Dysfunction in the Cystic Fibrosis Transmembrane Regulator in Chronic Obstructive Pulmonary Disease as a Potential Target for Personalised Medicine

In recent years, numerous pathways were explored in the pathogenesis of COPD in the quest for new potential therapeutic targets for more personalised medical care. In this context, the study of the cystic fibrosis transmembrane conductance regulator (CFTR) began to gain importance, especially since the advent of the new CFTR modulators which had the potential to correct this protein’s dysfunction in COPD. The CFTR is an ion transporter that regulates the hydration and viscosity of mucous secretions in the airway. Therefore, its abnormal function favours the accumulation of thicker and more viscous secretions, reduces the periciliary layer and mucociliary clearance, and produces inflammation in the airway, as a consequence of a bronchial infection by both bacteria and viruses. Identifying CFTR dysfunction in the context of COPD pathogenesis is key to fully understanding its role in the complex pathophysiology of COPD and the potential of the different therapeutic approaches proposed to overcome this dysfunction. In particular, the potential of the rehydration of mucus and the role of antioxidants and phosphodiesterase inhibitors should be discussed. Additionally, the modulatory drugs which enhance or restore decreased levels of the protein CFTR were recently described. In particular, two CFTR potentiators, ivacaftor and icenticaftor, were explored in COPD. The present review updated the pathophysiology of the complex role of CFTR in COPD and the therapeutic options which could be explored

La democracia participativa: de los presupuestos a los supuestos participativos en la ciudad de Sevilla

Es mucho suponer que los Presupuestos Participativos de Sevilla incorporen todos los supuestos participativos, aunque si nos dan la oportunidad de experimentar otros modos de construir ciudadanía, desde nosotr@s mism@s, donde estamos invitadas las cuatro ciudadanías (la asociada, la no asociada, la técnica y la política). Sin embargo quedarían sin tener la repercusión social y estructural deseada si no consiguiésemos democratizar las estructuras económicas, culturales, ambientales, educativas y políticas, y esta oportunidad nos la brindan unos invitados de lujo, que con sus nuevos modos de ser, estar y hacer nos posibilitan encarar este nuevo reto que es la democracia participativa, por lo menos con el reconocimiento del estatutos de ciudadan@ de todos y todas las personas que convivimos en la comunidad de nuestro centro educativo, la calle, la plaza, el barrio, el distrito o la ciudad. Ell@s los grandes ausentes de todos y cada uno de los procesos participativos en nuestra ciudad, nos enseñan que la participación puede ser de otra manera, y que debe hacerse y cocinarse con otros ingredientes, l@s niñ@s, chavales/as y jóvenes protagonizan el gran cambio en los presupuestos participativos de Sevilla

Dysfunction in the Cystic Fibrosis Transmembrane Regulator in Chronic Obstructive Pulmonary Disease as a Potential Target for Personalised Medicine

In recent years, numerous pathways were explored in the pathogenesis of COPD in the quest for new potential therapeutic targets for more personalised medical care. In this context, the study of the cystic fibrosis transmembrane conductance regulator (CFTR) began to gain importance, especially since the advent of the new CFTR modulators which had the potential to correct this protein's dysfunction in COPD. The CFTR is an ion transporter that regulates the hydration and viscosity of mucous secretions in the airway. Therefore, its abnormal function favours the accumulation of thicker and more viscous secretions, reduces the periciliary layer and mucociliary clearance, and produces inflammation in the airway, as a consequence of a bronchial infection by both bacteria and viruses. Identifying CFTR dysfunction in the context of COPD pathogenesis is key to fully understanding its role in the complex pathophysiology of COPD and the potential of the different therapeutic approaches proposed to overcome this dysfunction. In particular, the potential of the rehydration of mucus and the role of antioxidants and phosphodiesterase inhibitors should be discussed. Additionally, the modulatory drugs which enhance or restore decreased levels of the protein CFTR were recently described. In particular, two CFTR potentiators, ivacaftor and icenticaftor, were explored in COPD. The present review updated the pathophysiology of the complex role of CFTR in COPD and the therapeutic options which could be explored.Ye

Predictors of single bronchodilation treatment response for copd: an observational study with the trace database cohort

