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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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- Bowman, E. M. L., et al.
(författare)
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Advancing specificity in delirium: The delirium subtyping initiative
- 2024
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Ingår i: Alzheimers & Dementia. - 1552-5260. ; 20:1, s. 183-194
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUNDDelirium, a common syndrome with heterogeneous etiologies and clinical presentations, is associated with poor long-term outcomes. Recording and analyzing all delirium equally could be hindering the field's understanding of pathophysiology and identification of targeted treatments. Current delirium subtyping methods reflect clinically evident features but likely do not account for underlying biology. METHODSThe Delirium Subtyping Initiative (DSI) held three sessions with an international panel of 25 experts. RESULTSMeeting participants suggest further characterization of delirium features to complement the existing Diagnostic and Statistical Manual of Mental Disorders Fifth Edition Text Revision diagnostic criteria. These should span the range of delirium-spectrum syndromes and be measured consistently across studies. Clinical features should be recorded in conjunction with biospecimen collection, where feasible, in a standardized way, to determine temporal associations of biology coincident with clinical fluctuations. DISCUSSIONThe DSI made recommendations spanning the breadth of delirium research including clinical features, study planning, data collection, and data analysis for characterization of candidate delirium subtypes. HighlightsDelirium features must be clearly defined, standardized, and operationalized.Large datasets incorporating both clinical and biomarker variables should be analyzed together.Delirium screening should incorporate communication and reasoning.
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- Simons, Gwenda, et al.
(författare)
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Systematic review of quantitative preference studies of treatments for rheumatoid arthritis among patients and at-risk populations
- 2022
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Ingår i: Arthritis Research & Therapy. - : Springer Nature. - 1478-6362. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- Treatments used for rheumatoid arthritis (RA) are under investigation for their efficacy to prevent RA in at risk groups. It is therefore important to understand treatment preferences of those at risk. We systematically reviewed quantitative preference studies of drugs to treat, or prevent RA, to inform the design of further studies and trials of RA prevention. Stated preference studies for RA treatment or prevention were identified through a search of five databases. Study characteristics and results were extracted, and the relative importance of different types of treatment attributes was compared across populations. Twenty three studies were included 20 of RA treatments (18 of patients; 2 of the general public) and 3 prevention studies with first-degree relatives (FDRs). Benefits, risks, administration method and cost (when included) were important determinants of treatment choice. A benefit was more important than a risk attribute in half of the studies of RA treatment that included a benefit attribute and 2/3 studies of RA prevention. There was variability in the relative importance of attributes across the few prevention studies. In studies with non-patient participants, attributes describing confidence in treatment effectiveness/safety were more important determinants of choice than in studies with patients. Most preference studies relating to RA are of treatments for established RA. Few studies examine preferences for treatments to prevent RA. Given intense research focus on RA prevention, additional preference studies in this context are needed. Variation in treatment preferences across different populations is not well understood and direct comparisons are needed.
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