Análisis de la neurotoxicidad del β-N-Metilamino-L-Alanina (L-BMAA: estudios en cultivos de neuroblastoma humano (SH-SY5Y) y en cerebelo de rata

Debido a su similitud estructural con el glutamato, el β-N-metilamino-L-alanina (L-BMAA) va a tener una acción excitotóxica causando alteraciones en el interior de las células, como son un incremento del estrés oxidativo, una disfunción mitocondrial, la alteración de la síntesis y degradación proteica y un desequilibrio enzimático puesto que se puede incorporar a proteínas. Las neuronas son células especialmente susceptibles a daños en el plegamiento y la acumulación de proteínas aberrantes dado que no realizan división celular. El cerebelo es un centro motor subcortical que asegura que los movimientos sean realizados con precisión espacial y temporal, con lo cual un daño cerebelar causado por el L-BMAA podría desencadenar una patología neurodegenerativa. El objetivo principal de la presente tesis es analizar la citotoxicidad causada por el L-BMAA en tres sistemas experimentales: un cultivo de neuroblastoma humano (SH-SY5Y) con el que establecimos las bases de la neurodegeneración causada, por otro lado se realizaron ensayos con tratamientos in vivo con L-BMAA en ratas para evaluar la afectación cerebelar y también se llevaron a cabo estudios incubando con L-BMAA cortes de cerebelo para descifrar el mecanismo de acción del tóxico en un sistema en el que poder analizar el papel neuroprotector de moléculas potencialmente terapéuticas como la esfingosina-1-fosfato. Entre las conclusiones obtenidas cabe destacar que las células de neuroblastoma tratadas con L-BMAA, se podrían proponer como un modelo celular para el estudio tanto de los mecanismos de procesos neurodegenerativos, como para el ensayo de moléculas potencialmente terapéuticas. Además, queda demostrado el daño cerebelar causado en ratas tras el tratamiento con L-BMAA. Las ratas afectadas no pueden reestablecer las funciones normales del cerebelo. Y por último, los cortes cerebelo tratados con L-BMAA constituyen un método sencillo y válido para el estudio tanto de mecanismos de procesos neurodegenerativos y para el ensayo de moléculas potencialmente terapéuticas

