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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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- Ardern, C. L., et al.
(författare)
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2018 International Olympic Committee consensus statement
- 2019
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Ingår i: Journal of Orthopaedic and Sports Physical Therapy. - : Elsevier BV. - 0190-6011. ; 35:2, s. 98-122
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Tidskriftsartikel (refereegranskat)abstract
- - In October 2017, the International Olympic Committee hosted an international expert group of physiotherapists and orthopaedic surgeons who specialise in treating and researching paediatric ACL injuries. Representatives from the American Orthopaedic Society for Sports Medicine, European Paediatric Orthopaedic Society, European Society for Sports Traumatology, Knee Surgery & Arthroscopy, International Society of Arthroscopy Knee Surgery and Orthopaedic Sports Medicine, Pediatric Orthopaedic Society of North America and Sociedad Latinoamericana de Artroscopia, Rodilla y Deporte attended. Physiotherapists and orthopaedic surgeons with clinical and research experience in the field, and an ethics expert with substantial experience in the area of sports injuries also participated. Injury management is challenging in the current landscape of clinical uncertainty and limited scientific knowledge. Injury management decisions also occur against the backdrop of the complexity of shared decision-making with children and the potential long-term ramifications of the injury. This consensus statement addresses six fundamental clinical questions regarding the prevention, diagnosis and management of paediatric ACL injuries. The aim of this consensus statement is to provide a comprehensive, evidence-informed summary to support the clinician, and help children with ACL injury and their parents/guardians make the best possible decisions. © 2019
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- Ardern, Clare, et al.
(författare)
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2018 International Olympic Committee consensus statement on prevention, diagnosis and management of paediatric anterior cruciate ligament (ACL) injuries
- 2018
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Ingår i: Knee Surgery Sports Traumatology Arthroscopy. - : Springer Science and Business Media LLC. - 0942-2056 .- 1433-7347. ; 26:4, s. 989-1010
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Tidskriftsartikel (refereegranskat)abstract
- In October 2017, the International Olympic Committee hosted an international expert group of physiotherapists and orthopaedic surgeons who specialise in treating and researching paediatric anterior cruciate ligament (ACL) injuries. Representatives from the American Orthopaedic Society for Sports Medicine, European Paediatric Orthopaedic Society, European Society for Sports Traumatology, Knee Surgery and Arthroscopy, International Society of Arthroscopy Knee Surgery and Orthopaedic Sports Medicine, Pediatric Orthopaedic Society of North America, and Sociedad Latinoamericana de Artroscopia, Rodilla y Deporte attended. Physiotherapists and orthopaedic surgeons with clinical and research experience in the field, and an ethics expert with substantial experience in the area of sports injuries also participated. Injury management is challenging in the current landscape of clinical uncertainty and limited scientific knowledge. Injury management decisions also occur against the backdrop of the complexity of shared decision-making with children and the potential long-term ramifications of the injury. This consensus statement addresses six fundamental clinical questions regarding the prevention, diagnosis, and management of paediatric ACL injuries. The aim of this consensus statement is to provide a comprehensive, evidence-informed summary to support the clinician, and help children with ACL injury and their parents/guardians make the best possible decisions.
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| 6. |
- Ardern, Clare, et al.
(författare)
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2018 International Olympic Committee consensus statement on prevention, diagnosis and management of paediatric anterior cruciate ligament (ACL) injuries
- 2018
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Ingår i: British Journal of Sports Medicine. - : BMJ. - 0306-3674 .- 1473-0480. ; 52:7, s. 422-438
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Tidskriftsartikel (refereegranskat)abstract
- In October 2017, the International Olympic Committee hosted an international expert group of physiotherapists and orthopaedic surgeons who specialise in treating and researching paediatric ACL injuries. Representatives from the American Orthopaedic Society for Sports Medicine, European Paediatric Orthopaedic Society, European Society for Sports Traumatology, Knee Surgery & Arthroscopy, International Society of Arthroscopy Knee Surgery and Orthopaedic Sports Medicine, Pediatric Orthopaedic Society of North America and Sociedad Latinoamericana de Artroscopia, Rodilla y Deporte attended. Physiotherapists and orthopaedic surgeons with clinical and research experience in the field, and an ethics expert with substantial experience in the area of sports injuries also participated. Injury management is challenging in the current landscape of clinical uncertainty and limited scientific knowledge. Injury management decisions also occur against the backdrop of the complexity of shared decision-making with children and the potential long-term ramifications of the injury. This consensus statement addresses six fundamental clinical questions regarding the prevention, diagnosis and management of paediatric ACL injuries. The aim of this consensus statement is to provide a comprehensive, evidence-informed summary to support the clinician, and help children with ACL injury and their parents/guardians make the best possible decisions.
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| 7. |
- Ardern, C. L., et al.
