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.

Quality assurance for precast plants and treatment of imperfections for architectural facades

Quality is the threshold or minimum level required to satisfy the consumer´s demands. In construction the quality is objective, and established by standards. It is very difficult to establish the costs of “no quality” in construction. Each precast unit shall be traceable to a specific set of quality control records.

Diagnosis and Management of Grain-Induced Asthma

Grain-induced asthma is a frequent occupational allergic disease mainly caused by inhalation of cereal flour or powder. The main professions affected are bakers, confectioners, pastry factory workers, millers, farmers, and cereal handlers. This disorder is usually due to an IgE-mediated allergic response to inhalation of cereal flour proteins. The major causative allergens of grain-related asthma are proteins derived from wheat, rye and barley flour, although baking additives, such as fungal α-amylase are also important. This review deals with the current diagnosis and treatment of grain-induced asthma, emphasizing the role of cereal allergens as molecular tools to enhance diagnosis and management of this disorder. Asthma-like symptoms caused by endotoxin exposure among grain workers are beyond the scope of this review. Progress is being made in the characterization of grain and bakery allergens, particularly cereal-derived allergens, as well as in the standardization of allergy tests. Salt-soluble proteins (albumins plus globulins), particularly members of the α-amylase/trypsin inhibitor family, thioredoxins, peroxidase, lipid transfer protein and other soluble enzymes show the strongest IgE reactivities in wheat flour. In addition, prolamins (not extractable by salt solutions) have also been claimed as potential allergens. However, the large variability of IgE-binding patterns of cereal proteins among patients with grain-induced asthma, together with the great differences in the concentrations of potential allergens observed in commercial cereal extracts used for diagnosis, highlight the necessity to standardize and improve the diagnostic tools. Removal from exposure to the offending agents is the cornerstone of the management of grain-induced asthma. The availability of purified allergens should be very helpful for a more refined diagnosis, and new immunomodulatory treatments, including allergen immunotherapy and biological drugs, should aid in the management of patients with this disorder.

Propuesta metodológica para el análisis y protección de la calidad del agua subterránea de acuerdo con los requerimientos de la Directiva Marco y la Directiva derivada de Aguas Subterráneas