Estudi per a la restauració del molí fariner de la Mola

Els molins fariners han estat un sistema per obtenir farina a partir dels cereals, utilitzant aquells recursos naturals propis de la zona on es troba localitzat. A la Pobleta de Bellveí, un poble situat al inici de la Vall Fosca (Lleida), s’hi troba La Mola, un edifici que conté un molí fariner i una mini-central hidroelèctrica, propietat de la família Castells. La restauració total de La Mola, que va començar l’any 2016 amb la recuperació de la mini-central hidroelèctrica, es trobarà completa quan el molí fariner i tot el sistema de transport del blat que conté, és torni a posar en funcionament. L’objectiu d’aquest treball és l’estudi del sistema de transmissió del moviment del molí, perfilant els elements que s’han de reconstruir i pressupostar el cost de la restauració. Primer de tot s’ha fet un estudi de l’estat actual mitjançant fotografies, seguidament s’han buscat opcions de restauració dels elements de fusta que conté el molí, intentant conservar el major nombre d’elements originals i, en cas de no poder ser, fer el possible per mantenir l’aspecte i material del que estan fets. En aquest treball no es prenen decisions definitives per a la restauració, sinó que es fan propostes i suggeriments per tal que la propietària prengui la decisió que trobi més oportuna. És presenta l’estudi de la part inferior del molí, el perfil de les dents de fusta que contenen alguns dels engranatges i el cost màxim i mínim d’aquesta restauració. També s’ha fet un estudi del funcionament del sistema graduador i aixecador dels molins de la Mola, que degut al seu tren d’engranatges, és peculiar i diferent a la majoria de molins fariners existentsHistóricamente los molinos harineros fueron un sistema de obtención de harina utilizando los recursos naturales correspondientes a la zona en la que se que se encontraban ubicados. En la Pobleta de Bellveí, un pueblo situado al principio de la Vall Fosca en la provincia de Lérida, se encuentra La Mola, un edificio que contiene un molino harinero y una mini- central hidroeléctrica, propiedad de la familia Castells. La restauración total de La Mola, que se inicio en 2016 con la recuperación de la mini- central hidroeléctrica, se completará cuando el molino harinero y todo su sistema de transporte del trigo, se pongan en marcha de nuevo. El objetivo de este trabajo, es el estudio del sistema de transmisión de movimiento del molino, perfilando los elementos que se han de reconstruir y presupuestando el coste de la restauración. Para realizar el estudio se ha seguido un protocolo. Primero se ha hecho un estudio fotográfico del estado actual, seguidamente se han buscado opciones de restauración de los elementos de madera que contiene el molino, intentando conservar el mayor número de elementos originales, y en caso de no poder conservarlos, hacer todo lo posible para mantener el aspecto y materiales del que están hechos. En el trabajo no se toman decisiones definitivas para la restauración, se realizan propuestas y sugerencias para que la propietaria escoja la opción que encuentre más oportuna. Se presenta el estudio de la parte inferior del molino, el perfil de los dientes de madera que contienen algunos de los engranajes y el coste máximo y mínimo de la restauración que tendrá esta zona. También se ha estudiado el funcionamiento del sistema graduador y levantador de los molinos de la Mola, que debido a su sistema de engranajes es peculiar y distinto al de la mayoría de molinos harineros existentes.Flour mills have been a way for obtaining flour from wheat using the natural resources from the area where they are located. In La Pobleta de Bellvei, a village located at the beginning of la Vall Fosca (Lleida), there is La Mola, a building that houses a flour mill and a mini-hydroelectric power station, owned by Castells family. The complete restoration of La Mola, which began the year 2016 with the recovery of the mini-hydroelectric power station, will be finished when the flour mill and the entire grain transport system that it contains are put back into operation. The goal of this work is to study the transmission system of the mill, outlining the elements that need to be reconstructed and estimating the cost of the restoration. First of all, a photographic study of the current state has been done, followed by the research of restoration options for the wooden elements of the mill, aiming to preserve as many original elements as possible. In cases where the preservation of the original elements is not possible, maintaining the appearance and material of the original elements will be essential. This work does not make definitive decisions for restoration, instead, it offers proposals and suggestions so that the owner can makes the most appropriate decision. The study of the lower part of the mills is presented, including the profile of the wooden teeth containing some of the gears, and the maximum and minimum cost of the restoration in this area. The functioning of the grading and lifting systems of la Mola’s mills have also been studied, which are unique and different from most of the existing flour mills due to it’s gear syste

Seroprevalence of meningococcal serogroup C bactericidal antibodies in the Portuguese population, a decade after vaccine introduction in the National Immunisation Programme

Background: The incidence of invasive meningococcal disease due to serogroup C (MenC) decreased in Portugal since the introduction of the conjugate vaccine (MCC) in the free market in 2001 and in the National Immunisation Plan in 2006. Considering the potential waning of the antibody response reported in the literature, the different vaccination schemes that were used in our country over the past decade, and that Neisseria meningitidis serogroup C continues to circulate, the Portuguese population may currently be at increased risk of infection. In the absence of national data, we evaluated the seroprotection level of the Portuguese population against MenC, in order to identify the protected fraction of the population and ponder on the necessity of a booster dose of the MCC vaccine. Methods: We measured serum bactericidal antibody levels against MenC in a representative sample of the population (n = 1500) aged 2-64 years who participated in the 2015/2016 National Serological Survey. Results: A total of 31.1% (466/1500, 95%CI: 29-33%) of the individuals studied were protected against MenC. The geometric mean titre was 6.5. The proportion of seroprotected was particularly low in children aged 2-4 years (<16%) who received a single dose of the vaccine at 12 months of age (vaccination strategy since 2012). The proportion of seroprotected was higher (44.7% to 53.5%) in adolescent and young adults (15-24 years of age), resulting from vaccination during the catch-up campaign at 5-15 years of age. The highest protection rates were observed when the vaccine was administered during adolescence. Conclusion: The small fraction of population seroprotected, combined with the already known waning effect of the antibody response over time, may indicate that the Portuguese population will become progressively more exposed to the risk of infection. Taking in consideration our results, we recommend to change the current vaccination strategy and introduce a booster dose of the MCC vaccine during adolescence.National Institute of Health Doutor Ricardo Jorge, Lisboa, Portugal, and GlaxoSmithKline.info:eu-repo/semantics/publishedVersio

Neonatal sepsis by bacteria: a big problema for children.

