Is guided self-help family-based treatment for parents of adolescents with anorexia nervosa on treatment waitlists feasible? A pilot trial.

OBJECTIVE: The aim of the study was to assess the feasibility (recruitment and retention) of an online 12-session guided self-help family-based treatment (GSH-FBT) for families on the waitlist for face-to-face FBT utilizing trainee psychologists to assist carers of children with anorexia nervosa (AN) or atypical AN. METHOD: The primary outcomes were feasibility of GSH-FBT for families on the waitlist and secondary exploratory outcomes examined improvement of child and parental function. RESULTS: Of 187 eligible families on the waitlist, 24 (13%) expressed interest in the study; 16 (67%) of these families completed baseline, 13 (54%) completed GSH-FBT over a 6-month recruitment period. Children (mean age = 13.92, SD = .86; mean body mass index [BMI] centile = 29.47, SD = 24.80) had an average weight gain of 6 kg (BMI centile effect size = 2.61, 95% CI: 1.77-3.44) and a decrease in eating disorder behaviors (effect size = 1.11, 95% CI: .27-1.95). Improvements also occurred for general mood and behaviors in the child, and the impact of eating disorder symptoms on their functioning. Parents reported improvements in knowledge, skills, and confidence in managing AN. DISCUSSION: Use of this low-cost intervention while families are on the waitlist for FBT is engaging and useful but strategies to improve initial recruitment are needed. PUBLIC SIGNIFICANCE STATEMENT: Although most eligible families did not enroll in an online 12-session guided self-help family-based treatment for families on the waitlist for face-to-face FBT for anorexia nervosa, families who participated found it engaging. The children experienced improvements in BMI centile, eating and behavior. Parents reported increased confidence, knowledge, and skills. We need to examine how families can be encouraged to participate on online training when on waitlists for treatment.

Challenges and practical recommendations for successfully recruiting inactive, statin-free older adults to clinical trials.

OBJECTIVES: To outline the challenges and provide practical recommendations for recruiting inactive, statin-free older adults to facilitate feasible study designs. Data was obtained from a double-blind randomised-controlled clinical trial investigating the effects of acipimox versus placebo on muscle function and metabolism in older (65-75 years), inactive, statin-free males. The initial recruitment target was 20 volunteers within 12 months (November 2016-November 2017). RESULTS: Recruitment occurred via the Exeter 10,000 database containing 236 'eligible' males, a Facebook campaign reaching > 8000 ≥ 65 years old males, 400 directly-addressed letters to ≥ 66 year old males, > 1500 flyers distributed within the community, > 40 emails to local community groups, 4 recruitment talks, 2 magazine adverts and 1 radio advert. Widespread recruitment efforts reaching > 120,000 people led to the recruitment of 20 volunteers (18 completed the clinical trial) within a 25-month timeframe, highlighting the challenge of the timely recruitment of inactive, statin-free older adults for clinical trials. We recommend recruitment for future clinical trials should take a multi-pronged approach from the outset, prioritising the use of volunteer databases, Facebook campaigns and delivering recruitment talks.

An engaged research study to assess the effect of a 'real-world' dietary intervention on urinary bisphenol A (BPA) levels in teenagers.

OBJECTIVE: Bisphenol A (BPA) has been associated with adverse human health outcomes and exposure to this compound is near-ubiquitous in the Western world. We aimed to examine whether self-moderation of BPA exposure is possible by altering diet in a real-world setting. DESIGN: An Engaged Research dietary intervention study designed, implemented and analysed by healthy teenagers from six schools and undertaken in their own homes. PARTICIPANTS: A total of 94 students aged between 17 and 19 years from schools in the South West of the UK provided diet diaries and urine samples for analysis. INTERVENTION: Researcher participants designed a set of literature-informed guidelines for the reduction of dietary BPA to be followed for 7 days. MAIN OUTCOME MEASURES: Creatinine-adjusted urinary BPA levels were taken before and after the intervention. Information on packaging and food/drink ingested was used to calculate a BPA risk score for anticipated exposure. A qualitative analysis was carried out to identify themes addressing long-term sustainability of the diet. RESULTS: BPA was detected in urine of 86% of participants at baseline at a median value of 1.22 ng/mL (IQR 1.99). No effect of the intervention diet on BPA levels was identified overall (P=0.25), but there was a positive association in those participants who showed a drop in urinary BPA concentration postintervention and their initial BPA level (P=0.003). Qualitative analysis identified themes around feelings of lifestyle restriction and the inadequacy of current labelling practices. CONCLUSIONS: We found no evidence in this self-administered intervention study that it was possible to moderate BPA exposure by diet in a real-world setting. Furthermore, our study participants indicated that they would be unlikely to sustain such a diet long term, due to the difficulty in identifying BPA-free foods.

