| 1. |
- Ferrari, P, et al.
(author)
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Alcohol dehydrogenase and aldehyde dehydrogenase gene polymorphisms, alcohol intake and the risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition study
- 2012
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In: European Journal of Clinical Nutrition. - : Springer Science and Business Media LLC. - 0954-3007 .- 1476-5640. ; 66:12, s. 1303-1308
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Journal article (peer-reviewed)abstract
- BACKGROUND/OBJECTIVES: Heavy alcohol drinking is a risk factor of colorectal cancer (CRC), but little is known on the effect of polymorphisms in the alcohol-metabolizing enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) on the alcohol-related risk of CRC in Caucasian populations.SUBJECTS/METHODS: A nested case-control study (1269 cases matched to 2107controls by sex, age, study centre and date of blood collection) was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC) to evaluate the impact of rs1229984 (ADH1B), rs1573496 (ADH7) and rs441 (ALDH2) polymorphisms on CRC risk. Using the wild-type variant of each polymorphism as reference category, CRC risk estimates were calculated using conditional logistic regression, with adjustment for matching factors.RESULTS: Individuals carrying one copy of the rs1229984(A) (ADH1B) allele (fast metabolizers) showed an average daily alcohol intake of 4.3 g per day lower than subjects with two copies of the rs1229984(G) allele (slow metabolizers) (P-diff<0.01). None of the polymorphisms was associated with risk of CRC or cancers of the colon or rectum. Heavy alcohol intake was more strongly associated with CRC risk among carriers of the rs1573496(C) allele, with odds ratio equal to 2.13 (95% confidence interval: 1.26-3.59) compared with wild-type subjects with low alcohol consumption P-((interaction)=0.07).CONCLUSIONS: The rs1229984(A) (ADH1B) allele was associated with a reduction in alcohol consumption. The rs1229984 (ADH1B), rs1573496 (ADH7) and rs441 (ALDH2) polymorphisms were not associated with CRC risk overall in Western-European populations. However, the relationship between alcohol and CRC risk might be modulated by the rs1573496 (ADH7) polymorphism. European Journal of Clinical Nutrition (2012) 66, 1303-1308; doi: 10.1038/ejcn.2012.173; published online 14 November 2012
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| 2. |
- Kyro, C., et al.
(author)
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ALKYLRESORCINOLS (BIOMARKERS OF WHOLE-GRAIN INTAKE) AND RISK OF COLORECTAL CANCER IN THE EUROPEAN PROSPECTIVE INVESTIGATION INTO CANCER AND NUTRITION
- 2013
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In: Annals of Nutrition and Metabolism. - : S. Karger. - 0250-6807 .- 1421-9697. ; 63:Supplement 1, s. 1207-1208
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Journal article (other academic/artistic)abstract
- Background and objectives: Few studies have investigatedthe association between whole-grain intake and colorectal cancer.Whole-grain products are one of the dietary items proneto measurement errors, making the use of objective measures,such as biomarkers, highly relevant. The objective of the studywas to investigate the association between biomarkers ofwhole-grain intake, alkylresorcinols, and colorectal cancer ina nested case-control study within the European ProspectiveInvestigation into Cancer and Nutrition (EPIC). Methods: We included 1372 first incident colorectal cancercases and 1372 individually matched controls and calculatedthe incidence rate ratios (IRR) for overall and sub-sites of colorectalcancer using conditional logistic regression adjusted forpotential confounders.Results: Plasma total alkylresorcinol concentrations werenot associated with risk of overall colorectal cancer, proximalcolon cancer or rectal cancer. However, high plasma total alkylresorcinolconcentrations were statistically significantly associatedwith lower incidence of cancer located in the distal (leftor descending) part of the colon. Adjusted IRR of distal coloncancer for highest versus lowest quartile of plasma alkylresorcinolwas 0.48 (95% confidence interval = 0.28 to 0.83). Furthermore,we observed an inverse association with colon cancerfor the Scandinavian part of the participants. Alkylresorcinolsmay be more appropriate as biomarkers in Middle Europe andScandinavia i.e. in areas where whole grains are regularly consumed.Conclusions: Whole-grain intake, assessed by alkylresorcinols,was associated with a lower incidence of distal coloncancer. Alkylresorcinols seem useful as objective biomarkersof whole-grain intake in populations where whole-grains are astaple part of the diet. Acknowledgements: This work was supportedby World Cancer Research Fund International (WCRF)and WCRF Netherlands (WCRF NL) (2011/436), and NordForsk(Centre of Excellence programme HELGA (070015)).
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| 4. |
- Jenab, Mazda, et al.
