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The COVID-19 pandemic has overwhelmed healthcare systems and triggered global economic downturns. While vaccines have reduced the lethality rate of SARS-CoV-2 to 0.9% as of October 2024, the continuous evolution of variants remains a significant public health challenge. Next-generation medical therapies offer hope in addressing this threat, especially for immunocompromised individuals who experience prolonged infections and severe illnesses, contributing to viral evolution. These cases increase the risk of new variants emerging. This study explores miniACE2 decoys as a novel strategy to counteract SARS-CoV-2 variants. Using in silico design and molecular dynamics, blocking proteins (BPs) were developed with stronger binding affinity for the receptor-binding domain of multiple variants than naturally soluble human ACE2. The BPs were expressed in E. coli and tested in vitro, showing promising neutralizing effects. Notably, miniACE2 BP9 exhibited an average IC50 of 4.9 µg/mL across several variants, including the Wuhan strain, Mu, Omicron BA.1, and BA.2 This low IC50 demonstrates the potent neutralizing ability of BP9, indicating its efficacy at low concentrations.Based on these findings, BP9 has emerged as a promising therapeutic candidate for combating SARS-CoV-2 and its evolving variants, thereby positioning it as a potential emergency biopharmaceutical.
Assuntos
Enzima de Conversão de Angiotensina 2 , Anticorpos Neutralizantes , COVID-19 , Simulação de Dinâmica Molecular , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/imunologia , Humanos , COVID-19/virologia , COVID-19/imunologia , Enzima de Conversão de Angiotensina 2/metabolismo , Enzima de Conversão de Angiotensina 2/química , Anticorpos Neutralizantes/imunologia , Glicoproteína da Espícula de Coronavírus/metabolismo , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/imunologia , Simulação por Computador , Pandemias , Ligação Proteica , Betacoronavirus/imunologia , Betacoronavirus/efeitos dos fármacos , Testes de NeutralizaçãoRESUMO
OBJECTIVE: This study aimed to evaluate the role of pepsin inhibitors in the inflammatory response and their effects on laryngeal mucosal integrity during gastroesophageal reflux (GERD) under in vivo conditions. METHODS: A surgical model of GERD was used, in which mice were treated with pepstatin (0.3 mg/kg) or darunavir (8.6 mg/kg) for 3 days. On the third day after the experimental protocol, the laryngeal samples were collected to assess the severity of inflammation (wet weight and myeloperoxidase activity) and mucosal integrity (transepithelial electrical resistance and paracellular epithelial permeability to fluorescein). RESULTS: The surgical GERD model was reproduced. It showed features of inflammation and loss of barrier function in the laryngeal mucosa. Pepstatin and darunavir administration suppressed laryngeal inflammation and preserved laryngeal mucosal integrity. CONCLUSION: Pepsin inhibition by the administration of pepstatin and darunavir improved inflammation and protected the laryngeal mucosa in a mouse experimental model of GERD. LEVEL OF EVIDENCE: NA Laryngoscope, 134:3080-3085, 2024.
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Refluxo Gastroesofágico , Pepsina A , Animais , Masculino , Camundongos , Modelos Animais de Doenças , Refluxo Gastroesofágico/tratamento farmacológico , Inflamação/tratamento farmacológico , Inflamação/prevenção & controle , Mucosa Laríngea/efeitos dos fármacos , Mucosa Laríngea/patologia , Pepstatinas/farmacologiaRESUMO
Se analiza el estado de la investigación en Latinoamérica, haciendo un énfasis central en Bolivia, concluyendo que la investigación básica en este contexto es muy escaza y casi nula, siendo que, más bien, se hace énfasis en otro tipo de investigaciones que, desde la postura adoptada, no constituyen actividades científicas propiamente dichas. Por otra parte, se expone las diferencias entre ciencia y tecnología realizando sus respectivos análisis. Por último, se expone los beneficios de realizar investigaciones a nivel básico para las problemáticas sociales con base en las propuestas de las líneas de investigación teórico- analíticas e interdisciplinarias.
