Tratamiento de Artritis reumatoide con antagonistas del factor de necrosis tumoral alfa y su asociación con el desarrollo de melanoma cutáneo: revisión sistemática de la literatura y meta-análisis.

Introducción: El tratamiento con antagonistas del factor de necrosis tumoral alfa (anti TNF) ha impactado el pronóstico y la calidad de vida de los pacientes con artritis reumatoide (AR) positivamente, sin embargo, se interroga un incremento en el riesgo de desarrollar melanoma. Objetivo: Conocer la asociación entre el uso de anti TNF y el desarrollo de melanoma maligno en pacientes con AR. Metodología: Se realizó una búsqueda sistemática en MEDLINE, EMBASE, COCHRANE LIBRARY y LILACS para ensayos clínicos, estudios observacionales, revisiones y meta-análisis en pacientes adultos con diagnóstico de AR y manejo con anti TNF (Certolizumab pegol, Adalimumab, Etanercept, Infliximab y Golimumab). Resultados: 37 estudios clínicos cumplieron los criterios de inclusión para el meta-análisis, con una población de 16567 pacientes. El análisis de heterogeneidad no fue significativo (p=1), no se encontró diferencia en el riesgo entre los grupos comparados DR -0.00 (IC 95% -0.001; -0.001). Un análisis adicional de los estudios en los que se reportó al menos 1 caso de melanoma (4222 pacientes) tampoco mostró diferencia en el riesgo DR -0.00 (IC 95% -0.004 ; -0.003). Conclusión: En la evidencia disponible a la fecha no encontramos asociación significativa entre el tratamiento con anti TNF en pacientes con diagnóstico de AR y el desarrollo de melanoma cutáneo.Introduction: Treatment with antagonists of the tumor necrosis factor alpha (anti- TNF) has impacted the prognosis and quality of life of patients with rheumatoid arthritis (RA) positively, however, there may be an incrased risk for cutaneous melanoma with this therapy. Objective: To determine the association between the use of anti- TNF and the development of malignant melanoma in patients with RA. Methods: A systematic search of MEDLINE, EMBASE, Cochrane Library and LILACS for clinical trials, observational studies, reviews and meta-analyzes in adult patients with RA diagnosis and management with anti TNF (certolizumab pegol, adalimumab, etanercept, infliximab and Golimumab) was performed. Results: 37 trials met the inclusion criteria for the meta-analysis, with a population of 16567 patients. The analysis of heterogeneity was not significant (p = 1), no difference was found in risk between the compared groups risk difference (RD) -0.00 (95% -0.001, -0.001). Further analysis of studies in which at least 1 case of melanoma (4222 patients) reported no difference in risk showed RD -0.00 (95% -0.004, -0.003). Conclusion: On the available evidence to date ther is no significant association between treatment with anti TNF and the development of cutaneous melanoma in patients with RA diagnosis

La pedagogía narrativa en el Prácticum de Educación Primaria Escritura, conversación y reescritura de relatos como medios para profundizar sobre el oficio docente

En el presente artículo exponemos las reflexiones fruto de una investigación desarrollada una vez concluidos los tres períodos de prácticas del Grado de Maestros en Educación Primaria de la Universidad de Málaga. Tres estudiantes junto a una investigadora nos reunimos para desarrollar un proceso de edición de relatos de aula, a lo largo de dos meses a través de encuentros semanales. Cada una de nosotras escogió un relato de aula escrito con anterioridad, lo presentó ante el resto de las participantes y se establecieron conversaciones, reflexiones y sugerencias que fueron atendidas por cada una para llevar a cabo las diversas re-escrituras. A través de estas acciones se posibilitó un espacio para indagar y dar sentido profesional a lo vivido en las escuelas. En base a esto, hemos construido un artículo donde reflejamos las reflexiones y los aprendizajes que consensuamos en dichas reuniones. Hemos fundamentado el marco teórico en el concepto de pedagogía narrativa, la escritura como medio para desarrollar el pensamiento y herramientas que han posibilitado la reflexión. Dentro de los hallazgos más relevantes podemos destacar el valor de la escritura y la conversación en la formación inicial de maestras y maestros y desarrollar saberes vinculados a la experiencia. Esto implica conectar las historias vividas durante las prácticas, con las propias vivencias como docentes en formación. Así como permitirnos realizar un desplazamiento en nuestro pensamiento acerca del oficio docente, centrándonos en las relaciones pedagógicas

