Body mass index and risk of head and neck cancer in a pooled analysis of case-control studies in the International Head and Neck Cancer Epidemiology (INHANCE) Consortium.

BACKGROUND: Head and neck cancer (HNC) risk is elevated among lean people and reduced among overweight or obese people in some studies; however, it is unknown whether these associations differ for certain subgroups or are influenced by residual confounding from the effects of alcohol and tobacco use or by other sources of biases. METHODS: We pooled data from 17 case-control studies including 12 716 cases and the 17 438 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for associations between body mass index (BMI) at different ages and HNC risk, adjusted for age, sex, centre, race, education, tobacco smoking and alcohol consumption. RESULTS: Adjusted ORs (95% CIs) were elevated for people with BMI at reference (date of diagnosis for cases and date of selection for controls) 25.0-30.0 kg/m(2) (0.52, 0.44-0.60) and BMI >/=30 kg/m(2) (0.43, 0.33-0.57), compared with BMI >18.5-25.0 kg/m(2). These associations did not differ by age, sex, tumour site or control source. Although the increased risk among people with BMI 25 kg/m(2) was present only in smokers and drinkers. CONCLUSIONS: In our large pooled analysis, leanness was associated with increased HNC risk regardless of smoking and drinking status, although reverse causality cannot be excluded. The reduced risk among overweight or obese people may indicate body size is a modifier of the risk associated with smoking and drinking. Further clarification may be provided by analyses of prospective cohort and mechanistic studies.

Functional analysis of a missense mutation in the serine protease inhibitor SPINT2 associated with congenital sodium diarrhea.

Membrane-bound serine proteases play important roles in different biological processes. Their regulation by endogenous inhibitors is poorly understood. A Y163C mutation in the SPINT2 gene encoding the serine protease inhibitor Hepatocyte Growth Factor Inhibitor HAI-2 is associated with a congenital sodium diarrhea. The functional consequences of this mutation on HAI-2 activity and its physiological targets are unknown. We established a cellular assay in Xenopus laevis oocytes to study functional interactions between HAI-2 and candidate membrane-bound serine proteases expressed in the gastro-intestinal tract. We found that the wild-type form of HAI-2 is a potent inhibitor of nine gastro-intestinal serine proteases. The Y163C mutation in the second Kunitz domain of HAI-2 resulted in a complete loss of inhibitory activity on two intestinal proteases, prostasin and tmprss13. The effect of the mutation of the homologous Y68C in the first Kunitz domain of HAI-2 is consistent with a differential contribution of the two Kunitz domains of HAI-2 in the inhibition of serine proteases. By contrast to the Tyr to Cys, the Tyr to Ser substitution did not change the inhibitory potency of HAI-2, indicating that the thiol-group of the cysteine rather than the Tyr deletion is responsible for the HAI-2 loss of function. Our functional assay allowed us to identify membrane-bound serine proteases as cellular target for inhibition by HAI-2 wild type and mutants, and to better define the role of the Tyr in the second Kunitz domain in the inhibitory activity of HAI-2.

Role of fat oxidation in the long-term stabilization of body weight in obese women.

Two studies were performed to investigate the association between body fat mass and fat oxidation. The first, a cross-sectional study of 106 obese women maintaining stable body weight, showed that these two variables were significantly correlated (r = 0.56, P less than 0.001) and the regression coefficient indicated that a 10-kg change in fat mass corresponded to a change in fat oxidation of approximately 20 g/d. The second, a prospective study, validated this estimate and quantifies the long-term adaptations in fat oxidation resulting from body fat loss. Twenty-four moderately obese women were studied under controlled dietary conditions at stable weight before and after mean weight and fat losses of 12.7 and 9.8 kg, respectively. The reduction in fat oxidation was identical to that predicted by the above regression. We conclude that changes in fat mass significantly affect fat oxidation and that this process may contribute to the long-term regulation of fat and energy balance in obese individuals.