The state of research in Latin America is analyzed, with a central emphasis on Bolivia, concluding that basic research in this context is very scarce and almost null, and that emphasis is placed on other types of research which, from the position adopted, do not constitute scientific activities in the strict sense of the word. On the other hand, the differences between science and technology are presented with their respective analyses. Finally, the benefits of conducting research at a basic level for social problems based on the proposal of theoretical-analytical and interdisciplinary lines of research are presented.
Analisa-se o estado da investigação na América Latina, com ênfase central na Bolívia, concluindo-se que a investigação básica neste contexto é muito escassa e quase inexistente, e que se dá ênfase a outros tipos de investigação que, do ponto de vista adoptado, não constituem actividades científicas no sentido estrito do termo. Por outro lado, as diferenças entre ciência e tecnologia são apresentadas e analisadas. Finalmente, são apresentados os benefícios de realizar investigação a um nível básico para problemas sociais com base na proposta de linhas teórico-analíticas e interdisciplinares de investigação.
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BACKGROUND: The external rotation and abduction of shoulder are considered one of the priorities of reconstruction in brachial plexus injury. The aim of this study was to evaluate the functional results and complications of shoulder arthrodesis in patients with brachial plexus injury to better comprehend the benefits of this procedure. METHODS: Between 2015 and 2019, 15 shoulder arthrodesis were performed in patients with long-standing brachial plexus injury. The main indication for arthrodesis was absent or poor recovery of shoulder abduction and external rotation. Patients presented different levels of injury. Shoulder measurements of active abduction and external rotation were made based on image records of the patients. A long 4.5-mm reconstruction plate was fit along the scapular spine, acromion, and lateral proximal third of the humerus. Structured bone graft was fit into the subacromial space. RESULTS: The mean preoperative abduction was 16°, and the mean postoperative abduction was 42°. The mean preoperative external rotation was -59°, and the mean postoperative external rotation was -13°. The mean increase in abduction and external rotation was 25° and 45°, respectively. Bone union was achieved in all cases at an average time of 5.23 months. We experienced humeral fractures in 26.66% of the cases, which were all successfully treated nonoperatively. CONCLUSIONS: Shoulder arthrodesis is a rewarding procedure for patients with brachial plexus injuries. A marked improvement in the upper limb positioning was observed in all patients. It should be considered as the main therapeutic option in cases where nerve reconstruction is no longer possible.
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Neuropatias do Plexo Braquial , Plexo Braquial , Articulação do Ombro , Humanos , Ombro/inervação , Articulação do Ombro/cirurgia , Plexo Braquial/lesões , Neuropatias do Plexo Braquial/etiologia , Neuropatias do Plexo Braquial/cirurgia , Artrodese/métodosRESUMO
Resumo: Introdução: A avaliação do estudante é componente essencial de todo programa educacional. O aprendizado das ciências básicas é fundamental para dar sentido ao que se aprende na fase clínica da formação de um profissional em saúde. Entretanto, a maioria dos treinamentos de elaboradores de testes de múltipla escolha (TME) é voltada à formulação de questões clínicas e não inclui abordagem específica para questões das ciências básicas. Relato de experiência: Foi realizada uma oficina para a capacitação docente na elaboração de TME de aplicação dos conhecimentos de ciências básicas, visando à elaboração de uma prova a ser aplicada no final do ciclo básico de seis cursos da saúde. O material instrucional foi elaborado pelos autores, que ofereceram uma oficina no formato on-line. Um diferencial dessa capacitação foi a aplicação de modelos de elaboração de enunciados com contextos definidos, utilizando momentos de preparo assíncronos e encontro síncrono. Após a oficina, aplicaram-se questionários sobre a satisfação e aprendizagem dos participantes. A maioria avaliou a oficina como boa ou muito boa e referiu aumento da percepção de capacidade para elaborar TME, e, ao final, somente 7% se sentiram pouco preparados para elaborar um TME seguindo as boas práticas. Houve melhora na qualidade dos TME elaborados, tendo como referencial os índices de dificuldade e discriminação. Discussão: Existem evidências do valor do desenvolvimento do corpo docente na melhoria da qualidade das questões produzidas. O formato de oficina proposto foi bem avaliado pelos participantes e contribuiu para a qualidade das questões de provas aplicadas ao final do ciclo básico. Conclusão: Estratégias como a descrita qualificam as avaliações dentro da escola e contribuem para a organização de provas externas.
