Medical Research Council MRC Human Nutrition Research

Cambridge, United Kingdom

Medical Research Council MRC Human Nutrition Research

Cambridge, United Kingdom
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Sansone S.-A.,University of Oxford | Rocca-Serra P.,University of Oxford | Field D.,Natural Environment Research Council | Maguire E.,University of Oxford | And 56 more authors.
Nature Genetics | Year: 2012

To make full use of research data, the bioscience community needs to adopt technologies and reward mechanisms that support interoperability and promote the growth of an open 'data commoning' culture. Here we describe the prerequisites for data commoning and present an established and growing ecosystem of solutions using the shared 'Investigation-Study-Assay' framework to support that vision. © 2012 Nature America, Inc. All rights reserved.

PubMed | University of Witwatersrand, Medical Research Council MRC Human Nutrition Research, McGill University, University of Helsinki and 3 more.
Type: | Journal: The Journal of steroid biochemistry and molecular biology | Year: 2016

The Department of Nutrition for Health and Development of the World Health Organization (WHO) in collaboration with the Executive Committee of the 18th Vitamin D Workshop (VDW), organised a joint symposium on the prevention and consequences of vitamin D deficiency in pregnant women and children, convening experts on vitamin D, clinicians and policy-makers. The overall aim was to identify priority areas for research and to discuss the need for global options for policy, with a focus on the prevention of rickets in infants and children and vitamin D deficiency in pregnant women. The scope and purpose were: (i) to present the WHO research strategy for health, addressing vitamin D-related public health problems and the process for the development of evidence-informed guidelines in general and how vitamin D interventions in diverse populations could be prioritised; (ii) to provide an overview of vitamin D status in children and pregnant and lactating women across the world; (iii) to review the health risks associated with vitamin D deficiency in children and in pregnant women and their offspring; (iv) to understand the aetiology of vitamin D deficiency in pregnant women and children; (v) to identify and interpret biomarkers to assess vitamin D status and to consider possible clinical and biochemical screening tools for determining the prevalence of nutritional rickets in at risk groups or communities; and (vi) to provide an overview of policies and recommendations on vitamin D across the world. The format of the symposium was a composite of comprehensive scientific presentations and a panel debate with international experts on WHO guidelines, nutritional rickets, nutritional policy and consequences of vitamin D deficiency during pregnancy. This paper summarizes the content and outcomes of the panel debate.

PubMed | University of Cambridge, Medical Research Council MRC Human Nutrition Research, University of Colorado at Boulder and University of California at Davis
Type: | Journal: Scientific reports | Year: 2017

Human milk oligosaccharides (HMOs) play an important role in the health of an infant as substrate for beneficial gut bacteria. Little is known about the effects of HMO composition and its changes on the morbidity and growth outcomes of infants living in areas with high infection rates. Mothers HMO composition and infant gut microbiota from 33 Gambian mother/infant pairs at 4, 16, and 20 weeks postpartum were analyzed for relationships between HMOs, microbiota, and infant morbidity and growth. The data indicate that lacto-N-fucopentaose I was associated with decreased infant morbidity, and 3-sialyllactose was found to be a good indicator of infant weight-for-age. Because HMOs, gut microbiota, and infant health are interrelated, the relationship between infant health and their microbiome were analyzed. While bifidobacteria were the dominant genus in the infant gut overall, Dialister and Prevotella were negatively correlated with morbidity, and Bacteroides was increased in infants with abnormal calprotectin. Mothers nursing in the wet season (July to October) produced significantly less oligosaccharides compared to those nursing in the dry season (November to June). These results suggest that specific types and structures of HMOs are sensitive to environmental conditions, protective of morbidity, predictive of growth, and correlated with specific microbiota.

