Cloning, expression and purification of the complete domain of the η-carbonic anhydrase from Plasmodium falciparum.

The antimalarial drugs are of fundamental importance in the control of malaria, especially for the lack of efficient treatments and acquired resistance to the existing drugs. For this reason, there is a continuous work in identifying novel, less toxic and effective chemotherapies as well as new therapeutic targets against the causative agents of malaria. In this context, a superfamily of metalloenzymes named carbonic anhydrases (CAs, EC 4.2.1.1) has aroused a great interest as druggable enzymes to limit the development of Plasmodium falciparum gametocytes. CAs catalyze a common reaction in all life domains, the carbon dioxide hydration to bicarbonate and protons (CO2 + H2O HCO3- + H+). P. falciparum synthesizes pyrimidines de novo starting from HCO3-, which is generated from CO2 through the action of the ?-CA identified in the genome of the protozoan. Here, we propose a procedure for the preparation of a wider portion of the protozoan ?-CA, named PfCAdom (358 amino acid residues), with respect to the truncated form prepared by Krungkrai et al. (PfCA1, 235 amino acid residues). The results evidenced that the recombinant PfCAdom, produced as a His-tag fusion protein, was 2.7 times more active with respect the truncated form PfCA1

309. Optimization of Dual AAV Vectors for Gene Therapy of Inherited Retinal Diseases

Retinal gene therapy with adeno-associated viral (AAV) vectors is safe and effective in humans. However, AAV limited cargo capacity prevents its application to therapies of inherited retinal diseases (IRD) due to mutations in genes over 5 kb. Dual AAV vectors, each containing one of the two halves of a large gene expression cassette, are emerging as promising tools to overcome this limitation. Dual AAV trans-splicing and hybrid vectors transduce efficiently the mouse and pig retina and are effective in animal models of IRD. However, some of dual AAV limitations include lower levels of transgene expression compared to a single AAV vector and the production of proteins shorter than expected from either the 5'- or 3'-half AAV. Thus, further development of dual AAV vectors is required before their clinical translation. To increase dual AAV recombination we have exploited various regions of homology while to mediate the degradation of the proteins shorter than expected we have tested the ability of various degradation signals. We found that the levels of transgene expression achieved with the alternative regions of homology are similar to those achieved with dual AAV vectors carrying the AK region of homology we have previously shown to be effective. Notably, we have identified a degradation signal which mediates the degradation of proteins shorter than expected from dual AAV vectors. In conclusion, our study outlines optimized features of dual AAV vectors that improve their safety and efficacy. This represents a step towards the clinical translation of dual AAV for retinal gene therapy

You Can't Get There from Here

You Can’t Get There from Here was commissioned by the Sound Festival 2015 with funding from Creative Scotland. The idea, emerging initially from New Music Scotland’s 2014 ‘Time Out’ composer residency, was to experiment with a method of collaborating on music that was fully integrated but at the same time allowed for some emergence of individual voice. This resulted in a process whereby the six composers in the group each started a fragment of music, and each passed that fragment on to another member of the group, according to a predetermined schedule. Each composer then altered, added to, or took away from, the material that they were given, and then passed it to the next. This process continued until the transformed fragment arrived back at the composer it started with. The performance of the final six-part collaboration occurred on October 22, 2015 at the Sound Festival in Aberdeen, Scotland. BBC Radio Scotland broadcast a feature on "Classics Unwrapped" with Jamie MacDougall in early November 2015

A "calculable man"?

A Psicanálise, na medida em que ganha espaço como um discurso explicativo do comportamento humano e dos laços sociais é confrontada com a necessidade de pensá-los como registros em que a transmissão simbólica pode e deve ocorrer. Como ser de linguagem, o homem pode transmitir as marcas simbólicas constitutivas de sua cultura, tendo em vista encontrar nela o seu lugar. A técnica e a tecnologia, que fazem parte deste legado, vêm sendo priorizadas no âmbito dos vários níveis do ensino. Sustentamos que a educação não pode ser reduzida a elas, já que a transmissão simbólica ultrapassa em muito uma formação cujo objetivo seja o ensino de competências técnicas produtoras do que denominamos de "homem calculável".En la medida en que gana terreno como un discurso explicativo de la conducta humana y, por lo tanto, de las relaciones sociales, incluso de los del campo de la educación escolar, el Psicoanálisis se enfrenta, en cada momento, a la necesidad de pensar en ellos como registros donde puede y debe ocurrir la transmisión simbólica. Como un ser del lenguaje, el hombre puede organizar y transmitir los signos simbólicos constitutivos de su cultura, con el fin de encontrar su lugar. La técnica y la tecnología, que son partes de este legado, se han priorizado dentro de los diversos niveles de educación. Este artículo sostiene que la educación no puede reducirlos. La transmisión simbólica de la cultura inherente y necesaria a la educación va mucho más allá de una formación profesional, que al tener sus metas de enseñanza/aprendizaje de carácter técnico, sería productora de lo que podría considerarse "un hombre calculable".Psychoanalysis, to the extent that it is gaining ground as an explanatory discourse of human behavior and, therefore, social relations, even referring to those in the field of school education, is confronted, at every moment, with the need to think them while records in which the symbolic transmission can and should occur. As linguistic beings, humans can systematize and transmit the constitutive symbolic marks of their culture, in order to find their place in it. The technique and technology, which are part of this legacy, have been prioritized within the various levels of education. This paper argues that education cannot be reduced to them. The symbolic transmission, inherent and necessary to education, goes far beyond a vocational training to teaching/learning technical skills, producing what could be considered a "calculable man"