Abstract: Introduction: Student assessment is an essential component of all educational programs. Basic science learning is essential for making clinical knowledge meaningful to healthcare students. However, most item writer training is focused on the formulation of clinical questions and does not include a specific approach to basic science questions. Experience Report: Workshops on item writing for knowledge application on basic sciences were carried out with the aim of planning a test to be applied at the end of the basic cycle of six health courses. The instructional material was prepared by the authors, who offered online workshops. A differential of this training was the application of models of item lead-in elaboration with defined contexts, using moments of asynchronous preparation and synchronous encounter. After each workshop, surveys were applied to assess participants' satisfaction and learning. Most participants rated the workshop as good or very good and reported an increase in their perceived ability to prepare single best answer multiple-choice questions. At the end, only 7% reported they were not prepared to write an item following good practices. There was an improvement in the quality of the items prepared, using the difficulty and discrimination indexes as a reference. Discussion: There is evidence of the value of faculty development in improving the quality of the questions produced. The proposed workshop format was well evaluated by the participants and contributed to the quality of tests applied to students at the end of the basic science cycle. Conclusion: Strategies such this qualify assessments within the school and contribute to the organization of external exams.
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Seminal works have now revealed the gut microbiota is connected with several diseases, including renal disorders. The balance between optimal and dysregulated host-microbiota interactions has completely changed our understanding of immunity and inflammation. Kidney injury is associated with accumulation of uremic toxins in the intestine, augmented intestinal permeability, and systemic inflammation. Intestinal bacteria can signal through innate receptors and induce immune cell activation in the lamina propria and release of inflammatory mediators into the bloodstream. But the gut microbiota can also modulate immune functions through soluble products as short-chain fatty acids (SCFAs). The three most common SCFAs are propionate, butyrate, and acetate, which can signal through specific G-protein coupled receptors (GPCRs), such as GPR43, GPR41, and GPR109a, expressed on the surface of epithelial, myeloid, endothelial, and immune cells, among others. The triggered signaling can change cell metabolism, immune cell activation, and cell death. In this study, we reviewed the gut-kidney axis, how kidney cells can sense SCFAs, and its implication in kidney diseases.
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Ácidos Graxos Voláteis , Microbioma Gastrointestinal , Bactérias/metabolismo , Rim/metabolismo , Receptores Acoplados a Proteínas GRESUMO
BACKGROUND: Faculty development programs, studied both within the USA and internationally, have been shown to be helpful for enhancing scholarly and academic work for academic faculty in teaching institutions. This project investigates the impact of a well-studied faculty development program applied to basic science teachers in an academic medical center in the Dominican Republic. METHODS: A faculty cohort of physician educators in the Basic Sciences at Universidad Iberoamericana (UNIBE) School of Medicine in the Dominican Republic underwent training in the Stanford Faculty Development Center (SFDC) model of teaching through a sequence of seven workshops that were adapted for basic science content. A validated retrospective pre- and post-test instrument was used to measure study outcomes on specific teaching behaviors at the end of the workshops, at 3-month and at 12-month post-intervention. Thematic analysis of specific teaching techniques and barriers to their teaching were compiled. RESULTS: Fourteen faculty participants completed the study. All participants found the workshops valuable. Significant improvement in self-reported teaching abilities was seen comparing the mean pre-intervention scores of 106.21 (maximum score = 145, standard deviation [SD] = 12.70) with mean immediate post-intervention scores of 138.28 (SD = 6.12), the 3-month post-intervention scores of 129.79 (SD = 11.12) and the 1-year post-intervention scores of 131.86 (SD = 11.26). Several consistent themes were found among participants. CONCLUSIONS: Faculty development for improving teaching of basic science concepts by clinicians can be performed across the cultures of the USA and the Dominican Republic.