(author)
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Association between pre-diagnostic circulating vitamin D concentration and risk of colorectal cancer in European populations : a nested case-control study
- 2010
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In: BMJ. British Medical Journal. - : BMJ Publishing Group. - 0959-8146 .- 0959-535X. ; 340, s. b5500-
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To examine the association between pre-diagnostic circulating vitamin D concentration, dietary intake of vitamin D and calcium, and the risk of colorectal cancer in European populations. DESIGN: Nested case-control study. Setting The study was conducted within the EPIC study, a cohort of more than 520 000 participants from 10 western European countries. PARTICIPANTS: 1248 cases of incident colorectal cancer, which developed after enrolment into the cohort, were matched to 1248 controls MAIN OUTCOME MEASURES: Circulating vitamin D concentration (25-hydroxy-vitamin-D, 25-(OH)D) was measured by enzyme immunoassay. Dietary and lifestyle data were obtained from questionnaires. Incidence rate ratios and 95% confidence intervals for the risk of colorectal cancer by 25-(OH)D concentration and levels of dietary calcium and vitamin D intake were estimated from multivariate conditional logistic regression models, with adjustment for potential dietary and other confounders. RESULTS: 25-(OH)D concentration showed a strong inverse linear dose-response association with risk of colorectal cancer (P for trend <0.001). Compared with a pre-defined mid-level concentration of 25-(OH)D (50.0-75.0 nmol/l), lower levels were associated with higher colorectal cancer risk (<25.0 nmol/l: incidence rate ratio 1.32 (95% confidence interval 0.87 to 2.01); 25.0-49.9 nmol/l: 1.28 (1.05 to 1.56), and higher concentrations associated with lower risk (75.0-99.9 nmol/l: 0.88 (0.68 to 1.13); >or=100.0 nmol/l: 0.77 (0.56 to 1.06)). In analyses by quintile of 25-(OH)D concentration, patients in the highest quintile had a 40% lower risk of colorectal cancer than did those in the lowest quintile (P<0.001). Subgroup analyses showed a strong association for colon but not rectal cancer (P for heterogeneity=0.048). Greater dietary intake of calcium was associated with a lower colorectal cancer risk. Dietary vitamin D was not associated with disease risk. Findings did not vary by sex and were not altered by corrections for season or month of blood donation. CONCLUSIONS: The results of this large observational study indicate a strong inverse association between levels of pre-diagnostic 25-(OH)D concentration and risk of colorectal cancer in western European populations. Further randomised trials are needed to assess whether increases in circulating 25-(OH)D concentration can effectively decrease the risk of colorectal cancer.
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| 5. |
- Kazemi Seresht, Ali, 1980, et al.
(author)
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Long-Term Adaptation of Saccharomyces cerevisiae to the Burden of Recombinant Insulin Production
- 2013
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In: Biotechnology and Bioengineering. - : Wiley. - 0006-3592 .- 1097-0290. ; 110:10, s. 2749-2763
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Journal article (peer-reviewed)abstract
- High-level production of heterologous proteins is likely to impose a metabolic burden on the host cell and can thus affect various aspects of cellular physiology. A data-driven approach was applied to study the secretory production of a human insulin analog precursor (IAP) in Saccharomyces cerevisiae during prolonged cultivation (80 generations) in glucose-limited aerobic chemostat cultures. Physiological characterization of the recombinant cells involved a comparison with cultures of a congenic reference strain that did not produce IAP, and time-course analysis of both strains aimed at identifying the metabolic adaptation of the cells towards the burden of IAP production. All cultures were examined at high cell density conditions (30g/L dry weight) to increase the industrial relevance of the results. The burden of heterologous protein production in the recombinant strain was explored by global transcriptome analysis and targeted metabolome analysis, including the analysis of intracellular amino acid pools, glycolytic metabolites, and TCA intermediates. The cellular re-arrangements towards IAP production were categorized in direct responses, for example, enhanced metabolism of amino acids as precursors for the formation of IAP, as well as indirect responses, for example, changes in the central carbon metabolism. As part of the long-term adaptation, a metabolic re-modeling of the IAP-expressing strain was observed, indicating an augmented negative selection pressure on glycolytic overcapacity, and the emergence of mitochondrial dysfunction. The evoked metabolic re-modeling of the cells led to less optimal conditions with respect to the expression and processing of the target protein and thus decreased the cellular expression capacity for the secretory production of IAP during prolonged cultivation.
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| 8. |
- Ng-Kamstra, J. S., et al.
