Regulação da Septina 9 na síndrome do desconforto respiratório agudo associado à malária / The role of Septin 9 in regulating vascular permeability in malarial respiratory distress syndrome

A malária é um problema mundial de saúde, com 249 milhões de casos de infecção, ocasionando 608 mil mortes no ano de 2022. Causada pelo gênero Plasmodium, são cinco principais espécies causadoras da malária no ser humano, o Plasmodium malariae, Plasmodium ovale, Plasmodium knowlesi, Plasmodium vivax e Plasmodium falciparum sendo os dois últimos responsáveis pelo maior número de casos clínicos e mortes ao redor do mundo, transmitida pelo mosquito fêmea do gênero Anopheles durante o repasto sanguíneo. Sabe-se ainda que eritrócitos infectados por Plasmodium berghei ANKA causam alteração no citoesqueleto de actina, consequentemente levando a hiperpermeabiliade da barreira endotelial. Em experimentos in vitro, a imunofluorescência, foi observada alteração do citoesqueleto de actina em células estimuladas com eritrócitos parasitados por PbA (EP), em contrapartida, aquelas não estimuladas (NE) e estimuladas com eritrócitos não parasitados por PbA (EnP), não mostraram alterações no mesmo. Nos experimentos in vivo, ao observar dados coletados, sendo estes respiratórios (penh e frequência respiratória) e parasitemia coletados no 7º DPI, foi observado um mesmo padrão entre o experimento 1 e o experimento 2. Os animais infectados com 106 de eritrócitos infectados, foram alocados em dois grupos, sendo eles hiperparasitemia (HP) ou síndrome do desconforto respiratório agudo-associado a malária (SDRA/SDRA-MA) e comparados àqueles não infectados (NI). Os animais NI, não apresentam parasitemia, em contrapartida, os animais SDRA, tem maior parasitemia que os HP, visto que estes têm aumento em sua parasitemia após o 12º DPI, e assim seguem aumentando gradativamente até levar os animais a óbito.O penh tem o mesmo padrão que a parasitemia, os NI com penh mais baixa que os HPs e os SDRA, sendo dentre estes, o grupo SDRA o mais elevado. A frequência respiratória, por sua vez se apresenta mais elevada no grupo NI, sendo o grupo SDRAmenor que o HP, um achado tido como normal, visto que os pulmões de animais com SDRA sofrem maior dano que os HPs. Apesar de não apresentar um valor significativo, as imagens de gel SDS-PAGE (WB) mostram maior concentração da Septina 9 nos animais com SDRA em comparação com os HPs e com os NIs. O mesmo é observado na qRT-PCR, mesmo sem significância estatística, o valor mostrado nos gráficos temmaior concentração nos SDRA. Assim, a Septina 9 está presente nas CEPP, e, mesmo sem significância estatística, da mesma forma que está presente nas amostras de tecido pulmonar utilizadas no WB e qT-PCR. É hipotetizado ainda que esta proteína pode ser ativada e assim sofrer alteração em sua localização intracelular

Malaria is a global health problem, with 249 million cases of infection, causing 608 thousand deaths in the year 2022. Caused by the genus Plasmodium, there are five main species that cause malaria in humans, Plasmodium malariae, Plasmodium ovale, Plasmodium knowlesi, Plasmodium vivax and Plasmodium falciparum, the last two being responsible for the largest number of clinical cases and deaths around the world, transmitted by the female mosquito of the genus Anopheles during blood meal. It is also known that erythrocytes infected by Plasmodium berghei ANKA (PbA) cause changes in the actin cytoskeleton, consequently leading to hyperpermeability of the endothelial barrier. In in vitro experiments, immunofluorescence, changes in the actin cytoskeleton were observed in cells stimulated with erythrocytes parasitized by PbA (EP), in contrast, those not stimulated (NE) and stimulated with erythrocytes not parasitized by PbA (EnP), did not show changes the same. In the in vivo experiments, when observing collected data, these being respiratory (penh and respiratory frequency) and parasitemia collected on the 7th DPI, the same pattern was observed between experiment 1 and experiment 2. Animals infected with 106 infected erythrocytes were allocated into two groups, namely hyperparasitemia (HP) or malaria-associated acute respiratory distress syndrome (ARDS/ARDS-MA) and compared to those not infected (NI). NI animals do not present parasitemia, on the other hand, ARDS animals have greater parasitemia than HP animals, as the latter have an increase in their parasitemia after the 12th DPI, and thus continue to gradually increase until the animals die. the same pattern as parasitemia, NI with lower penh than HPs and ARDS, among these, the ARDS group being the highest. The respiratory rate, in turn, is higher in the NI group, with the ARDS group being lower than the HP, a finding considered normal, given that the lungs of animals with ARDS suffer greater damage than the HPs. Despite not showing a significant value, SDS-PAGE (WB) gel images show a higher concentration of Septin 9 in animals with ARDS compared to HPs and NIs. The same is observed in qRT-PCR, even without statistical significance, the value shown in the graphs has a higher concentration in ARDS. Thus, Septin 9 is present in CEPP, and, even without statistical significance, in the same way that it is present in lung tissue samples used in WB and qT-PCR. It is also hypothesized that this protein can be activated and thus undergo changes in its intracellular location

