Three-dimensional CAD/CAM reconstruction of the iliac bone following DCIA composite flap harvest.

This article reports a new technique to restore iliac bone integrity with a customized titanium device designed by CAD/CAM, in patients undergoing deep circumflex iliac artery (DCIA) composite flap harvest. Eight consecutive patients who underwent the repair of major head and neck defects with DCIA flaps were enrolled retrospectively. Computed tomography scans of the pelvis were obtained preoperatively. Starting from DICOM data, each personalized device was designed using modelling software and was finally made by additive manufacturing using a laser sintering machine. After surgery, the patients were followed up at 3-month intervals to evaluate the incidence of complications and the long-term outcome at the donor site. A subcutaneous seroma developed in one patient and an inguinal skin burn occurred in another. At a median follow-up of 12 months, the patients did not report pain, or any gait or sensory disturbance at the donor site. There was no occurrence of bulging, herniation, or instability or inflammation near the device for the entire follow-up duration. All patients were satisfied with the aesthetic result. In conclusion, reconstruction of the iliac bone with a customized device is safe and well tolerated. We recommend use of this device in patients deemed at high risk of herniation. Further studies are needed to confirm the stability of the device in the long term.

Methylsulfonylmethane and mobilee prevent negative effect of IL-1ß in human chondrocyte cultures via NF-κB signaling pathway.

Nutraceuticals are compounds that serve as nutrition with an easy accessibility and favourable safety profile. Recent studies showed their potential activity on osteoarthritis (OA) inflammation and cartilage metabolism. We investigated the effect of methylsulfonylmethane (MSM) and mobilee in human OA chondrocyte cultures exposed to interleukin (IL)-1ß. OA cartilage was obtained from femoral heads of five patients undergoing total replacement surgery. Chondrocytes were incubated with mobilee (200 and 500 µM) and MSM (2000 and 6000 µM) in presence of IL-1ß (10 ng/mL) and nuclear factor (NF)-κB inhibitor (BAY 11-7082, 1 µM), for 24 and 48 h. Viability and apoptosis were performed by MMT and flow cytometry. The metalloproteinase (MMP)-1,-3,-13 and type II collagen (Col2a1) were analyzed by qRT-PCR and ELISA, and NF-κB activation by immunofluorescence. IL-1ß stimulus determined a significant regulation of survival, apoptotic ratio, as well as of gene expression and serum levels of MMP-1,-3,-13 and Col2a1 in OA chondrocytes compared to baseline. Mobilee and MSM incubation significantly reversed the effect of IL-1ß. IL-1ß significantly induced NF-κB p50 nuclear translocation, which was significantly counteracted by the pre-treatment of OA chodrocytes with the tested compounds. BAY11-7082 significantly modulated MMPs and Col2a1 expression respectively to basal state. Co-treatment of IL-1ß with mobilee, MSM and BAY11-7082 didn't cause changes of MMPs or Col2a1 beyond that caused by each single treatment. We demonstrated that MSM and mobilee have a beneficial effect on OA chondrocytes metabolism, probably due to the modulation of NF-κB pathway, providing a powerful rationale for the use of these substances in OA treatment.

Claimed effects, outcome variables and methods of measurement for health claims proposed under regulation (EC) 1924/2006 and related to cognitive function in adults.

Some food/food components have been the object of request of authorization to the use of health claims related to cognitive function in adults and compliant with the Regulation (EC) 1924/2006. Most of the requests have received a negative opinion by the European Food Safety Authority (EFSA) also because of the choice of not appropriate outcome variables (OVs) and methods of measurement (MMs) selected in the trials used to substantiate the claim. This manuscript referes to the collection, collation and critical analysis of OVs and MMs related to cognitive function in adults. OVs and MMs were collected from the EFSA Guidance document and the applications for authorization of health claims pursuant to the Articles 13(5). The critical analysis of OVs and MMs, performed by a literature review, was aimed at defining their appropriateness in the context of a specific claimed effect. The results highlight the importance of an adequate choice of OVs and MMs for an effective substantiation of the claims related to cognitive functioning. The information provided in this document may serve to EFSA for updating the guidance on the scientific requirements for health claims related to cognitive functions, but also for a better design of randomized controlled trials aimed at substantiating such health claims.

Combined use of a wristband and a smartphone to reduce body weight in obese children: randomized controlled trial.

