Evolution and treatment of vitamin B12 deficiency as a risk factor for (cognitive and functional) neurodegenerative diseases in institutionalized elderly = Evolución y tratamiento de la deficiencia de vitamina B12 como factor de riesgo de enfermedades neurodegenerativas (cognitivas y funcionales) en las personas mayores institucionalizadas.

Prevalence of vitamin B12 deficiency is very common in elderly people and can reach values as high as 40.5% of the population. It can be the result of the interaction among several factors. Vitamin B12 deficiencies have been associated with neurological, cognitive deterioration, haematological abnormalities and cardiovascular diseases that have an important influence on the health of the elderly and their quality of life. It is necessary to approach the problems arisen from the lack of data relative to them. The main objective of this thesis was to analyse the evolution of vitamin B12 status and related parameters, lipid and haematological profiles and their relationship to health risk factors, and to functional and cognitive status over one year and to determine the effect of an oral supplementation of 500 μg of cyanocobalamin for a short period of 28 days. An additional objective was to analyze the possible effects of medicine intakes on vitamin B status. Three studies were performed: a) a one year longitudinal follow-up with four measure points; b) an intervention study providing an oral liquid supplement of 500 μg of cyanocobalamin for a 28 days period; and c) analysis of the possible effect of medication intake on vitamin B status using the ATC classification of medicines. The participants for these studies were recruited from nursing homes for the elderly in the Region of Madrid. Sixty elders (mean age 84 _ 7y, 19 men and 41 women) were recruited for Study I and 64 elders (mean age 82 _ 7y, 24 men and 40 women) for Study II. For Study III, baseline data from the initially recruited participants of the first two studies were used. An informed consent was obtained from all participants or their mentors. The studies were approved by the Ethical Committee of the University of Granada. Blood samples were obtained at each examination date and were analyzed for serum cobalamin, holoTC, serum and RBC folate and total homocysteine according to laboratory standard procedures. The haematological parameters analyzed were haematocrit, haemoglobin and MCV. For the lipid profile TG, total cholesterol, LDL- and HDLcholesterol were analyzed. Anthropometric measures (BMI, skinfolds [triceps and subscapular], waist girth and waist to hip ratio), functional tests (hand grip, arm and leg strength tests, static balance) and MMSE were obtained or administered by trained personal. The vitamin B12 supplement of Study II was administered with breakfast and the medication intake was taken from the residents’ anamnesis. Data were analyzed by parametric and non-parametric statistics depending on the obtained data. Comparisons were done using the appropriate ANOVAs or non-parametric tests. Pearsons’ partial correlations with the variable “time” as control were used to define the association of the analyzed parameters. XIII The results showed that: A) Over one year, in relationship to vitamin B status, serum cobalamin decreased, serum folate and mean corpuscular volumen increased significantly and total homocysteine concentrations were stable. Regarding blood lipid profile, triglycerides increased and HDL-cholesterol decreased significantly. Regarding selected anthropometric measurements, waist circumference increased significantly. No significant changes were observed for the rest of parameters. B) Prevalence of hyperhomocysteinemia was high in the elderly studied, ranging from 60% to 90 % over the year depending on the cut-off used for the classification. LDL-cholesterol values were high, especially among women, and showed a tendency to increase over the year. Results of the balance test showed a deficiency and a tendency to decrease; this indicates that the population studied is at high risk for falls. Lower extremity muscular function was deficient and showed a tendency to decrease. A highly significant relationship was observed between the skinfold of the triceps and blood lipid profile. C) Low cobalamin concentrations correlated significantly with low MMSE scores in the elderly studied. No correlations were observed between vitamin B12 status and functional parameters. D) Regarding vitamin B12 status, holo-transcobalamin seems to be more sensitive for diagnosis; 5-10% of the elderly had a deficiency using serum cobalamin as a criterion, and 45-52% had a deficiency when using serum holotranscobalamin as a criterion. E) 500 μg of cyanocobalamin administered orally during 28 days significantly improved vitamin B12 status and significantly decreased total homocysteine concentrations in institutionalized elderly. No effect of the intervention was observed on functional and cognitive parameters. F) The relative change (%) of improvement of vitamin B12 status was higher when using serum holo-transcobalamin as a criterion than serum cobalamin. G) Antiaenemic drug intake normalized cobalamin, urologic drugs and corticosteroids serum folate, and psychoanaleptics holo-transcobalamin levels. Drugs treating pulmonary obstruction increased total homocysteine concentration significantly. H) The daily mean drug intake was 5.1. Fiftynine percent of the elderly took medication belonging to 5 or more different ATC groups. The most prevalent were psycholeptic (53%), antiacid (53%) and antithrombotic (47%) drugs.

