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High muscular fitness (MF) and high adherence to the Southern European Atlantic Diet (the SEADiet) have been associated with several positive metabolic outcomes. The purpose of the present study was two-fold: (i) to explore the independent associations between MF and C-reactive protein (CRP) levels; and (ii) to investigate the combined impact of MF and SEADiet on the CRP levels in a sample of adolescents. A cross-sectional school-based study was conducted on 463 adolescents (272 girls) aged 15–18 years, from the Portuguese Azorean Archipelago. Anthropometric indicators (stature, body mass, waist circumference (WC)) were measured by standardized protocols and pubertal stages were assessed by Tanner criteria. Blood samples were taken after an overnight fast. MF was assessed by the curl-up and push-up tests (from the Fitnessgram test battery). Adherence to the SEADiet was assessed with a semi-quantitative food frequency questionnaire. Linear regression models showed that MF was inversely associated with hs-CRP (unstandardizedB = −0.127;p < .009), after adjustments for age, sex, and pubertal stage, adherence of SEADiet, total energy intake and low-energy reporter and WC. Analysis of covariance (ANCOVA) showed a significant difference between the low adherence of SEADiet with low MF group and those with a high adherence of SEADiet and high MF (p < .05) (F(5, 453) = 2.238,p = .040). Our results showed that MF is inversely associated with hs-CRP. In addition, the adolescents with Low adherence of SEADiet/Low MF group had high levels of hs-CRP compared those who with high adherence of SEADiet/high MF group. [ABSTRACT FROM AUTHOR]

The study aims to examine the individual and combined association of early life factors (birth weight, birth length, and any and exclusive breastfeeding) with attention capacity in adolescents. The study included 421 European adolescents (243 girls), aged 12.5-17.5 years, who participated in the Healthy Lifestyle in Europe by Nutrition in Adolescence Study. Body weight and length at birth of adolescents were collected from parental records. The duration of any and exclusive breastfeeding were self-reported. The d2 Test of Attention was administered to assess attention capacity. The main results showed that birth weight, birth length, breastfeeding, and exclusive breastfeeding were related to attention capacity in boys ( β ranging from 0.144 to 0.196; all p < .05) after adjustment for age, centre, gestational age, maternal education, family affluence scale, and body mass index. Among boys, differences in attention capacity were found according to tertiles of birth weight and birth length ( p < .05), as well as borderline significant differences across groups of any and exclusive breastfeeding ( p = 0.055 and p = 0.108, respectively) after adjusting for potential confounders. In addition, boys with 3 early life risk factors (low birth weight, low birth length, and <3 months of breastfeeding) had significantly lower scores in attention capacity compared with boys with 0 risk factors (percentile score − 15.88; p = 0.009). In conclusion, early life factors, both separately and combined, may influence attention capacity in male European adolescents. Importantly, the combination of the 3 early life risk factors, low birth weight, low birth length, and <3 months of breastfeeding, even in normal ranges, may provide the highest reduction in attention capacity. [ABSTRACT FROM AUTHOR]

