Convocatoria de ayudas de Proyectos de Investigación Fundamental no orientada

TECHNICAL ANNEX FOR TYPE A or B PROJECTS 1. SUMMARY OF THE PROPOSAL (the summary must be also filled in Spanish)

PROJECT: FOLLOW-UP IN HEALTHY SCHOOLCHILDREN AND IN ADOLESCENTS WITH DOWN SYNDROME: PSYCHO-ENVIRONMENTAL AND GENETIC DETERMINANTS OF PHYSICAL ACTIVITY AND ITS IMPACT ON FITNESS, CARDIOVASCULAR DISEASES, INFLAMMATORY BIOMARKERS AND MENTAL HEALTH. ACRONYM: UP&DOWN PRINCIPAL INVESTIGATOR: Prof. Ascension Marcos SUMMARY (brief and precise, outlining only the most relevant topics and the proposed objectives): Physical inactivity is worldwide considered the biggest public health problem of the 21st century. Nowadays, it is well documented that the genesis of chronic diseases occurs in early ages –even though the clinical symptoms are not observed until adulthood. The UP&DOWN study is a 3-yr longitudinal study to carry out in healthy schoolchildren and in adolescents with Down syndrome to assess the impact over time of physical activity and sedentary behaviours on health indicators such as physical fitness, metabolic and cardiovascular disease risk factors, novel inflammation-immunity biomarkers, mental health as well as to identify the psycho-environmental and genetic determinants of an active lifestyle in these populations. The main objectives in the UP&DOWN study are the following: a) To determine the patterns, interrelationships and impact on health indicators of objectively and subjectively measured physical activity, sedentary behaviours and health-related fitness (including fatness) in healthy primary and secondary schoolchildren and in adolescents with Down syndrome along a 3-yr follow-up; b) To identify the main psycho-social and environmental determinants of physical activity and sedentary behaviours in healthy primary and secondary schoolchildren along a 3-yr follow-up; c) To investigate genotype-lifestyle interactions in healthy primary and secondary schoolchildren and in adolescents with Down syndrome along a 3-yr follow-up; d) To evaluate the effect of physical activity, sedentary behaviours and health-related fitness on traditional and novel cardiovascular disease risk factors through the assessment of inflammatory biomarkers in healthy primary and secondary schoolchildren and in adolescents with Down syndrome along a 3-yr follow-up; e) To develop an on-line tool to collect epidemiological data on lifestyle and health indicators and test its potential application to school evaluation and formative task to school children. Moreover, two complementary objectives are included: f) To evaluate the food intake and hydration habits in the studies cohorts (except for adolescents with Down syndrome) along a 3-yr follow-up; g) To analyze gender differences in all research phenomena, and when possible differences between native and immigrant populations. Measurements of lifestyle behaviours and health indicators will be performed over a 3-year period in two thousand healthy schoolchildren from primary (n = 1000, Cadiz) and secondary (n = 1000, Madrid) schools, and in two hundred adolescents with Down syndrome (n = 200, Madrid). Initiatives as the UP&DOWN study will contribute to the development of the Global Strategy on Diet, Physical Activity and Health (WHO), the Spanish Strategy for Nutrition, Physical Activity and the Prevention of Obesity (NAOS Strategy from the Ministry of Health and Consumption, the current Ministry of Health and Social Policy) and the recently launched Integral Plan on Physical Activity and Sport (A+D Plan, Spanish National Sport Council).

