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.

A machine learning approach to identify clinical trials involving nanodrugs and nanodevices from ClinicalTrials.gov

BACKGROUND: Clinical Trials (CTs) are essential for bridging the gap between experimental research on new drugs and their clinical application. Just like CTs for traditional drugs and biologics have helped accelerate the translation of biomedical findings into medical practice, CTs for nanodrugs and nanodevices could advance novel nanomaterials as agents for diagnosis and therapy. Although there is publicly available information about nanomedicine-related CTs, the online archiving of this information is carried out without adhering to criteria that discriminate between studies involving nanomaterials or nanotechnology-based processes (nano), and CTs that do not involve nanotechnology (non-nano). Finding out whether nanodrugs and nanodevices were involved in a study from CT summaries alone is a challenging task. At the time of writing, CTs archived in the well-known online registry ClinicalTrials.gov are not easily told apart as to whether they are nano or non-nano CTs-even when performed by domain experts, due to the lack of both a common definition for nanotechnology and of standards for reporting nanomedical experiments and results. METHODS: We propose a supervised learning approach for classifying CT summaries from ClinicalTrials.gov according to whether they fall into the nano or the non-nano categories. Our method involves several stages: i) extraction and manual annotation of CTs as nano vs. non-nano, ii) pre-processing and automatic classification, and iii) performance evaluation using several state-of-the-art classifiers under different transformations of the original dataset. RESULTS AND CONCLUSIONS: The performance of the best automated classifier closely matches that of experts (AUC over 0.95), suggesting that it is feasible to automatically detect the presence of nanotechnology products in CT summaries with a high degree of accuracy. This can significantly speed up the process of finding whether reports on ClinicalTrials.gov might be relevant to a particular nanoparticle or nanodevice, which is essential to discover any precedents for nanotoxicity events or advantages for targeted drug therapy.

Estudio de las dinámicas de pérdida de peso corporal en los programas de ejercicio físico y nutrición = Study of the dynamics of body weight loss in exercise and nutritional programs