Expanding and Validating a Typology of Intimate Partner Violence: Intersections of Violence and Control Within Relationships.

This research explored an expanded typology of intimate partner violence (IPV), intersecting violent and controlling behaviors of partners. Secondary data were analyzed ( n = 714). Cluster analyses indicated that elements of IPV (control perpetration, control victimization, violence victimization, and violence perpetration) all clustered in high/low patterns, which intersected to form 10 unique categories of IPV. Support for all of Johnson's categories of IPV was found, but there was also evidence for the three control-related categories: Unidirectional Control, Bidirectional Control, and Control Resistance. This expanded typology can move research, practice, and policies beyond the gender symmetry debate.

Avaliação técnico-regulatória dos requisitos de qualidade para registro de medicamentos biológicos e biossimilares humanos: perspectivas e desafios no Brasil / Technical and regulatory evaluation of quality requirements for the registration of human biological and biosimilar drugs: perspectives and challenges in Brazil

Medicamentos biológicos são obtidos a partir de fluidos biológicos ou tecidos de origem animal por procedimentos biotecnológicos e, a partir do vencimento das suas patentes, surge a possibilidade da produção de suas cópias, os chamados biossimilares. Este tema, além de polêmico, por ainda apresentar divergências de entendimento da classe científica, também engloba 4 das 5 classes terapêuticas de medicamentos mais vendidas, e apresenta evolução crescente no mercado farmacêutico. Com o aumento da demanda, cresce o interesse na produção de medicamentos biológicos de alta qualidade, com a mesma eficácia, porém a preços mais baixos. Dessa forma, é possível entender a responsabilidade das regulamentações, principalmente no que diz respeito aos biossimilares, a fim de que eles respeitem os requisitos mínimos necessários para serem comparáveis ao seu medicamento biológico novo. Assim, este trabalho teve como objetivo avaliar questões técnico-regulatórias e os requisitos de qualidade para registro de medicamentos biológicos e biossimilares humanos frente a diferentes Autoridades Sanitárias mundiais. A análise foi baseada em três moléculas biológicas, sendo a clássica heparina e moléculas novas, filgrastim e infliximabe. Foi constatado que na teoria, a legislação brasileira é baseada em regulamentos internacionais, especialmente da Federal and Drug Administration (FDA) e European Medicines Agency (EMA), e que na prática, o Brasil tem se mostrado mais conservador na extrapolação de indicação e na aprovação dos biossimilares. Ainda, foi possível notar que independente do país, as Farmacopeias ainda necessitam de aprimoramento com relação a este tema, pois em sua maioria, não existe padronização dos parâmetros e testes a serem realizados. Pesquisa demonstrou que o conhecimento sobre biossimilares ainda não está consolidado entre profissionais médicos e que, portanto, há necessidade de programas para esclarecimentos, com a finalidade de estimular seu uso, quando possível e com custos mais interessantes

Biological drugs are obtained from biological fluids or animals tissues by biotechnological procedures and, from the expiration of their patents, the possibility of producing their "copies", the so-called biosimilars, arises. In addition to being a controversial subject, as it still presents divergences of understanding by the scientific class, it also encompasses 4 of the 5 therapeutic classes of best-selling drugs, and it presents an increasing evolution in the pharmaceutical market. As demand increases, interest in the production of high-quality biological drugs with the same effectiveness, but at lower prices, also increases. In this way, it is possible to understand the responsibility of regulations, especially with regard to biosimilars, so that they comply with the minimum requirements needed to be comparable to their reference biological medicine. Thus, the objective of this project was to evaluate technical and regulatory topics, as well as quality requirements for the registration of human biological and biosimilar medicines under the perspective of different Health Authorities around the world. The analysis was based on three biological molecules, being the classic heparin and new molecules, filgrastim and infliximab. It was found that in theory, Brazilian regulation is based on international regulations, especially the Federal and Drug Administration (FDA) and the European Medicines Agency (EMA), and that in practice, Brazil has been more conservative in the extrapolation of indication and approval of biosimilars. Also, it was possible to note that, regardless the country, Pharmacopoeias still need to be improved for this topic, since in general, there is no standardization of the parameters and tests to be performed. Research showed that the knowledge about biosimilars is not yet consolidated among doctors and that, therefore, there is a need for clarification programs, with the purpose of stimulating their use, when possible and at lower costs

