Implications of cholesterol and cholesterol-lowering therapy in Alzheimer s disease

BACKGROUND: Alzheimer s disease (AD) is a severe neurodegenerative disease that mainly afflicts elderly persons, with a characteristic progressive decline of cognitive functions and dementia. It is believed that the majority of all AD patients are affected by the sporadic form, thus caused by the combined effects of several risk factors, such as elevated cholesterol levels in midlife and deficiencies in the lipoprotein transporters apolipoprotein E (ApoE). Cholesterol play an essential role in the central nervous system (CNS) were it maintains normal physiological conditions, and is a requirement for the ability of neurons to communicate. It has previously been demonstrated that the cholesterol homeostasis in the CNS is maintained by a slow conversion of brain cholesterol into 24(S)-hydroxycholesterol, with a net flux of 27-hydroxycholesterol from the circulation into the brain. The importance of a preserved cholesterol homeostasis has been supported by the observation that dietary cholesterol may induce an inflammation in the CNS, and increase the levels of pro-inflammatory mediators. It has, in direct association with these observations, been demonstrated that plasma levels of pro-inflammatory proteins, such as interleukin-6, are increased before the clinical onset of AD, after which a chronic state of inflammation often is found. Accordingly, it has been suggested that memory and cognitive functions could benefit from a cholesterol-lowering therapy. STUDIES: The research presented in this thesis has examined the effect of cholesterol and cholesterol-lowering therapy with rosuvastatin, on key factors associated with AD. The experimental setup consisted of in vitro-models with human neuroblastoma SH-SY5Y cells (paper I II), and in vivo-models with wild type (WT) and ApoE knockout (ApoE-/-) mice, provided with high levels of dietary cholesterol for 18 weeks (paper III IV). The hydrophilic compound rosuvastatin is an effective inhibitor of cholesterol synthesis and has been demonstrated to be an effective treatment for hypercholesterolemia, with an indirect effect on microglial activation and inflammation through isoprenoid depletion. RESULTS: Paper I describes the selective non-amyloidogenic processing (alpha-secretase activity) of the amyloid precursor protein (APP), induced by 24(S)-hydroxycholesterol, with a subsequent increased ratio of alpha-/beta-secretase activity, and increased levels of soluble APPalpha and total soluble sAPP; effects significantly decreased by the presence of 27-hydroxycholesterol. Paper II describes the effect of pre-treating in vitro-cultures with rosuvastatin prior exposure to Abeta oligomers. The treatment was found to decrease caspase-3 activity and promote cell survival, with a selective non-amyloidogenic processing of APP. However, no influence was observed on cell viability, with a potential explanation in a downregulated metabolism. Paper III IV describes the effect of high levels of dietary cholesterol in vivo, with increased microglial activation in WT mice, increased gliosis in ApoE-/- mice and subsequent increased plasma IL-6 levels in WT and ApoE-/- mice. The elevated levels of total cholesterol (TC) were found to be caused by increased levels of HDL and LDL in WT mice, whereas only LDL where increased in ApoE-/- mice. Plasma TC levels were correlated with body weight gain in WT and ApoE-/- mice. Furthermore, the selective and ApoE-associated influence induced by the rosuvastatin therapy, on the effects of dietary cholesterol, is described. We observed a decreased microglial activation and gliosis in WT and ApoE-/- mice, with plasma IL-6 levels decreased by 45% in WT mice, without reaching significance. The elevated levels of TC and LDL were decreased in WT mice, whereas no effect was observed on the levels of TC, HDL or LDL in ApoE-/- mice. Body weight gain was decreased in WT mice, with a previously unpublished age- and ApoE-associated declining response to the therapy observed in ApoE-/- mice. SUMMARY: The presented thesis has examined the connection between Alzheimer s disease and cholesterol, and demonstrated a selection of detrimental effects which may be induced by high levels of dietary cholesterol. Furthermore, the thesis has demonstrated the potential for a cholesterol-lowering therapy with rosuvastatin to exercise a preventive influence, with an age- and ApoE-associated response. The latter is an important observation, which indicates that rosuvastatin may be an effective therapy up to a certain point in the progression of the disease, after which the effects decline. In conclusion, the results discussed in this thesis offer a hypothetical explanation, at least in part, for the discrepancies observed in clinical trials on statins. In addition, this thesis have been able to support the theoretical connection between AD and plasma cholesterol levels with the observation that 27-hydroxycholesterol may exhibit an inhibitory influence on 24(S)-hydroxycholesterol and non-AD processes. It is suggested that persons with high risk of developing AD may benefit from a rosuvastatin therapy, in combination with lifestyle precautions taken in early midlife. The approach could be an effective lifestyle-preventive strategy, with preserved cognitive functions and quality of life at high age

