Perceptions of co-teaching as a pedagogical approach to integrate basic and clinical sciences.

Background: Medical curricula must provide students with basic and clinical competencies for critical reasoning and diagnosing. These competencies are better acquired when basic and clinical science are taught in an integrated and collaborative manner. In this study, we investigate whether supportive co-teaching (SCT) is an effective approach to promote integrated and reasoned learning as well as to help medical students applying theoretical concepts to clinical scenarios taught in a team-based learning (TBL) framework. Methods: We conducted a concurrent mixed methods study. For the qualitative part, we performed a focus group and semi-structured interviews to clinical and basic science teachers and medical students. Using conventional content analysis, themes were identified deductively. For the quantitative part, an analytical and descriptive observational study of the 2019-2020 cohort of first-year undergraduate medical students was conducted (107 students out of 220 completed the survey). For the descriptive study, questions were grouped into 5 categories. Results: Deductive themes from the analysis include relationship between clinical and basic science teachers, knowledge integration, methodology, teamwork and integrated Medicine and curricular design. Basic science and clinical teachers highlighted their relationship as critical to increase their mutual knowledge. This was supported by the student's opinion who very much valued their joint feedback. Regarding knowledge integration, both teachers and students found that horizontal and vertical integration enhanced applicability of basic knowledge to future clinical practice. The TBL methodology was very well perceived by both students and teachers and was highly motivating for students even though the need for commitment. Students considered that this program presented a great opportunity and expressed their interest in maintaining it in the future. These results were supported by the quantitative data. Conclusion: Our work supports the value of co-teaching in basic and clinical sciences within a TBL framework set in real clinical case scenarios. By employing this approach, students can actively apply their theoretical knowledge to clinical practice, enhancing their critical thinking, problem-solving, and clinical reasoning skills. Our findings can inform curriculum design and improved educational practice, leading to enhanced learning experiences for healthcare students and ultimately better patient care.

Enhancing academic performance and student engagement in health education: insights from Work Station Learning Activities (WSLA).

Making health science students aware of the importance of basic science knowledge for professional practice is a major educational challenge, especially during the early years of preclinical courses. Here, using an integrated curricular approach, we analyze whether Work Station Learning Activities (WSLA), which combine active learning methodologies for teaching basic science in clinical scenarios, can help to develop deeper learning and student engagement. In order to increase student motivation, we evaluated the effectiveness of WSLA using statistical analyses and an observation tool based on the ICAP (Interactive, Constructive, Active, and Passive) framework, which categorizes learning tasks based on the nature of student engagement. Statistical analyses revealed positive correlations between the different summative evaluations along the development of the activities, indicating the learning process inherent to WSLA progression and affirming the positive influence of WSLA on academic outcomes. Comparing the pre- and post-tests, students scored significantly higher on the post-test (statistically significant p < 0.001). WSLA promotes both constructivist and interactive learning, as validated by its alignment with the ICAP model. The study examines student engagement through systematic observation, revealing a relationship between student engagement and final grades. Students who exhibit constructive learning consistently earn higher grades, emphasizing the positive impact of active engagement. Thus, passive behavior profiles show a significant proportion of fails (40%), while constructive profiles stand out as the sole recipients of the coveted excellent rating. Ultimately, this study contributes to our understanding of the effectiveness of WSLA in promoting active learning and enhancing student engagement within integrated health education curricula. It highlights the importance of active learning behaviors for academic success and suggests avenues for further research to optimize integrated teaching methodologies in medical education.

Learning and assessment strategies to develop specific and transversal competencies for a humanized medical education.

