Proyectos

Es proyecto busca comparar los efectos de diversos programas de ejercicio físico en diversos parametros pronosticos en pacientes con EPOC severo

This project aims to analyze the dressing discursive-material entanglements and the political effects of apparel design on fat people. From new materialisms and posthumanisms, the body-wardrobe relationship may be thought in a continuum (Braidotti, 2015): discursive and material issues are articulated and intertwined in design (Bari, 2019; Coleman, 2008; Hekman, 2014, 2010). In this sense, apparel design is not limited to garment shapes, but as an activity or practice that installs a way of being in the world. In other words, this can be understood as a becoming, which is also material, discursive, bodily and technological. Studying clothing, as a practice, from design allows us to investigate a way of being in/with the world or worldings in which a diversity of matters occur (Haraway, 2008) that are not limited only to the constitution of the self through the use of garments. We seek to articulate the way of becoming human through design and clothing and overcome the construction of inequities and the need to reformulate design based on these dynamics. Investigating the design and clothing of the fat body overcomes the opposition between body/being and appearance. Rather, they are entangled issues (Bari, 2019) where, to name a few, not only the body and clothing are articulated, but also networks (Forlano, 2017), accessories (Merrill and Filstrup, 2013), technologies and environmental issues (Forlano, 2017). From this perspective, the human/non-human distinction is outweighed: dressing is not the action of choosing objects to wear, but a doing where things that are constituted as a network or phenomenon (Barad, 2007) in which entities and relationships have multiple forms, where objects do things. This has significant implications for the study of the fat body, as it is not only that there are no clothes which allow a diversity of possible identities, but that both fat and apparel design are constantly made in dressing: they are part of a worlding that goes away creating openly and critically in which discrimination and violence emerge but where other worldings are possible (Forlano, 2017). This research comprises a post-qualitative epistemological approach (Lather and St. Pierre, 2013), characterized by the speculative commitment of the research team which focuses on what is done, rather than what is, developing latent possibilities of what is being investigated and avoiding the logic based on the representation. Lather (2013) refers to this as QUAL 4.0; a work technique which is focused on becoming, carrying out innovative material practices in research that allow knowledge production in a different way. The project is designed in three modules: (i) Garments ethnographies (we seek to document practices, objects, agencies, bodies, technologies and apparel, among others, that are entangled in fat people apparel design and dressing), (ii) Focus groups (aim to document discriminatory practices in relation to the "being fat" experience and (iii) Design of a collection (the purpose is to intervene the entanglements where the fat body and clothing intra-act). Three kind of results are expected: (i) Fat discrimination has been widely documented in English-speaking countries; however, we do not have data on Chile. This project aims to produce information and situated knowledge about fat discrimination. (ii) It is expected to articulate different disciplines such as socialpsychology, so ciology and design in a transdisciplinary and novel relationship. And (iii) as part of the research we expect to intervene the reality we are studying. This is, the design of a clothing collection will be made with a co-participatory strategy as praxis (Lather, 1986), as a form of action and participation.

