Metabolic Signatures of Healthy Lifestyle Patterns and Colorectal Cancer Risk in a European Cohort

BACKGROUND & AIMS: Colorectal cancer risk can be lowered by adherence to the World Cancer Research Fund/ American Institute for Cancer Research (WCRF/AICR) guidelines. We derived metabolic signatures of adherence to these guidelines and tested their associations with colorectal cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort. METHODS: Scores reflecting adherence to the WCRF/AICR recommendations (scale, 1–5) were calculated from participant data on weight maintenance, physical activity, diet, and alcohol among a discovery set of 5738 cancer-free European Prospective Investigation into Cancer and Nutrition participants with metabolomics data. Partial least-squares regression was used to derive fatty acid and endogenous metabolite signatures of the WCRF/AICR score in this group. In an independent set of 1608 colorectal cancer cases and matched controls, odds ratios (ORs) and 95% CIs were calculated for colorectal cancer risk per unit increase in WCRF/AICR score and per the corresponding change in metabolic signatures using multivariable conditional logistic regression. RESULTS: Higher WCRF/AICR scores were characterized by metabolic signatures of increased odd-chain fatty acids, serine, glycine, and specific phosphatidylcholines. Signatures were inversely associated more strongly with colorectal cancer risk (fatty acids: OR, 0.51 per unit increase; 95% CI, 0.29–0.90; endogenous metabolites: OR, 0.62 per unit change; 95% CI, 0.50–0.78) than the WCRF/AICR score (OR, 0.93 per unit change; 95% CI, 0.86–1.00) overall. Signature associations were stronger in male compared with female participants. CONCLUSIONS: Metabolite profiles reflecting adherence to WCRF/AICR guidelines and additional lifestyle or biological risk factors were associated with colorectal cancer. Measuring a specific panel of metabolites representative of a healthy or unhealthy lifestyle may identify strata of the population at higher risk of colorectal cancer.World Cancer Research Fund International (WCRF) 20131002European Commission grant EU-FP7/BBMRI-LPC 313010International Agency for Research on CancerDanish Cancer SocietyLigue Contre le Cancer (France)General ElectricInstitut Gustave-Roussy (France)Mutuelle Generale de l'Education Nationale (France)Institut National de la Sante et de la Recherche Medicale (Inserm)Deutsche Krebshilfe German Cancer Research Center (Germany) Federal Ministry of Education & Research (BMBF) Deutsche KrebshilfeHellenic Health Foundation (Greece)Fondazione AIRC per la ricerca sul cancroConsiglio Nazionale delle Ricerche (CNR)Dutch Ministry of Public Health, Welfare and Sports (The Netherlands) Netherlands Cancer Registry (The Netherlands) Netherlands GovernmentNordic Centre of Excellence Programme on Food, Nutrition and Health (Norway)Instituto de Salud Carlos III PI13/00061 PI13/01162Junta de AndaluciaBasque GovernmentRegional Government of MurciaRegional Government of NavarraInstituto de Salud Carlos III Cooperative Research in Health (Spain) RD06/0020Swedish Cancer Society Swedish Research CouncilCounty Council of Skane (Sweden) County Council of Vasterbotten (Sweden)Cancer Research UK 14136 C570/A16491 C8221/A19170UK Research & Innovation (UKRI)Medical Research Council UK (MRC) 1000143 MR/M012190/

Using projective invariants for constant time library indexing in model based vision

Projectively invariant shape descriptors allow fast indexing into model libraries, because recognition proceeds without reference to object pose. This paper describes progress in building a large model based vision system which uses many projectively invariant descriptors. We give a brief account of these descriptors and then describe the recognition system, giving examples of the invariant techniques working on real images. We demonstrate the ease of model acquisition in our system, where models are generated directly from images. We demonstrate fast recognition without determining object pose or camera parameters

Urinary Deoxynivalenol Is Correlated with Cereal Intake in Individuals from the United Kingdom

