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1.  Genetic and Molecular Insights Into the Role of PROX1 in Glucose Metabolism 
Diabetes  2013;62(5):1738-1745.
Genome-wide association studies have shown that the rs340874 single nucleotide polymorphism (SNP) in PROX1 is a genetic susceptibility factor for type 2 diabetes. We conducted genetic and molecular studies to better understand the role of PROX1 in type 2 diabetes. We assessed the impact of the whole common genetic variability of PROX1 (80 SNPs) on type 2 diabetes–related biochemical traits in the HELENA (Healthy Lifestyle in Europe by Nutrition in Adolescence) study (n = 1,155). Three SNPs (rs340838, rs340837, and rs340836) were significantly associated with fasting plasma insulin levels (P ≤ 0.00295). We evaluated the impact of nine PROX1 SNPs (the three insulin-associated SNPs plus six SNPs in strong linkage disequilibrium) on luciferase reporter gene expression. The insulin-lowering alleles of rs340874, rs340873, and rs340835 were associated with lower luciferase activity in MIN6 and HepG2 cells (except for rs340874, which was in HepG2 cells only). Electrophoretic mobility shift assays indicated that specific nuclear protein bindings occur at the three SNPs in HepG2 cells, with allele-binding differences for rs340874. We also showed that the knockdown of Prox1 expression by small interfering RNAs in INS-1E cells resulted in a 1.7-fold reduction in glucose-stimulated insulin secretion. All together, we propose that reduced expression of PROX1 by cis-regulatory variants results in altered β-cell insulin secretion and thereby confers susceptibility to type 2 diabetes.
doi:10.2337/db12-0864
PMCID: PMC3636631  PMID: 23274905
2.  Effect of child health status on parents’ allowing children to participate in pediatric research 
BMC Medical Ethics  2013;14:7.
Background
To identify motivational factors linked to child health status that affected the likelihood of parents’ allowing their child to participate in pediatric research.
Methods
Parents were invited to return their completed questionnaires anonymously to assess motivational factors and factors that might improve participation in pediatric research.
Results
Of 573 eligible parents, 261 returned the completed questionnaires. Of these, 126 were parents of healthy children (group 1), whereas 135 were parents of sick children who were divided into two groups according to the severity of their pathology, i.e., 99 ambulatory children (group 2) and 36 nonambulatory children (group 3). The main factor motivating participation in a pediatric clinical research study was “direct benefits for their child” (87.7%, 100%, and 100% for groups 1, 2, and 3, respectively). The other factors differed significantly between the three groups, depending on the child’s health status (all p < 0.05). Factors that might have a positive impact on parental consent to the participation of their child in a pediatric clinical research study differed significantly (χ2 test, all p ≤ 0.04), depending on the child’s health status. The main factor was “a better understanding of the study and its regulation” for the healthy children and ambulatory sick children groups (31.2% and 82.1%, respectively), whereas this was the third factor for the nonambulatory sick children group (50%).
Conclusions
Innovative strategies should be developed based on a child’s health status to improve information provision when seeking a child’s participation in pediatric research. Parents would like to spend more time in discussions with investigators.
doi:10.1186/1472-6939-14-7
PMCID: PMC3582492  PMID: 23414421
Ethics; Pediatric research; Parents’ acceptance; Motivation
3.  Validation of the Vivago Wrist-Worn accelerometer in the assessment of physical activity 
BMC Public Health  2012;12:690.
Background
Most accelerometers are worn around the waist (hip or lower back) to assess habitual physical activity. Wrist-worn accelerometers may be an alternative to the waist-worn monitors and may improve compliance in studies with prolonged wear. The aim of this study was to validate the Vivago® Wrist-Worn Accelerometer at various intensities of physical activity (PA) in adults.
Methods
Twenty-one healthy adults aged 20–34 years were recruited for the study. Accelerometer data and oxygen uptake (VO2) were measured at sedentary, light, moderate and vigorous levels of PA.
Results
Activity categories and accelerometer counts were: sedentary, 0–15 counts·min−1; light, 16–40 counts·min−1; moderate, 41–85 counts·min−1; and vigorous activity, >; 85 counts·min−1. ANOVA repeated measures was used to determine the relationship between accelerometry data output and oxygen consumption (r = .89; p <; .001). The Bland and Altman method showed good agreement in the assessment of energy expenditure between the indirect calorimetry and the data obtained by the accelerometer.