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TÍTULO DEL PROYECTO: SEGUIMIENTO EN ESCOLARES Y EN ADOLESCENTES CON SINDROME DE DOWN: DETERMINANTES PSICO-AMBIENTALES Y GENÉTICOS DE LA ACTIVIDAD FÍSICA Y SU IMPACTO EN LA CONDICIÓN FÍSICA, ENFERMEDADES CARDIOVASCULARES, MARCADORES INFLAMATORIOS Y SALUD MENTAL ACRÓNIMO: UP&DOWN RESUMEN (breve y preciso, exponiendo sólo los aspectos más relevantes y los objetivos propuestos): La inactividad física es considerada mundialmente como el problema de salud publica más importante del siglo XXI. En la actualidad ya se ha documentado suficientemente el hecho de que la genesis de las enfermedades crónicas se producen a edades tempranas, a pesar de que los síntomas clínicos no se observen hasta la edad adulta. El estudio UP&DOWN es un estudio longitudinal de 3 años para llevar a cabo en escolares sanos y en adolescents con síndrome de Down que pretende observar el impacto en el tiempo de la actividad física y el sedentarismo sobre indicadores de salud como la condición física, factores de riesgo de enfermedades cardiovasculares y metabólicas, nuevos biomarcadores de inmuno-inflamación y salud mental, así como identificar los determinantes psico-ambientales y genéticos de un estilo de vida activo en estas poblaciones. Los principales objetivos del estudio UP&DOWN son: a) Determinar los patrones, interrelaciones e impacto sobre la salud de la actividad física medida de forma objetiva y subjetiva, los habitos sedentarios y la condición física en escolares de educación primaria y secundaria, y en adolescentes con síndrome de Down durante un periodo de 3 años; b) Identificar los principales determinantes psico-sociales y ambientales de la actividad física y el sedentarismo en escolares de primaria y secundaria durante un periodo de 3 años; c) Investigar las interacciones entre genética y estilo de vida en escolares de educación primaria y secundaria, y en adolescentes con sindrome de Down durante un periodo de 3 años; d) Evaluar el efecto de la actividad física, los hábitos sedentarios y la condición física en factores de riesgo cardiovascular mediante la valoración de marcadores de inflamación tradicionales y nuevos en escolares de educación primaria y secundaria, y en adolescentes con sindrome de Down durante un periodo de 3 años; e) Desarollar un herramienta on-line para recoger datos epidemiológicos sobre el estilo de vida e indicadores de salud, y valorar su potencial aplicación para tareas de evaluación escolar y formativas en escolares. Además, se incluyen dos objetivos complementarios: f) Evaluar la ingesta de alimentos y los hábitos de hidratación en las cohortes de estudio (excepto para los adolescentes con síndrome de Down) durante un periodo de 3 años; g) Analizar las diferencias de género en todos los fenómenos de investigación, y cuando sea posible, entre las poblaciones autóctona e inmigrante. Las mediciones del estilo de vida y los indicadores de salud se llevarán a cabo durante un período de 3 años en dos mil escolares de primaria (n=1000, Cádiz) y secundaria (n=1000, Madrid), y doscientos adolescentes con síndrome de Down (n=200, Madrid). Iniciativas como el estudio UP&DOWN contribuyen al desarrollo de la Estrategia Mundial sobre Régimen Alimentario, Actividad Física y Salud (OMS), la Estrategia Española para la Nutrición, Actividad Física y la Prevención de la Obesidad (Estrategia NAOS del Ministerio de Salud y Consumo, actual Ministerio de Sanidad y Política Social) y el recientemente promovido Plan Integral de Actividad Física y Deporte (A + D, Consejo Superior de Deportes).

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2. INTRODUCTION (maximum 5 pages)

The UP&DOWN study is a 3-yr longitudinal study to carry out in healthy schoolchildren and in adolescents with Down syndrome to assess the impact over time of physical activity and sedentary behaviours on health indicators (physical fitness, metabolic and cardiovascular disease risk factors, new inflammation-immunity biomarkers, mental health and cognitive performance) as well as to identify the psycho-environmental and genetic determinants of an active lifestyle in these populations.

Physical activity is defined as “any bodily movement produced by skeletal muscles that results in energy