Background Deoxynivalenol (DON) is a toxic fungal metabolite that frequently contaminates cereal crops. DON is toxic to animals, but the effects on humans are poorly understood, in part because exposure estimates are of limited precision. Objectives In this study we used the U.K. adult National Diet and Nutrition Survey to compare 24-hr urinary DON excretion with cereal intake. Methods One hundred subjects were identified for each of the following cereal consumption groups: low (mean, 107 g cereal/day; range, 88–125), medium (mean, 179 g/day; range, 162–195) and high (mean, 300 g/day; range, 276–325). DON was analyzed in 24-hr urine samples by liquid chromatography–mass spectrometry after purification on immunoaffinity columns. Results DON was detected in 296 of 300 (98.7%) urine samples. Cereal intake was significantly associated with urinary DON (p < 0.0005), with the geometric mean urinary levels being 6.55 μg DON/day [95% confidence interval (CI), 5.71–7.53]; 9.63 μg/day (95% CI, 8.39–11.05); and 13.24 μg/day (95% CI, 11.54–15.19) for low-, medium-, and high-intake groups, respectively. In multivariable analysis, wholemeal bread (p < 0.0005), white bread (p < 0.0005), “other” bread (p < 0.0005), buns/cakes (p = 0.003), high-fiber breakfast cereal (p = 0.016), and pasta (p = 0.017) were significantly associated with urinary DON. Wholemeal bread was associated with the greatest percent increase in urinary DON per unit of consumption, but white bread contributed approximately twice as much as wholemeal bread to the urinary DON levels because it was consumed in higher amounts. Conclusion The majority of adults in the United Kingdom appear to be exposed to DON, and on the basis of the urinary levels, we estimate that some individuals may exceed the European Union (EU) recommended maximum tolerable daily intake of 1,000 ng DON/kg (bw). This exposure biomarker will be a valuable tool for biomonitoring as part of surveillance strategies and in etiologic studies of DON and human disease risk

Development of expertise in elite and sub-elite British rugby league players: A comparison of practice experiences

Previous studies have investigated how individuals reach an expert level by counting the number of hours engaged in specific practice types. Here we sought to understand and compare the microstructure (e.g. practice tasks undertaken) of these practice hours experienced by elite and sub-elite British rugby league players. Semi-structured interviews explored the practice experiences of eight international and eight domestic level players. A two-staged thematic analysis was used to interpret the data. The analysis revealed that both player groups experienced a rich and narrow landscape of affordances and were exposed to early diversification of sports experiences during childhood. Differences were identified in domestic level players’ experiences of amateur and professional sports, where episodes of negative developmental environments were reported. International players’ practice experiences revealed differences in their professional careers, where exposure to scenario-based practice and dynamic learning environments were reported. The findings suggest that insights from ecological dynamics provide a suitable theoretical framework to guide coaches in the design of practice environments that should consider the physical, psychological, emotional and social dimensions of expertise acquisition

Dietary polyphenol intake and their major food sources in the Mexican Teachers' Cohort

Several descriptive studies on the intake of polyphenols, mostly flavonoids, have been published, especially in Europe and the USA, but insufficient data are still available in Latin-American countries, where different types of foods are consumed and different dietary habits are observed. The goal of this cross-sectional study was to estimate dietary intakes of polyphenols, including grand total, total per classes and subclasses and individual compounds, and to identify their main food sources in Mexican women. The Mexican Teachers' Cohort includes 115 315 female teachers, 25 years and older, from twelve states of Mexico, including urban and rural areas. Dietary data were collected in the period 2008-2011 using a validated FFQ, and individual polyphenol intake was estimated using food composition data from the Phenol-Explorer database. Median total polyphenol intake was the highest in Baja California (750 mg/d) and the lowest in Yucatan (536 mg/d). The main polyphenols consumed were phenolic acids (56.3-68.5 % total polyphenols), followed by flavonoids (28.8-40.9 %). Intake of other polyphenol subclasses (stilbenes, lignans and others) was insignificant. Coffee and fruits were the most important food sources of phenolic acids and flavonoids, respectively. Intake of a total of 287 different individual polyphenols could be estimated, of which forty-two were consumed in an amount 1 mg/d. The most largely consumed polyphenols were several caffeoylquinic acids (ranging from 20 and 460 mg/d), ferulic acid, hesperidin and proanthocyanidins. This study shows a large heterogeneity in intakes of individual polyphenols among Mexican women, but a moderate heterogeneity across Mexican states. Main food sources were also similar in the different states