BACKGROUND: Technological instruments may help control paediatric obesity. OBJECTIVE: We tested whether a personalized programme based on the energy expenditure obtained from a wristband (WB) and the energy intake obtained from a smartphone application (APP) is superior to a standard approach at promoting weight loss. METHODS: We performed a randomized controlled trial in obese children aged 10-17 years. The experimental (EXP) and control (CTR) groups were given a low-energy diet and a prescription for physical activity. The EXP group was equipped with a WB and an APP and given personalized feedback every 7 days. The main outcome was weight loss at 3 months. RESULTS: The mean (standard deviation) z-score of body mass index at the enrollment was 2.20 (0.47) in the EXP (n = 16 out of 23) and 2.09 (0.34) in the CTR group (n = 14 out of 20) of children who completed the trial. The mean (95%CI) difference in weight loss at 3 months was 0.07 kg (95%CI: 2.81 to 2.96) for EXP vs. the CTR. CONCLUSION: A personalized lifestyle programme based on a WB and an APP was not superior to a standard lifestyle programme at promoting weight loss in obese children.

Comparison between Bilistick System and transcutaneous bilirubin in assessing total bilirubin serum concentration in jaundiced newborns.

OBJECTIVE: To compare the performance and accuracy of the JM-103 transcutaneous bilirubinometer and Bilistick System in measuring total serum bilirubin for the early identification of neonatal hyperbilirubinemia. STUDY DESIGN: The study was performed on 126 consecutive term and near-term (⩾36 weeks' gestational age) jaundiced newborns in Cairo University Children Hospital NICU, Egypt. Total serum bilirubin was assayed concurrently by the clinical laboratory and Bilistick System and estimated using the JM-103 transcutaneous bilirubin instrument. Bland-Altman analysis was used to evaluate the agreement between determinations. RESULT: The limits of agreement of the Bilistick System (-5.8 to 3.3 mg dl-1) and JM-103 system (-5.4 to 6.0 mg dl-1) versus the clinical laboratory results were similar. CONCLUSION: The Bilistick System is an accurate alternative to transcutaneous (TcB) determination for early diagnosis and proper management of the neonatal jaundice.

Claimed effects, outcome variables and methods of measurement for health claims proposed under European Community Regulation 1924/2006 in the framework of protection against oxidative damage and cardiovascular health.

BACKGROUND AND AIMS: The high number of negative opinions from the European Food Safety Authority (EFSA) to the requests for authorization of health claims is largely due to the design of human intervention studies, including the inappropriate choice of outcome variables (OVs) and of their methods of measurement (MMs). The present manuscript reports the results of an investigation aimed to collect, collate and critically analyse the information in relation to claimed effects, OVs and MMs, in the context of protection against oxidative damage and cardiovascular health compliant with Regulation 1924/2006. METHODS AND RESULTS: Claimed effects, OVs and the related MMs were collected from EFSA Guidance documents and applications for authorization of health claims under Articles 13.5 and 14. The OVs and their MMs were evaluated only if the claimed effect was sufficiently defined and was considered beneficial by EFSA. The collection, collation and critical analysis of the relevant scientific literature consisted in the definition of the keywords, the PubMed search strategies and the creation of databases of references. The critical analysis of the OVs and their MMs was performed on the basis of the literature review and was aimed at defining the appropriateness of OVs and MMs in the context of the specific claimed effects. CONCLUSIONS: The information provided in this document could serve to EFSA for the development of further guidance on the scientific requirements for health claims, as well as to the stakeholders for the proper design of human intervention studies aimed to substantiate such health claims.

Time to onset of bisphosphonate-related osteonecrosis of the jaws: a multicentre retrospective cohort study.