Evaluation of an intervention program for the initiation to basketball aimed at teaching the game's rules / Evaluación de un programa de intervención de iniciación al baloncesto a través de la enseñanza de las reglas

The rules of a game determine the technical and tactical skills necessary for the game, such as in basketball. An intervention program was designed that aimed to teach the rules that were considered to be the most important for the initiation to basketball and to teach the players the technical and tactical skills from these rules. The objective of the present study was to develop and assess an intervention program based on the coach´s perceptions of the program. The study´s sample was a mini-basketball team of 14 players and the team´s coach. The program lasted 8 months and had three weekly practice sessions. The instruments utilized for data collection were the daily training reflections, action research cycles, and the audio recordings. The data were analyzed qualitatively. The coding was done by the research team, and after several trial sessions, a Kappa index of K=.78 was achieved, which assured inter-coder reliability. Among the results, it should be highlighted that the rules were the backbone of the program. As the program progressed, the players better understood their use. Likewise, they understood the relationship between the technical and tactical skills and the rules, fostering their involvement in the learning process and their familiarization with the game. In conclusion, the experience of teaching basketball initiation through familiarizing players with the rules was positive due to the cognitive involvement of the players in the learning process

Las reglas condicionan los aspectos técnicos y tácticos del juego, como el baloncesto. Se diseñó un programa de intervención basado en la enseñanza de las reglas consideradas más importantes para la iniciación y, a partir de éstas, el aprendizaje de los medios técnicos y tácticos. El objetivo del presente trabajo se centró en el desarrollo y evaluación del programa de intervención a través de la percepción de la entrenadora. La muestra del estudio fue un equipo de 14 jugadores de minibasket y su entrenadora. El programa duró 8 meses con tres entrenamientos semanales. Los instrumentos utilizados para la recogida de datos han sido los Diarios de entrenamiento, Ciclos de Supervisión y Ciclos de Audio. Los datos fueron analizados cualitativamente. La codificación fue realizada por el equipo de investigación y tras varios entrenamientos se alcanzó un índice Kappa de K=.78, lo que garantizó la fiabilidad inter-codificadores. Entre los resultados, se destaca que las reglas pueden suponer el eje vertebrador de la programación. A medida que avanzó el programa, los jugadores fueron entendiendo su utilidad. Asimismo, comprendieron la relación entre los aspectos técnico-tácticos y las reglas fomentando su implicación en el proceso de aprendizaje y la familiarización con el juego. A modo de conclusión, la experiencia de enseñar la iniciación al baloncesto a través de las reglas ha sido positiva por la implicación cognitiva de los jugadores en el proceso de aprendizaje

Analysis of shooting effectiveness and decision-making during shooting according to basket height modifications at the youth stage / Indicencia del uso de un protopio de canasta con modificación de la altura del cesto sobre la eficacia y la toma de decisió del lanzamiento en el ámbito escolar

The aim of the present study was to identify the effect of a basketball unit of work that modifies the height of the hoop on the shooting effectiveness, the shooting decision-making process, and the ball possessions ending with a shot. The study was a cuasiexperiment with control and experimental groups measured pre and post intervention. The basketball unit of work was composed of 10 lessons that were applied to a sample of 74 students (14 years old). Control group received the lessons with the regular height of the basket (3.05m) and the experimental group received the lessons with variations in the height of the basket according to each task. The evaluation task was a 3 vs. 3 game situation. The results showed that experimental group increased the number of shots, the shooting effectiveness, as well as the decision-making process related to shooting action. The results enhance the need to modify and adapt the basketball height to the tasks and exercises specificity, and then to improve the shooting efficiency and effectiveness