PubMed | Medical University of Vienna, Medical Research Council MRC Human Nutrition Research, Innsbruck Medical University and University of Innsbruck
Type: Journal Article | Journal: PloS one | Year: 2016

Ferric carboxymaltose (FCM) and iron isomaltoside 1000 (IIM) are increasingly used because they allow correction of severe iron deficiency in a single infusion. A transient decrease in serum phosphate concentrations is a frequent side effect of FCM.To characterize this adverse event and search for its predictors in a gastroenterology clinic patient cohort.Electronic medical records of patients attending the University Hospital of Innsbruck were searched for the keywords ferric carboxymaltose or iron isomaltoside. Eighty-one patients with documented administration of FCM or IIM with plasma phosphate concentrations before and after treatment were included.The prevalence of hypophosphatemia (<0.8 mmol/L) increased from 11% to 32.1% after treatment with i.v. iron. The hypophosphatemia risk was greater after FCM (45.5%) compared with IIM (4%). Severe hypophosphatemia (<0.6 mmol/L) occurred exclusively after FCM (32.7%). The odds for hypophosphatemia after i.v. iron treatment were independently determined by baseline phosphate and the choice of i.v. iron preparation (FCM vs. IIM-OR = 20.8; 95% CI, 2.6-166; p = 0.004). The median time with hypophosphatemia was 41 days, but prolonged hypophosphatemia of 2 months was documented in 13 of 17 patients in whom follow-up was available. A significant increase in the phosphaturic hormone intact FGF-23 in hypophosphatemic patients shows that this adverse event is caused by FCM-induced hormone dysregulation.Treatment with FCM is associated with a high risk of developing severe and prolonged hypophosphatemia and should therefore be monitored. Hypophosphatemia risk appears to be substantially lower with IIM.

PubMed | University of Otago, Public Health England, Medical Research Council MRC Human Nutrition Research, University of Benin and 6 more.
Type: Journal Article | Journal: The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease | Year: 2016

Greater Banjul and Upper River Regions, The Gambia.To investigate tractable social, environmental and nutritional risk factors for childhood pneumonia.A case-control study examining the association of crowding, household air pollution (HAP) and nutritional factors with pneumonia was undertaken in children aged 2-59 months: 458 children with severe pneumonia, defined according to the modified WHO criteria, were compared with 322 children with non-severe pneumonia, and these groups were compared to 801 neighbourhood controls. Controls were matched by age, sex, area and season.Strong evidence was found of an association between bed-sharing with someone with a cough and severe pneumonia (adjusted OR [aOR] 5.1, 95%CI 3.2-8.2, P < 0.001) and non-severe pneumonia (aOR 7.3, 95%CI 4.1-13.1, P < 0.001), with 18% of severe cases estimated to be attributable to this risk factor. Malnutrition and pneumonia had clear evidence of association, which was strongest between severe malnutrition and severe pneumonia (aOR 8.7, 95%CI 4.2-17.8, P < 0.001). No association was found between pneumonia and individual carbon monoxide exposure as a measure of HAP.Bed-sharing with someone with a cough is an important risk factor for severe pneumonia, and potentially tractable to intervention, while malnutrition remains an important tractable determinant.

Ambrosini G.L.,Medical Research Council MRC Human Nutrition Research | Emmett P.M.,University of Bristol | Northstone K.,University of Bristol | Howe L.D.,University of Bristol | And 2 more authors.
International Journal of Obesity | Year: 2012

Background:Specific dietary risk factors for excess adiposity in young people are poorly understood. However, studies in adults suggest dietary energy density, fat and fibre are critical dietary factors. Objective:To examine longitudinal relationships between a dietary pattern (DP) characterised by dietary energy density, % total energy from fat and fibre density and fat mass (FM) in children from 7 to 15 years of age. Design:Subjects were 6772 children from the UK Avon Longitudinal Study of Parents and Children. Dietary intake was assessed using a 3-day food diary at 7, 10 and 13 years of age. An energy-dense, high-fat, low-fibre DP was identified using reduced rank regression and subjects scored for the DP at each age. FM was measured at 11, 13 and 15 years and FM index (FMI) calculated as FM/height (x). Longitudinal models were adjusted for dietary misreporting, physical activity and maternal factors. Results:DP z-scores at all ages were positively associated with later FMI. A 1 s.d. unit increase in DP z-score was longitudinally associated with an average increase in FMI z-score of 0.04 s.d. units (95% confidence interval (CI), 0.01-0.07). For each 1 s.d. unit increase in DP z-score, the odds of being in the highest quintile for FMI (as a marker of excess adiposity) increased by 13% (95% CI, 1-27%). Conclusions:Dietary habits during childhood are associated with increased adiposity in adolescence, with specific implications for dietary energy density, fat and fibre intake. Improving diet quality may reduce the risk of obesity in young people.International Journal of Obesity advance online publication, 7 August 2012; doi:10.1038/ijo.2012.127.