Use of constant denaturant capillary electrophoresis of pooled blood samples to identify single-nucleotide polymorphisms in the genes (Scnn1a and Scnn1b) encoding the alpha and beta subunits of the epithelial sodium channel.

BACKGROUND: The epithelial sodium channel (ENaC) is composed of three homologous subunits: alpha, beta, and gamma. Mutations in the Scnn1b and Scnn1g genes, which encode the beta and the gamma subunits of ENaC, cause a severe form of hypertension (Liddle syndrome). The contribution of genetic variants within the Scnn1a gene, which codes for the alpha subunit, has not been investigated. METHODS: We screened for mutations in the COOH termini of the alpha and beta subunits of ENaC. Blood from 184 individuals from 31 families participating in a study on the genetics of hypertension were analyzed. Exons 13 of Scnn1a and Scnn1b, which encode the second transmembrane segment and the COOH termini of alpha- and beta-ENaC, respectively, were amplified from pooled DNA samples of members of each family by PCR. Constant denaturant capillary electrophoresis (CDCE) was used to detect mutations in PCR products of the pooled DNA samples. RESULTS: The detection limit of CDCE for ENaC variants was 1%, indicating that all members of any family or up to 100 individuals can be analyzed in one CDCE run. CDCE profiles of the COOH terminus of alpha-ENaC in pooled family members showed that the 31 families belonged to four groups and identified families with genetic variants. Using this approach, we analyzed 31 rather than 184 samples. Individual CDCE analysis of members from families with different pooled CDCE profiles revealed five genotypes containing 1853G-->T and 1987A-->G polymorphisms. The presence of the mutations was confirmed by DNA sequencing. For the COOH terminus of beta-ENaC, only one family showed a different CDCE profile. Two members of this family (n = 5) were heterozygous at 1781C-->T (T594M). CONCLUSION: CDCE rapidly detects point mutations in these candidate disease genes.

Drumming in immersive virtual reality: the body shapes the way we play

It has been shown that it is possible to generate perceptual illusions of ownership in immersive virtual reality (IVR) over a virtual body seen from first person perspective, in other words over a body that visually substitutes the person's real body. This can occur even when the virtual body is quite different in appearance from the person's real body. However, investigation of the psychological, behavioral and attitudinal consequences of such body transformations remains an interesting problem with much to be discovered. Thirty six Caucasian people participated in a between-groups experiment where they played a West-African Djembe hand drum while immersed in IVR and with a virtual body that substituted their own. The virtual hand drum was registered with a physical drum. They were alongside a virtual character that played a drum in a supporting, accompanying role. In a baseline condition participants were represented only by plainly shaded white hands, so that they were able merely to play. In the experimental condition they were represented either by a casually dressed dark-skinned virtual body (Casual Dark-Skinned - CD) or by a formal suited light-skinned body (Formal Light-Skinned - FL). Although participants of both groups experienced a strong body ownership illusion towards the virtual body, only those with the CD representation showed significant increases in their movement patterns for drumming compared to the baseline condition and compared with those embodied in the FL body. Moreover, the stronger the illusion of body ownership in the CD condition, the greater this behavioral change. A path analysis showed that the observed behavioral changes were a function of the strength of the illusion of body ownership towards the virtual body and its perceived appropriateness for the drumming task. These results demonstrate that full body ownership illusions can lead to substantial behavioral and possibly cognitive changes depending on the appearance of the virtual body. This could be important for many applications such as learning, education, training, psychotherapy and rehabilitation using IVR.