Phenol-Explorer 2.0: a major update of the Phenol-Explorer database integrating data on polyphenol metabolism and pharmacokinetics in humans and experimental animals

Phenol-Explorer, launched in 2009, is the only comprehensive web-based database on the content in foods of polyphenols, a major class of food bioactives that receive considerable attention due to their role in the prevention of diseases. Polyphenols are rarely absorbed and excreted in their ingested forms, but extensively metabolized in the body, and until now, no database has allowed the recall of identities and concentrations of polyphenol metabolites in biofluids after the consumption of polyphenol-rich sources. Knowledge of these metabolites is essential in the planning of experiments whose aim is to elucidate the effects of polyphenols on health. Release 2.0 is the first major update of the database, allowing the rapid retrieval of data on the biotransformations and pharmacokinetics of dietary polyphenols. Data on 375 polyphenol metabolites identified in urine and plasma were collected from 236 peer-reviewed publications on polyphenol metabolism in humans and experimental animals and added to the database by means of an extended relational design. Pharmacokinetic parameters have been collected and can be retrieved in both tabular and graphical form. The web interface has been enhanced and now allows the filtering of information according to various criteria. Phenol-Explorer 2.0, which will be periodically updated, should prove to be an even more useful and capable resource for polyphenol scientists because bioactivities and health effects of polyphenols are dependent on the nature and concentrations of metabolites reaching the target tissues. The Phenol-Explorer database is publicly available and can be found online at http://www.phenol-explorer.eu. Database URL: http://www.phenol-explorer.eu

Systematic analysis of the polyphenol metabolome using the Phenol-Explorer database

SCOPE: The Phenol-Explorer web database details 383 polyphenol metabolites identified in human and animal biofluids from 221 publications. Here we exploit these data to characterize and visualize the polyphenol metabolome, the set of all metabolites derived from phenolic food components. METHODS AND RESULTS: Qualitative and quantitative data on 383 polyphenol metabolites as described in 424 human and animal intervention studies were systematically analyzed. Of these metabolites, 301 were identified without prior enzymatic hydrolysis of biofluids, and included glucuronide and sulfate esters, glycosides, aglycones, and O-methyl ethers. Around one third of these compounds are also known as food constituents and corresponded to polyphenols absorbed without further metabolism. Many ring-cleavage metabolites formed by gut microbiota were noted, mostly derived from hydroxycinnamates, flavanols and flavonols. Median maximum plasma concentrations (Cmax ) of all human metabolites were 0.09 μM and 0.32 μM when consumed from foods or dietary supplements respectively. Median time to reach maximum plasma concentration in humans (Tmax ) was 2.18 h. CONCLUSION: These data show the complexity of the polyphenol metabolome and the need to take into account biotransformations to understand in vivo bioactivities and the role of dietary polyphenols in health and disease. This article is protected by copyright. All rights reserved

Biomarkers of intake for coffee, tea and sweetened beverages

Non-alcoholic beverages are important sources of nutrients and bioactive compounds that may influence human health and increase or decrease the risk of chronic diseases. A wide variety of beverage constituents are absorbed in the gut, found in the systemic circulation and excreted in urine. They may be used as compliance markers in intervention studies or as biomarkers of intake to improve measurements of beverage consumption in cohort studies and reveal new associations with disease outcomes that may have been overlooked when using dietary questionnaires. Here, biomarkers of intake of some major non-alcoholic beverages coffee, tea, sugar-sweetened beverages, and low-calorie-sweetened beverages are reviewed. Results from dietary intervention studies and observational studies are reviewed and analyzed, and respective strengths and weaknesses of the various identified biomarkers discussed. A variety of compounds derived from phenolic acids, alkaloids, and terpenes were shown to be associated with coffee intake and trigonelline and cyclo(isoleucylprolyl) showed a particularly high specificity for coffee intake. Epigallocatechin and 4′-O-methylepigallocatechin appear to be the most sensitive and specific biomarkers for green or black tea, while 4-O-methylgallic acid may be used to assess black tea consumption. Intake of sugar-sweetened beverages has been assessed through the measurement of carbon-13 enrichment of whole blood or of blood alanine in North America where sugar from sugarcane or corn is used as a main ingredient. The most useful biomarkers for low-calorie-sweetened beverages are the low-calorie sweeteners themselves. Further studies are needed to validate these biomarkers in larger and independent populations and to further evaluate their specificity, reproducibility over time, and fields of application

