HE PREVALENCE OF OVERweight in adolescents is increasing worldwide. In the United States, the proportion of adolescents with a body mass index (BMI) at or above the 95th percentile for age, a widely accepted definition of obesity in adolescents, 1,2 has increased 15.5% to 23.4% in certain ethnic minorities. 3 A similar picture is seen in European countries: the prevalence of overweight in adolescents has increased 8% to 21% in northern European countries and 17% to 23% in southern European countries. 4 Excess weight in adolescents is associated with an increased risk of disorders such as hyperlipidemia and type 2 diabetes 5 and can result in decreased emotional and physical quality of life. 6,7 In addition, childhood obesity results in increased risk of morbidity and mortality in adulthood. 8,9 Long-term follow-up studies of children and adolescents indicate that overweight children have a 15-fold greater risk of becoming overweight adults compared with those children and adolescents who were not overweight. 8 Effective weight management in children and adolescents may therefore have important immediate and future societal health benefits. Treatment of obesity in the pediatric age group, and in particular during adolescence, 10 is notoriously difficult. While behavioral therapy has had some success in treating obesity in young children (aged 6-12 years), most stud-For editorial comment see p 2932.
Congenital hypogonadotropic hypogonadism (CHH) and its anosmia-associated form (Kallmann syndrome [KS]) are genetically heterogeneous. Among the >15 genes implicated in these conditions, mutations in FGF8 and FGFR1 account for ~12% of cases; notably, KAL1 and HS6ST1 are also involved in FGFR1 signaling and can be mutated in CHH. We therefore hypothesized that mutations in genes encoding a broader range of modulators of the FGFR1 pathway might contribute to the genetics of CHH as causal or modifier mutations. Thus, we aimed to (1) investigate whether CHH individuals harbor mutations in members of the so-called "FGF8 synexpression" group and (2) validate the ability of a bioinformatics algorithm on the basis of protein-protein interactome data (interactome-based affiliation scoring [IBAS]) to identify high-quality candidate genes. On the basis of sequence homology, expression, and structural and functional data, seven genes were selected and sequenced in 386 unrelated CHH individuals and 155 controls. Except for FGF18 and SPRY2, all other genes were found to be mutated in CHH individuals: FGF17 (n = 3 individuals), IL17RD (n = 8), DUSP6 (n = 5), SPRY4 (n = 14), and FLRT3 (n = 3). Independently, IBAS predicted FGF17 and IL17RD as the two top candidates in the entire proteome on the basis of a statistical test of their protein-protein interaction patterns to proteins known to be altered in CHH. Most of the FGF17 and IL17RD mutations altered protein function in vitro. IL17RD mutations were found only in KS individuals and were strongly linked to hearing loss (6/8 individuals). Mutations in genes encoding components of the FGF pathway are associated with complex modes of CHH inheritance and act primarily as contributors to an oligogenic genetic architecture underlying CHH.
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.
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