Neonatal sepsis is an important but underestimated problem around the world. It is defined as disease affecting newborns ≤ 1 month of age with clinical symptoms and positive blood cultures. Infection is an important cause of morbidity and mortality during the neonatal period, despite the great improvements in intensive neonatal care and the use of extended spectrum antimicrobial agents. The incidence of this disease in developed countries is 1/1,000 in normal term neonates and 4/1,000 in preterm neonates. These values increase in low-weight preterm neonates. In developing countries, this incidence increases to 2.2-8.6/1,000 live births. Neonatal sepsis can be subdivided into early-onset neonatal sepsis and late-onset neonatal sepsis

Dados da norma do sistema de Vigilância Epidemiológica das Resistências aos Antimicrobianos (Norma 004/2013, DGS)

O Instituto Nacional de Saúde Doutor Ricardo Jorge (INSA) divulga os relatórios anuais da vigilância epidemiológica da infeção causada por Clostridioides difficile (ICD) referentes aos anos 2016, 2017 e 2018, elaborados pelo Laboratório Nacional de Referência das Infeções Gastrintestinais do seu Departamento de Doenças Infeciosas (DDI), em colaboração com o Programa Nacional de Prevenção e Controlo de Infeções e das Resistências aos Antimicrobianos (PPCIRA). A vigilância epidemiológica da ICD insere-se no PPCIRA, coordenado pela Direção-Geral da Saúde, cujos dados, notificados pelos laboratórios clínicos ao abrigo da norma 004/2013, atualizada em novembro de 2015, são analisados pelo Laboratório Nacional de Referência para as Infeções Gastrintestinais do INSA. Da análise dos dados, destacam-se os seguintes resultados: i) O número de doentes com ICD em Portugal mostra uma tendência crescente, embora pouco acentuada, com 1021 casos em 2016, 1104 casos em 2017 e 1117 em 2018, observando-se o maior aumento na região de Lisboa e vale do Tejo. VT (378 no ano 2016, 372 no ano 2017 e 482 no ano 2018); ii) A taxa de positividade média aumentou de 6,6% em 2016 para 8,3% em 2018; iii) A média de hospitais que notificam dados de ICD é inferior a 65%; iv) Cerca de 30% dos laboratórios clínicos utilizam algoritmos de diagnóstico laboratorial que carecem de melhoria.info:eu-repo/semantics/publishedVersio

Rasgos de personalidad en conductores infractores y factores de riesgo en la conducción

El presente artículo tiene como primer objetivo dar respuesta a las siguientes preguntas: 1) ¿Existen diferencias significativas de dimensiones de personalidad, entre los conductores infractores y la población general? 2) ¿El perfil del conductor infractor (consumo de alcohol u otras drogas, velocidad, distracción, incumplimiento de normas y señales) está relacionado con su dimensión de personalidad? y 3) ¿En la muestra de conductores infractores existen diferencias de perfiles de riesgo en la conducción entre hombres y mujeres? El segundo objetivo, en el caso de encontrar alguna respuesta afirmativa a las preguntas planteadas, es proponer una revisión de los programas formativos que actualmente se utilizan en los cursos de sensibilización y reeducación vial para conductores infractores en Cataluña. Los datos de esta investigación se han obtenido de una muestra de conductores que por comisión de infracciones o delitos contra la seguridad del tráfico han asistido, como alumnos, a los cursos de sensibilización y reeducación vial en centros situados en diversas poblaciones de Cataluña. Para medir las dimensiones de personalidad se ha utilizado el instrumento EPQ-RA, que es una versión reducida del cuestionario de personalidad original de Eysenck (1994)The main objective of this paper is to answer the following questions: 1) Are there significant differences in personality dimensions between infringing drivers and the general population? 2) Is the profile of the offending driver (consumption of alcohol or other drugs, speed, distraction, breach of rules and signals) related to his or her personality dimension? and 3) In the sample of offending drivers, are there differences in risk profiles in driving between men and women? The second objective, in the case of finding an affirmative answer to the questions posed, is to propose a review of the training programs that are currently used in awareness and road re-education courses for delinquent drivers in Catalonia. The data for this research has been obtained from a sample of drivers who, as a result of incurring infractions or crimes against trafic safety, have attended, as students, awareness and road re-education courses in centers located in different towns in Catalonia. To measure personality dimensions the EPQ-R test, a reduced version of the Eysenck's original personality questionnaire (1994), has been used