The Dakota Famer Atlas: Up-to-date Indexed Maps of North Dakota, South Dakota, Montana and Wyoming; Also Upto-date Maps of the World, United States, Alaska and the Panama Canal

Cover title Up-to-date indexed maps of North Dakota, South Dakota, Montana and Wyoming; also up-to-date maps of the world, United States, Alaska and the Panama Canal.https://openprairie.sdstate.edu/archives_rare-books/1004/thumbnail.jp

Defenda o SUS! Podcast como ferramenta de comunicação em saúde

Os podcasts são uma inovação relativamente recente tendo se mostrado como uma ferramenta de comunicação bastante interessante. Semelhantes a programas de rádio, diferenciam-se por ficarem hospedados em plataformas às quais o ouvinte pode ter acesso a qualquer momento. Podem ser realizados por um indivíduo ou um grupo, mais ou menos fixo, podendo utilizar-se de diferentes estratégias de interação e abordando temas variados. Desenvolvimento: O objetivo do artigo é descrever a experiência de criação do podcast Defenda o SUS!, no âmbito do Curso de Bacharelado em Saúde Coletiva da Universidade Federal do Rio Grande do Sul (UFRGS). A partir da solicitação de um trabalho de uma disciplina do Curso, em formato de podcast, foi pensado como seria interessante, diante da campanha de desinformação vigente no país e das estratégias de fragilização e destruição do Sistema Único de Saúde (SUS), criar-se um programa que pudesse abordar temas desconhecidos pela população em geral e que tivessem um formato agradável e amigável, que pudesse ser ouvido na realização de outras atividades. O podcast tem um formato que não ultrapassa uma hora de duração, tendo temas e estratégias variados, com informações sobre saúde a populações específicas por meio de entrevistas com pessoas que contam suas experiências de formação e atuação no campo da Saúde Coletiva. Resultados: O projeto é recente, mas já foi possível perceber que é uma estratégia que facilita o desenvolvimento de diversas competências de Comunicação em Saúde. Conclusão: A materialidade dá-se no exercício de escrita e de síntese na sua criação; assim representando uma inovação no campo da Comunicação em Saúde, para a construção de um produto barato e acessível a uma parcela da população que não tem outros meios para ampliar seus conhecimentos sobre saúde e informações fidedignas sobre variados temas.Los podcasts son una innovación relativamente reciente mostrándose como una herramienta de comunicación muy interesante. Semejantes a programas de radio, se diferencian por estar hospedados en plataformas a las cuales el oyente puede tener acceso en cualquier momento. Pueden ser realizados por un individuo o un grupo, más o menos fijo, pudiendo utilizarse de diferentes estrategias de interacción y abordando temas variados. Desarrollo: El objetivo del artículo es describir la experiencia de creación del podcast Defenda o SUS!, en el ámbito del Curso de Licenciatura en Salud Colectiva de la Universidad Federal de Rio Grande do Sul (UFRGS). A partir de la solicitud de un trabajo de una disciplina del Curso, en formato de podcast, fue pensado lo interesante de, ante la campaña de desinformación vigente en Brasil y de las estrategias de fragilización y destrucción del Sistema Único de Salud (SUS), crear un programa que pudiese abordar temas desconocidos por la población en general y que tuviesen un formato agradable y amigable, que pudiese ser oído mientras se realizan otras actividades. El podcast tiene un formato que no supera una hora de duración, teniendo temas y estrategias variados, con informaciones sobre salud a público específico por medio de entrevistas con personas que cuentan su experiencia de formación y actuación en el campo de la Salud Colectiva. Resultados: El proyecto es reciente, pero ya fue posible percibir que es una estrategia que facilita el desarrollo de diversas competencias de Comunicación en Salud. Conclusión: La materialidad se da en el ejercicio de escritura y de síntesis en su creación; representando así una innovación en el campo de la Comunicación en Salud, para la construcción de un producto barato y accesible para una parte de la población que no tiene otros medios para ampliar sus conocimientos sobre salud e informaciones fidedignas sobre varios temas

