| 1. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes
- 2008
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Ingår i: Autophagy. - : Landes Bioscience. - 1554-8627 .- 1554-8635. ; 4:2, s. 151-175
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Forskningsöversikt (refereegranskat)abstract
- Research in autophagy continues to accelerate,1 and as a result many new scientists are entering the field. Accordingly, it is important to establish a standard set of criteria for monitoring macroautophagy in different organisms. Recent reviews have described the range of assays that have been used for this purpose.2,3 There are many useful and convenient methods that can be used to monitor macroautophagy in yeast, but relatively few in other model systems, and there is much confusion regarding acceptable methods to measure macroautophagy in higher eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers of autophagosomes versus those that measure flux through the autophagy pathway; thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from fully functional autophagy that includes delivery to, and degradation within, lysosomes (in most higher eukaryotes) or the vacuole (in plants and fungi). Here, we present a set of guidelines for the selection and interpretation of the methods that can be used by investigators who are attempting to examine macroautophagy and related processes, as well as by reviewers who need to provide realistic and reasonable critiques of papers that investigate these processes. This set of guidelines is not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to verify an autophagic response.
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| 2. |
- Danesh, John, et al.
(författare)
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Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis
- 2005
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Ingår i: JAMA: The Journal of the American Medical Association. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 294:14, s. 1799-1809
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Forskningsöversikt (refereegranskat)abstract
- CONTEXT: Plasma fibrinogen levels may be associated with the risk of coronary heart disease (CHD) and stroke. OBJECTIVE: To assess the relationships of fibrinogen levels with risk of major vascular and with risk of nonvascular outcomes based on individual participant data. DATA SOURCES: Relevant studies were identified by computer-assisted searches, hand searches of reference lists, and personal communication with relevant investigators. STUDY SELECTION: All identified prospective studies were included with information available on baseline fibrinogen levels and details of subsequent major vascular morbidity and/or cause-specific mortality during at least 1 year of follow-up. Studies were excluded if they recruited participants on the basis of having had a previous history of cardiovascular disease; participants with known preexisting CHD or stroke were excluded. DATA EXTRACTION: Individual records were provided on each of 154,211 participants in 31 prospective studies. During 1.38 million person-years of follow-up, there were 6944 first nonfatal myocardial infarctions or stroke events and 13,210 deaths. Cause-specific mortality was generally available. Analyses involved proportional hazards modeling with adjustment for confounding by known cardiovascular risk factors and for regression dilution bias. DATA SYNTHESIS: Within each age group considered (40-59, 60-69, and > or =70 years), there was an approximately log-linear association with usual fibrinogen level for the risk of any CHD, any stroke, other vascular (eg, non-CHD, nonstroke) mortality, and nonvascular mortality. There was no evidence of a threshold within the range of usual fibrinogen level studied at any age. The age- and sex- adjusted hazard ratio per 1-g/L increase in usual fibrinogen level for CHD was 2.42 (95% confidence interval [CI], 2.24-2.60); stroke, 2.06 (95% CI, 1.83-2.33); other vascular mortality, 2.76 (95% CI, 2.28-3.35); and nonvascular mortality, 2.03 (95% CI, 1.90-2.18). The hazard ratios for CHD and stroke were reduced to about 1.8 after further adjustment for measured values of several established vascular risk factors. In a subset of 7011 participants with available C-reactive protein values, the findings for CHD were essentially unchanged following additional adjustment for C-reactive protein. The associations of fibrinogen level with CHD or stroke did not differ substantially according to sex, smoking, blood pressure, blood lipid levels, or several features of study design. CONCLUSIONS: In this large individual participant meta-analysis, moderately strong associations were found between usual plasma fibrinogen level and the risks of CHD, stroke, other vascular mortality, and nonvascular mortality in a wide range of circumstances in healthy middle-aged adults. Assessment of any causal relevance of elevated fibrinogen levels to disease requires additional research.
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| 3. |
- Aguilar, Maria I., et al.
