| 1. |
- 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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| 2. |
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| 3. |
- Filipe, A., et al.
(författare)
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White Book on Physical and Rehabilitation Medicine in Europe Introductions, Executive Summary, and Methodology
- 2018
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Ingår i: European Journal of Physical and Rehabilitation Medicine. - : Edizioni Minerva Medica. - 1973-9087 .- 1973-9095. ; 54:2, s. 125-155
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Tidskriftsartikel (refereegranskat)abstract
- The White Book (WB) of Physical and Rehabilitation Medicine (PRM) in Europe is produced by the 4 European PRM Bodies (European Academy of Rehabilitation Medicine - EARM, European Society of PRM - ESPRM, European Union of Medical Specialists - PRM Section, European College of PRM-ECPRM served by the European Union of Medical Specialists-PRM Board) and constitutes the reference book for PRM physicians in Europe. It has now reached its third edition; the first was published in 1989 and the second in 2006/2007. The WB has multiple purposes, including providing a unifying framework for European countries, to inform decision-makers on European and national level, to offer educational material for PRM trainees and physicians and information about PRM to the medical community, other rehabilitation professionals and the public. The WB states the importance of PRM, a primary medical specialty that is present all over Europe, with a specific corpus disciplinae, a common background and history throughout Europe. PRM is internationally recognized and a partner of major international bodies, including the World Health Organization (WHO). PRM activities are strongly based on the documents of the United Nations (UN) and WHO, such as the Convention of the Rights of Persons with Disabilities (2006), the World Report on Disability (2011), the WHO Global Disability Action Plan 2014-2021 (2014) and the WHO initiative "Rehabilitation 2030: a call for action" (2017). The WB is organized in 4 sections, 11 chapters and some appendices. The WB starts with basic definitions and concepts of PRM and continues with why rehabilitation is needed by individuals and society. Rehabilitation focuses not only on health conditions but also on functioning. Accordingly. PRM is the medical specialty that strives to improve functioning of people with a health condition or experiencing disability. The fundamentals of PRM, the history of the PRM specialty, and the structure and activities of PRM organizations in Europe are presented, followed by a thorough presentation of the practice of PRM, i.e. knowledge and skills of PRM physicians, the clinical field of competence of PRM, the place of the PRM specialty in the healthcare system and society, education and continuous professional development of PRM physicians, specificities and challenges of science and research in PRM. The WB concludes with the way forward for the specialty: challenges and perspectives for the future of PRM.
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| 4. |
- Paixão, Gabriela M. M., et al.
(författare)
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Electrocardiographic Predictors of Mortality: Data from a Primary Care Tele-Electrocardiography Cohort of Brazilian Patients
- 2021
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Ingår i: Hearts. - : MDPI AG. - 2673-3846. ; 2:4, s. 449-458
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Tidskriftsartikel (refereegranskat)abstract
- Computerized electrocardiography (ECG) has been widely used and allows linkage to electronic medical records. The present study describes the development and clinical applications of an electronic cohort derived from a digital ECG database obtained by the Telehealth Network of Minas Gerais, Brazil, for the period 2010–2017, linked to the mortality data from the national information system, the Clinical Outcomes in Digital Electrocardiography (CODE) dataset. From 2,470,424 ECGs, 1,773,689 patients were identified. A total of 1,666,778 (94%) underwent a valid ECG recording for the period 2010 to 2017, with 1,558,421 patients over 16 years old; 40.2% were men, with a mean age of 51.7 [SD 17.6] years. During a mean follow-up of 3.7 years, the mortality rate was 3.3%. ECG abnormalities assessed were: atrial fibrillation (AF), right bundle branch block (RBBB), left bundle branch block (LBBB), atrioventricular block (AVB), and ventricular pre-excitation. Most ECG abnormalities (AF: Hazard ratio [HR] 2.10; 95% CI 2.03–2.17; RBBB: HR 1.32; 95%CI 1.27–1.36; LBBB: HR 1.69; 95% CI 1.62–1.76; first degree AVB: Relative survival [RS]: 0.76; 95% CI0.71–0.81; 2:1 AVB: RS 0.21 95% CI0.09–0.52; and RS 0.36; third degree AVB: 95% CI 0.26–0.49) were predictors of overall mortality, except for ventricular pre-excitation (HR 1.41; 95% CI 0.56–3.57) and Mobitz I AVB (RS 0.65; 95% CI 0.34–1.24). In conclusion, a large ECG database established by a telehealth network can be a useful tool for facilitating new advances in the fields of digital electrocardiography, clinical cardiology and cardiovascular epidemiology.
