In-vitro model systems to study Hepatitis C Virus

Hepatitis C virus (HCV) is a major cause of chronic liver diseases including steatosis, cirrhosis and hepatocellular carcinoma. Currently, there is no vaccine available for prevention of HCV infection due to high degree of strain variation. The current treatment of care, Pegylated interferon α in combination with ribavirin is costly, has significant side effects and fails to cure about half of all infections. The development of in-vitro models such as HCV infection system, HCV sub-genomic replicon, HCV producing pseudoparticles (HCVpp) and infectious HCV virion provide an important tool to develop new antiviral drugs of different targets against HCV. These models also play an important role to study virus lifecycle such as virus entry, endocytosis, replication, release and HCV induced pathogenesis. This review summarizes the most important in-vitro models currently used to study future HCV research as well as drug design

Proof of concept, randomized, placebo-controlled study of the effect of simvastatin on the course of age-related macular degeneration

BACKGROUND: HMG Co-A reductase inhibitors are ubiquitous in our community yet their potential role in age-related macular degeneration (AMD) remains to be determined. METHODOLOGY/PRINCIPAL FINDINGS: OBJECTIVES: To evaluate the effect of simvastatin on AMD progression and the effect modification by polymorphism in apolipoprotein E (ApoE) and complement factor H (CFH) genes. DESIGN: A proof of concept double-masked randomized controlled study. PARTICIPANTS: 114 participants aged 53 to 91 years, with either bilateral intermediate AMD or unilateral non-advanced AMD (with advanced AMD in fellow eye), BCVA ≥ 20/60 in at least one eye, and a normal lipid profile. INTERVENTION: Simvastatin 40 mg/day or placebo, allocated 1:1. MAIN OUTCOME MEASURES: Progression of AMD either to advanced AMD or in severity of non-advanced AMD. Results. The cumulative AMD progression rates were 70% in the placebo and 54% in the simvastatin group. Intent to treat multivariable logistic regression analysis, adjusted for age, sex, smoking and baseline AMD severity, showed a significant 2-fold decrease in the risk of progression in the simvastatin group: OR 0.43 (0.18-0.99), p = 0.047. Post-hoc analysis stratified by baseline AMD severity showed no benefit from treatment in those who had advanced AMD in the fellow eye before enrolment: OR 0.97 (0.27-3.52), p = 0.96, after adjusting for age, sex and smoking. However, there was a significant reduction in the risk of progression in the bilateral intermediate AMD group compared to placebo [adjusted OR 0.23 (0.07-0.75), p = 0.015]. The most prominent effect was observed amongst those who had the CC (Y402H) at risk genotype of the CFH gene [OR 0.08 (0.02-0.45), p = 0.004]. No evidence of harm from simvastatin intervention was detected. CONCLUSION/SIGNIFICANCE: Simvastatin may slow progression of non-advanced AMD, especially for those with the at risk CFH genotype CC (Y402H). Further exploration of the potential use of statins for AMD, with emphasis on genetic subgroups, is warranted. TRIAL REGISTRATION: Australian New Zealand Clinical Trial Registry (ANZCTR) ACTRN1260500032065

The Effectiveness of Mindfulness Training for Children with ADHD and Mindful Parenting for their Parents

This study evaluated the effectiveness of an 8-week mindfulness training for children aged 8–12 with ADHD and parallel mindful parenting training for their parents. Parents (N = 22) completed questionnaires on their child’s ADHD and ODD symptoms, their own ADHD symptoms, parenting stress, parental overreactivity, permissiveness and mindful awareness before, immediately after the 8-week training and at 8-week follow-up. Teachers reported on ADHD and ODD behavior of the child. A within-group waitlist was used to control for the effects of time and repeated measurement. Training was delivered in group format. There were no significant changes between wait-list and pre-test, except on the increase of teacher-rated ODD behavior. There was a significant reduction of parent-rated ADHD behavior of themselves and their child from pre-to posttest and from pre- to follow-up test. Further, there was a significant increase of mindful awareness from pre-to posttest and a significant reduction of parental stress and overreactivity from pre-to follow-up test. Teacher-ratings showed non-significant effects. Our study shows preliminary evidence for the effectiveness of mindfulness for children with ADHD and their parents, as rated by parents. However, in the absence of substantial effects on teacher-ratings, we cannot ascertain effects are due to specific treatment procedures

The genetic and environmental aetiology of spatial, mathematics and general anxiety

Individuals differ in their level of general anxiety as well as in their level of anxiety towards specific activities, such as mathematics and spatial tasks. Both specific anxieties correlate moderately with general anxiety, but the aetiology of their association remains unexplored. Moreover, the factor structure of spatial anxiety is to date unknown. The present study investigated the factor structure of spatial anxiety, its aetiology, and the origins of its association with general and mathematics anxiety in a sample of 1,464 19-21-year-old twin pairs from the UK representative Twins Early Development Study. Participants reported their general, mathematics and spatial anxiety as part of an online battery of tests. We found that spatial anxiety is a multifactorial construct, including two components: navigation anxiety and rotation/visualization anxiety. All anxiety measures were moderately heritable (30% to 41%), and non-shared environmental factors explained the remaining variance. Multivariate genetic analysis showed that, although some genetic and environmental factors contributed to all anxiety measures, a substantial portion of genetic and non-shared environmental influences were specific to each anxiety construct. This suggests that anxiety is a multifactorial construct phenotypically and aetiologically, highlighting the importance of studying anxiety within specific contexts

Perception of Parenting Style by Children with ADHD and Its Relation with Inattention, Hyperactivity/Impulsivity and Externalizing Symptoms

Children’s perception of their parents’ behavior is very important for their adjustment. Raising a child with Attention-Deficit/Hyperactivity Disorder (ADHD) can be particularly challenging. However, little is known about how children with ADHD perceive their parents’ childrearing style. The main purpose of this paper is to study how children with ADHD perceive acceptance and control in parent–child relationships and this perception’s relationship with inattention, hyperactivity/impulsivity, and externalizing behaviors. Participants were children between 7 and 13 years old with ADHD who were attending psychotherapy (ADHD), children without ADHD who were attending psychotherapy (APG), and children with unknown ADHD status who were not attending psychotherapy (NPG). Furthermore, one parent of each child participated in the study. An analysis of variance (ANOVA) showed that children with ADHD perceived higher levels of pathological control in their relationships with their mothers than did APG and NPG children. NPG children perceived higher extreme autonomy than ADHD and APG children. Linear regression analyses revealed that the perception of pathological parental control and extreme autonomy predicted externalizing symptoms in children with ADHD. The perception of maternal acceptance and pathological control predicted inattention in APG children. Also, perceived maternal pathological control and perceived paternal acceptance predicted externalizing symptoms in APG children. Thus, these results show the importance of taking into account children’s perception of their relationships with their parents in addition to parental reports of their own behavior.Fil: Molina, María Fernanda. Universidad de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Musich, Francisco Martín. Provincia de Buenos Aires. Ministerio de Salud. Hospital Interzonal de Agudos "Eva Perón"; Argentina. Universidad Favaloro; Argentin