Las interacciones entre los individuos (médicos, pacientes, familias, entre otros), objetos (protocolos, evidencia, infraestructura y medicamentos por ejemplo) y procedimientos (ensayos clínicos, la producción de evidencia, intervenciones médicas, etc.) forman redes socio-médicas y colectivos híbridos que moldean las decisiones de salud. Estas redes se encuentran atravesadas por tensiones como la relación médico-paciente, el mercado farmacéutivo y la producción de la evidencia científica. Sin embargo, en las enfermedades raras estas tensiones no se articulan de la misma forma. Para que una enfermedad sea denominada como rara, debe tener una incidencia menor a 1 en 2000 personas según el criterio europeo. A diferencia de las enfermedades frecuentes, quienes padecen una enfermedad rara tienen una expectativa de vida muy limitada, la relación médico-paciente se deconoce en un escenario donde el/la enfermo/a o sus cuidadores pueden saber más que el especialista y las muestras naturalmente pequeñas hacen difícil el desarrollo de evidencia científica para la construcción de guías y protocolos, así como para la aprobación de terapias farmacológicas. En este sentido, las enfermedades raras son objetos epistémicos. Esto es, objetos o cosas indeterminadas e incompletas en relación con los objetos cotidianos más sólidos y que se encuentran en un proceso continuo de ser definido materialmente. En ellos los fenómenos e instrumentos, el objeto y la experiencia, los conceptos y métodos están entremezclados en un proceso continuo de producción mutua. Las enfermedades raras, como categoría de objetos epistémicos, establecen relaciones intestables que producen simultáneamente diferentes formas de estar y ser en el mundo. Estudiar las decisiones de salud en enfermedades raras y los entramados que producen, no supone la exploración de diversas “perspectivas del mundo”, sino más bien la aceptación de “mundos” (la idea anglosajona de wordling); un giro ontológico que permite reparar la fractura cartesiana y sus efectos en las nociones de “verdad” y “adecuación”, por el reconocimiento de una pluralidad de mundos, compuestos por redes y ensamblajes de elementos heterogéneos, humanos y no humanos, cuyos tránsitos y guiones son negociados permanentemente entre sí. Para efectos de esta investigación las decisiones de salud no se consideran como cogniciones individuales, racionales y soberanas, sino como aquellas que se producen a partir de colectivos híbridos anclados en la idea de biociudadanía. De allí que no están localizadas en objetos o individuos particulares, sino en cogniciones colectivas producidas en redes socio-médicas -paráfrasis de las redes socio-técnicas- que permite subrayar el carácter biociudadano y biomédico que contexualizan a las decisiones de salud en el caso de las enfermedades raras. El objetivo que guía esta investigación es: Explorar las interacciones y relaciones cotidianas que constituyen colectivos híbridos y redes socio-médicas en relación a las enfermedades raras, y su impacto en las decisiones de salud en este heterogéneo tipo de condiciones. Para esto se proponen los siguientes objetivos específicos: 1. Explorar los colectivos híbridos y redes socio-médicas que individuos, objetos y procedimientos constituyen en este tipo de condiciones. 2. Analizar las prácticas, materialidades y lógicas que emergen de estas relaciones y son relevantes en la toma de decisiones de salud de enfermedades raras. 3. Explorar las subjetividades, identidades y biociudadanías producidas en los colectivos híbridos en torno a las enfermedades raras. 4. Analizar la configuración de escenarios de desigualdad y precariedad en torno a las enfermedades raras, desde la constitución de redes socio-médicas y colectivos híbridos en el contexto chileno. La metodología de esta investigación se desprende de un enfoque epistemológico post-cualitativo. El diseño consiste en tres modúlos: (1) Módulo de entramados normativos y prácticas expertas (análisis de documentos sobre diagnóstico y tratamiento de enfermedades raras en Chile, etnografía de dispositivos y entrevistas a expertos), (2) Módulo de biociudadanías (análisis de documentos de organizaciones de pacientes, etnografías de prácticas con organizaciones de pacientes y narrativas postcualitativas) y (3) Módulo de redes socio-médicas y colectivos híbridos (foros híbridos). En los resultados esperados, este estudio impacta en tres áreas de los estudios sociales de la salud: (1) Aproximadamente un 5,6% de la población chilena. Producir información respecto a la toma de decisiones de salud es una contribución a cualquier persona con este tipo de enfermedades.(2) La capacidad de acceder a diversas redes para la gestión de decisiones de salud es una dimensión que está cruzada por la desigualdad social, particularmente en el caso chileno donde vivir con una enfermedad rara es vivir en una doble vulneración. (3) Este estudio permite entender que hay cosas no-médicas que están en juego en las decisiones de salud, y en ese sentido, también aporta a pensar las decisiones en enfermedades frecuentes, en tanto permite explorar otras dimensiones de las decisiones de salud, que se invisibilizan más cuando están normalizadas por una ocurrencia más frecuente.