(författare)
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Treatment of warfarin-associated intracerebral hemorrhage: Literature review and expert opinion
- 2007
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Ingår i: Mayo Clinic Proceedings. - 0025-6196. ; 82:1, s. 82-92
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Forskningsöversikt (refereegranskat)abstract
- Wider use of oral anticoagulants has led to an increasing frequency of warfarin-related intracerebral hemorrhage (ICH). The high early mortality of approximately 50% has remained stable in recent decades. In contrast to spontaneous ICH, the duration of bleeding is, 12 to 24 hours in many patients, offering a longer opportunity for Intervention. Treatment varies widely, and optimal therapy has yet to be defined. An OVID search was conducted from January 1996 to January 2006, combining the terms warfarin or anticoagulation with intracranial hemorrhage or intracerebral hemorrhage. Seven experts on clinical stroke, neurologic intensive care, and hematology were provided with the available information and were asked to independently address 3 clinical scenarios about acute reversal and resumption of anticoagulation in the setting of warfarin-associated ICH. No randomized trials assessing clinical outcomes were found on management of warfarin-associated ICH. All experts agreed that anticoagulation should be urgently reversed, but how to achieve it varied from use of prothrombin complex concentrates only (3 experts) to recombinant factor Vila only (2 experts) to recombinant factor Vila along with fresh frozen plasma (1 expert) and prothrombin complex concentrates or fresh frozen plasma (1 expert). All experts favored resumption of warfarin therapy within 3 to 10 days of ICH in stable patients in whom subsequent anticoagulation is mandatory. No general agreement occurred regarding subsequent anticoagulation of patients with atrial fibrillation who survived warfarin-associated ICH. For warfarin-associated ICH, discontinuing warfarin therapy with administration of vitamin K does not reverse the hemostatic defect for many hours and is inadequate. Reasonable management based on expert opinion includes a wide range of additional measures to reverse anticoagulation in the absence of solid evidence.
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| 4. |
- Eller, Nanna H, et al.
(författare)
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Work-related psychosocial factors and the development of ischemic heart disease : a systematic review.
- 2009
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Ingår i: Cardiology in review. - 1538-4683. ; 17:2, s. 83-97
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Forskningsöversikt (övrigt vetenskapligt/konstnärligt)abstract
- The literature on the relationship between work-related psychosocial factors and the development of ischemic heart disease (IHD) was systematically reviewed: 33 articles presented 51 analyses of studies involving male participants, 18 analyses involving female participants, and 8 analyses with both genders. Twenty of the studies originated in the Nordic countries, and the major dimensions of the Demand-Control Model were the focus of 23 articles. A balanced evaluation of the studies indicates moderate evidence that high psychologic demands, lack of social support, and iso-strain are risk factors for IHD among men. Studies performed during recent years have not shown evidence for lack of control as a risk factor for IHD. Several studies have shown that job strain is a risk factor, but in the more recent ones, these associations can be fully explained by the association between demands and disease risk. Insufficient evidence was found for a relationship between IHD and effort-reward imbalance, injustice, job insecurity, or long working hours. Studies involving women are too few to draw any conclusion concerning women, work stress, and IHD.
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| 5. |
- Hardell, Lennart, et al.
(författare)
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Secret ties to industry and conflicting interests in cancer research
- 2007
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Ingår i: American Journal of Industrial Medicine. - : Wiley-Liss Inc.. - 0271-3586 .- 1097-0274. ; 50:3, s. 227-233
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Forskningsöversikt (refereegranskat)abstract
- Background: Recently it was reported that a Swedish professor in environmental health has for decades worked as a consultant for Philip Morris without reporting his employment to his academic employer or declaring conflicts of interest in his research. The potential for distorting the epidemiological assessments of hazard and risk through paid consultants, pretending to be independent, is not exclusive to the tobacco industry.Methods: Documentation is drawn from peer reviewed publications, websites, documents from the Environmental Protection Agency, University reports, Wellcome Library Special Collections and the Washington Post.Results: Some consulting firms employ university researchers for industry work thereby disguising industry links in the income of large departments. If the industry affiliation is concealed by the scientist, biases from conflicting interests in risk assessments cannot be evaluated and dealt with properly. Furthermore, there is reason to suspect that editors and journal staff may suppress publication of scientific results that are adverse to industry owing to internal conflict of interest between editorial integrity and business needs.Conclusions: Examples of these problems from Sweden, UK, and USA are presented. The shortfalls cited in this article illustrate the need for improved transparency, regulations that will help curb abuses as well as instruments for control and enforcement against abuses.