La protección de las aguas subterráneas es una prioridad de la política medioambiental de la UE. Por ello ha establecido un marco de prevención y control de la contaminación, que incluye provisiones para evaluar el estado químico de las aguas y reducir la presencia de contaminantes en ellas. Las herramientas fundamentales para el desarrollo de dichas políticas son la Directiva Marco del Agua y la Directiva Hija de Aguas Subterráneas. Según ellas, las aguas se consideran en buen estado químico si: • la concentración medida o prevista de nitratos no supera los 50 mg/l y la de ingredientes activos de plaguicidas, de sus metabolitos y de los productos de reacción no supera el 0,1 μg/l (0,5 μg/l para el total de los plaguicidas medidos) • la concentración de determinadas sustancias de riesgo es inferior al valor umbral fijado por los Estados miembros; se trata, como mínimo, del amonio, arsénico, cadmio, cloruro, plomo, mercurio, sulfatos, tricloroetileno y tetracloroetileno • la concentración de cualquier otro contaminante se ajusta a la definición de buen estado químico enunciada en el anexo V de la Directiva marco sobre la política de aguas • en caso de superarse el valor correspondiente a una norma de calidad o a un valor umbral, una investigación confirma, entre otros puntos, la falta de riesgo significativo para el medio ambiente. Analizar el comportamiento estadístico de los datos procedentes de la red de seguimiento y control puede resultar considerablemente complejo, debido al sesgo positivo que suelen presentar dichos datos y a su distribución asimétrica, debido a la existencia de valores anómalos y diferentes tipos de suelos y mezclas de contaminantes. Además, la distribución de determinados componentes en el agua subterránea puede presentar concentraciones por debajo del límite de detección o no ser estacionaria debida a la existencia de tendencias lineales o estacionales. En el primer caso es necesario realizar estimaciones de esos valores desconocidos, mediante procedimientos que varían en función del porcentaje de valores por debajo del límite de detección y el número de límites de detección aplicables. En el segundo caso es necesario eliminar las tendencias de forma previa a la realización de contrastes de hipótesis sobre los residuos. Con esta tesis se ha pretendido establecer las bases estadísticas para el análisis riguroso de los datos de las redes de calidad con objeto de realizar la evaluación del estado químico de las masas de agua subterránea para la determinación de tendencias al aumento en la concentración de contaminantes y para la detección de empeoramientos significativos, tanto en los casos que se ha fijado un estándar de calidad por el organismo medioambiental competente como en aquéllos que no ha sido así. Para diseñar una metodología que permita contemplar la variedad de casos existentes, se han analizado los datos de la Red Oficial de Seguimiento y Control del Estado Químico de las Aguas Subterráneas del Ministerio de Agricultura, Alimentación y Medio Ambiente (Magrama). A continuación, y dado que los Planes Hidrológicos de Cuenca son la herramienta básica de las Directivas, se ha seleccionado la Cuenca del Júcar, dada su designación como cuenca piloto en la estrategia de implementación común (CIS) de la Comisión Europea. El objetivo principal de los grupos de trabajo creados para ello se dirigió a implementar la Directiva Derivada de Agua Subterráneas y los elementos de la Directiva Marco del Agua relacionadas, en especial la toma de datos en los puntos de control y la preparación del primer Plan de Gestión de Cuencas Hidrográficas. Dada la extensión de la zona y con objeto de analizar una masa de agua subterránea (definida como la unidad de gestión en las Directivas), se ha seleccionado una zona piloto (Plana de Vinaroz Peñiscola) en la que se han aplicado los procedimientos desarrollados con objeto de determinar el estado químico de dicha masa. Los datos examinados no contienen en general valores de concentración de contaminantes asociados a fuentes puntuales, por lo que para la realización del estudio se han seleccionado valores de concentración de los datos más comunes, es decir, nitratos y cloruros. La estrategia diseñada combina el análisis de tendencias con la elaboración de intervalos de confianza cuando existe un estándar de calidad e intervalos de predicción cuando no existe o se ha superado dicho estándar. De forma análoga se ha procedido en el caso de los valores por debajo del límite de detección, tomando los valores disponibles en la zona piloto de la Plana de Sagunto y simulando diferentes grados de censura con objeto de comparar los resultados obtenidos con los intervalos producidos de los datos reales y verificar de esta forma la eficacia del método. El resultado final es una metodología general que integra los casos existentes y permite definir el estado químico de una masa de agua subterránea, verificar la existencia de impactos significativos en la calidad del agua subterránea y evaluar la efectividad de los planes de medidas adoptados en el marco del Plan Hidrológico de Cuenca. ABSTRACT Groundwater protection is a priority of the EU environmental policy. As a result, it has established a framework for prevention and control of pollution, which includes provisions for assessing the chemical status of waters and reducing the presence of contaminants in it. The measures include: • criteria for assessing the chemical status of groundwater bodies • criteria for identifying significant upward trends and sustained concentrations of contaminants and define starting points for reversal of such trends • preventing and limiting indirect discharges of pollutants as a result of percolation through soil or subsoil. The basic tools for the development of such policies are the Water Framework Directive and Groundwater Daughter Directive. According to them, the groundwater bodies are considered in good status if: • measured or predicted concentration of nitrate does not exceed 50 mg / l and the active ingredients of pesticides, their metabolites and reaction products do not exceed 0.1 mg / l (0.5 mg / l for total of pesticides measured) • the concentration of certain hazardous substances is below the threshold set by the Member States concerned, at least, of ammonium, arsenic, cadmium, chloride, lead, mercury, sulphates, trichloroethylene and tetrachlorethylene • the concentration of other contaminants fits the definition of good chemical status set out in Annex V of the Framework Directive on water policy • If the value corresponding to a quality standard or a threshold value is exceeded, an investigation confirms, among other things, the lack of significant risk to the environment. Analyzing the statistical behaviour of the data from the monitoring networks may be considerably complex due to the positive bias which often presents such information and its asymmetrical distribution, due to the existence of outliers and different soil types and mixtures of pollutants. Furthermore, the distribution of certain components in groundwater may have concentrations below the detection limit or may not be stationary due to the existence of linear or seasonal trends. In the first case it is necessary to estimate these unknown values, through procedures that vary according to the percentage of values below the limit of detection and the number of applicable limits of detection. In the second case removing trends is needed before conducting hypothesis tests on residuals. This PhD thesis has intended to establish the statistical basis for the rigorous analysis of data quality networks in order to conduct the evaluation of the chemical status of groundwater bodies for determining upward and sustained trends in pollutant concentrations and for the detection of significant deterioration in cases in which an environmental standard has been set by the relevant environmental agency and those that have not. Aiming to design a comprehensive methodology to include the whole range of cases, data from the Groundwater Official Monitoring and Control Network of the Ministry of Agriculture, Food and Environment (Magrama) have been analysed. Then, since River Basin Management Plans are the basic tool of the Directives, the Júcar river Basin has been selected. The main reason is its designation as a pilot basin in the common implementation strategy (CIS) of the European Commission. The main objective of the ad hoc working groups is to implement the Daughter Ground Water Directive and elements of the Water Framework Directive related to groundwater, especially the data collection at control stations and the preparation of the first River Basin Management Plan. Given the size of the area and in order to analyze a groundwater body (defined as the management unit in the Directives), Plana de Vinaroz Peñíscola has been selected as pilot area. Procedures developed to determine the chemical status of that body have been then applied. The data examined do not generally contain pollutant concentration values associated with point sources, so for the study concentration values of the most common data, i.e., nitrates and chlorides have been selected. The designed strategy combines trend analysis with the development of confidence intervals when there is a standard of quality and prediction intervals when there is not or the standard has been exceeded. Similarly we have proceeded in the case of values below the detection limit, taking the available values in Plana de Sagunto pilot area and simulating different degrees of censoring in order to compare the results obtained with the intervals achieved from the actual data and verify in this way the effectiveness of the method. The end result is a general methodology that integrates existing cases to define the chemical status of a groundwater body, verify the existence of significant impacts on groundwater quality and evaluate the effectiveness of the action plans adopted in the framework of the River Basin Management Plan.