Recognition and Management of Individuals With Hyperglycemia Because of a Heterozygous Glucokinase Mutation.

Glucokinase-maturity-onset diabetes of the young (GCK-MODY), also known as MODY2, is caused by heterozygous inactivating mutations in the GCK gene. GCK gene mutations are present in ∼1 in 1,000 of the population, but most are not diagnosed. They are common causes of MODY (10-60%): persistent incidental childhood hyperglycemia (10-60%) and gestational diabetes mellitus (1-2%). GCK-MODY has a unique pathophysiology and clinical characteristics, so it is best considered as a discrete genetic subgroup. People with GCK-MODY have a defect in glucose sensing; hence, glucose homeostasis is maintained at a higher set point resulting in mild, asymptomatic fasting hyperglycemia (5.4-8.3 mmol/L, HbA1c range 5.8-7.6% [40-60 mmol/mol]), which is present from birth and shows slight deterioration with age. Even after 50 years of mild hyperglycemia, people with GCK-MODY do not develop significant microvascular complications, and the prevalence of macrovascular complications is probably similar to that in the general population. Treatment is not recommended outside pregnancy because glucose-lowering therapy is ineffective in people with GCK-MODY and there is a lack of long-term complications. In pregnancy, fetal growth is primarily determined by whether the fetus inherits the GCK gene mutation from their mother. Insulin treatment of the mother is only appropriate when increased fetal abdominal growth on scanning suggests the fetus is unaffected. The impact on outcome of maternal insulin treatment is limited owing to the difficulty in altering maternal glycemia in these patients. Making the diagnosis of GCK-MODY through genetic testing is essential to avoid unnecessary treatment and investigations, especially when patients are misdiagnosed with type 1 or type 2 diabetes.

Interarm blood pressure difference in people with diabetes: measurement and vascular and mortality implications: a cohort study.

OBJECTIVE: Differences in blood pressure between arms are associated with vascular disease and increased mortality; this has not been reported in diabetes. We explored these associations, and assessed reference standard and pragmatic measurement techniques, in people with diabetes and in nondiabetic controls. RESEARCH DESIGN AND METHODS: A prospective cohort study in Devon, England, recruited 727 people with type 1 or type 2 diabetes and 285 nondiabetic controls. Simultaneous repeated measurements of bilateral blood pressure were made at recruitment. Data were used to inform a pragmatic measurement strategy. Interarm differences were examined for cross-sectional associations with target organ disease and prospective mortality associations (median follow-up 52 months). RESULTS: We found 8.6% of participants with diabetes and 2.9% of controls had systolic interarm differences ≥10 mmHg. Single pairs of blood pressure measurements had high negative predictive values (97-99%) for excluding interarm differences. Systolic interarm differences ≥10 mmHg in diabetes were associated with peripheral arterial disease (odds ratio [OR] 3.4 [95% CI 1.2-9.3]). Differences ≥15 mmHg were associated with diabetic retinopathy (OR 5.7 [1.5-21.6]) and chronic kidney disease (OR 7.0 [1.7-29.8]). Systolic interarm differences were associated prospectively with increased cardiovascular mortality: hazard ratios 3.5 (1.0-13.0) for ≥10 mmHg and 9.0 (2.0-41.0) for ≥15 mmHg. CONCLUSIONS: Blood pressure should be measured in both arms during initial assessment in diabetes. Systolic interarm differences can be excluded with a single pair of measurements. In the population with diabetes, systolic differences may be associated with an increased risk of morbidity and mortality.

Prevalence of vascular complications among patients with glucokinase mutations and prolonged, mild hyperglycemia.