Cheng K.-K.,University of Cambridge | Cheng K.-K.,University of Technology Malaysia | Akasaki Y.,Boston University | Akasaki Y.,Kagoshima University | And 6 more authors.
Journal of Proteome Research | Year: 2015

Akt1 is a serine/threonine kinase that promotes cell growth and survival. Previously, Akt1 activation in a double transgenic (DTG) mouse model fed a high-fat/high-sucrose (HF/HS) diet was found to promote type IIb muscle growth and to lead to a significant reduction in obesity. Here, we have used metabolomics to examine the metabolic perturbations in blood serum and liver and gastrocnemius tissues of the DTG mice. Multivariate statistics highlighted consistent metabolic changes in gastrocnemius muscle following Akt1 activation, which included significant reductions of serine and histidine-containing dipeptides (anserine and carnosine), in addition to increased concentrations of phosphorylated sugars. In addition, Akt1-mediated regression in obesity could be associated with increased glycolysis in gastrocnemius muscle as well as increased gluconeogenesis, glycogenolysis, and ketogenesis in the liver. In old DTG animals, Akt1 activation was found to improve glucose metabolism and confer a beneficial effect in the regression of age-related fat accumulation. This study identifies metabolic changes induced by Akt1-mediated muscle growth and demonstrates a cross-talk between distant organs that leads to a regression of fat mass. The current findings indicate that agents that promote Akt1 induction in muscle have utility in the regression of obesity. © 2014 American Chemical Society.

Browning L.M.,Medical Research Council MRC Human Nutrition Research | Walker C.G.,Medical Research Council MRC Human Nutrition Research | Mander A.P.,University of Cambridge | West A.L.,University of Southampton | And 6 more authors.
American Journal of Clinical Nutrition | Year: 2012

Background: Estimation of the intake of oily fish at a population level is difficult. The measurement of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in biological samples may provide a useful biomarker of intake. Objective: We identified the most appropriate biomarkers for the assessment of habitual oily fish intake and changes in intake by elucidating the dose- and time-dependent response of EPA and DHA incorporation into various biological samples that represent roles in fatty acid transport, function, and storage. Design: This was a double-blind, randomized, controlled intervention trial in 204men andwomen that lasted 12 mo. EPA andDHA capsules were provided in a manner to reflect sporadic consumption of oily fish (ie, 1, 2, or 4 times/wk). EPA and DHAwere assessed at 9 time points over 12 mo in 9 sample types (red blood cells, mononuclear cells, platelets, buccal cells, adipose tissue, plasma phosphatidylcholine, triglycerides, cholesteryl esters, and nonesterified fatty acids). Results: A dose response (P < 0.05) was observed for EPA and DHA in all pools except for red blood cell EPA (P = 0.057). EPA and DHA measures in plasma phosphatidylcholine and platelets were best for the discrimination between different intakes (P < 0.0001). The rate of incorporation varied between sample types, with the time to maximal incorporation ranging from days (plasma phosphatidylcholine) to months (mononuclear cells) to >12 mo (adipose tissue). Conclusions: Plasma phosphatidylcholine EPA plus DHAwas identified as the most suitable biomarker of acute changes in EPA and DHA intake, and platelet and mononuclear cell EPA plus DHAwere the most suitable biomarkers of habitual intake. This trial was registered at Current Controlled Trials ( as ISRCTN48398526. © 2012 American Society for Nutrition.

Braithwaite V.,Medical Research Council MRC Human Nutrition Research | Jarjou L.M.A.,MRC Keneba | Goldberg G.R.,Medical Research Council MRC Human Nutrition Research | Prentice A.,Medical Research Council MRC Human Nutrition Research
Bone | Year: 2012

A relationship between iron and fibroblast growth factor-23 (FGF23) metabolic pathways has been proposed. Iron deficiency anaemia is prevalent in The Gambia and concentrations of fibroblast growth factor-23 FGF23 are elevated in a large percentage of Gambian children with rickets-like bone deformity.We speculate that low iron status may be involved in the aetiology of Gambian rickets. The aim of this study was to determine if there was a relationship between haemoglobin, as a marker of iron status, and FGF23 in samples from children with and without a history of rickets-like bone deformities in The Gambia. We conducted a retrospective analysis of studies carried out from 2006 to 2008 in children from a rural community in The Gambia where iron deficiency anaemia is endemic and where elevated circulating concentrations of FGF23 have been found. To investigate the relationship between circulating FGF23 and haemoglobin concentrations we used an age-adjusted linear regression model on data from children < 18. y of age with a family or personal history of rickets-like bone deformity (BD) (n= 108) and from the local community (LC) (n= 382).We found that circulating concentration of FGF23 was inversely correlated with haemoglobin concentration. This effect was more pronounced in BD children compared with LC children (interaction: P≤0.0001). Anaemia and elevated FGF23 were more prevalent in BD children compared to LC children (P=0.0003 and P=0.0001 respectively).In conclusion, there is a stronger relationship between FGF23 and haemoglobin in Gambian children with a history of rickets compared to local community children. This study provides support for the contention that iron may be involved in FGF23 metabolic pathways. © 2012 Elsevier Inc.