5C.09: Heritability of renal function parameters and electrolyte levels in the Swiss population

OBJECTIVE: Electrolytes handling by the kidney is essential for volume and blood pressure (BP) homeostasis but their distribution and heritability are not well described. We estimated the heritability of kidney function as well as of serum and urine concentrations, renal clearances and fractional excretions for sodium, chloride, potassium, calcium, phosphate and magnesium in a Swiss population-based study. DESIGN AND METHOD: Nuclear families were randomly selected from the general population in Switzerland. We estimated glomerular filtration rate (eGFR) using the CKD-EPI and MDRD equations. Urine was collected separately during day and night over 24-hour. We used the ASSOC program (S.A.G.E.) to estimate narrow sense heritability, including as covariates in the model: age, sex, body mass index and study center. RESULTS: The 1128 participants (537 men and 591 women from 273 families), had mean (sd) age of 47.4(17.5) years, body mass index of 25.0 (4.5) kg/m2 and CKD-EPI of 98.0(18.5) mL/min/1.73 m2. Heritability estimates (SE) were 46.0% (0.06), 48.0% (0.06) and 18.0% (0.06) for CKD-EPI, MDRD and 24-hour creatinine clearance (P < 0.05), respectively. Heritability [SE] of serum concentration was highest for calcium (37%[0.06]) and lowest for sodium (13%[0.05]). Heritabilities [SE] of 24-h urine concentrations and excretions, and of fractional excretions were highest for calcium (51%[0.06], 44%[0.06] and 51%[0.06], respectively) and lowest for potassium (11%[0.05], 10%[0.05] and 16%[0.06], respectively). All results were statistically different from zero.(Figure is included in full-text article.) CONCLUSIONS: : Serum and urine levels, urinary excretions and renal handling of electrolytes, particularly calcium, are heritable in the general adult population. Identifying genetic variants involved in electrolytes homeostasis may provide useful insight into the pathophysiological mechanisms involved in common chronic diseases such as kidney diseases, hypertension and diabetes.

Validity of silhouette showcards as a measure of body size and obesity in a population in the African region : a practical research tool for general-purpose surveys.

BACKGROUND: The purpose of this study is to validate the Pulvers silhouette showcard as a measure of weight status in a population in the African region. This tool is particularly beneficial when scarce resources do not allow for direct anthropometric measurements due to limited survey time or lack of measurement technology in face-to-face general-purpose surveys or in mailed, online, or mobile device-based surveys. METHODS: A cross-sectional study was conducted in the Republic of Seychelles with a sample of 1240 adults. We compared self-reported body sizes measured by Pulvers' silhouette showcards to four measurements of body size and adiposity: body mass index (BMI), body fat percent measured, waist circumference, and waist to height ratio. The accuracy of silhouettes as an obesity indicator was examined using sex-specific receiver operator curve (ROC) analysis and the reliability of this tool to detect socioeconomic gradients in obesity was compared to BMI-based measurements. RESULTS: Our study supports silhouette body size showcards as a valid and reliable survey tool to measure self-reported body size and adiposity in an African population. The mean correlation coefficients of self-reported silhouettes with measured BMI were 0.80 in men and 0.81 in women (P < 0.001). The silhouette showcards also showed high accuracy for detecting obesity as per a BMI ≥ 30 (Area under curve, AUC: 0.91/0.89, SE: 0.01), which was comparable to other measured adiposity indicators: fat percent (AUC: 0.94/0.94, SE: 0.01), waist circumference (AUC: 0.95/0.94, SE: 0.01), and waist to height ratio (AUC: 0.95/0.94, SE: 0.01) amongst men and women, respectively. The use of silhouettes in detecting obesity differences among different socioeconomic groups resulted in similar magnitude, direction, and significance of association between obesity and socioeconomic status as when using measured BMI. CONCLUSIONS: This study highlights the validity and reliability of silhouettes as a survey tool for measuring obesity in a population in the African region. The ease of use and cost-effectiveness of this tool makes it an attractive alternative to measured BMI in the design of non-face-to-face online- or mobile device-based surveys as well as in-person general-purpose surveys of obesity in social sciences, where limited resources do not allow for direct anthropometric measurements.

