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Sökning: WFRF:(Gellert C)

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1.
  • Müezzinler, Aysel, et al. (författare)
  • Smoking and All-cause Mortality in Older Adults : Results From the CHANCES Consortium
  • 2015
  • Ingår i: American Journal of Preventive Medicine. - 0749-3797 .- 1873-2607. ; 49:5, s. e53-e63
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: Smoking is known to be a major cause of death among middle-aged adults, but evidence on its impact and the benefits of smoking cessation among older adults has remained limited. Therefore, we aimed to estimate the influence of smoking and smoking cessation on all-cause mortality in people aged ≥60 years.METHODS: Relative mortality and mortality rate advancement periods (RAPs) were estimated by Cox proportional hazards models for the population-based prospective cohort studies from Europe and the U.S. (CHANCES [Consortium on Health and Ageing: Network of Cohorts in Europe and the U.S.]), and subsequently pooled by individual participant meta-analysis. Statistical analyses were performed from June 2013 to March 2014.RESULTS: A total of 489,056 participants aged ≥60 years at baseline from 22 population-based cohort studies were included. Overall, 99,298 deaths were recorded. Current smokers had 2-fold and former smokers had 1.3-fold increased mortality compared with never smokers. These increases in mortality translated to RAPs of 6.4 (95% CI=4.8, 7.9) and 2.4 (95% CI=1.5, 3.4) years, respectively. A clear positive dose-response relationship was observed between number of currently smoked cigarettes and mortality. For former smokers, excess mortality and RAPs decreased with time since cessation, with RAPs of 3.9 (95% CI=3.0, 4.7), 2.7 (95% CI=1.8, 3.6), and 0.7 (95% CI=0.2, 1.1) for those who had quit <10, 10 to 19, and ≥20 years ago, respectively.CONCLUSIONS: Smoking remains as a strong risk factor for premature mortality in older individuals and cessation remains beneficial even at advanced ages. Efforts to support smoking abstinence at all ages should be a public health priority.
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  • McLennan, S.M., et al. (författare)
  • Elemental Geochemistry of Sedimentary Rocks at Yellowknife Bay, Gale Crater, Mars
  • 2014
  • Ingår i: Science. - 0036-8075 .- 1095-9203. ; 343:6169
  • Tidskriftsartikel (refereegranskat)abstract
    • Sedimentary rocks examined by the Curiosity rover at Yellowknife Bay, Mars, were derived from sources that evolved from an approximately average martian crustal composition to one influenced by alkaline basalts. No evidence of chemical weathering is preserved, indicating arid, possibly cold, paleoclimates and rapid erosion and deposition. The absence of predicted geochemical variations indicates that magnetite and phyllosilicates formed by diagenesis under low-temperature, circumneutral pH, rock-dominated aqueous conditions. Analyses of diagenetic features (including concretions, raised ridges, and fractures) at high spatial resolution indicate that they are composed of iron- and halogen-rich components, magnesium-iron-chlorine–rich components, and hydrated calcium sulfates, respectively. Composition of a cross-cutting dike-like feature is consistent with sedimentary intrusion. The geochemistry of these sedimentary rocks provides further evidence for diverse depositional and diagenetic sedimentary environments during the early history of Mars.
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4.
