Proteolytic degradation of atrial sarcomere proteins underlies contractile defects in atrial fibrillation.

Atrial fibrillation (AFib) is the most common cardiac rhythm disturbance, often treated via electrical cardioversion. Following rhythm restoration, a period of depressed mechanical function known as atrial stunning occurs, suggesting that defects in contractility occur in AFib and are revealed upon restoration of rhythm. This project aims to define the contractile remodeling that occurs in AFib. To assess contractile function, we used a canine atrial tachypacing model of induced AFib. Mass spectrometry analysis showed dysregulation of contractile proteins in samples from AFib compared with sinus rhythm atria. Atrial cardiomyocytes show reduced force of contraction, decreased resting tension, and increased calcium sensitivity in skinned single cardiomyocyte studies. These alterations correlated with degradation of myofilament proteins including myosin heavy chain altering force of contraction, titin altering resting tension, and troponin I altering calcium sensitivity. We measured degradation of other myofilament proteins, including cardiac myosin binding protein C and actinin, that show degradation products in the AFib samples that are absent in the sinus rhythm atria. Many of the degradation products appeared as discrete cleavage products that are generated by calpain proteolysis. We assessed calpain activity and found it to be significantly increased. These results provide an understanding of the contractile remodeling that occurs in AFib and provide insight into the molecular explanation for atrial stunning and the increased risk of atrial thrombus and stroke in AFib.NEW & NOTEWORTHY Atrial fibrillation is the most common cardiac rhythm disorder, and remodeling during atrial fibrillation is highly variable between patients. This study has defined the biophysical changes in contractility that occur in atrial fibrillation along with identifying potential molecular mechanisms that may drive this remodeling. This includes proteolysis of several myofilament proteins including titin, troponin I, myosin heavy chain, myosin binding protein C, and actinin, which is consistent with the observed contractile deficits.

Simulation with a standardised patient to reduce stigma towards people with schizophrenia spectrum disorder among nursing students: A quasi-experimental study.

OBJECTIVES: This study examined the effectiveness of simulation with a standardised patient on the perception of stigma associated with schizophrenia among undergraduate nursing students. It also assessed the reliability of the AQ-27 questionnaire in this context. METHOD: A quasi-experimental study without a control group was conducted on a non-probabilistic sample. The simulation programme used a standardised patient portrayed by a nurse with mental health experience. RESULTS: After simulation, statistically significant stigma improvements were found in six out of nine dimensions; anger and help obtained larger effect sizes (r = 0.392 and 0,307, respectively). Regarding gender, the intragroup analysis revealed that simulation improved stigma among women in six dimensions and among men in four dimensions, with anger and fear showing the highest effect size (r = 0.414 and 0.446, respectively). Regarding previous contact with mental illness among the study participants, the intergroup analysis did not show differences. In the intragroup analysis, simulation improved fear only in the contact group (p = 0,040, r = 0.353). In contrast, simulation changed the response in six dimensions in the no-contact group, similar to the entire group. CONCLUSION: Simulation with a standardised patient is an effective teaching tool for reducing the stigmatisation of people with schizophrenia, thus reducing people's perception of internal causal attribution. It allows for experiencing situations that may be anticipated in clinical practice and reflectively addressing emerging aspects during simulation.

Mechanisms of Sarcomere Protein Mutation-Induced Cardiomyopathies.

PURPOSE OF REVIEW: The pace of identifying cardiomyopathy-associated mutations and advances in our understanding of sarcomere function that underlies many cardiomyopathies has been remarkable. Here, we aim to synthesize how these advances have led to the promising new treatments that are being developed to treat cardiomyopathies. RECENT FINDINGS: The genomics era has identified and validated many genetic causes of hypertrophic and dilated cardiomyopathies. Recent advances in our mechanistic understanding of sarcomere pathophysiology include high-resolution molecular models of sarcomere components and the identification of the myosin super-relaxed state. The advances in our understanding of sarcomere function have yielded several therapeutic agents that are now in development and clinical use to correct contractile dysfunction-mediated cardiomyopathy. New genes linked to cardiomyopathy include targets with limited clinical evidence and require additional investigation. Large portions of cardiomyopathy with family history remain genetically undiagnosed and may be due to polygenic disease.