The School Integration Program (PIE) is one of the most critical educational inclusion policies in Chile. PIE is a form of special subsidy to schools, using as criteria temporary and permanent special educational needs. It is found throughout the national territory, considered successful at the implementation level and in the integration of new support professionals. However, it has received criticism such as the low relationship with concepts such as school effectiveness, the individualization, and stigmatization of program users by focusing on deficits and not so much on barriers and facilitators of inclusion, as well as the low access and participation of students with disabilities. Furthermore, few studies list children participating in PIE as primary informants. The present study seeks to know and analyze boys' and girls' daily experiences with disabilities in various areas of the national territory. The conceptual framework is the social studies on disability to understand the experience of children with disabilities in a social context that can be both beneficial and detrimental to their school inclusion. The other reference for the project is the new social studies of childhood while promoting that children are valid informants of their realities. Objectives: This study aims to analyze the perspectives of children in situations of motor and sensory disability participating in the PIE about the barriers and facilitators for inclusion in their daily school experiences, as well as the influence that PIE has had on their school lives. Methodology: it is a qualitative study of an analytical nature to be carried out in 5 macro zones of the national territory for three years, through specially designed narrative interviews with 31 children with motor and sensory disabilities, including interviews with the PIE coordinators of their schools. Expected results: The project hopes to generate knowledge about PIE and disability as a special educational need, based on the experience of children with disabilities, to account for their specific experiences and needs, and possible solutions to the barriers presented. It also seeks to generate specific methodological knowledge to collect data with children with disabilities. It is a transdisciplinary project in that disability is a phenomenon that must be studied from different fields; therefore, an educational psychologist, a social psychologist, an educator, and a kinesiologist are included in the researchers' team.

1. La hipertensión arterial esencial es el principal factor de riesgo cardiovascular, con una prevalencia del 30-40 % en la población adulta, que llega al 75% en mayores de 65 años. A pesar del desarrollo de fármacos, la efectividad de los tratamientos actuales es limitada. En cerca de 50% de los pacientes, el tratamiento farmacológico no logra controlar la presión arterial elevada. La hipertensión es de origen multifactorial, pero existe consenso que la disfunción endotelial juega un papel primordial en su desarrollo. La bio-disponibilidad del óxido nítrico (NO), que es el principal vasodilatador, está reducida en la mayoría de las enfermedades vasculares debido al estrés oxidativo y al aumento de la expresión y actividad de arginasa, una enzima que compite por el sustrato del NO. Este proyecto desarrollamos una nueva combinación farmacológica dirigida a proteger el NO, combinando las propiedades vasodilatadoras y anti-remodeladoras del inhibidor de la arginasa ácido 2(s)-Amino-6-Boronohexanoico (ABH) y de del antioxidante N-Acetilcisteína (NAC). Buscamos introducir una nueva forma de enfocar el tratamiento para la hipertensión arterial, atacando con esta formulación farmacológica los mecanismos moleculares que subyacen a la disfunción endotelial: baja bio-disponibilidad de NO y aumento del estrés oxidativo. En un modelo de hipertensión en ratas inducido por hipoxia intermitente crónica, cuya presión fue monitorizada por telemetría, evaluamos el efecto de la combinación sobre la hipertensión arterial y la disfunción vascular. La combinación ABH+NAC reduce la presión arterial elevada, revierte la reducción del diámetro interno de las arterias, regulariza la función endotelial y contráctil en arterias y disminuye el estrés oxidativo. No encontramos efectos adversos sobre la función renal y hepática. Estos resultados dieron origen a la presentación de dos solicitudes de patentes en Chile y de protección CTP en el extranjero para un nuevo método de síntesis de ABH y de los efectos benéficos de la combinación sobre la hipertensión y disfunción endotelial. En conjunto con el Laboratorio Andrómaco se estableció una estrategia de propiedad industrial ex post, así como las acciones científico-tecnológicas conducentes a las siguientes fases de desarrollo del medicamento: pruebas preclínicas en otros modelos de hipertensión, desarrollo galénico y/o fase clínica I. Dado que el resultado de producción de la formulación deberá pasar aún por pruebas clínicas antes de ser dispuesto a los beneficiarios, la patente de este nuevo fármaco podrá ser utilizada como activo principal para capturar capital de inversión que permita continuar con este proceso, o bien para licenciar a empresas con interés en el rubro. Junto a la Fundación del Adulto Mayor, desarrollamos actividades de extensión con la finalidad de informar a la comunidad y con ello contribuir a prevenir los efectos deletéreos de la hipertensión en la población de mayor riesgo cardiovascular. En esta propuesta se espera validar una nueva terapia antihipertensiva que ataque los mecanismos fisiopatológicos principales de la disfunción vascular que conduce a la hipertensión arterial esencial.

