Reply to Roy and Pucadyil: A gain of function by a GTPase-impaired Drp1

A.V.S. was supported by Spain Ministry of Science and Innovation/National Research Agency/European Regional Development Fund grant PGC2018-099971-B-I00. I.P.J. acknowledges a predoctoral fellowship from the University of the Basque Country. P.M.M. and R.R. were supported by NIH R01 grant GM121583

Preventing and addressing the stress reactions of health care workers caring for patients with COVID-19: Development of a digital platform (Be + against COVID)

Background: COVID-19 became a major public health concern in March 2020. Due to the high rate of hospitalizations for COVID-19 in a short time, health care workers and other involved staff are subjected to a large workload and high emotional distress. Objective: The objective of this study is to develop a digital tool to provide support resources that might prevent and consider acute stress reactions in health care workers and other support staff due to the COVID-19 pandemic. Methods: The contents of the digital platform were created through an evidence-based review and consensus conference. The website was built using the Google Blogger tool. The Android version of the app was developed in the Java and XML languages using Android Studio version 3.6, and the iOS version was developed in the Swift language using Xcode version 11.5. The app was evaluated externally by the Andalusian Agency for Healthcare Quality. Results: We detected the needs and pressing situations of frontline health care workers, and then, we proposed a serial of recommendations and support resources to address them. These resources were redesigned using the feedback received. A website in three different languages (Spanish, English, and Portuguese) and a mobile app were developed with these contents, and the AppSaludable Quality Seal was granted to the app. A specific self-report scale to measure acute stress and additional tools were included to support the health care workforce. This instrument has been used in several Latin American countries and has been adapted considering cultural differences. The resources section of the website was the most visited with 18, 516 out of 68, 913 (26.9%) visits, and the “Self-Report Acute Stress Scale” was the most visited resource with 6468 out of 18, 516 (34.9%) visits. Conclusions: The Be + against COVID platform (website and app) was developed and launched to offer a pool of recommendations and support resources, which were specifically designed to protect the psychological well-being and the work morale of health care workers. This is an original initiative different from the usual psychological assistance hotlines

Validation of miR-1228-3p as Housekeeping for MicroRNA Analysis in Liquid Biopsies from Colorectal Cancer Patients

BACKGROUND: Circulating microRNA (miRNA) analysis is a growing research field. However, it usually requires an endogenous control or housekeeping (HK) in order to normalize expression of specific miRNAs throughout different samples. Unfortunately, no adequate HK for circulating miRNA analysis is still known in the colorectal cancer (CRC) context whereas several have been suggested. Hence, our aims were to validate the previously suggested miR-1228-3p as HK for CRC studies, to compare its suitability with the widely used miR-16-5p, and to evaluate the influence of hemolysis on both miRNAs. METHODS: We analyzed by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) the expression of miR-1228-3p, miR-16-5p and the spike-in cel-miR-39 in a set of 297 plasmas (92 CRC, 101 advanced adenomas -AA-, and 100 controls) and 213 serum samples (59 CRC, 74 AA and 80 controls). We also analyzed both miRNAs depending on the hemolysis degree in 7 plasmas and 31 serums. RESULTS: Levels of miR-1228-3p and miR-16-5p did not show significant differences between groups although miR-16-5p exhibited more variability in plasma and serum samples. Importantly, the combination of cel-miR-39 and miR-1228-3p was the most stable one. Moreover, we observed that miR-16-5p was significantly influenced by hemolysis in contrast with miR-1228-3p that exhibited no correlation with this confounding factor in both biofluids. CONCLUSION: MiR-1228-3p has been validated as an adequate endogenous control for circulating miRNA analysis in CRC and AA liquid biopsies

A set of quality and safety indicators for hospitals of the «Agencia Valenciana de Salud»

