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- Jenab, M, et al.
(författare)
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Plasma and dietary carotenoid, retinol and tocopherol levels and the risk of gastric adenocarcinomas in the European prospective investigation into cancer and nutrition
- 2006
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 1532-1827 .- 0007-0920. ; 95:3, s. 406-415
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Tidskriftsartikel (refereegranskat)abstract
- Despite declining incidence rates, gastric cancer (GC) is a major cause of death worldwide. Its aetiology may involve dietary antioxidant micronutrients such as carotenoids and tocopherols. The objective of this study was to determine the association of plasma levels of seven common carotenoids, their total plasma concentration, retinol and alpha- and gamma-tocopherol, with the risk of gastric adenocarcinoma in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), a large cohort involving 10 countries. A secondary objective was to determine the association of total sum of carotenoids, retinol and alpha-tocopherol on GCs by anatomical subsite (cardia/noncardia) and histological subtype (diffuse/intestinal). Analytes were measured by high-performance liquid chromatography in prediagnostic plasma from 244 GC cases and 645 controls matched by age, gender, study centre and date of blood donation. Conditional logistic regression models adjusted by body mass index, total energy intake, smoking and Helicobacter pylori infection status were used to estimate relative cancer risks. After an average 3.2 years of follow-up, a negative association with GC risk was observed in the highest vs the lowest quartiles of plasma beta-cryptoxanthin (odds ratio (OR) = 0.53, 95% confidence intervals (CI) = 0.30-0.94, P(trend) = 0.006), zeaxanthin (OR = 0.39, 95% CI = 0.22-0.69, P(trend) = 0.005), retinol (OR = 0.55, 95% CI = 0.33-0.93, P(trend) = 0.005) and lipid-unadjusted alpha-tocopherol (OR = 0.59, 95% CI = 0.37-0.94, P(trend) = 0.022). For all analytes, no heterogeneity of risk estimates or significant associations were observed by anatomical subsite. In the diffuse histological subtype, an inverse association was observed with the highest vs lowest quartile of lipid-unadjusted alpha-tocopherol (OR = 0.26, 95% CI = 0.11-0.65, P(trend) = 0.003). These results show that higher plasma concentrations of some carotenoids, retinol and alpha-tocopherol are associated with reduced risk of GC.
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- Grimsholm, O., et al.
(författare)
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The Interplay between CD27(dull) and CD27(brig)(ht) B Cells Ensures the Flexibility, Stability, and Resilience of Human B Cell Memory
- 2020
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 30:9
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Tidskriftsartikel (refereegranskat)abstract
- Memory B cells (MBCs) epitomize the adaptation of the immune system to the environment. We identify two MBC subsets in peripheral blood, CD27(dull) and CD27(bright) MBCs, whose frequency changes with age. Heavy chain variable region (VH) usage, somatic mutation frequency replacement-to-silent ratio, and CDR3 property changes, reflecting consecutive selection of highly antigen-specific, low cross-reactive antibody variants, all demonstrate that CD27(du)(ll) and CD27(bright) MBCs represent sequential MBC developmental stages, and stringent antigen-driven pressure selects CD27(du)(ll) into the CD27(bright) MBC pool. Dynamics of human MBCs are exploited in pregnancy, when 50% of maternal MBCs are lost and CD27(du)(ll) MBCs transit to the more differentiated CD27 bright stage. In the postpartum period, the maternal MBC pool is replenished by the expansion of persistent CD27(du)(ll) clones. Thus, the stability and flexibility of human B cell memory is ensured by CD27(du)(ll) MBCs that expand and differentiate in response to change.
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- Apple, FS, et al.
