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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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- Amgarth-Duff, Ingrid, et al.
(författare)
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Reporting essentials for DElirium bioMarker studies (REDEEMS) : explanation and elaboration
- 2022
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Ingår i: Delirium Communications. - : European Delirium Association. - 2959-104X.
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Tidskriftsartikel (refereegranskat)abstract
- Despite many studies of potential delirium biomarkers, delirium pathophysiology remains unclear. Evidence shows that the quality of reporting delirium biomarker studies is sub-optimal. Better reporting of delirium biomarker studies is needed to understand delirium pathophysiology better. To improve robustness, transparency and uniformity of delirium biomarker study reports, the REDEEMS (Reporting Essentials for DElirium bioMarker Studies) guideline was developed by an international group of delirium researchers through a three-stage process, including a systematic review, a three-round Delphi study, and a follow-up consensus meeting. This process resulted in a 9-item guideline to inform delirium fluid biomarker studies. To enhance implementation of the REDEEMS guideline, this Explanation and Elaboration paper provides a detailed explanation of each item. We anticipate that the REDEEMS guideline will help to accelerate our understanding of delirium pathophysiology by improving the reporting of delirium biomarker research and, consequently the capacity to synthesise results across studies.
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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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- Carrino, David A, et al.
(författare)
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Age-related changes in the proteoglycans of human skin - Specific cleavage of decorin to yield a major catabolic fragment in adult skin
- 2003
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 278:19, s. 17566-17572
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Tidskriftsartikel (refereegranskat)abstract
- Dramatic changes occur in skin as a function of age, including changes in morphology, physiology, and mechanical properties. Changes in extracellular matrix molecules also occur, and these changes likely contribute to the overall age-related changes in the physical properties of skin. The major proteoglycans detected in extracts of human skin are decorin and versican. In addition, adult human skin contains a truncated form of decorin, whereas fetal skin contains virtually undetectable levels of this truncated decorin. Analysis of this molecule, herein referred to as decorunt, indicates that it is a catabolic fragment of decorin rather than a splice variant. With antibody probes to the core protein, decorunt is found to lack the carboxyl-terminal portion of decorin. Further analysis by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry shows that the carboxyl terminus of decorunt is at Phe(170) of decorin. This result indicates that decorunt represents the amino-terminal 43% of the mature decorin molecule. Such a structure is inconsistent with alternative splicing of decorin and suggests that decorunt is a catabolic fragment of decorin. A neoepitope antiserum, anti-VRKVTF, was generated against the carboxyl terminus of decorunt. This antiserum does not recognize intact decorin in any skin proteoglycan sample tested on immunoblots but recognizes every sample of decorunt tested. The results with anti-VRKVTF confirm the identification of the carboxyl terminus of decorunt. Analysis of collagen binding by surface plasmon resonance indicates that the affinity of decorunt for type I collagen is 100-fold less than that of decorin. This observation correlates with the structural analysis of decorunt, in that it lacks regions of decorin previously shown to be important for interaction with type I collagen. The detection of a catabolic fragment of decorin suggests the existence of a specific catabolic pathway for this proteoglycan. Because of the capacity of decorin to influence collagen fibrillogenesis, catabolism of decorin may have important functional implications with respect to the dermal collagen network.
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- Molander, Anders, 1951, et al.
(författare)
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Improved quality of root fillings provided by general dental practitioners educated in nickel-titanium rotary instrumentation.
- 2007
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Ingår i: International endodontic journal. - : Wiley. - 0143-2885 .- 1365-2591. ; 40:4, s. 254-60
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To test the hypothesis that an increased utilization of nickel-titanium rotary instrumentation (NTRI) by general dental practitioners will lead to an increased frequency of good quality root fillings. A second aim was to determine whether the educational format would exert influence on the quality. METHODOLOGY: Dentists were assigned at random to three intervention groups: a 4-h lecture (L-group, n = 40); a 4-h lecture plus a full day hands-on course (LH-group, n = 40); or a control group receiving no instruction (n = 68). The control group received education later on in the study. Radiographs of two root filled molar teeth per dentist were selected at random before the start of the education program and after a 6-month clinical learning period. Using length, seal and shape of root-fillings a 5-level variable was created. RESULTS: The rate of good quality root fillings increased after the introduction of NTRI. Calculated over all types of roots the frequency of excellent (score 1) root fillings increased from 31% to 51% (P = 0.006) in the L-group and from 27% to 47% (P = 0.016) in the LH-group. The frequency of low quality root-fillings (score 5) dropped in the L-group from 22% to 16% (P = 0.29) and in the LH-group from 13% to 9% (P = 0.48). No statistically significant difference was seen among the controls. CONCLUSIONS: When NTRI technology replaced manual stainless steel techniques the rate of good quality root fillings increased. A significant drop in the rate of low quality root fillings was not found.
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- Reit, Claes, 1946, et al.
(författare)
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The effect of educational intervention on the adoption of nickel-titanium rotary instrumentation in a Public Dental Service.
- 2007
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Ingår i: International endodontic journal. - : Wiley. - 0143-2885 .- 1365-2591. ; 40:4, s. 268-74
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To study the influence of two educational programmes on the adoption of nickel-titanium rotary instrumentation (NTRI) amongst general dental practitioners in a short-term as well as a long-term perspective. METHODOLOGY: All dentists employed in the Gothenburg Dental service (n = 148) were enrolled in the study. The clinics in the organization were randomly assigned to one of two educational programmes. In the first programme a 4-h lecture on root canal instrumentation was given. In the second programme the lecture course was supplemented by a 6-h hands-on training session. The short-term effect was measured by a questionnaire distributed 6 months after completed education. The long-term effect was evaluated 4 years later. RESULTS: The overall utilization rate of NTRI increased from 4% to 73%. However, lectures in combination with hands-on training resulted in a better short-term acceptance rate (94%) than if teaching was given only in lecture-format (53%) (P = 0.000). As a consequence, all staff were offered hands-on training. The long-term adoption rate was 88%. Reasons for accepting the new technology usually were found within the 'relative advantage' category. Common reasons for dentists not to adopt NTRI were that they could not get started or that they found no advantage over the old technology. CONCLUSIONS: The short-term adoption of a new technology might be influenced by the design of an introductory educational programme. For clinical procedures, such as root canal instrumentation, the inclusion of hands-on training sessions seems to be important to reach a high acceptance rate.
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- Tallheden, Tommi, 1972, et al.
(författare)
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Phenotypic plasticity of human articular chondrocytes.
- 2003
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Ingår i: The Journal of bone and joint surgery. American volume. - 0021-9355. ; 85-A Suppl 2, s. 93-100
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Tidskriftsartikel (refereegranskat)abstract
- Progenitor cells in mesenchymal tissues are important in the maintenance of tissue homeostasis and regeneration capacity. Articular cartilage is a tissue with a very low capacity for repair. One explanation could be the lack of chondrogenic progenitor cells within the adult tissue. As a test of chondrogenic differentiation potential, we examined the ability of isolated chondrocytes to take on several phenotypic identities within the mesenchymal lineage by applying culture techniques and markers used in the study of the phenotypic plasticity of marrow-derived mesenchymal stem cells (MSCs).
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