expenditure” (Caspersen et al. 1985). Likewise, the dose of physical activity can be defined by its intensity, frequency, duration and mode (Caspersen et al. 1985). An accurate assessment of physical activity in humans, especially in children, represents the most important challenge for health-related research (Welk, 2002). The most accurate techniques (e.g. direct observations, doubly labelled water or indirect calorimetry) are not very feasible in large samples or to assess physical activity in free-living conditions (Sirard et al. 2001). Other objective techniques such as heart rate monitors, pedometers or accelerometers also have limitations for large-scale research projects (e.g. costs, data processing). Self-report instruments offer some advantages for assessing large populations but, because they are subjective in nature and typically rely on recall, it is important to carefully take all limitations into account when interpreting the data (Sirard et al. 2001). On the other hand, physical activity is considered a critical measure for the effective prevention of chronic diseases in children and adolescents. Evidence-based has associated physical activity with obesity, cardiorespiratory fitness, bone mass, cardiovascular risk factors, metabolic syndrome and psychological well-being in schoolchildren (Strong et al. 2005). The documented declines in physical activity levels from childhood to adulthood (Nader et al. 2008; Telama et al. 2005) are a particular concern since they may imply an increased risk for the development of chronic diseases later in life. There is currently only one study that has shown the levels of physical activity measure by objective techniques (accelerometry) in samples of Spanish children and adolescents (Martinez-Gomez et al. 2009). These studies found that approximately 30-50% of children and adolescents don’t meet the current physical activity recommendations for youth (60 min/d in moderate-to-vigorous physical activity). In addition, sedentary behaviours (TV, computer use, sitting) have been recently related to chronic diseases independently of physical activity (Hamilton et al. 2007). In Spain, available data show that between 30-45% of youth exceed the recommendations of watching TV<2 hrs/d (Vicente-Rodriguez et al. 2008; Klepp et al. 2007) and spent 8 hrd/d in sedentary activity (Martinez-Gomez et al. 2009).

Physical fitness is an important marker of health in adults and recent evidence suggest that this is also the

case for children and adolescents (Ruiz et al. 2009; Ortega et al. 2008). Health-related physical fitness refers to those components of fitness that have a relationship with health: (i) cardiorespiratory fitness, (ii) musculoskeletal fitness, (iii) motor fitness and (iv) body composition (Bouchard et al. 1994). Cardiorespiratory fitness reflects the overall capacity of the cardiovascular and pulmonary systems to supply oxygen during sustained exercise, as well as the ability to perform such exercise (Taylor et al. 1955). Results from cross-sectional studies indicate that high cardiorespiratory fitness during childhood and adolescence has been associated with a favourable plasma lipid profile (Mesa et al. 2006), with total and central body fat (Ortega et al. 2007; Ruiz et al. 2006), features of the metabolic syndrome (Ruiz et al. 2007a; Brage et al. 2004), blood pressure (Ruiz et al. 2007b), novel cardiovascular disease risk factors (Ruiz et al. 2007c), and with arterial compliance (Reed et al. 2005). Findings from longitudinal studies suggest that higher levels of cardiorespiratory fitness in childhood and adolescence are associated with a healthier cardiovascular profile later in life (Ruiz et al. 2009). The role of muscular strength in the performance of activities of daily living and exercise, as well as in the prevention of chronic diseases is increasingly being recognized (Stump et al. 2006; Wolfe, 2006). Muscular strength is associated with lipid profile (Garcia-Artero), low-grade inflammatory proteins (Ruiz et al. 2008), and insulin resistance in children and adolescents (Benson et al. 2006). Follow-up studies revealed that muscular strength improvements from childhood to adolescence are negatively associated with changes in overall adiposity (Ruiz et al. 2009). Motor fitness (also called skill-related physical fitness) is considered a marker of bone health and pubertal development (Ortega et al. 2008). Controlled trials and cross-sectional studies have reported a positive association between motor fitness (i.e. speed) levels and bone mineral content in adolescents (Ortega et al. 2008). There is no doubt about the key role that body composition plays on the health status already in the first decade of life. Body composition at childhood and adolescence seems to be a predictor of cardiovascular disease risk factors such as blood lipids and carotid artery intima media thickness later in life (Ruiz et al. 2009).

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Health-related physical fitness can be objectively and accurately measured through laboratory tests. However, due to their high cost, necessity of sophisticated instruments, qualified technicians and time constraints, their use is limited in the school setting and in population-based studies. Field-based tests provide a reasonable alternative since they are time-efficient, low-cost and low-equipment requirements, and can be easily administered to a large number of people simultaneously. The ALPHA (Assessing Levels of Physical Activity) study was a recently finished EU funded project initiated with the aim of providing a set of instruments for assessing levels of physical activity as well as health-related physical fitness in a comparable way within the European Union (http://www.thealphaproject.eu/). One of the main outcomes of the ALPHA study was to provide a set field-based fitness tests for the assessment of health-related physical fitness in children and adolescents. The tests had to be related with well established health markers, and were valid, reliable, objective and feasible to be used in children and adolescents. The selected tests were: (i) the 20m shuttle run test to assess cardiorespiratory fitness; (ii) the handgrip strength and (iii) standing broad jump to assess musculoskeletal fitness, (iv) the 4x10m to assess motor fitness, and (v) body mass index, (vi) waist circumference, and (vii) skinfold thickness (triceps and subscapular) to assess body composition.

