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- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes
- 2008
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In: Autophagy. - : Landes Bioscience. - 1554-8627 .- 1554-8635. ; 4:2, s. 151-175
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Research review (peer-reviewed)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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- Partonen, Timo, et al.
(author)
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Three circadian clock genes Per2, Arnt1, and Npas2 contribute to winter depression
- 2007
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In: Annals of Medicine. - New York : Informa Healthcare. - 0785-3890 .- 1365-2060. ; 39:3, s. 229-238
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Journal article (peer-reviewed)abstract
- Background. Multiple lines of evidence suggest that the circadian clock contributes to the pathogenesis of winter depression or seasonal affective disorder (SAD). We hypothesized that sequence variations in three genes, including Per2, Arntl, and Npas2, which form a functional unit at the core of the circadian clock, predispose to winter depression.Methods. In silico analysis of the biological effects of allelic differences suggested the target single-nucleotide polymorphisms (SNPs) to be analyzed in a sample of 189 patients and 189 matched controls. The most relevant SNP in each gene was identified for the interaction analysis and included in the multivariate assessment of the combined effects of all three SNPs on the disease risk.Results. SAD was associated with variations in each of the three genes in gene-wise logistic regression analysis. In combination analysis of variations of Per2, Arntl, and Npas2, we found additive effects and identified a genetic risk profile for the disorder. Carriers of the risk genotype combination had the odds ratio of 4.43 of developing SAD as compared with the remaining genotypes, and of 10.67 as compared with the most protective genotype combination.Conclusion. Variations in the three circadian clock genes Per2, Arntl, and Npas2 are associated with the disease, supporting the hypothesis that the circadian clock mechanisms contribute to winter depression.
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- Zimmermann, Stefan, et al.
(author)
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Outcomes of contemporary interventional therapy of ST elevation infarction in patients older than 75 years
- 2009
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In: Clinical Cardiology. - : Wiley. - 0160-9289 .- 1932-8737. ; 32:2, s. 87-93
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Journal article (peer-reviewed)abstract
- BACKGROUND:Data on contemporary real-world outcomes of interventional revascularization in patients > or = 75 y of age with ST elevation infarction (STEMI) are limited.METHODS:We analyzed all 504 consecutive patients who underwent angiography for acute STEMI between 1999 and 2005 at our center, and followed them up over one year. Outcomes in patients > or = 75 y of age were compared with younger patients.RESULTS:Patients > or = 75 y of age (n = 115) were majority females (55% versus 21%, p < 0.001), more cases of diabetes (42% versus 27%, p = 0.004), hypertension (78% versus 65%, p = 0.03) and a history of coronary events (25% versus 15%, p = 0.002). Younger patients were more often smokers (63% versus 30%, p < 0.001). After coronary angiography patients > or = 75 y of age underwent less frequent intervention (PCI; 84% versus 93%, p = 0.01). However, if PCI was performed, technical success rates were similar to younger patients (84% versus 86%). The 30-d mortality was 13% versus 6.4% (p = 0.03), but after successful PCI, the 30-d mortality rate was not significantly higher in old patients (7.4% versus 3.9%, p = 0.23). Bleeding complications were very low in both age groups if the radial access route was chosen. Multivariate predictors of 30-d mortality were cardiogenic shock/survived cardiac arrest, ejection fraction < 30%, conservative treatment or unsuccessful PCI (OR 3.01), renal insufficiency, diabetes, and age. One-y mortality was higher in the elderly (24.3% versus 9.9%, p < 0.001). Among 30-d-survivors, only multivessel disease and age were multivariate predictors of 1-y mortality.CONCLUSION:Patients > or = 75 y of age benefit from PCI in STEMI, and failed or unattempted PCI worsens prognosis in the old as well as in younger patients.
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| 5. |
- Zimmermann, Stefan, et al.
(author)
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Short-term prognosis of contemporary interventional therapy of ST-elevation myocardial infarction : does gender matter?
- 2009
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In: Clinical Research in Cardiology. - : Springer Science and Business Media LLC. - 1861-0684 .- 1861-0692. ; 98:11, s. 709-715
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Journal article (peer-reviewed)abstract
- BACKGROUND:A higher mortality risk for women with acute ST-elevation myocardial infarction (STEMI) has been a common finding in the past, even after acute percutaneous coronary intervention (PCI). We set out to analyze whether there are gender differences in real-world contemporary treatment and outcomes of STEMI.PATIENTS AND METHODS:A retrospective analysis of all consecutive patients with STEMI and acute coronary angiography with the intention of performing a PCI at our center 6/1999-6/2006 was carried out (n = 566). Data were examined for gender-specific differences regarding patients' characteristics, referral patterns, timing of acute symptoms, angiographic findings, procedural details, and adverse events at 30 days after PCI.RESULTS:Women (n = 161) were on average 8 years older than men (n = 405), had higher co-morbidity, were more often transported to the hospital by ambulance and presented less often to the emergency room on their own (4.2% vs. 12.6% in men, P = 0.02). The pre-hospital delay from symptom onset to admission was significantly longer for women (median 185 vs. 135 min, P < 0.02). There was no gender difference in time from admission to PCI (median 46 min vs. 48 min, P = 0.42). Both genders received PCI with similar frequency (88.8% vs. 92.4%, P = 0.19), with similar success rates (83.2% vs. 85.3%, P = 0.68). Thirty-day overall mortality for women was not significantly higher than for men (8.7% vs. 7.2%, P = 0.6). Re-infarction or stroke within 30 days were rare for both genders without gender-specific differences whereas bleeding necessitating blood replacement was significantly more frequent in women (16.8% vs. 5.9%, P < 0.001). In multivariate analysis, female gender was not independently associated with a higher risk of 30-day mortality (OR 0.964, P = 0.93).CONCLUSIONS:Women underwent PCI therapy for STEMI with the same frequency and the same angiographic success as men. Despite their more advanced age and the higher prevalence of co-morbidities, they did not have a significantly higher 30-day mortality rate than men. Female gender was not an independent risk factor of 30-day mortality. Longer pre-hospital delays before hospital admission in women indicate that awareness of risk from coronary artery disease should be further raised in women.
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