Validation of a short version of the high-fidelity simulation satisfaction scale in nursing students.

BACKGROUND: Clinical simulation provides a practical and effective learning method during the undergraduate education of health professions. Currently there is only one validated scale in Spanish to assess nursing students' satisfaction with the use of high-fidelity simulation, therefore, our objective is to validate a brief version of this scale in undergraduate nursing students with or without clinical experience. METHOD: A cross-sectional descriptive study was performed. Between 2018 and 2020, the students from all academic courses of the Fundación Jiménez Díaz nursing school completed the satisfaction scale at the end of their simulation experiences. To validate this scale, composed of 33 items and eight dimensions, exploratory factor analysis (EFA) of the principal components was performed, the internal consistency was studied using Cronbach's alpha, and the corrected item-test correlation of each of the items of the total scale was reviewed. RESULTS: 425 students completed the scale, after the exploratory factor analysis, a scale consisting of 25 items distributed into six subscales, each containing between two and six items, explained a variance of 66.5%. The KMO test (Kaiser-Meyer-Olkin) obtained a value of 0.938, Bartlett's sphericity test was < 0.01 and Goodness of Fit Index (GFI) was 0.991. CONCLUSION: The modified ESSAF scale, reduced from 33 to 25 items and divided into six subscales, is as valid and reliable as the original scale for use in nursing students of different levels, with, or without clinical experience.

Partial and complete loss of myosin binding protein H-like cause cardiac conduction defects.

A premature truncation of MYBPHL in humans and a loss of Mybphl in mice is associated with dilated cardiomyopathy, atrial and ventricular arrhythmias, and atrial enlargement. MYBPHL encodes myosin binding protein H-like (MyBP-HL). Prior work in mice indirectly identified Mybphl expression in the atria and in small puncta throughout the ventricle. Because of its genetic association with human and mouse cardiac conduction system disease, we evaluated the anatomical localization of MyBP-HL and the consequences of loss of MyBP-HL on conduction system function. Immunofluorescence microscopy of normal adult mouse ventricles identified MyBP-HL-positive ventricular cardiomyocytes that co-localized with the ventricular conduction system marker contactin-2 near the atrioventricular node and in a subset of Purkinje fibers. Mybphl heterozygous ventricles had a marked reduction of MyBP-HL-positive cells compared to controls. Lightsheet microscopy of normal perinatal day 5 mouse hearts showed enrichment of MyBP-HL-positive cells within and immediately adjacent to the contactin-2-positive ventricular conduction system, but this association was not apparent in Mybphl heterozygous hearts. Surface telemetry of Mybphl-null mice revealed atrioventricular block and atrial bigeminy, while intracardiac pacing revealed a shorter atrial relative refractory period and atrial tachycardia. Calcium transient analysis of isolated Mybphl-null atrial cardiomyocytes demonstrated an increased heterogeneity of calcium release and faster rates of calcium release compared to wild type controls. Super-resolution microscopy of Mybphl heterozygous and homozygous null atrial cardiomyocytes showed ryanodine receptor disorganization compared to wild type controls. Abnormal calcium release, shorter atrial refractory period, and atrial dilation seen in Mybphl null, but not wild type control hearts, agree with the observed atrial arrhythmias, bigeminy, and atrial tachycardia, whereas the proximity of MyBP-HL-positive cells with the ventricular conduction system provides insight into how a predominantly atrial expressed gene contributes to ventricular arrhythmias and ventricular dysfunction.

Inulin Improves Diet-Induced Hepatic Steatosis and Increases Intestinal Akkermansia Genus Level.

