Fenofibrate increases the population of non-classical monocytes in asymptomatic Chagas disease patients and modulates inflammatory cytokines in PBMC

Chronic Chagas disease cardiomyopathy (CCC) is the most important clinical manifestation of infection with Trypanosma cruzi (T. cruzi) due to its frequency and effects on morbidity and mortality. Peripheral blood mononuclear cells (PBMC) infiltrate the tissue and differentiate into inflammatory macrophages. Advances in pathophysiology show that myeloid cell subpopulations contribute to cardiac homeostasis, emerging as possible therapeutic targets. We previously demonstrated that fenofibrate, PPARα agonist, controls inflammation, prevents fibrosis and improves cardiac function in a murine infection model. In this work we investigated the spontaneous release of inflammatory cytokines and chemokines, changes in the frequencies of monocyte subsets, and fenofibrate effects on PBMC of seropositive patients with different clinical stages of Chagas disease. The results show that PBMC from Chagas disease patients display higher levels of IL-12, TGF-β, IL-6, MCP1, and CCR2 than cells from uninfected individuals (HI), irrespectively of the clinical stage, asymptomatic (Asy) or with Chagas heart disease (CHD). Fenofibrate reduces the levels of pro-inflammatory mediators and CCR2 in both Asy and CHD patients. We found that CHD patients display a significantly higher percentage of classical monocytes in comparison with Asy patients and HI. Besides, Asy patients have a significantly higher percentage of non-classical monocytes than CHD patients or HI. However, no difference in the intermediate monocyte subpopulation was found between groups. Moreover, monocytes from Asy or CHD patients exhibit different responses upon stimulation in vitro with T. cruzi lysates and fenofibrate treatment. Stimulation with T. cruzi significantly increases the percentage of classical monocytes in the Asy group whereas the percentage of intermediate monocytes decreases. Besides, there are no changes in their frequencies in CHD or HI. Notably, stimulation with T. cruzi did not modify the frequency of the non-classical monocytes subpopulation in any of the groups studied. Moreover, fenofibrate treatment of T. cruzi-stimulated cells, increased the frequency of the non-classical subpopulation in Asy patients. Interestingly, fenofibrate restores CCR2 levels but does not modify HLA-DR expression in any groups. In conclusion, our results emphasize a potential role for fenofibrate as a modulator of monocyte subpopulations towards an anti-inflammatory and healing profile in different stages of chronic Chagas disease.Fil: Pieralisi, Azul Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Cevey, Ágata Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Penas, Federico Nicolás. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; ArgentinaFil: Prado, Nilda. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital General de Agudos Doctor Cosme Argerich; ArgentinaFil: Mori, Ana. Gobierno de la Ciudad Autónoma de Buenos Aires. Hospital General de Agudos Doctor Cosme Argerich; ArgentinaFil: Gili, Mónica. Hospital Municipal de Rehabilitacion Respiratoria Maria Ferrer ; Gobierno de la Ciudad Autonoma de Buenos Aires;Fil: Mirkin, Gerardo Ariel Isidoro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Gagliardi, Juan. Hospital Municipal de Rehabilitacion Respiratoria Maria Ferrer ; Gobierno de la Ciudad Autonoma de Buenos Aires;Fil: Goren, Nora Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas en Retrovirus y Sida. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas en Retrovirus y Sida; Argentin

Cost-efficiency assessment of Advanced Life Support (ALS) courses based on the comparison of advanced simulators with conventional manikins

<p>Abstract</p> <p>Background</p> <p>Simulation is an essential tool in modern medical education. The object of this study was to assess, in cost-effective measures, the introduction of new generation simulators in an adult life support (ALS) education program.</p> <p>Methods</p> <p>Two hundred fifty primary care physicians and nurses were admitted to ten ALS courses (25 students per course). Students were distributed at random in two groups (125 each). Group A candidates were trained and tested with standard ALS manikins and Group B ones with new generation emergency and life support integrated simulator systems.</p> <p>Results</p> <p>In group A, 98 (78%) candidates passed the course, compared with 110 (88%) in group B (p < 0.01). The total cost of conventional courses was €7689 per course and the cost of the advanced simulator courses was €29034 per course (p < 0.001). Cost per passed student was €392 in group A and €1320 in group B (p < 0.001).</p> <p>Conclusion</p> <p>Although ALS advanced simulator systems may slightly increase the rate of students who pass the course, the cost-effectiveness of ALS courses with standard manikins is clearly superior.</p

Estudio coste-efectividad de la implantación de un programa de desfibrilación externa semiautomática en Galicia