IMPORTANCE: Glycemic targets in diabetes have been developed to minimize complication risk. Patients with heterozygous, inactivating glucokinase (GCK) mutations have mild fasting hyperglycemia from birth, resulting in an elevated glycated hemoglobin (HbA1c) level that mimics recommended levels for type 1 and type 2 diabetes. OBJECTIVE: To assess the association between chronic, mild hyperglycemia and complication prevalence and severity in patients with GCK mutations. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study in the United Kingdom between August 2008 and December 2010. Assessment of microvascular and macrovascular complications in participants 35 years or older was conducted in 99 GCK mutation carriers (median age, 48.6 years), 91 nondiabetic, familial, nonmutation carriers (control) (median age, 52.2 years), and 83 individuals with young-onset type 2 diabetes (YT2D), diagnosed at age 45 years or younger (median age, 54.7 years). MAIN OUTCOMES AND MEASURES: Prevalence and severity of nephropathy, retinopathy, peripheral neuropathy, peripheral vascular disease, and cardiovascular disease. RESULTS: Median HbA1c was 6.9% in patients with the GCK mutation, 5.8% in controls, and 7.8% in patients with YT2D. Patients with GCK had a low prevalence of clinically significant microvascular complications (1% [95% CI, 0%-5%]) that was not significantly different from controls (2% [95% CI, 0.3%-8%], P=.52) and lower than in patients with YT2D (36% [95% CI, 25%-47%], P<.001). Thirty percent of patients with GCK had retinopathy (95% CI, 21%-41%) compared with 14% of controls (95% CI, 7%-23%, P=.007) and 63% of patients with YT2D (95% CI, 51%-73%, P<.001). Neither patients with GCK nor controls required laser therapy for retinopathy compared with 28% (95% CI, 18%-39%) of patients with YT2D (P<.001). Neither patients with GCK patients nor controls had proteinuria and microalbuminuria was rare (GCK, 1% [95% CI, 0.2%-6%]; controls, 2% [95% CI, 0.2%-8%]), whereas 10% (95% CI, 4%-19%) of YT2D patients had proteinuria (P<.001 vs GCK) and 21% (95% CI, 13%-32%) had microalbuminuria (P<.001). Neuropathy was rare in patients with GCK (2% [95% CI, 0.3%-8%]) and controls (95% CI, 0% [0%-4%]) but present in 29% (95% CI, 20%-50%) of YT2D patients (P<.001). Patients with GCK had a low prevalence of clinically significant macrovascular complications (4% [95% CI, 1%-10%]) that was not significantly different from controls (11% [95% CI, 5%-19%]; P=.09), and lower in prevalence than patients with YT2D (30% [95% CI, 21%-41%], P<.001). CONCLUSIONS AND RELEVANCE: Despite a median duration of 48.6 years of hyperglycemia, patients with a GCK mutation had low prevalence of microvascular and macrovascular complications. These findings may provide insights into the risks associated with isolated, mild hyperglycemia.

Use of HbA1c in the identification of patients with hyperglycaemia caused by a glucokinase mutation: observational case control studies.

AIMS: HaemoglobinA1c (HbA1c) is recommended for diabetes diagnosis but fasting plasma glucose (FPG) has been useful for identifying patients with glucokinase (GCK) mutations which cause lifelong persistent fasting hyperglycaemia. We aimed to derive age-related HbA1c reference ranges for these patients to determine how well HbA1c can discriminate patients with a GCK mutation from unaffected family members and young-onset type 1 (T1D) and type 2 diabetes (T2D) and to investigate the proportion of GCK mutation carriers diagnosed with diabetes using HbA1c and/or FPG diagnostic criteria. METHODS: Individuals with inactivating GCK mutations (n = 129), familial controls (n = 100), T1D (n = 278) and T2D (n = 319) aged ≥18years were recruited. Receiver Operating Characteristic (ROC) analysis determined effectiveness of HbA1c and FPG to discriminate between groups. RESULTS: HbA1c reference ranges in subjects with GCK mutations were: 38-56 mmol/mol (5.6-7.3%) if aged ≤40years; 41-60 mmol/mol (5.9-7.6%) if >40years. All patients (123/123) with a GCK mutation were above the lower limit of the HbA1c age-appropriate reference ranges. 69% (31/99) of controls were below these lower limits. HbA1c was also effective in discriminating those with a GCK mutation from those with T1D/T2D. Using the upper limit of the age-appropriate reference ranges to discriminate those with a mutation from those with T1D/T2D correctly identified 97% of subjects with a mutation. The majority (438/597 (73%)) with other types of young-onset diabetes had an HbA1c above the upper limit of the age-appropriate GCK reference range. HbA1c ≥48 mmol/mol classified more people with GCK mutations as having diabetes than FPG ≥7 mmol/l (68% vs. 48%, p = 0.0009). CONCLUSIONS: Current HbA1c diagnostic criteria increase diabetes diagnosis in patients with a GCK mutation. We have derived age-related HbA1c reference ranges that can be used for discriminating hyperglycaemia likely to be caused by a GCK mutation and aid identification of probands and family members for genetic testing.