Direct-current-dependent shift of theta-burst-induced plasticity in the human motor cortex

Animal studies using polarising currents have shown that induction of synaptic long-term potentiation (LTP) and long-term depression (LTD) by bursts of patterned stimulation is affected by the membrane potential of the postsynaptic neurone. The aim of the present experiments was to test whether it is possible to observe similar phenomena in humans with the aim of improving present protocols of inducing synaptic plasticity for therapeutic purposes. We tested whether the LTP/LTD-like after effects of transcranial theta-burst stimulation (TBS) of human motor cortex, an analogue of patterned electrical stimulation in animals, were affected by simultaneous transcranial direct-current stimulation (tDCS), a non-invasive method of polarising cortical neurones in humans. Nine healthy volunteers were investigated in a single-blind, balanced cross-over study; continuous TBS (cTBS) was used to introduce LTD-like after effects, whereas intermittent TBS (iTBS) produced LTP-like effects. Each pattern was coupled with concurrent application of tDCS (<200 s, anodal, cathodal, sham). Cathodal tDCS increased the response to iTBS and abolished the effects of cTBS. Anodal tDCS changed the effects of cTBS towards facilitation, but had no impact on iTBS. Cortical motor thresholds and intracortical inhibitory/facilitatory networks were not altered by any of the stimulation protocols. We conclude that the after effects of TBS can be modulated by concurrent tDCS. We hypothesise that tDCS changes the membrane potential of the apical dendrites of cortical pyramidal neurones and that this changes the response to patterned synaptic input evoked by TBS. The data show that it may be possible to enhance LTP-like plasticity after TBS in the human cortex

Updating a systematic review – what difference did it make? Case study of nicotine replacement therapy

AIMS: To examine the effect of updating a systematic review of nicotine replacement therapy on its contents and conclusions. METHODS: We examined the effects of regular updating of a systematic review of nicotine replacement therapy for smoking cessation. We considered two outcomes. First, we assessed the effect of adding new data to meta-analyses, comparing results in 2000 with the results in 1994. Second, we assessed qualitatively the ways inwhich the nature of the questions addressed by the review had changed between the two dates. For the first outcome, we compared the number of trials, the pooled estimate of effect using the odds ratio, and the results of pre-specified subgroup analyses, for nicotine gum and patch separately. Using a test for interaction, we assessed whether differences between estimates were statistically significant. RESULTS: There were ten new trials of nicotine gum between 1994 and 2000, and the meta-analytic effect changed little. For the nicotine patch the number of trials increased from 9 to 30, and the meta-analytic effect fell from 2.07 (95% CI 1.64 – 2.62) to 1.73 (95% CI 1.56 – 1.93). Apparent differences in relative effect in sub-groups found in 1994 were not found in 2000. The updated systematic review addressed a number of questions not identified in the original version. CONCLUSIONS: Updating the meta-analyses lead to a more precise estimate of the likely effect of the nicotine patch, but the clinical message was unchanged. Further placebo controlled NRT trials are not likely to add to the evidence base. It is questionable whether updating the meta-analyses to include them is worthwhile. The content of the systematic review has, however, changed, with the addition of data addressing questions not considered in the original review. There is a tension between the principle of identifying the important questions prior to conducting a review, and keeping the review up to date as primary research identifies new avenues of enquiry