In the majority of countries worldwide, the incidence of metabolic and cardiovascular diseases (CVD) has

increased in the last decade. Each year, the American Heart Association, in conjunction with the Centres for Disease Control and Prevention, the National Institutes of Health, and other government agencies, brings together the most up-to-date statistics on heart disease, stroke, other vascular diseases, and their risk factors and presents them in its Heart Disease and Stroke Statistical Update (Lloyd-Jones et al., 2009). On the basis of 2006 mortality rate data, nearly 2300 Americans die of CVD each day, an average of 1 death every 38 seconds. The 2007 overall preliminary death rate from CVD was 250.4. In 2010, an estimated 785 000 Americans will have a new coronary attack, and approximately 470 000 will have a recurrent attack. It is estimated that an additional 195 000 silent first myocardial infarctions occur each year. In Europe, each year CVD causes over 4.35 million deaths and over 1.9 million deaths in the EU. CVD causes nearly half of all deaths in Europe (49 %) and in the EU (42 %). CVD is the main cause of death in women in all countries of Europe and is the main cause of death in men in all countries except France and San Marino. CVD is the main cause of years of life lost from early death in Europe and the EU – around a third of years of life lost are due to CVD (European Cardiovascular Disease Statistics, 2005). The metabolic related disease is associated with an approximate two-fold increased risk of incident CV morbidity and mortality in a European population (Dekker et al. 2005).

Over 48 million adults in Europe and 23 million adults in the EU suffer from diabetes and the prevalence is

increasing (European Cardiovascular Disease Statistics. 2005). Moreover, the rising prevalence of type 2 diabetes mellitus in children and adolescents was initially recognized in the United States in the 1990s. Type 2 diabetes mellitus, which 15 years ago accounted for less than 3 % of all cases of new-onset diabetes in children and adolescents, today accounts for up to 45 % of new-onset cases among adolescents. Later studies conducted in Europe revealed a similar pattern, and more recently, reports on type 2 diabetes mellitus in children and adolescents have begun to mount worldwide (Pinhas-Hamiel et al. 2005).

New evidence indicating that the generation of pro-inflammatory biomarkers might be one mechanism

through which unhealthy lifestyles are linked to metabolic and cardiovascular diseases. In this direction, inflammatory mediators such as tumour-necrosis factor (TNF), interleukin-6 (IL-6) and C-reactive protein (CRP) appear to be important for mediating both metabolic and cardiovascular disorders. Recently, it is enough evident that there are prototypic adipocytokines such as adiponectin, leptin, resistin and visfatin providing an important link between obesity, insulin resistance and related inflammatory disorders (Mannino et al. 2006; Weisberg et al. 2006). Various other products of adipose tissue that have been characterized including IL-1 and CC-chemokine ligand 2 (CCL2; also known as MCP1) and mediators such as plasminogen-activator inhibitor type 1 and certain complement factors (Calle et al. 2004). All these and other new biomarkers have well-known roles at the interface between the immune and metabolic systems.

While sedentary behaviour has been identified as a stronger predictor of chronic diseases than risk factors such

as hypertension, hyperlipidemia, diabetes and obesity (Myers et al., 2004), regular physical activity seems to offer protection against a wide variety of these chronic disease related risk factors, probably due to its anti-inflammatory effect (Pedersen et al. 2006). Anyway, few studies have prospectively examined the effect of exercise training on low-grade inflammatory status, and the data obtained from intervention studies are less consistent when compared to cross-sectional population studies or with clinical experiments (Wärnberg et al., 2009). Data from cross-sectional observational studies have shown that both physical activity and fitness are inversely associated with low-grade inflammation in adults and elderly populations (Wärnberg et al., 2009); but this inverse association has been less consistent in children and

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adolescents (Wärnberg et al., 2007). Although several studies in children and adolescents have negatively correlated fitness with CRP, IL-6 and TNF- levels (not always been clearly independent of body fat), an objective measure of total physical activity measured by accelerometry, no cross-sectional associations with physical activity and inflammation (either CRP, fibrinogen, C3 or C4) were observed (Ruiz et al. 2007). Therefore, more research seems to be needed to elucidate the links between physical activity and fitness on inflammation and CVD.