(författare)
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2018 International Olympic Committee Consensus Statement on Prevention, Diagnosis, and Management of Pediatric Anterior Cruciate Ligament Injuries
- 2018
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Ingår i: Orthopaedic Journal of Sports Medicine. - : SAGE Publications. - 2325-9671. ; 6:3
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Tidskriftsartikel (refereegranskat)abstract
- In October 2017, the International Olympic Committee hosted an international expert group of physical therapists and orthopaedic surgeons who specialize in treating and researching pediatric anterior cruciate ligament (ACL) injuries. The purpose of this meeting was to provide a comprehensive, evidence-informed summary to support the clinician and help children with ACL injury and their parents/guardians make the best possible decisions. Representatives from the following societies attended: American Orthopaedic Society for Sports Medicine; European Paediatric Orthopaedic Society; European Society for Sports Traumatology, Knee Surgery, and Arthroscopy; International Society of Arthroscopy, Knee Surgery and Orthopaedic Sports Medicine; Pediatric Orthopaedic Society of North America; and Sociedad Latinoamericana de Artroscopia, Rodilla, y Deporte. Physical therapists and orthopaedic surgeons with clinical and research experience in the field and an ethics expert with substantial experience in the area of sports injuries also participated. This consensus statement addresses 6 fundamental clinical questions regarding the prevention, diagnosis, and management of pediatric ACL injuries. Injury management is challenging in the current landscape of clinical uncertainty and limited scientific knowledge. Injury management decisions also occur against the backdrop of the complexity of shared decision making with children and the potential long-term ramifications of the injury.
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| 8. |
- Carey, J. L., et al.
(författare)
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Novel Arthroscopic Classification of Osteochondritis Dissecans of the Knee
- 2016
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Ingår i: American Journal of Sports Medicine. - : SAGE Publications. - 0363-5465 .- 1552-3365. ; 44:7, s. 1694-1698
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Tidskriftsartikel (refereegranskat)abstract
- Background: Several systems have been proposed for classifying osteochondritis dissecans (OCD) of the knee during surgical evaluation. No single classification includes mutually exclusive categories that capture all of the salient features ov stability, chondral fissuring,0and fragment detachment. Furthermore, no study has assessed the reliability of these classification systems. Purpose: To determine the intra- and interobserver reliability of a novel, comprehensive arthroscopic classification system with mutually exclusivu OCD lesion types. Study Design: Cohort study (diagnosis); Level of evidence, 3. Methods: The Research in OsteoChondritis of the Knee (ROCK) study group developed a classification system for arthroscopic evaluation of OCD of the knee that includes 6 arthroscopic categories - 3 immobile types and 3 mobile types. To optymize comprehensibility and applycability, each was developed with a memorable name, a brief description, a line diagram corresponding to the archetypal arthroscopic appearance, and an arthroscopic photograph depicting this archetype. Thirty representative arthroscopic videos were evaluated by 10 orthopaedic surgeon raters, who classified each lesion. After 4 weeks, the raters again classified the OCD lesions depicted in the 30 videos in a new, randomly selected order. Reliability was assessed via the intraclass correlation coefficient (ICC). Results: The interobserver reliability of this novel arthroscopy classification was estimated by an ICC of 0.94 (95% CI, 0.91-0.97) for the first round and 0.95 (95% CI, 0.93-0.98) for the second round. According to the standards for the magnitude of the reliability coefficient of Altman, these ICCs indicate that interobserver reliability was very good. The intraobserver reliability was estimated by an ICC of 0.96 (95% CI, 0.95-0.97), which indicates that the intraobserver reliability was similarly very good. Conclusion: The ROCK OCD knee arthroscopy classification system demonstrated excellent intra- and interobserver reliability. In light of this reliability, this classification system may be used clinically and to facilitate future research, including multicenter studies for OCD. © American Orthopaedic Society for Sports Medicine.
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| 9. |
- Long, Maeve, et al.
(författare)
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DGAT1 activity synchronises with mitophagy to protect cells from metabolic rewiring by iron depletion
- 2022
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Ingår i: EMBO Journal. - : John Wiley & Sons. - 0261-4189 .- 1460-2075. ; 41
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Tidskriftsartikel (refereegranskat)abstract
- Mitophagy removes defective mitochondria via lysosomal elimination. Increased mitophagy coincides with metabolic reprogramming, yet it remains unknown whether mitophagy is a cause or consequence of such state changes. The signalling pathways that integrate with mitophagy to sustain cell and tissue integrity also remain poorly defined. We performed temporal metabolomics on mammalian cells treated with deferiprone, a therapeutic iron chelator that stimulates PINK1/PARKIN-independent mitophagy. Iron depletion profoundly rewired the metabolome, hallmarked by remodelling of lipid metabolism within minutes of treatment. DGAT1-dependent lipid droplet biosynthesis occurred several hours before mitochondrial clearance, with lipid droplets bordering mitochondria upon iron chelation. We demonstrate that DGAT1 inhibition restricts mitophagy in vitro, with impaired lysosomal homeostasis and cell viability. Importantly, genetic depletion of DGAT1 in vivo significantly impaired neuronal mitophagy and locomotor function in Drosophila. Our data define iron depletion as a potent signal that rapidly reshapes metabolism and establishes an unexpected synergy between lipid homeostasis and mitophagy that safeguards cell and tissue integrity.
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