The prevalence of the metabolic syndrome is high among obese children and adolescents, and it increases with worsening obesity. Biomarkers of an increased risk of adverse cardiovascular outcomes are already present in these youngsters.

Insulin resistance is a major factor in the pathogenesis of type 2 diabetes in the elderly. To investigate how insulin resistance arises, we studied healthy, lean, elderly and young participants matched for lean body mass and fat mass. Elderly study participants were markedly insulinresistant as compared with young controls, and this resistance was attributable to reduced insulinstimulated muscle glucose metabolism. These changes were associated with increased fat accumulation in muscle and liver tissue assessed by 1 H nuclear magnetic resonance (NMR) spectroscopy, and with a ∼40% reduction in mitochondrial oxidative and phosphorylation activity, as assessed by in vivo 13 C/ 31 P NMR spectroscopy. These data support the hypothesis that an ageassociated decline in mitochondrial function contributes to insulin resistance in the elderly.Type 2 diabetes is the most common chronic metabolic disease in the elderly, affecting ∼30 million individuals 65 years of age or older in developed countries (1). The estimated economic burden of diabetes in the United States is ∼$100 billion per year, of which a substantial proportion can be attributed to persons with type 2 diabetes in the elderly age group (2). Epidemiological studies have shown that the transition from the normal state to overt type 2 diabetes in aging is typically characterized by a deterioration in glucose * To whom correspondence should be addressed. gerald.shulman@yale.edu. [11][12][13]. Increases in the intracellular concentration of fatty acid metabolites have been postulated to activate a serine kinase cascade leading to defects in insulin signaling in muscle (14-17) and the liver (18), which results in reduced insulinstimulated muscle glucose transport activity (14), reduced glycogen synthesis in muscle (19,20), and impaired suppression of glucose production by insulin in the liver (11-13).To examine whether insulin resistance in the elderly is associated with similar increases in intramyocellular and/or liver triglyceride content, we studied healthy elderly and young people that we matched for lean body mass (LBM) and fat mass. All study participants were non-smoking, sedentary, lean [body mass index (BMI) < 25 m 2 /kg], and taking no medications. Sixteen elderly volunteers (ages 61 to 84 years, 8 male and 8 female) were screened with a 3-hour oral glucose (75 g) tolerance test and underwent dual-energy x-ray absorptiometry to assess LBM and fat mass (21). One elderly man was excluded from the study because of an abnormal glucose profile. Thirteen young volunteers (ages 18 to 39 years, 6 male and 7 female), who had no family history of diabetes or hypertension, were matched to the older participants for BMI and habitual physical activity, which was assessed by means of an activity index questionnaire (22). All participants underwent a complete medical history and physical examination, as well as blood tests to confirm that they were in excellent health (23).Young and elderly participants had similar fat mass, percent fat mass, and LBM (Table 1...

Context Tourette disorder is a chronic and typically impairing childhood-onset neurological condition. Antipsychotic medications, the first-line treatments for moderate to severe tics, are often associated with adverse effects. Behavioral interventions, although promising, have not been evaluated in large-scale controlled trials. Objective To determine the efficacy of a comprehensive behavioral intervention for reducing tic severity in children and adolescents. Design, Setting, Participants Randomized, observer-blind, controlled trial of 126 youngsters recruited from December, 2004 through May, 2007 and aged 9–17 years with impairing Tourette or chronic tic disorder as primary diagnosis randomized to 8 sessions over 10 weeks of behavior therapy (n=61) or a control treatment consisting of supportive therapy and education (n=65). Responders received 3 monthly treatment booster sessions and were reassessed at 3- and 6-months post-treatment. Intervention Comprehensive behavioral intervention. Main Outcome Measures Yale Global Tic Severity Scale (range 0–40, score >15 indicating clinically significant tics), Clinical Global Impression-Improvement Scale (range 1-very much improved to 8-very much worse). Results Behavioral intervention led to a significantly greater decrease on the Yale Global Tic Severity Scale (24.7; CI:23.1,26.3) to 17.1 CI:15.1,19.1) from baseline to endpoint compared to the control treatment (24.6 CI:23.2,26.0) to 21.1 CI:19.2,23.0) (P<.001; 95% CI for difference between groups: 6.2, 2.0); (effect size=0.68). Compared to children in control treatment, significantly more children receiving behavioral intervention were rated as “very much” or “much improved” on the Clinical Global Impression-Improvement scale (52.5% to 18.5%, respectively; P<0.001; number-needed-to-treat=3). Attrition was low (12/126 or 9.5%); tic worsening was reported by 4% of children (5/126). Treatment gains were durable with 87% of available responders to behavior therapy showing continued benefit 6 months post-treatment. Conclusions A comprehensive behavioral intervention, compared with supportive therapy and education, resulted in greater improvement in symptom severity among children with Tourette and chronic tic disorder.

Among patients with degenerative grade I spondylolisthesis, the addition of lumbar spinal fusion to laminectomy was associated with slightly greater but clinically meaningful improvement in overall physical health-related quality of life than laminectomy alone. (Funded by the Jean and David Wallace Foundation and others; SLIP ClinicalTrials.gov number, NCT00109213.).

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