Lifestyle factors such as diet, physical activity play a critical role in children and adolescent’s health. In addition,

genetic determinants may modulate the lifestyle impact on metabolic disorders. Accordingly, individuals exposed to an unhealthy lifestyle will develop metabolic abnormalities which may be aggravated if they also have an unfavourable genetic background (Ordovas and Mooser 2004). Dietary habits and physical activity are key lifestyle factors that may modulate gene expression throughout the various stages of life (Heck et al. 2004, Ordovas and Mooser 2004).

Over the past decade, several genetic loci have been associated with nutrition-related phenotypes such as obesity,

lipid disorders, and energy balance regulation (Loktionov 2003, Thorleifsson et al. 2009, Willer et al. 2009). Furthermore, information on the modulating effect of dietary factors and physical activity on these associations has been reported (Heck et al. 2004, Ordovas and Mooser 2004). However, most of these studies were conducted in adults and little information is available in children and adolescents.

The determinants of cardiovascular disease risk factors, how they change over time, and how changes in

lifestyle factors affect the risk of cardiovascular disease in childhood and adolescence is still not well understood. There are reasons to believe that the genotype-lifestyle interactions could also be involved in the susceptibility of individuals to develop comorbidities associated with obesity such us diabetes, hyperlipidemia, hypertension and coronary heart disease. Definition of these interaction effects for phenotypes related to these diseases is therefore important because it will eventually allow the identification of individuals at risk of the development of complications and the identification of those likely to be resistant to lifestyle interventions. The study of these genetic markers in youth and their relationship with several phenotypic characteristics of the population will permit a better understanding of the pathogenic mechanisms that are involved in non-communicable diseases.

Several studies suggested that the deleterious effect of several polymorphisms could be attenuated by

modifying the lifestyle factors, yet there are contradictory results (Heck et al. 2004, Ordovas and Mooser 2004). Moreover, it is important to highlight that most of these studies were mainly focused on adult populations. To elucidate whether physical activity and sedentary behaviours can modify the deleterious effect of certain genes polymorphisms associated with cardiovascular disease risk factors in young people is of clinical and public health relevance.

Indicators of mental health in youth are usually related to anxiety, depression, and self-concept. There are

also too few studies of physical activity and other important aspects of mental health, such as perceived stress. It must be noted that there is no studies using physical activity measures. Moreover, the dearth of prospective population cohort studies and randomized controlled trials limits conclusions about causality in results that are derived mainly from cross-sectional and quasi-experimental studies (Strong et al. 2005). On the other hand, health behaviours as academic performance are important for both public health and educational purposes. Physical activity and sedentary behaviours have shown associations with cognitive performance and academic grades in subjects such as Maths, Language and Sciences in children and adolescents, thereby the evidence is limited to cross-sectional studies or experimental studies in physical education interventions (Strong et al. 2005).

Social determinants of physical activity in youth are commonly gender, socioeconomic status (SES) and

immigrant groups (Singh et al. 2008; Van Der Horst et al. 2007). Differences in lifestyle behaviours between groups may lead specific disparities on health later in life (Hanefel, 2008). Several studies show that girls (low SES and immigrants) had lower levels of physical activity and higher levels in sedentary activities (Singh et al. 2008; Van Der Horst et al. 2007). Hence, these indicators advise culturally relevant promotion strategies to promote physical activity in these populations, but the effects of these determinants over time during childhood and adolescence have not been shown in the scientific literature.

Research addressed to identify potential determinants of physical activity and sedentary behaviour in

different population groups is essential to build effective interventions to increase physical activity levels as public health strategy. Physical activity determinants are defined as those factors that could have a causal relationship with physical

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activity/inactivity behaviour. Therefore, changing exposition to them may make a difference to expect modification of physical activity/inactivity levels. More simple approach to identification of these potential determinants are cross-sectional studies which try to identify factors associated to physical activity/inactivity levels, but any causal relationship could be infer from them. Most studies published are cross-sectional and only a few are prospective or interventional studies, which allow identifying causal relationships (Van Der Horst et al.2007).