Bryant M.,University of Leeds | Ashton L.,University of Leeds | Brown J.,University of Leeds | Jebb S.,Medical Research Council MRC Human Nutrition Research | And 3 more authors.
Health Technology Assessment | Year: 2014

Background: Lack of uniformity in outcome measures used in evaluations of childhood obesity treatment interventions can impede the ability to assess effectiveness and limits comparisons across trials. Objective: To identify and appraise outcome measures to produce a framework of recommended measures for use in evaluations of childhood obesity treatment interventions. Data sources: Eleven electronic databases were searched between August and December 2011, including MEDLINE; MEDLINE In-Process and Other Non-Indexed Citations; EMBASE; PsycINFO; Health Management Information Consortium (HMIC); Allied and Complementary Medicine Database (AMED); Global Health, Maternity and Infant Care (all Ovid); Cumulative Index to Nursing and Allied Health Literature (CINAHL) (EBSCOhost); Science Citation Index (SCI) [Web of Science (WoS)]; and The Cochrane Library (Wiley) - from the date of inception, with no language restrictions. This was supported by review of relevant grey literature and trial databases. Review methods: Two searches were conducted to identify (1) outcome measures and corresponding citations used in published childhood obesity treatment evaluations and (2) manuscripts describing the development and/or evaluation of the outcome measures used in the childhood intervention obesity evaluations. Search 1 search strategy (review of trials) was modelled on elements of a review by Luttikhuis et al. (Oude Luttikhuis H, Baur L, Jansen H, Shrewsbury VA, O'Malley C, Stolk RP, et al. Interventions for treating obesity in children. Cochrane Database Syst Rev 2009;1:CD001872). Search 2 strategy (methodology papers) was built on Terwee et al.'s search filter (Terwee CB, Jansma EP, Riphagen II, de Vet HCW. Development of a methodological PubMed search filter for finding studies on measurement properties of measurement instruments. Qual Life Res 2009;18:1115-23). Eligible papers were appraised for quality initially by the internal project team. This was followed by an external appraisal by expert collaborators in order to agree which outcome measures should be recommended for the Childhood obesity Outcomes Review (CoOR) outcome measures framework. Results: Three hundred and seventy-nine manuscripts describing 180 outcome measures met eligibility criteria. Appraisal of these resulted in the recommendation of 36 measures for the CoOR outcome measures framework. Recommended primary outcome measures were body mass index (BMI) and dual-energy X-ray absorptiometry (DXA). Experts did not advocate any self-reported measures where objective measurement was possible (e.g. physical activity). Physiological outcomes hold potential to be primary outcomes, as they are indicators of cardiovascular health, but without evidence of what constitutes a minimally importance difference they have remained as secondary outcomes (although the corresponding lack of evidence for BMI and DXA is acknowledged). No preference-based quality-of-life measures were identified that would enable economic evaluation via calculation of quality-adjusted life-years. Few measures reported evaluating responsiveness. Limitations: Proposed recommended measures are fit for use as outcome measures within studies that evaluate childhood obesity treatment evaluations specifically. These may or may not be suitable for other study designs, and some excluded measures may be more suitable in other study designs. Conclusions: The CoOR outcome measures framework provides clear guidance of recommended primary and secondary outcome measures. This will enhance comparability between treatment evaluations and ensure that appropriate measures are being used. Where possible, future work should focus on modification and evaluation of existing measures rather than development of tools de nova. In addition, it is recommended that a similar outcome measures framework is produced to support evaluation of adult obesity programmes. Funding: The National Institute for Health Research Health Technology Assessment programme. © Queen's Printer and Controller of HMSO 2014.

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