Compelling evidence shows that adverse intrauterine conditions increase the risk to develop cardiometabolic diseases in the adulthood. This concept has been called ‘Developmental Origins of Health and Disease’ (DOHaD) and relies on the activation of mechanisms sensing and signaling a diversity of stimuli during early development that later lead to higher risk of disease. The mechanisms that have been broadly suggested to be involved in these processes are epigenetic modifications in key gene promoters that could ‘record’ normal and abnormal perinatal stimuli. Intrauterine oxidative stress is a common feature in conditions with altered fetal growth (i.e. intrauterine growth restriction –IUGR-, or macrosomia). Several cellular processes require the participation of pro-oxidant molecules which are normally neutralized by antioxidant defenses. However, under determined conditions the pro-oxidants overcome these defenses inducing oxidative stress. The latter is an important stimulus that regulates vascular function and cardiovascular physiology, playing a key role in the development of cardiovascular diseases, regulating negatively the bioavailability of the main vasodilator nitric oxide (NO). In addition, the vascular system presents a high phenotypic plasticity during life, which is modulated and restricted by epigenetic mechanisms (including DNA methylation, histone post-translational modifications and micro RNAs). Interestingly, cultured placental endothelium derived from complicated pregnancies presents persistent abnormal phenotypes, characterized by altered expression of proteins involved in NO-dependent vasodilation (i.e. eNOS and arginase), suggesting an early onset of endothelial dysfunction. Preliminary data from in vitro experiments, show that this altered expression of eNOS in IUGR placenta-derived endothelial cells is accompanied by epigenetic alterations in the promoter of its gene. Moreover, these cells can be reprogrammed to a “normal type”, interfering with the molecular machinery that preserves the DNA methylation pattern. However, there are no studies addressing the role of the pro-oxidant status associated to IUGR on the epigenetic programming of placental vascular dysfunction, and whether these epigenetic changes reflect those present in other fetal vascular beds or in the adult cardiovascular system. Therefore, we hypothesized that the in utero oxidative stress, that characterizes IUGR, induces an epigenetic programming of the endothelial function, which is linked to abnormal umbilical and fetal vascular reactivity and higher risk of adult cardiovascular disease. These epigenetic changes lead to an altered expression of endothelial function-related proteins and to their response to superimposed oxidative stress in umbilical and systemic arteries in the fetus and adult guinea pig. If true, the development of IUGR in the presence of antioxidant treatment should prevent the vascular impairment in the fetus and the adult guinea pig. This hypothesis will be tested in an IUGR guinea pig model according to the following general aims (GA): GA-1. To determine whether the IUGR-associated oxidative stress induces endothelial dysfunction in umbilical and systemic arteries, altering the basal expression of proteins implicated in the NO-dependent vasodilation (NO-DV) pathway and their response to oxidative stress; GA-2. To determine in umbilical artery (UAEC) and aortic (AEC) endothelial cells whether endothelial dysfunction induced by fetal oxidative stress associates with epigenetic changes in the promoter of genes implicated in the NO-DV pathway, altering their response to oxidative stress in vitro; GA-3. To determine in adult life whether the IUGR-associated oxidative stress results in increased markers of endothelial dysfunction, oxidative stress and cardiovascular disease. GA-4. To determine in AEC of adults born with IUGR whether endothelial dysfunction induced by fetal oxidative stress is associated with epigenetic changes in the promoter of genes implicated in the NO-DV pathway and their response to oxidative stress in vitro, correlating them with those found at term of gestation. IUGR will be induced by uterine artery ligation in a pregnant sow, and the role of oxidative stress in the vascular programming will be analyzed treating IUGR pregnancies with the antioxidant N-acetylcysteine. The acute effect of pro- and anti-oxidants on vascular reactivity and NO-dependent vasodilation will be determined by wire-myography in IUGR near-term fetuses and adults guinea pig arteries. Further, the presence of proteins related with NO-dependent vasodilation (eNOS, arginase, HO-1, NQO1 and DHFR) in these vessels will be determined by immunohistochemistry. Endothelial epigenetic programming will be analyzed in primary cell cultures from UAEC and AEC in near-term fetuses and AEC in adult guinea pigs. Our expected outcome is to demonstrate that oxidative stress is one of the main sources of the IUGR-induced dysfunction in fetal and adult vascular beds. Further, we expect that the NAC treatment should be able to prevent partially or totally the programmed vascular impairment. This project is not only relevant to uncover the developmental mechanisms that determine short- and long-term vascular dysfunction, but also to propose eventual treatments in complicated pregnancies, that unfortunately present a very high rate in humans.