Results from previous cross-sectional studies about physical activity correlates are considerable inconsistent

and only a few are consistently associated. Most of them have studied biological/demographic, psychological/behavioural or social correlates but quite a few have examined environmental correlates of physical activity, and only a few have studied correlates of sedentary behaviour. Both activity and sedentary behaviour have been recently shown to be independent behaviours that act independently over health (Pate et al. 2008). Moreover, concepts to understand the determinants of healthy behaviours are changing and the evaluation of environmental factors is becoming essential in an ecological approach (Sallis et al., 2006). Thus, environmental factors should be deeply studied in order to know which one/s could influence physical activity levels in children and adolescents. Furthermore, many of the key correlates of physical activity and sedentary behaviours seem to be different between children and adolescents (Van Der Horst et al. 2007) and these differences should be examined in depth.

It is important to stress the fact that most of the scientific literature deal with physical activity/sedentary

behaviour measured by self-reports, whose important limitations are nowadays widely recognized, especially in children and adolescents (Welk, 2002). Therefore, a new generation of studies on physical activity correlates are beginning to introduce objective physical activity measurements (Morgan et al. 2008; Nilsson et al., 2009; Pfeiffer et al. 2009), which permit to distinguish between different levels of physical activity intensity. This is a relevant issue since key correlates of physical activity could be different for several intensities. In addition, longitudinal studies can permit to identify causal interactions (quasi-experimental design) and correlates of evolution patterns, i.e. increase or decline over time (Van Der Horst et al. 2007).

Down syndrome (DS), which occurs once in every 800 births, is associated with a trisomy on locus 21. Down

syndrome is the most common chromosomal abnormality among live-born infants and is characterized by a variety of dysmorphic features and congenital malformations (Roizen et al., 2003). DS is associated with several pathologic conditions including immunodeficiency and high risk of infections (Yang et al., 2002) leading to high mortality in the early adulthood. An increased early apoptotic cells (especially T cells) have been recently proposed as possible mechanism explaining the predisposition of children with DS to infections (Elsayed et al. 2009). Moreover, other abnormalities in DS individual are several blood dyscrasias, including childhood leukaemias, namely acute myeloid leukemia and acute lymphoblastic or lymphocytic leukaemia. Assessments of physical activity are a challenge using subjective measures (Maher et al. 2007) and only several attempts have been conducted with objective measures (Shields et al. 2009). Similarly, fitness assessments are also complex in this population (Skowronski et al. 2009). Little is known with regard to the effect of physical activity and fitness in metabolic, CVD and immunity in this population, and the limited evidence is related to cross-sectional studies and very small samples. Thus, adolescence seems to be a key life period to develop specific strategies to promote physical activity in DS whether there is a beneficial effect on health over time; however, this is unexplored research area.

Cross-sectional studies are concerned with and designed only to describe the existing distribution of

variables, as well as the relationships between them. However, these studies only provide indicative evidence (associations) with regard to the true causal relationship (effect) between predictor variables and outcomes, thereby may lead up to erroneous conclusions (e.g. physical activity vs. obesity: 1) An obese adolescent is less physically active because of his/her obesity; 2) A low level of physical activity leads to be an obese adolescent. Likewise, cross-sectional studies describe an unchanged world by answering questions such as who, what, why, when, and where without considering time period variability in persons or environments. Thus, cross-sectional studies should be limited to trend analysis, as well as planning and obtaining hypothesis. Important cross-sectional studies have shown descriptive results in children and adolescent populations and formulated hundreds of unanswered research questions. Although only experimental designed interventions might draw causal inferences, these studies have inherent disadvantages (e.g. expensiveness, feasibility, multi-factorial interventions, sample sizes, recruitment, etc.). Another possibility to obtain the temporal effect between variables is the observational longitudinal study. Observational longitudinal studies are defined as studies in which the outcome variables are repeatedly measured and there is no specific intervention in plausible predictor variables. The rationale about possible causation in this design is called “quasi-causal relationship”.

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Moreover, in this design, the observations of one individual over time are not independent each other, and hence, individual growth/deterioration processes in all the variables may be described over time.