  • Mons, Ute, et al. (författare)
  • Impact of smoking and smoking cessation on cardiovascular events and mortality among older adults : meta-analysis of individual participant data from prospective cohort studies of the CHANCES consortium
  • 2015
  • Ingår i: BMJ. British Medical Journal. - : BMJ PUBLISHING GROUP. - 1756-1833. ; 350
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE To investigate the impact of smoking and smoking cessation on cardiovascular mortality, acute coronary events, and stroke events in people aged 60 and older, and to calculate and report risk advancement periods for cardiovascular mortality in addition to traditional epidemiological relative risk measures. DESIGN Individual participant meta-analysis using data from 25 cohorts participating in the CHANCES consortium. Data were harmonised, analysed separately employing Cox proportional hazard regression models, and combined by meta-analysis. RESULTS Overall, 503 905 participants aged 60 and older were included in this study, of whom 37 952 died from cardiovascular disease. Random effects meta-analysis of the association of smoking status with cardiovascular mortality yielded a summary hazard ratio of 2.07 (95% CI 1.82 to 2.36) for current smokers and 1.37 (1.25 to 1.49) for former smokers compared with never smokers. Corresponding summary estimates for risk advancement periods were 5.50 years (4.25 to 6.75) for current smokers and 2.16 years (1.38 to 2.39) for former smokers. The excess risk in smokers increased with cigarette consumption in a dose-response manner, and decreased continuously with time since smoking cessation in former smokers. Relative risk estimates for acute coronary events and for stroke events were somewhat lower than for cardiovascular mortality, but patterns were similar. CONCLUSIONS Our study corroborates and expands evidence from previous studies in showing that smoking is a strong independent risk factor of cardiovascular events and mortality even at older age, advancing cardiovascular mortality by more than five years, and demonstrating that smoking cessation in these age groups is still beneficial in reducing the excess risk.
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5.
  • Neuzil, J., et al. (författare)
  • Mitochondria transmit apoptosis signalling in cardiomyocyte-like cells and isolated hearts exposed to experimental ischemia-reperfusion injury
  • 2007
  • Ingår i: Redox report. - 1351-0002 .- 1743-2928. ; 12:3, s. 148-162
  • Tidskriftsartikel (refereegranskat)abstract
    • Ischemia-reperfusion (I/R) is a condition leading to serious complications due to death of cardiac myocytes. We used the cardiomyocyte-like cell line H9c2 to study the mechanism underlying cell damage. Exposure of the cells to simulated I/R lead to their apoptosis. Over-expression of Bcl-2 and Bcl-xL protected the cells from apoptosis while over-expression of Bax sensitized them to programmed cell death induction. Mitochondria-targeted coenzyme Q (mitoQ) and superoxide dismutase both inhibited accumulation of reactive oxygen species (ROS) and apoptosis induction. Notably, mtDNA-deficient cells responded to I/R by decreased ROS generation and apoptosis. Using both in situ and in vivo approaches, it was found that apoptosis occurred during reperfusion following ischemia, and recovery was enhanced when hearts from mice were supplemented with mitoQ. In conclusion, I/R results in apoptosis in cultured cardiac myocytes and heart tissue largely via generation of mitochondria-derived superoxide, with ensuing apoptosis during the reperfusion phase. © W. S. Maney & Son Ltd.
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6.
  • Lanza, Nina L., et al. (författare)
  • Oxidation of manganese in an ancient aquifer, Kimberley formation, Gale crater, Mars
  • 2016
  • Ingår i: Geophysical Research Letters. - 0094-8276 .- 1944-8007. ; 43:14, s. 7398-7407
  • Tidskriftsartikel (refereegranskat)abstract
    • The Curiosity rover observed high Mn abundances (>25wt % MnO) in fracture-filling materials that crosscut sandstones in the Kimberley region of Gale crater, Mars. The correlation between Mn and trace metal abundances plus the lack of correlation between Mn and elements such as S, Cl, and C, reveals that these deposits are Mn oxides rather than evaporites or other salts. On Earth, environments that concentrate Mn and deposit Mn minerals require water and highly oxidizing conditions; hence, these findings suggest that similar processes occurred on Mars. Based on the strong association between Mn-oxide deposition and evolving atmospheric dioxygen levels on Earth, the presence of these Mn phases on Mars suggests that there was more abundant molecular oxygen within the atmosphere and some groundwaters of ancient Mars than in the present day
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7.
