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- 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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| 3. |
- Dyson, Kylie, et al.
(författare)
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International variation in survival after out-of-hospital cardiac arrest : A validation study of the Utstein template.
- 2019
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Ingår i: Resuscitation. - : Elsevier BV. - 0300-9572 .- 1873-1570. ; 138, s. 168-181
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Out-of-hospital cardiac arrest (OHCA) survival varies greatly between communities. The Utstein template was developed and promulgated to improve the comparability of OHCA outcome reports, but it has undergone limited empiric validation. We sought to assess how much of the variation in OHCA survival between emergency medical services (EMS) across the globe is explained by differences in the Utstein factors. We also assessed how accurately the Utstein factors predict OHCA survival.METHODS: We performed a retrospective analysis of patient-level prospectively collected data from 12 OHCA registries from 12 countries for the period 1 Jan 2006 through 31 Dec 2011. We used generalized linear mixed models to examine the variation in survival between EMS agencies (n=232).RESULTS: Twelve registries contributed 86,759 cases. Patient arrest characteristics, EMS treatment and patient outcomes varied across registries. Overall survival to hospital discharge was 10% (range, 6% to 22%). Overall survival with Cerebral Performance Category of 1 or 2 (available for 8/12 registries) was 8% (range, 2% to 20%). The area-under-the-curve for the Utstein model was 0.85 (Wald CI: 0.85-0.85). The Utstein factors explained 51% of the EMS agency variation in OHCA survival.CONCLUSIONS: The Utstein factors explained 51% of the variation in survival to hospital discharge among multiple large geographically separate EMS agencies. This suggests that quality improvement and public health efforts should continue to target modifiable Utstein factors to improve OHCA survival. Further study is required to identify the reasons for the variation that is incompletely understood.
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