Hepatic steatosis is characterized by triglyceride accumulation within hepatocytes in response to a high calorie intake, and it may be related to intestinal microbiota disturbances. The prebiotic inulin is a naturally occurring polysaccharide with a high dietary fiber content. Here, we evaluate the effect of inulin on the intestinal microbiota in a non-alcoholic fatty liver disease model. Mice exposed to a standard rodent diet or a fat-enriched diet, were supplemented or not, with inulin. Liver histology was evaluated with oil red O and H&E staining and the intestinal microbiota was determined in mice fecal samples by 16S rRNA sequencing. Inulin treatment effectively prevents liver steatosis in the fat-enriched diet group. We also observed that inulin re-shaped the intestinal microbiota at the phylum level, were Verrucomicrobia genus significantly increased in the fat-diet group; specifically, we observed that Akkermansia muciniphila increased by 5-fold with inulin supplementation. The family Prevotellaceae was also significantly increased in the fat-diet group. Overall, we propose that inulin supplementation in liver steatosis-affected animals, promotes a remodeling in the intestinal microbiota composition, which might regulate lipid metabolism, thus contributing to tackling liver steatosis.

Nursing students' experience and training in healthcare aid during the COVID-19 pandemic in Spain.

BACKGROUND: During the COVID-19 pandemic health crisis, in some countries such as Spain, nursing students have offered to provide health assistance, but the role they have played, their degree of preparedness to face the situation, and what must be improved in their training to be ready for these situations is unknown. OBJECTIVE: Describe the experience and perceptions of students of the Nursing university degree during their participation as health support in the COVID-19 health crisis in Spain. DESIGN: We conducted a cross-sectional survey study. METHOD: 503 students enrolled in the 4th course of the Nursing degree in Spain during the months of March and April 2020. An online questionnaire was developed, based on a pilot study and distributed through the Nursing Association, students' unions and students' associations. Variables were used to describe their participation, degree of preparedness and training needs to determine how to improve training through descriptive statistics, as well as nonparametric tests to analyse the relationship between training and degree of preparedness nursing students. Results are reported according to the STROBE Statement. RESULTS: 73.2% (368) of students offered to participate in healthcare aid, of which 225 were actively involved. 27.8% carried out nursing tasks without supervision, and 47.7% assisted COVID-19 patients as any other nurse. Only 3.4% felt very prepared to work in the field of intensive care, finding that those students who perceived a higher degree of preparedness had received previous training in personal protective equipment and mechanical ventilation (p < 0.005). The highest scores for training activities that may improve their preparedness were simulations to improve levels of anxiety and stress when managing critical patients, simulation in ventilatory support and mandatory practices in services where ventilators are used. CONCLUSIONS: Although three out of four students were willing to provide health assistance, they recognise that they were not specially prepared in the field of intensive care and demand training with simulation to improve anxiety and stress levels in the management of critical patients and simulation in ventilatory support. RELEVANCE TO CLINICAL PRACTICE: Students have been vital resources for our health system and society when they have been needed. It is now up to us, both teachers and health authorities, to share their efforts by implementing the necessary improvements in training and safety measures not only because these affects the health and safety of the patient, but because they will be essential parts in future pandemics.

Thrombin induces Ca2+-dependent glutamate release from RPE cells mediated by PLC/PKC and reverse Na+/Ca2+ exchange.