  • Neuzil, J., et al. (författare)
  • Induction of cancer cell apoptosis by a-tocopheryl succinate : Molecular pathways and structural requirements
  • 2001
  • Ingår i: The FASEB Journal. - 0892-6638 .- 1530-6860. ; 15:2, s. 403-415
  • Tidskriftsartikel (refereegranskat)abstract
    • The vitamin E analog a-tocopheryl succinate (a-TOS) can induce apoptosis. We show that the proapoptotic activity of a-TOS in hematopoietic and cancer cell lines involves inhibition of protein kinase C (PKC), since phorbol myristyl acetate prevented a-TOS-triggered apoptosis. More selective effectors indicated that a-TOS reduced PKCa isotype activity by increasing protein phosphatase 2A (PP2A) activity. The role of PKCa inhibition in a-TOS-induced apoptosis was confirmed using antisense oligonucleotides or PKCa overexpression. Gain- or loss-of-function bcl-2 mutants implied modulation of bcl-2 activity by PKC/PP2A as a mitochondrial target of a-TOS-induced proapoptotic signals. Structural analogs revealed that a-tocopheryl and succinyl moieties are both required for maximizing these effects. In mice with colon cancer xenografts, a-TOS suppressed tumor growth by 80%. This epitomizes cancer cell killing by a pharmacologically relevant compound without known side effects.
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  • Alleva, R., et al. (författare)
  • Coenzyme Q blocks biochemical but not receptor-mediated apoptosis by increasing mitochondrial antioxidant protection
  • 2001
  • Ingår i: FEBS Letters. - 0014-5793 .- 1873-3468. ; 503:1, s. 46-50
  • Tidskriftsartikel (refereegranskat)abstract
    • Generation of free radicals is often associated with the induction and progression of apoptosis. Therefore, antioxidants can prove anti-apoptotic, and can help to elucidate specific apoptotic pathways. Here we studied whether coenzyme Q, present in membranes in reduced (ubiquinol) or oxidised (ubiquinone) forms, can affect apoptosis induced by various stimuli. Exposure of Jurkat cells to a-tocopheryl succinate (a-TOS), hydrogen peroxide, anti-Fas IgM or TRAIL led to induction of apoptosis. Cell death due to the chemical agents was suppressed in cells enriched with the reduced form of coenzyme Q. However, coenzyme Q did not block cell death induced by the immunological agents. Ubiquinol-10 inhibited reactive oxygen species (ROS) generation in cells exposed to a-TOS, and a mitochondrially targeted coenzyme Q analogue also blocked apoptosis triggered by a-TOS or hydrogen peroxide. Therefore, it is plausible that ubiquinol-10 protects cells from chemically-induced apoptosis by acting as an antioxidant in mitochondria. Our results also indicate that generation of free radicals may not be a critical step in induction of apoptosis by immunological agents. © 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.
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10.
  • Arvidson, R. E., et al. (författare)
  • Opportunity Mars Rover mission : Overview and selected results from Purgatory ripple to traverses to Endeavour crater
  • 2011
  • Ingår i: Journal of Geophysical Research. - Hoboken : Wiley-Blackwell. - 0148-0227 .- 2156-2202. ; 116, s. E00F15-
  • Tidskriftsartikel (refereegranskat)abstract
    • Opportunity has been traversing the Meridiani plains since 25 January 2004 (sol 1), acquiring numerous observations of the atmosphere, soils, and rocks. This paper provides an overview of key discoveries between sols 511 and 2300, complementing earlier papers covering results from the initial phases of the mission. Key new results include (1) atmospheric argon measurements that demonstrate the importance of atmospheric transport to and from the winter carbon dioxide polar ice caps; (2) observations showing that aeolian ripples covering the plains were generated by easterly winds during an epoch with enhanced Hadley cell circulation; (3) the discovery and characterization of cobbles and boulders that include iron and stony-iron meteorites and Martian impact ejecta; (4) measurements of wall rock strata within Erebus and Victoria craters that provide compelling evidence of formation by aeolian sand deposition, with local reworking within ephemeral lakes; (5) determination that the stratigraphy exposed in the walls of Victoria and Endurance craters show an enrichment of chlorine and depletion of magnesium and sulfur with increasing depth. This result implies that regional-scale aqueous alteration took place before formation of these craters. Most recently, Opportunity has been traversing toward the ancient Endeavour crater. Orbital data show that clay minerals are exposed on its rim. Hydrated sulfate minerals are exposed in plains rocks adjacent to the rim, unlike the surfaces of plains outcrops observed thus far by Opportunity. With continued mechanical health, Opportunity will reach terrains on and around Endeavour's rim that will be markedly different from anything examined to date. Copyright 2011 by the American Geophysical Union.
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