Psycho-education and group cognitive-behavioural therapy for clinical perfectionism: a case-series evaluation.

BACKGROUND: Research indicates that psycho-education and cognitive behavioural interventions can reduce perfectionism but to date no group treatments have been examined. AIMS: The current study utilized a case series design to compare psycho-education materials and subsequent eight-week group cognitive behaviour therapy (CBT) to a baseline waitlist in an outpatient community psychiatry sample (n = 21). METHOD: Participants were assessed on five occasions: baseline, 4 weeks later (waitlist), 4 weeks after receiving psycho-education material, post-treatment (8 weeks after receiving the group intervention), and 3-month follow-up. RESULTS: There was a main effect of time for perfectionism and negative affect from baseline to post-group (effect sizes ranging from 1.46 to 1.91) that were maintained at 3-month follow-up. CONCLUSIONS: These results suggested that group CBT for clinical perfectionism may be beneficial, but that psycho-education alone is not effective for reducing perfectionism or negative affect.

Insights into the pathogenicity of rare missense GCK variants from the identification and functional characterization of compound heterozygous and double mutations inherited in cis.

OBJECTIVE: To demonstrate the importance of using a combined genetic and functional approach to correctly interpret a genetic test for monogenic diabetes. RESEARCH DESIGN AND METHODS: We identified three probands with a phenotype consistent with maturity-onset diabetes of the young (MODY) subtype GCK-MODY, in whom two potential pathogenic mutations were identified: [R43H/G68D], [E248 K/I225M], or [G261R/D217N]. Allele-specific PCR and cosegregation were used to determine phase. Single and double mutations were kinetically characterized. RESULTS: The mutations occurred in cis (double mutants) in two probands and in trans in one proband. Functional studies of all double mutants revealed inactivating kinetics. The previously reported GCK-MODY mutations R43H and G68D were inherited from an affected father and unaffected mother, respectively. Both our functional and genetic studies support R43H as the cause of GCK-MODY and G68D as a neutral rare variant. CONCLUSIONS: These data highlight the need for family/functional studies, even for previously reported pathogenic mutations.

People of the British Isles: preliminary analysis of genotypes and surnames in a UK-control population.

There is a great deal of interest in a fine-scale population structure in the UK, both as a signature of historical immigration events and because of the effect population structure may have on disease association studies. Although population structure appears to have a minor impact on the current generation of genome-wide association studies, it is likely to have a significant part in the next generation of studies designed to search for rare variants. A powerful way of detecting such structure is to control and document carefully the provenance of the samples involved. In this study, we describe the collection of a cohort of rural UK samples (The People of the British Isles), aimed at providing a well-characterised UK-control population that can be used as a resource by the research community, as well as providing a fine-scale genetic information on the British population. So far, some 4000 samples have been collected, the majority of which fit the criteria of coming from a rural area and having all four grandparents from approximately the same area. Analysis of the first 3865 samples that have been geocoded indicates that 75% have a mean distance between grandparental places of birth of 37.3 km, and that about 70% of grandparental places of birth can be classed as rural. Preliminary genotyping of 1057 samples demonstrates the value of these samples for investigating a fine-scale population structure within the UK, and shows how this can be enhanced by the use of surnames.

Motivation-focused treatment for eating disorders: a sequential trial of enhanced cognitive behaviour therapy with and without preceding motivation-focused therapy.