PREDIRCAM eHealth platform for individualized telemedical assistance for lifestyle modification in the treatment of obesity, diabetes, and cardiometabolic risk prevention: a pilot study (PREDIRCAM 1)

Background: Healthy diet and regular physical activity are powerful tools in reducing diabetes and cardiometabolic risk. Various international scientific and health organizations have advocated the use of new technologies to solve these problems. The PREDIRCAM project explores the contribution that a technological system could offer for the continuous monitoring of lifestyle habits and individualized treatment of obesity as well as cardiometabolic risk prevention. Methods: PREDIRCAM is a technological platform for patients and professionals designed to improve the effectiveness of lifestyle behavior modifications through the intensive use of the latest information and communication technologies. The platform consists of a web-based application providing communication interface with monitoring devices of physiological variables, application for monitoring dietary intake, ad hoc electronic medical records, different communication channels, and an intelligent notification system. A 2-week feasibility study was conducted in 15 volunteers to assess the viability of the platform. Results: The website received 244 visits (average time/session: 17 min 45 s). A total of 435 dietary intakes were recorded (average time for each intake registration, 4 min 42 s ± 2 min 30 s), 59 exercises were recorded in 20 heart rate monitor downloads, 43 topics were discussed through a forum, and 11 of the 15 volunteers expressed a favorable opinion toward the platform. Food intake recording was reported as the most laborious task. Ten of the volunteers considered long-term use of the platform to be feasible. Conclusions: The PREDIRCAM platform is technically ready for clinical evaluation. Training is required to use the platform and, in particular, for registration of dietary food intake.