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| 2. |
- Blauenfeldt, Rolf Ankerlund, et al.
(författare)
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Remote Ischemic Conditioning for Acute Stroke : The RESIST Randomized Clinical Trial
- 2023
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Ingår i: JAMA. - 0098-7484. ; 330:13, s. 1236-1246
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Despite some promising preclinical and clinical data, it remains uncertain whether remote ischemic conditioning (RIC) with transient cycles of limb ischemia and reperfusion is an effective treatment for acute stroke. Objective: To evaluate the effect of RIC when initiated in the prehospital setting and continued in the hospital on functional outcome in patients with acute stroke. Design, Setting, and Participants: This was a randomized clinical trial conducted at 4 stroke centers in Denmark that included 1500 patients with prehospital stroke symptoms for less than 4 hours (enrolled March 16, 2018, to November 11, 2022; final follow-up, February 3, 2023). Intervention: The intervention was delivered using an inflatable cuff on 1 upper extremity (RIC cuff pressure, ≤200 mm Hg [n = 749] and sham cuff pressure, 20 mm Hg [n = 751]). Each treatment application consisted of 5 cycles of 5 minutes of cuff inflation followed by 5 minutes of cuff deflation. Treatment was started in the ambulance and repeated at least once in the hospital and then twice daily for 7 days among a subset of participants. Main Outcomes and Measures: The primary end point was improvement in functional outcome measured as a shift across the modified Rankin Scale (mRS) score (range, 0 [no symptoms] to 6 [death]) at 90 days in the target population with a final diagnosis of ischemic or hemorrhagic stroke. Results: Among 1500 patients who were randomized (median age, 71 years; 591 women [41%]), 1433 (96%) completed the trial. Of these, 149 patients (10%) were diagnosed with transient ischemic attack and 382 (27%) with a stroke mimic. In the remaining 902 patients with a target diagnosis of stroke (737 [82%] with ischemic stroke and 165 [18%] with intracerebral hemorrhage), 436 underwent RIC and 466 sham treatment. The median mRS score at 90 days was 2 (IQR, 1-3) in the RIC group and 1 (IQR, 1-3) in the sham group. RIC treatment was not significantly associated with improved functional outcome at 90 days (odds ratio [OR], 0.95; 95% CI, 0.75 to 1.20, P =.67; absolute difference in median mRS score, -1; -1.7 to -0.25). In all randomized patients, there were no significant differences in the number of serious adverse events: 169 patients (23.7%) in the RIC group with 1 or more serious adverse events vs 175 patients (24.3%) in the sham group (OR, 0.97; 95% CI, 0.85 to 1.11; P =.68). Upper extremity pain during treatment and/or skin petechia occurred in 54 (7.2%) in the RIC group and 11 (1.5%) in the sham group. Conclusions and Relevance: RIC initiated in the prehospital setting and continued in the hospital did not significantly improve functional outcome at 90 days in patients with acute stroke. Trial Registration: ClinicalTrials.gov Identifier: NCT03481777.
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| 3. |
- Hörder, Helena M, et al.
(författare)
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Home as a health promotion setting for older adults
- 2014
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Ingår i: Scandinavian Journal of Public Health. - : SAGE Publications. - 1403-4948 .- 1651-1905. ; 42:Suppl 15, s. 36-40
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Tidskriftsartikel (refereegranskat)abstract
- Background: The number and the proportion of older persons is growing in the Nordic Countries. The growth in the older population has a clear impact on the care system for older persons. One trend is to prioritise home care instead of care in institutions. Another trend is to emphasise preventive and health promotion care. As official guidelines in the Nordic countries state that home is the best place to grow old, it is essential that older persons keep their health and functional capacity in order to be able to live at home for as long as possible. As current policy emphasises living at home, home care, preventive work and health promotion it becomes essential to study the home as a health promotion setting. Objective: The aim of this study was to reach a new understanding of home as a health promotion setting for older persons. Study design: The method used was a literature reflection and analysis with a hermeneutical approach. Results: The results show that with increasing age the home environment becomes a crucial determinant for independence. The home environment supports the self as people age; it has associations with the past, can provide proximity to family, and a sense of being a part of neighbourhood life. Conclusions: Only by taking into consideration the meaning of home and the resources of the individual older person can home function as a true health promoting setting. If health personnel focus solely on risk prevention, they can neglect the perspectives of the older person, resulting in dis-empowerment not health promotion.
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| 4. |
- 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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| 5. |
- Nivestam, Anna, et al.
(författare)
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Health promotion in ageing research in a Nordic context: : A scoping review of doctoral theses
- 2023
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Konferensbidrag (refereegranskat)abstract
- Background: This scoping review is conducted by the ‘healthy ageing’ research group which is part of the Nordic Health Promotion Research Network. Aim: The overall aim is to explore how ageing research under the label ‘health promotion’ is undertaken in a Nordic context. Method: A scoping review method is used where different data bases in Denmark, Finland, Norway, and Sweden were searched for theses published between the years 2011 and 2021. Findings: The preliminary results show that both qualitative and quantitative methods were used. Data was collected mainly from healthy older-home dwelling persons. Theoretical perspectives varied and were sometimes absent. This also applied to definitions of health promotion. The number of thesis published differed between the Nordic countries. Conclusion: To conclude, doctoral theses within the field of healthy ageing research must be more specific about the meaning and use of the concept of Health Promotion. The use of a health promotive theoretical perspectives could help develop a solid theoretical foundation that could guide healthy ageing research.