OBJECTIVES: Osteonecrosis of the jaw (ONJ) is a potentially severe adverse effect of bisphosphonates (BP). Although the risk of ONJ increases with increasing duration of BP treatment, there are currently no reliable estimates of the ONJ time to onset (TTO). The objective of this study was to estimate the TTO and associated risk factors in BP-treated patients. SUBJECTS AND METHODS: Retrospective analysis of data from 22 secondary care centres in seven countries relevant to 349 patients who developed BP-related ONJ between 2004 and 2012. RESULTS: The median (95%CI) TTO was 6.0 years in patients treated with alendronate (n = 88) and 2.2 years in those treated with zoledronate (n = 218). Multivariable Cox regression showed that dentoalveolar surgery was inversely associated, and the use of antiangiogenics directly associated, with the TTO in patients with cancer treated with zoledronate. CONCLUSIONS: The incidence of ONJ increases with the duration of BP therapy, with notable differences observed with respect to BP type and potency, route of administration and underlying disease. When data are stratified by BP type, a time of 6.0 and 2.2 years of oral alendronate and intravenous zoledronate therapy, respectively, is required for 50% of patients to develop ONJ. After stratification by disease, a time of 5.3 and 2.2 years of BP therapy is required for 50% of patients with osteoporosis and cancer, respectively, to develop ONJ. These findings have significant implications for the design of future clinical studies and the development of risk-reduction strategies aimed at either assessing or modulating the risk of ONJ associated with BP.

Nutritional status, metabolic state and nutrient intake in children with bronchiolitis.

Nutrition has a coadjuvant role in the management of children with acute diseases. We aimed to examine nutritional status, macronutrient requirements and actual macronutrient delivery in bronchiolitis. The nutritional status was classified according to WHO criteria and resting energy expenditure (MREE) was measured using an indirect calorimeter. Bland-Altman analysis was used to examine the agreement between MREE and estimated energy expenditure (EEE) with standard equations. Based on the ratio MREE/EEE in relation to Schofield equation on admission, we defined the subjects' metabolic status. A total of 35 patients were enrolled and 46% were malnourished on admission, and 25.8% were hypermetabolic, 37.1% hypometabolic and 37.1% normometabolic. We performed a 24-h recall in 10 children and 80% were overfed (AEI: MREE >120%). Mean bias (limits of agreement) with MREE was 8.9 (-73.9 to 91.8%) for Schofield; 61.0 (-41 to 163%) for Harris-Benedict; and 9.9 (-74.4 to 94.2%) for FAO-WHO equation. Metabolism of infants with bronchiolitis is not accurately estimated by equations.

Predictors of blood pressure at 7-13 years: The "new millennium baby" study.

BACKGROUND AND AIMS: The purpose of this study is to evaluate the association between blood pressure (BP) at 7-13 years of age and body mass index (BMI), early feeding, lifestyle indicators, and parental characteristics. METHODS AND RESULTS: Retrospective plus cross-sectional cohort study was started in 1294 children born in 2000-2004, right from their birth in primary care settings. Early feeding was estimated by measuring breast-feeding (BF) duration, complementary feeding (CF) introduction time, and lifestyle indicators such as daily screen time and weekly extracurricular sports activity time. Parental education, smoking, and obesity-related diseases were also considered. Multivariable linear regression and mediation analysis were used. CF introduction at 5-6 months of age was a negative predictor of systolic and diastolic BP (mean systolic BP-standard deviation score (SDS) -0.38 [95% CI: -0.47, -0.29] (p < 0.001); mean diastolic BP-SDS -0.32 [95% CI: -0.40, -0.24]) (p < 0.001); BMI was a positive predictor of systolic and diastolic BP (p < 0.001); and parental hypertension was a positive predictor of diastolic BP (p < 0.05). Predictors of mean BMI-SDS at 7-13 years of age were birth weight, screen time, and parental obesity and smoking (p < 0.001). BF had no effect on BP or BMI. Mediation analysis showed virtually no indication of the effect of CF on BP mediated by BMI. CONCLUSIONS: CF introduction between 5 and 6 months of age could be associated with low BP at 7-13 years. The effect of CF on BP seems to be independent of BMI. Low screen time is associated with low BMI. CF time may play a role in the occurrence of surrogates of noncommunicable disorders in future.

Does segmental body composition differ in women with Prader-Willi syndrome compared to women with essential obesity?