Introduction: Medical education should promote the development of skills and abilities that can be applied to real-world work performance. The aim of this study is to evaluate technical and methodological knowledge, as well as physician-patient communication skills, as one of the most important transversal competencies that a good physician should acquire; all this in a reliable, accurate and objective way. Methods: We present a rubric specifically designed and implemented for the evaluation of specific and transversal competencies in the physiology practical sessions, during the second year of the medical degree. The assessment consists in two evaluation tests: 1) a theoretical test that consists of multiple-choice questions. Students must demonstrate that they have acquired adequate theoretical knowledge (specific competency "to know"); 2) a practical test, in which students are evaluated by the rubric through the simulation of a medical consultation. Thus, demonstrating their ability to execute/apply what they have learned in class (specific competency "to know how to do"). They are also evaluated on the transversal competencies that we call "communication with the patient" (transversal competency "to know how to be there") and "dealing with the patient" (transversal competency "to know how to be"). Results: We evaluated whether there were differences in the grades obtained by students when the transversal competencies were not assessed (academic years 2017-2018 and 2018-2019; n = 289), and when the transversal competencies were assessed by applying the rubric in the academic years 2019-2020, 2021-2022, and 2022-2023 (n = 526). Furthermore, we present a student perception that supports the use of clinical simulation and our rubric as a good method within the competency learning process. Discussion: The acquisition of these competencies, starting from the first courses of undergraduate education, helps to raise the students' awareness in the development of a more humanized medicine, allowing a better response to the patients' needs. Our rubric, which clearly indicate the performance criteria, have become an excellent method to carry out the assessment of competencies, both for students and teachers, since they allow to obtain clear evidence of the level of acquisition and application of knowledge.

Quantitative and qualitative evaluation of a learning model based on workstation activities.

BACKGROUND: Moving towards a horizontal and vertical integrated curriculum, Work-Station Learning Activities (WSLA) were designed and implemented as a new learning instrument. Here, we aim to evaluate whether and how this specific learning model affects academic performance. To better understand how it is received by medical students, a mixed methods research study was conducted. METHODS: In the quantitative strand, two cohorts of first year students were compared: academic year 2015-2016 n = 320 with no exposure to WSLA, and academic year 2016-2017 n = 336 with WSLA. Learning objectives at different levels of Bloom's taxonomy were identified and performance evaluated from multiple-choice questions. In the qualitative strand, a total of six students were purposely selected considering academic performance and motivation, and submitted to semistructured interviews. RESULTS: Performance at both cohorts for learning objectives at lower levels of Bloom's taxonomy was similar (38.8 vs. 39.0%; p = 0.955). In contrast, students in the WSLA group outperformed significantly those not exposed for learning objectives involving upper levels (68.5 vs. 54.2%; p <0.001). A multivariate analysis confirmed that the probability of mastering the second (more complex) objective is 1.64 times higher in students with WSLA methodology (OR 95% CI, 1.15-2.34; p = 0.007) than with traditional methodology. In the interviews, students perceived the clinical scenario of WSLA as a motivator and recognized this methodology as a more constructive framework for understanding of complicated concepts. CONCLUSIONS: In summary, our mixed methods research supports WSLA as a strategy that promotes deep learning and has a positive impact on academic performance for learning objectives involving higher order thinking skills in medical curricula.

A specific isoform of Pyd/ZO-1 mediates junctional remodeling and formation of slit diaphragms.

The podocyte slit diaphragm (SD), responsible for blood filtration in vertebrates, is a major target of injury in chronic kidney disease. The damage includes severe morphological changes with destabilization of SDs and their replacement by junctional complexes between abnormally broadened foot processes. In Drosophila melanogaster, SDs are present in nephrocytes, which filter the fly's hemolymph. Here, we show that a specific isoform of Polychaetoid/ZO-1, Pyd-P, is essential for Drosophila SDs, since, in pyd mutants devoid of Pyd-P, SDs do not form and the SD component Dumbfounded accumulates at ectopic septate-like junctions between abnormally aggregated nephrocytes. Reintroduction of Pyd-P leads to junctional remodeling and their progressive normalization toward SDs. This transition requires the coiled-coil domain of Pyd-P and implies formation of nonclathrin vesicles containing SD components and their trafficking to the nephrocyte external membrane, where SDs assemble. Analyses in zebrafish suggest a conserved role for Tjp1a/ZO-1 in promoting junctional remodeling in podocytes.