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RESUMO O objetivo deste estudo foi conhecer como pesquisadores da Psicologia Social brasileira a concebem, considerando a dicotomia ciência-prática. Participaram 100 representantes de grupos de pesquisa dessa disciplina. Estes responderam questionário online com cinco partes: concepções da psicologia social, representantes da área, periódicos de referência, atitudes frente à disciplina como ciência aplicada e básica e informações demográficas. A psicologia social foi concebida como sócio-histórico-crítica, polarizando entre Silvia Lane e Aroldo Rodrigues. Considerou-se Psicologia & Sociedadec omo mais apropriada para publicações desta área, destacando-se internacionalmente o Journal of Personality and Social Psychology. As atitudes dos participantes a caracterizaram como mais aplicada. Concluindo, predomina a perspectiva abrapsiana no Brasil, divergindo alguns pesquisadores da psicologia social clássica.
ABSTRACT This study aimed to gain knowledge regarding the way Brazilian Social Psychology researchers conceive their field, considering the science-practice dichotomy. Participants were 100 representatives of research groups of this discipline. They answered an online questionnaire with five parts: conceptions of social psychology, area representatives, reference journals, attitudes toward the discipline as basic and applied sciences and demographic questions. Social psychology was conceived as socio-historical-critical, polarizing between Silvia Lane and Aroldo Rodrigues. The journal Psicologia & Sociedade was considered the most appropriate for publications in this area, while internationally the Journal of Personality and Social Psychology was highlighted. Participants' attitudes characterized this discipline as applied rather than basic science. In conclusion, the abrapsian perspective is predominant in Brazil, diverging some researchers of the classic social psychology.
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OBJECTIVES: The purpose of this study was to evaluate the effects of low-intensity pulsed ultrasound at 1.0 MHz on the healing process of fractures with bone loss in the rat fibula by alkaline phosphate level measurement and radiologic analyses. METHODS: Thirty 70-day-old male Wistar rats underwent a bone resection of 2.5 to 3.0 mm between the proximal and middle third of the right fibular diaphysis. The animals were randomly divided into 3 experimental groups: reference (uninjured), control (injured only), and treated (injured and treated with 5 applications of ultrasound, interspersed by 2 days of rest, beginning 24 hours after the osteotomy). Euthanasia was performed at experimental periods of 7 and 14 days. The right hind limb was removed for radiologic analysis. The blood was collected via cardiac puncture to determine the serum alkaline phosphatase activity. RESULTS: The bone fractures had not been completely consolidated in the treated and control group when analysis of the bone took place. At day 7, the serum alkaline phosphatase activity was higher in the treated group (mean ± SD, 72.17 ± 7.02 U/L) compared to the control (65.26 ± 8.41 U/L) and reference (67.21 ± 7.86 U/L) groups. At day 14, higher alkaline phosphatase activity was seen in the control group (68.96 ± 8.12 U/L) compared to the treated (66.09 ± 8.46 U/L) and reference (67.14 ± 7.96 U/L) groups. CONCLUSIONS: The biochemical and radiologic results suggest that low-intensity pulsed ultrasound can be used as an auxiliary method to consolidate fractures and probably reduces the bone healing time, offering clinical benefits.
Assuntos
Regeneração Óssea/fisiologia , Regeneração Óssea/efeitos da radiação , Consolidação da Fratura/efeitos da radiação , Fraturas Ósseas/fisiopatologia , Fraturas Ósseas/terapia , Ondas de Choque de Alta Energia/uso terapêutico , Terapia por Ultrassom/métodos , Animais , Calcificação Fisiológica/efeitos dos fármacos , Relação Dose-Resposta à Radiação , Fraturas Ósseas/diagnóstico por imagem , Masculino , Doses de Radiação , Radiografia , Ratos , Ratos Wistar , Resultado do TratamentoRESUMO
This aim of this paper is to briefly report the education methodology employed at the Santa Casa School of Medical Sciences undergraduate program, founded in 1963, Sao Paulo, Brazil. Some relevant historical aspects are also brought out in order to provide readers with a glimpse of the social scenario that have yielded such successful model, based on integrative, practice-based strategies. Developed from simple concepts, innovative at that time, the educational system, the building structure of the hospital-university facilities and the pedagogical method remains modern and still inspires educators nowadays. The Department of Morphology is in alignment with these principles, working with the minimum possible lectures and exploring practical experience to the maximum. The disciplines of anatomy, histology and embryology comprise the curricular unit, elaborated per organ system, in a pedagogical program based on: timeline organization of the disciplines, strong theory-practice linkage, and a proactive learning system. The faculty members are trained in multiple areas to be as versatile as possible, delivering lectures and assisting in the practical training. New teaching methods may aggregate value to this model. We believe that such didactic approach can provide students with a realistic perspective of the main purpose and applicability of the basic sciences.
