Simplifying Detection of Copy-Number Variations in Maturity-Onset Diabetes of the Young.

OBJECTIVES: Copy-number variations (CNVs) are large-scale deletions or duplications of DNA that have required specialized detection methods, such as microarray-based genomic hybridization or multiplex ligation probe amplification. However, recent advances in bioinformatics have made it possible to detect CNVs from next-generation DNA sequencing (NGS) data. Maturity-onset diabetes of the young (MODY) 5 is a subtype of autosomal-dominant diabetes that is often caused by heterozygous deletions involving the HNF1B gene on chromosome 17q12. We evaluated the utility of bioinformatic processing of raw NGS data to detect chromosome 17q12 deletions in MODY5 patients. METHODS: NGS data from 57 patients clinically suspected to have MODY but who were negative for pathogenic mutations using a targeted panel were re-examined using a CNV calling tool (CNV Caller, VarSeq version 1.4.3). Potential CNVs for MODY5 were then confirmed using whole-exome sequencing, cytogenetic analysis and breakpoint analysis when possible. RESULTS: Whole-gene deletions in HNF1B, ranging from 1.46 to 1.85 million basepairs in size, were detected in 3 individuals with features of MODY5. These were confirmed by independent methods to be part of a more extensive 17q12 deletion syndrome. Two additional patients carrying a 17q12 deletion were subsequently diagnosed using this method. CONCLUSIONS: Large-scale deletions are the most common cause of MODY5 and can be detected directly from NGS data, without the need for additional methods.

Comparison of soft-tissue profiles after treatment with headgear or Herbst appliance.

INTRODUCTION: Herbst and headgear appliances are considered effective for correcting Class II malocclusions in growing patients, although their skeletal and dental effects differ. In the literature, there is no comparison between profile esthetic outcomes with the Herbst and headgear. The purpose of this study was to provide that comparison. METHODS: Lateral cephalometric radiographs of 48 matched pairs of growing Class II Division 1 patients treated with either the Herbst appliance or headgear (both combined with fixed appliances) were used to generate pretreatment and posttreatment standardized silhouettes. The silhouettes were randomly arranged and judged by lay people and orthodontic residents using a 7-point Likert scale. Statistical analyses including nonparametric procedures and intraclass correlation were used to compare initial, final, and change profile esthetic scores for the 2 groups of subjects and agreement between evaluators. RESULTS: Both groups of subjects had significant profile improvements with treatment (P <.05), and there were no statistically significant differences between the groups in average final profile scores. Overall, there was strong agreement between the evaluations of laypersons and orthodontic residents. CONCLUSIONS: Class II Division 1 growing patients treated with either Herbst appliance or headgear (both combined with fixed appliances) will benefit from significantly improved profiles that are equally attractive.

Healthy Buddies: a novel, peer-led health promotion program for the prevention of obesity and eating disorders in children in elementary school.

OBJECTIVE: We designed and tested a novel health promotion program for elementary schools that was based on peer teaching from older to younger schoolchildren ("Healthy Buddies"). SUBJECTS AND METHODS: This prospective pilot study compared the effect of our program (2-3 hours/week, 21 weeks) in 2 Canadian elementary schools (intervention: n = 232 children, the whole school implementing the program; control: n = 151). Older students (4th through 7th grade) were given direct instruction from 1 intervention teacher and were paired with younger students (kindergarten through 3rd grade) for the whole school year. Students in 4th through 7th grade then acted as teachers for their younger "buddies." All lessons included 3 components of healthy living: nutrition, physical activity, and healthy body image. The students first learned how to be positive buddies and learned the 3 components of a healthy life. Thereafter, they learned how to overcome challenges to living a healthy life. Outcome measures (intervention and control schools at the beginning and end of the school year) included validated questionnaires that assessed healthy-living knowledge, behavior and attitude, a 9-minute fitness run, self-competence, body satisfaction, disordered eating symptoms, and anthropometry (BMI, blood pressure, and heart rate). RESULTS: Compared with control students, both older and younger intervention students showed an increase in healthy-living knowledge, behavior, and attitude scores and a smaller increase in systolic blood pressure. BMI and weight increased less in the intervention students in 4th through 7th grade and height more in the intervention students in kindergarten through 3rd grade. CONCLUSIONS: Our student-led curriculum improved knowledge not only in older schoolchildren but also in their younger buddies. It also decreased weight velocity in the older students. Student-led teaching may be an efficient, easy-to-implement way of promoting a healthy lifestyle from kindergarten to 7th grade.

Substance use in female adolescents with eating disorders.

To determine the prevalence of substance use in adolescents with eating disorders, compare the results with a data set of Ontario high school students, and explore why adolescents with eating disorders do, or do not, use various substances. From January 1999 to March 2000, 101 female adolescents who met the DSM-IV criteria for an eating disorder were followed up in a tertiary care pediatric treatment center. They were asked to participate in a cross-sectional study using a self-administered questionnaire assessing substance use and investigating reasons for use and nonuse; 95 agreed to participate and 77 completed the questionnaire (mean age, 15.2 years). The patients were divided into two groups: 63 with restrictive symptoms only, 17 with purging symptoms. The rates of drug use between subjects and their comparison groups were compared by z-scores, with the level of significance set at.05. During the preceding year, restrictors used significantly less tobacco, alcohol, and cannabis than grade- and sex-matched comparison populations, and purgers used these substances at rates similar to those of comparison subjects. Other drugs seen frequently in the purgers included hallucinogens, tranquilizers, stimulants, LSD, PCP, cocaine, and "ecstasy." Both groups used caffeine and laxatives, but few used diet pills. Restrictors said they did not use substances because they were bad for their health, tasted unpleasant, were contrary to their beliefs, and were too expensive. Purgers generally used substances to relax, relieve anger, avoid eating, and "get away" from problems. Female adolescents with eating disorders who have restrictive symptoms use substances less frequently than the general adolescent population but do not abstain from their use. Those with purging symptoms use substances with a similar frequency to that found in the general adolescent population. Because the sample size for the purging group was small, firm conclusions cannot be drawn from our analysis. Health care providers who treat adolescents with eating disorders are in a good position to identify those who use substances and may be at risk for substance abuse.