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| 6. |
- Ahrensbøll-Friis, Ulrik, et al.
(författare)
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Allergic contact dermatitis from dyes used in the temple of spectacles
- 2022
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Ingår i: Contact Dermatitis. - : Wiley. - 0105-1873 .- 1600-0536. ; 86:1, s. 25-28
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Tidskriftsartikel (refereegranskat)abstract
- Background: We observed an increasing number of patients who presented with facial or retro-auricular dermatitis after skin contact with plastic spectacles or plastic covered temples. Objectives: To identify the allergens in plastic spectacles that may cause allergic contact dermatitis. Methods: All patients with suspected allergic contact dermatitis to eyewear were tested with Solvent Orange 60 (SO60), four additionally with Solvent Yellow 14 (SY14), and five with scrapings from their own spectacles. In one case, a chemical analysis of the spectacles was performed to uncover the causative allergen. Results: Three patients were allergic to SO60, two patients to SY14, and two patients were allergic to both SO60 and SY14. Conclusion: Patients with suspected allergic contact dermatitis from spectacles should be tested with SO60 and SY14, and based on findings from previous reports, also with Solvent Red 179.
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| 7. |
- Carlsson, Sven R, et al.
(författare)
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Membrane dynamics in autophagosome biogenesis
- 2015
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Ingår i: Journal of Cell Science. - : The Company of Biologists LTD. - 0021-9533 .- 1477-9137. ; 128:2, s. 193-205
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Bilayered phospholipid membranes are vital to the organization of the living cell. Based on fundamental principles of polarity, membranes create borders allowing defined spaces to be encapsulated. This compartmentalization is a prerequisite for the complex functional design of the eukaryotic cell, yielding localities that can differ in composition and operation. During macroautophagy, cytoplasmic components become enclosed by a growing double bilayered membrane, which upon closure creates a separate compartment, the autophagosome. The autophagosome is then primed for fusion with endosomal and lysosomal compartments, leading to degradation of the captured material. A large number of proteins have been found to be essential for autophagy, but little is known about the specific lipids that constitute the autophagic membranes and the membrane modeling events that are responsible for regulation of autophagosome shape and size. In this Commentary, we review the recent progress in our understanding of the membrane shaping and remodeling events that are required at different steps of the autophagy pathway.
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| 8. |
- Carlsson, Sven R, 1952-, et al.
(författare)
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Recycling endosomes and autophagy
- 2015
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Ingår i: Cell Technology (Saibou Kougaku). - Tokyo : Gakken Medical Shujunsha Co.. ; 34:2, s. 138-142
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 9. |
- Corkery, Dale, et al.
(författare)
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Vibrio cholerae cytotoxin MakA induces noncanonical autophagy resulting in the spatial inhibition of canonical autophagy
- 2021
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Ingår i: Journal of Cell Science. - : The Company of Biologists. - 0021-9533 .- 1477-9137. ; 134:5
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Tidskriftsartikel (refereegranskat)abstract
- Autophagy plays an essential role in the defense against manymicrobial pathogens as a regulator of both innate and adaptive immunity. Some pathogens have evolved sophisticated mechanisms that promote their ability to evade or subvert host autophagy. Here, we describe a novel mechanism of autophagy modulation mediated by the recently discovered Vibrio cholerae cytotoxin, motility-associatedkilling factor A (MakA). pH-dependent endocytosis of MakA by host cells resulted in the formation of a cholesterol-rich endolysosomal membrane aggregate in the perinuclear region. Aggregate formation induced the noncanonical autophagy pathway driving unconventional LC3 (herein referring to MAP1LC3B) lipidation on endolysosomal membranes. Subsequent sequestration of the ATG12-ATG5-ATG16L1 E3-like enzyme complex, required for LC3 lipidation at the membranous aggregate, resulted in an inhibition of both canonical autophagy and autophagy-related processes, including the unconventional secretion of interleukin-1β (IL-1β). These findings identify a novel mechanismof host autophagy modulation and immune modulation employed by V. cholerae during bacterial infection.
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| 10. |
- Durgan, Joanne, et al.
(författare)
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Non-canonical autophagy drives alternative ATG8 conjugation to phosphatidylserine
- 2021
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Ingår i: Molecular Cell. - : Elsevier. - 1097-2765 .- 1097-4164. ; 81:9, s. 2031-2040
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Tidskriftsartikel (refereegranskat)abstract
- Autophagy is a fundamental catabolic process that uses a unique post-translational modification, the conjugation of ATG8 protein to phosphatidylethanolamine (PE). ATG8 lipidation also occurs during non-canonical autophagy, a parallel pathway involving conjugation of ATG8 to single membranes (CASM) at endolysosomal compartments, with key functions in immunity, vision, and neurobiology. It is widely assumed that CASM involves the same conjugation of ATG8 to PE, but this has not been formally tested. Here, we discover that all ATG8s can also undergo alternative lipidation to phosphatidylserine (PS) during CASM, induced pharmacologically, by LC3-associated phagocytosis or influenza A virus infection, in mammalian cells. Importantly, ATG8-PS and ATG8-PE adducts are differentially delipidated by the ATG4 family and bear different cellular dynamics, indicating significant molecular distinctions. These results provide important insights into autophagy signaling, revealing an alternative form of the hallmark ATG8 lipidation event. Furthermore, ATG8-PS provides a specific “molecular signature” for the non-canonical autophagy pathway.
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