Background. This intercontinental study aimed to study gram-negative rod (GNR) resistance in hematopoietic stem cell transplantation (HSCT). Methods. GNR bacteremias occurring during 6 months post-HSCT (February 2014-May 2015) were prospectively collected, and analyzed for rates and risk factors for resistance to fluoroquinolones, noncarbapenem anti-Pseudomonas β-lactams (noncarbapenems), carbapenems, and multidrug resistance. Results. Sixty-five HSCT centers from 25 countries in Europe, Australia, and Asia reported data on 655 GNR episodes and 704 pathogens in 591 patients (Enterobacteriaceae, 73%; nonfermentative rods, 24%; and 3% others). Half of GNRs were fluoroquinolone and noncarbapenem resistant; 18.5% carbapenem resistant; 35.2% multidrug resistant. The total resistance rates were higher in allogeneic HSCT (allo-HSCT) vs autologous HSCT (auto-HSCT) patients (P < .001) but similar in community-acquired infections. Noncarbapenem resistance and multidrug resistance were higher in auto-HSCT patients in centers providing vs not providing fluoroquinolone prophylaxis (P < .01). Resistance rates were higher in southeast vs northwest Europe and similar in children and adults, excluding higher fluoroquinolone- and β-lactam/β-lactamase inhibitor resistance rates in allo-HSCT adults. Non-Klebsiella Enterobacteriaceae were rarely carbapenem resistant. Multivariable analysis revealed resistance risk factors in allo-HSCT patients: fluoroquinolone resistance: adult, prolonged neutropenia, breakthrough on fluoroquinolones; noncarbapenem resistance: hospital-acquired infection, breakthrough on noncarbapenems or other antibiotics (excluding fluoroquinolones, noncarbapenems, carbapenems), donor type; carbapenem resistance: breakthrough on carbapenem, longer hospitalization, intensive care unit, previous other antibiotic therapy; multidrug resistance: longer hospitalization, breakthrough on β-lactam/β-lactamase inhibitors, and carbapenems. Inappropriate empiric therapy and mortality were significantly more common in infections caused by resistant bacteria. Conclusions. Our data question the recommendation for fluoroquinolone prophylaxis and call for reassessment of local empiric antibiotic protocols. Knowledge of pathogen-specific resistance enables early appropriate empiric therapy. Monitoring of resistance is crucial. Clinical Trials Registration. NCT02257931 [ABSTRACT FROM AUTHOR]

Purpose: Milk provides a significant source of calcium, protein, vitamins and other minerals to Western populations throughout life. Due to its widespread use, the metabolic and health impact of milk consumption warrants further investigation and biomarkers would aid epidemiological studies. Methods: Milk intake assessed by a validated food frequency questionnaire was analyzed against fasting blood metabolomic profiles from two metabolomic platforms in females from the TwinsUK cohort ( n = 3559). The top metabolites were then replicated in two independent populations (EGCUT, n = 1109 and KORA, n = 1593), and the results from all cohorts were meta-analyzed. Results: Four metabolites were significantly associated with milk intake in the TwinsUK cohort after adjustment for multiple testing ( P < 8.08 × 10) and covariates (BMI, age, batch effects, family relatedness and dietary covariates) and replicated in the independent cohorts. Among the metabolites identified, the carnitine metabolite trimethyl-N-aminovalerate ( β = 0.012, SE = 0.002, P = 2.98 × 10) and the nucleotide uridine ( β = 0.004, SE = 0.001, P = 9.86 × 10) were the strongest novel predictive biomarkers from the non-targeted platform. Notably, the association between trimethyl-N-aminovalerate and milk intake was significant in a group of MZ twins discordant for milk intake ( β = 0.050, SE = 0.015, P = 7.53 × 10) and validated in the urine of 236 UK twins ( β = 0.091, SE = 0.032, P = 0.004). Two metabolites from the targeted platform, hydroxysphingomyelin C14:1 ( β = 0.034, SE = 0.005, P = 9.75 × 10) and diacylphosphatidylcholine C28:1 ( β = 0.034, SE = 0.004, P = 4.53 × 10), were also replicated. Conclusions: We identified and replicated in independent populations four novel biomarkers of milk intake: trimethyl-N-aminovalerate, uridine, hydroxysphingomyelin C14:1 and diacylphosphatidylcholine C28:1. Together, these metabolites have potential to objectively examine and refine milk-disease associations. [ABSTRACT FROM AUTHOR]