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| 6. |
- O'Donoghue, Michelle, et al.
(författare)
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Early invasive vs conservative treatment strategies in women and men with unstable angina and non-ST-segment elevation myocardial infarction : a meta-analysis
- 2008
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Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 300:1, s. 71-80
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Forskningsöversikt (refereegranskat)abstract
- CONTEXT: Although an invasive strategy is frequently used in patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS), data from some trials suggest that this strategy may not benefit women. OBJECTIVE: To conduct a meta-analysis of randomized trials to compare the effects of an invasive vs conservative strategy in women and men with NSTE ACS. DATA SOURCES: Trials were identified through a computerized literature search of the MEDLINE and Cochrane databases (1970-April 2008) using the search terms invasive strategy, conservative strategy, selective invasive strategy, acute coronary syndromes, non-ST-elevation myocardial infarction, and unstable angina. STUDY SELECTION: Randomized clinical trials comparing an invasive vs conservative treatment strategy in patients with NSTE ACS. DATA EXTRACTION: The principal investigators for each trial provided the sex-specific incidences of death, myocardial infarction (MI), and rehospitalization with ACS through 12 months of follow-up. DATA SYNTHESIS: Data were combined across 8 trials (3075 women and 7075 men). The odds ratio (OR) for the composite of death, MI, or ACS for invasive vs conservative strategy in women was 0.81 (95% confidence interval [CI], 0.65-1.01; 21.1% vs 25.0%) and in men was 0.73 (95% CI, 0.55-0.98; 21.2% vs 26.3%) without significant heterogeneity between sexes (P for interaction = .26). Among biomarker-positive women, an invasive strategy was associated with a 33% lower odds of death, MI, or ACS (OR, 0.67; 95% CI, 0.50-0.88) and a nonsignificant 23% lower odds of death or MI (OR, 0.77; 95% CI, 0.47-1.25). In contrast, an invasive strategy was not associated with a significant reduction in the triple composite end point in biomarker-negative women (OR, 0.94; 95% CI, 0.61-1.44; P for interaction = .36) and was associated with a nonsignificant 35% higher odds of death or MI (OR, 1.35; 95% CI, 0.78-2.35; P for interaction = .08). Among men, the OR for death, MI, or ACS was 0.56 (95% CI, 0.46-0.67) if biomarker-positive and 0.72 (95% CI, 0.51-1.01) if biomarker-negative (P for interaction = .09). CONCLUSIONS: In NSTE ACS, an invasive strategy has a comparable benefit in men and high-risk women for reducing the composite end point of death, MI, or rehospitalization with ACS. In contrast, our data provide evidence supporting the new guideline recommendation for a conservative strategy in low-risk women.
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| 7. |
- Post, Eric, et al.
(författare)
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Ecological Dynamics Across the Arctic Associated with Recent Climate Change
- 2009
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 325:5946, s. 1355-1358
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Forskningsöversikt (refereegranskat)abstract
- At the close of the Fourth International Polar Year, we take stock of the ecological consequences of recent climate change in the Arctic, focusing on effects at population, community, and ecosystem scales. Despite the buffering effect of landscape heterogeneity, Arctic ecosystems and the trophic relationships that structure them have been severely perturbed. These rapid changes may be a bellwether of changes to come at lower latitudes and have the potential to affect ecosystem services related to natural resources, food production, climate regulation, and cultural integrity. We highlight areas of ecological research that deserve priority as the Arctic continues to warm.
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