Analysing the effect caused by increasing the molecular volume in M1-AChR receptor agonists and antagonists: a structural and computational study.

M1 muscarinic acetylcholine receptor (M1-AChR), a member of the G protein-coupled receptors (GPCR) family, plays a crucial role in learning and memory, making it an important drug target for Alzheimer's disease (AD) and schizophrenia. M1-AChR activation and deactivation have shown modifying effects in AD and PD preclinical models, respectively. However, understanding the pharmacology associated with M1-AChR activation or deactivation is complex, because of the low selectivity among muscarinic subtypes, hampering their therapeutic applications. In this regard, we constructed two quantitative structure-activity relationship (QSAR) models, one for M1-AChR agonists (total and partial), and the other for the antagonists. The binding mode of 59 structurally different compounds, including agonists and antagonists with experimental binding affinity values (pKi), were analyzed employing computational molecular docking over different structures of M1-AChR. Furthermore, we considered the interaction energy (Einter), the number of rotatable bonds (NRB), and lipophilicity (ilogP) for the construction of the QSAR model for agonists (R2 = 89.64, QLMO2 = 78, and Qext2 = 79.1). For the QSAR model of antagonists (R2 = 88.44, QLMO2 = 82, and Qext2 = 78.1) we considered the Einter, the fraction of sp3 carbons fCsp3, and lipophilicity (MlogP). Our results suggest that the ligand volume is a determinant to establish its biological activity (agonist or antagonist), causing changes in binding energy, and determining the affinity for M1-AChR.

Diseño curricular de un diplomado en enseñanza de fisiología / Curricular design of a physiology training diploma course

Introducción: Los conceptos fundamentales de la fisiología representan un avance significativo en la pedagogía de esta disciplina, y proporcionan una base sólida para la enseñanza y el aprendizaje. Estos conceptos enfatizan los principios metodológicos y disciplinarios necesarios para que los estudiantes comprendan la fisiología de manera efectiva. Además, guían tanto a estudiantes como a profesores, e influyen en el diseño de programas académicos de pregrado y posgrado. Materiales y métodos: Diseño curricular basado en las necesidades formativas de docentes de la carrera de médico cirujano de México. El análisis de necesidades formativas se desarrolló según el perfil de egreso de médicos mexicanos. Resultados: Como resultado primario, se obtuvo el programa académico de posgrado llamado ‘Diplomado en enseñanza de fisiología’, con un enfoque constructivista y que utiliza los conceptos fundamentales de la fisiología como su piedra angular. Este programa ha estado en funcionamiento durante cuatro años y ha capacitado a 35 profesores de más de 10 universidades en México. Está estructurado en cinco etapas de formación, que abarcan desde la ciencia del aprendizaje hasta la planificación de sesiones teóricas y prácticas, y en cada etapa se explora y se reflexiona sobre los conceptos fundamentales de la fisiología. Conclusiones: Los académicos valoran positivamente la inclusión de los conceptos fundamentales de la fisiología como ejes de enseñanza y aprendizaje trasversales.(AU)

Introduction: The core concepts of physiology represent a significant advancement in the pedagogy of this discipline, providing a solid foundation for teaching and learning. These concepts emphasize the methodological and disciplinary principles necessary for students to effectively understand physiology. Moreover, they guide both students and teachers, influencing the design of undergraduate and postgraduate academic programs.Materials and methods: Curricular design based on the training needs of professors in the medical career in Mexico; the analysis of training needs was developed according to the profile of graduating Mexican doctors. Results: The primary outcome was the academic program for the postgraduate program called ‘Certificate in Physiology Teaching’, with a constructivist approach that uses the core concepts of physiology as its cornerstone. This program has been in operation for four years and has trained 35 professors from more than ten universities in Mexico. It is structured in five training stages that range from the science of learning to the planning of theoretical and practical sessions, and in each stage, the core concepts of physiology are explored and reflected upon. Conclusions: Academics positively value the inclusion of the core concepts of physiology as cross-cutting teaching andlearning axes.(AU)

Clavulanic Acid and its Potential Therapeutic Effects on the Central Nervous System.

