Anthropometric risk factors for ovarian cancer in the NIH-AARP Diet and Health Study.

OBJECTIVE: Identifying potentially modifiable risk factors for ovarian cancer is essential for prevention because this cancer is predominantly detected at a late stage. Here, we estimated the relations of general adiposity and measures reflecting body fat distribution to the risk of epithelial ovarian cancer. METHODS: We ascertained 683 ovarian epithelial cancers (343 high-grade serous, 141 non-high grade serous) among 145,575 women, aged 50-72 years (median follow-up 12.6 years), from the National Institutes of Health-American Association of Retired Persons (NIH-AARP) Diet and Health Study. Using Cox models, we estimated confounder-adjusted hazard ratios (HRs) and 95% confidence intervals (CI) for associations of overall ovarian cancer, high-grade serous and non-high-grade serous carcinoma with body mass index, waist circumference, hip circumference, waist-hip ratio, waist-height ratio, body adiposity index, body shape index, and abdominal volume index. RESULTS: Anthropometric measures were unrelated to overall ovarian cancer, high-grade serous cancer, and non-high-grade serous cancer. For example, the HR for overall ovarian cancer per standard deviation increment of body mass index at baseline was 0.98 (95% CI 0.88-1.10). Similar associations were observed with measurements of body fat distribution. CONCLUSION: These results do not indicate that adult adiposity is associated with ovarian cancer risk in post-menopausal women.

Visceral adipose tissue but not subcutaneous adipose tissue is associated with urine and serum metabolites.

Obesity is a complex multifactorial phenotype that influences several metabolic pathways. Yet, few studies have examined the relations of different body fat compartments to urinary and serum metabolites. Anthropometric phenotypes (visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), the ratio between VAT and SAT (VSR), body mass index (BMI), waist circumference (WC)) and urinary and serum metabolite concentrations measured by nuclear magnetic resonance spectroscopy were measured in a population-based sample of 228 healthy adults. Multivariable linear and logistic regression models, corrected for multiple testing using the false discovery rate, were used to associate anthropometric phenotypes with metabolites. We adjusted for potential confounding variables: age, sex, smoking, physical activity, menopausal status, estimated glomerular filtration rate (eGFR), urinary glucose, and fasting status. In a fully adjusted logistic regression model dichotomized for the absence or presence of quantifiable metabolite amounts, VAT, BMI and WC were inversely related to urinary choline (ß = -0.18, p = 2.73*10-3), glycolic acid (ß = -0.20, 0.02), and guanidinoacetic acid (ß = -0.12, p = 0.04), and positively related to ethanolamine (ß = 0.18, p = 0.02) and dimethylamine (ß = 0.32, p = 0.02). BMI and WC were additionally inversely related to urinary glutamine and lactic acid. Moreover, WC was inversely associated with the detection of serine. VAT, but none of the other anthropometric parameters, was related to serum essential amino acids, such as valine, isoleucine, and phenylalanine among men. Compared to other adiposity measures, VAT demonstrated the strongest and most significant relations to urinary and serum metabolites. The distinct relations of VAT, SAT, VSR, BMI, and WC to metabolites emphasize the importance of accurately differentiating between body fat compartments when evaluating the potential role of metabolic regulation in the development of obesity-related diseases, such as insulin resistance, type 2 diabetes, and cardiovascular disease.

Evaluation of dilution and normalization strategies to correct for urinary output in HPLC-HRTOFMS metabolomics.

Reliable identification of features distinguishing biological groups of interest in urinary metabolite fingerprints requires the control of total metabolite abundance, which may vary significantly as the kidneys adjust the excretion of water and solutes to meet the homeostatic needs of the body. Failure to account for such variation may lead to misclassification and accumulation of missing data in case of less concentrated urine specimens. Here, different pre- and post-acquisition methods of normalization were compared systematically for their ability to recover features from liquid chromatography-mass spectrometry metabolite fingerprints of urine that allow distinction between patients with chronic kidney disease and healthy controls. Methods of normalization that were employed prior to analysis included dilution of urine specimens to either a fixed creatinine concentration or osmolality value. Post-acquisition normalization methods applied to chromatograms of 1:4 diluted urine specimens comprised normalization to creatinine, osmolality, and sum of all integrals. Dilution of urine specimens to a fixed creatinine concentration resulted not only in the least number of missing values, but it was also the only method allowing the unambiguous classification of urine specimens from healthy and diseased individuals. The robustness of classification could be confirmed for two independent patient cohorts of chronic kidney disease patients and yielded a shared set of 49 discriminant metabolite features. Graphical Abstract Dilution to a uniform creatinine concentration across urine specimens yields more comparable urinary metabolite fingerprints.

Relations of Visceral and Abdominal Subcutaneous Adipose Tissue, Body Mass Index, and Waist Circumference to Serum Concentrations of Parameters of Chronic Inflammation.