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| 5. |
- Pink, David A., et al.
(författare)
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Modeling the solid-liquid phase transition in saturated triglycerides
- 2010
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Ingår i: Journal of Chemical Physics. - : AIP Publishing. - 0021-9606 .- 1089-7690. ; 132:5, s. 054502/1-054502/11
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Tidskriftsartikel (refereegranskat)abstract
- We investigated theor. two competing published scenarios for the melting transition of the triglyceride trilaurin (TL): those of (1) Corkery et al., in which the av. state of each TL mol. in the liq. phase is a discotic "Y" conformer whose three chains are dynamically twisted, with an av. angle of ∌120° between them, and those of (2) Cebula et al., in which the liq.-state conformation of the TL mol. in the liq. phase is a nematic h*-conformer whose three chains are in a modified "chair" conformation. We developed two competing models for the two scenarios, in which TL mols. are in a nematic compact-chair (or "h") conformation, with extended, possibly all-trans, chains at low-temps., and in either a Y conformation or an h* conformation in the liq. state at temps. higher than the phase-transition temp., T* = 319 K. We defined an h-Y model as a realization of the proposal of R. Corkery et al. (2007), and explored its predictions by mapping it onto an Ising model in a temp.-dependent field, performing a mean-field approxn., and calcg. the transition enthalpy ΔH. We found that the most plausible realization of the h-Y model, as applied to the solid-liq. phase transition in TL, and likely to all satd. triglycerides, gave a value of ΔH in reasonable agreement with the expt. We then defined an alternative h-h* model as a realization of the proposal of D. J. Cebula et al. (1992), in which the liq. phase exhibits an av. symmetry breaking similar to an h conformation, but with twisted chains, to see whether it could describe the TL phase transition. The h-h* model gave a value of ΔH that was too small by a factor of ∌3-4. We also predicted the temp. dependence of the 1132 cm-1 Raman band for both models, and performed measurements of the ratios of three TL Raman bands in the temp. range of -20° ≀ T ≀ 90°. The exptl. results were in accord with the predictions of the h-Y model and support the proposal of that the liq. state is made up of mols. that are each, on av., in a Y conformation. Finally, we carried out computer simulations of minimal-model TLs in the liq. phase, and concluded that although the individual TL mols. are, on av., Y conformers, long-range discotic order is unlikely to exist.
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| 6. |
- Ribeiro, Antônio H., et al.
(författare)
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Automatic diagnosis of the 12-lead ECG using a deep neural network
- 2020
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- The role of automatic electrocardiogram (ECG) analysis in clinical practice is limited by the accuracy of existing models. Deep Neural Networks (DNNs) are models composed of stacked transformations that learn tasks by examples. This technology has recently achieved striking success in a variety of task and there are great expectations on how it might improve clinical practice. Here we present a DNN model trained in a dataset with more than 2 million labeled exams analyzed by the Telehealth Network of Minas Gerais and collected under the scope of the CODE (Clinical Outcomes in Digital Electrocardiology) study. The DNN outperform cardiology resident medical doctors in recognizing 6 types of abnormalities in 12-lead ECG recordings, with F1 scores above 80% and specificity over 99%. These results indicate ECG analysis based on DNNs, previously studied in a single-lead setup, generalizes well to 12-lead exams, taking the technology closer to the standard clinical practice. The role of automatic electrocardiogram (ECG) analysis in clinical practice is limited by the accuracy of existing models. In that context, the authors present a Deep Neural Network (DNN) that recognizes different abnormalities in ECG recordings which matches or outperform cardiology and emergency resident medical doctors.
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