Arquitectura Petite: Charlotte Perriand & Kazuyo Sejima. Una historia transnacional

La tesis revela paralelismos y conexiones entre las arquitectas/diseñadoras Charlotte Perriand (1903-1999) y Kazuyo Sejima (n. 1956), reflejados en una serie de proyectos de pequeña escala que denomino arquitectura petite—mobiliario tecnológico habitable—, resultado de momentos semejantes de cambio social, cultural, económico, industrial y transnacional en Francia en la década de 1920 y en Japón en la década de 1980. Este trabajo dirige su atención a la arquitectura doméstica concebida desde el interior por arquitectos con una formación complementaria en diseño de mobiliario. A su vez, profundiza en la relación que se establece entre el diseño de una casa y el diseño de un mueble, una máquina o un vestido. Los pequeños proyectos, próximos al mobiliario, diseñados por Sejima, no han sido suficientemente estudiados, al igual que los proyectos de arquitectura experimental proyectados por Perriand. Ambas trayectorias analizadas desde estos renovados puntos de vista se encuentran en lo que denominamos arquitectura petite. Surge así un nuevo paradigma espacial en un contexto de poder de lo femenino—en los medios de comunicación—y de intercambio cultural transnacional. Cuando el mobiliario crece y se equipa tecnológicamente para hacerse habitable por un grupo de personas, con cualidades suficientes de confort sensorial, es arquitectura petite. En 2009, Toyo Ito mostró en una conferencia en Madrid, una imagen de Sejima posando en su proyecto Pao I. Justo ochenta años antes, en 1929, Le Corbusier presentó en Buenos Aires la imagen de Perriand posando para su Chaise Longue. La coincidencia de ambas fotografías, junto con la lectura de dos inspiradores artículos de Toyo Ito, “Adèle’s dream” (1984)—cuyo enigmático título utiliza un nombre francés femenino para describir una casa japonesa—y “Simple lines for Le Corbusier” (1994), dieron origen a la hipótesis central de una investigación: la comparación de dos arquitectas, sus maestros y dos objetos pertenecientes a dos momentos y lugares distantes. Perriand y Sejima fueron emblemas del concepto de Nueva Feminidad, ambas tenían éxito en la prensa generalista del momento antes de ser contratadas por Le Corbusier y Toyo Ito respectivamente. Junto a sus maestros de entonces, concibieron dos iconos de la era de la maquina y de la electrónica respectivamente, la Chaise Longue (1928) y Pao I (1985), diseñados para ellas mismas. Perriand y Sejima usaron su propio cuerpo como unidad de medida y su imagen como reclamo publicitario para la promoción de los dos objetos respectivamente. La precisión técnica, materiales de lujo y enfoque de la relajación que compartieron la Chaise Longue y Pao I sugirió un nomadismo lúdico que anticipó el desarrollo posterior de lo que denominamos de arquitectura petite por parte de Perriand y Sejima. Ambos prototipos son los antecedentes de una arquitectura de talla precisa o petite (objetos híbridos entre casa, mueble y máquina con la sensualidad como característica distintiva) que ambas arquitectas han proyectado a lo largo de su carrera, y que aúnan su interés mutuo por las propiedades físicas de los materiales, así como su formación en diseño de mobiliario y su fascinación por la moda. La tesis concluye que la arquitectura petite es la depositaria de los manifiestos de una época, la que sigue a la era de la máquina enunciada por Le Corbusier y a la era de la electrónica descrita por Toyo Ito. En este sentido, la tesis evidencia la forma en la que importantes arquitectos han concentrado ideas ambiciosas en pequeños proyectos. Las características de petite se resumen en el hecho de ser una arquitectura de límites precisos, desmontable y por tanto temporal, que explora el potencial técnico y formal de nuevos materiales importados de otras industrias, incorpora condiciones sensuales propias de su escala antropométrica, y está destinada al ocio de un grupo de personas. A modo de colofón, la tesis descubre la existencia de