El Desarrollo sostenible desde el área física del ITM

Con esta investigación se pretende obtener una visión más clara sobre el actuar del Área Física del ITM vista bajo la lupa del Desarrollo Sostenible enmarcado desde su gestión para el mantenimiento y conservación de la planta física y la infraestructura. Con lo cual se lograría determinar cual es el panorama de la institución desde esta área frente a la sostenibilidad dándole un enfoque administrativo y contemplando algunas de las implicaciones que tiene en la economía de la organización. Así que partiendo del concepto del DS (Desarrollo Sostenible) y sus diversas implicaciones de orden gerencial sobre aspectos como; equilibrio e impacto social, impacto ambiental, inversión sobre la planta física e infraestructura, y en general sobre la planificación y desarrollo de la institución. Se busca conocer como está el Área Física del ITM frente a la implementación y aplicación de políticas o acciones que propendan por mantener la institución en el tiempo al mínimo de impacto ambiental y contribuyendo por el bienestar social futuro en conjunto con unos resultados económicos favorables que permitan que el ITM logre desarrollar una sostenibilidad en el tiempo. Para lograr verificar esta situación se tomaran aspectos como la forma como está estructurada la fuerza administrativa y las diferentes políticas que tiene el ITM para su gestión. Así como cual es la participación y aporte sobre el tema del DS del Área Física desde el grupo del Área de apoyo, es decir que contribución tiene desde su gestión al interior del ITMThis research aims to obtain a clearer view on the action of Physics ITM Area under the magnifying glass view of sustainable development framed from management to maintenance and upkeep of the physical plant and infrastructure. Achieved thus determine which is the picture of the institution from the area in front of an administrative approach giving sustainability and watching some of the implications on the economy of the organization. So based on the concept of SD (Sustainable Development) and its various implications on issues such as order management, balance and social impact, environmental impact, investment on physical facilities and infrastructure, and on the general planning and development of the institution. Wanted to know how is the physical area of the ITM against the deployment and implementation of policies or actions that tend to keep the institution in time to the minimum environmental impact and contributing to future social welfare together with favorable economic results that allow the ITM able to develop a long-term sustainability. To achieve this will be taken to check such things as how power is structured and the different administrative policies that have the ITM for management. And which is the participation and contribution on the subject of Physics DS Area from the Area Support Group, which means that contribution is from the management within the ITM

Belween Words and Things ... Infinite Forms of Control

Neste artigo procuro sintetizar algumas das categorias trabalhadas por Foucault e por Deleuze ao analisarem associedades "de soberania", as "disciplinares" e as "de controle". Apropriando-me das análises feitas por estes autores em relação a estas sociedades, procuro descrever algunsdos conflitos pelos quais estamos passando para tentarmos sobreviver nesta sociedadecontemporânea, caracterizada por uma hegemônica globalização sócio-econômico-cultural, de nenhuma liberdade e infinitos controles.This article is an attempt to synthesize some of the categories worked out by Foucault and Deleuze,in examining the "sovereignty", "disciplinary" and "control" societies. Taking theauthors' analysis regarding those societies, I try to describe some of the conflicts weare going through in trying to survive in contemporary society, characterized by anhegemonic social, economic and cultural globalization, where there is no freedom butplenty of infinite controls

Brasil, um país de todos? : As faces da hostilidade em narrativas de estudantes universitários refugiados