Purpose: We analyzed the molecular mechanisms leading to glutamate release from rat primary cultures of RPE cells, under isosmotic conditions. Thrombin has been shown to stimulate glutamate release from astrocytes and retinal glia; however, the effect of thrombin on glutamate release from RPE cells has not been examined. Our previous work showed that upon the alteration of the blood-retina barrier, the serine protease thrombin could contribute to the transformation, proliferation, and migration of RPE cells. In this condition, elevated extracellular glutamate causes neuronal loss in many retinal disorders, including glaucoma, ischemia, diabetic retinopathy, and inherited photoreceptor degeneration. Methods: Primary cultures of rat RPE cells were preloaded with 1 µCi/ml 3H-glutamate in Krebs Ringer Bicarbonate (KRB) buffer for 30 min at 37 °C. Cells were rinsed and super-perfused with 1 ml/min KRB for 15 min. Stable release was reached at the 7th minute, and on the 8th minute, fresh KRB containing stimuli was added. Results: This study showed for the first time that thrombin promotes specific, dose-dependent glutamate release from RPE cells, induced by the activation of protease-activated receptor 1 (PAR-1). This effect was found to depend on the Ca2+ increase mediated by the phospholipase C-ß (PLC-ß) and protein kinase C (PKC) pathways, as well as by the reverse activity of the Na+/Ca2+ exchanger. Conclusions: Given the intimate contact of the RPE with the photoreceptor outer segments, diffusion of RPE-released glutamate could contribute to the excitotoxic death of retinal neurons, and the development of thrombin-induced eye pathologies.

Thrombin promotes the expression of Ccnd1 gene in RPE cells through the activation of converging signaling pathways.

The breakdown of the blood-retina barrier exposes retinal pigment epithelium (RPE) to serum components, thrombin among them. In addition to coagulation, thrombin acting through Protease-Activated Receptors (PARs 1-4) participates in a number of processes including cell proliferation, transformation, and migration. The purpose of this study was to identify interacting signaling pathways by which the activation of PAR1 by thrombin triggers cyclin D1 gene (Ccnd1) expression and the proliferation of RPE cells, characteristic of proliferative vitreoretinopathy (PVR). Our results demonstrate that thrombin induces the expression of the c-fos gene (c-fos), the activation of the (fos/jun) AP-1 site and the expression of Ccnd1, in precise correlation with the activation of CREB. Although the expression of both, c-fos and Ccnd1 requires the activation of conventional PKC isoforms and PI3K, downstream signaling from PI3K differs for both genes. Whereas the expression of c-fos requires PI3K-induced PDK1/Akt activity, that of Ccnd1 is mediated by PDK1-independent PKCζ signaling. Additionally, CREB activation may contribute to the induction of Ccnd1 expression through binding to the Ca/CRE element in the Ccnd1 gene promoter. Since cyclin D1 is a key regulator of cell cycle G1/S phase progression essential for proliferation, these findings further strengthen the critical involvement of thrombin in the development of proliferative retinopathies and may provide pharmacologic targets for the prevention or treatment of these diseases.

The impact of incorporating a simulation program into the undergraduate nursing curricula: A cross-sectional descriptive study.

AIM: To determine the degree of satisfaction for each academic year and according to the type of simulation performed (simulated patient actor/advanced simulator) among nursing students after the use of clinical simulation. INTRODUCTION: Clinical simulation is currently being incorporated in a cross-cutting manner throughout undergraduate nursing education. Its implementation requires a novel curricular design and educational changes throughout the academic subjects. DESIGN: A cross-sectional descriptive study was performed. METHODS: During the academic years 2018-2019 and 2019-2020, 425 students completed the High-Fidelity Simulation Satisfaction Reduced Scale for Students based on 25 questions and six factors, with a total score between 0 and 125. In total, 91 simulation sessions were performed among students who had different degrees of clinical and previous experience with simulation as well as standardized patient versus advanced simulator. A bivariate analysis was performed, comparing the total scores and the different subscales by sex, previous experience, academic year, and simulation methodology. Linear regression was used for both bivariate and multivariate analysis. RESULTS: The mean scale score was 116.8 (SD=7.44). The factor with the highest score was "F2: feedback or subsequent reflection", with a mean score of 14.71 (SD=0.73) out of 15. Fourth year students scored the highest (mean=119.17; SD=5.28). Students who underwent simulation training with a simulated patient actor presented a higher level of overall satisfaction (p<0.05) (Mean=120.31; SD=4.91), compared to students who used an advanced simulator (Mean=118.11; SD=5.75). CONCLUSIONS: Satisfaction with the simulation program was higher in fourth-year students compared to first-year students and was also higher when a simulated patient actor was used compared to an advanced simulator. The most highly valued aspect was the subsequent debriefing or reflective process.