(författare)
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IFCC educational materials on selected analytical and clinical applications of high sensitivity cardiac troponin assays
- 2015
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Ingår i: Clinical Biochemistry. - : Elsevier BV. - 0009-9120 .- 1873-2933. ; 48:4-5, s. 201-203
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Tidskriftsartikel (refereegranskat)abstract
- In 2011, the IFCC Task Force on Clinical Applications of Cardiac Bio-Markers (TF-CB) was formed, with the purpose of providing evidence based educational materials to assist all biomarker users, i.e. laboratorians, clinicians, researchers, in-vitro diagnostics and regulatory agencies, in better understanding important analytical and clinical aspects of established and novel cardiac biomarkers for use in clinical practice and research. The goal of the task force was to promulgate the same information conjointly through the in vitro diagnostic industry to the laboratory, emergency department and cardiologists. The initial undertaking of the TF-CB, which is comprised of laboratory medicine scientists, emergency medicine physicians and cardiologists, was to address two key issues pertaining to implementing high-sensitivity cardiac troponin (hs-cTn) assays in clinical practice: the 99th percentile upper reference limit (URL) and calculating serial change values in accord with the Universal Definition of AMI. The highlights of both concepts from IFCC statements are described.
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- Mair, J., et al.
(författare)
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How is cardiac troponin released from injured myocardium?
- 2018
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Ingår i: European Heart Journal-Acute Cardiovascular Care. - : Oxford University Press (OUP). - 2048-8726 .- 2048-8734. ; 7:6, s. 553-560
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Tidskriftsartikel (refereegranskat)abstract
- Cardiac troponin I and cardiac troponin T are nowadays the criterion biomarkers for the laboratory diagnosis of acute myocardial infarction due to their very high sensitivities and specificities for myocardial injury. However, still many aspects of their degradation, tissue release and elimination from the human circulation are incompletely understood. Myocardial injury may be caused by a variety of different mechanisms, for example, myocardial ischaemia, inflammatory and immunological processes, trauma, drugs and toxins, and myocardial necrosis is preceded by a substantial reversible prelethal phase. Recent experimental data in a pig model of myocardial ischaemia demonstrated cardiac troponin release into the circulation from apoptotic cardiomyocytes as an alternative explanation for clinical situations with increased cardiac troponin without any other evidence for myocardial necrosis. However, the comparably lower sensitivities of all currently available imaging modalities, including cardiac magnetic resonance imaging for the detection of particularly non-focal myocardial necrosis in patients, has to be considered for cardiac troponin test result interpretation in clinical settings without any other evidence for myocardial necrosis apart from increased cardiac troponin concentrations as well.
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| 24. |
- O'Gorman, Eoin J., et al.
(författare)
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Impacts of Warming on the Structure and Functioning of Aquatic Communities : Individual-to Ecosystem-Level Responses
- 2012
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Ingår i: Advances in Ecological Research, Vol 47. - : Elsevier. - 9780123983152 ; , s. 81-176
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Bokkapitel (refereegranskat)abstract
- Environmental warming is predicted to rise dramatically over the next century, yet few studies have investigated its effects in natural, multi-species systems. We present data collated over an 8-year period from a catchment of geothermally heated streams in Iceland, which acts as a natural experiment on the effects of warming across different organisational levels and spatiotemporal scales. Body sizes and population biomasses of individual species responded strongly to temperature, with some providing evidence to support temperature size rules. Macroinvertebrate and meiofaunal community composition also changed dramatically across the thermal gradient. Interactions within the warm streams in particular were characterised by food chains linking algae to snails to the apex predator, brown trout These chains were missing from the colder systems, where snails were replaced by much smaller herbivores and invertebrate omnivores were the top predators. Trout were also subsidised by terrestrial invertebrate prey, which could have an effect analogous to apparent competition within the aquatic prey assemblage. Top-down effects by snails on diatoms were stronger in the warmer streams, which could account for a shallowing of mass-abundance slopes across the community. This may indicate reduced energy transfer efficiency from resources to consumers in the warmer systems and/or a change in predator-prey mass ratios. All the ecosystem process rates investigated increased with temperature, but with differing thermal sensitivities, with important implications for overall ecosystem functioning (e.g. creating potential imbalances in elemental fluxes). Ecosystem respiration rose rapidly with temperature, leading to increased heterotrophy. There were also indications that food web stability may be lower in the warmer streams.