OBJECTIVE: To evaluate the effectiveness of a motivation-focused intervention prior to individual cognitive behavioural eating disorder treatment. METHOD: Enhanced cognitive-behavioural therapy (CBT-E) in its usual form was compared with CBT-E preceded by four sessions of motivation-focused therapy (MFT) (MFT + CBT-E). Participants were adult outpatients seen at a specialist eating disorder clinic in Western Australia, who met criteria for a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition eating disorder. A sequential trial of CBT-E as usual (n = 43) and MFT + CBT-E (n = 52) was conducted over a 40-month period. RESULTS: The MFT phase was associated with significant increases in readiness to change. There were no significant between-group differences in treatment completion rates, and treatment completers in both conditions reported comparable reductions in eating disorder symptoms over time. CONCLUSION: In this sample, MFT + CBT-E was not associated with superior treatment outcome when compared with CBT-E as usual.

Bulimic symptomatology: the role of adaptive perfectionism, shape and weight concern, and self-esteem.

An interactive model implicating high perfectionism, high weight and shape concern, and low self-esteem in the onset and maintenance of bulimic symptoms (Bardone, Vohs, Abramson, Heatherton, & Joiner, 2000; Vohs, Bardone, Joiner, Abramson, & Heatherton, 1999) has received mixed support. This study aimed to replicate the cross-sectional model in a clinical sample of women with eating disorders, and to investigate whether the model could predict changes in binge eating and purging at the end of treatment. Eating disorder outpatients (n=353) completed measures of perfectionism, weight/shape concern, self-esteem, and bulimic symptoms at pre-treatment and discharge. Contrary to the hypotheses, the three-way interaction did not predict binge eating or purging cross-sectionally or prospectively as a moderator of psychotherapy outcome. It was concluded that the robustness of the interactive model seems questionable and may be impacted by an inadequate conceptualization of the perfectionism construct.

Perfectionism and its relation to overevaluation of weight and shape and depression in an eating disorder sample.

OBJECTIVE: To examine the relative association between psychopathology (depression and overevaluation of weight and shape) and measures of perfectionism and self-criticism in an eating disorder sample. METHOD: Participants (n = 39) completed measures of independent variables (perfectionism and self-criticism) and dependent variables (depression and overevaluation of weight and shape). RESULTS: Simultaneous multiple regression analyses suggest that clinical perfectionism has a unique association with depression. Self-criticism and clinical perfectionism had a stronger association with overevaluation of weight and shape than other measures of perfectionism. DISCUSSION: Clinical perfectionism and self-criticism may be of more relevance than existing measures of multidimensional perfectionism in terms of explaining maintenance of depression and overevaluation of weight and shape.

Self-efficacy as a robust predictor of outcome in guided self-help treatment for broadly defined bulimia nervosa.

OBJECTIVE: To examine predictors of guided self-help (GSH) treatment outcome in bulimia nervosa (BN). METHOD: Data were included from 87 individuals who participated in one of two randomized controlled trials evaluating GSH interventions for BN. Participants received eight sessions of GSH over a 6- to 8-week period and were assessed at baseline, pretreatment, posttreatment, and 6-month follow-up. RESULTS: Motivation (confidence in ability to change) proved to be the most robust predictor of outcome, across three of the four outcome measures. Baseline measures of concern over mistakes perfectionism also uniquely predicted outcome at posttreatment. Posttreatment measures of stress, eating disorder-related automatic thoughts, and frequency of binge episodes predicted outcome at 6-month follow-up. DISCUSSION: This study suggests that tackling motivation early in therapy, with a particular focus on confidence in succeeding in change, could be of benefit to outcome in BN treatment.

A randomised trial investigating guided self-help to reduce perfectionism and its impact on bulimia nervosa: a pilot study.