El objetivo del presente estudio fue identificar el efecto de una unidad didáctica de baloncesto en la que se modifica la altura del aro sobre la efectividad de tiro, el proceso de toma de toma de decisiones, y el número de fases de ataque que finalizan en lanzamiento. El estudio fue estudio cuasi-experimental con grupo control y experimental medidos antes y después de la intervención. La unidad didáctica de baloncesto se compone de 10 sesiones que se aplicaron a una muestra de 74 estudiantes (14 años). El grupo control recibió las sesiones con la canasta a una altura normal de (3.05m) y el grupo experimental recibió las sesiones con variaciones en la altura de la canasta de acuerdo a cada tarea. La tarea de evaluación era una situación de juego 3 vs 3. Los resultados mostraron que el grupo experimental aumentó el número de lanzamientos, el número de fases de ataque que finalizan en lanzamiento, así como el proceso de toma de decisiones relacionadas con el lanzamiento. Los resultados señalan la necesidad de modificar y adaptar la altura de baloncesto a las tareas y ejercicios, para mejorar la eficiencia y eficacia del lanzamiento en baloncesto

Uso de mapas cognitivos borrosos para conocer el impacto económico de las prestaciones del sistema para la autonomía y atención a la dependencia / Analyzing the impact of decisions in the scope of long term care by fuzzy cognitive maps, Spain

El Sistema para la Autonomía y Atención a la Dependencia (SAAD) fue creado con el fin de proporcionar un marco de protección a las personas en situación de dependencia. La prioridad de las prestaciones en servicios frente a las económicas, según la Ley, y la gestión eficiente de los recursos públicos destinados al SAAD hacían prever retornos económicos, como la generación de empleo. Las variables que influyen en la implantación del SAAD son extremadamente complejas y dinámicas, existiendo múltiples relaciones entre las mismas. El objetivo de este trabajo es analizar la problemática de satisfacer una demanda creciente de protección al mínimo coste y aprovechar los retornos económicos mediante la lógica borrosa (mapa cognitivo borroso). Esta técnica se configura como una herramienta para la toma de decisiones en este ámbito, porque permite analizar la evolución de las variables causales hasta un estado de equilibrio. Para ello, se han ideado 4 escenarios (E1:Envejecimiento, E2: Envejecimiento y prestaciones en servicios, E3: Envejecimiento y prestaciones económicas, E4: Envejecimiento y prestación económica para cuidados en el entorno familiar), con el fin de analizar la evolución de las variables, especialmente el gasto público y el empleo. Entre los principales resultados obtenidos destacan: el envejecimiento es determinante en el incremento del gasto en todos los escenarios, pero solamente en E1 y E2 se genera empleo. La prestación residencial no se altera, ni siquiera en E2. La teleasistencia aumenta en todos los escenarios y la prestación económica por asistente personal aumenta en E1 y E2(AU)

System for Autonomy and Care for Dependency (Spanish acronym SAAD) was created to provide a framework for the protection of dependent people. The priority established by law on benefits in kind over cash benefits, together with the efficient management of public resources provided economic returns for the SAAD, such as employment generation. The variables that influence the implementation of the SAAD are extremely complex and dynamic, and there are multiple relationships between them. The aim of this paper is to analyze the problem of satisfying a growing demand for protection, at minimum cost, and reaps the economic returns using fuzzy logic (fuzzy cognitive map). This technique is designed as a tool for decision-making in this area, to analyze the evolution of causal variables to a state of equilibrium. To do this, we have developed 4 scenarios (E1: Ageing, E2: Ageing and benefits in kind, E3: Ageing and cash benefits, E4: Ageing and cash benefit for care in the family), to analyze the evolution of variables, especially public expenditure and employment. Among the main results are: ageing is critical for the increased spending in all scenarios, but only in E1 and E2 is generated employment, residential care is not altered, even in E2; Telecare increases in all scenarios, and the cash benefit for personal attendant increases in E1 and E2(AU)

Movimientos sociales: lugares de lucha y construcción de sujeto / Social movements: places of struggle and subject construction

El presente artículo fruto de un ardua investigación tiene como propósito re-conocer el sentido – pedagógico y político – del “estar juntos”, e interpretar los procesos, las herramientas y las tareas de carácter formativo y político de las organizaciones sociales que conforman y/o potencian la construcción de la Coalición de Movimientos Sociales en Colombia.

This article which is the fruit of an arduous research aims to re-knowing - pedagogical and political--sense of "being together", and to interpret the processes, tools, and tasks of formative and political character of the social organizations that comprise and/or enhance the construction of the Coalition of Social Movements in Colombia.

Regulatory challenges of on-line hemodiafiltration.