BACKGROUND: Subjects with Prader-Willi syndrome (PWS) have a higher fat mass and a lower fat-free mass compared to subjects with essential obesity. However, few data are presently available on the segmental body composition (BC) of PWS subjects. AIM: To evaluate whether women with PWS and women with essential obesity, matched for age and percent body fat, differ in segmental fat distribution and surrogate markers of cardiometabolic disease (CMD). SUBJECTS AND METHODS: 35 women with PWS and 50 women with essential obesity were matched for age and percent body fat using coarsened exact matching. BC was measured by dual-energy X-ray absorptiometry. Oral glucose tolerance testing and measurements of cholesterol, triglycerides, C-reactive protein, and blood pressure were performed. Comparisons between PWS and obese women were performed using generalized linear models. RESULTS: Trunk fat was lower in PWS than in obese women on both absolute [-7.3 (95% confidence interval -9.4 to -5.2) kg] and relative [-4.1 (-6.9 to -1.4)% of body fat] grounds. PWS and obese women had similar surrogate markers of CMD, with the exception of HDL-cholesterol, which was higher in PWS women. CONCLUSION: Trunk fat is lower in obese women with PWS than in those with essential obesity. Surrogate markers of CMD are, however, mostly similar in the two groups.

Early retesting by GHRH + arginine test shows normal GH response in most children with idiopathic GH deficiency.

PURPOSE: Most children with idiopathic isolated GH deficiency (IGHD) normalize GH response to stimulation tests when retested at the completion of growth. The objective of this study was to test the effectiveness of early retesting in challenging the diagnosis of idiopathic IGHD and critically review the diagnostic workup leading to this diagnosis in children with short stature. METHODS: We cross-sectionally retested 38 children with idiopathic IGHD and still on GH treatment. The initial diagnosis of idiopathic IGHD was based on subnormal GH responses to two stimulation tests and normal brain imaging or minor/nonspecific findings at magnetic resonance. The GH response normalization at retesting was considered as the main outcome measure. Clinical features of children who were falsely classified as idiopathic IGHD based on first GH testing were retrospectively analyzed. RESULTS: GH secretion was normal in 36/38 children (95%). Two children showed slightly reduced peak GH responses and normal IGF-I levels. Fourteen children underwent GH retesting before puberty, 24 children during puberty. CONCLUSION: The diagnostic process should be improved to minimize the rate of false positive at GH testing and, in case of unsatisfactory response to GH treatment, the diagnosis of isolated idiopathic GHD should be challenged with early retesting.

Randomised clinical trial: The beneficial effects of VSL#3 in obese children with non-alcoholic steatohepatitis.

BACKGROUND: Gut microbiota modifiers may have beneficial effects of non-alcoholic fatty liver disease (NAFLD) but randomised controlled trials (RCT) are lacking in children. AIM: To perform a double-blind RCT of VSL#3 vs. placebo in obese children with biopsy-proven NAFLD. METHODS: Of 48 randomised children, 44 (22 VSL#3 and 22 placebo) completed the study. The main outcome was the change in fatty liver severity at 4 months as detected by ultrasonography. Secondary outcomes were the changes in triglycerides, insulin resistance as detected by the homoeostasis model assessment (HOMA), alanine transaminase (ALT), body mass index (BMI), glucagon-like peptide 1 (GLP-1) and activated GLP-1 (aGLP-1). Ordinal and linear models with cluster confidence intervals were used to evaluate the efficacy of VSL#3 vs. placebo at 4 months. RESULTS: At baseline, moderate and severe NAFLD were present in 64% and 36% of PLA children and in 55% and 45% of VSL#3 children. The probability that children supplemented with VSL#3 had none, light, moderate or severe FL at the end of the study was 21%, 70%, 9% and 0% respectively with corresponding values of 0%, 7%, 76% and 17% for the placebo group (P < 0.001). No between-group differences were detected in triglycerides, HOMA and ALT while BMI decreased and GLP-1 and aGLP1 increased in the VSL#3 group (P < 0.001 for all comparisons). CONCLUSIONS: A 4-month supplement of VSL#3 significantly improves NAFLD in children. The VSL#3-dependent GLP-1 increase could be responsible for these beneficial effects. Trial identifier: NCT01650025 (www.clinicaltrial.gov).

Comparison of dual-energy X-ray absorptiometry, air displacement plethysmography and bioelectrical impedance analysis for the assessment of body composition in morbidly obese women.