An adenoviral-vectored vaccine confers seroprotection against capsular group B meningococcal disease

Adenoviral-vectored vaccines are licensed for prevention of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Ebola virus, but, for bacterial proteins, expression in a eukaryotic cell may affect the antigen's localization and conformation or lead to unwanted glycosylation. Here, we investigated the potential use of an adenoviral-vectored vaccine platform for capsular group B meningococcus (MenB). Vector-based candidate vaccines expressing MenB antigen factor H binding protein (fHbp) were generated, and immunogenicity was assessed in mouse models, including the functional antibody response by serum bactericidal assay (SBA) using human complement. All adenovirus-based vaccine candidates induced high antigen-specific antibody and T cell responses. A single dose induced functional serum bactericidal responses with titers superior or equal to those induced by two doses of protein-based comparators, as well as longer persistence and a similar breadth. The fHbp transgene was further optimized for human use by incorporating a mutation abrogating binding to the human complement inhibitor factor H. The resulting vaccine candidate induced high and persistent SBA responses in transgenic mice expressing human factor H. The optimized transgene was inserted into the clinically relevant ChAdOx1 backbone, and this vaccine has now progressed to clinical development. The results of this preclinical vaccine development study underline the potential of vaccines based on genetic material to induce functional antibody responses against bacterial outer membrane proteins

Propuesta de disposición final del residual de brea de hulla generado en la industria farmacéutica

El residuo de brea de hulla está formado por los sedimentos acumulados de la preparación del licor Picis Carbonis, ingrediente del producto farmacéutico Champú de Brea. Este residuo se acumuló durante años sin que se aplicara una opción de manejo final para el mismo. El objetivo de este trabajo fue proponer alternativas de disposición final del residuo de brea de hulla. Se realizó la caracterización físico-química y microbiológica, utilizando métodos establecidos y a partir de los resultados obtenidos se analizaron como posibles alternativas de disposición: la biorremediación, la incorporación en cementos asfálticos y la dosificación a combustibles pesados (crudo nacional y fuel oíl). Los resultados demostraron que es factible dosificar y mezclar el residuo con los combustibles pesados, siendo la mejor variante la mezcla con crudo nacional en las proporciones 1, 3, 5 y 10%. Se propuso aplicar esta variante en instalaciones existentes, lo cual es ambientalmente aceptable teniendo en cuenta los valores de concentración de metales presentes en el mismo. Por otro lado, se demostró que las otras dos alternativas evaluadas no resultaron viables. Se recomendaron las medidas a cumplir para el almacenamiento, transportación y disposición segura de este desecho peligroso que incluye su aprovechamiento energético. Se manifestó la factibilidad técnica y ambiental de este residual mezclado con combustible, así como la importancia de la disposición segura de un desecho peligroso y la necesidad del cumplimiento del manejo adecuado del mism

Whole-exome sequencing reveals ZNF408 as a new gene associated with autosomal recessive retinitis pigmentosa with vitreal alterations