Conclusions
Results of the study suggest that the Vivago® wrist-worn accelerometer is a valid measure of PA at varying levels of intensity. The study has also defined threshold values at 4 intensities and hence te Vivago® accelerometer may be used to quantify PA in free living conditions among adults. This device has possible application in treating a variety of important health concerns.
doi:10.1186/1471-2458-12-690
PMCID: PMC3495030  PMID: 22913286
Cut-off; Accelerometry; Exercise; Validation; Calibration
4.  Main characteristics and participation rate of European adolescents included in the HELENA study 
Archives of Public Health  2012;70(1):14.
Background
Participation rate and response rate are key issues in a cross sectional large-scale epidemiological study. The objective of this paper is to describe the study population and to evaluate participation and response rate as well as the key nutritional status variables in male and female adolescents involved in the HELENA study.
Methods
A multi-stage random cluster sampling with a target sample of 3000 adolescents aged [12.5 to 17.5] years, stratified for geographical location and age, was carried out. Information for participants and non-participants (NP) was compared, and participation and response rates to specific questionnaires were discussed.
Results
3,865 adolescents aged [12.5 to 17.5] years (1,845 females) participated in the HELENA study, of whom 1,076 (568 females) participated in the blood sampling. 3,528 (1,845 females) adolescents were finally kept for statistical analysis. Participation rates for the schools and classes differed importantly between countries. The participation rate of pupils within the participating classes also differed importantly between countries. Sex ratio, mean age and BMI were similar between NP and participating adolescents within each centre, and in the overall sample. For all the questionnaires included in the database, the response rate of questionnaires was high (more than 80% of questions were completed).
Conclusion
From this study it could be concluded that participation rate differed importantly between countries, though no bias could be identified when comparing the key study variables between participants and non-participants. Response rate for questionnaires was very high. Future studies investigating lifestyle and health in adolescents can optimize their methods when considering the opportunities and barriers observed in the HELENA study.
doi:10.1186/0778-7367-70-14
PMCID: PMC3490738  PMID: 22958310
5.  A conative educational model for an intervention program in obese youth 
BMC Public Health  2012;12:416.
Background
Obesity in children has increased in recent years throughout the world and is associated with adverse health consequences. Early interventions, including appropriate pedagogy strategies, are important for a successful intervention program. The aim of this study was to assess changes in body mass index, the ability to perform sport activities, behavior in the classroom and academic performance following one year of a health-wellness intervention program in obese youth.
Methods
The CEMHaVi program included 37 obese children (19 girls and 18 boys). Participants received an intervention program consisting of physical activity and health education. Assessment included body mass index, academic performance, classroom performance and ability to perform sport activities. Paired t tests were used to assess the effects of intervention, and chi square was used to assess inter-action between measures.
Results
Findings of the study suggest significant decrease in Z scores of Body Mass Index and an improvement of academic performance, classroom behavior and the ability to perform sport activities (p < 0.05). Chi square testing showed significant positive inter-actions between body mass index, classroom behavior and academic performance.
Conclusions
Results following year one of CEMHaVi showed that a program of physical activity and health education had positive effects on obesity, behavior in the classroom and the ability to perform sport activities in obese adolescents. Significant inter-action in changes between variables was observed. Findings are important for designing intervention models to improve health in obese youth.
doi:10.1186/1471-2458-12-416
PMCID: PMC3403991  PMID: 22676244
Obesity; Physical activity; Intervention strategy
6.  Comparison of two ActiGraph accelerometer generations in the assessment of physical activity in free living conditions 
BMC Research Notes  2012;5:187.
Background
The aim of this study was to compare physical activity measured using GT1M ActiGraph and GT3X ActiGraph accelerometers in free living conditions.
Findings
Twenty-five adults wore GT1M and GT3X Actigraph accelerometers simultaneously during a typical weekday of activity. Data were uploaded from the monitor to a computer at the end of test (one day). Previously established thresholds were used for defining time spent at each level of physical activity, physical activity was assessed at varying intensities comparing data from the two accelerometers by ANOVA and Bland and Altman statistical analysis. The concordance correlation coefficient between accelerometers at each intensity level was 0.99. There were no significant differences between accelerometers at any of the activity levels. Differences between data obtained in minutes with the GT1M accelerometer and the GT3X monitor were to 0.56, 0.36, 0.52 and 0.44% for sedentary, light, moderate and vigorous, respectively. The Bland and Altman method showed good agreement between data obtained for the two accelerometers.