Rasgos de personalidad en conductores infractores y factores de riesgo en la conducción

The main objective of this paper is to answer the following questions: 1) Are there significant differences in personality dimensions between infringing drivers and the general population? 2) Is the profile of the offending driver (consumption of alcohol or other drugs, speed, distraction, breach of rules and signals) related to his or her personality dimension? and 3) In the sample of offending drivers, are there differences in risk profiles in driving between men and women? The second objective, in the case of finding an affirmative answer to the questions posed, is to propose a review of the training programs that are currently used in awareness and road re-education courses for delinquent drivers in Catalonia. The data for this research has been obtained from a sample of drivers who, as a result of incurring infractions or crimes against traffic safety, have attended, as students, awareness and road re-education courses in centers located in different towns in Catalonia. To measure personality dimensions the EPQ-R test, a reduced version of the Eysenck’s original personality questionnaire (1994), has been used. El presente artículo tiene como primer objetivo dar respuesta a las siguientes preguntas: 1) ¿Existen diferencias significativas de dimensiones de personalidad, entre los conductores infractores y la población general? 2) ¿El perfil del conductor infractor (consumo de alcohol u otras drogas, velocidad, distracción, incumplimiento de normas y señales) está relacionado con su dimensión de personalidad? y 3) ¿En la muestra de conductores infractores existen diferencias de perfiles de riesgo en la conducción entre hombres y mujeres? El segundo objetivo, en el caso de encontrar alguna respuesta afirmativa a las preguntas planteadas, es proponer una revisión de los programas formativos que actualmente se utilizan en los cursos de sensibilización y reeducación vial para conductores infractores en Cataluña. Los datos de esta investigación se han obtenido de una muestra de conductores que por comisión de infracciones o delitos contra la seguridad del tráfico han asistido, como alumnos, a los cursos de sensibilización y reeducación vial en centros situados en diversas poblaciones de Cataluña. Para medir las dimensiones de personalidad se ha utilizado el instrumento EPQ-RA, que es una versión reducida del cuestionario de personalidad original de Eysenck (1994).

Effects of a mutation in the gyrA gene on the virulence of uropathogenic Escherichia coli

Fluoroquinolones are among the drugs most extensively used for the treatment of bacterial infections in human and veterinary medicine. Resistance to quinolones can be chromosome or plasmid mediated. The chromosomal mechanism of resistance is associated with mutations in the DNA gyrase- and topoisomerase IV-encoding genes and mutations in regulatory genes affecting different efflux systems, among others. We studied the role of the acquisition of a mutation in the gyrA gene in the virulence and protein expression of uropathogenic Escherichia coli (UPEC). The HC14366M strain carrying a mutation in the gyrA gene (S83L) was found to lose the capacity to cause cystitis and pyelonephritis mainly due to a decrease in the expression of the fimA, papA, papB, and ompA genes. The levels of expression of the fimA, papB, and ompA genes were recovered on complementing the strain with a plasmid containing the gyrA wild-type gene. However, only a slight recovery was observed in the colonization of the bladder in the GyrA complement strain compared to the mutant strain in a murine model of ascending urinary tract infection. In conclusion, a mutation in the gyrA gene of uropathogenic E. coli reduced the virulence of the bacteria, likely in association with the effect of DNA supercoiling on the expression of several virulence factors and proteins, thereby decreasing their capacity to cause cystitis and pyelonephritis