BACKGROUND: Epidemiological evidence on the association between ambient air pollution and breast cancer risk is inconsistent. OBJECTIVE: We examined the association between long-term exposure to ambient air pollution and incidence of postmenopausal breast cancer in European women. METHODS: In 15 cohorts from nine European countries, individual estimates of air pollution levels at the residence were estimated by standardized land-use regression models developed within the European Study of Cohorts for Air Pollution Effects (ESCAPE) and Transport related Air Pollution and Health impacts - Integrated Methodologies for Assessing Particulate Matter (TRANSPHORM) projects: particulate matter (PM) ≤2:5 μm, ≤10 μm, and 2:5-10 μm in diameter (PM2.5, PM10, and PMcoarse, respectively); PM2.5 absorbance; nitrogen oxides (NO2 and NOx); traffic intensity; and elemental composition of PM. We estimated cohort-specific associations between breast cancer and air pollutants using Cox regression models, adjusting for major lifestyle risk factors, and pooled cohort-specific estimates using random-effects meta-analyses. RESULTS: Of 74,750 postmenopausal women included in the study, 3,612 developed breast cancer during 991,353 person-years of follow-up. We found positive and statistically insignificant associations between breast cancer and PM2.5 {hazard ratio (HR)=1:08 [95% confidence interval (CI): 0.77, 1.51] per 5 μg = m3}, PM10 [1.07 (95% CI: 0.89, 1.30) per 10 μg = m3], PMcoarse [1.20 (95% CI: 0.96, 1.49 per 5 μg = m3], and NO2 [1.02 (95% CI: 0.98, 1.07 per 10 μg = m3], and a statistically significant association with NOx [1.04 (95% CI: 1.00, 1.08) per 20 μg = m3, p = 0:04]. CONCLUSIONS: We found suggestive evidence of an association between ambient air pollution and incidence of postmenopausal breast cancer in European women. [ABSTRACT FROM AUTHOR]

Background: We aimed to describe gender and region differences in the prevalence of binge drinking and in the association between binge drinking and well-being, among older adult Europeans. Methods: This is a cross-sectional study using the Survey of Health, Ageing and Retirement in Europe (SHARE) wave 4, conducted between 2011 and 2012, including 58 489 individuals aged 50 years or older. Sixteen European countries were grouped in four drinking culture regions: South, Central, North and East. We categorized drinking patterns as: never, former, no-binge and binge drinkers. We used the CASP-12 questionnaire to measure well-being. To assess the association between binge drinking and well-being, we fitted two-level mixed effects linear models. Results: The highest percentage of binge drinkers was found in Central Europe (17.25% in men and 5.05% in women) and the lowest in Southern Europe (9.74% in men and 2.34% in women). Former, never and binge drinkers had a significant negative association with well-being as compared with no-binge drinkers. There was a significant interaction in this association by gender and region. Overall, associations were generally stronger in women and in Southern and Eastern Europe. The negative association of binge drinking with well-being was especially strong in Southern European women (β = -3.80, 95%CI: -5.16 to -2.44, P value <0.001). Conclusion: In Southern and Eastern European countries the association between binge drinking and well-being is stronger, especially in women, compared with Northern and Central Europe. Cultural factors (such as tolerance to drunkenness) should be further explored. [ABSTRACT FROM AUTHOR]

Objectives. The arachidonate 5-lipoxygenase activating protein (ALOX5AP) regulates synthesis of leuko-trienes (LTs), which are important mediators of inflammation and connective tissue remodelling. The aim of this study was to evaluate if single nucleotide polymorphisms (SNPs) of ALOX5AP confer risk of SSc and/ or SSc-related organ involvement. Methods. Seven SNPs of ALOX5AP (rs17222814, rs17216473, rs10507391, rs4769874, rs9551963, rs9315050 and rs7222842) were genotyped in a cohort of 977 patients with SSc and 558 healthy controls from centres collaborating within the European Scleroderma Trials and Research group. In 22 SSc patients, concentrations of cysteinyl LTs and LT B4 (LTB4) were measured in the supernatants of ionophore-stimulated peripheral blood mononuclear cells (PBMCs) by means of commercially available enzyme immunoassay kits. Results. Significant association was found between rs10507391 polymorphism (T/A) of ALOX5AP and the risk of SSc [odds ratio (OR) 1.27 (95% CI 1.07, 1.50), P < 0.05 vs controls], the presence of SSc-related interstitial lung disease on high-resolution CT of the lungs [OR 1.45 (95% CI 1.17, 1.79), P < 0.05 vs patients without SSc-related interstitial lung disease] as well as with restrictive ventilatory defect [forced vital capacity <70% of predicted; OR 1.51 (95% CI 1.16, 1.97), P < 0.05 vs SSc patients without pulmonary restriction]. PBMCs from SSc carriers of rs10507391 allele A synthesized greater amounts of cysteinyl LTs as compared with SSc patients with rs10507391 TT genotype (P < 0.05). Synthesis of LTB4 did not differ significantly between the two groups. Conclusion. The results of our study indicate that the genetic variants of ALOX5AP might play a role in the development of SSc-related pulmonary fibrosis. [ABSTRACT FROM AUTHOR]