Objective: To assess the cost-effectiveness of semiautomatic external defibrillator use in a program started in 2001 by the emergency service of the public health service in Galicia, Spain (the FPUS-061 service). Methods: We calculated the survival rate after cardiorespiratory arrest before and after starting use of semiautomatic external defibrillators; pre-program data for 1999-2000 were compared with data for 2006, when the program was in full operation. All costs related to the program were identified, classified, and recorded; increases were then calculated. Percentages of improvement between the baseline (100%) and second measurement periods were assessed for 3 measures of effectiveness: attempted resuscitations after cardiorespiratory arrest, recovery of vital constants, and survival on hospital discharge. The cost-effectiveness ratio for all cardiorespiratory arrests was compared with the ratio for arrests treated with a semiautomatic external defibrillator. Results: Attempted resuscitations increased by 72% over baseline, recovery of vital constants increased by 107%, and survival increased by 221 %. Total costs related to implementing the use of semiautomatic external defibrillators rose by � 122 974.57. The cost per survivor discharged after a cardiorespiratory arrest that was treated with a semiautomatic external defibrillator was � 8783.90. Conclusions: The FPUS-061 program for using semiautomatic external defibrillators is clearly effective in terms of the number of cardiorespiratory arrests attended, recovery of vital constants, and survival at hospital discharge. Survival increased more than 200% over the baseline situation. This study reveals that the cost-effectiveness ratio is very high.Objetivo: Evaluar la relación coste-efectividad (C-E) del programa de desfibrilación externa semiautomática (DESA) puesto en marcha en el año 2001 por la Fundación Pública Urxencias Sanitarias de Galicia-061 (FPUS-061). Método: Se valora la tasa de supervivencia de las paradas cardiorrespiratorias (PCR), antes y después de la implantación del programa DESA. Se utilizan los años 1999-2000 (pre-DESA) y 2006 (programa DESA implantado en su totalidad). Se calculó el coste incremental del programa mediante la identificación, clasificación y cuantificación de la estructura de costes del mismo. Se definieron tres índices para valorar la efectividad del programa, que estimaban el porcentaje de mejora clínica obtenida en el segundo periodo respecto al primero (valor basal 100%) en relación a tres criterios: resucitaciones intentadas (IC-1), recuperación de constantes (IC-2) y supervivencia al alta hospitalaria (IC-3). Se calculó también el C-E de la PCR en total y en la PCR tratada con DESA. Resultados: Respecto a la efectividad del programa DESA, se obtuvo un IC-1 de + 72%, un IC-2 de + 107% Y un IC-3 de + 221 % como porcentaje de cambio relativo respecto al periodo inicial. Respecto al C-E de la implantación del programa DESA, el coste incremental total del programa DESA en el año 2006 fue de 122.974,57 �. El coste por paciente dado de alta hospitalaria que ha sufrido una PCR y ha sido tratado con un DESA en 2006 fue de 8.783,90 �. Conclusiones: El programa DESA puesto en marcha por la FPUS-061 es claramente efectivo, con incremento en el número de PCR atendidas (IC-1), de recuperación de constantes (IC-2) y de altas hospitalarias (IC-3). La supervivencia se incrementó en un 200% respecto al periodo anterior a su implantación, y la relación C-E del programa DESA es muy elevada

El impacto de la crisis del COVID-19 en las minorías religiosas en España: desafíos para un escenario futuro

Depto. de Antropología Social y Psicología SocialFac. de Ciencias Políticas y SociologíaFALSEpu

Cognitive Function with PCSK9 Inhibitors: A 24-Month Follow-Up Observational Prospective Study in the Real World—MEMOGAL Study

Introduction The cognitive safety of monoclonal antibody proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) has been established in clinical trials, but not yet in real-world observational studies. We assessed the cognitive function in patients initiating PCSK9i, and differences in cognitive function domains, to analyze subgroups by the low-density lipoprotein cholesterol (LDL-C) achieved, and differences between alirocumab and evolocumab. Methods This has a multicenter, quasi-experimental design carried out in 12 Spanish hospitals from May 2020 to February 2023. Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). Results Among 158 patients followed for a median of 99 weeks, 52% were taking evolocumab and 48% alirocumab; the mean change from baseline in MoCA score at follow-up was + 0.28 [95% CI (− 0.17 to 0.73; p = 0.216)]. There were no significant differences in the secondary endpoints—the visuospatial/executive domain + 0.04 (p = 0.651), naming domain − 0.01 (p = 0.671), attention/memory domain + 0.01 (p = 0.945); language domain − 0.10 (p = 0.145), abstraction domain + 0.03 (p = 0.624), and orientation domain − 0.05 (p = 0.224)—but for delayed recall memory the mean change was statistically significant (improvement) + 0.44 (p = 0.001). Neither were there any differences in the three stratified subgroups according to lowest attained LDL-C level—0–54 mg/dL, 55–69 mg/dL and ≥ 70 mg/dL; p = 0.454—or between alirocumab and evolocumab arms. Conclusion We did not find effect of monoclonal antibody PCSK9i on neurocognitive function over 24 months of treatment, either in global MoCA score or different cognitive domains. An improvement in delayed recall memory was shown. The study showed no differences in the cognitive function between the prespecified subgroups, even among patients who achieved very low levels of LDL-C. There were no differences between alirocumab and evolocumab. Registration ClinicalTtrials.gov Identifier number NCT04319081Open Access funding provided thanks to the CRUE-CSIC agreement with Springer NatureS

La Historia en la literatura española del siglo XIX

Editors literaris: José Manuel González Herrán, Marisa Sotelo Vázquez, Cristina Carbonell, Hazel Gold, Dolores Thion Soriano-Mollá, Blanca Ripoll Sintes i Jessica Cáliz MontesEste volumen recoge los frutos del VII Coloquio de la Sociedad de Literatura Española del Siglo XIX, celebrado en Barcelona entre el 22 y el 24 de octubre de 2014. El encuentro contó con una nutrida participación de especialistas procedentes de universidades españolas y de otros países europeos, norteamericanas y japonesas. Las cuarenta y siete ponencias se agrupan en seis secciones que abordan los diferentes aspectos de las relaciones entre la literatura y la historia desde el Romanticismo hasta el fin de siglo, así como la interacción de la historia con los distintos géneros literarios, especialmente la novela y el teatro, sin olvidar otras vertientes culturales como la prensa. Asimismo, se dedican sendas secciones monográficas a Benito Pérez Galdós y Emilia Pardo Bazán