Introducción. La obesidad puede definirse como una enfermedad metabólica crónica de origen multifactorial, lo que provoca trastornos o problemas físicos y psicológicos a la persona, con patologías asociadas que limitan la esperanza de vida y deterioran la calidad de la misma, siendo determinante para sus áreas sociales y laborales. Este trastorno metabólico crónico se caracteriza por una acumulación excesiva de energía en el cuerpo en forma de grasa, lo que lleva a un aumento de peso con respecto al valor esperado por sexo, edad y altura. La gestión y el tratamiento de la obesidad tienen objetivos más amplios que la pérdida de peso e incluyen la reducción del riesgo y la mejora de la salud. Estos pueden ser alcanzados por la pérdida modesta de peso (es decir, 10.5% del peso corporal inicial), la mejora del contenido nutricional de la dieta y un modesto incremento en la actividad física y condición física. La dieta es uno de los métodos más populares para perder peso corporal. El ejercicio es otra alternativa para perder peso corporal. El aumento de ejercicio provoca un desequilibrio cuando se mantiene la ingesta calórica. También tiene ventajas, como la mejora del tono muscular, la capacidad cardiovascular, fuerza y flexibilidad, aumenta el metabolismo basal y mejora el sistema inmunológico. Objetivos. El objetivo de esta tesis es contribuir en un estudio de intervención para aclarar la evolución del peso corporal durante una intervención de dieta y ejercicio. Para ello, se evaluaron los efectos de la edad, sexo, índice de masa corporal inicial y el tipo de tratamiento en las tendencias de pérdida de peso. Otro objetivo de la tesis era crear un modelo de regresión lineal múltiple capaz de predecir la pérdida de peso corporal después del periodo de intervención. Y, por último, determinar el efecto sobre la composición corporal (peso corporal, índice de masa corporal, la masa grasa, y la masa libre de grasa) de las diferentes intervenciones basadas en ejercicios (fuerza, resistencia, resistencia combinada con fuerza, y las recomendaciones de actividad física (grupo control)) en combinación con dieta de adultos con sobrepeso y obesidad, después de la intervención, así como los cambios de la composición corporal 3 años más tarde. Diseño de la investigación. Los datos empleados en el análisis de esta tesis son parte del proyecto “Programas de Nutrición y Actividad Física para el tratamiento de la obesidad” (PRONAF). El proyecto PRONAF es un estudio clínico sobre programas de nutrición y actividad física para el sobrepeso y la obesidad, desarrollado en España durante varios años de intervención. Fue diseñado, en parte, para comparar diferentes tipos de intervención, con el objetivo de evaluar su impacto en las dinámicas de pérdida de peso, en personas con sobrepeso y obesidad. Como diseño experimental, el estudio se basó en una restricción calórica, a la que, en algunos casos, se le añadió un protocolo de entrenamiento (fuerza, resistencia, o combinado, en igualdad de volumen e intensidad). Las principales variables para la investigación que comprende esta tesis fueron: el peso corporal y la composición corporal (masa grasa y masa libre de grasa). Conclusiones. En esta tesis, para los programas de pérdida de peso en personas con sobrepeso y obesidad con un 25-30% de la restricción calórica, el peso corporal se redujo significativamente en ambos sexos, sin tener en cuenta la edad y el tipo de tratamiento seguido. Según los resultados del estudio, la pérdida de peso realizada por un individuo (hombre o mujer) durante los seis meses puede ser representada por cualquiera de las cinco funciones (lineal, potencial, exponencial, logarítmica y cuadrática) en ambos sexos, siendo la cuadrática la que tiende a representarlo mejor. Además, se puede concluir que la pérdida de peso corporal se ve afectada por el índice de masa corporal inicial y el sexo, siendo mayor para las personas obesas que para las de sobrepeso, que muestran diferencias entre sexos sólo en la condición de sobrepeso. Además, es posible calcular el peso corporal final de cualquier participante involucrado en una intervención utilizando la metodología del proyecto PRONAF sólo conociendo sus variables iniciales de composición corporal. Además, los cuatro tipos de tratamientos tuvieron resultados similares en cambios en la composición corporal al final del período de intervención, con la única excepción de la masa libre de grasa, siendo los grupos de entrenamiento los que la mantuvieron durante la restricción calórica. Por otro lado, sólo el grupo combinado logra mantener la reducción de la masa grasa (%) 3 años después del final de la intervención. ABSTRACT Introduction. Obesity can be defined as a chronic metabolic disease from a multifactorial origin, which leads to physical and psychological impacts to the person, with associated pathologies that limit the life expectancy and deteriorate the quality of it, being determinant for the social and labor areas of the person. This chronic metabolic disorder is characterized by an excessive accumulation of energy in the body as fat, leading to increased weight relative to the value expected by sex, age and height. The management and treatment of obesity have wider objectives than weight loss alone and include risk reduction and health improvement. These may be achieved by modest weight loss (i.e. 5–10% of initial body weight), improved nutritional content of the diet and modest increases in physical activity and fitness. Weight loss through diet is one of the most popular approaches to lose body weight. Exercise is another alternative to lose body weight. The increase of exercise causes an imbalance when the caloric intake is maintained. It also has advantages such as improved muscle tone, cardiovascular fitness, strength and flexibility, increases the basal metabolism and improves immune system. Objectives. The aim of this thesis is to contribute with an interventional study to clarify the evolution of the body weight during a diet and exercise intervention. For this, the effects of age, sex, initial body mass index and type of treatment on weight loss tendencies were evaluated. Another objective of the thesis was to create a multiple linear regression model able to predict the body weight loss after the intervention period. And, finally, to determine the effect upon body composition (body weight, body mass index, fat mass, and fat-free mass of different exercise-based interventions (strength, endurance, combined endurance and strength, and physical activity recommendations group (control group)) combined with diet in overweight and obese adults, after intervention as well as body composition changes 3 years later. Research Design. The data used in the analysis of this thesis are part of the project "Programs of Nutrition and Physical Activity for the treatment of obesity" (PRONAF). The PRONAF project is a clinical trial program about nutrition and physical activity for overweight and obesity, developed in Spain for several years of intervention. It was designed, in part, to compare different types of intervention, in order to assess their impact on the dynamics of weight loss in overweight and obese people. As experimental design, the study was based on caloric restriction, which, in some cases, added a training protocol (strength, endurance, or combined in equal volume and intensity). The main research variables comprising this thesis were: body weight and body composition outcomes (fat mass and fat-free mass). Conclusions. In this thesis, for weight loss programs in overweight and obese people with 25-30% of caloric restriction, the body weight was significantly decreased in both sexes, regardless the age and type of followed treatment. According to the results of the study, the weight loss performed by an individual (male or female) during six months can be represented by any of the five functions (linear, power law, exponential, logarithmic and quadratic) in both sexes, being the quadratic one which tends to represent it better. In addition, it can be concluded that the body weight loss is affected by the initial body mass index and sex condition, being greater for the obese people than for the overweight one, showing differences between sexes only in the overweight condition. Moreover, it is possible to calculate the final body weight of any participant engaged in an intervention using the PRONAF Project methodology only knowing their initial body composition variables. Furthermore, the four types of treatments had similar results on body composition changes at the end of the intervention period, with the only exception of fat-free mass, being the training groups the ones that maintained it during the caloric restriction. On the other hand, only the combined group achieved to maintain the fat mass (%) reduced 3 years after the end of the intervention.