Bidirectional relationship between the Body Mass Index and Substance Use in Young Men

BACKGROUND: Obesity and substance use are major concern in young people. This study explored the bidirectional longitudinal relationships between the body mass index (BMI) of young men and their use of: 1) four classes of non-medical prescription drugs; 2) alcohol; 3) tobacco; and 4) cannabis. METHODS: Baseline and follow-up data from the Cohort Study on Substance Use Risk Factors were used (n=5,007). A cross-lagged panel model, complemented by probit models as sensitivity analysis, was run to determine the bidirectional relationships between BMI and substance use. Alcohol was assessed using risky single-occasion drinking (RSOD); tobacco, using daily smoking; and cannabis, using hazardous cannabis use (defined as twice-weekly or more cannabis use). Non-medical prescription drugs use (NMPDU) included opioid analgesics, sedatives/sleeping pills, anxiolytics and stimulants. RESULTS: Different associations were found between BMI and substance use. Only RSOD (β= -.053, p=.005) and NMPDU of anxiolytics (β=.040, p=.020) at baseline significantly predicted BMI at follow-up. Baseline RSOD predicted a lower BMI at follow-up while baseline NMPDU of anxiolytics predicted higher BMI at follow-up. Furthermore, BMI at baseline significantly predicted daily smoking (β=.050, p=.007) and hazardous cannabis use (β=.058, p=.030). CONCLUSIONS: Our results suggest different associations between BMI and the use of various substances by young men. However, only RSOD and NMPDU of anxiolytics predicted BMI, whereas BMI predicted daily smoking and hazardous cannabis use.

Whole-body magnetic resonance imaging in children: state of the art

Whole-body imaging in children was classically performed with radiography, positron-emission tomography, either combined or not with computed tomography, the latter with the disadvantage of exposure to ionizing radiation. Whole-body magnetic resonance imaging (MRI), in association with the recently developed metabolic and functional techniques such as diffusion-weighted imaging, has brought the advantage of a comprehensive evaluation of pediatric patients without the risks inherent to ionizing radiation usually present in other conventional imaging methods. It is a rapid and sensitive method, particularly in pediatrics, for detecting and monitoring multifocal lesions in the body as a whole. In pediatrics, it is utilized for both oncologic and non-oncologic indications such as screening and diagnosis of tumors in patients with genetic syndromes, evaluation of disease extent and staging, evaluation of therapeutic response and post-therapy follow-up, evaluation of non neoplastic diseases such as multifocal osteomyelitis, vascular malformations and syndromes affecting multiple regions of the body. The present review was aimed at describing the major indications of whole-body MRI in pediatrics added of technical considerations.

Ideal Body Size as a Mediator for the Gender-Specific Association Between Socioeconomic Status and Body Mass Index: Evidence From an Upper-Middle-Income Country in the African Region.

While obesity continues to rise globally, the associations between body size, gender, and socioeconomic status (SES) seem to vary in different populations, and little is known on the contribution of perceived ideal body size in the social disparity of obesity in African countries. We examined the gender and socioeconomic patterns of body mass index (BMI) and perceived ideal body size in the Seychelles, a middle-income small island state in the African region. We also assessed the potential role of perceived ideal body size as a mediator for the gender-specific association between SES and BMI. A population-based survey of 1,240 adults aged 25 to 64 years conducted in December 2013. Participants' BMI was calculated based on measured weight and height; ideal body size was assessed using a nine-silhouette instrument. Three SES indicators were considered: income, education, and occupation. BMI and perceived ideal body size were both higher among men of higher versus lower SES (p< .001) but lower among women of higher versus lower SES (p< .001), irrespective of the SES indicator used. Multivariate analysis showed a strong and direct association between perceived ideal body size and BMI in both men and women (p< .001) and was consistent with a potential mediating role of perceived ideal body size in the gender-specific associations between SES and BMI. Our study emphasizes the importance of gender and socioeconomic differences in BMI and ideal body size and suggests that public health interventions that promote perception of healthy weight could help mitigate SES-related disparities in BMI.