Clavulanic acid (CLAV) is a non-antibiotic ß-lactam that has been used since the late 1970s as a ß-lactamase inhibitor in combination with amoxicillin, another ß-lactam with antibiotic activity. Its long-observed adverse reaction profile allows it to say that CLAV is a well-tolerated drug with mainly mild adverse reactions. Interestingly, in 2005, it was discovered that ß-lactams enhance the astrocytic expression of GLT-1, a glutamate transporter essential for maintaining synaptic glutamate homeostasis involved in several pathologies of the central nervous system (CNS). This finding, along with a favorable pharmacokinetic profile, prompted the appearance of several studies that intended to evaluate the effect of CLAV in preclinical disease models. Studies have revealed that CLAV can increase GLT-1 expression in the nucleus accumbens (NAcc), medial prefrontal cortex (PFC), and spinal cord of rodents, to affect glutamate and dopaminergic neurotransmission, and exert an anti-inflammatory effect by modulating the levels of the cytokines TNF-α and interleukin 10 (IL-10). CLAV has been tested with positive results in preclinical models of epilepsy, addiction, stroke, neuropathic and inflammatory pain, dementia, Parkinson's disease, and sexual and anxiety behavior. These properties make CLAV a potential therapeutic drug if repurposed. Therefore, this review aims to gather information on CLAV's effect on preclinical neurological disease models and to give some perspectives on its potential therapeutic use in some diseases of the CNS.

La autoevaluación basada en criterios como elemento de evaluación en asignaturas de carga cognitiva elevada / Self-assessment based on criteria as an evaluation element in subjects with a high cognitive load

Introducción: La autoevaluación se ha definido como el proceso mediante el cual los alumnos deciden si han alcanzado o no los estándares definidos. La autoevaluación es una herramienta valiosa para identificar debilidades y fortalezas en los estudiantes de Medicina. Objetivo: Comparar los resultados de una prueba de autoevaluación basada en criterios con los resultados de un examen estandarizado para evaluar conocimientos disciplinares en Fisiología. Sujetos y métodos: En este trabajo desarrollamos y aplicamos una herramienta de autoevaluación a estudiantes de segundo año de la carrera de Medicina en la asignatura de Fisiología de la Facultad de Medicina de la Universidad Nacional Autónoma de México. Luego recopilamos comentarios y los dividimos en calificaciones clasificadas como ‘calificaciones altas’ y ‘calificaciones bajas’. Finalmente, comparamos los resultados de la autoevaluación con los de una prueba objetiva (prueba estandarizada) que evalúa los conocimientos disciplinares de fisiología. Resultados: Los alumnos que consideran que han realizado un esfuerzo y trabajo constante durante el curso se valoran mejor que los alumnos que no lo hacen. Por otro lado, encontramos diferencias significativas entre la prueba objetiva y la autoevaluación. Conclusiones: La autoevaluación basada en criterios puede ayudar a evaluar cualidades más allá del conocimiento disciplinario.(AU)

Introduction: Self-assessment has been defined as the process by which students decide whether or not they haveachieved the defined standards. Self-assessment is a valuable tool to identify weaknesses and strengths in medical students. Objective: To compare the results of a self-assessment test based on criteria with the results of a standardized exam to assess disciplinary knowledge in physiology. Subjects and methods. In this work we developed and applied a self-assessment tool to second-year medical students in the physiology course of the Faculty of Medicine of the National Autonomous University of Mexico. We then collected feedback and divided it into ratings categorized as: ‘high scores’ and ‘low scores.’ Finally, we compared the results of the self-assessment with those of an objective test (standardized test) that assesses disciplinary knowledge of physiology. Result: Students who consider that they have made a constant effort and work during the course value themselves better than students who do not. On the other hand, we found significant differences between the objective test and the selfassessment. Conclusions: Criteria-based self-assessment can help assess qualities beyond disciplinary knowledge.(AU)

Reflections on the design of an ultrasound study program in medical undergraduate / Reflexiones sobre el diseño de un programa de estudio de ultrasonido en el grado de medicina

Introduction: The use of didactic tools for teaching basic sciences in the medical career focuses on anatomical models, electrodiagnostic equipment, and simulation. Only some study programs incorporate images for teaching basic sciences; some of the reasons are the cost of the ultrasound equipment. However, many medical schools have the infrastructure to do so. Materials and methods: We conducted a review of the scientific literature in the Scopus, Web of Science, and Google Academic databases, after which the researchers conducted discussion sessions to select the main ideas that would help build the educational proposal. Results: Describe a proposal for curricular design for creating training programs and teacher training that allows maximizing the use of ultrasound as a teaching tool for the basic sciences of the medical career. Conclusion: The best way to strengthen the teaching of medical sciences is through constant academic training, both in disciplinary content and in teaching. Only in this way can we face the great need to train doctors who are very aware of their social responsibility.(AU)