una historia de ficción que vincula a Charlotte Perriand y Kazuyo Sejima a través de Toyo Ito: “El diario de Adèle”. ABSTRACT This dissertation reveals parallels between the architects/designers Charlotte Perriand (1903- 1999) and Kazuyo Sejima (b. 1956), reflected in a series of small projects I call petite architecture—habitable technological furniture—, which formed during similar periods of social, cultural, economic, industrial and transnational change in France in the 1920s and in Japan in the 1980s. This research focuses on domestic architecture conceived from the inside by architects with additional training in furniture design. At the same time, it explores the relationships established between the design of a house, a piece of furniture, a machine, or a dress. Small architectural projects, close to the furniture, designed by Sejima have not been sufficiently studied, as well as the experimental architectural projects designed by Perriand. Both of their experimental trajectories analyzed from this renovated point of view converge on what we call petite architecture. Thus, it raises a new spatial paradigm in the context of feminine power within the media, as direct consumers, and transnational cultural exchange. When furniture expands and is technologically equipped to the point where it becomes habitable by a group, or groups of people, providing its occupants with sensorial comfort, it is petite architecture. In 2009, at a conference in Madrid, Ito showed a picture of Sejima posing at his Pao I (1985). Just eighty years earlier, in 1929, Le Corbusier exhibited in a conference in Buenos Aires an image of Perriand posing for his Chaise Longue (1928). The coincidence of the two photographs, along with two inspiring articles by Toyo Ito "Adèle's dream" (1984) — whose enigmatic title uses a French female name to describe a Japanese house — and "Simple lines for Le Corbusier" (1994) led to a hypothesis and an investigation comparing the two architects, their mentors, and two objects, each belonging to two distant times and places. Perriand and Sejima were emblems of the concept of New Femininity, both had success in the media of their time before being hired by Le Corbusier and Toyo Ito respectively. Together with their mentors they designed two objects that became icons of the Machine Age and the Electronic Age respectively: the Chaise Longue (1928) and Pao I (1985). Designed "for themselves," Perriand and Sejima used their own bodies as a measuring unit and their image as a publicity stunt to promote the two objects respectively. Both objects are the embryonic capsules of the architecture that pampers the scale or petite (objects that conflate residence, machine and furniture, and have sensuality as a distinctive feature). From the technical precision, luxurious materials, and approach towards relaxation, emerged a playful nomadism, which anticipated the further development of what we call petite architecture. Perriand and Sejima would develop these ideas throughout their career, pooling their interests on the physical properties of materials, formation in furniture design, and their intense interest in fashion. The dissertation concludes that petite architecture is the manifestation of an age, which follows the Machine Age defined by Le Corbusier and the Electronic Age described by Toyo Ito. In this sense, the dissertation demonstrates the way in which important architects have focused their ambitious ideas on small projects. petite characteristics are summarized as being: architecture that pampers the scale, is (de)mountable and therefore temporary, explores the formal and technical potential of novel materials and techniques imported from other industries, incorporates sensual conditions according with its anthropometric scale, and is conceived for the leisure of a group of people. In addition, by way of colophon, the dissertation discovers the existence of a fictional story that links Charlotte Perriand and Kazuyo Sejima through Toyo Ito: "Adèle's Diary".