BACKGROUND/OBJECTIVES: We evaluated the agreement of air displacement plethysmography (ADP) and bioelectrical impedance analysis (BIA) with dual-energy X-ray absorptiometry (DXA) for the assessment of percent fat mass (%FM) in morbidly obese women. SUBJECTS/METHODS: Fifty-seven women aged 19-55 years and with a body mass index (BMI) ranging from 37.3 to 55.2 kg/m(2) were studied. Values of %FM were obtained directly from ADP and DXA, whereas for BIA we estimated fat-free mass (FFM) from an equation for morbidly obese subjects and calculated %FM as (weight-FFM)/weight. RESULTS: The mean (s.d.) difference between ADP and DXA for the assessment of %FM was -2.4% (3.3%) with limits of agreement (LOA) from -8.8% to 4.1%. The mean (s.d.) difference between BIA and DXA for the assessment of %FM was 1.7% (3.3%) with LOA from -4.9% to 8.2%. CONCLUSION: ADP-DXA and BIA-DXA are not interchangeable methods for the assessment of body composition in morbidly obese women.

Waist circumference-to-height ratio predicts adiposity better than body mass index in children and adolescents.

OBJECTIVE: Body mass index (BMI) is the surrogate measure of adiposity most commonly employed in children and adults. Waist circumference (WC) and the waist circumference-to-height ratio (WCHt) have been proposed as markers of adiposity-related morbidity in children. However, no study to date has compared WCHt, WC, BMI and skinfolds thickness for their ability to detect body adiposity. AIM: To compare WCHt, WC, BMI and skinfolds for their accuracy in predicting percent body fat (PBF), percent trunk fat (PTF) and fat mass index (FMI) in a large sample of children and adolescents. DESIGN, SETTING AND PARTICIPANTS: We studied 2339 children and adolescents aged 8-18 years from the US National Health and Nutrition Examination Survey 2003/2004. Body fat was measured using dual-energy X-ray absorptiometry. Multivariable regression splines were used to model the association between PBF, PTF, FMI and the predictors of interest. RESULTS: WCHt alone explained 64% of PBF variance as compared with 31% for WC, 32% for BMI and 72% for the sum of triceps and subscapular skinfolds (SF2) (P<0.001 for all). When age and gender were added to the predictors, the explained variance increased to 80% for the WCHt model, 72% for the WC model, 68% for the BMI model and 84% for the SF2 model. There was no practical advantage to add the ethnic group as further predictor. Similar relationships were observed with PTF and FMI. CONCLUSIONS: WCHt is better than WC and BMI at predicting adiposity in children and adolescents. It can be a useful surrogate of body adiposity when skinfold measurements are not available.

Docosahexaenoic acid for the treatment of fatty liver: randomised controlled trial in children.

BACKGROUND AND AIM: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in children. We tested whether dietary supplementation with docosahexaenoic acid (DHA) can decrease liver fat content in children with NAFLD. METHODS AND RESULTS: We performed a randomized controlled trial of DHA supplementation (250 mg/day and 500 mg/day) vs. placebo in 60 children with NAFLD (20 children per group). The main outcome was the change in liver fat as detected by ultrasonography after 6, 12, 18 and 24 months of treatment. Secondary outcomes were changes in triglycerides, alanine transaminase (ALT), body mass index (BMI) and homeostasis model assessment of insulin resistance (HOMA). The odds of more severe versus less severe liver steatosis decreased to the same degree at 6 months in children treated with DHA 250 mg/day and DHA 500 mg/day vs. placebo and persisted virtually unmodified for 24 months (OR ≤ 0.02, p ≤ 0.05 for all time points). Triglycerides were lower in the DHA groups than in the placebo group at any time point and ALT was lower in these groups from month 12 onwards. HOMA was lower in the DHA 250 mg group vs. placebo at months 6 and 12. CONCLUSION: DHA supplementation improves liver steatosis in children with NAFLD. Doses of 250 mg/day and 500 mg/day of DHA appear to be equally effective in reducing liver fat content.

Metabolic syndrome in adult patients with Prader-Willi syndrome.