Ações educativas durante a assistência pré-natal: percepção de gestantes atendidas na rede básica de Maringá-PR

A dimensão educativa é parte integrante e inovadora na assistência pré-natal. Desta forma o estudo objetivou conhecer a percepção de gestantes usuárias da rede básica de saúde de Maringá/PR sobre educação em saúde e como ela ocorre. Estudo de natureza qualitativa, do qual participaram 25 gestantes de cinco unidades básicas de saúde do município. Os dados foram coletados em novembro de 2009, por meio de entrevistas semiestruturadas e submetidos à análise de conteúdo. Os resultados demonstraram que, das mulheres em estudo, grande parte delas conhecem e identificam as ações de educação em saúde realizadas pelos profissionais. De forma geral atribuem grande importância a estas ações, principalmente para a prevenção de doenças e agravos durante a gestação e também para aprender sobre os cuidados com o bebê após o parto. Concluiu-se que ainda existe uma lacuna no que concerne às ações educativas direcionadas a assistência pré-natal na atenção primária à saúde. Descritores: Educação em Saúde; Enfermagem; Gestantes; Atenção Primária à Saúde

The educational work of nurses in the Family Health Strategy: difficulties and perspectives on change

Este estudo objetivou conhecer as dificuldades e perspectivas de mudanças que os enfermeiros identificam no desenvolvimento das ações educativas na Estratégia Saúde da Família (ESF). Trata-se de uma pesquisa qualitativa descritivo-exploratória. Os dados foram coletados junto a 20 enfermeiros que atuam na ESF, no âmbito da 10ª Regional de Saúde do Paraná, por meio de entrevistas semiestruturadas, no mês de abril de 2010, as quais foram submetidas à análise de conteúdo. Os resultados demonstraram que os enfermeiros enfrentam dificuldades no desenvolvimento da educação em saúde junto aos usuários, à equipe, aos gestores e quanto à falta de recursos físicos, materiais e financeiros. Mas, a partir das dificuldades sentidas, buscam alternativas diversificadas para superá-las e sugerem modificações visando à melhoria na atenção primária à saúde da população, principalmente, no que tange ao trabalho educativo.The objective of this study was to understand the difficulties and perspectives on change that nurses have identified in developing educational interventions in the Family Health Strategy (FHS). This is a qualitative, descriptive-exploratory study. The data were collected with 20 nurses working in the FHS of the 10th Regional Health District of Paraná, by means of semi-structured interviews carried out in April 2010, which were subjected to content analysis. The results demonstrated that nurses face difficulties in developing health education strategies with the clients, healthcare team, and administrators, especially in regards to the lack of physical, material and financial resources. However, based on the difficulties they encounter, they seek alternatives to overcome them and suggest changes aimed at improving the delivery of primary health care to the population, particularly regarding educational practices.Este estudio objetivó conocer las dificultades y perspectivas de cambio que identifican los enfermeros en el desarrollo de acciones educativas en la Estrategia Salud de la Familia (ESF). Se trate de investigación cualitativa descriptivo-exploratoria. Los datos se recolectaron a través de veinte enfermeros que actúan en la ESF en el ámbito de la 10a Regional de Salud de Paraná, mediante entrevistas semiestructuradas, en abril de 2010, y fueron sometidos a análisis de contenido. Los resultados demostraron que los enfermeros enfrentan dificultades en el desarrollo de la educación en salud junto a los pacientes, al equipo, a los administradores y respecto de la falta de recursos físicos, materiales y financieros. Pero, a partir de las dificultades detectadas, buscan alternativas diversas para superarlas y sugieren modificaciones apuntando a la mejora en la atención primaria de salud de la población; principalmente, en lo que atañe al trabajo educativo

Implementing a robotic liver resection program does not always require prior laparoscopic experience

