The effect of the Talking Diabetes consulting skills intervention on glycaemic control and quality of life in children with type 1 diabetes: cluster randomised controlled trial (DEPICTED study)

Objective To evaluate the effectiveness on glycaemic control of a training programme in consultation skills for paediatric diabetes teams

KSR2 mutations are associated with obesity, insulin resistance, and impaired cellular fuel oxidation.

Kinase suppressor of Ras 2 (KSR2) is an intracellular scaffolding protein involved in multiple signaling pathways. Targeted deletion of Ksr2 leads to obesity in mice, suggesting a role in energy homeostasis. We explored the role of KSR2 in humans by sequencing 2,101 individuals with severe early-onset obesity and 1,536 controls. We identified multiple rare variants in KSR2 that disrupt signaling through the Raf-MEKERK pathway and impair cellular fatty acid oxidation and glucose oxidation in transfected cells; effects that can be ameliorated by the commonly prescribed antidiabetic drug, metformin. Mutation carriers exhibit hyperphagia in childhood, low heart rate, reduced basal metabolic rate and severe insulin resistance. These data establish KSR2 as an important regulator of energy intake, energy expenditure, and substrate utilization in humans. Modulation of KSR2-mediated effects may represent a novel therapeutic strategy for obesity and type 2 diabetes.This work was supported by the Wellcome Trust (098497/Z/12/Z; 077016/Z/05/Z; 096106/Z/11/Z) (ISF and LRP), Medical Research Council (MC_U106179471) (NW), NIHR Cambridge Biomedical Research Centre (ISF, IB and SOR), and European Research Council (ISF). This study makes use of data generated by the UK10K Consortium (WT091310). A full list of the investigators who contributed to the generation of the data is available from http://www.UK10K.org.This is the final published version. It first appeared at http://www.cell.com/abstract/S0092-8674%2813%2901276-2

In-frame seven amino-acid duplication in AIP arose over the last 3000 years, disrupts protein interaction and stability and is associated with gigantism.

Mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are associated with pituitary adenoma, acromegaly and gigantism. Identical alleles in unrelated pedigrees could be inherited from a common ancestor or result from recurrent mutation events.EDGE Project ID: 172

Development and Evaluation of a Psychosocial Intervention for Children and Teenagers Experiencing Diabetes (DEPICTED): a protocol for a cluster randomised controlled trial of the effectiveness of a communication skills training programme for healthcare professionals working with young people with type 1 diabetes

Background Diabetes is the third most common chronic condition in childhood and poor glycaemic control leads to serious short-term and life-limiting long-term complications. In addition to optimal medical management, it is widely recognised that psychosocial and educational factors play a key role in improving outcomes for young people with diabetes. Recent systematic reviews of psycho-educational interventions recognise the need for new methods to be developed in consultation with key stakeholders including patients, their families and the multidisciplinary diabetes healthcare team. Methods/design Following a development phase involving key stakeholders, a psychosocial intervention for use by paediatric diabetes staff and not requiring input from trained psychologists has been developed, incorporating a communication skills training programme for health professionals and a shared agenda-setting tool. The effectiveness of the intervention will be evaluated in a cluster-randomised controlled trial (RCT). The primary outcome, to be measured in children aged 4-15 years diagnosed with type 1 diabetes for at least one year, is the effect on glycaemic control (HbA1c) during the year after training of the healthcare team is completed. Secondary outcomes include quality of life for patients and carers and cost-effectiveness. Patient and carer preferences for service delivery will also be assessed. Twenty-six paediatric diabetes teams are participating in the trial, recruiting a total of 700 patients for evaluation of outcome measures. Half the participating teams will be randomised to receive the intervention at the beginning of the trial and remaining centres offered the training package at the end of the one year trial period. Discussion The primary aim of the trial is to determine whether a communication skills training intervention for specialist paediatric diabetes teams will improve clinical and psychological outcomes for young people with type 1 diabetes. Previous research indicates the effectiveness of specialist psychological interventions in achieving sustained improvements in glycaemic control. This trial will evaluate an intervention which does not require the involvement of trained psychologists, maximising the potential feasibility of delivery in a wider NHS context. Trial registration Current Controlled Trials ISRCTN61568050

Significant benefits of AIP testing and clinical screening in familial isolated and young-onset pituitary tumors

Context Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs). Objective To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients. Design 12-year prospective, observational study. Participants & Setting We studied probands and family members of FIPA kindreds and sporadic patients with disease onset ≤18 years or macroadenomas with onset ≤30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases. Interventions & Outcome AIP testing and clinical screening for pituitary disease. Comparison of characteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients (n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310). Results Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases, AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy, suprasellar extension, and more patients required multimodal therapy, including radiotherapy. AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650). Conclusions Prospectively diagnosed AIPmut patients show better outcomes than clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course

Assessment of Sexual Health in Aging Men in Europe: Development and Validation of the European Male Ageing Study Sexual Function Questionnaire

Introduction Assessment of male sexual dysfunction has been the focus of substantial scientific effort. Less research has focused on the development of instruments for the measurement of sexual functioning in aging men. Aims The aims of this study were: (i) to characterize the psychometric properties of a new brief, reliable, and valid measure of male sexual functioning for use in a large population survey of middle-aged and elderly European men; and (ii) specifically, to determine whether the new instrument, the European Male Ageing Study–sexual function questionnaire (EMAS–SFQ), discriminates between men with high and low levels of circulating testosterone (T) (total T, free T, and bioavailable T). Method One thousand six hundred men aged 40–79 years completed the self-administered EMAS–SFQ, the Beck depression inventory, and provided a blood sample for assessment of sex hormones. Eighty-five men aged 35–74 years completed the EMAS–SFQ twice, 2 weeks apart to examine the test–retest reliability of the instrument. Main Outcome Measures Scores on the EMAS–SFQ in relation to age and T levels. Results Principal component analysis showed that the EMAS–SFQ had four distinct domains (overall sexual functioning [OSF], masturbation, sexual functioning-related distress, and change in sexual functioning). The instrument demonstrated excellent internal and test–retest reliability, as well as convergent, divergent, and discriminant validity. Men with the lowest levels of total, free, and bioavailable T reported lower OSF scores compared to men with the highest T levels. Conclusions The EMAS–SFQ is a valid and reproducible instrument, sensitive to age and T levels. It should be suitable for the assessment of sexual health in population samples of men in epidemiological studies of aging. O'Connor DB, Corona G, Forti G, Tajar A, Lee DM, Finn JD, Bartfai G, Boonen S, Casanueva FF, Giwercman A, Huhtaniemi IT, Kula K, O'Neill TW, Pendleton N, Punab M, Silman AJ, Vanderschueren D, Wu FCW, and the European Male Ageing Study group. Assessment of sexual health in aging men in Europe: Development and validation of the European Male Ageing Study sexual function questionnaire

A new scale of social desirability independent of psychopathology.

It has long been recognized that personality test scores are influenced by non-test-relevant response determinants. Wiggins and Rumrill (1959) distinguish three approaches to this problem. Briefly, interest in the problem of response distortion has been concerned with attempts at statistical correction for "faking good " or "faking bad " (Meehl & Hathaway, 1946), the analysis of response sets (Cron-bach, 1946,1950), and ratings of the social de-sirability of personality test items (Edwards, 19 5 7). A further distinction can be made, how-ever, which results in a somewhat different division of approaches to the question of re-sponse distortion. Common to both the Meeh