During the last decades, compelling evidence shows how the context in which early life takes place impinges risk or protection for later development of non-communicable chronic diseases. In this regard, impaired fetal growth, as occur in the fetal growth restriction (FGR), leads to a higher risk for later cardiovascular diseases, an effect that would be mediated by accelerated aging at molecular, structural, and functional levels. FGR remains a leading cause of perinatal morbidity and mortality, affecting ~10% of pregnancies, but ranging 5 to 25% depending on the nutritional and health conditions of the population surveyed, with a higher prevalence among pregnant women of low socioeconomic status. In the clinic, FGR is normally defined by a fetal weight below the 10th percentile, however, new evidence shows that impaired intrauterine growth may affect several neonates born over the 10th percentile, which may be missed from the perinatal survey for preventing adverse outcomes. This points out the need for further studies to improve the understanding and identification of altered fetal growth trajectories and their consequences on vascular function. Studies in placenta show that FGR vascular dysfunction is also found at birth in chorionic and umbilical arteries. We have demonstrated the presence of functional and molecular markers (e.g. epigenetic changes) of endothelial dysfunction in human umbilical and chorionic vessels, findings that have been further confirmed by comparing systemic (aorta and femoral arteries) and umbilical arteries in animal models of FGR. These traits suggest that umbilical artery endothelial cells (HUAEC) can be used as a surrogate to explore the vascular programming within the fetus, however, their translation to clinical preventive applications for promoting healthy aging deserves further studies. It worth noting that fetal reduced oxygen supply (i.e. fetal hypoxia) and altered blood flow patterns (i.e. shear stress) are key clinical markers in the FGR, independently of the constraints leading to impaired growth, and both factors exert a tight control of vascular development and function across life. However, how these key stimuli interact and impose an epigenetic program on the endothelial function remains elusive. This proposal will focus on the crosstalk between hypoxia and shear stress that results in the endothelial programming related to impaired fetal growth, and the molecular mechanisms that mediate the vascular responses to these stimuli. Furthermore, we will address if these molecular markers may allow detecting early vascular aging in FGR subjects beyond the 10th centile cutoff. We hypothesize that “Impaired fetal growth conditions are associated with epigenetic programming of aging- and mechanosensing-related miRNAs and transcripts in the endothelium, which can be triggered by the confluence of altered flow patterns and hypoxia resulting in molecular and structural pro-hypertensive biomechanical vascular properties”. This hypothesis will be addressed by three General Objectives (GO) involving ex vivo, in vitro, and in vivo observational and mechanistic approaches: GO1 To demonstrate, in HUAEC, whether late FGR results in epigenetic changes related to the regulation of vascular aging and the expression of mechanosensing mechanisms involved in the endothelial-dependent relaxation, and their relationship with general prenatal parameters of vascular health. GO1 will be performed by recruiting HUAEC samples from late FGR and control pregnancies, to assess transcriptomic and DNA methylation analyses that will be crossed with prenatal clinical data. GO2 To study, in vivo, whether stimuli related to FGR (i.e. hypoxia and altered shear stress) differentially regulate mechanosensing pathways involved in the endothelial-dependent relaxation and their relationship with the in vivo and ex vivo vascular properties (e.g. functional and biomechanical). GO2 will be performed in chicken embryos exposed to hypoxia and treated with agents targeting mechanosensing pathways, in which wall shear stress will be determined by Ultrasound Localization Microscopy, with complementary functional, structural, and molecular analyses. GO 3. To study, in cultured HUAEC, whether stimuli related to impaired fetal growth converge in the regulation of mechanosensing-and aging-related transcripts and miRNA, contributing to the cellular programming of endothelial dysfunction. OG3 will be performed in HUAEC exposed, in vitro, to sustained hypoxia and diverse flow patterns (shear stress), in which target DNA methylation, miRNA, transcripts, and proteins will be assessed. Our expected outcome is to improve the knowledge about the endothelial epigenetic programming after FGR and enhance the characterization of in vivo shear stress patterns and mechanisms induced by chronic fetal hypoxia. This project is not only relevant to uncover the developmental approaches for diagnosing and treatments in complicated pregnancies.