The aim of the study was to investigate longitudinally hepatitis B virus (HBV)-specific T-cell reactivity and viral behavior versus treatment response in tolerant children during combined antiviral therapy. Twenty-three children with infancy-acquired hepatitis B (HBeAg ؉ ) belonging to a published pilot study of 1-year treatment with lamivudine/alpha interferon (IFN-␣) were investigated. Five seroconverted to anti-HBs (responders). Nine were HLA-A2 ؉ (4 responders and 5 nonresponders). Mutations within the HBV core gene were determined at baseline in liver and in serial serum samples by direct sequencing at baseline; during treatment week 2 (TW2), TW9, TW28, and TW52; and after follow-up week 24 (FUW24) and FUW52. HBV-specific reactivity was evaluated by T-cell proliferation with 16 HBV core 20-mer overlapping peptides and by HLA-A2-restricted core 18-27 pentamer staining and CD8؉ IFN-␥ enzyme-linked immunospot (ELISPOT) assay. HBV core-specific T-cell proliferative and CD8 responses were more vigorous and broader among responders than among nonresponders at TW28 and TW52, while the number of mutations within HBV core gene immunodominant epitopes was lower at TW28 and was negatively associated with HBV-specific T-cell proliferative responses at both time points. The HBV DNA viral load was negatively associated with HBV-specific T-cell proliferative and CD8 responses during treatment, especially at TW28. Treatment-induced transition from immunotolerance to HBV immune control is characterized by the emergence of efficient virus-specific immune responses capable of restraining mutations and preventing viral evasion.

In our experience, the creation of permanent hemodialysis access in the elderly with AVF is not only possible but also proved to have a short hospital stay, high patency rates, and an acceptable rate of further intervention.

Using the largest international familial schizophrenia cohort to date, we showed that a substantial portion of the phenotypic correlation between schizophrenia and cognition is caused by shared genetic effects. However, because the phenotypic and genetic correlations are far from unity, the genetics of schizophrenia are clearly not merely the genetics of cognition.

Complications of vascular access are an important cause of morbidity and mortality in hemodialysis patients. 1 It is widely accepted that an arteriovenous fistula (AVF) is the optimal form of vascular access, with better patency and lower infection rates than arteriovenous grafts and central

BackgroundThe initial therapy for a stenosis in an arteriovenous fistula used for haemodialysis is radiological balloon dilatation or angioplasty. The benefit of angioplasty is often short-lived, intervention-free survival is reported to be 40–50 % at 1 year. Previous small studies and observational data suggest that paclitaxel-coated balloons may be of benefit in improving outcomes after fistuloplasty of stenotic arteriovenous fistulae.Methods/designWe have designed a multicentre, double-blind randomised controlled trial to test the superiority of paclitaxel-coated balloons for preventing restenosis after fistuloplasty in patients with a native arteriovenous fistula. Two hundred and eleven patients will be followed up for a minimum of 1 year. Inclusion criteria include a clinical indication for a fistuloplasty, an access circuit that is free of synthetic graft material or stents, and a residual stenosis of 30 % or less after plain balloon fistuloplasty. Exclusion criteria include a synchronous venous lesion in the same access circuit, location of the stenosis central to the thoracic inlet or a thrombosed access circuit at the time of treatment. The primary endpoint is time to end of target lesion primary patency. This is defined as a clinically-driven radiological or surgical re-intervention at the treatment segment, thrombosis that includes the treatment segment, or abandonment of the access circuit due to an inability to re-treat the treatment segment. Secondary endpoints include angiographic late lumen loss, time to end of access circuit cumulative patency, the total number of interventions, and quality of life. The trial is funded by the National Institute for Health Research.DiscussionWe anticipate that this trial will provide rigorous data that will determine the efficacy of additional paclitaxel-coated balloon fistuloplasty versus plain balloon fistuloplasty only to preserve the patency of arteriovenous fistulae used for haemodialysis.Trial registrationISRCTN14284759. Registered on 28 October 2015.

