Prognostic impact of treatment with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in the acute phase and medium-term on COVID-19 infected patients

Traballo Fin de Grao en Medicina. Curso 2020-2021El primer caso de infección por COVID-19 fue descrito en Wuhan, China, en diciembre de 2019. Poco después se notificaron casos de transmisión limitada entre seres humanos en otros países, haciendo que la OMS declare el brote como una emergencia de salud pública de importancia internacional (ESPII) el 30 de enero de 2020. Recientes estudios señalan que el tratamiento con inhibidores de la enzima de conversión de la angiotensina (IECA) y los antagonistas de los receptores de la angiotensina II (ARA-II) en el momento agudo de la infección por COVID-19 no tiene efectos en el pronóstico en fase aguda, pero no está claro si el tratamiento con estos fármacos tiene un impacto a medio plazo en el pronóstico de los pacientes infectados. El objetivo de este estudio es determinar la implicación clínica que tiene el uso de los IECA/ARA II en el momento agudo y en seguimiento a medio plazo en los pacientes tras COVID-19. Es un estudio analítico observacional de cohortes de todos los pacientes consecutivos diagnosticados de COVID-19 que ingresaron durante la primera ola de la pandemia en el Hospital Universitario de Santiago de Compostela. Del total de la población estudiada, 447.979 habitantes, 1.030 (0.23%) fueron diagnosticados de infección por COVID-19, de los cuales 196 (19%) estaban bajo tratamiento con IECA/ARA-II en el momento diagnóstico. Los principales resultados muestran que el tratamiento con IECA/ARA-II (combinado e individualmente) no tuvo efecto sobre la mortalidad (HazardRatio [HR]: 1.64, 95% Intervalo de Confianza [IC]0.98 2.76, p=0.062), insuficiencia cardíaca (HR:0.98, 95% IC0.53 1.79, p=0.942), eventos trombóticos (HR: 1.02, 95% IC0.22 4.83, p=0.98) y eventos cardiovasculares adversos mayores (HR: 0.88, 95% IC0.48 1.60, p=0.665). En conclusión, el tratamiento con IECA/ARA-II en pacientes con COVID-19 no tuvo efecto en el pronóstico a 6 meses, definido como mortalidad, insuficiencia cardíaca o eventos cardiovasculares adversos mayoresO primeiro caso de infección pola COVID-19 describiuse en Wuhan, China, en decembro de 2019. Pouco despois, informáronse casos de transmisión limitada de home a home noutros países, o que provocou que a OMS declarase o brote como unha emerxencia de saúde pública de importancia internacional (ESPII) o 30 de xaneiro de 2020. Estudos recentes indican que o tratamento con inhibidores do encima convertedor de anxiotensina (IECA) e antagonistas do receptor de angiotensina II (ARB) no momento agudo da infección por COVID-19 non ten ningún efecto sobre o pronóstico a curto prazo, pero non está claro se o tratamento con estes medicamentos ten un impacto a medio prazo no prognóstico dos pacientes infectados. O obxectivo deste estudo é determinar a implicación clínica do uso de IECA/ARA-II no momento agudo e no seguimento a medio prazo en pacientes despois do COVID-19. É un estudo analítico de cohorte observacional de todos os pacientes consecutivos diagnosticados de COVID-19 que foron ingresados durante a primeira onda da pandemia no Hospital Universitario de Santiago de Compostela. Do total da poboación estudada, 447.979 habitantes, a 1.030 (0,23%) diagnosticáronlles infección por COVID-19, dos cales 196 (19%) estaban en tratamento con IECA/ARA-II no momento do diagnóstico. Os principais resultados mostran que o tratamento IECA/ARA-II (combinado e individualmente) non tivo ningún efecto sobre a mortalidade (Hazard Ratio [HR]: 1,64, Intervalo de Confianza [IC] do 95% 0,98 2,76, p = 0,062), insuficiencia cardíaca (HR: 0,98, IC do 95% 0,53 1,79, p = 0,942), eventos trombóticos (HR: 1,02, IC do 95% 0,22 4,83, p = 0,98) e eventos cardiovasculares adversos maiores (HR: 0,88, IC do 95% 0,48 1,60, p = 0,665). En conclusión, o tratamento con IECA/ARA-II en pacientes con COVID-19 non tivo ningún efecto no prognóstico de 6 meses, definido como mortalidade, insuficiencia cardíaca ou eventos cardiovasculares adversos maioresThe first case of COVID-19 infection was described in Wuhan, China, in December 2019. Shortly after, cases of limited human-to-human transmission were reported in other countries, which made the WHO declare the outbreak a Public Health Emergency of International Concern (ESPII) on January 30, 2020. Recent studies suggest that treatment with angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) during the acute time of COVID-19 infection has no effect on acute phase prognosis, but it is no evidence regarding the medium-term clinical implication of previous treatment with ACEI/ARB on the prognosis of patients with COVID-19 infection. The aim of this study is to evaluate the clinical implication of the use of ACEI/ARB in the acute moment and medium-term follow-up in patients after COVID-19. It is an analytical observational cohort study of all consecutive patients diagnosed with COVID-19 who were admitted during the first wave of the pandemic at the University Hospital of Santiago de Compostela. Of the total population studied, 447,979 inhabitants, 1,030 (0.23%) were diagnosed with COVID-19 infection, of which 196 (19%) were under treatment with ACEI/ARB at the time of diagnosi