Retinitis pigmentosa (RP) is a group of progressive inherited retinal dystrophies that cause visual impairment as a result of photoreceptor cell death. RP is heterogeneous, both clinically and genetically making difficult to establish precise genotype–phenotype correlations. In a Spanish family with autosomal recessive RP (arRP), homozygosity mapping and whole-exome sequencing led to the identification of a homozygous mutation (c.358_359delGT; p.Ala122Leufs*2) in the ZNF408 gene. A screening performed in 217 additional unrelated families revealed another homozygous mutation (c.1621C>T; p.Arg541Cys) in an isolated RP case. ZNF408 encodes a transcription factor that harbors 10 predicted C2H2-type fingers thought to be implicated in DNA binding. To elucidate the ZNF408 role in the retina and the pathogenesis of these mutations we have performed different functional studies. By immunohistochemical analysis in healthy human retina, we identified that ZNF408 is expressed in both cone and rod photoreceptors, in a specific type of amacrine and ganglion cells, and in retinal blood vessels. ZNF408 revealed a cytoplasmic localization and a nuclear distribution in areas corresponding with the euchromatin fraction. Immunolocalization studies showed a partial mislocalization of the p.Arg541Cys mutant protein retaining part of the WT protein in the cytoplasm. Our study demonstrates that ZNF408, previously associated with Familial Exudative Vitreoretinopathy (FEVR), is a new gene causing arRP with vitreous condensations supporting the evidence that this protein plays additional functions into the human retina.This work is supported by CIBERER (06/07/0036), FIS (PI013/00226), Ministry of Economy and Competitiveness-FEDER (BFU2012-36845), RETICS (RD12/0034/0010), Fundación ONCE, Fundaluce and grants BIO2011-27069 from the Spanish Ministry of Economy and Competitiveness, and PROMETEOII/2014/025 from the Conselleria de Educacio of the Valencia Community. PC is supported by Fundación Conchita Rábago (FCR), MC by Miguel Servet ISCIII (CP/03256) and dS by CAPES Foundation, Ministry of Education of Brazil

Diagnostic validity of five clinical prediction scales for deep vein thrombosis (DVT)

Introduction: Thedeep vein thrombosis (DVT) is a common entity that mainly affects the deep venous system of the lower limbs, for which multiple clinical prediction scales have been developed, which have been constructed and validated in outpatients and in-patients.Objetives: We aimed to validated five clinical predic-tion scores for the diagnosis of lower limb DVT in pa-tients from La Sabana de Bogota, Colombia. Methods: A cross-sectional study with analysis of a diagnostic test was carried out in patiens with sus-pected deep vein thrombosis, including those who had venous Doppler ultrasound of the lower limbs for suspected DVT. The performance of five clini-cal prediction scales for DVT (classic and modified Wells, Oudega, CEBI and Constans) for outpatients and inpatients was calculated in those scores who are validated in both populations and only in am-bulatory or hospitalized patients for those that are specific scores. Results: Nine hundred seventy-four patients were en-tered into the analysis, of which 485 (49.7%) presen-ted DVT. The Constans scale had a better diagnostic performance among inpatients and outpatients with an area under the ROC curve of 0.73 (95% 0.70-0.78) when compared with classic Wells, modified Wells, Oudega and CEBI. When we compared Constans performance in both groups of patients separately, we observed better per-formance with respect to the other scores. Conclusion: The Constans scale presents a better diagnostic performance compared to the other scales when applied to inpatients and outpatients

ISLES 2016 and 2017-Benchmarking ischemic stroke lesion outcome prediction based on multispectral MRI

Performance of models highly depend not only on the used algorithm but also the data set it was applied to. This makes the comparison of newly developed tools to previously published approaches difficult. Either researchers need to implement others' algorithms first, to establish an adequate benchmark on their data, or a direct comparison of new and old techniques is infeasible. The Ischemic Stroke Lesion Segmentation (ISLES) challenge, which has ran now consecutively for 3 years, aims to address this problem of comparability. ISLES 2016 and 2017 focused on lesion outcome prediction after ischemic stroke: By providing a uniformly pre-processed data set, researchers from all over the world could apply their algorithm directly. A total of nine teams participated in ISLES 2015, and 15 teams participated in ISLES 2016. Their performance was evaluated in a fair and transparent way to identify the state-of-the-art among all submissions. Top ranked teams almost always employed deep learning tools, which were predominately convolutional neural networks (CNNs). Despite the great efforts, lesion outcome prediction persists challenging. The annotated data set remains publicly available and new approaches can be compared directly via the online evaluation system, serving as a continuing benchmark (www.isles-challenge.org).Fundacao para a Ciencia e Tecnologia (FCT), Portugal (scholarship number PD/BD/113968/2015). FCT with the UID/EEA/04436/2013, by FEDER funds through COMPETE 2020, POCI-01-0145-FEDER-006941. NIH Blueprint for Neuroscience Research (T90DA022759/R90DA023427) and the National Institute of Biomedical Imaging and Bioengineering (NIBIB) of the National Institutes of Health under award number 5T32EB1680. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. PAC-PRECISE-LISBOA-01-0145-FEDER-016394. FEDER-POR Lisboa 2020-Programa Operacional Regional de Lisboa PORTUGAL 2020 and Fundacao para a Ciencia e a Tecnologia. GPU computing resources provided by the MGH and BWH Center for Clinical Data Science Graduate School for Computing in Medicine and Life Sciences funded by Germany's Excellence Initiative [DFG GSC 235/2]. National Research National Research Foundation of Korea (NRF) MSIT, NRF-2016R1C1B1012002, MSIT, No. 2014R1A4A1007895, NRF-2017R1A2B4008956 Swiss National Science Foundation-DACH 320030L_163363