Background: We previously found that the introduction of small quantities of gluten at 4-6 mo of age did not reduce the risk of celiac disease (CD) in a group of high-risk children. However, the consumption of high amounts of gluten early in life has been suggested to increase CD risk. Objective: The aim of this study was to evaluate this hypothesis by using data from the previous study of the PreventCD trial (www. preventcd.com). Design: Gluten intake was prospectively quantified by using specific food records between 11 and 36 mo of age in 715 children positive for the human leukocyte antigen (HLA)-DQ2 and/or HLA-DQ8 from 5 European countries. According to the PreventCD protocol, infants received 100 mg immunologically active gluten/d or placebo from 4 to 6 mo of age, with a stepwise and fixed gluten increase until age 10 mo and unrestricted intake thereafter. The primary outcome of the present study was the impact of the amount of gluten consumed from age 10 mo onward on CD development. Results: Mean daily gluten intakes from 10 mo onward were significantly different between countries for children at all ages (P < 0.001) but not between children who developed CD and those who did not within the same country (P > 0.05). The variables country, sex, intervention group, and gluten consumption pattern did not show significant associations with CD development risk (HRs not significant). In addition, the interaction between HLA risk group and gluten consumption pattern showed no significant risk on CD development, except for the DQ2.2/DQ7 haplotype (HR: 5.81; 95% CI: 1.18, 28.74; P = 0.031). Conclusions: Gluten consumption patterns as well as the amount of gluten consumed at 11-36 mo of age do not influence CD development for most related HLA genotypes in children with a genetic risk. This study reports the gluten consumption pattern in children at risk of CD from different European countries. This trial was registered at www.controlled-trials.com as ISRCTN74582487. [ABSTRACT FROM AUTHOR]

Purpose: This cross-sectional study assesses the relationship between consumption frequencies of food items and high-sensitivity C-reactive protein (hs-CRP) in European children. Methods: Out of the baseline sample ( N = 16.228) of the IDEFICS study, 6.403 children (1.315 boys aged 2 to <6, 1.908 boys aged 6 to <10, 1.204 girls aged 2 to <6 and 1.976 girls aged 6 to <10 years) had hs-CRP measured and the Children's Eating Habits Questionnaire filled, including a food frequency questionnaire. Logistic regression adjusted for body mass index z-score, education of the mother, breast-feeding and self-reported hours of physical activity in a sport club per week was conducted. Results: Mean frequency intake of raw vegetable was lower in boys ( p = 0.022 in young and p = 0.020 in old) and older girls ( p = 0.026) with high hs-CRP concentration, while in younger girls ( p = 0.008) the same occurred with the cooked vegetables. The probability of having higher hs-CRP concentration was significantly associated with having low consumption frequency of vegetables ( p = 0.004 in older boys, raw vegetables; and p = 0.0032 in younger girls, cooked vegetables). Also, honey/jam intake decreased the probability of having higher concentration of hs-CRP, whereas soft drinks with sugar, mayonnaise and cereals milled increased this probability. Conclusions: Out of all food items associated with hs-CRP, frequency intake of vegetables presented more associations across all the analysis. Findings suggest that a high-frequency intake of vegetables is inversely related to an inflammatory status in children. More studies are needed to assess the association between diet and inflammation. [ABSTRACT FROM AUTHOR]