The present article aims to analyze the formation of the experience of cultural differences and the acceptance difficulties faced by refugee students in a federal public university. The study adopts a qualitative and exploratory approach, using individual narrative interviews with the refugee students themselves. From the collected narratives, it is observed that conditioned hospitality emerges as a significant obstacle in the refugees’ journey, intertwined with memories that highlight the persistent presence of structural racism and xenophobia. The presence of migrants in the Brazilian territory, although in some cases facilitated by university access policies, is affected by feelings such as guilt, shame, and fear, which directly impact their strategies for adaptation and survival in the country. These challenges extend to the realms of work, education, and health. The constant threat of extradition remains latent, both in the racist discourses and attitudes that permeate Brazilian daily life and in institutional practices that segregate bodies considered “foreign”.El presente artículo tiene como propósito analizar la formación de la experiencia de las diferencias culturales y las dificultades de aceptación enfrentadas por los estudiantes refugiados en una universidad pública federal. El estudio adopta un enfoque cualitativo y exploratorio, utilizando entrevistas narrativas individuales con los propios estudiantes refugiados. A partir de las narrativas recopiladas, se observa que la hospitalidad condicionada se revela como un obstáculo significativo en el camino de los refugiados, entrelazada con recuerdos que resaltan la persistente presencia del racismo estructural y la xenofobia. La presencia de los migrantes en el territorio brasileño, aunque en algunos casos sea facilitada por políticas de acceso a la universidad, se ve afectada por sentimientos como culpa, vergüenza y miedo, que impactan directamente en sus estrategias de adaptación y supervivencia en el país. Estos desafíos se extienden a los ámbitos del trabajo, la educación y la salud. La constante amenaza de extradición permanece latente, tanto en los discursos y actitudes racistas que impregnan el día a día brasileño, como en las prácticas institucionales que segregan a los cuerpos considerados “extraños”.O presente artigo tem como propósito analisar a formação da vivência das diferenças culturais e as dificuldades de aceitação enfrentadas pelos estudantes refugiados em uma universidade pública federal. O estudo adota uma abordagem qualitativa e exploratória, utilizando entrevistas narrativas individuais com os próprios estudantes refugiados. A partir das narrativas coletadas, observa-se que a hospitalidade condicionada se revela como um obstáculo marcante na jornada dos refugiados, entrelaçada com lembranças que destacam a presença persistente do racismo estrutural e da xenofobia. A presença dos migrantes no território brasileiro, embora em alguns casos seja facilitada por políticas de acesso à universidade, é impactada por sentimentos como culpa, vergonha e medo, que afetam diretamente suas estratégias de adaptação e sobrevivência no país. Tais desafios se estendem às esferas do trabalho, da educação e da saúde. A constante ameaça de extradição permanece latente, tanto nos discursos e atitudes racistas que permeiam o cotidiano brasileiro quanto nas práticas institucionais que segregam os corpos considerados “estranhos”

Fabrication and aero dynamic levitation of chalcogenide glass spheres

Spheres of gallium-lanthanum sulphide (GLS) and gallium lanthanum sulphite (GLSO) have been produced by laser irradiation on a copper hearth. Although similar fabrication techniques have been applied to oxide glasses, the technique has been overlooked for the production of chalcogenide glasses due to the perceived problem of the volatility of the chalcogens. In this work, glass microspheres of GLS/GLSO have been fabricated by laser irradiation of micron size irregular shaped glass particles on a Cu plate. In this material we found that evaporation of sulphur was not substantial as it appears to be more strongly chemically bound [1]. In addition to this method we have also established that it is possible to form larger spheres (mm diameter) of GLSO by aerodynamic levitation and laser heating using a CO2 laser (10.6 µm wavelength). Our studies involve overheating and supercooling of liquids and melts, outgassing analysis, high temperature resistivity measurements, and crystallization/structural studies [1-3]. In both fabrication methods the glasses could be melted and re-vitrified with low sulphur mass loss. We conclude that the production of glass spheres by laser irradiation[4] from irregular shaped starting material on a substrate using the wetting principle has substantial benefits for making microspheres and nanospheres