TDC-2: Multimodal Foundation for Therapeutic Science.

Therapeutics Data Commons (tdcommons.ai) is an open science initiative with unified datasets, AI models, and benchmarks to support research across therapeutic modalities and drug discovery and development stages. The Commons 2.0 (TDC-2) is a comprehensive overhaul of Therapeutic Data Commons to catalyze research in multimodal models for drug discovery by unifying single-cell biology of diseases, biochemistry of molecules, and effects of drugs through multimodal datasets, AI-powered API endpoints, new multimodal tasks and model frameworks, and comprehensive benchmarks. TDC-2 introduces over 1,000 multimodal datasets spanning approximately 85 million cells, pre-calculated embeddings from 5 state-of-the-art single-cell models, and a biomedical knowledge graph. TDC-2 drastically expands the coverage of ML tasks across therapeutic pipelines and 10+ new modalities, spanning but not limited to single-cell gene expression data, clinical trial data, peptide sequence data, peptidomimetics protein-peptide interaction data regarding newly discovered ligands derived from AS-MS spectroscopy, novel 3D structural data for proteins, and cell-type-specific protein-protein interaction networks at single-cell resolution. TDC-2 introduces multimodal data access under an API-first design using the model-view-controller paradigm. TDC-2 introduces 7 novel ML tasks with fine-grained biological contexts: contextualized drug-target identification, single-cell chemical/genetic perturbation response prediction, protein-peptide binding affinity prediction task, and clinical trial outcome prediction task, which introduce antigen-processing-pathway-specific, cell-type-specific, peptide-specific, and patient-specific biological contexts. TDC-2 also releases benchmarks evaluating 15+ state-of-the-art models across 5+ new learning tasks evaluating models on diverse biological contexts and sampling approaches. Among these, TDC-2 provides the first benchmark for context-specific learning. TDC-2, to our knowledge, is also the first to introduce a protein-peptide binding interaction benchmark.

Clinical Simulation Program for the Training of Health Profession Residents in Confidentiality and the Use of Social Networks.

BACKGROUND: In the transition to a professional learning environment, healthcare professionals in their first year of specialized postgraduate clinical training (known as residents in Spain) are suddenly required to handle confidential information with little or no prior training in the safe and appropriate use of digital media with respect to confidentiality issues. The aims of this study were: (1) to explore the usefulness of an advanced clinical simulation program for educating residents from different healthcare disciplines about confidentiality and the dissemination of clinical data or patient images; (2) to explore the use of social networks in healthcare settings; and (3) to explore participants' knowledge and attitudes on current regulations regarding confidentiality, image dissemination, and the use of social networks; Methods: This was a cross-sectional study. Data were collected from all 49 first-year residents of different health professions at a Spanish hospital between June and August 2022. High-fidelity clinical simulation sessions designed to address confidentiality and health information dissemination issues in hospital settings, including the use of social networks, were developed and implemented. Data were assessed using a 12-item ad hoc questionnaire on confidentiality and the use of social media in the healthcare setting. Descriptive of general data and chi-square test or Fisher's exact test were performed using the SPSS 25.0 software; Results: All the participants reported using the messaging application WhatsApp regularly during their working day. A total of 20.4% of the participants stated that they had taken photos of clinical data (radiographs, analyses, etc.) without permission, with 40.8% claiming that they were unaware of the legal consequences of improper access to clinical records. After the course, the participants reported intending to modify their behavior when sharing patient data without their consent and with respect to how patients are informed; Conclusions: The use of advanced simulation in the training of interprofessional teams of residents is as an effective tool for initiating attitudinal change and increasing knowledge related to patient privacy and confidentiality. Further follow-up studies are needed to see how these attitudes are incorporated into clinical practice.