BACKGROUND AND AIMS: Prader-Willi syndrome (PWS), the most common genetic cause of obesity, is characterized by elevated morbility and mortality in all ages. In this context, non-obese PWS children showed low frequency of metabolic syndrome (MetS), while a comparable prevalence was observed in obese PWS and obese controls. Aim of this study was to estimate the occurrence of MetS and its components in a large group of PWS adults, according to obesity status. METHODS AND RESULTS: A cross-sectional study was performed in 108 PWS aged 18.0-43.2 years (87 obese and 21 non-obese) and in 85 controls with nonsyndromic obesity matched for age, gender, and BMI with obese PWS. Non-obese PWS showed lower waist circumference, insulin, HOMA-index, triglycerides, diastolic blood pressure, and higher HDL-C than both obese PWS and obese controls (p < 0.017). Obese PWS showed higher glucose and systolic blood pressure than both non-obese PWS and obese controls (p < 0.017). MetS was found in 1/21 (4.8%) non-obese PWS, 36/87 (41.4%) obese PWS and 39/85 (45.9%) obese controls. Non-obese PWS showed lower frequency for each MetS component as compared with obese PWS and obese controls. PWS patients with deletion of the chromosome 15q11-13 showed a lower risk for low HDL-C (p < 0.01) and a trend towards a lower MetS risk (p < 0.06) compared to subjects without deletion. CONCLUSION: Our findings suggest the main role that obesity status plays on the individual metabolic risk clustering in PWS adults. Early identification of MetS could be helpful to improve morbidity and prevent mortality in such patients.

Changes of body mass index in celiac children on a gluten-free diet.

BACKGROUND AND AIM: Studies of adults and children with celiac disease (CD) performed mostly in tertiary care centers have reported an increased risk of overweight during gluten-free diet (GFD). We measured body mass index (BMI) of CD children followed by family pediatricians in order to estimate prevalence of underweight and overweight at diagnosis and to describe BMI changes during GFD. METHODS AND RESULTS: We compared 150 CD children (age range 2-16 yrs) under GFD from a median (IQR) time of 4.4 (4.2) years with 288 healthy children matched for gender and age. We also evaluated retrospectively BMI changes between CD diagnosis and the current evaluation. The median (IQR) BMI of CD patients was significantly lower than that of controls [-0.38 (1.46) vs. 0.09 (1.18) SDS, p < 0.0001, Italian reference data]. Using the International Obesity Task Force classifications, CD children were less frequently overweight or obese (12% vs. 23.3%, p = 0.014) and more frequently underweight (16% vs. 4.5%, p < 0.001) than controls. During GFD, there was a marked decrease of number of underweight subjects (13 vs. 27) and a minimal increase of number of overweight subjects (9 vs. 6) (p < 0.001). CONCLUSIONS: The frequency of overweight and obesity at diagnosis of CD and during GFD in children followed by family pediatricians is substantially lower than that reported in tertiary care centers. On the other hand, the high frequency of underweight at diagnosis confirms the need of careful personalized nutritional management.

Early retinol-binding protein levels are associated with growth changes in infants born to diabetic mothers.

BACKGROUND: Biochemical predictors of infants' growth changes are not available. OBJECTIVES: We tested whether retinol-binding protein (RBP), docosahexaenoic acid and insulin (I) measured within 72 h from birth are associated with growth changes in infants born to mothers with gestational diabetes mellitus (GDM). METHODS: Fifty-six children, 32 born to diabetic mothers treated with insulin (GDM-I) and 24 born to diabetic mothers treated with diet (GDM-D), were evaluated at 0, 1, 3, 6 and 12 months of life. RESULTS: At multivariable regression performed using generalized estimating equations, early RBP levels and maternal body mass index were associated to average weight changes and early RBP and insulin levels to average length changes, respectively. There was no difference between GDM-I and GDM-D infants. CONCLUSIONS: This exploratory study suggests that early RBP levels may be a predictor of growth changes.

The potential role of fatty liver in paediatric metabolic syndrome: a distinct phenotype with high metabolic risk?

BACKGROUND: The prevalence of obesity and its metabolic consequences has dramatically increased in the last two decades urging physicians to find a reliable definition for early detection, treatment and possibly prevention of metabolic syndrome (MS). MS could be diagnosed in adult patients in the presence of a large waist circumference and ≥2 of the following features: high serum triglycerides, low serum high-density lipoprotein cholesterol, high blood pressure and high fasting glucose. The definition of MS in children is more problematic, and the potential role of its single components on metabolic risk remains largely undefined. Recent evidence strongly suggests not only a relationship between non-alcoholic fatty liver disease (NAFLD) and MS in obese children, adolescents and adults, but also the key role exerted by liver fat deposition in the pathogenesis of MS. CONCLUSION: We propose that NAFLD should be routinely checked in obese subjects because early lifestyle changes may be effective in reducing the overall risk of MS.