Background: Preliminary experience in laparoscopic liver surgery is usually suggested prior to implementation of a robotic liver resection program. Methods: This was a retrospective cohort analysis of patients undergoing robotic (RLR) versus laparoscopic liver resection (LLR) for hepatocellular carcinoma at a center with concomitant initiation of robotic and laparoscopic programs RESULTS: A total of 92 consecutive patients operated on between May 2014 and February 2019 were included: 40 RLR versus 52 LLR. Median age (69 vs. 67; p = 0.74), male sex (62.5% vs. 59.6%; p = 0.96), incidence of chronic liver disease (97.5% vs.98.1%; p = 0.85), median model for end-stage liver disease (MELD) score (8 vs. 9; p = 0.92), and median largest nodule size (22 vs. 24 mm) were similar between RLR and LLR. In the LLR group, there was a numerically higher incidence of nodules located in segment 4 (20.0% vs. 16.6%; p = 0.79); a numerically higher use of Pringle's maneuver (32.7% vs. 20%; p = 0.23), and a shorter duration of surgery (median of 165.5 vs. 217.5 min; p = 0.04). Incidence of complications (25% vs.32.7%; p = 0.49), blood transfusions (2.5% vs.9.6%; p = 0.21), and median length of stay (6 vs. 5; p = 0.54) were similar between RLR and LLR. The overall (OS) and recurrence-free (RFS) survival rates at 1 and 5 years were 100 and 79 and 95 and 26% for RLR versus 96.2 and 76.9 and 84.6 and 26.9% for LLR (log-rank p = 0.65 for OS and 0.72 for RFS). Conclusions: Based on our results, concurrent implementation of a robotic and laparoscopic liver resection program appears feasible and safe, and is associated with similar oncologic long-term outcomes

Latency to Reward Predicts Social Dominance in Rats: A Causal Role for the Dopaminergic Mesolimbic System

Reward signals encoded in the mesolimbic dopaminergic system guide approach/seeking behaviors to all varieties of life-supporting stimuli (rewards). Differences in dopamine (DA) levels have been found between dominant and submissive animals. However, it is still unclear whether these differences arise as a consequence of the rewarding nature of the acquisition of a dominant rank, or whether they preexist and favor dominance by promoting reward-seeking behavior. Given that acquisition of a social rank determines animals’ priority access to resources, we hypothesized that differences in reward-seeking behavior might affect hierarchy establishment and that modulation of the dopaminergic system could affect the outcome of a social competition. We characterized reward-seeking behaviors based on rats’ latency to get a palatable-reward when given temporary access to it. Subsequently, rats exhibiting short (SL) and long (LL) latency to get the rewards cohabitated for more than 2 weeks, in order to establish a stable hierarchy. We found that SL animals exhibited dominant behavior consistently in social competition tests [for palatable-rewards and two water competition tests (WCTs)] after hierarchy was established, indicating that individual latency to rewards predicted dominance. Moreover, because SL animals showed higher mesolimbic levels of DA than LL rats, we tested whether stimulation of mesolimbic DA neurons could affect the outcome of a social competition. Indeed, a combination of optical stimulation of mesolimbic DA neurons during individual training and during a social competition test for palatable rewards resulted in improved performance on this test

Centros de Nacimiento en Brasil: revisión de la producción científica

Este artigo consiste em uma revisão narrativa com o objetivo de identificar a produção científica brasileira relacionada ao processo assistencial e aos resultados maternos e perinatais em centro de parto normal (CPN). As publicações foram recuperadas nas bases de dados e portais de periódicos PubMed/MEDLINE, CINAHAL, SciELO e REVENF. Incluíram-se, também, publicação em livro e produção não publicada de grupo de pesquisa. Foram selecionados oito estudos do tipo descritivo, dois transversais e dois casos-controle, realizados com 5.407 mulheres e 5.395 recém-nascidos, divulgados entre 2005 e 2009. Os estudos analisaram variáveis sócio-demográficas e obstétricas, práticas na assistência ao parto e nascimento e remoções maternas e neonatais para o hospital. A produção científica sobre CPN apresenta dados da última década, relativos a sete serviços. São, principalmente, estudos descritivos, com foco nas práticas obstétricas e nos resultados maternos, com ênfase menor na assistência neonatal.This article is a narrative review with the aim of identifying the Brazilian scientific production related to the care process and maternal and perinatal outcomes in birth centres (BC). The papers were recovered in the databases and portals PubMed/MEDLINE, CINAHAL, SciELO and REVENF. There were also included one book and the non published studies from a researcher group. There were selected eight descriptive, two cross-sectional and two case-control studies conducted with 5,407 women and 5,395 newborns, which were reported in the period from 2005 to 2009. These studies analyzed socio-demographic and obstetric outcomes in childbirth and maternal and neonatal transfers to the hospital setting. BC scientific production presents data about seven services, from the last decade. There are mainly descriptive studies, with focus on obstetric practices and maternal outcomes, with less emphasis on neonatal care.Este artículo es una revisión narrativa, con el objetivo de identificar la producción científica brasileña relacionada con la atención y los resultados maternos y perinatales en centros de nacimiento (CN). Las publicaciones fueron recuperadas en las bases de datos y portales PubMed/MEDLINE, CINAHAL, SciELO y REVENF. Fueron incluidos también libro publicado y los trabajos no publicados de un grupo de investigadores. Fueron seleccionados ocho estudios de tipo descriptivo, dos transversales y dos casos-control, realizados con 5.407 mujeres y 5.395 recién-nacidos, divulgados en el período de 2005 a 2009. Los estudios analizaron variables socio-demográficas y obstétricas, prácticas en la atención al parto y nacimiento y el traslado materno y neonatal hacia al hospital. La producción científica sobre CN presenta datos de la última década, relativos a siete servicios. Son estudios principalmente descriptivos, con enfoque en las prácticas obstétricas y en los resultados maternos, con menos énfasis en la atención neonatal