El descubrimiento de nuevos fármacos, concepto umbral en farmacología

[EN] The so-called “threshold concepts” are present in all areas of study. Its acquisition by the student represents a milestone in the advancement of the conceptual understanding of a subject. They are often difficult to learn, but when they are overcome they generate a reconceptualization that allows progress and deepening in the subject of study. We present an activity designed to develop a key threshold concept in pharmacology, the drug discovery process. To do this, we develop a practical laboratory project that will integrate both the extraction and search for active ingredients and the simulation of some aspects of their clinical trials in the phase I.[ES] Los llamados “conceptos umbral” se encuentran presentes en todas las áreas de estudio. Su adquisición por el estudiante representa un hito en el avance de la comprensión conceptual de una asignatura. A menudo resultan difíciles de aprender, pero cuando son superados generan una reconceptualización que permite el progreso y profundización en la materia de estudio. Presentamos una actividad diseñada para desarrollar un concepto umbral clave en farmacología, el proceso de descubrimiento de fármacos. Para ello, desarrollamos un proyecto práctico de laboratorio que integrará tanto la extracción y búsqueda de principios activos como la simulación de algunos aspectos de sus ensayos clínicos en fase I.Sanmartin Santos, I.; Revert Ros, F.; Almela Camañas, C.; Ventura, I.; Prieto Ruíz, J.; Lloret, A. (2021). El descubrimiento de nuevos fármacos, concepto umbral en farmacología. En IN-RED 2021: VII Congreso de Innovación Edicativa y Docencia en Red. Editorial Universitat Politècnica de València. 1597-1604. https://doi.org/10.4995/INRED2021.2021.13807OCS1597160

Desarrollo temprano de competencias relacionadas con el “aprendizaje de por vida”

[EN] The activity is intended to enhance the learning process of the students. The objective is to provide a new perspective on the changing nature of knowledge and the need for "lifelong learning". Additionally, it develops very interesting skills and learning for the students, such as designing and conducting experiments, interpreting the results and writing scientific papers. Students will generate "new scientific knowledge" themselves in two laboratory sessions, testing the neuroprotective effect of a family of drugs on a strain of the nematode C. elegans. Each group will experiment with a drug, elaborating a simple mini scientific article with their results, sharing it with the rest of the class in a workshop implemented in the Moodle platform for peer review. From all the articles generated, each student must write a "textbook" style paragraph that will synthesize all the information and upload it as homework.[ES] La actividad pretende una mejora del proceso de aprendizaje de los alumnos. El objetivo es proporcionar una nueva perspectiva acerca de la naturaleza cambiante del conocimiento y la necesidad del “aprendizaje de por vida”. Adicionalmente, desarrolla competencias y aprendizajes muy interesantes para los estudiantes, como el diseño y realización de experimentos, la interpretación de los resultados y la redacción de artículos científicos. Los alumnos generarán ellos mismos “conocimiento científico nuevo” en dos sesiones de laboratorio, testando el efecto neuroprotector de una familia de fármacos en una cepa del nematodo C. elegans. Cada grupo experimentará con un fármaco, elaborando un sencillo mini artículo científico con sus resultados, compartiéndolo con el resto de la clase en un taller implementado en la plataforma Moodle para su evaluación por pares. A partir de todos los artículos generados, cada alumno debe escribir un párrafo con estilo “libro de texto” que sintetizará toda la información y que subirá como tarea.Sanmartin Santos, IS.; Almela Camañas, C.; Revert Ros, F.; Ventura González, I.; Prieto Ruíz, JÁ. (2022). Desarrollo temprano de competencias relacionadas con el “aprendizaje de por vida”. Editorial Universitat Politècnica de València. 1144-1151. https://doi.org/10.4995/INRED2022.2022.159121144115

Caracterització hídrica dels parcs de Barcelona : informe final

Sol·licitant de l’informe: Barcelona Cicle de l'Aigua, S.A

Non-motor symptom burden in patients with Parkinson's disease with impulse control disorders and compulsive behaviours : results from the COPPADIS cohort

The study was aimed at analysing the frequency of impulse control disorders (ICDs) and compulsive behaviours (CBs) in patients with Parkinson's disease (PD) and in control subjects (CS) as well as the relationship between ICDs/CBs and motor, nonmotor features and dopaminergic treatment in PD patients. Data came from COPPADIS-2015, an observational, descriptive, nationwide (Spain) study. We used the validated Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) for ICD/CB screening. The association between demographic data and ICDs/CBs was analyzed in both groups. In PD, this relationship was evaluated using clinical features and treatment-related data. As result, 613 PD patients (mean age 62.47 ± 9.09 years, 59.87% men) and 179 CS (mean age 60.84 ± 8.33 years, 47.48% men) were included. ICDs and CBs were more frequent in PD (ICDs 12.7% vs. 1.6%, p < 0.001; CBs 7.18% vs. 1.67%, p = 0.01). PD patients had more frequent previous ICDs history, premorbid impulsive personality and antidepressant treatment (p < 0.05) compared with CS. In PD, patients with ICDs/CBs presented younger age at disease onset, more frequent history of previous ICDs and premorbid personality (p < 0.05), as well as higher comorbidity with nonmotor symptoms, including depression and poor quality of life. Treatment with dopamine agonists increased the risk of ICDs/CBs, being dose dependent (p < 0.05). As conclusions, ICDs and CBs were more frequent in patients with PD than in CS. More nonmotor symptoms were present in patients with PD who had ICDs/CBs compared with those without. Dopamine agonists have a prominent effect on ICDs/CBs, which could be influenced by dose