La hipótesis infecciosa de las enfermedades neurodegenerativas: Enfermedad de Parkinson y enfermedad de Alzheimer

Treball Final de Grau en Medicina. Codi: MD1158. Curs acadèmic: 2020/2021En la última década, se han realizado numerosos estudios que apoyan el papel de distintas infecciones en la etiopatogénesis de las enfermedades neurodegenerativas. Dada la enorme bibliografía existente al respecto, imposible de abarcar de manera rigurosa con la limitación temporal existente, para esta revisión sistemática nos hemos centrado en las enfermedades infecciosas virales y bacterianas como causa etiológica de las enfermedades de Alzheimer y de Parkinson. Para ello, se ha analizado pormenorizadamente las evidencias existentes desde el año 2010 hasta el año 2020 en PubMed y Scopus. Una vez aplicados los criterios de inclusión y exclusión, se analizaron cuatro artículos exclusivamente sobre la enfermedad de Parkinson, cinco sobre la enfermedad de Alzheimer, uno sobre la patogénesis de las enfermedades neurodegenerativas y dos que tratan el papel de las infecciones y la neuroinflamación en ambas enfermedades. Todos estos estudios fueron realizados en humanos, y como comentaremos, varios de ellos recogen también posibles enfoques terapéuticos. A pesar de que existen estudios en los que no se observa una relación infección – neurodegeneración, una amplia bibliografía considera la infección y desregulación del sistema inmune como un factor clave en la etiopatogénesis de la EA y EP. Por tanto, nuestros hallazgos apoyan la hipótesis infecciosa del desarrollo de ciertos tipos de enfermedad de Alzheimer y de Parkinson, constituyendo la infección un factor de riesgo importante para su desarrollo tanto directa - debido a la neuroinflamación inducida por bacterias, hongos y virus – como indirectamente - mediante la respuesta inmune periférica asociada-. Sin embargo, se precisa una mayor investigación para detectar en qué pacientes existe mayor riesgo de que se de esta relación causal infección-neurodegeneración y para establecer modos de prevenirla, evitando con ello el indeseado desenlace.During the last decade, different researchers have carried out numerous studies that support infections play an important role in the etiopathogenesis of neurodegenerative diseases. Considering the extensive bibliography published in this respect, impossible to fully cover in detail regarding the time limits, in order to write this systemic review, we focused on viral and bacterial infections as etiological causes of Alzheimer’s and Parkinson’s diseases. To this end, we closely analyzed the existing evidence from 2010 to 2020 in PubMed and Scopus. After applying the inclusion and exclusion criteria, we analyzed four articles about Parkinson’s disease, five about Alzheimer’s disease, one that refers to neurodegenerative diseases’ pathogenesis and two concerning the role of infections and neurodegeneration in both diseases. All of them are human studies. Despite some studies did not find a link between infection and neurodegeneration, a wide biography considers infections and immune dysregulation as a key factor in the EA’s and EP’s etiopathogenesis. Therefore, we support the infectious hypothesis of the development of some types of Alzheimer’s and Parkinson’s diseases, being an infection an important risk factor to develop them both directly – through the neuroinflammation induced by bacteria, fungi and viruses – and indirectly – via the peripheral immune response triggered. However, research is still needed to be able to detect witch patients are in major risk of suffering from this infection-neurodegeneration causal relation and to stablish ways to prevent it, thus avoiding the undesirable outcome