Introducción: El uso de herramientas didácticas para la enseñanza de las ciencias básicas en la carrera de medicina se centra en modelos anatómicos, equipos de electrodiagnóstico y simulación. Solo algunos programas de estudio incorporan imágenes para la enseñanza de las ciencias básicas; algunas de las razones son el costo del equipo de ultrasonido. Sin embargo, muchas escuelas de medicina tienen la infraestructura para hacerlo. Materiales y métodos: Se realizó una revisión de la literatura científica en las bases de datos Scopus, Web of Science y Google Academic, tras lo cual los investigadores realizaron sesiones de discusión para seleccionar las ideas principales que ayudarían a construir la propuesta educativa. Resultados: Describir una propuesta de diseño curricular para la creación de programas de formación y formación docente que permita maximizar el uso de la ecografía como herramienta didáctica de las ciencias básicas de la carrera de medicina. Conclusión: La mejor manera de fortalecer la enseñanza de las ciencias médicas es a través de la formación académica constante, tanto en los contenidos disciplinares como en la docencia. Solo así podremos afrontar la gran necesidad de formar médicos muy conscientes de su responsabilidad social.(AU)

Perceived academic stress in Mexican medical students. The role of sex emotional distress, burnout, academic-social support, current abuse experiences, and coping strategies / Percepción del estrés académico en estudiantes de medicina mexicanos. El papel del sexo, distrés emocional, burnout, apoyo académico-social, experiencias actual es de abuso y estrategias de afrontamiento

Abstract Introduction Academic stress is a common problem among medical students that has a negative physiological, social, and learning impact. Perceived academic stress indicates how stressed a student is about academic issues over a given period of time and the ability to handle that stress. Objective To determine the prevalence of PAS and evaluate possible risk factors, focusing on sex differences, burnout, emotional distress, academic-social support, and coping strategies. Method A cross-sectional, retrospective, and comparative study was conducted through an online survey with medical students (MS) willing to participate anonymously. Results All students reported PAS and the majority to a moderate-severe degree. Comparing the presence of abuse within the academic environment between men and women, we found differences in the frequency of reporting emotional abuse and sexual. Also, we found differences in perceived academic social support from teachers and family members. Multiple logistic regression analysis showed sex and current sexual abuse inside school had the strongest association with PAS in MS, followed by a family history of depression and perceived less academic social support from family. Discussion and conclusion Timely identification of individuals at-risk will be critical to establish preventive strategies to limit the impact of PAS in MS, stress management programs, training coping skills, and offer prompt therapeutic alternatives when needed.

Resumen Introducción El estrés académico es un problema común entre los estudiantes de medicina que tiene un impacto negativo a nivel fisiológico, social y de aprendizaje. El estrés académico percibido (PAS) indica lo estresado que está un estudiante por cuestiones académicas durante un periodo de tiempo determinado y la capacidad para manejar ese estrés. Objetivo Determinar la prevalencia del PAS y evaluar los posibles factores de riesgo, centrándose en las diferencias por sexo, burnout, el malestar emocional, el apoyo académico-social y las estrategias de afrontamiento. Método Se realizó un estudio transversal, retrospectivo y comparativo a través de una encuesta en línea con estudiantes de medicina dispuestos a participar de forma anónima. Resultados Todos los estudiantes reportaron PAS y la mayoría en un grado moderado-severo. Comparando la presencia de maltrato dentro del ámbito académico entre hombres y mujeres, encontramos diferencias en la frecuencia de denuncia de maltrato emocional y sexual. Asimismo, encontramos diferencias en el apoyo social académico percibido por parte de docentes y familiares. El análisis de regresión logística múltiple mostró que el sexo y el abuso sexual actual dentro de la escuela tenían la asociación más fuerte con PAS, seguidos por antecedentes familiares de depresión y menos apoyo social académico percibido por parte de la familia. Discusión y conclusión La identificación oportuna de las personas en riesgo será fundamental para establecer estrategias preventivas para limitar el impacto de PAS, programas de manejo del estrés, capacitación en habilidades de afrontamiento y ofrecer alternativas terapéuticas rápidas cuando sea necesario.

Sex Differences in Vascular Reactivity to Angiotensin II During the Evolution of Myocardial Infarction.

The influence of sex on the vascular response during the progression of myocardial infarction (MI) has not been extensively studied. In this work, we analyzed the differences of the vasoconstriction induced by angiotensin II (Ang II) in the absence and presence of valsartan (200 nM) on the aortic rings of male and female Wistar rats at 2, 4, 24, and 48 hours and 1, 2, 3, and 4 weeks after induction of MI. In the aortic rings of males, an increase was observed in the contractile response that lasts up to 4 weeks; on females, this effect is diminished since 48 hours until reaching sham group values at 2 weeks of coronary occlusion. The incubation of valsartan generated greater reduction on vasoconstriction in males than females. In relation to the determination of infarct areas, we found them between 30% and 40% in all experimental groups. In addition, the index of hypertrophy was determined and no significant changes were observed in female rats, while in males we reported an increase at 2, 3, and 4 weeks. In conclusion, we found differences in vascular reactivity due to sex, as well as on the response of Ang II via AT1 during the evolution of MI.