Chronic obstructive pulmonary disease (COPD) patients constitute a heterogeneous population in terms of treatment response. Our objective was to identify possible predictive factors of response to treatment with single bronchodilation monotherapy in patients diagnosed with COPD. The Time-based Register and Analysis of COPD Endpoints (TRACE; clinicaltrials.gov NCT03485690) is a prospective cohort of COPD patients who have been attending annual visits since 2012. Patients who were kept on a single bronchodilator during the first year of follow-up were selected. The responders were defined according to all of the following variables: any improvement in morning post-dose forced expiratory volume in 1 s or deterioration <100 mL, no change or improvement in dyspnea score, and no occurrence of exacerbations. Significant and plausible variables were analyzed using a proportional hazard Cox regression for single bronchodilator responders. We analyzed 764 cases, of whom 128 (16.8%) were receiving monotherapy with one bronchodilator. Of these, 85 patients (66.4%) were responders. Factors affecting responder status were: female gender (hazard ratio (HR) 0.276; 95% confidence interval (CI) 0.089–0.858), dyslipidemia (HR 0.436; 95%CI 0.202–0.939), not performing regular exercise (HR 0.523; 95%CI 0.254–1.076), active smoking (HR 0.413; 95%CI 0.186–0.920), and treatment adherence (HR 2.527; 95%CI 1.271–5.027). The factors associated with a single bronchodilation response are mainly non-pharmacological interventions and comorbidities.Gebro Pharm

Inflammatory response in human lung cells stimulated with plasma from COPD patients.

Chronic obstructive pulmonary disease (COPD) is a condition resulting from a persistent inflammatory state in the airways even after smoking cessation. Intriguingly, the reasons behind this persistence of the inflammatory influx without smoking exposure have not been fully unraveled. We aimed to explore the hypothesis that systemic inflammation in COPD patients influences lung cell inflammatory response. We cultured human lung fibroblast and human airway epithelial cell lines with plasma from COPD patients (four emphysematous-COPD, four asthma-COPD overlap, four chronic bronchitis-COPD, and four bronchiectasis- COPD), and four smokers or ex-smokers without COPD as controls. Non-stimulated cells were used as controls. We measured Interleukine-8 (IL-8), C-reactive protein (CRP) and matrix metalloproteinase-9 (MMP-9) in plasma and culture supernatants by ELISA. Cells stimulated with plasma from COPD patients and non-COPD smoker subjects produced higher CRP, IL- 8 and MMP-9 levels, an increase for COPD in CRP (p=0.029) in epithelial cells and IL-8 (p=0.039) in fibroblasts and decrease for MMP-9 (p=0.039) in fibroblasts, compared with non-stimulated cells. The response was higher in epithelial cells for IL-8 (p=0.003) and in fibroblasts for MMP-9 (p=0.063). The plasma from chronic bronchitis and bronchiectasis phenotypes induced higher IL-8 in fibroblasts. Plasma from COPD patients increases the inflammatory response in lung epithelial cells and lung fibroblasts, with a different response depending on the cell type and clinical phenotype

The Physical Properties of the SVS 13 Protobinary System: Two Circumstellar Disks and a Spiraling Circumbinary Disk in the Making

International audienceWe present Very Large Array (VLA) and Atacama Large Millimeter/submillimeter Array (ALMA) observations of the close (0.″3 = 90 au separation) protobinary system SVS 13. We detect two small circumstellar disks (radii ~12 and ~9 au in dust, and ~30 au in gas) with masses of ~0.004-0.009 M ⊙ for VLA 4A (the western component) and ~0.009-0.030 M ⊙ for VLA 4B (the eastern component). A circumbinary disk with prominent spiral arms extending ~500 au and a mass of ~0.052 M ⊙ appears to be in the earliest stages of formation. The dust emission is more compact and with a very high optical depth toward VLA 4B, while toward VLA 4A the dust column density is lower, allowing the detection of stronger molecular transitions. We infer rotational temperatures of ~140 K, on scales of ~30 au, across the whole source, and a rich chemistry. Molecular transitions typical of hot corinos are detected toward both protostars, being stronger toward VLA 4A, with several ethylene glycol transitions detected only toward this source. There are clear velocity gradients, which we interpret in terms of infall plus rotation of the circumbinary disk, and pure rotation of the circumstellar disk of VLA 4A. We measured orbital proper motions and determined a total stellar mass of 1 M ⊙. From the molecular kinematics, we infer the geometry and orientation of the system, and stellar masses of ~0.26 M ⊙ for VLA 4A and ~0.60 M ⊙ for VLA 4B

Revolution: Museo de las estrellas un paseo por la fama : Hollywood

Convocatoria proyectos de innovación de Extremadura 2020/2021Se describe un proyecto llevado a cabo entre 13 centros educativos extremeños que consistió en desarrollar cinco unidades de trabajo gamificadas, cinco historias detectivescas con misterios por resolver, donde se ponían a prueba las habilidades de lógica, la capacidad de observación, de concentración y de atención de los alumnos. Los objetivos principales de la propuesta fueron: promover la puesta en práctica de proyectos intercentros; impulsar pedagogías activas; desarrollar la competencia digital a través del uso de las pedagogías emergentes lo que ha permitido llevar a cabo una enseñanza presencial, híbrida y virtual y atender a la diversidadExtremaduraES