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Sökning: WFRF:(O'Doherty E)

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  • Jankovic, N., et al. (författare)
  • ASSOCIATION BETWEEN A HEALTHY DIET ACCORDING TO WHO GUIDELINES AND ALL-CAUSE MORTALITY IN EUROPEAN AND AMERICAN ELDERLY, THE CHANCES PROJECT
  • 2013
  • Ingår i: Annals of Nutrition and Metabolism. - : S. Karger. - 0250-6807 .- 1421-9697. ; 63:Supplement 1, s. 234-234
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
    • Background and objectives: The Healthy Diet Indicator(HDI) measures adherence to the WHO guidelines for preventingdiet related chronic diseases, and can be applied to assessassociations of diet with health across populations. We examinedthe association between the HDI and all-cause mortalityin European and American elderly people aged 60 years andabove.Methods: We analysed data on 395,863 men and womenfrom 11 prospective cohort studies from the Consortium onHealth and Ageing: Network of Cohorts In Europe And TheUnited States (CHANCES). Across cohorts, the follow-upperiods ranged from 10 to 20 yrs. Diet was assessed throughvalidated methods. For the translation of foods to nutrients,country specific food composition tables were used. The continuouslyscored HDI (range mean and SD HDI score 45±9to 54±7 across cohorts) was based on intakes of saturated andpolyunsaturated fatty acids, mono-and disaccharides, protein,cholesterol, dietary fibre and fruits and vegetables. The associationbetween the HDI and all-cause mortality was evaluated ineach cohort separately, by multiple Cox proportional hazardsregression. A pooled hazard ratio (HR) was subsequently estimatedusing a random-effects model.Results: Across all cohorts, 84,863 people died during4,492,298 person-years of follow-up. Adjusted HR of death, fora 10 point increment in HDI score, ranged between 0.81 (95%CI 0.77-0.86) in Denmark and 0.99 (95% CI, 0.84-1.16) in Poland.The pooled adjusted HR estimate showed a significantinverse association of 0.90 (95% CI 0.87-0.93) but there was asignificant heterogeneity between studies (p=0.001, I2=66%).Conclusion: Our results show that higher dietary quality isinversely associated with all- cause mortality but
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  • Murphy, E. F., et al. (författare)
  • Composition and energy harvesting capacity of the gut microbiota : relationship to diet, obesity and time in mouse models
  • 2010
  • Ingår i: Gut. - : BMJ Publishing Group Ltd. - 0017-5749 .- 1468-3288. ; 59:12, s. 1635-42
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND AND AIMS: Increased efficiency of energy harvest, due to alterations in the gut microbiota (increased Firmicutes and decreased Bacteroidetes), has been implicated in obesity in mice and humans. However, a causal relationship is unproven and contributory variables include diet, genetics and age. Therefore, we explored the effect of a high-fat (HF) diet and genetically determined obesity (ob/ob) for changes in microbiota and energy harvesting capacity over time.METHODS: Seven-week-old male ob/ob mice were fed a low-fat diet and wild-type mice were fed either a low-fat diet or a HF-diet for 8 weeks (n=8/group). They were assessed at 7, 11 and 15 weeks of age for: fat and lean body mass (by NMR); faecal and caecal short-chain fatty acids (SCFA, by gas chromatography); faecal energy content (by bomb calorimetry) and microbial composition (by metagenomic pyrosequencing).RESULTS: A progressive increase in Firmicutes was confirmed in both HF-fed and ob/ob mice reaching statistical significance in the former, but this phylum was unchanged over time in the lean controls. Reductions in Bacteroidetes were also found in ob/ob mice. However, changes in the microbiota were dissociated from markers of energy harvest. Thus, although the faecal energy in the ob/ob mice was significantly decreased at 7 weeks, and caecal SCFA increased, these did not persist and faecal acetate diminished over time in both ob/ob and HF-fed mice, but not in lean controls. Furthermore, the proportion of the major phyla did not correlate with energy harvest markers.CONCLUSION: The relationship between the microbial composition and energy harvesting capacity is more complex than previously considered. While compositional changes in the faecal microbiota were confirmed, this was primarily a feature of high-fat feeding rather than genetically induced obesity. In addition, changes in the proportions of the major phyla were unrelated to markers of energy harvest which changed over time. The possibility of microbial adaptation to diet and time should be considered in future studies.
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  • Mulcahy, P., et al. (författare)
  • Development and characterisation of a novel rat model of Parkinson's disease induced by sequential intranigral administration of AAV-α-synuclein and the pesticide, rotenone.