Liderando el cambio: hacia un currículo integrado para ciencias biomédicas. Experiencia de la Universidad Europea de Madrid / Leading change: moving towards an integrated curriculum suitable for biomedical sciences. Experience from Universidad Europea de Madrid

Las ciencias biomédicas han experimentado una gran revolución en un corto período. Este avance es posible a través del estudio continuado de los mecanismos moleculares, genéticos y fisiológicos de los procesos biológicos, y ello contribuye a una mejor comprensión del funcionamiento normal de nuestro cuerpo y establece el conocimiento de las bases de la patología. Esto implica que los profesionales de ciencias de la salud deben desarrollar competencias y capacidades especiales que les permitan establecer nexos dinámicos entre las ciencias básicas y su práctica profesional. El diseño curricular más adecuado para la formación en estas competencias y capacidades se logra a través del currículo integrado. El aprendizaje integrado es un proceso centrado en el alumno, mediante el cual se adquieren conocimientos de manera flexible e individualizada a largo plazo. En la Universidad Europea de Madrid hemos afrontado esta nueva necesidad utilizando un modelo de aprendizaje integrado de materias básicas indicado para abordar la integración curricular progresiva, y que hemos denominado WSLA (Work Stations Learning Activities). Se basa en una modificación del aprendizaje basado en equipos adaptada a las directrices europeas y españolas, especialmente indicada para los grados de ciencias de la salud. Utilizando el modelo WSLA podemos crear módulos de actividades de aprendizaje integrado adaptables a distintas situaciones, desde clases magistrales hasta gamificación o prácticas de laboratorio. Proponemos nuestro modelo WSLA como una opción flexible y escalable para adoptar la integración de manera escalonada como paso previo a la integración curricular completa

Biomedical sciences have faced a strong developmental shift in a short period of time. This advance has been boosted by the study of the molecular, genetic and physiological mechanisms of the biological processes. This has a direct effect on the better understanding of the normal functioning of our body and establishes the bases of pathology knowledge. Thus, health science professionals must develop new skills and abilities that allow them to establish links between basic sciences and their professional practice. The most appropriate curricular design for competency and capacity building is achieved through the integrated curriculum. Integrated learning is a student-centered process, through which knowledge is developed lifelong in a flexible and individualized manner. At the Universidad Europea de Madrid we have faced new demands by using a model of integrated learning of basic subjects especially suitable to achieve progressive curricular integration. We have named this new model WSLA (Work Stations Learning Activities) and it is based on a modification of the team based learning adapted to the European and Spanish guidelines especially indicated for the Degrees of Health Sciences. Using the WSLA model different modules of integrated learning activities can be created and adapted to different situations, including master classes, gamification or laboratory practices. We propose our WSLA model as a scalable and flexible option to adopt the stepwise integration as a stage prior to the complete curricular integration

Src64B phosphorylates Dumbfounded and regulates slit diaphragm dynamics: Drosophila as a model to study nephropathies.

Drosophila nephrocytes are functionally homologous to vertebrate kidney podocytes. Both share the presence of slit diaphragms that function as molecular filters during the process of blood and haemolymph ultrafiltration. The protein components of the slit diaphragm are likewise conserved between flies and humans, but the mechanisms that regulate slit diaphragm dynamics in response to injury or nutritional changes are still poorly characterised. Here, we show that Dumbfounded/Neph1, a key diaphragm constituent, is a target of the Src kinase Src64B. Loss of Src64B activity leads to a reduction in the number of diaphragms, and this effect is in part mediated by loss of Dumbfounded/Neph1 tyrosine phosphorylation. The phosphorylation of Duf by Src64B, in turn, regulates Duf association with the actin regulator Dock. We also find that diaphragm damage induced by administration of the drug puromycin aminonucleoside (PAN model) directly associates with Src64B hyperactivation, suggesting that diaphragm stability is controlled by Src-dependent phosphorylation of diaphragm components. Our findings indicate that the balance between diaphragm damage and repair is controlled by Src-dependent phosphorylation of diaphragm components, and point to Src family kinases as novel targets for the development of pharmacological therapies for the treatment of kidney diseases that affect the function of the glomerular filtration barrier.