Oxigenación con membrana extracorpórea en el paciente COVID-19: resultados del Registro Español ECMO-COVID de la Sociedad Española de Cirugía Cardiovascular y Endovascular (SECCE)

Background and aim: COVID-19 patients with severe heart or respiratory failure are potential candidates for extracorporeal membrane oxygenation (ECMO). Indications and management of these patients are unclear. Our aim is to describe the results of a prospective registry of COVID-19 patients treated with ECMO. Methods: An anonymous prospective registry of COVID-19 patients treated with veno-arterial (V-A) or veno-venous (V-V) ECMO was created on march 2020. Clinical, analytical and respiratory preimplantation variables, implantation data and post-implantation course data were recorded. The primary endpoint was all cause in-hospital mortality. Secondary events were functional recovery and the combined endpoint of mortality and functional recovery in patients followed at least 3 months after discharge. Results: Three hundred and sixty-six patients from 25 hospitals were analyzed, 347 V-V ECMO and 18 V-A ECMO patients (mean age 52.7 and 49.5 years respectively). Patients with V-V ECMO were more obese, had less frequently organ damage other than respiratory failure and needed less inotropic support; Thirty three percent of V-A ECMO and 34.9% of V-A ECMO were discharged (P = NS). Hospital mortality was non-significantly different, 56.2% versus 50.9% respectively, mainly during ECMO therapy and mostly due to multiorgan failure. Other 51 patients (14%) remained admitted. Mean follow-up was 196 +/- 101.7 days (95%CI: 170.8-221.6). After logistic regression, body weight (OR 0.967, 95%CI: 0.95-0.99, P = 0.004) and ECMO implantation in the own centre (OR 0.48, 95%CI: 0.27-0.88, P = 0.018) were protective for hospital mortality. Age (OR 1.063, 95%CI: 1.005-1.12, P = 0.032), arterial hypertension (3.593, 95%CI: 1.06-12.19, P = 0.04) and global (2.44, 95%CI: 0.27-0.88, P = 0.019), digestive (OR 4,23, 95%CI: 1.27-14.07, P = 0.019) and neurological (OR 4.66, 95%CI: 1.39-15.62, P = 0.013) complications during ECMO therapy were independent predictors of primary endpoint occurrence. Only the post-discharge day at follow-up was independent predictor of both secondary endpoints occurrence. Conclusions: Hospital survival of severely ill COVID-19 patients treated with ECMO is near 50%. Age, arterial hypertension and ECMO complications are predictors of hospital mortality, and body weight and implantation in the own centre are protective. Functional recovery is only predicted by the follow-up time after discharge. A more homogeneous management of these patients is warranted for clinical results and future research optimization. (C) 2022 Sociedad Espanola de Cirugia Cardiovascular y Endovascular. Published by Elsevier Espana, S.L.U

Efecto repelente y tiempo de protección de aceites esenciales frente al estadio adulto de Aedes aegypti