Conclusions
Findings suggest that the two accelerometers provided similar results and therefore the GT3X may be used in clinical and epidemiological studies without additional calibration or validation studies.
doi:10.1186/1756-0500-5-187
PMCID: PMC3477007  PMID: 22534207
Accelerometry; Physical activity; Assessment; Equivalence
7.  Comparison of uniaxial and triaxial accelerometry in the assessment of physical activity among adolescents under free-living conditions: the HELENA study 
Background
Different types of devices are available and the choice about which to use depends on various factors: cost, physical characteristics, performance, and the validity and intra- and interinstrument reliability. Given the large number of studies that have used uniaxial or triaxial devices, it is of interest to know whether the different devices give similar information about PA levels and patterns. The aim of this study was to compare physical activity (PA) levels and patterns obtained simultaneously by triaxial accelerometry and uniaxial accelerometry in adolescents in free-living conditions.
Methods
Sixty-two participants, aged 13-16 years, were recruited in this ancillary study, which is a part of the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA). All participants wore a uniaxial accelerometer (ActiGraph GT1M®, Pensacola, FL) and a triaxial accelerometer (RT3®, Stayhealthy, Monrovia, CA) simultaneously for 7 days. The patterns were calculated by converting accelerometer data output as a percentage of time spent at sedentary, light, moderate, and vigorous PA per day. Analysis of output data from the two accelerometers were assessed by two different tests: Equivalence Test and Bland & Altman method.
Results
The concordance correlation coefficient between the data from the triaxial accelerometer and uniaxial accelerometer at each intensity level was superior to 0.95. The ANOVA test showed a significant difference for the first three lower intensities while no significant difference was found for vigorous intensity. The difference between data obtained with the triaxial accelerometer and the uniaxial monitor never exceeded 2.1% and decreased as PA level increased. The Bland & Altman method showed good agreement between data obtained between the both accelerometers (p < 0.05).
Conclusions
Uniaxial and triaxial accelerometers do not differ in their measurement of PA in population studies, and either could be used in such studies.
doi:10.1186/1471-2288-12-26
PMCID: PMC3378459  PMID: 22409718
Accelerometers; Human locomotion; Energy expenditure; Youth
8.  Relationship between self-reported dietary intake and physical activity levels among adolescents: The HELENA study 
Background
Evidence suggests possible synergetic effects of multiple lifestyle behaviors on health risks like obesity and other health outcomes. Therefore it is important to investigate associations between dietary and physical activity behavior, the two most important lifestyle behaviors influencing our energy balance and body composition. The objective of the present study is to describe the relationship between energy, nutrient and food intake and the physical activity level among a large group of European adolescents.
Methods
The study comprised a total of 2176 adolescents (46.2% male) from ten European cities participating in the HELENA (Healthy Lifestyle in Europe by Nutrition in Adolescence) study. Dietary intake and physical activity were assessed using validated 24-h dietary recalls and self-reported questionnaires respectively. Analyses of covariance (ANCOVA) were used to compare the energy and nutrient intake and the food consumption between groups of adolescents with different physical activity levels (1st to 3rd tertile).
Results
In both sexes no differences were found in energy intake between the levels of physical activity. The most active males showed a higher intake of polysaccharides, protein, water and vitamin C and a lower intake of saccharides compared to less active males. Females with the highest physical activity level consumed more polysaccharides compared to their least active peers. Male and female adolescents with the highest physical activity levels, consumed more fruit and milk products and less cheese compared to the least active adolescents. The most active males showed higher intakes of vegetables and meat, fish, eggs, meat substitutes and vegetarian products compared to the least active ones. The least active males reported the highest consumption of grain products and potatoes. Within the female group, significantly lower intakes of bread and cereal products and spreads were found for those reporting to spend most time in moderate to vigorous physical activity. The consumption of foods from the remaining food groups, did not differ between the physical activity levels in both sexes.
