Nutrient regulation of pancreatic beta-cell function in diabetes: problems and potential solutions

increasing prevalence of obesity combined with longevity will produce an epidemic of Type 2 (non-insulin-dependent) diabetes in the next 20 years. This. disease is associated with defects in insulin secretion, specifically abnormalities of insulin secretory kinetics and pancreatic beta-cell glucose responsiveness. Mechanisms underlying beta-cell dysfunction include glucose toxicity, lipotoxicity and beta-cell hyperactivity. Defects at various sites in beta-cell signal transduction pathways contribute, but no single lesion can account for the common form of Type 2 diabetes. Recent studies highlight diverse beta-cell actions of GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide). These intestinal hormones target the beta-cell to stimulate glucose-dependent insulin secretion through activation of protein kinase A and associated pathways. Both increase gene expression and proinsulin biosynthesis, protect against apoptosis and stimulate replication/neogenesis of beta-cells. Incretin hormones therefore represent an exciting future multi-action solution to correct beta-cell defect in Type 2 diabetes.

Psychological problems in children with cerebral palsy: A cross-sectional European study

Objectives: To describe psychological symptoms in 8–12-year-old children with cerebral palsy; to investigate predictors of these symptoms and their impact on the child and family.

Design: A cross-sectional multi-centre survey.

Participants: Eight hundred and eighteen children with cerebral palsy, aged 8–12 years, identified from population-based registers of cerebral palsy in eight European regions and from multiple sources in one further region.

Main outcome measures: The Strengths and Difficulties Questionnaire (SDQ)P4-16 and the Total Difficulties Score (TDS) dichotomised into normal/borderline (TDS = 16) versus abnormal (TDS > 16).

Statistical analysis: Multilevel, multivariable logistic regression to relate the presence of psychological symptoms to child and family characteristics.

Results: About a quarter of the children had TDS > 16 indicating significant psychological symptoms, most commonly in the domain Peer Problems. Better gross motor function, poorer intellect, more pain, having a disabled or ill sibling and living in a town were independently associated with TDS > 16. The risk of TDS > 16 was odds ratio (OR) = .2 (95% CI: .1 to .3) comparing children with the most and least severe functional limitations; OR = 3.2 (95%CI: 2.1 to 4.8) comparing children with IQ < 70 and others; OR = 2.7 (95% CI: 1.5 to 4.6) comparing children in severe pain and others; OR = 2.7 (95% CI:1.6 to 4.6) comparing children with another disabled sibling or OR = 1.8 (95%CI: 1.2 to 2.8) no siblings and others; OR = 1.8 (95% CI: 1.1 to 2.8) comparing children resident in a town and others. Among parents who reported their child to have psychological problems, 95% said they had lasted over a year, 37% said they distressed their child and 42% said they burdened the family at least ‘quite a lot’.

Conclusions: A significant proportion of children with cerebral palsy have psychological symptoms or social impairment sufficiently severe to warrant referral to specialist services. Care must be taken in the assessment and management of children with cerebral palsy to ensure psychological problems are not overlooked and potentially preventable risk factors like pain are treated effectively. The validity of the SDQ for children with severe disability warrants further assessment.

Common psychology problems in cerebral palsy

Cerebral palsy (CP) refers to a collection of motor impairments which result in abnormal posture and movement following an insult or damage to the developing brain. Psychological adjustment in children with CP is under researched with little population-based or longitudinal data, but there is sufficient evidence to suggest that children with CP are at increased risk for psychological problems. The types of difficulties they experience include emotional, hyperactivity and peer problems with conduct disorder being more prevalent in mildly affected children. The origins of psychological problems in this group are complex but include ‘disease’ and ‘psychosocial’ factors related to having a brain-based disability in the family, as well as other factors that influence adjustment in all children. There are no intervention studies in children with CP aimed at preventing psychological problems or promoting mental wellbeing. However, evidence from other work suggests it is possible to work with the child and family to develop skills, manage symptoms, and build confidence and resilience. Acting as early as possible has been found to be beneficial for bonding, child development and reducing parental anxiety.

Feasibility of a Clinical Chemical Analysis Approach to Predict Misuse of Growth Promoting Hormones in Cattle

A study was performed to determine if targeted metabolic profiling of cattle sera could be used to establish a predictive tool for identifying hormone misuse in cattle. Metabolites were assayed in heifers (n ) 5) treated with nortestosterone decanoate (0.85 mg/kg body weight), untreated heifers (n ) 5), steers (n ) 5) treated with oestradiol benzoate (0.15 mg/kg body weight) and untreated steers (n ) 5). Treatments were administered on days 0, 14, and 28 throughout a 42 day study period. Two support vector machines (SVMs) were trained, respectively, from heifer and steer data to identify hormonetreated animals. Performance of both SVM classifiers were evaluated by sensitivity and specificity of treatment prediction. The SVM trained on steer data achieved 97.33% sensitivity and 93.85% specificity while the one on heifer data achieved 94.67% sensitivity and 87.69% specificity. Solutions of SVM classifiers were further exploited to determine those days when classification accuracy of the SVM was most reliable. For heifers and steers, days 17-35 were determined to be the most selective. In summary, bioinformatics applied to targeted metabolic profiles generated from standard clinical chemistry analyses, has yielded an accurate, inexpensive, high-throughput test for predicting steroid abuse in cattle.

Child abuse as a complex and wicked problem: Reflecting on policy developments in the United Kingdom in working with children and families with multiple problems

In spite of significant public concern, professional efforts and financial expenditure, there has been a perceived lack of progress in reducing the incidence of child abuse, and in improving the outcomes for children in both the short and longer term. In this article the authors reflect on recent policy developments in the United Kingdom relating to children and families experiencing multiple adversities, and argue that the current conceptualisation of child abuse is flawed. In adopting a rational technical approach to the management of child abuse, there is a tendency to focus on shorter term outcomes for the child, such as immediate safety, that primarily reflect the outputs of the child protection system. However, by viewing child abuse as a wicked problem, that is complex and less amenable to being solved, then child welfare professionals can be supported to focus on achieving longer term outcomes for children that are more likely to meet their needs. The authors argue for an earlier identification of and intervention with children who are experiencing multiple adversity, such as those living with parents misusing substances and exposed to intimate partner violence.