The aim of this was to evaluate the repellent effect and protection time of essential oils against the adult Aedes aegypti mosquito. A completely randomized design was used with a factorial arrangement that included 10 essential oils (Minthostachys mollis, Schinus molle, Ruta graveolens, Piper aduncun, Myrica pubescens, Lippia alba, Mentha piperita, Lantana glutinosa, Cymbopogon citratus, Eucalyptus globulus and the DEET control. 10%) and four concentrations of the oils (125, 250, 500 and 1000 mg/ml). Each experimental group consisted of 50 adult female A. aegypti mosquitoes raised in the laboratory and the repellent effect and protection time were evaluated using a sedated animal bait (Rattus rattus) with applications of 0.1 ml of the oils on the legs, tail and face. The rats and mosquitoes were found in two communicating cages of 25x25x40 cm. The oils with the greatest repellent effect and protection time, respectively, were C. citratus (97.4%; 165 minutes), E. globulus (95.8%; 165 minutes), L. glutinosa (93.8%; 180 minutes) and M. piperite (93.5%; 180 minutes) in its highest concentration (1000 mg/l); with differences between oils and between concentrations (p<0.001). Likewise, DEET 10% obtained a repellency of 95.3% and a protection time of 173 minutes. It is concluded that the essential oils of C. citratus, E. globulus, L. glutinosa and M. piperita can be considered as having natural repellent potential for A. aegypti.El estudio tuvo como objetivo evaluar el efecto repelente y tiempo de protección de aceites esenciales frente al mosquito adulto de Aedes aegypti. Se trabajó con un diseño completamente al azar con arreglo factorial que incluyó 10 aceites esenciales (Minthostachys mollis, Schinus molle, Ruta graveolens, Piper aduncun, Myrica pubescens, Lippia alba, Mentha piperita, Lantana glutinosa, Cymbopogon citratus, Eucalyptus globulus y el control DEET 10%) y cuatro concentraciones de los aceites (125, 250, 500 y 1000 mg/ml). Cada grupo experimental se constituyó por 50 mosquitos hembra adultos de A. aegypti criados en laboratorio y el efecto repelente y tiempo de protección se evaluaron usando un cebo animal sedado (Rattus rattus) con aplicaciones de 0.1 ml de los aceites en patas, cola y cara. Las ratas y los mosquitos se encontraron en dos jaulas comunicadas de 25x25x40 cm. Los aceites con mayor efecto repelente y tiempo de protección, respectivamente, fueron: C. citratus (97.4%; 165 minutos), E. globulus (95.8%; 165 minutos), L. glutinosa (93.8%; 180 minutos) y M. piperita (93.5%; 180 minutos) en su concentración mayor concentración (1000 mg/l); con diferencias entre aceites y entre concentraciones (p<0.001). Asimismo, el DEET 10% obtuvo una repelencia de 95.3 % y tiempo de protección de 173 minutos. Se concluye que los aceites esenciales de C. citratus, E. globulus, L. glutinosa y M. piperita pueden considerarse con potencial repelente natural para A. aegypti

Clinical trial to assess the effect of physical exercise on endothelial function and insulin resistance in pregnant women

<p>Abstract</p> <p>Background</p> <p>Preeclampsia (PE) is a common maternal disease that complicates 5 to 10% of pregnancies and remains as the major cause of maternal and neonatal mortality. Cost-effective interventions aimed at preventing the development of preeclampsia are urgently needed. However, the pathogenesis of PE is not well known. Multiple mechanisms such as oxidative stress, endothelial dysfunction and insulin resistance may contribute to its development. Regular aerobic exercise recovers endothelial function; improves insulin resistance and decreases oxidative stress. Therefore the purpose of this clinical trial is to determine the effect of regular aerobic exercise on endothelial function, on insulin resistance and on pregnancy outcome.</p> <p>Methods and design</p> <p>64 pregnant women will be included in a blind, randomized clinical trial, and parallel assignment. The exercise group will do regular aerobic physical exercise: walking (10 minutes), aerobic exercise (30 minutes), stretching (10 minutes) and relaxation exercise (10 minutes) in three sessions per week. Control group will do the activities of daily living (bathing, dressing, eating, and walking) without counselling from a physical therapist.</p> <p>Trial registration</p> <p>NCT00741312.</p