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- Aradi, Daniel, et al.
(författare)
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Platelet function testing in acute cardiac care - is there a role for prediction or prevention of stent thrombosis and bleeding?
- 2015
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Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 113:2, s. 221-230
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Tidskriftsartikel (refereegranskat)abstract
- The role of platelet function testing in acute coronary syndrome patients undergoing percutaneous coronary intervention remains controversial despite the fact that high platelet reactivity is an independent predictor of stent thrombosis and emerging evidence suggests also a link between low platelet reactivity and bleeding. In this expert opinion paper, the Study Group on Biomarkers in Cardiology of the Acute Cardiovascular Care Association and the Working Group on Thrombosis of the European Society of Cardiology aim to provide an overview of current evidence in this area and recommendations for practicing clinicians.
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- Bronson, P. G., et al.
(författare)
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Common variants at PVT1, ATG13-AMBRA1, AHI1 and CLEC16A are associated with selective IgA deficiency
- 2016
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 48:11, s. 1425-1429
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Tidskriftsartikel (refereegranskat)abstract
- Selective immunoglobulin A deficiency (IgAD) is the most common p rimary immunodeficiency in Europeans. Our genome-wide association study (GWAS) meta-analysis of 1,635 patients with IgAD and 4,852 controls identified four new significant (P < 5 x 10(-8)) loci and association with a rare IFIH1 variant (p.11e923Val). Peak new variants (PVT1, P = 4.3 x 10(-11); ATG13-AMBRA1, P = 6.7 x 10(-10); AHI1, P = 8.4 x 10(-10); CLEC16A, P = 1.4 x 10(-9)) overlapped with autoimmune markers (3/4) and correlated with 21 putative regulatory variants, including expression quantitative trait loci (eQTLs) for AHI1 and DEXI and DNase hypersensitivity sites in FOXP3(+) regulatory T cells. Pathway analysis of the meta-analysis results showed striking association with the KEGG pathway for IgA production (pathway P < 0.0001), with 22 of the 30 annotated pathway genes containing at least one variant with P <= 0.05 in the IgAD meta-analysis. These data suggest that a complex network of genetic effects, including genes known to influence the biology of IgA production, contributes to IgAD.
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| 33. |
- Capella, Gabriel, et al.
(författare)
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DNA repair polymorphisms and the risk of stomach adenocarcinoma and severe chronic gastritis in the EPIC-EURGAST study
- 2008
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Ingår i: International Journal of Epidemiology. - : Oxford University Press (OUP). - 1464-3685 .- 0300-5771. ; 37:6, s. 1316-1325
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Tidskriftsartikel (refereegranskat)abstract
- Background The contribution of genetic variation in DNA repair genes to gastric cancer (GC) risk remains essentially unknown. The aim of this study was to explore the relative contribution of DNA repair gene polymorphisms to GC risk and severe chronic atrophic gastritis (SCAG). Method A nested case control study within the EPIC cohort was performed including 246 gastric adenocarcinomas and 1175 matched controls. Controls with SCAG (n 91), as defined by low pepsinogen A (PGA) levels, and controls with no SCAG (n 1061) were also compared. Twelve polymorphisms at DNA repair genes (MSH2, MLH1, XRCC1, OGG1 and ERCC2) and TP53 gene were analysed. Antibodies against Helicobacter pylori were measured. Results No association was observed for any of these polymorphisms with stomach cancer risk. However, ERCC2 K751Q polymorphism was associated with an increased risk for non-cardial neoplasm [odds ratio (OR) 1.78; 95 confidence interval (CI) 1.023.12], being ERCC2 K751Q and D312N polymorphisms associated with the diffuse type. ERCC2 D312N (OR 2.0; 95 CI 1.093.65) and K751Q alleles (OR 1.82; 95 CI 1.013.30) and XRCC1 R399Q (OR 1.69; 95 CI 1.022.79) allele were associated with an increased risk for SCAG. Conclusion Our study supports a role of ERCC2 in non-cardial GC but not in cardial cancer. A concordant result was observed for subjects with low PGA levels. XRCC1 allele was associated also with SCAG. This is the first prospective study suggesting that individual variation in DNA repair may be relevant for gastric carcinogenesis, a finding that will require further confirmation validation in larger independent studies.
