| 1. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are 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 monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 2. |
- Axfors, Cathrine, et al.
(författare)
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Mortality outcomes with hydroxychloroquine and chloroquine in COVID-19 from an international collaborative meta-analysis of randomized trials
- 2021
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Substantial COVID-19 research investment has been allocated to randomized clinical trials (RCTs) on hydroxychloroquine/chloroquine, which currently face recruitment challenges or early discontinuation. We aim to estimate the effects of hydroxychloroquine and chloroquine on survival in COVID-19 from all currently available RCT evidence, published and unpublished. We present a rapid meta-analysis of ongoing, completed, or discontinued RCTs on hydroxychloroquine or chloroquine treatment for any COVID-19 patients (protocol: https://osf.io/QESV4/). We systematically identified unpublished RCTs (ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, Cochrane COVID-registry up to June 11, 2020), and published RCTs (PubMed, medRxiv and bioRxiv up to October 16, 2020). All-cause mortality has been extracted (publications/preprints) or requested from investigators and combined in random-effects meta-analyses, calculating odds ratios (ORs) with 95% confidence intervals (CIs), separately for hydroxychloroquine and chloroquine. Prespecified subgroup analyses include patient setting, diagnostic confirmation, control type, and publication status. Sixty-three trials were potentially eligible. We included 14 unpublished trials (1308 patients) and 14 publications/preprints (9011 patients). Results for hydroxychloroquine are dominated by RECOVERY and WHO SOLIDARITY, two highly pragmatic trials, which employed relatively high doses and included 4716 and 1853 patients, respectively (67% of the total sample size). The combined OR on all-cause mortality for hydroxychloroquine is 1.11 (95% CI: 1.02, 1.20; I-2=0%; 26 trials; 10,012 patients) and for chloroquine 1.77 (95%CI: 0.15, 21.13, I-2=0%; 4 trials; 307 patients). We identified no subgroup effects. We found that treatment with hydroxychloroquine is associated with increased mortality in COVID-19 patients, and there is no benefit of chloroquine. Findings have unclear generalizability to outpatients, children, pregnant women, and people with comorbidities. Hydroxychloroquine and chloroquine have been investigated as a potential treatment for Covid-19 in several clinical trials. Here the authors report a meta-analysis of published and unpublished trials, and show that treatment with hydroxychloroquine for patients with Covid-19 was associated with increased mortality, and there was no benefit from chloroquine.
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| 3. |
- Erlinge, David, et al.
(författare)
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Diagnosis and management of non-STEMI coronary syndromes
- 2016. - 2
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Ingår i: Oxford Textbook of Critical Care. - : Oxford University Press. - 9780199600830 ; , s. 678-681
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Bokkapitel (refereegranskat)abstract
- Acute coronary syndromes are classified as ST segment elevation myocardial infarction (STEMI), non-STEMI (NSTEMI) or unstable angina. Most patients with NSTEMI present with a history of chest pain that has subsided spontaneously before or soon after arrival at the emergency room, but with positive cardiac markers (usually troponin T or I) indicative of myocardial infarction. NSTEMI has a risk of recurrent myocardial infarction of 15–20% and a 15% chance of 1-year mortality. Patients with non-STE-acute coronary syndromes are at similar risk as a STEMI patient at 1 year. The strongest objective signs of NSTEMI are a positive troponin and ST segment depression. NSTEMI should be acutely treated with aspirin, an adenosine diphosphate-receptor antagonist, and an anticoagulant (fondaparinux or low molecular weight heparins). NSTEMI should be investigated with coronary angiography within 72 hours. Curative treatment is percutaneous coronary intervention or coronary artery bypass grafting.
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| 4. |
- Erlinge, David, et al.
(författare)
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Diagnosis and management of ST-elevation of myocardial infarction
- 2016. - 2
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Ingår i: Oxford Textbook of Critical Care. - : Oxford University Press. - 9780199600830 - 9780199600830 ; , s. 682-687
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Bokkapitel (refereegranskat)abstract
- ST-elevation myocardial infarction (STEMI) is generally caused by a ruptured plaque that triggers local thrombus formation, which occludes the coronary artery. STEMI should be diagnosed rapidly, based on the combination of ST-segment elevation and symptoms of acute myocardial infarction. The main treatment objective is myocardial tissue reperfusion as quickly as possible. The preferred method of reperfusion is primary percutaneous coronary interventionif transport time is below 2 hours, and thrombolysis if longer STEMI patients with acute onset cardiogenic shock should be evaluated by echocardiography to exclude mechanical complications, such as flail mitral insufficiency, ventricular septal defect or tamponade. Secondary prevention includes aspirin, adenosine diphosphate receptor antagonists, statins, beta-blockers, angiotensin-converting enzymeinhibitors, and lifestyle changes.
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