  • 2012
  • Ingår i: Neuroscience. - : Elsevier BV. - 1873-7544 .- 0306-4522. ; 203, s. 170-179
  • Tidskriftsartikel (refereegranskat)abstract
    • Modeling Parkinson's disease remains a major challenge for preclinical researchers, as existing models fail to reliably recapitulate all of the classic features of the disease, namely, the progressive emergence of a bradykinetic motor syndrome with underlying nigrostriatal alpha-synuclein protein accumulation and nigrostriatal neurodegeneration. One limitation of the existing models is that they are normally induced by a single neuropathological insult, whereas the human disease is thought to be multifactorial with genetic and environmental factors contributing to the disease pathogenesis. Thus, in order to develop a more relevant model, we sought to determine if administration of the Parkinson's disease-associated pesticide, rotenone, into the substantia nigra of rats overexpressing the Parkinson's disease-associated protein, alpha-synuclein, could reliably model the triad of classic features of the human disease. To do so, rats underwent stereotaxic surgery for unilateral delivery of the adenoassociated virus (AAV)-alpha-synuclein into the substantia nigra. This was followed 13 weeks later by delivery of rotenone into the same site. The effect of the genetic and environmental insults alone or in combination on lateralised motor performance (Corridor, Stepping, and Whisker Tests), nigrostriatal integrity (tyrosine hydroxylase immunohistochemistry), and alpha-synucleinopathy (alpha-synuclein immunohistochemistry) was assessed. We found that rats treated with either AAV-alpha-synuclein or rotenone developed significant motor dysfunction with underlying nigrostriatal neurodegeneration. However, when the genetic and environmental insults were sequentially administered, the detrimental impact of the combined insults on motor performance and nigrostriatal integrity was significantly greater than the impact of either insult alone. This indicates that sequential exposure to relevant genetic and environmental insults is a valid approach to modeling human Parkinson's disease in the rat. 2011 IBRO. Published by Elsevier Ltd. All rights reserved.
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  • O'Doherty, Jim, et al. (författare)
  • Tissue viability imaging (TiVi) in the assessment of divergent beam UV-B provocation
  • 2011
  • Ingår i: Archives of Dermatological Research. - : Springer. - 0340-3696 .- 1432-069X. ; 303:2, s. 79-87
  • Tidskriftsartikel (refereegranskat)abstract
    • In routine clinical phototesting and in basic research, naked eye dermatological assessment is the "gold standard" for determining the patient's minimal erythemal dose (MED). In UV-B testing with a divergent, radially attenuating beam of characterised dosimetry, laser Doppler perfusion imaging has been previously used to give quantitative description of reactivity to doses above the MED in addition to a "single-dose" objective determination of the MED itself. In the present paper, the recently developed tissue viability imaging (TiVi) technology is presented for the first time as a reliable, easily applicable, high-resolution alternative to LDPI in the divergent beam testing concept. Data obtained after provocation with a range of doses was analysed in order to determine the reaction diameter, which can be related to the MED using field dosimetry. The dose-response features of exposure above the MED and the relationship between naked eye readings and the diameter were determined from the image data. TiVi data were obtained faster than LDPI data and at a higher spatial resolution of 100 μm instead of 1 mm. A tool was developed to centre over the erythema area of the acquired image. Response data could be plotted continuously against dose. Thresholding of processed images compared to naked eye "gold standard" readings showed that the normal skin value +4 standard deviations produced a good fit between both methods. A linear fitting method for the dose-response data provided a further method of determination of the reaction diameter (MED). Erythemal "volume under the surface (VUS)" for the reaction provided a new concept for visualising information. TiVi offers advantages over LDPI in the acquisition and analysis of data collected during divergent beam testing. An increased amount of data compared to traditional phototesting is easily and more objectively obtained which increases applicability in the clinical and research environment.
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  • Ordóñez-Mena, José Manuel, et al. (författare)
  • Quantification of the smoking-associated cancer risk with rate advancement periods : meta-analysis of individual participant data from cohorts of the CHANCES consortium
  • 2016
  • Ingår i: BMC Medicine. - : Springer Science and Business Media LLC. - 1741-7015. ; 14
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Smoking is the most important individual risk factor for many cancer sites but its association with breast and prostate cancer is not entirely clear. Rate advancement periods (RAPs) may enhance communication of smoking related risk to the general population. Thus, we estimated RAPs for the association of smoking exposure (smoking status, time since smoking cessation, smoking intensity, and duration) with total and site-specific (lung, breast, colorectal, prostate, gastric, head and neck, and pancreatic) cancer incidence and mortality.Methods: This is a meta-analysis of 19 population-based prospective cohort studies with individual participant data for 897,021 European and American adults. For each cohort we calculated hazard ratios (HRs) for the association of smoking exposure with cancer outcomes using Cox regression adjusted for a common set of the most important potential confounding variables. RAPs (in years) were calculated as the ratio of the logarithms of the HRs for a given smoking exposure variable and age. Meta-analyses were employed to summarize cohort-specific HRs and RAPs.Results: Overall, 140,205 subjects had a first incident cancer, and 53,164 died from cancer, during an average follow-up of 12 years. Current smoking advanced the overall risk of developing and dying from cancer by eight and ten years, respectively, compared with never smokers. The greatest advancements in cancer risk and mortality were seen for lung cancer and the least for breast cancer. Smoking cessation was statistically significantly associated with delays in the risk of cancer development and mortality compared with continued smoking.Conclusions: This investigation shows that smoking, even among older adults, considerably advances, and cessation delays, the risk of developing and dying from cancer. These findings may be helpful in more effectively communicating the harmful effects of smoking and the beneficial effect of smoking cessation.
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