Background: Studies of the role of dietary factors in epithelial ovarian cancer (EOC) development have been limited, and no specific dietary factors have been consistently associated with EOC risk. Objective: We used a nutrient-wide association study approach to systematically test the association between dietary factors and invasive EOC risk while accounting for multiple hypothesis testing by using the false discovery rate and evaluated the findings in an independent cohort. Design: We assessed dietary intake amounts of 28 foods/food groups and 29 nutrients estimated by using dietary questionnaires in the EPIC (European Prospective Investigation into Cancer and Nutrition) study (n = 1095 cases). We selected 4 foods/nutrients that were statistically significantly associated with EOC risk when comparing the extreme quartiles of intake in the EPIC study (false discovery rate = 0.43) and evaluated these factors in the NLCS (Netherlands Cohort Study; n = 383 cases). Cox regression models were used to estimate HRs and 95% CIs. Results: None of the 4 dietary factors that were associated with EOC risk in the EPIC study (cholesterol, polyunsaturated and saturated fat, and bananas) were statistically significantly associated with EOC risk in the NLCS; however, in meta-analysis of the EPIC study and the NLCS, we observed a higher risk of EOC with a high than with a low intake of saturated fat (quartile 4 compared with quartile 1; overall HR: 1.21; 95% CI: 1.04, 1.41). Conclusion: In the meta-analysis of both studies, there was a higher risk of EOC with a high than with a low intake of saturated fat. [ABSTRACT FROM AUTHOR]

Background: Higher coffee intake has been purportedly related to a lower risk of liver cancer. However, it remains unclear whether this association may be accounted for by specific biological mechanisms. Objective: We aimed to evaluate the potential mediating roles of inflammatory, metabolic, liver injury, and iron metabolism biomarkers on the association between coffee intake and the primary form of liver cancer--hepatocellular carcinoma (HCC). Design: We conducted a prospective nested case-control study within the European Prospective Investigation into Cancer and Nutrition among 125 incident HCC cases matched to 250 controls using an incidence-density sampling procedure. The association of coffee intake with HCC risk was evaluated by using multivariable-adjusted conditional logistic regression that accounted for smoking, alcohol consumption, hepatitis infection, and other established liver cancer risk factors. The mediating effects of 21 biomarkers were evaluated on the basis of percentage changes and associated 95% CIs in the estimated regression coefficients of models with and without adjustment for biomarkers individually and in combination. Results: The multivariable-adjusted RR of having ≥4 cups (600 mL) coffee/d compared with,2 cups (300 mL)/d was 0.25 (95% CI: 0.11, 0.62; P-trend = 0.006). A statistically significant attenuation of the association between coffee intake and HCC risk and thereby suspected mediation was confirmed for the inflammatory biomarker IL-6 and for the biomarkers of hepatocellular injury glutamate dehydrogenase, alanine aminotransferase, aspartate aminotransferase (AST), γ-glutamyltransferase (GGT), and total bilirubin, which--in combination--attenuated the regression coefficients by 72% (95% CI: 7%, 239%). Of the investigated biomarkers, IL-6, AST, and GGT produced the highest change in the regression coefficients: 40%, 56%, and 60%, respectively. Conclusion: These data suggest that the inverse association of coffee intake with HCC risk was partly accounted for by biomarkers of inflammation and hepatocellular injury. [ABSTRACT FROM AUTHOR]