Cerebrospinal fluid (CSF) has often been used as the source of choice for biomarker discovery with the goal to support the diagnosis of neurodegenerative diseases. For this study, we selected 15 CSF protein markers which were identified in previously published clinical investigations and proposed as potential biomarkers for PD diagnosis. We aimed at investigating and confirming their suitability for early stage diagnosis of the disease. The current study was performed in a two-fold confirmatory approach. Firstly, the CSF protein markers were analysed in confirmatory cohort I comprising 80 controls and 80 early clinical PD patients. Through univariate analysis we found significant changes of six potential biomarkers (α-syn, DJ-1, Aβ42, S100β, p-Tau and t-Tau). In order to increase robustness of the observations for potential patient differentiation, we developed–based on a machine learning approach—an algorithm which enabled identifying a panel of markers which would improve clinical diagnosis. Based on that model, a panel comprised of α-syn, S100β and UCHL1 were suggested as promising candidates. Secondly, we aimed at replicating our observations in an independent cohort (confirmatory cohort II) comprising 30 controls and 30 PD patients. The univariate analysis demonstrated Aβ42 as the only reproducible potential biomarker. Taking into account both technical and clinical aspects, these observations suggest that the large majority of the investigated CSF proteins currently proposed as potential biomarkers lack robustness and reproducibility in supporting diagnosis in the early clinical stages of PD.

The importance of the innate immune system, including complement, in causing transplant injury and augmenting adaptive immune responses is increasingly recognized. Therefore variability in graft outcome may in part be due to genetic polymorphism in genes encoding proteins of the immune system. This study assessed the relationship between single nucleotide polymorphisms (SNPs) in complement genes and outcome after transplantation. Analysis was performed on two patient cohorts of 650 and 520 transplant recipients. 505 tagged SNPs in 47 genes were typed in both donor and recipient. The relationships between SNPs and graft survival, serum creatinine, delayed graft function and acute rejection were analyzed. One recipient SNP in the gene encoding mannose binding lectin was associated with graft outcome after correction for analysis of multiple SNPs (p=6.41 × 10(-5)). When further correction was applied to account for analysis of the effect of SNPs in both donor and recipient this lost significance. Despite association p values of <0.001 no SNP was significantly associated with clinical phenotypes after Bonferroni correction. In conclusion, the variability seen in transplant outcome in this patient cohort cannot be explained by variation in complement genes. If causal genetic effects exist in these genes, they are too small to be detected by this study.

Background: Several studies indicate that changes in cerebrospinal fluid (CSF) composition depend on the disease stage and reflect modification of brain energy metabolism (BEM). Also, it has been reported that a decline in cognitive functions may be mitigated by incorporating nutraceuticals in the diet. Objective: Assuming the beneficial effect of nutraceuticals on BEM and oxidative damage, the aim of this study was to determine if the administration of a nutraceutical compound results in changes of select CSF biomarkers in healthy adult Beagle dogs. Methods: Two separate CSF and blood samples were obtained from 11 healthy adult Beagle dogs, before and after 50 days of treatment with a veterinary combined nutraceutical. CSF analysis included a total nucleated cell count, total protein, glucose, sodium, chloride, potassium, pyruvate, and lactate concentrations, and calculation of lactate/pyruvate ratio. CBC and serum biochemistry were also performed. The Wilcoxon test was used to analyze the significance of the changes after nutraceutical treatment. Results: All studied variables remained within reference intervals, before and after treatment. A significant increase in CSF sodium and glucose concentration, and a decrease in lactate levels, was observed after treatment (P < .05), and the lactate/pyruvate ratio was decreased after treatment (P = .05). In serum, sodium and chloride concentrations were significantly increased (P < .05), and creatinine concentration was significantly decreased (P < .05) after treatment. Conclusions: After 50 days of treatment with a nutraceutical compound, CSF glucose, sodium, and lactate concentrations, and L/P ratio were significantly different, suggesting an influence of nutraceuticals' administration on CSF composition.