(author)
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Perioperative mortality rates in low-income and middle-income countries: a systematic review and meta-analysis
- 2018
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In: Bmj Global Health. - : BMJ. - 2059-7908. ; 3:3
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Journal article (peer-reviewed)abstract
- Introduction The Lancet Commission on Global Surgery proposed the perioperative mortality rate (POMR) as one of the six key indicators of the strength of a country's surgical system. Despite its widespread use in high-income settings, few studies have described procedure-specific POMR across low-income and middle-income countries (LMICs). We aimed to estimate POMR across a wide range of surgical procedures in LMICs. We also describe how POMR is defined and reported in the LMIC literature to provide recommendations for future monitoring in resource-constrained settings. Methods We did a systematic review of studies from LMICs published from 2009 to 2014 reporting POMR for any surgical procedure. We extracted select variables in duplicate from each included study and pooled estimates of POMR by type of procedure using random-effects meta-analysis of proportions and the Freeman-Tukey double arcsine transformation to stabilise variances. Results We included 985 studies conducted across 83 LMICs, covering 191 types of surgical procedures performed on 1 020 869 patients. Pooled POMR ranged from less than 0.1% for appendectomy, cholecystectomy and caesarean delivery to 20%-27% for typhoid intestinal perforation, intracranial haemorrhage and operative head injury. We found no consistent associations between procedure-specific POMR and Human Development Index (HDI) or income-group apart from emergency peripartum hysterectomy POMR, which appeared higher in low-income countries. Inpatient mortality was the most commonly used definition, though only 46.2% of studies explicitly defined the time frame during which deaths accrued. Conclusions Efforts to improve access to surgical care in LMICs should be accompanied by investment in improving the quality and safety of care. To improve the usefulness of POMR as a safety benchmark, standard reporting items should be included with any POMR estimate. Choosing a basket of procedures for which POMR is tracked may offer institutions and countries the standardisation required to meaningfully compare surgical outcomes across contexts and improve population health outcomes.
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| 9. |
- Selck, H., et al.
(author)
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Assessing and managing multiple risks in a changing worldThe Roskilde recommendations
- 2017
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In: Environmental Toxicology and Chemistry. - Hoboken, NJ : Wiley. - 0730-7268 .- 1552-8618. ; 36:1, s. 7-16
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Journal article (peer-reviewed)abstract
- Roskilde University (Denmark) hosted a November 2015 workshop, Environmental RiskAssessing and Managing Multiple Risks in a Changing World. This Focus article presents the consensus recommendations of 30 attendees from 9 countries regarding implementation of a common currency (ecosystem services) for holistic environmental risk assessment and management; improvements to risk assessment and management in a complex, human-modified, and changing world; appropriate development of protection goals in a 2-stage process; dealing with societal issues; risk-management information needs; conducting risk assessment of risk management; and development of adaptive and flexible regulatory systems. The authors encourage both cross-disciplinary and interdisciplinary approaches to address their 10 recommendations: 1) adopt ecosystem services as a common currency for risk assessment and management; 2) consider cumulative stressors (chemical and nonchemical) and determine which dominate to best manage and restore ecosystem services; 3) fully integrate risk managers and communities of interest into the risk-assessment process; 4) fully integrate risk assessors and communities of interest into the risk-management process; 5) consider socioeconomics and increased transparency in both risk assessment and risk management; 6) recognize the ethical rights of humans and ecosystems to an adequate level of protection; 7) determine relevant reference conditions and the proper ecological context for assessments in human-modified systems; 8) assess risks and benefits to humans and the ecosystem and consider unintended consequences of management actions; 9) avoid excessive conservatism or possible underprotection resulting from sole reliance on binary, numerical benchmarks; and 10) develop adaptive risk-management and regulatory goals based on ranges of uncertainty. Environ Toxicol Chem 2017;36:7-16. (c) 2016 SETAC
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| 10. |
- Baudin, M., et al.
(author)
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MD simulations of a doped ceria surface - very large surface ion motion
- 2001
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In: Chemical Physics Letters. - 0009-2614 .- 1873-4448. ; 335:06-maj, s. 517-523
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Journal article (peer-reviewed)abstract
- Mean-square displacements (MSDs) and individual-ion square-displacements (ISDs) for the different constituents in Ca-doped CeO2(0 1 1) slabs at 300 K have been studied as a function of depth from the surface. Constant pressure-constant temperature MD simulations were used. The MSDs are 2-3 times larger at the surface than in the bulk, but ISDs as large as ca. 150 times the surface MSD value were observed during short-time periods for anions next to an anion vacancy at the surface. The chemical implications of this kind of motion are important, since transient structural distortions of this magnitude will lead to large electron re-distributions.
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