Characterisation of the 11Kb DNA region adjacent to the gene encoding Desulfovibrio gigas flavoredoxin

Abstract: Flavoredoxin is an FMN binding protein that functions as an electron carrier in the sulphate metabolism of Desulfovibrio gigas. The neighbouring DNA regions of the gene encoding flavoredoxin were sequenced and characterised. Transcript analysis of the flavoredoxin gene resulted in a positive band corresponding to the size of the coding region, suggesting that flavoredoxin is encoded by a monocystronic unit, as previously suggested by sequence analysis

O trabalho colaborativo em plataforma LMS (Moodle) e a aprendizagem matemática

Tese de mestrado, Educação (Tecnologias de Informação e Comunicação em Educação), Universidade de Lisboa, Faculdade de Ciências, 2009Este estudo procura analisar o contributo que as ferramentas da educação à distância podem dar ao ensino presencial, no campo da educação matemática. Procuramos também contribuir para uma melhor compreensão da forma como o professor pode dinamizar e envolver os alunos, tirando partido dos conhecimentos e vontade de utilizar as tecnologias de informação e comunicação, para a aprendizagem matemática. Na área da educação matemática, o estudo sobre as ferramentas digitais, em particular o uso de software próprio, tem sido alvo de estudos nas últimas duas décadas. Vamos explorar o Geogebra, enquanto software de geometria dinâmica, incorporado numa plataforma de gestão de aprendizagem, Moodle, no apoio às aprendizagens dos conteúdos de geometria do 8º ano. Neste sentido, o presente estudo analisa e descreve o modo como os alunos tiram vantagem dos recursos tecnológicos que lhes são colocados à disposição. Não só em sala de aula, como também em casa, no sentido de aprofundar as aprendizagens e partilhar, em comunidade, as dúvidas e os esclarecimentos. A investigação seguiu uma abordagem de estudo de caso mista, qualitativa e quantitativa, aproveitando os dados fornecidos pela plataforma no processo de análise dos acessos, e os registos do professor enquanto investigador. O estudo procura explorar as potencialidades das plataformas de gestão de aprendizagem, bem como a fácil construção de actividades, com recurso ao software de geometria dinâmica, dentro do espaço da disciplina/turma. Foi também evidente a dinâmica, dentro da plataforma, criada em redor das actividades construídas com o Geogebra.This study seeks to examine the contribution that the tools of distance education can provide for students in the field of mathematics education. We seek to contribute to a better understanding of how the teacher can stimulate and engage students, taking advantage of knowledge and willingness to use information technology and communication for learning mathematics. In the area of mathematics education, the study on digital tools, in particular the use of proprietary software, has been investigated in the last two decades. Let's explore the Geogebra as dynamic geometry software, incorporated into a management platform for learning, Moodle, in supporting the learning of the content of geometry in the 8th grade. In this sense, this study analyzes and describes how students take advantage of technological resources that they are made available. Not only in the classroom, but also at home, to deepen the learning and sharing in the community, the doubts and clarifications. Research has adopted a case study of mixed qualitative and quantitative, using data provided by the platform in the review process of access, and records of the teacher as researcher. The study seeks to explore the potential of management platforms to learn and easy construction activities, using the dynamic geometry software, within the scope of the course/class. It was also clear the dynamics within the platform, created around the activities built with GeoGebra

Deletion of flavoredoxin gene in Desulfovibrio gigas reveals its participation in thiosulfate reduction

