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  We highlight the rationale for pharmacological targeting of the perivascular and epicardial adipose tissue or associated signaling pathways as potential disease modifying approaches in cardiometabolic syndromes. © 2020 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.CONTEXT Plasma branched chain amino acid (BCAA) concentrations correlate positively with body mass index (BMI), measures of insulin resistance (IR) and severity of non-alcoholic fatty liver disease (NAFLD). Moreover, plasma BCAA concentrations also differ between the sexes, which display different susceptibilities to cardio-metabolic diseases. OBJECTIVE Assess whether plasma BCAA concentrations associate with NAFLD severity independently of BMI, IR and sex. PATIENTS Patients visiting the obesity clinic of the Antwerp University Hospital were consecutively recruited from 2006 to 2014. DESIGN AND SETTING A cross-sectional study cohort of 112 obese patients (59 women and 53 men) was divided into four groups according to NAFLD severity. Groups were matched for sex, age, BMI, HOMA-IR and HbA1c. MAIN OUTCOME MEASURES Fasting plasma BCAA concentrations were measured by tandem mass spectrometry using the aTRAQ™ method. RESULTS In the study cohort, a modest positive correlation was observed between plasma BCAA concentrations and NAFLD severity, as well as a strong effect of sex on plasma BCAA levels. Subgroup analysis by sex revealed that while plasma BCAA concentrations increased with severity of NAFLD in women, they tended to decrease in men. Additionally, only women displayed significantly increased plasma BCAAs with increasing fibrosis. CONCLUSION Plasma BCAA concentrations display sex-dimorphic changes with increasing severity of NAFLD, independently of BMI, IR and age.  https://www.selleckchem.com/JAK.html  Additionally, plasma BCAA are associated with significant fibrosis in women, but not in men.  https://www.selleckchem.com/JAK.html  These results highlight the importance of a careful consideration of sex as a major confounding factor in cross-sectional studies of NAFLD. © Endocrine Society 2020. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.Enterovirus A71 (EV-A71) has been noted for its tendency to lead to neurological manifestations in young children and infants. Although the alimentary tract has been identified as the primary replication site of this virus, how EV-A71 replicates in the gut and is transmitted to other organs remains unclear. By using differentiated C2BBe1 cells as a model, we observed that intestinal epithelial cells (IECs) were permissive to EV-A71 infection and viral particles were released in a nonlytic manner. The coexistence of active caspase 3 and EV-A71 protein was observed in the infected undifferentiated C2BBe1 and RD cells but not in the infected and differentiated C2BBe1 cells. Furthermore, EV-A71 infection caused differentiated C2BBe1 and intestinal organoids to secrete exosomes containing viral components and have the ability to establish active infection. Inhibition of the exosome pathway decreased EV-A71 replication and release in vitro and increased the survival rates of infected animals. Our findings showed that EV-A71 is able to be actively replicated in enterocytes, and that the exosome pathway is involved in the nonlytic release of viral particles, which may be useful for developing antiviral strategies. © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.CONTEXT An obesogenic perinatal environment contributes to adverse offspring metabolic health. Previous studies have been limited by lack of direct adiposity measurements and failure to account for potential confounders. OBJECTIVE Examine the joint associations of maternal mid-pregnancy BMI and glycemia with direct adiposity measures in 10-14 year old offspring. DESIGN AND SETTING International, epidemiological study Hyperglycemia and Adverse Pregnancy Outcome (HAPO) and HAPO Follow-up Study, conducted 2000-2006 and 2013-2016, respectively. PARTICIPANTS AND MAIN OUTCOME MEASURES In 4,832 children, adiposity measures BMI, body fat with air displacement plethysmography, skinfold thickness, and waist circumference were obtained at mean age 11.4 years. RESULTS Maternal BMI and glucose, as continuous and categorical variables, were the primary predictors. In fully adjusted models controlling for child age, sex, field center, and maternal characteristics, maternal BMI had significant, positive associations with allights reserved. For permissions, please e-mail journals.permissions@oup.com.CONTEXT The clinical and radiological aspects of normocalcaemic hyperparathyroidism (NHPT) are confounded by differing methods used to rule out secondary hyperparathyroidism and by the small sample size. OBJECTIVE To assess the clinical, biochemical and radiological profile of NHPT compared to primary hyperparathyroidism (PHPT) and control subjects. DESIGN Multicentric cross-sectional study. SETTING outpatient clinic. PATIENTS 47NHPT,41 PHPT and 39age and sex-matched control subjects. MAIN OUTCOME MEASURES calcium metabolism and bone turnover markers (BTM). Lumbar spine, total hip, femoral neck, one-third distal radius bone mineral density (BMD). Morphometric vertebral fracture (VF) assessed by DXA. RESULTS NHPT patients had significantly higher PTH, 25(OH)-Vitamin D levels and lower Ca*P than controls (p less then 0.001). Compared to PHPT, NHPT group had significantly higher 25(OH) Vitamin D levels (P=0.016). NHPT had BTM levels similar to controls and PHPT. NHPT, PHPT and controls have similar lumbar spine and femoral neck BMD. NHPT and controls had a similar radial BMD, while PHPT patients had a lower radial BMD compared to both NHPT (P=0.031) and controls (P less then 0.05). Using the control group as the reference, after adjustment for interacting factor, there was no increase in risk of moderate-severe VF in NHPT(OR 1.04,95% CI 0.25-4.55), while PHPT subjects had an increased risk (OR 3.81,95% CI 1.15-15.12). 79% of NHPT and 59% of PHPT patients fulfilled the criteria for asymptomatic hyperparathyroidism. CONCLUSIONS The biochemical phenotype of NHPT is intermediate between PHPT and controls. In contrast, the bone phenotype resembles controls with normal bone turnover, no significant BMD impairment and no increased risk of VF. © Endocrine Society 2020. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.