Two complexes derived from the reaction of M3(CO)12 clusters (M = Ru, Os) with the 9-(triphenylphosphonio)fluorenide ylide: tricarbonyl[9-(triphenylphosphonio)fluorenylidene]ruthenium and nonacarbonyl-µ3-fluorenylidene-µ2-hydrido-triangulo-triosmium(III).

Tricarbonyl[9-(triphenylphosphonio)fluorenylidene]ruthenium, [Ru(C31H21P)(CO)3], (I), is mononuclear, consisting of a single Ru centre, to which three carbonyl units and a chelating µ3-9-(triphenylphosphonio)fluorenide ylide bind to generate a distorted octahedral RuC6 core. Nonacarbonyl-µ3-fluorenylidene-µ2-hydrido-triangulo-triosmium(III), [Os3H(C13H7)(CO)9], (II), is trinuclear and presents a triangular triosmium core, nine carbonyl ligands and one fluorenylidene ligand. Two of the Os(III) centres present a highly distorted hexacoordinated Os(Os2C4) core and are in turn bridged by a hydride ligand. The remaining Os(III) cation is octacoordinated, with an Os(Os2C6) nucleus. The crystal structures of both compounds are the result of nondirectional forces, much resembling the packing of weakly interacting quasi-spherical units, viz. the molecules themselves in (I) and centrosymmetric π-π-bonded dimers in (II).

[Clinical simulation as a training tool for clinical teams and care change facilitator]. / La simulación clínica: entrenamiento de equipos clínicos y facilitador de cambios asistenciales.

OBJECTIVE: The objective of this article is to describe and show the results of a simulation training interprofesional program to meet a training need of Surgical area professionals in management in cardiovascular surgery emergencies in Valdecilla Hospital. MATERIAL: The activity was aimed to train at the 42 nurses in rotation in the surgical area, nursing assistances, cardiovascular surgeons and anesthetists. For it was made a study of the training needs and were designed clinical simulation escenarios, theoretical sessions as well in workshops usual workplace. RESULTS: The training project was conducted in four phases between May 21 to June 18, 2012, within which were 3 clinical cases for multidisciplinary training in emergency usual CCV. With the full participation of 65 professionals and 17 instructors, after further analysis to cases, results were achieved improved teamwork, and picked up, several changes to be made in the organization of the service. CONCLUSIONS: Clinical simulation mode responds to adult learning, based on their own experience and personal reflection, and all in an environment that does not risk to patients or professionals. It is really helpful and flexible to meet different institutional challenges and where participants highlighted two key aspects in this activity such as the multidisciplinary team where they could train the professional standard and the possibility of analysis and reflection after the event to share experiences and look for areas of improvement among all the clinical team.

Proteolytic degradation of atrial sarcomere proteins underlies contractile defects in atrial fibrillation.

Aims: Atrial fibrillation (AFib) is the most common cardiac rhythm disturbance. Treatment of AFib involves restoration of the atrial electrical rhythm. Following rhythm restoration, a period of depressed mechanical function known as atrial stunning occurs that involves decreased blood flow velocity and reduced atrial contractility. This suggests that defects in contractility occur in AFib and are revealed upon restoration of rhythm. The aim of this project is to define the contractile remodeling that occurs in AFib. Methods and Results: To assess contractile function, we used a canine atrial tachypacing model of induced AFib. Mass spectrometry analysis showed dysregulation of contractile proteins in samples from AFib compared to sinus rhythm atria. Atrial cardiomyocytes showed reduced force of contraction in skinned single cardiomyocyte calcium-force studies. There were no significant differences in myosin heavy chain isoform expression. Resting tension is decreased in the AFib samples correlating with reduced full-length titin in the sarcomere. We measured degradation of other myofilament proteins including cMyBP-C, actinin, and cTnI, showing significant degradation in the AFib samples compared to sinus rhythm atria. Many of the protein degradation products appeared as discrete cleavage products that are generated by calpain proteolysis. We assessed calpain activity and found it to be significantly increased. Skinned cardiomyocytes from AFib atria showed decreased troponin I phosphorylation, consistent with the increased calcium sensitivity that was found within these cardiomyocytes. Conclusions: With these results it can be concluded that AFib causes alterations in contraction that can be explained by both molecular changes occurring in myofilament proteins and overall myofilament protein degradation. These results provide an understanding of the contractile remodeling that occurs in AFib and provides insight into the molecular explanation for atrial stunning and the increased risk of atrial thrombus and stroke in AFib.

