OBJECTIVE To examine 36-month effects of bilateral subthalamic nucleus deep brain stimulation (STN-DBS) on non-motor symptoms (NMS) compared with standard-of-care medical treatment (MED) in Parkinson's disease (PD). METHODS Here we report the 36-month follow-up of a prospective, observational, controlled, international multicentre study of the NILS cohort. Assessments included NMSScale (NMSS), PDQuestionnaire-8 (PDQ-8), Scales for Outcomes in PD (SCOPA)-motor examination, -activities of daily living, and -complications, and levodopa equivalent daily dose (LEDD). Propensity score matching resulted in a pseudo-randomised sub-cohort balancing baseline demographic and clinical characteristics between the STN-DBS and MED groups. Within-group longitudinal outcome changes were analysed using Wilcoxon signed-rank and between-group differences of change scores with Mann-Whitney U test. Strength of clinical responses was quantified with Cohen's effect size. In addition, bivariate correlations of change scores were explby BMJ.OBJECTIVE To determine the prevalence of antibodies to Epstein-Barr virus (EBV) in a large cohort of patients with early multiple sclerosis (MS). METHODS Serum samples were collected from 901 patients with a clinically isolated syndrome (CIS) or early relapsing-remitting multiple sclerosis (RRMS) participating in the German National MS cohort, a prospective cohort of patients with early MS with stringent inclusion criteria. Epstein-Barr nuclear antigen (EBNA)-1 and viral capsid antigen (VCA) antibodies were measured in diluted sera by chemiluminescence immunoassays (CLIAs). Sera of EBNA-1 and VCA antibody-negative patients were retested undiluted by an EBV IgG immunoblot. For comparison, we retrospectively analysed the EBV seroprevalence across different age cohorts, ranging from 0 to >80 years, in a large hospital population (N=16 163) from Berlin/Northern Germany. RESULTS EBNA-1 antibodies were detected by CLIA in 839 of 901 patients with CIS/RRMS. Of the 62 patients without EBNA-1 antibodies, 45 had antibodies to VCA as detected by CLIA. In all of the remaining 17 patients, antibodies to EBV were detected by immunoblot. Altogether, 901 of 901 (100%) patients with CIS/RRMS were EBV-seropositive. EBV seropositivity increased with age in the hospital population but did not reach 100% in any of the investigated age cohorts. CONCLUSION The complete EBV seropositivity in this large cohort of patients with early MS strengthens the evidence for a role of EBV in MS. It also suggests that a negative EBV serology in patients with suspected inflammatory central nervous system disease should alert clinicians to consider diagnoses other than MS. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.INTRODUCTION To assess vascular function and characterize insulin secretion using a physiological approach in Japanese women with family history of type 2 diabetes (FHD). RESEARCH DESIGN AND METHODS Standardized mixed-meal tests were performed with multiple postprandial glucose, insulin and free fatty acids (FFA) measurements over a 30-120 min period in 31 Japanese women aged 21-24 years. Arterial distensibility was assessed as well. RESULTS Fasting glucose, triglyceride and insulin averaged less then 90 mg/dL, less then 60 mg/dL and less then 5 μU/mL, respectively, and did not differ cross-sectionally between 10 with (FHD+) and 21 without FHD (FHD-). FHD+ showed higher insulin responses not only during the first 30 min (p=0.005) but also during the second hour (60-120 min, p less then 0,05) in spite of identical postprandial suppression of FFA and identical fasting and postprandial glucose and FFA concentrations, except for higher 60 min FFA in FHD+. Further, FHD+ had decreased arterial distensibility (p=0.003). On multivariate regression analysis, arterial distensibility emerged as the only significant independent predictor of FHD+. Endurance training in FHD+ did not alter decreased arterial distensibility whereas it abolished postprandial hyperinsulinemia. CONCLUSIONS FHD was associated with decreased arterial distensibility and postprandial hyperinsulinemia despite nearly identical postprandial glycemia and postprandial FFA suppression, suggesting that impaired vascular insulin sensitivity may precede glucose and lipid dysmetabolism in normal weight Japanese women aged 22 years. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. https://www.selleckchem.com/products/myk-461.html See rights and permissions. Published by BMJ.OBJECTIVES The aim of this study was to identify the parameters that predict the risk of future foot ulcer occurrence in patients with diabetes. RESEARCH DESIGN AND METHODS 1810 (male (M)/female (F) 1012/798) patients, with no foot ulcer at baseline, participated in this study. Data from a set of 28 parameters were collected at baseline. During follow-up, 123 (M/F 68/55) patients ulcerated. Survival analyses together with logistic regression were used to identify the parameters that could predict the risk of future diabetic foot ulcer occurrence. RESULTS A number of parameters (HR (95% CI)) including neuropathy (2.525 (1.680 to 3.795)); history of ulceration (2.796 (1.029 to 7.598)); smoking history (1.686 (1.097 to 2.592)); presence of callus (1.474 (0.999 to 2.174)); nail ingrowth (5.653 (2.078 to 15.379)); foot swelling (3.345 (1.799 to 6.218)); dry skin (1.926 (1.273 to 2.914)); limited ankle (1.662 (1.365 to 2.022)) and metatarsophalangeal (MTP) joint (2.745 (1.853 to 4.067)) ranges of motion; and decrea1.14)); and temperature tolerance threshold to warm stimuli (1.001 (1.000 to 1.002)) were significant predictors of foot ulceration risk in the final model. The mean time to ulceration was significantly (p less then 0.05) shorter for patients with dry skin (χ2=11.015), nail ingrowth (χ2=14.688), neuropathy (χ2=21.284), or foot swelling (χ2=16.428). CONCLUSION Nail ingrowth and dry skin were found to be strong indicators of vulnerability of patients to diabetic foot ulceration. Results highlight that assessments of neuropathy in relation to both small and larger fiber impairment need to be considered for predicting the risk of diabetic foot ulceration. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.