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BACKGROUND: Acute coronary syndrome (ACS), specifically ST-segment elevation myocardial infarction is a major cause of morbidity and mortality throughout Europe. Diagnosis in the acute setting is mainly based on clinical symptoms and physician's interpretation of an electrocardiogram (ECG), which may be subject to errors. ST-segment elevation is the leading criteria to activate urgent reperfusion therapy, but a clear ST-elevation pattern might not be present in patients with coronary occlusion and ST-segment elevation might be seen in patients with normal coronary arteries. METHODS: The ASSIST project is a retrospective observational study aiming to improve the ECG-assisted assessment of ACS patients in the acute setting by incorporating an artificial intelligence platform, Willem™ to analyze 12lead ECGs. Our aim is to improve diagnostic accuracy and reduce treatment delays. ECG and clinical data collected during this study will enable the optimization and validation of Willem™. A retrospective multicenter study will collect ECG, clinical, and coronary angiography data from 10,309 patients. The primary outcome is the performance of this tool in the correct identification of acute myocardial infarction with coronary artery occlusion. Model performance will be evaluated internally with patients recruited in this retrospective study while external validation will be performed in a second stage. CONCLUSION: ASSIST will provide key data to optimize Willem™ platform to detect myocardial infarction based on ECG-assessment alone. Our hypothesis is that such a diagnostic approach may reduce time delays, enhance diagnostic accuracy, and improve clinical outcomes.
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Endothelial microparticles (EMPs) are endothelium-derived submicron vesicles that are released in response to diverse stimuli and are elevated in cardiovascular disease, which is correlated with risk factors. This study investigates the effect of EMPs on endothelial cell function and dysfunction in a model of free fatty acid (FFA) palmitate-induced oxidative stress. EMPs were generated from TNF-α-stimulated HUVECs and quantified by using flow cytometry. HUVECs were treated with and without palmitate in the presence or absence of EMPs. EMPs were found to carry functional eNOS and to protect against oxidative stress by positively regulating eNOS/Akt signaling, which restored NO production, increased superoxide dismutase and catalase, and suppressed NADPH oxidase and reactive oxygen species (ROS) production, with the involvement of NF-erythroid 2-related factor 2 and heme oxygenase-1. Conversely, under normal conditions, EMPs reduced NO release and increased ROS and redox-sensitive marker expression. In addition, functional assays using EMP-treated mouse aortic rings that were performed under homeostatic conditions demonstrated a decline in endothelium-dependent vasodilatation, but restored the functional response under lipid-induced oxidative stress. These data indicate that EMPs harbor functional eNOS and potentially play a role in the feedback loop of damage and repair during homeostasis, but are also effective in protecting against FFA-induced oxidative stress; thus, EMP function is reflected by the microenvironment.-Mahmoud, A. M., Wilkinson, F. L., McCarthy, E. M., Moreno-Martinez, D., Langford-Smith, A., Romero, M., Duarte, J., Alexander, M. Y. Endothelial microparticles prevent lipid-induced endothelial damage via Akt/eNOS signaling and reduced oxidative stress.
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Micropartículas Derivadas de Células/metabolismo , Endotélio Vascular/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Proteína Oncogênica v-akt/metabolismo , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Células Endoteliais/metabolismo , Humanos , Lipídeos/farmacologia , NADPH Oxidases/metabolismo , Vasodilatação/efeitos dos fármacosRESUMO
BACKGROUND: The learning process in clinical placements for health care students is a multifaceted endeavor that engages numerous actors and stakeholders, including students, clinical tutors, link teachers, and academic assessors. Successfully navigating this complex process requires the implementation of tasks and mentorships that are synchronized with educational and clinical processes, seamlessly embedded within their respective contexts. Given the escalating number of students and the rising demand for health care services from the general population, it becomes imperative to develop additional tools that support the learning process. These tools aim to simplify day-to-day clinical practice, allowing a concentrated focus on value-based activities. This paper introduces a project funded by the European Commission that involves 5 European countries. The project's objective is to comprehensively outline the entire process of development and ultimately implement mobile technology in practice placements. The project tackles the existing gap by constructing tailored mobile apps designed for students, teachers, tutors, and supervisors within each participating organization. This approach leverages practice-based learning, mobile technology, and technology adoption to enhance the overall educational experience. OBJECTIVE: This study aims to introduce mobile technology in clinical practice placements with the goal of facilitating and enhancing practice-based learning. The objective is to improve the overall effectiveness of the process for all stakeholders involved. METHODS: The "4D in the Digitalization of Learning in Practice Placement" (4D Project) will use a mixed methods research design, encompassing 3 distinct study phases: phase 1 (preliminary research), which incorporates focus groups and a scoping review, to define the problem, identify necessities, and analyze contextual factors; phase 2 (collaborative app development), which involves researchers and prospective users working together to cocreate and co-design tailored apps; and phase 3, which involves feasibility testing of these mobile apps within practice settings. RESULTS: The study's potential impact will primarily focus on improving communication and interaction processes, fostering connections among stakeholders in practice placements, and enhancing the assessment of training needs. The literature review and focus groups will play a crucial role in identifying barriers, facilitators, and factors supporting the integration of mobile technology in clinical education. The cocreation process of mobile learning apps will reveal the core values and needs of various stakeholders, including students, teachers, and health care professionals. This process also involves adapting and using mobile apps to meet the specific requirements of practice placements. A pilot study aimed at validating the app will test and assess mobile technology in practice placements. The study will determine results related to usability and design, learning outcomes, student engagement, communication among stakeholders, user behavior, potential issues, and compliance with regulations. CONCLUSIONS: Health care education, encompassing disciplines such as medicine, nursing, midwifery, and others, confronts evolving challenges in clinical training. Essential to addressing these challenges is bridging the gap between health care institutions and academic settings. The introduction of a new digital tool holds promise for empowering health students and mentors in effectively navigating the intricacies of the learning process. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/53284.