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- Maccari, Maria Elena, et al.
(författare)
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Activated phosphoinositide 3-kinase δ syndrome: Update from the ESID Registry and comparison with other autoimmune-lymphoproliferative inborn errors of immunity.
- 2023
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Ingår i: The Journal of allergy and clinical immunology. - 1097-6825. ; 152:4
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Tidskriftsartikel (refereegranskat)abstract
- Activated phosphoinositide-3-kinase δ syndrome (APDS) is an inborn error of immunity (IEI) with infection susceptibility and immune dysregulation, clinically overlapping with other conditions. Management depends on disease evolution, but predictors of severe disease are lacking.This study sought to report the extended spectrum of disease manifestations in APDS1 versus APDS2; compare these to CTLA4 deficiency, NFKB1 deficiency, and STAT3 gain-of-function (GOF) disease; and identify predictors of severity in APDS.Data was collected from the ESID (European Society for Immunodeficiencies)-APDS registry and was compared with published cohorts of the other IEIs.The analysis of 170 patients with APDS outlines high penetrance and early onset of APDS compared to the other IEIs. The large clinical heterogeneity even in individuals with the same PIK3CD variant E1021K illustrates how poorly the genotype predicts the disease phenotype and course. The high clinical overlap between APDS and the other investigated IEIs suggests relevant pathophysiological convergence of the affected pathways. Preferentially affected organ systems indicate specific pathophysiology: bronchiectasis is typical of APDS1; interstitial lung disease and enteropathy are more common in STAT3 GOF and CTLA4 deficiency. Endocrinopathies are most frequent in STAT3 GOF, but growth impairment is also common, particularly in APDS2. Early clinical presentation is a risk factor for severe disease in APDS.APDS illustrates how a single genetic variant can result in a diverse autoimmune-lymphoproliferative phenotype. Overlap with other IEIs is substantial. Some specific features distinguish APDS1 from APDS2. Early onset is a risk factor for severe disease course calling for specific treatment studies in younger patients.
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| 41. |
- Manjer, Jonas, et al.
(författare)
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Vitamins B2 and B6 and genetic polymorphisms related to one-carbon metabolism as risk factors for gastric adenocarcinoma in the European prospective investigation into cancer and nutrition.
- 2010
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 19:1, s. 28-38
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Tidskriftsartikel (refereegranskat)abstract
- B vitamins and polymorphisms in genes coding for enzymes involved in one-carbon metabolism may affect DNA synthesis and methylation and thereby be implicated in carcinogenesis. Previous data on vitamins B2 and B6 and genetic polymorphisms other than those involving MTHFR as risk factors for gastric cancer (GC) are sparse and inconsistent. In this case-control study nested within the European Prospective Investigation into Cancer and Nutrition cohort, cases (n = 235) and controls (n = 601) were matched for study center, age, sex, and time of blood sampling. B2 and B6 species were measured in plasma, and the sum of riboflavin and flavin mononucleotide was used as the main exposure variable for vitamin B2 status, whereas the sum of pyridoxal 5'-phosphate, pyridoxal, and 4-pyridoxic acid was used to define vitamin B6 status. In addition, we determined eight polymorphisms related to one-carbon metabolism. Relative risks for GC risk were calculated with conditional logistic regression, adjusted for Helicobacter pylori infection status and smoking status. Adjusted relative risks per quartile (95% confidence interval, P(trend)) were 0.85 (0.72-1.01, 0.06) for vitamin B2 and 0.78 (0.65-0.93, <0.01) for vitamin B6. Both relations were stronger in individuals with severe chronic atrophic gastritis. The polymorphisms were not associated with GC risk and did not modify the observed vitamin-cancer associations. In summary, results from this large European cohort study showed an inverse association between vitamin B2 and GC risk, which is borderline significant, and a significant inverse association between vitamin B6 and GC risk.