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Humanos , Anatomia/educação , Educação/métodos , Embriologia/educação , Ensino/métodos , Histologia/educação , AprendizagemRESUMO
Se plantea un bosquejo histórico del desarrollo de la psicología en Argentina, desde sus orígenes hacia el final del siglo XIX (El escenario de la siembra) hasta la actualidad (El escenario de la cosecha adeudada). Entre medio se plantea la extinción, por retiros laborales por edad o por defunción, de las líneas de quienes fueron los pioneros que surgieron en este país algo menos de veinte años después de la fundación del Laboratorio de Psicología Experimental por parte de Wundt, un período de vacancia de la disciplina y el múltiple surgimiento de las carreras de psicología en las universidades públicas, con posterioridad a 1954 (El escenario de la germinación), con grandes falencias teórico-científicas y fuertes distorsiones generadas por el modelo médico-clínico. Si bien en la actualidad se está modificando esta situación, importantes falencias y sesgos permanecen vigentes.(AU)
We review the historical development of Psychology in Argentina, from its origins at the end of the nineteenth century (the sowing period) until present times (the period of the owed harvest). We explain the extinction - due to retirement or death - of the paths set up by pioneers who emerged in this country two decades after Wundt founded the Experimental Psychology Laboratory, followed by a vacancy period in the discipline and the multiple emergence of psychology degrees at public universities after 1954. This gestation period had important theoretical and scientific flaws and strong distortions created by the medical-clinical model. Although these circumstances are changing nowadays, there remain some important flaws and bias.(AU)
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Los sistemas educativos tradicionales han convertido a los estudiantes en entidades pasivas que guardan información transitoriamente, sin mayores capacidades para procesarla y aplicarla a la solución de situaciones de la vida diaria. La discusión generalizada entre los investigadores de la educación plantea la necesidad de cambiar las estrategias pedagógicas que han favorecido esas situaciones, para permitir una formación integral del individuo como ser capaz de razonar, crear, innovar y desarrollarse autónomamente. Las exigencias gubernamentales, institucionales e incluso las políticas de la globalización y el desarrollo del ser humano basado en la economía del conocimiento reclaman ese cambio de estrategias en el sistema pedagógico de enseñanza-aprendizaje; pues aunque éste se encuentre amenazado por la resistencia natural que ofrece el enfrentamiento con una cultura establecida, debe darse desde el aula de una manera inmediata. Como respuesta a esa necesidad, la Unidad de Bioquímica del Instituto de Ciencias Básicas de la Facultad de Medicina (Universidad del Rosario) plantea una estrategia no tradicional en pos del cambio.
Traditional educative systems, had convert students in passive recipient, who are keeping information without any possibility to process and apply it for the solution of daily problems. General discussion between educative researchers, had been establish the necessity to change the educative strategies that have been supporting those situations, looking for an integral education of the individual in terms of the capacity to argue, to create, to innovate, to develop by him self with independence. Governments, institutions and the politics requirements, that handle the globalization and the human development based in the knowledge economy, demand changes in the pedagogical system strategies in spite of the barriers from the traditional educative system. Responding to these necessity, the Biochemistry Department belong to the Basic Sciences Institute from the Medicine Faculty in the University of Rosario, is applying a different pedagogical strategy.