AIM: The purpose of the present study was to evaluate reducing perfectionism as a potential treatment target for individuals with Bulimia Nervosa (BN). METHOD: Forty-eight individuals meeting DSM-IV criteria for BN or eating disorder - not otherwise specified with binge eating [objective or subjective] or purging at least once per week were recruited. Participants were randomly assigned to receive 8 sessions of manual-based guided self-help (GSH) over a 6-week period that was focused on either cognitive behaviour therapy (CBT) for perfectionism, CBT for BN, or a placebo. Individuals were assessed at baseline, pre-treatment, post-treatment and at six-month follow-up on 12 outcome variables, including diagnostic criteria and psychological variables. RESULTS: There was no significant change in any of the outcome variables over a 6-week no-treatment period but at post-treatment and 6-month follow-up there were significant main effects of time for 10 and 8 outcome variables respectively, suggesting that all groups reported significant reductions in bulimic symptomatology and related psychopathology at post-treatment and follow-up. CONCLUSIONS: These findings show potential for the use of novel interventions in GSH for BN.

Motivational interviewing for modifying diabetes risk: a randomised controlled trial.

BACKGROUND: Around 10-15% of adults aged over 40 years have pre-diabetes, which carries a high risk of progression to type 2 diabetes. Intensive lifestyle intervention reduces progression by as much as 58%. However, the cost and personnel requirements of these interventions are major obstacles to delivery in NHS primary care. AIM: To assess the effectiveness of a low-cost intervention, delivered in primary care by non-NHS staff, to reduce the risk of diabetes through weight loss and physical activity. DESIGN OF STUDY: Pragmatic single-blind randomised controlled trial with researchers and statistician blinded to group allocation. SETTING: UK primary care. METHOD: One-hundred and forty-one participants with a body mass index of 28 kg/m2 or more, but without diabetes or heart disease, received either information leaflets or individual behavioural counselling using motivational interviewing techniques. The intervention was delivered by five counsellors recruited from the local community. The primary outcomes were the proportions of participants meeting predefined targets for weight loss (5%) and moderate physical activity (150 minutes/week) after 6 months. RESULTS: Using intention-to-treat analysis, more people in the intervention group achieved the weight-loss target (24% versus 7% for controls; odds ratio [OR]=3.96; 95% confidence interval [Cl]=1.4 to 11.4; number needed to treat [NNT]=6.1 (95% Cl=4 to 21). The proportion achieving the physical activity target did not increase significantly (38% versus 28% for controls; OR=1.6; 95% Cl=0.7 to 3.8). CONCLUSION: Short-term weight loss, at a level which, if sustained, is clinically meaningful for reducing diabetes risk, is achievable in primary care, without excessive use of NHS monetary or personnel resources.

The diabetic phenotype in HNF4A mutation carriers is moderated by the expression of HNF4A isoforms from the P1 promoter during fetal development.

OBJECTIVE: Mutations in the alternatively spliced HNF4A gene cause maturity-onset diabetes of the young (MODY). We characterized the spatial and developmental expression patterns of HNF4A transcripts in human tissues and investigated their role as potential moderators of the MODY phenotype. RESEARCH DESIGN AND METHODS: We measured the expression of HNF4A isoforms in human adult tissues and gestationally staged fetal pancreas by isoform-specific real-time PCR. The correlation between mutation position and age of diagnosis or age-related penetrance was assessed in a cohort of 190 patients with HNF4A mutations. RESULTS: HNF4A was expressed exclusively from the P2 promoter in adult pancreas, but from 9 weeks until at least 26 weeks after conception, up to 23% of expression in fetal pancreas was of P1 origin. HNF4A4-6 transcripts were not detected in any tissue. In whole pancreas, HNF4A9 expression was greater than in islets isolated from the endocrine pancreas (relative level 22 vs. 7%). Patients with mutations in exons 9 and 10 (absent from HNF4A3, HNF4A6, and HNF4A9 isoforms) developed diabetes later than those with mutations in exons 2-8, where all isoforms were affected (40 vs. 24 years; P = 0.029). Exon 9/10 mutations were also associated with a reduced age-related penetrance (53 vs. 10% without diabetes at age 55 years; P < 0.00001). CONCLUSIONS: We conclude that isoforms derived from the HNF4A P1 promoter are expressed in human fetal, but not adult, pancreas, and that their presence during pancreatic development may moderate the diabetic phenotype in individuals with mutations in the HNF4A gene.

Macrosomia and hyperinsulinaemic hypoglycaemia in patients with heterozygous mutations in the HNF4A gene.