Objetivos: Elaborar un conjunto de indicadores de calidad y seguridad en el contexto de los hospitales de la Agencia Valenciana de Salud. Material y métodos: Se utilizó la técnica Metaplan® para identificar propuestas sobre sostenibilidad y enfermería. Se empleó el catálogo de la Sociedad Espanola ˜ de Calidad Asistencial como punto de partida para los indicadores clínicos. Utilizando la Técnica Delphi 207 profesionales fueron invitados a participar en el proceso para identificar los indicadores más fiables y factibles. Finalmente, la propuesta resultante fue validada por los directivos de 12 hospitales, teniendo en cuenta la variabilidad, objetividad, factibilidad, fiabilidad y sensibilidad de los indicadores. Resultados: La tasa de participación osciló entre el 66,67 y 80,71%. De los 159 indicadores de la propuesta inicial se priorizaron y seleccionaron 68 (21 económicos o de gestión, 22 de cuidados de enfermería y 25 clínicos). De ellos 3 eran comunes a las 3 categorías y 2 no cumplían los criterios específicos de la fase de validación, por lo que el conjunto final consta de 63 indicadores. Conclusiones: Se ha elaborado un conjunto de indicadores de calidad y seguridad. El sistema de información actual permite su monitorización.Objectives: To prepare a set of quality and safety indicators for Hospitals of the «Agencia Valenciana de Salud». Material and methods: The qualitative technique Metaplan® was applied in order to gather proposals on sustainability and nursing. The catalogue of the «Spanish Society of Quality in Healthcare» was adopted as a starting point for clinical indicators. Using the Delphi technique, 207 professionals were invited to participate in the selecting the most reliable and feasible indicators. Lastly, the resulting proposal was validated with the managers of 12 hospitals, taking into account the variability, objectivity, feasibility, reliability and sensitivity, of the indicators. Results: Participation rates varied between 66.67% and 80.71%. Of the 159 initial indicators, 68 were prioritized and selected (21 economic or management indicators, 22 nursing indicators, and 25 clinical or hospital indicators). Three of them were common to all three categories and two did not match the specified criteria during the validation phase, thus obtaining a final catalogue of 63 indicators. Conclusions: A set of quality and safety indicators for Hospitals was prepared. They are currently being monitored using the hospital information systems.Medicin

Allosteric control of dynamin-related protein 1 through a disordered C-terminal Short Linear Motif

The mechanochemical GTPase dynamin-related protein 1 (Drp1) catalyzes mitochondrial and peroxisomal fission, but the regulatory mechanisms remain ambiguous. Here we find that a conserved, intrinsically disordered, six-residue Short Linear Motif at the extreme Drp1 C-terminus, named CT-SLiM, constitutes a critical allosteric site that controls Drp1 structure and function in vitro and in vivo. Extension of the CT-SLiM by non-native residues, or its interaction with the protein partner GIPC-1, constrains Drp1 subunit conformational dynamics, alters self-assembly properties, and limits cooperative GTP hydrolysis, surprisingly leading to the fission of model membranes in vitro. In vivo, the involvement of the native CT-SLiM is critical for productive mitochondrial and peroxisomal fission, as both deletion and non-native extension of the CT-SLiM severely impair their progression. Thus, contrary to prevailing models, Drp1-catalyzed membrane fission relies on allosteric communication mediated by the CT-SLiM, deceleration of GTPase activity, and coupled changes in subunit architecture and assembly-disassembly dynamics

Allosteric control of dynamin-related protein 1 through a disordered C-terminal Short Linear Motif

© The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.The mechanochemical GTPase dynamin-related protein 1 (Drp1) catalyzes mitochondrial and peroxisomal fission, but the regulatory mechanisms remain ambiguous. Here we find that a conserved, intrinsically disordered, six-residue Short Linear Motif at the extreme Drp1 C-terminus, named CT-SLiM, constitutes a critical allosteric site that controls Drp1 structure and function in vitro and in vivo. Extension of the CT-SLiM by non-native residues, or its interaction with the protein partner GIPC-1, constrains Drp1 subunit conformational dynamics, alters self-assembly properties, and limits cooperative GTP hydrolysis, surprisingly leading to the fission of model membranes in vitro. In vivo, the involvement of the native CT-SLiM is critical for productive mitochondrial and peroxisomal fission, as both deletion and non-native extension of the CT-SLiM severely impair their progression. Thus, contrary to prevailing models, Drp1-catalyzed membrane fission relies on allosteric communication mediated by the CT-SLiM, deceleration of GTPase activity, and coupled changes in subunit architecture and assembly-disassembly dynamics.Work in the A.V.S. laboratory was supported by the PGC2018-099971-B-I00 and PID2021-127844NB-I00 grants funded by MCIN/AEI/10.13039/501100011033/ and by “ERDF A way of making Europe” and by the Basque Government Grant IT1625-22.Peer reviewe