Drosophila araucan and caupolican integrate intrinsic and signalling inputs for the acquisition by muscle progenitors of the lateral transverse fate.

A central issue of myogenesis is the acquisition of identity by individual muscles. In Drosophila, at the time muscle progenitors are singled out, they already express unique combinations of muscle identity genes. This muscle code results from the integration of positional and temporal signalling inputs. Here we identify, by means of loss-of-function and ectopic expression approaches, the Iroquois Complex homeobox genes araucan and caupolican as novel muscle identity genes that confer lateral transverse muscle identity. The acquisition of this fate requires that Araucan/Caupolican repress other muscle identity genes such as slouch and vestigial. In addition, we show that Caupolican-dependent slouch expression depends on the activation state of the Ras/Mitogen Activated Protein Kinase cascade. This provides a comprehensive insight into the way Iroquois genes integrate in muscle progenitors, signalling inputs that modulate gene expression and protein activity.

Anti-beta1-adrenergic receptor autoantibodies are potent stimulators of the ERK1/2 pathway in cardiac cells.

OBJECTIVE: Antibodies specific for the beta1-adrenergic receptor (beta1AR) are highly prevalent in patients with idiopathic dilated cardiomyopathy (DCM) and known to contribute to the pathogenesis of heart failure, though the precise molecular mechanisms involved are largely unknown. METHODS: We have explored the effects of beta(1)AR autoantibodies obtained from DCM patients on extracellular signal-regulated kinase (ERK) activation in murine cardiomyocytes. RESULTS: We find that human beta(1)AR autoantibodies potently stimulate ERK1/2 in cardiac cells by using signalling pathways different from those triggered by the classic beta-agonist isoproterenol, also leading to a different pattern of activated ERK subcellular localization. The extent of ERK stimulation by endogenous cardiac beta(1)AR is markedly enhanced in the presence of both beta(1)AR-autoantibodies and isoproterenol. Interestingly, beta(1)AR-autoantibody-mediated ERK activation is not blocked by some betaAR antagonists used in the treatment of heart failure. CONCLUSIONS: Our results suggest that these antibodies elicit a distinct beta(1)AR active conformation that would lead to the engagement of signaling effectors different from those recruited by classic beta-agonists, a finding that could lead to better understanding of DCM pathogenesis and aid in designing diagnostic and therapeutic strategies.

Functional interplay between endothelial nitric oxide synthase and membrane type 1 matrix metalloproteinase in migrating endothelial cells.

Nitric oxide (NO) is essential for vascular homeostasis and is also a critical modulator of angiogenesis; however, the molecular mechanisms of NO action during angiogenesis remain elusive. We have investigated the potential relationship between NO and membrane type 1-matrix metalloproteinase (MT1-MMP) during endothelial migration and capillary tube formation. Endothelial NO synthase (eNOS) colocalizes with MT1-MMP at motility-associated structures in migratory human endothelial cells (ECs); moreover, NO is produced at these structures and is released into the medium during EC migration. We have therefore addressed 2 questions: (1) the putative regulation of MT1-MMP by NO in migratory ECs; and (2) the requirement for MT1-MMP in NO-induced EC migration and tube formation. NO upregulates MT1-MMP membrane clustering on migratory human ECs, and this is accompanied by increased degradation of type I collagen substrate. MT1-MMP membrane expression and localization are impaired in lung ECs from eNOS-deficient mice, and these cells also show impaired migration and tube formation in vitro. Inhibition of MT1-MMP with a neutralizing antibody impairs NOinduced tube formation by human ECs, and NO-induced endothelial migration and tube formation are impaired in lung ECs from mice deficient in MT1-MMP. MT1-MMP thus appears to be a key molecular effector of NO during the EC migration and angiogenic processes, and is a potential therapeutic target for NO-associated vascular disorders.