Background: An improved understanding of the contribution of the diet to health and disease risks requires accurate assessments of dietary exposure in nutritional epidemiologic studies. The use of dietary biomarkers may improve the accuracy of estimates. Objective: We applied a metabolomic approach in a large cohort study to identify novel biomarkers of intake for a selection of polyphenolcontaining foods. The large chemical diversity of polyphenols and their wide distribution over many foods make them ideal biomarker candidates for such foods. Design: Metabolic profiles were measured with the use of highresolution mass spectrometry in 24-h urine samples from 481 subjects from the large European Prospective Investigation on Cancer and Nutrition cohort. Peak intensities were correlated to acute and habitual dietary intakes of 6 polyphenol-rich foods (coffee, tea, red wine, citrus fruit, apples and pears, and chocolate products) measured with the use of 24-h dietary recalls and food-frequency questionnaires, respectively. Results: Correlation (r . 0.3, P , 0.01 after correction for multiple testing) and discriminant [pcorr (1) . 0.3, VIP . 1.5] analyses showed that .2000 mass spectral features from urine metabolic profiles were significantly associated with the consumption of the 6 selected foods. More than 80 polyphenol metabolites associated with the consumption of the selected foods could be identified, and large differences in their concentrations reflecting individual food intakes were observed within and between 4 European countries. Receiver operating characteristic curves showed that 5 polyphenol metabolites, which are characteristic of 5 of the 6 selected foods, had a high predicting ability of food intake. Conclusion: Highly diverse food-derived metabolites (the so-called food metabolome) can be characterized in human biospecimens through this powerful metabolomic approach and screened to identify novel biomarkers for dietary exposures, which are ultimately essential to better understand the role of the diet in the cause of chronic diseases. [ABSTRACT FROM AUTHOR]

Background: Short sleep duration has been associated with greater risks of obesity, hypertension, diabetes, and cardiovascular disease. Also, common genetic variants in the human Circadian Locomotor Output Cycles Kaput (CLOCK) show associations with ghrelin and total energy intake. Objectives: We examined associations between habitual sleep duration, body mass index (BMI), and macronutrient intake and assessed whether CLOCK variants modify these associations. Design: We conducted inverse-variance weighted, fixed-effect meta-analyses of results of adjusted associations of sleep duration and BMI and macronutrient intake as percentages of total energy as well as interactions with CLOCK variants from 9 cohort studies including up to 14,906 participants of European descent from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Results: We observed a significant association between sleep duration and lower BMI (β ± SE = 0.16 ± 0.04, P < 0.0001) in the overall sample; however, associations between sleep duration and relative macronutrient intake were evident in age- and sex-stratified analyses only. We observed a significant association between sleep duration and lower saturated fatty acid intake in younger (aged 20-64 y) adults (men: 0.11 6 0.06%, P = 0.03; women: 0.10 ± 0.05%, P = 0.04) and with lower carbohydrate (20.31 ± 0.12%, P < 0.01), higher total fat (0.18 ± 0.09%, P = 0.05), and higher PUFA (0.05 ± 0.02%, P = 0.02) intakes in older (aged 65-80 y) women. In addition, the following 2 nominally significant interactions were observed: between sleep duration and rs12649507 on PUFA intake and between sleep duration and rs6858749 on protein intake. Conclusions: Our results indicate that longer habitual sleep duration is associated with lower BMI and age- and sex-specific favorable dietary behaviors. Differences in the relative intake of specific macronutrients associated with short sleep duration could, at least in part, explain previously reported associations between short sleep duration and chronic metabolic abnormalities. In addition, the influence of obesity-associated CLOCK variants on the association between sleep duration and macronutrient intake suggests that longer habitual sleep duration could ameliorate the genetic predisposition to obesity via a favorable dietary profile. Trials related to this study were registered at clinicaltrials.gov as NCT00005133 (Cardiovascular Health Study), NCT00005121 (Framingham Offspring Study), NCT01331512 [Invecchiare in Chianti (Aging in the Chianti Area) study], NCT00289237 (Inter99), and NCT00005487 (Multi-Ethnic Study of Atherosclerosis). [ABSTRACT FROM AUTHOR]