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BACKGROUND: The high failure rate of innovation projects motivates us to understand the perceptions about resistances and barriers of the main stakeholders to improving success rates. OBJECTIVE: This study aims to analyze the readiness for change in the implementation of a 3D printing project in a Catalan tertiary hospital prior to its implementation. METHODS: We used a web-based, voluntary, and anonymous survey using the Normalization Measurement Development questionnaire (NoMAD) to gather views and perceptions from a selected group of health care professionals at Germans Trias i Pujol University Hospital. RESULTS: In this study, 58 professionals, including heads of service (n=30, 51%), doctors (n=18, 31%), nurses (n=7, 12%), and support staff (n=3, 5%), responded to the questionnaire. All groups saw the value of the project and were willing to enroll and support it. Respondents reported the highest scores (out of 5) in cognitive participation (mean 4.45, SD 0.04), coherence (mean 3.72, SD 0.13), and reflective monitoring (mean 3.80, SD 0.25). The weakest score was in collective action (mean 3.52, SD 0.12). There were no statistically significant differences in scores among professions in the survey. CONCLUSIONS: The 3D printing project implementation should pay attention to preparing, defining, sharing, and supporting the operational work involved in its use and implementation. It should also understand, assess, and communicate the ways in which the new set of practices can affect the users and others around them. We suggest that health officers and politicians consider this experience as a solid ground toward the development of a more efficient health innovation system and as a catalyst for transformation.
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Atitude do Pessoal de Saúde , Médicos , Humanos , Centros de Atenção Terciária , Inquéritos e Questionários , Pessoal de SaúdeRESUMO
Acute myeloid leukemia (AML) is an hematologic neoplasia characterized by the accumulation of transformed immature myeloid cells in bone marrow. Although the response rate to induction therapy is high, survival rate 5-year after diagnosis is still low, highlighting the necessity of new novel agents. To identify agents with the capability to abolish the self-renewal capacity of AML blasts, an in silico screening was performed to search for small molecules that induce terminal differentiation. Emetine, a hit compound, was validated for its anti-leukemic effect in vitro, ex vivo and in vivo. Emetine, a second-line anti-protozoa drug, differentially reduced cell viability and clonogenic capacity of AML primary patient samples, sparing healthy blood cells. Emetine treatment markedly reduced AML burden in bone marrow of xenotransplanted mice and decreased self-renewal capacity of the remaining engrafted AML cells. Emetine also synergized with commonly used chemotherapeutic agents such as ara-C. At a molecular level, emetine treatment was followed by a reduction in HIF-1α protein levels. This study validated the anti-leukemiceffect of emetine in AML cell lines, a group of diverse AML primary samples, and in a human AML-transplanted murine model, sparing healthy blood cells. The selective anti-leukemic effect of emetine together with the safety of the dose range required to exert this effect support the development of this agent in clinical practice.
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Antineoplásicos/farmacologia , Emetina/farmacologia , Leucemia Mieloide Aguda/tratamento farmacológico , Inibidores da Síntese de Proteínas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Seguimentos , Humanos , Leucemia Mieloide Aguda/patologia , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Células Tumorais Cultivadas , Ensaio Tumoral de Célula-TroncoRESUMO
Acute myeloid leukemia (AML) is a neoplasia characterized by the rapid expansion of immature myeloid blasts in the bone marrow, and marked by poor prognosis and frequent relapse. As such, new therapeutic approaches are required for remission induction and prevention of relapse. Due to the higher chemotherapy sensitivity and limited life span of more differentiated AML blasts, differentiation-based therapies are a promising therapeutic approach. Based on public available gene expression profiles, a myeloid-specific differentiation-associated gene expression pattern was defined as the therapeutic target. A XIAP inhibitor (Dequalinium chloride, DQA) was identified in an in silico screening searching for small molecules that induce similar gene expression regulation. Treatment with DQA, similarly to Embelin (another XIAP inhibitor), induced cytotoxicity and differentiation in AML. XIAP inhibition differentially impaired cell viability of the most primitive AML blasts and reduced clonogenic capacity of AML cells, sparing healthy mature blood and hematopoietic stem cells. Taken together, these results suggest that XIAP constitutes a potential target for AML treatment and support the evaluation of XIAP inhibitors in clinical trials.