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Exercise triggers ARVC phenotype in mice expressing a disease-causing mutated version of human plakophilin-2.

BACKGROUND Exercise has been proposed as a trigger for arrhythmogenic right ventricular cardiomyopathy (ARVC) phenotype manifestation; however, research is hampered by the limited availability of animal models in which disease-associated mutations can be tested. OBJECTIVES This study evaluated the impact of exercise on ARVC cardiac manifestations in mice after adeno-associated virus (AAV)-mediated gene delivery of mutant human PKP2, which encodes the desmosomal protein plakophilin-2. METHODS We developed a new model of cardiac tissue-specific transgenic-like mice on the basis of AAV gene transfer to test the potential of a combination of a human PKP2 mutation and endurance training to trigger an ARVC-like phenotype. RESULTS Stable cardiac expression of mutant PKP2 (c.2203C>T), encoding the R735X mutant protein, was achieved 4 weeks after a single AAV9-R735X intravenous injection. High-field cardiac magnetic resonance over a 10-month postinfection follow-up did not detect an overt right ventricular (RV) phenotype in nonexercised (sedentary) mice. In contrast, endurance exercise training (initiated 2 weeks after AAV9-R735X injection) resulted in clear RV dysfunction that resembled the ARVC phenotype (impaired global RV systolic function and RV regional wall motion abnormalities on cardiac magnetic resonance). At the histological level, RV samples from endurance-trained R735X-infected mice displayed connexin 43 delocalization at intercardiomyocyte gap junctions, a change not observed in sedentary mice. CONCLUSIONS The introduction of the PKP2 R735X mutation into mice resulted in an exercise-dependent ARVC phenotype. The R735X mutation appears to function as a dominant-negative variant. This novel system for AAV-mediated introduction of a mutation into wild-type mice has broad potential for study of the implication of diverse mutations in complex cardiomyopathies.S

Historia del Colegio Viejo de S. Bartholomé Mayor de la celebre Universidad de Salamanca : vida del ... Sr. Don Diego de Anaya Maldonado ... : primera parte

Les il. són els grav. calc. de capçalera, la majoria signats: "Prieto"El grav. calc. de port. representa al Col·legiEls f. de grav. calc., retrats de Carles III i de D. Diego de Anaya MaldonadoSign.: ¶-¶¶¶4, A-Kkkk4, Llll6Port. amb grav. calc. en capçaleraLletres inicials adornades, frisos tip. decoratius i capçaleres calcNotes a peu de pàg. i reclam

Influence of Stone Bunds on Vegetation and Soil in an Area Reforested with Pinus engelmannii Carr. in the Forests of Durango, Mexico

The forest ecosystems of Mexico experience soil degradation mainly due to water erosion, which causes low vegetation regeneration. One of the strategies to diminish soil loss is through the construction of stone bunds (SB)&mdash;hand-made structures to trap sediment and store water for longer periods. However, little is known about their effects on pine establishment. The objectives of this study were to evaluate the effect of SB on the survival and growth of individual P. engelmannii Carr. specimens with respect to the distance of their planted. The study additionally sought to analyse how SB would affect changes in the production of aerial phytomass, herbaceous vegetation cover and soil characteristics in a reforested area of Durango State in north-central Mexico. Three treatments were evaluated by planting pine trees at three distances with respect to the SB: 80 cm upslope bund (UB), 80 cm downslope bund (DB) and between upper and lower bunds (BB). The variables analysed were the following: The survival and growth of reforestation, aerial coverage and the production of herbaceous plants, and the physicochemical characteristics of the soil. Survival showed significant differences (p &lt; 0.05) among treatments, UB (80%), DB (27%) and BB (30%). The production of aerial phytomass did not show significant differences between treatments UB (1651 kg ha&minus;1) and DB (1058 kg ha&minus;1), although these two were different (p &lt; 0.05) to BB (600 kg ha&minus;1). On the other hand, the vegetation cover and soil characteristics did not show statistical differences. These results highlight the importance of the effect of SB on the survival of P. engelmannii Carr. and the growth of herbaceous vegetation