The launch of on-line hemodiafiltration happened at a very peculiar time from the regulatory standpoint. The directives on medical devices were at their very beginning and the medicinal products regulatory regime was considering, after 30 years of operation of Directive 65/65/EEC, whether it was the case to go for greater harmonization. The success in the introduction of the therapy was strictly linked to the possibility of having the entire system approved for the European market according a single procedure. I had the pleasure to be part of the team, which included Dr. Wolfgang Kümmerle and my old friend Dr. Emanuele Gatti, which succeeded in gathering consensus on the classification of the on-line hemodiafiltration system as a medical device.

Aids e juventude: gênero, classe e raça / Aids and youth: gender, class and race

Dois problemas pouco visíveis na área da saúde são destacados neste livro: a violência resultante das desigualdades de gênero e raça/etnia e a feminização da Aids. Esta última está diretamente relacionada à primeira, pois é consequência não só do aumento da vulnerabilidade às DST/Aids provocada pela dificuldade das mulheres, em especial as jovens e negras, de negociar com seus parceiros práticas sexuais seguras, mas também das violências sexual e institucional. A feminização da Aids tem se intensificado nos últimos anos, reduzindo a razão entre homens e mulheres infectados de 26 para um, em 1986, para 1,4 para um, em 2005. Convidamos, então, o leitor a refletir sobre os dados deste estudo e contribuir para uma ação efetiva de enfrentamento à violência baseada no gênero e na raça que reduza as desigualdades e aperfeiçoe a qualidade da atenção a esse estrato populacional nos serviços de saúde.

Of germs, public hygiene, and the healthy body: the making of the medicalizing state in Thailand.

The historical study of Western medicine in nineteenth-century Siam has emphasized the dichotomy between Western medicine and traditional Thai medical practice. The former is often represented as a monolith, and the epistemological transformation of Western medicine during the nineteenth century is glossed over without sufficient attention. Pasteurian medicine, especially the idea of germs, was introduced to Siam by the American missionary Dan Beach Bradley. Its introduction spurred a process of negotiation with both pre-Pasteurian Western and traditional Thai medicine. In its pre-Pasteurian and Pasteurian variants, Western medicine was constituted as a new medical practice and disciplinary regime in Siam. As a discursive instrument of state hegemony, the ideas, structures, policies, and institutions of Western medicine furthered the understanding and management of virulent epidemics, the institution of the sanitary system, the shaping of new concepts of population and a healthy workforce, and not least, the framing of a medicalizing project to police people's bodies pursued by the Thai state in the 1930s.

Using the theory of planned behavior and a stage model of persuasion to evaluate a safety message for firefighters.

A field study was conducted to evaluate the effectiveness of a National Institute for Occupational Safety and Health (NIOSH) health and safety message targeted at firefighters and to examine predictors of safety intentions among this group. This project examined: (a) the ability of the theory of planned behavior (TPB) to predict behavioral intentions for firefighters receiving a NIOSH occupational safety and health message; and (b) the use of a persuasion output matrix to assess message impact. A message about firefighting safety was nationally distributed to 36,000 fire chiefs, from which 781 were randomly selected to complete a survey assessing message impact and behavioral intentions. Results indicate message impact was weakest at the exposure, recall, and action stages of persuasion output. The TPB variables were found to significantly predict safety intentions.

Generating a taxonomy of regulatory responses to emerging issues in biomedicine.

In the biomedical field, calls for the generation of new regulations or for the amendment of existing regulations often follow the emergence of apparently new research practices (such as embryonic stem cell research), clinical practices (such as facial transplantation) and entities (such as Avian Influenza/'Bird Flu'). Calls for regulatory responses also arise as a result of controversies which bring to light longstanding practices, such as the call for increased regulation of human tissue collections that followed the discovery of unauthorised post-mortem organ retention. Whilst it seems obvious that new regulations should only be generated if existing regulations are inadequate (a practice referred to in this paper as 'regulatory syncretism'), this does not always occur in practice. This paper examines the conceptual steps involved in generating regulatory responses to emerging phenomena. Two decision points are identified. First, a stance is taken as to whether the emerging phenomenon raises unique ethical or legal issues (exceptionalism versus non-exceptionalism). Second, the decision is made as to whether new regulation should be generated only for truly unique phenomena (syncretism versus asyncretism). It is argued here that it is important to make a careful assessment of novelty, followed by a reflective and deliberative choice of regulatory syncretism or asyncretism, since each type of regulatory response has advantages which need to be harnessed and disadvantages which need to be managed--something that can only occur if regulators are attentive to the choices they are making.