Evaluation of ECDC Influenza-like illness (ILI) case definition to detect respiratory syncytial virus (RSV) infection through the Influenza Surveillance System in Portugal, 2010-2018

INSA-DDI em colaboração com Emma Sáez-López (programa EUPHEM) e INSA-DEP.Poster abstract publicado em: ESCAIDE 2018: Abstract book, pp. 87-88. Disponível em: https://www.escaide.eu/sites/escaide/files/documents/book_escaide2018_updated-dec-2018.pdfBackground: One of the main problems to implement a global Respiratory syncytial virus (RSV) surveillance system is the lack of a suitable case definition for RSV disease. In Portugal, RSV cases are detected through the Influenza Surveillance System (ISS) using the ECDC Influenza-like illness (ILI) case definition. The aim of this study was to evaluate the suitability of this case definition to detect RSV infections in Portugal. Methods: We conducted a retrospective and observational cross-sectional study of 4,711 cases with individual clinical symptoms and laboratory-confirmed result for respiratory virus between October 2010 and May 2017. Association between clinical characteristics and RSV detection using bivariate and multinomial logistic regression was carried out. The ILI case definition accuracy was assessed by its sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). A 0.05 significance level was accepted. Results: A total of 141 (3%) samples were laboratory-confirmed RSV positive cases, being highly significant among children less than 5 years old (8.5%) and among adults ≥ 65 years old (23%). Cough (OR=2.71; 95CI 1.19-6.18) and difficulty breathing (OR=2.16; 95CI 1.53-3.06) were the best predictors for RSV infections. However, fever or feverishness (OR=0.4; 95CI 0.27-0.59), headache (OR=0.65; 95CI0.46-0.93) and myalgia (OR=0.34; 95CI 0.23-0.5) were negative associated with RSV disease although were significantly associated with influenza positive cases. The ILI case definition was not significant and showed a sensitivity of 80.9% (73.4-87), specificity of 19.7% (18.6-20.9) and an AUC of 0.623. Conclusions: We showed that ILI case definition was not accurate for RSV detection in Portugal. Therefore, the case definition should be adapted within the ISS or a specific RSV surveillance system should be implemented in Portugal.N/

Performance of surveillance case definitions for respiratory syncytial virus infections through the sentinel influenza surveillance system, Portugal, 2010 to 2018

Background: Well-established influenza surveillance systems (ISS) can be used for respiratory syncytial virus (RSV) surveillance. In Portugal, RSV cases are detected through the ISS using the European Union (EU) influenza-like illness (ILI) case definition. Aim: To investigate clinical predictors for RSV infection and how three case definitions (EU ILI, a modified EU acute respiratory infection, and one respiratory symptom) performed in detecting RSV infections in Portugal. Methods: This observational retrospective study used epidemiological and laboratory surveillance data (October 2010–May 2018). Associations between clinical characteristics and RSV detection were analysed using logistic regression. Accuracy of case definitions was assessed through sensitivity, specificity, and area under the receiver operating characteristic curve (AUC). A 0.05 significance level was accepted. Results: The study involved 6,523 persons, including 190 (2.9%) RSV cases. Among 183 cases with age information, RSV infection was significantly more frequent among individuals < 5 years (n = 23; 12.6%) and ≥ 65 years (n = 45; 24.6%) compared with other age groups (p < 0.0001). Cough (odds ratio (OR): 2.4; 95% confidence interval (CI): 1.2–6.5) was the best RSV-infection predictor considering all age groups, while shortness of breath was particularly associated with RSV-positivity among ≤ 14 year olds (OR: 6.7; 95% CI: 2.6–17.4 for 0–4 year olds and OR: 6.7; 95% CI: 1.5–28.8 for 5–14 year olds). Systemic symptoms were significantly associated with RSV-negative and influenza-positive cases. None of the case definitions were suitable to detect RSV infections (AUC = 0.51). Conclusion: To avoid underestimating the RSV disease burden, RSV surveillance within the Portuguese sentinel ISS would require a more sensitive case definition than ILI and, even a different case definition according to age.info:eu-repo/semantics/publishedVersio