BACKGROUND: Different measures of body fat composition may vary in their relations to parameters of chronic inflammation. METHODS: We assessed the relations of visceral (VAT) and subcutaneous adipose tissue (SAT), BMI, and waist circumference (WC) to serum concentrations of high-sensitive C-reactive protein (hs-CRP), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), resistin, and adiponectin in 97 healthy adults using multivariate linear regression models, adjusted for age, sex, smoking, physical activity, menopausal status, and use of aspirin or non-steroidal anti-inflammatory drugs (NSAIDs). Parameters of chronic inflammation were mutually adjusted. RESULTS: VAT (ß = 0.34), SAT (ß = 0.43), BMI (ß = 0.40), and WC (ß = 0.47) were all significantly associated with hs-CRP. BMI was additionally inversely related to adiponectin (ß = -0.29). In exploratory subgroup analyses defined by gender, BMI, smoking, and use of aspirin or NSAIDs, VAT was the strongest indicator for increased levels of IL-6, SAT was the most consistent indicator for increased levels of hs-CRP, and BMI was the most consistent indicator for decreased levels of adiponectin. WC showed to be a weak indicator for increased levels of hs-CRP and decreased levels of adiponectin. CONCLUSION: VAT, SAT, BMI, and WC show distinct associations with parameters of chronic inflammation. Whether these differences reflect differential metabolic risks requires clarification by longitudinal studies.

Evaluating Written Patient Information for Eczema in German: Comparing the Reliability of Two Instruments, DISCERN and EQIP.

Patients actively seek information about how to cope with their health problems, but the quality of the information available varies. A number of instruments have been developed to assess the quality of patient information, primarily though in English. Little is known about the reliability of these instruments when applied to patient information in German. The objective of our study was to investigate and compare the reliability of two validated instruments, DISCERN and EQIP, in order to determine which of these instruments is better suited for a further study pertaining to the quality of information available to German patients with eczema. Two independent raters evaluated a random sample of 20 informational brochures in German. All the brochures addressed eczema as a disorder and/or therapy options and care. Intra-rater and inter-rater reliability were assessed by calculating intra-class correlation coefficients, agreement was tested with weighted kappas, and the correlation of the raters' scores for each instrument was measured with Pearson's correlation coefficient. DISCERN demonstrated substantial intra- and inter-rater reliability. It also showed slightly better agreement than EQIP. There was a strong correlation of the raters' scores for both instruments. The findings of this study support the reliability of both DISCERN and EQIP. However, based on the results of the inter-rater reliability, agreement and correlation analyses, we consider DISCERN to be the more precise tool for our project on patient information concerning the treatment and care of eczema.

Body mass index, physical activity, and risk of adult meningioma and glioma: A meta-analysis.

OBJECTIVE: Whether adiposity and lack of physical activity affect the risk for developing meningioma and glioma is poorly understood. Our objective was to characterize these associations in detail. METHODS: We conducted a systematic review and meta-analysis of adiposity and physical activity in relation to meningioma and glioma using cohort and case-control studies published through February 2015. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: We identified 12 eligible studies of body mass index (BMI) and 6 studies of physical activity, comprising up to 2,982 meningioma cases and 3,057 glioma cases. Using normal weight as the reference group, overweight (summary relative risk [RR] = 1.21, 95% confidence interval [CI] = 1.01-1.43) and obesity (RR = 1.54, 95% CI = 1.32-1.79) were associated with increased risk of meningioma. In contrast, overweight (RR = 1.06, 95% CI = 0.94-1.20) and obesity (RR = 1.11, 95% CI = 0.98-1.27) were unrelated to glioma. Similarly, dose-response meta-analyses revealed a statistically significant positive association of BMI with meningioma, but not glioma. High vs low physical activity levels showed a modest inverse relation to meningioma (RR = 0.73, 95% CI = 0.61-0.88) and a weak inverse association with glioma (RR = 0.86, 95% CI = 0.76-0.97). Relations persisted when the data were restricted to prospective studies, except for the association between physical activity and glioma, which was rendered statistically nonsignificant (RR = 0.91, 95% CI = 0.77-1.07). CONCLUSIONS: Adiposity is related to enhanced risk for meningioma but is unassociated with risk for glioma. Based on a limited body of evidence, physical activity is related to decreased risk of meningioma but shows little association with risk of glioma.

Reproducibility and validity of ultrasound for the measurement of visceral and subcutaneous adipose tissues.

BACKGROUND: Ultrasound represents a low-cost and widely available field method for assessing visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) but its measurement properties are uncertain. The aim of the current study was to examine the reproducibility and validity of ultrasound to quantify abdominal fat compartments. METHODS: In two study centers, VAT and SAT thicknesses were quantified by ultrasound two times by two observers each among 127 adults aged 20-70 years. In a separate sample of 30 adults, the ultrasound method was validated by comparing VAT and SAT thicknesses with VAT and SAT areas at vertebrae L2/L3 as obtained by a single magnetic resonance imaging (MRI) slice. RESULTS: For VAT, the intra-rater reproducibility values for observers 1 and 2 were r=0.996 (95% CI=0.994-0.997) and r=0.999 (95% CI=0.999-0.999), respectively. For SAT, the intra-rater reproducibility values were r=0.992 (95% CI=0.989-0.994) and r=0.993 (95% CI=0.990-0.995), respectively. The inter-rater reproducibility values for VAT and SAT were r=0.998 (95% CI=0.997-0.999) and r=0.990 (95% CI=0.986-0.993), respectively. For VAT and SAT, the correlation coefficients between ultrasound and MRI measurements were r=0.898 (P<0.001) and r=0.705 (P<0.001), respectively. CONCLUSION: Ultrasound provides reproducible and valid estimates of VAT and SAT and represents a useful method to assess abdominal fat in large scale epidemiologic studies.