Abstract: The gene encoding Desulfovibrio gigas flavoredoxin was deleted to elucidate its physiological role in the sulfate metabolism. Disruption of flr gene strongly inhibited the reduction of thiosulfate and exhibited a reduced growth in the presence of sulfite with lactate as electron donor. The growth with sulfate was not however affected by the lack of this protein. Additionally, flr mutant cells revealed a decrease of about 50% in the H-2 consumption rate using thiosulfate as electron acceptor. Altogether, our results show in vivo that during sulfite respiration, trithionate and thiosulfate are produced and that flavoredoxin is specific for thiosulfate reduction

Molecular determinants for FMN-binding in Desulfovibrio gigas flavoredoxin

Abstract: Flavoredoxin participates in Desulfovibrio gigas thiosulfate reduction pathway. Its 3-dimensional model was generated allowing the oxidized riboflavin-5'-phosphate (FMN) site to be predicted. Residues likely to be involved in FMN-binding were identified (N29, W35, T56, K92, H131 and F164) and mutated to alanine. Fluorescence titration with apoprotein showed that FMN is strongly bound in the wild-type protein. Comparison of K-d values for mutants suggests that interactions with the phosphate group of FMN, contribute more to binding than the interactions with the isoalloxazine ring. The redox potential of bound FMN determined for wild-type and mutants revealed shifts to less negative values. These findings were correlated with the protein structure in order to contribute to a better understanding of the structure-function relationships in flavoredoxin. (c) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved

Molecular cloning of the gene encoding flavoredoxin, a flavoprotein from Desulfovibrio gigas

Sulfate-reducing bacteria are rich in unique redox proteins and electron carriers that participate in a variety of essential pathways. Several studies have been carried out to characterize these proteins, but the structure and function of many are poorly understood. Many Desulfovibrio species can grow using hydrogen as the sole energy source, indicating that the oxidation of hydrogen with sulfite as the terminal electron acceptor is an energy-conserving mechanism. Flavoredoxin is an FMN-binding protein isolated from the sulfate-reducing bacteria Desulfovibrio gigas that participates in the reduction of bisulfite from hydrogen. Here we report the cloning and sequencing of the flavoredoxin gene. The derived amino acid sequence exhibits similarity to several flavoproteins which are members of a new family of flavin reductases suggested to bind FMN in a novel mode. (C) 2000 Academic Pres

Searching for gene clusters related to virulence by coding sequence conservation

Motivation: Due to the increasing world population, the need to improve food production is growing. This can be helped byfighting the pathogens which affect the main crops as maize, wheat, barley and sugar cane. Among those, biotrophic parasitessuch as smut fungi can be found. To study how those microorganisms infect their host, the model system Ustilago maydis canbe used.U. maydis secretes protein effectors to infect its host, and at least 25% of them are known to be grouped in 13 different geneclusters. In addition to these characterized clusters, 7 new clusters have been described in the bibliography but notexperimentally tested. The aim of this work is to find out new clusters with features similar to the known ones (controls), mainlylow conservation, which can affect the infection process.Methods: To achieve this goal, candidate gene clusters were initially discovered based on coding sequence conservation viathe computational tool AnABlast [1], which highlitghted genomic coding region with conservation signal similar to the initialcontrols. Then, the candidates were functionally annotated using the tool Sma3s_v2 [2]. To select the best candidates, aprincipal component analysis (PCA) was done using the following factors, which were trained with the controls: sequenceconservation obtained by a similarity search by Blast against close organisms (Ensembl fungi phylogeny), expression dataduring infection, and signal peptide presence (SignalP and TargetP), usually present in effectors.Currently, a laboratory experiment has been began to elucidate if the chosen candidates affect the pathogenity, deleting themby homologous recombination.Results: We have been able to identify 49 new clusters by comparing their coding signal with those already known. After thesubsequent analysis three of them, and one from the bibliography have been chosen to be tested in laboratory to elucidatetheir virulence phenotype (swelling and tumors).In the PCA our best candidate is located among the clusters previously described as pathogenic, showing genes beingsecreted with high levels of expressionConclusions: In brief, we propose that putative cluster of virulence sequences could be found by the presented strategy. So,it could constitute a new silico approach to find out specific genes involved in different biological processes such as inffection