Sonic Hedgehog (Shh) signalling cascade is one of the intricate signal transduction mechanisms that govern the precisely regulated developmental processes of multicellular organisms. Along with establishing the patterns of cellular differentiation to direct complex organ formation, it also has an important role in post-embryonic tissue regeneration and repair processes. Especially, Shh signalling is implicated in the induction of multifarious neuronal populations in central nervous system. There is compelling evidence of the involvement of Shh protein in the signalling network that regulates various morphogenetic processes such as the exquisite neural tube pattern formation. In the morphogenetic field, the activation of Shh signalling processes is intricately linked to the alterations at the molecular level in the structure of Shh protein that leads to its altered biophysical and biochemical reactivity. This brief article gives an overview of such complex cascade of events in Shh signalling and its transduction pathways.

The development of eating disorders including anorexia nervosa, bulimia nervosa, binge eating disorder, and atypical eating disorders that affect many young women and even men in the productive period of their lives is complex and varied. While numbers of presumed risk factors contributing to the development of eating disorders are increasing, previous evidence for biological, psychological, developmental, and sociocultural effects on the development of eating disorders have not been conclusive. Despite the fact that a huge body of research has carefully examined the possible risk factors associated with the eating disorders, they have failed not only to uncover the exact etiology of eating disorders, but also to understand the interaction between different causes of eating disorders. This failure may be due complexities of eating disorders, limitations of the studies or combination of two factors. In this review, some risk factors including biological, psychological, developmental, and sociocultural are discussed.

The pattern of neurodegeneration in Huntington’s disease (HD) is very characteristic of regional locations as well as that of neuronal types in striatum. The different striatal neuronal populations demonstrate different degree of degeneration in response to various pathological events in HD. In the striatum, medium spiny GABA neurons (MSN) are preferentially degenerate while others are relatively spared. Vulnerability of specific neuronal populations within the striatum to pathological events constitutes an important hallmark of degeneration in HD. In an attempt to explain a likely mechanism of degeneration of striatal neuronal populations in HD, possible causes underlying differential vulnerability of neuronal subtypes to excitoxic insults and neurotrophic factors are discussed in this paper.

Objective: Attention-deficit/hyperactivity disorder (ADHD) is an etiologically complex heterogeneous behavioral disorder. Several studies have reported that ADHD subjects are more likely to be overweight/ obese and that this comorbidity may be due to shared genetic factors. The objective of this study is to explore the association between ADHD and FTO, a gene strongly associated with obesity in genomewide studies. Design and Methods: One tag SNP (single-nucleotide polymorphism, rs8050136, risk allele A) in the FTO gene was selected and its association with ADHD was tested. Family-based association tests (FBATs) were conducted with the categorical diagnosis of ADHD as well as behavioral and cognitive phenotypes related to ADHD. Furthermore, stratified FBAT analyses based on maternal smoking during pregnancy (MSDP) status were conducted. Results: Statistically significant associations were observed between rs8050136 and several of the traits tested in the total sample. These associations were stronger when the analysis was restricted to children who were not exposed to MSDP. Conclusions: These exploratory results suggest the involvement of the FTO SNP rs8050136 in modulating the risk for ADHD, particularly in those children who were not exposed to MSDP. If confirmed, they may explain, at least in part, the complex links between obesity and ADHD.

Background Alemtuzumab efficacy versus subcutaneous interferon-β-1a (SC IFNB-1a) was demonstrated over 2 years in patients with relapsing-remitting multiple sclerosis, with continued efficacy over 7 additional years. Alemtuzumab is included as a recommended treatment for patients with highly active disease (HAD) by the American Academy of Neurology Practice Guidelines, and the label indication in Europe was recently restricted to the treatment of HAD patients. There is currently no consensus definition for HAD, and alemtuzumab efficacy across various HAD definitions has not been explored previously. Objectives In this post hoc analysis, we assess the efficacy and safety of alemtuzumab in Comparison of Alemtuzumab and Rebif ® Efficacy in Multiple Sclerosis (CARE-MS) trial patients who met criteria for at least one of four separate definitions of HAD (one primary and three alternatives). Over 2 years, alemtuzumab-treated HAD patients were compared with SC IFNB-1a-treated HAD patients, with additional 7-year follow-up in patients from the alemtuzumab arm. Methods Patients in the CARE-MS studies received either alemtuzumab (baseline: 5 days; 12 months later: 3 days) or SC IFNB-1a (3 times weekly). Alemtuzumab-treated patients who enrolled in the extensions could receive additional courses ≥ 12 months apart. Four definitions of HAD were applied to assess alemtuzumab efficacy: the pre-specified primary definition (two or more relapses in the year prior to baseline and at least one gadolinium [Gd]-enhancing lesion at baseline) and three alternative definitions that focused on relapse, magnetic resonance imaging (MRI), or prior treatment response criteria. Efficacy outcomes were annualized relapse rate, change in Expanded Disability Status Scale score, 6-month confirmed disability worsening, 6-month confirmed disability improvement, MRI disease activity, and brain volume change. Adverse events were summarized for HAD patients meeting the primary definition. Results In the pooled CARE-MS population, 208 alemtuzumab-treated patients met the primary HAD definition. Annualized relapse rate was 0.27 in years 0-2 and 0.16 in years 3-9. Over 9 years, 62% of patients were free of 6-month confirmed disability worsening, 50% had 6-month confirmed disability improvement, and median cumulative change in brain volume was − 2.15%. During year 9, 62% had no evidence of disease activity, and 69% were free of MRI disease activity. Similar efficacy outcomes were observed using an alternative relapse-driven HAD definition. For patients meeting alternative HAD definitions focused on either higher MRI lesion counts or disease activity while on prior therapy, reduced efficacy for some endpoints was seen. Safety was consistent with the overall CARE-MS population through year 9. Conclusions Over 9 years, alemtuzumab efficacy was maintained in CARE-MS HAD patients based on four HAD definitions. These results support intervention with alemtuzumab in patients with early indicators of HAD, including frequent relapse without high MRI activity. No sa...

These results provide evidence for the interaction between a genetic and environmental factor independently shown to be associated with ADHD. If confirmed in independent large studies, they may present a step forward in unraveling the complex etiology of ADHD.

ObjectiveAttention-Deficit/Hyperactivity Disorder (ADHD) is a complex and heterogeneous childhood disorder that often coexists with other psychiatric and somatic disorders. Recently, a link between ADHD and body weight dysregulation has been reported and often interpreted as impaired self-regulation that is shared between the two conditions. The objective of this study is to investigate the relation between body weight/BMI and cognitive, emotional and motor characteristics in children with ADHD.Methods284 ADHD children were stratified by weight status/BMI according to WHO classification and compared with regard to their neurocognitive characteristics, motivational style, and motor profile as assessed by a comprehensive battery of tests. All comparisons were adjusted for demographic characteristics of relevance including, socioeconomic status (SES).ResultsBoth Obese and overweight ADHD children exhibited significantly lower SES compared to normal weight ADHD children. No significant differences were observed between the three groups with regards to their neurocognitive, emotional and motor profile.ConclusionsOur findings provide evidence that differences in weight/BMI are not accounted for by cognitive, motivational and motor profiles. Socio-economic characteristics are strongly associated with overweight and obesity in ADHD children and may inform strategies aimed at promoting healthier weight.

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