Conclusion
It can be concluded that dietary habits diverge between adolescents with different self-reported physical activity levels. For some food groups a difference in intake could be found, which were reflected in differences in some nutrient intakes. It can also be concluded that physically active adolescents are not always inclined to eat healthier diets than their less active peers.
doi:10.1186/1479-5868-8-8
PMCID: PMC3045277  PMID: 21294914
9.  Breast-Feeding Modulates the Influence of the Peroxisome Proliferator–Activated Receptor-γ (PPARG2) Pro12Ala Polymorphism on Adiposity in Adolescents 
Diabetes Care  2009;33(1):190-196.
OBJECTIVE
The peroxisome proliferator–activated receptor-γ2 (PPARG2) Pro12Ala polymorphism has been associated with a higher BMI and a lower risk of type 2 diabetes in adulthood. The association between adiposity and PPARG variants can be influenced by environmental factors such as early growth, dietary fat, and (as recently shown) breast-feeding. The objectives of this study were to assess 1) the influence of the PPARG2 Pro12Ala polymorphism on adiposity markers in adolescents and 2) a possible modulating effect of breast-feeding on these associations.
RESEARCH DESIGN AND METHODS
Data on breast-feeding duration, BMI, and genotypes for the Pro12Ala polymorphism were available for 945 adolescents (mean age 14.7 years). The breast-feeding duration was obtained from parental records. We measured weight, height, waist circumference, and six skinfold thicknesses.
RESULTS
No significant associations between the Pro12Ala polymorphism and any of the above-mentioned anthropometric parameters were found. There were significant interactions between the PPARG2 Pro12Ala polymorphism and breast-feeding with regard to adiposity measurements (all adjusted P < 0.05). Indeed, in children who had not been breast-fed, Ala12 allele carriers had higher adiposity parameters (e.g., Δ BMI +1.88 kg/m2, adjusted for age, sex, and center, P = 0.007) than Pro12Pro adolescents. In contrast, in breast-fed subjects, there was no significant difference between Ala12 allele carriers and Pro12Pro children in terms of adiposity measurements, whatever the duration of breast-feeding.
CONCLUSIONS
Breast-feeding appears to counter the deleterious effect of the PPARG2 Pro12Ala polymorphism on anthropometric parameters in adolescents.
doi:10.2337/dc09-1459
PMCID: PMC2797971  PMID: 19846795
10.  Dietary n-3 fatty acids have suppressive effects on mucin upregulation in mice infected with Pseudomonas aeruginosa 
Respiratory Research  2007;8(1):39.
Background
Mucin hypersecretion and mucus plugging in the airways are characteristic features of chronic respiratory diseases like cystic fibrosis (CF) and contribute to morbidity and mortality. In CF, Pseudomonas aeruginosa superinfections in the lung exacerbate inflammation and alter mucus properties. There is increasing evidence that n-3 polyunsaturated fatty acids (PUFAs) exhibit anti-inflammatory properties in many inflammatory diseases while n-6 PUFA arachidonic acid (AA) favors inflammatory mediators such as eicosanoids prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) that may enhance inflammatory reactions. This suggests that n-3 PUFAs may have a protective effect against mucus over-production in airway diseases. Therefore, we hypothesized that n-3 PUFAs may downregulate mucins expression.
Methods
We designed an absolute real-time PCR assay to assess the effect of a 5-week diet enriched either with n-3 or n-6 PUFAs on the expression of large mucins in the lungs of mice infected by P. aeruginosa.
Results
Dietary fatty acids did not influence mucin gene expression in healthy mice. Lung infection induced an increase of the secreted gel-forming mucin Muc5b and a decrease of the membrane bound mucin Muc4. These deregulations are modulated by dietary fatty acids with a suppressive effect of n-3 PUFAs on mucin (increase of Muc5b from 19-fold up to 3.6 × 105-fold for the n-3 PUFAs treated group and the control groups, respectively, 4 days post-infection and decrease of Muc4 from 15-fold up to 3.2 × 104-fold for the control and the n-3 PUFAs treated groups, respectively, 4 days post-infection).
Conclusion
Our data suggest that n-3 PUFAs enriched diet represents an inexpensive strategy to prevent or treat mucin overproduction in pulmonary bacterial colonization.
doi:10.1186/1465-9921-8-39
PMCID: PMC1899493  PMID: 17550583

Results 1-10 (10)