Plasma MicroRNA Signature Validation for Early Detection of Colorectal Cancer

OBJECTIVES: Specific microRNA (miRNA) signatures in biological fluids can facilitate earlier detection of the tumors being then minimally invasive diagnostic biomarkers. Circulating miRNAs have also emerged as promising diagnostic biomarkers for colorectal cancer (CRC) screening. In this study, we investigated the performance of a specific signature of miRNA in plasma samples to design a robust predictive model that can distinguish healthy individuals from those with CRC or advanced adenomas (AA) diseases. METHODS: Case control study of 297 patients from 8 Spanish centers including 100 healthy individuals, 101 diagnosed with AA, and 96 CRC cases. Quantitative real-time reverse transcription was used to quantify a signature of miRNA (miRNA19a, miRNA19b, miRNA15b, miRNA29a, miRNA335, and miRNA18a) in plasma samples. Binary classifiers (Support Vector Machine [SVM] linear, SVM radial, and SVM polynomial) were built for the best predictive model. RESULTS: Area under receiving operating characteristic curve of 0.92 (95% confidence interval 0.871-0.962) was obtained retrieving a model with a sensitivity of 0.85 and specificity of 0.90, positive predictive value of 0.94, and negative predictive value of 0.76 when advanced neoplasms (CRC and AA) were compared with healthy individuals. CONCLUSIONS: We identified and validated a signature of 6 miRNAs (miRNA19a, miRNA19b, miRNA15b, miRNA29a, miRNA335, and miRNA18a) as predictors that can differentiate significantly patients with CRC and AA from those who are healthy. However, large-scale validation studies in asymptomatic screening participants should be conducted

Fostering Professional Ethical Competence During Teacher Training Practice

Professionals who have undergone their training at university should possess not only the knowledge-base necessary to practice in their chosen profession, but also the ethical principles that ensure responsible professional practice and the corresponding benefits for society. The research project addressed in the present article aimed to contribute to fostering ethical competence and commitment amongst future teachers. During the experience the participants had the opportunity to design tasks that stimulated reflection, critique and ethical awareness.Specialistai, įgiję universitetinį išsilavinimą, turi būti sukaupę ne tik žinių, kurios būtinos profesinėje veikloje, bet ir gebėti vadovautis etikos principais, kurie užtikrintų atsakingą ir visuomenės gerovei reikalingą profesinę veiklą. Tyrime, pristatomame šiame straipsnyje, analizuojamos būsimųjų mokytojų etinės kompetencijos plėtros ir atsidavimo darbui problemos. Tyrimo dalyviai turėjo galimybę kurti užduotis, kurios skatino refleksiją, kritiką ir etinį sąmoningumą.Les professionnels ayant reçu leur formation auprès des Universités disposeront, non seulement des connaissances de base nécessaires à l'exercice de leur métier, mais aussi les principes éthiques garantissant un exercice professionnel responsable portant bénéfice sur la société. Le projet de recherche présenté sous ce titre a comme objectif la contribution à la favorisation de la compétence éthique et de l'engagement parmi les futurs enseignants. Lors de cette expérience, les participants ont eu l'occasion d'élaborer des tâches favorisant la réflexion, la critique et la pensée critique.Профессионалы, получившие университетское образование, не только получают основные знания для работы по своей профессии, но и моральные принципы, которые обеспечивают ответственную профессиональную работу и соответствующую выгоду для общества. Целью исследовательского проекта,представленного под этим именем, является участие в стимуляции профессиональной этики и компромисса среди будущих преподавателей. Во время проведения эксперимента, участники получили возможность разработать задания, стимулирующие размышление, критику и критичиское сознание.Los profesionales que han recibido su formación en la Universidad, poseerán no solo el conocimiento base necesario para la práctica en su profesión, sino también los principios éticos que aseguran la práctica profesional responsable y el correspondiente beneficio para la sociedad. El proyecto de investigación presentado con este título tiene como objetivo contribuir a estimular la competencia ética y el compromiso entre los futuros docentes. Durante la experiencia, los participantes tuvieron la oportunidad de diseñar tareas que estimularan la reflexión, la crítica y la conciencia crítica

Long -term feeding with high plant protein based diets in gilthead seabream (Sparus aurata, L.) leads to changes in the inflammatory and immune related gene expression at intestinal level

