The association between HBV infection and incident thrombocytopenia among subjects without cirrhosis or splenomegaly is unknown. Therefore, we sought to elucidate the association between HBV infection and the development of thrombocytopenia in a large cohort of apparently healthy men and women. A cohort study was performed in 122 200 participants without liver cirrhosis or splenomegaly who underwent comprehensive health examinations and were followed until December 2014. HBV infection was defined by the presence of hepatitis B surface antigen (HBsAg) at baseline. Thrombocytopenia was defined as a platelet count <150 000/μL. Cox proportional hazard models were used to estimate adjusted hazard ratios with 95% confidence intervals (CIs) for incident thrombocytopenia. HBsAg was positive in 4857 of 122 200 subjects (4.0%) at baseline. During 883 983 person-years of follow-up, 2037 incident cases of thrombocytopenia were identified (incident rate 2.3 per 1000 person-years). HBsAg-positive subjects had a higher incidence of thrombocytopenia than did healthy controls (11.2 vs 1.9 per 1000 person-years, respectively). The multivariate-adjusted hazard ratio (95% CI) for incident thrombocytopenia comparing HBsAg-positive to HBsAg-negative subjects was 5.71 (5.10-6.38). Strong associations between HBsAg positivity and thrombocytopenia were consistently observed across prespecified subgroups. In this large cohort study of an apparently healthy population, HBsAg positivity was strongly and independently associated with incident thrombocytopenia, indicating that mechanisms of thrombocytopenia other than portal hypertension may exist in healthy HBV carriers.

No cohort studies have evaluated the effect of obesity on the risk of cellulitis according to metabolic health status. We investigated an association of BMI and metabolic health status with the development of cellulitis. We conducted a cohort study of 171,322 Korean adults who underwent a health checkup examination and were followed from 2011 to 2016 for cellulitis and hospital admission related to cellulitis, which were ascertained through the linkage to the Health Insurance and Review Agency database. Being metabolically healthy was defined as not having any metabolic syndrome component and having a homeostasis model assessment of insulin resistance <2.5. During 638,240.4 person-years of follow-up, 14,672 cases of incident cellulitis were identified with 225 cases of cellulitis-related admission. After adjustment for possible confounders, the multivariable-adjusted hazard ratios (95% CI) for incident cellulitis comparing BMIs 23–24.9, 25–29.9, and ≥30 with a BMI of 18.5–22.9 kg/m2 as the reference were 1.07 (1.02–1.11), 1.09 (1.04-1.13), and 1.19 (1.08-1.31), respectively, whereas the corresponding multivariable-adjusted hazard ratios (95% CI) for cellulitis-related admission were 1.55 (1.05–2.3), 2.47 (1.73–3.53), and 4.8 (2.86–8.05), respectively. These associations were consistently observed in both metabolically healthy and unhealthy individuals with no significant interaction. In a large cohort of apparently healthy adults, increased BMI was associated with an increased risk of cellulitis and hospitalization for cellulitis in both metabolically healthy and unhealthy individuals. Obesity appears to be an independent risk factor for cellulitis regardless of metabolic phenotype.

Research on misfolding of tau proteins will help to better understand the formation process of neurofibrillary tangles, a hallmark of Alzheimer’s disease. Mutation and histidine tautomeric effects have been considered the two most important inherent factors for tau protein misfolding. In current research, replica-exchange molecular dynamics (REMD) were performed to characterize the structural properties of the key fragment R3 of tau protein under the collective effects of P332L mutation and histidine tautomerism. Simulation results suggest that though the content β-sheet of P332L R3 εδ isomer is slightly lower than that of the WT P332L R3 fragment, the total stable secondary structures including β-sheet and helix of P332L R3 isomers are generally more prevalent than those of wild type R3, which may be the reason that P332L R3 has a higher aggregation tendency. Further analysis showed that the hydrogen bond networks are affected by the mutation and histidine tautomerism. Furthermore, the interactions between N-terminus and C-terminus play a crucial role in β-hairpin formation in all isomers. The current study will contribute to revealing the collective effects of P332L and histidine tautomerism on the misfolding of tau proteins.