Novel genetic variant in FTO influences insulin levels and insulin resistance in severely obese children and adolescents

Background: The global prevalence of obesity and overweight is increasing rapidly among adults as well as among children and adolescents. Recent genome-wide association studies have provided strong support for association between variants in the FTO gene and obesity. We sequenced regions of the FTO gene to identify novel variants that are associated with obesity and related metabolic traits. Results: We screened exons 3 and 4 including exon-intron boundaries in FTO in 48 obese children and adolescents and identified three novel single nucleotide polymorphism in the fourth intronic region, (c.896 + 37A > G, c.896 + 117C > G and c.896 + 223A > G). We further genotyped c.896 + 223A > G in 962 subjects, 450 well-characterized obese children andadolescents and 512 adolescents with normal weight. Evidence for differences in genotype frequencies were not detected for the c.896 + 223A > G variant between extremely obese children and adolescents and normal weight adolescents (P = 0.406, OR = 1.154 (0.768-1.736)). Obese subjects with the GG genotype, however, had 30% increased fasting serum insulin levels (P = 0.017) and increased degree of insulin resistance (P = 0.025). There were in addition no differences in body mass index (BMI) or BMI standard deviation score (SDS) levels among the obese subjects according to genotype and the associations with insulin levels and insulin resistance remained significant when adjusting for BMI SDS. Conclusion: These findings suggest that this novel variant in FTO is affecting metabolic phenotypes such as insulin resistance, which are not mediated through differences in BMI levels

Management of radiation oncology patients with a pacemaker or ICD: A new comprehensive practical guideline in The Netherlands

<p>Abstract</p> <p>Current clinical guidelines for the management of radiotherapy patients having either a pacemaker or implantable cardioverter defibrillator (both CIEDs: Cardiac Implantable Electronic Devices) do not cover modern radiotherapy techniques and do not take the patient’s perspective into account. Available data on the frequency and cause of CIED failure during radiation therapy are limited and do not converge. The Dutch Society of Radiotherapy and Oncology (NVRO) initiated a multidisciplinary task group consisting of clinical physicists, cardiologists, radiation oncologists, pacemaker and ICD technologists to develop evidence based consensus guidelines for the management of CIED patients. CIED patients receiving radiotherapy should be categorised based on the chance of device failure and the clinical consequences in case of failure. Although there is no clear cut-off point nor a clear linear relationship, in general, chances of device failure increase with increasing doses. Clinical consequences of device failures like loss of pacing, carry the most risks in pacing dependent patients. Cumulative dose and pacing dependency have been combined to categorise patients into low, medium and high risk groups. Patients receiving a dose of less than 2 Gy to their CIED are categorised as low risk, unless pacing dependent since then they are medium risk. Between 2 and 10 Gy, all patients are categorised as medium risk, while above 10 Gy every patient is categorised as high risk. Measures to secure patient safety are described for each category. This guideline for the management of CIED patients receiving radiotherapy takes into account modern radiotherapy techniques, CIED technology, the patients’ perspective and the practical aspects necessary for the safe management of these patients. The guideline is implemented in The Netherlands in 2012 and is expected to find clinical acceptance outside The Netherlands as well.</p

Robot Programming to Empower Higher Cognitive Functions in Early Childhood

This chapter describes a new approach of educational robotics (ER) aimed at empowering higher cognitive functions in school. As robot programming requires mentally planning complex action sequences before the motor act, ER may promote several crucial cognitive processes underlying learning. During robot programming, the child has to first set the target, second sequentially think through the steps needed to achieve that target, then verify the goal, and eventually reset the plan. All these mental acts involve executive functions (EFs), which are complex higher cognitive processes, crucial in early development because they are the base for abstraction and logical reasoning, decision-making, sequential thinking, and maintaining and updating information in memory and problem-solving. Robot programming may empower EFs not only by improving top-down cognitive control, working memory, and inhibition skills but also by placing the child, more than other passive thought technologies, in front of “objects to think with” in a group setting that stimulates the use of EFs for social and emotional purposes. Recent studies demonstrating, through a rigorous and scientific approach, the effect of ER on EFs in typical and atypical development will be discussed