Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Barreras para la implementación de la práctica basada en la evidencia (EBP): una encuesta de fisioterapeutas colombianos y españoles

In countries such as Australia, Spain, United States, Colombia, and United Kingdom, the use, teaching and evaluation of ‘evidence-based physical therapy’ (EBPT) in clinical practice has been recently included in educational curriculum. As consequence, PT have support the EBPT, proposing a series of initiatives designed to generate, evaluate and disseminate research, and to implement these results in practice. Despite most research has focused on the use of evidence, including a critical review of studies and scientific literature in clinical practice, if it is desiderate that the use of EBP becomes a reality, it is important to examine the numerous perceived barriers to using research in clinical settings, despite the paucity of studies in this topic. This is especially true for professions such as physiotherapy that has a small research base and few resources compared with other professions. Typically, barriers are context-dependent; therefore, the implementation of strategies should be tailored according to the context and the specific barriers identified. The most commonly reported barrier among PT is the limited time, which constrains the identification and interpretation of research evidence, as well as the ability to apply research findings in clinical practice

Genetic analyses of aplastic anemia and idiopathic pulmonary fibrosis patients with short telomeres, possible implication of DNA-repair genes

Altres ajuts: Funded by one ACCI project from CIBERER and one grant to the FPI cohort from CIBERES.Background: Telomeres are nucleoprotein structures present at the terminal region of the chromosomes. Mutations in genes coding for proteins involved in telomere maintenance are causative of a number of disorders known as telomeropathies. The genetic origin of these diseases is heterogeneous and has not been determined for a significant proportion of patients. Methods: This article describes the genetic characterization of a cohort of patients. Telomere length was determined by Southern blot and quantitative PCR. Nucleotide variants were analyzed either by high-resolution melting analysis and Sanger sequencing of selected exons or by massive sequencing of a panel of genes. Results: Forty-seven patients with telomere length below the 10% of normal population, affected with three telomeropathies: dyskeratosis congenita (4), aplastic anemia (22) or pulmonary fibrosis (21) were analyzed. Eighteen of these patients presented known pathogenic or novel possibly pathogenic variants in the telomere-related genes TERT, TERC, RTEL1, CTC1 and ACD. In addition, the analyses of a panel of 188 genes related to haematological disorders indicated that a relevant proportion of the patients (up to 35%) presented rare variants in genes related to DNA repair or in genes coding for proteins involved in the resolution of complex DNA structures, that participate in telomere replication. Mutations in some of these genes are causative of several syndromes previously associated to telomere shortening. Conclusion: Novel variants in telomere, DNA repair and replication genes are described that might indicate the contribution of variants in these genes to the development of telomeropathies. Patients carrying variants in telomere-related genes presented worse evolution after diagnosis than the rest of patients analyzed

Improving flood resilience through governance strategies: Gauging the state of the art

There has been an upsurge in studies of flood risk governance (FRG): steering and decision-making by public and private actors as a complement to risk assessments and technical management options. The scholarly debate is, however, highly fragmented, complicating the production of cumulative insights. To address this knowledge gap, we used six governance strategies for achieving flood resilience that previously have been put forward as a conceptual framework to review 121 articles published between 2016 and 2019, complemented with insights contained in recent overview articles, to gauge the state-of-the-art in FRG literature: to (a) diversify flood risk management strategies; (b) align the strategies; (c) adequately involve private actors, including citizens; (d) put an adequate rule system in place; (e) cater for sufficient monetary and non-monetary resources; (f) inspire an open and inclusive normative debate. We found, first, that literature is producing insights on increasingly technically advanced risk assessments and agent-based models but societal debate on justice in flood risk governance is getting attention. A clearly emerging topic is that of citizen engagement in flood risk governance. Second, the geographical focus of the studies is still skewed toward the Global North. To make progress in understanding flood risk governance for better resilience more systematic and comparative empirical assessments of flood risk governance in order to derive generalizable lessons while better taking into account the context-specificity of FRG. Testing flood risk governance solutions against comparative cases, by balancing the geographical scope of research efforts, and enhancing interdisciplinary and transdisciplinary working is a way to deliver knowledge for more resilience. This article is categorized under: Human Water > Water Governance Engineering Water > Planning Water