Association of 14-3-3 proteins to beta1-adrenergic receptors modulates Kv11.1 K+ channel activity in recombinant systems.

We identify a new mechanism for the beta(1)-adrenergic receptor (beta(1)AR)-mediated regulation of human ether-a-go-go-related gene (HERG) potassium channel (Kv11.1). We find that the previously reported modulatory interaction between Kv11.1 channels and 14-3-3epsilon proteins is competed by wild type beta(1)AR by means of a novel interaction between this receptor and 14-3-3epsilon. The association between beta(1)AR and 14-3-3epsilon is increased by agonist stimulation in both transfected cells and heart tissue and requires cAMP-dependent protein kinase (PKA) activity. The beta(1)AR/14-3-3epsilon association is direct, since it can be recapitulated using purified 14-3-3epsilon and beta(1)AR fusion proteins and is abolished in cells expressing beta(1)AR phosphorylation-deficient mutants. Biochemical and electrophysiological studies of the effects of isoproterenol on Kv11.1 currents recorded using the whole-cell patch clamp demonstrated that beta(1)AR phosphorylation-deficient mutants do not recruit 14-3-3epsilon away from Kv11.1 and display a markedly altered agonist-mediated modulation of Kv11.1 currents compared with wild-type beta(1)AR, increasing instead of inhibiting current amplitudes. Interestingly, such differential modulation is not observed in the presence of 14-3-3 inhibitors. Our results suggest that the dynamic association of 14-3-3 proteins to both beta(1)AR and Kv11.1 channels is involved in the adrenergic modulation of this critical regulator of cardiac repolarization and refractoriness.

Mechanisms of regulation of G protein-coupled receptor kinases (GRKs) and cardiovascular disease.

The G protein-coupled receptor kinases (GRKs) participate with arrestins in the regulation and signal propagation of multiple G protein-coupled receptors (GPCR) of key physiological and pharmacological relevance in the cardiovascular system. The complex mechanisms of regulation of GRK expression, degradation and function are being unveiled gradually. The levels of these kinases are known to change in pathological situations such as heart failure, hypertrophy and hypertension, and in animal models of these diseases. A better understanding of the mechanisms underlying these changes and of how these alterations participate in the triggering or progression of cardiovascular disease may contribute to the design of novel diagnostic and therapeutic strategies.

Polymorphism in genes involved in adrenergic signaling associated with Alzheimer's.

To investigate the potential involvement of adrenergic signaling in Alzheimer's disease (AD) pathogenesis, we performed genetic and functional studies of genes initiating the cascade. We chose two functional single-nucleotide polymorphisms (SNPs) in the beta1-adrenergic receptor (ADRB1) and the G protein beta3 subunit (GNB3) genes, respectively, and analyzed their allelic frequencies in a case-control sample of AD. We found that the GNB3 T allele produces a significant risk for AD in individuals homozygous for the ADRB1 C allele, suggesting that the combined effect of both polymorphisms influences AD susceptibility. Interestingly, the co-expression of GNB3 T and ADRB1 C alleles, compared with GNB3 C and ADRB1 G, produced increased cAMP levels and MAPK activation following adrenergic stimulation of transfected human cell lines. Furthermore, the co-expression of these alleles also produced increases in APP expression. These data strongly indicate that the combination of GNB3 and ADRB1 polymorphisms produces AD susceptibility by changing the cell responsiveness to adrenergic stimulation, pointing to the modulation of brain adrenergic receptors as a potential target for novel AD therapeutic strategies.