BACKGROUND: Macrosomia is associated with considerable neonatal and maternal morbidity. Factors that predict macrosomia are poorly understood. The increased rate of macrosomia in the offspring of pregnant women with diabetes and in congenital hyperinsulinaemia is mediated by increased foetal insulin secretion. We assessed the in utero and neonatal role of two key regulators of pancreatic insulin secretion by studying birthweight and the incidence of neonatal hypoglycaemia in patients with heterozygous mutations in the maturity-onset diabetes of the young (MODY) genes HNF4A (encoding HNF-4alpha) and HNF1A/TCF1 (encoding HNF-1alpha), and the effect of pancreatic deletion of Hnf4a on foetal and neonatal insulin secretion in mice. METHODS AND FINDINGS: We examined birthweight and hypoglycaemia in 108 patients from families with diabetes due to HNF4A mutations, and 134 patients from families with HNF1A mutations. Birthweight was increased by a median of 790 g in HNF4A-mutation carriers compared to non-mutation family members (p < 0.001); 56% (30/54) of HNF4A-mutation carriers were macrosomic compared with 13% (7/54) of non-mutation family members (p < 0.001). Transient hypoglycaemia was reported in 8/54 infants with heterozygous HNF4A mutations, but was reported in none of 54 non-mutation carriers (p = 0.003). There was documented hyperinsulinaemia in three cases. Birthweight and prevalence of neonatal hypoglycaemia were not increased in HNF1A-mutation carriers. Mice with pancreatic beta-cell deletion of Hnf4a had hyperinsulinaemia in utero and hyperinsulinaemic hypoglycaemia at birth. CONCLUSIONS: HNF4A mutations are associated with a considerable increase in birthweight and macrosomia, and are a novel cause of neonatal hypoglycaemia. This study establishes a key role for HNF4A in determining foetal birthweight, and uncovers an unanticipated feature of the natural history of HNF4A-deficient diabetes, with hyperinsulinaemia at birth evolving to decreased insulin secretion and diabetes later in life.

The interaction of perfectionism, perceived weight status, and self-esteem to predict bulimic symptoms: the role of 'benign' perfectionism.

The present study sought to replicate an interactive model of global perfectionism, perceived weight status, and self-esteem in predicting bulimic symptom development in a sample of young women [Bardone-Cone, et al. (2006). Predicting bulimic symptoms: An interactive model of self-efficacy, perfectionism, and perceived weight status. Behaviour Research and Therapy, 44, 27-42; Vohs, K. D., et al. (1999). Perfectionism, perceived weight status, and self-esteem interact to predict bulimic symptoms: A model of bulimic symptom development. Journal of Abnormal Psychology, 108, 695-700; Vohs, K. D., et al. (2001). Perfectionism, body dissatisfaction, and self-esteem: An interactive model of bulimic symptom development. Journal of Social and Clinical Psychology, 20, 476-497]. The aim was to investigate the role of 'problematic' and 'benign' perfectionism within this model, using data from 95 female university students over a 3-month period. Contrary to hypotheses, multivariate analyses revealed a significant three-way interaction only between 'benign' perfectionism, perceived weight status and self-esteem in predicting change in bulimic symptoms over a 3-month period. The predictive effect of the interaction between 'benign' perfectionism and perceived weight status on bulimic symptoms was strongest for women with high self-esteem, for whom feeling overweight and having perfectionistic attitudes preceded increased bulimic symptoms. These findings suggest that high self-esteem is insufficient to protect against the development of bulimic symptoms when both the perception of oneself as being overweight, and high levels of perfectionistic standards, are present. It would appear that the role of perfectionism within the context of disordered eating is complex.

Successful treatment of anisometropic amblyopia with spectacles alone.

BACKGROUND: The efficacy of treating anisometropic amblyopia with occlusion therapy is well known. However, this form of treatment can be associated with risks. Spectacle correction alone may be a successful and underutilized form of treatment. METHODS: The records of 28 patients treated successfully for anisometropic amblyopia with glasses alone were reviewed. Age, initial visual acuity and stereoacuity, and nature of anisometropia were analyzed to assess associations with time required for resolution, final visual acuity, and stereoacuity. Incidence of amblyopia recurrence and results of subsequent treatment, including patching, were also studied. RESULTS: Mean time to amblyopia resolution (interocular acuity difference