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- Plebani, Marco, et al.
(författare)
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Substratum-dependent responses of ciliate assemblages to temperature: a natural experiment in Icelandic streams
- 2015
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Ingår i: Freshwater Biology. - : Wiley. - 0046-5070. ; 60:8, s. 1561-1570
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Tidskriftsartikel (refereegranskat)abstract
- Ciliate assemblages play a significant role in the microbial food web. The effects of environmental temperature on assemblage composition may be influenced by abiotic factors such as seasonality and disturbance, but the effects of temperature on ciliate assemblages found on different substrata have not been explored. Sandy bottoms and submerged rocks harbour dissimilar ciliate assemblages, and it might be expected that their ciliate assemblages will respond differently to temperature. We studied how alpha diversity, beta diversity and total biomass of ciliate protist assemblages found on sandy bottoms and submerged rocks differed in 13 geothermally heated streams in Iceland whose mean temperatures range from 5 to 20 degrees C. We recorded number of operational taxonomic units (OTUs) and measured the size of cells in ciliate assemblages from both substrata. Effects of temperature on natural ciliate assemblages were substratum dependent. On rock surfaces, both total ciliate biomass and alpha diversity declined with increasing temperature, and beta diversity increased with increasing temperature difference due to OTU nestedness (assemblages from warm streams being composed chiefly of subsets of the OTUs found in colder streams). In sandy substrata, however, ciliate assemblage composition was independent of temperature. Substratum-specific responses may be due to differences in mechanical disturbance, nutrient availability or exposure to invertebrate grazers. Rock-surface assemblages may be more exposed to the flow and retain less nutrient than those of sandy substratum; thus, they may be more strongly resource limited and more responsive to direct effects of temperature on metabolism. Alternatively, rock-surface assemblages may be more exposed to grazing by invertebrates, which intensifies with temperature. Our study highlights the need to account for environmental context such as substratum type to fully understand the effect of temperature on microbial assemblages in streams. Future increases in global temperatures may affect fresh waters differently depending on their prevalent substratum. Those dominated by hard substrata may have their ciliate assemblages, and thus, food-web structures and ecosystem functioning more strongly affected by warming relative to systems dominated by soft substrata.
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| 47. |
- Thygesen, Kristian, et al.
(författare)
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Recommendations for the use of cardiac troponin measurement in acute cardiac care
- 2010
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 31:18, s. 2197-2204
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Tidskriftsartikel (refereegranskat)abstract
- The release of cardiomyocyte components, i.e. biomarkers, into the bloodstream in higher than usual quantities indicates an ongoing pathological process. Thus, detection of elevated concentrations of cardiac biomarkers in blood is a sign of cardiac injury which could be due to supply-demand imbalance, toxic effects, or haemodynamic stress. It is up to the clinician to determine the most probable aetiology, the proper therapeutic measures, and the subsequent risk implied by the process. For this reason, the measurement of biomarkers always must be applied in relation to the clinical context and never in isolation. There are a large number of cardiac biomarkers, but they can be subdivided into four broad categories, those related to necrosis, inflammation, haemodynamic stress, and/or thrombosis. Their usefulness is dependent on the accuracy and reproducibility of the measurements, the discriminatory limits separating pathology from physiology, and their sensitivity and specificity for specific organ damage and/or disease processes. In recent years, cardiac biomarkers have become important adjuncts to the delivery of acute cardiac care. Therefore, the Working Group on Acute Cardiac Care of the European Society of Cardiology established a committee to deal with ongoing and newly developing issues related to cardiac biomarkers. The intention of the group is to outline the principles for the application of various biomarkers by clinicians in the setting of acute cardiac care in a series of expert consensus documents. The first of these will focus on cardiac troponin, a pivotal marker of cardiac injury/necrosis.
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