[EN] Background: In order to ensure sustainability of aquaculture production of carnivourous fish species such as the gilthead seabream (Sparus aurata, L.), the impact of the inclusion of alternative protein sources to fishmeal, including plants, has been assessed. With the aim of evaluating long-term effects of vegetable diets on growth and intestinal status of the on-growing gilthead seabream (initial weight = 129 g), three experimental diets were tested: a strict plant protein-based diet (VM), a fishmeal based diet (FM) and a plant protein-based diet with 15% of marine ingredients (squid and krill meal) alternative to fishmeal (VM+). Intestines were sampled after 154 days. Besides studying growth parameters and survival, the gene expression related to inflammatory response, immune system, epithelia integrity and digestive process was analysed in the foregut and hindgut sections, as well as different histological parameters in the foregut. Results: There were no differences in growth performance (p = 0.2703) and feed utilization (p = 0.1536), although a greater fish mortality was recorded in the VM group (p = 0.0141). In addition, this group reported a lower expression in genes related to pro-inflammatory response, as Interleukine-1 beta (il1 beta, p = 0.0415), Interleukine-6 (il6, p = 0.0347) and cyclooxigenase-2 (cox2, p = 0.0014), immune-related genes as immunoglobulin M (igm, p = 0.0002) or bacterial defence genes as alkaline phosphatase (alp, p = 0.0069). In contrast, the VM+ group yielded similar survival rate to FM (p = 0.0141) and the gene expression patterns indicated a greater induction of the inflammatory and immune markers (il1 beta, cox2 and igm). However, major histological changes in gut were not detected. Conclusions: Using plants as the unique source of protein on a long term basis, replacing fishmeal in aqua feeds for gilthead seabream, may have been the reason of a decrease in the level of different pro-inflammatory mediators (il1 beta, il6 and cox2) and immune-related molecules (igm and alp), which reflects a possible lack of local immune response at the intestinal mucosa, explaining the higher mortality observed. Krill and squid meal inclusion in vegetable diets, even at low concentrations, provided an improvement in nutrition and survival parameters compared to strictly plant protein based diets as VM, maybe explained by the maintenance of an effective immune response throughout the assay.The research has been partially funded by Vicerrectorat d'Investigacio, Innovacio i Transferencia of the Universitat Politecnica de Valencia, which belongs to the project Aquaculture feed without fishmeal (SP20120603). 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Deprescribing interventions and their impact on medication adherence in community-dwelling older adults with polypharmacy: a systematic review

Background: Polypharmacy, and the associated adverse drug events such as non-adherence to prescriptions, is a common problem for elderly people living with multiple comorbidities. Deprescribing, i.e. the gradual withdrawal from medications with supervision by a healthcare professional, is regarded as a means of reducing adverse effects of multiple medications including non-adherence. This systematic review examines the evidence of deprescribing as an effective strategy for improving medication adherence amongst older, community dwelling adults. Methods: A mixed methods review was undertaken. Eight bibliographic database and two clinical trials registers were searched between May and December 2017. Results were double screened in accordance with pre-defined inclusion/exclusion criteria related to polypharmacy, deprescribing and adherence in older, community dwelling populations. The Mixed Methods Appraisal Tool (MMAT) was used for quality appraisal and an a priori data collection instrument was used. For the quantitative studies, a narrative synthesis approach was taken. The qualitative data was analysed using framework analysis. Findings were integrated using a mixed methods technique. The review was performed in accordance with the PRISMA reporting statement. Results: A total of 22 original studies were included, of which 12 were RCTs. Deprescribing with adherence as an outcome measure was identified in randomised controlled trials (RCTs), observational and cohort studies from 13 countries between 1996 and 2017. There were 17 pharmacy-led interventions; others were led by General Practitioners (GP) and nurses. Four studies demonstrated an overall reduction in medications of which all studies corresponded with improved adherence. A total of thirteen studies reported improved adherence of which 5 were RCTs. Adherence was reported as a secondary outcome in all but one study. Conclusions: There is insufficient evidence to show that deprescribing improves medication adherence. Only 13 studies (of 22) reported adherence of which only 5 were randomised controlled trials. Older people are particularly susceptible to non-adherence due to multi-morbidity associated with polypharmacy. Bio-psycho-social factors including health literacy and multi-disciplinary team interventions influence adherence. The authors recommend further study into the efficacy and outcomes of medicines management interventions. A consensus on priority outcome measurements for prescribed medications is indicated