The PKC-ζ pseudosubstrate peptide induces glutamate release from retinal pigment epithelium cells through kinase- independent activation of Best1.

AIMS: The retinal pigment epithelium (RPE) is a highly specialized cell monolayer, that plays a key role in the maintenance of photoreceptor function and the blood-retina barrier (BRB). In this study, we found that a myristoylated pseudosubstrate of PKC-ζ (PKCζ PS), considered as a PKC-ζ inhibitor, plays a distinct role in RPE. MAIN METHODS: We demonstrated that PKCζ PS stimulates the release of Glutamate (Glu) using in vitro3H-Glutamate release experiments. By western blot, kinase assays, and Fluoresence Ca+2 Concentration Measurements, we determined the cellular mechanisms involved in such release. KEY FINDINGS: Surprisingly, PKCζ PS has no effect on either phosphorylation of T560, essential for catalytic activity, nor it has an effect on kinase activity. It induces the dose-dependent release of Glu by increasing intracellular Ca+2 levels. Interestingly, this release was not observed upon stimulation by other non-competitive PKC-ζ inhibitors. We here demonstrated that the PKCζ PS stimulates the release of Glutamate from RPE by activating the Ca2+-dependent Cl channel Bestrophin 1 (Best1). SIGNIFICANCE: These results question PKCζ PS specificity as an inhibitor of this enzyme. Furthermore, the present results underline the relevance of clarifying the molecular mechanisms involved in glutamate release from the retina under conditions derived from excitotoxic stimuli.

Experiences and Perceptions of Nursing Students during the COVID-19 Crisis in Spain.

In the early stages of the 2019 coronavirus pandemic in Spain, the Spanish health system was overwhelmed, mainly due to a lack of personnel, and many hospital centers collapsed by following avalanche of patients with COVID-19; this meant that the National System of Health called for fourth-year nursing students to come to the hospital as health care personnel. Our aim was to describe the perceptions and experiences of a sample of nursing students during the early stages of the outbreak. We conducted a qualitative study with an empirical-phenomenological approach. Twenty nursing students in their final year of study in Spain were recruited using purposive and snowball sampling. They participated in in-depth interviews between 20 April and 10 May 2020. The interviews were transcribed and then analyzed using Haase's adaptation of Colaizzi's phenomenological method. Four main themes emerged from data analysis: "social responsibility and pride as a health worker", "pressure caused by working with COVID-19 patients", "feeling defenseless and let down", and "personal growth as a health worker". These main themes were further divided into 11 theme categories. Due to an intense work day for several days in a row, the students were tired and mentally exhausted. Even so, they managed to overcome any difficulties, demonstrating their professional dedication and resilience. Greater preparatory support should be provided to safeguard the well-being of these future healthcare providers. More intensive preparatory training is necessary for health sciences students to facilitate crisis preparedness and effective crisis management. It is necessary to implement support from healthcare systems, including sufficient personal protective equipment, as well as contracts that accurately reflect the work they do. It is necessary for nursing supervisors to have effective communication in the performance of their functions with nursing students; this dialogue helps to clearly explain which are the functions that students must perform when they are carrying out their internships. There is also a need for preparatory training in managing infectious diseases such as COVID-19.

New prophylaxis regimen for SARS-CoV-2 infection in health professionals with low doses of hydroxychloroquine and bromhexine: a randomised, double-blind placebo clinical trial (ELEVATE Trial).

