS-CoV-2 infection. RNA sequencing of infected feline lung tissues identified upregulation of multiple gene pathways associated with cytokine receptor interactions, chemokine signaling, and viral protein–cytokine interactions during acute infection with SARS-CoV-2. Weighted correlation network analysis (WGCNA) of differentially expressed genes identified several distinct clusters of dysregulated hub genes that are significantly correlated with both clinical signs and lesions during acute infection. Collectively, the results of these studies help to delineate the role of domestic cats in disease transmission and response to variant emergence, establish a flexible translational model to develop strategies to prevent the spread of SARS-CoV-2, and identify potential targets for downstream therapeutic development.     

Protective effectiveness of an endotoxin-depleted pertussis vaccine

Pertussis vaccine depleted of endotoxin by the polymyxin-Sepharose affinity chromatography method was tested for toxic activity and protective effectiveness in mice. Preparations containing 1000-fold and 1 000 O00-fold less endotoxin fulfilled the established experimental criteria for freedom from toxicity. A fourfold concentrate of the former demonstrated a protection rate only 10% less than that of standard, untreated pertussis vaccine.     

The Relationship between Habitual Coffee Drinking and the Prevalence of Metabolic Syndrome in Taiwanese Adults: Evidence from the Taiwan Biobank Database

Previous studies revealed inconsistent results between coffee drinking and metabolic syndrome (MetS). The aim of the study was to evaluate the relationship between habitual coffee drinking and the prevalence of MetS among men and women. We conducted a nationwide, cross-sectional study using 23,073 adults obtained from the Taiwan Biobank database (mean ± SD (range) age, 54.57 ± 0.07 (30–79) years; 8341 men and 14,731 (63.8%) women). Adults who drank more than one cup of coffee per day (n = 5118) and those who drank less than one cup per day (n = 4515) were compared with nondrinkers (n = 13,439). Multivariate logistic regression models were used to evaluate the risk of MetS between the two groups. Separate models were also estimated for sex-stratified and habitual coffee-type-stratified (black coffee (BC), coffee with creamer (CC), and coffee with milk (CM)) subgroup analyses. The MetS diagnosis was based on at least three of the five metabolic abnormalities. Coffee drinkers (≥1 cup/day) had a significantly lower prevalence of MetS than nondrinkers (AOR (95% CI): 0.80 (0.73–0.87)). Women who drank any amount of coffee and any type of coffee were more likely to have a significantly lower prevalence of MetS than nondrinkers. Only men who drank more than one cup of coffee per day or black coffee drinkers were more likely to have a lower prevalence of MetS. Our study results indicate that adults with habitual coffee drinking behaviors of more than one cup per day were associated with a lower prevalence of MetS. Moreover, women could benefit from habitual coffee drinking of all three coffee types, whereas men could only benefit from drinking BC.     

Diarrhetic Shellfish Poisoning,Washington, USA, 2011

Diarrhetic shellfish poisoning is a gastrointestinal illness caused by consumption of bivalves contaminated with dinophysistoxins. We report an illness cluster in the United States in which toxins were confirmed in shellfish from a commercial harvest area, leading to product recall. Ongoing surveillance is needed to prevent similar illness outbreaks.