INTRODUCTION: SARS-CoV-2 infection in Mexico has caused ~2.7 million confirmed cases; around 20%-25% of health workers will be infected by the virus at their workplace, with approximately 4.4% of mortality. High infectivity of SARS-CoV-2 is related with cell entry mechanism, through the ACE receptor. SARS-CoV-2 requires transmembrane protease serine 2 to cleave its spike glycoprotein and ensure fusion of host cell and virus membrane. We propose studying prophylactic treatment with hydroxychloroquine (HCQ) and bromhexine (BHH), which have been shown to be effective in preventing SARS-CoV-2 infection progression when administered in early stages. The aim of this study is to assess the efficacy of HCQ and BHH as prophylactic treatments for SARS-CoV-2 infection in healthy health workers exposed to the virus. METHODS AND ANALYSIS: Double-blind randomised clinical trial, with parallel allocation at a 1:1 ratio with placebo, of low doses of HCQ plus BHH, for 60 days. Study groups will be defined as follows: (1) HCQ 200 mg/day+BHH 8 mg/8 hours versus (2) HCQ placebo plus BHH placebo. Primary endpoint will be efficacy of both interventions for the prevention of SARS-CoV-2 infection, determined by the risk ratio of infected personnel and the absolute risk. At least a 16% reduction in absolute risk is expected between the intervention and placebo groups; a minimum of 20% infection is expected in the placebo group. The sample size calculation estimated a total of 214 patients assigned: two groups of 107 participants each. ETHICS AND DISSEMINATION: This protocol has been approved by the local Medical Ethics Committee (National Institute of Rehabilitation 'Luis Guillermo Ibarra Ibarra', approval number INRLGII/25/20) and by the Federal Commission for Protection against Sanitary Risks (COFEPRIS, approval number 203 300 410A0058/2020). The results of the study will be submitted for publication in peer-reviewed journals and disseminated through conferences. TRIAL REGISTRATION NUMBER: NCT04340349.

Effectiveness of an Educational Intervention With High-Fidelity Clinical Simulation to Improve Attitudes Toward Teamwork Among Health Professionals.

BACKGROUND: Failures in teamwork are a common reason for adverse medical events. The goals of this study are to evaluate attitudes toward teamwork among an interprofessional group of health professionals and to analyze the effectiveness of an educational intervention with high-fidelity clinical simulation to improve these attitudes. METHOD: An educational intervention was developed that used a 6-hour session that included three simulated clinical cases. The Attitudes Toward Health Care Teams Scale was used for assessment. Mean difference before and after the intervention was calculated with the Wilcoxon test. RESULTS: Positive attitude toward teamwork after completion of the training activities was measured. The health care professionals who showed the most positive attitude toward teamwork were physicians (93.92, SD = 6.58) and resident physicians (95.01, SD = 6.33). The greatest increase was observed among orderlies (p < .001) and nursing assistants (p < .001). CONCLUSION: The use of clinical simulation for interprofessional training of health care professionals showed a positive effect on attitudes toward teamwork. [J Contin Educ Nurs. 2021;52(10):457-467.].

Thrombin-activated PAR1 membrane expression is regulated by Rab11a-RCP complex dissociation.

PAR1 activation by thrombin promotes intracellular signaling leading to RPE cell transformation, proliferation, and migration, characteristic of fibroproliferative eye diseases. Due to the cleavage of PAR1 N-terminal domain, carried by thrombin, the arrest of PAR1 signaling is achieved by transport into lysosomes and degradation. Recent findings suggest that the GTPase Rab11a in conjunction with its effector RCP may direct PAR1 to lysosomes. Hereby we demonstrate that thrombin-induced PAR1 internalization and lysosomal targeting requires the disassembly of the Rab11a/RCP complex, and that this process depends on thrombin-induced intracellular calcium increase and calpain activation. These findings unveil a novel mechanism that regulates thrombin activated PAR1 internalization and degradation.