WHO published the report titled Obesity: Preventing and Managing Global Epidemic, where epidemiological

evidence available and consequences of global growing of obesity through worldwide was analysed and discussed (WHO, 2000). Although aetiology of obesity is a complex phenomenon, increasing physical activity levels and improving diet quality are in the core of strategies to reduce its prevalence across the world. The 57th World Health Assembly endorsed the Global Strategy on Diet, Physical Activity and Health (Waxman et al. 2004) where national governments were recommended to develop national strategies to promote healthy diet and physical activity on every country populations because of its large impact on health, against obesity and a wide spectrum of chronic diseases. The Spanish Government was the first one in Europe that developed these WHO recommendations, endorsing the Spanish Strategy for Nutrition, Physical Activity and the Prevention of Obesity (NAOS Strategy), which aims to improve diet quality and encourages the regular practice of physical activity by all citizens, with special emphasis on children (Ballesteros-Arribas et al. 2007).

In the context of a remarkable increase of social awareness about the problem of physical inactivity in the

population, in May of 2009 the Spanish National Sports Council launched the Integral Plan on Physical Activity and Sport (A+D Plan). The main aim of this Plan is to drive coordinated actions to promote physical activity and sports in the Spanish population. One of the highlighted issues in this plan is the lack of objective data necessary to develop strategies and, therefore, the necessity to promote national research efforts in this area. The objectives drawn up in this proposal are related to five of the main areas pointed out in the A+D Plan: (i) Physical activity and health promotion, (ii) Promotion of physical activity and sports in school population, (iii) Promotion of physical activity and sports in disabled people, (iv) Gender issues related to physical activity and sports and (v) Physical activity and sports in people at deprived social risk. Therefore, the results obtained from the UP&DOWN study will be valuable for future development of the Spanish A+D Plan, and in addition they will be helpful to produce relevant scientific information.

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3. OBJETIVES (maximum 2 pages) υ 3.1 Describe the reasons to present this proposal and the initial hypothesis which support its objectives

(maximum 20 lines) Physical inactivity, that is, low physical activity, is worldwide considered the biggest public health problem of the 21st century. Relevant prospective studies in adults (e.g. Aerobic Centre Longitudinal Study) have shown that physical activity, health-related fitness and sedentariness are associated with death from all causes. Nowadays, it is well documented that the genesis of chronic diseases occurs in early ages –even though the clinical symptoms are not observed until adulthood. The decline in physical activity from childhood to adulthood might explain the increase of chronic diseases early in life. However, this supposed evidence is still weak due to the use of self-report physical activity measurements. Moreover, levels of physical activity, sedentary behaviour and physical fitness during childhood and adolescence have shown to be predictors of chronic diseases later in life. The mechanisms by which an active or less sedentary lifestyle may influence the development of several diseases have not been entirely clarified and the study of new biomarkers could play a role in the knowledge of this aetiology. Patterns of physical activity and sedentary behaviours in children and adolescents seem to be affected by cultural, psychological, environmental and early life determinants. Likewise, new evidence seems to indicate that genetic susceptibility to certain diseases might be attenuated by a healthy lifestyle. Down syndrome population is predisposed to early mortality and development of obesity, inflammatory processes and infections. However, evidence is limited in this population and expected results might confirm the beneficial role of a healthy lifestyle, especially that related to physical activity on risk factors in Down syndrome from adolescence to adulthood. On the other hand, available evidence from several survey studies in Spanish children and adolescents show increase trends in several risk factors (e.g. obesity, CVD, eating disorders) that become Spain as one of the unhealthiest developed countries. Hence, monitoring of lifestyle behaviours and health indicators as well as promoting healthy lifestyle behaviours during childhood and adolescence must be two basic objectives in the Spanish Education and Public Health System. For effective action strategies, findings from Spanish longitudinal studies such as the UP&DOWN study may be taken into consideration. υ 3.2. Indicate the background and previous results of your group or the results of other groups that

support the initial hypothesis The CSIC research group has reviewed the scientific literature and there is not information regarding the effects of physical activity and fitness on early development of metabolic and cardiovascular related risk novel factors in Spanish schoolchildren and adolescents with DS. Thus, the present study is innovative according to the determination of prototypic adipokines as novel biomarkers interfacing between the immune and metabolic systems in childhood and adolescence. Thus, data from AVENA study has shown that sedentary behaviours leading to obesity, seems to contribute to higher circulating concentrations of inflammatory serum proteins (CRP, ceruloplasmin, C3, and C4). These results suggest a proinflammatory action of the adipose tissue in apparently healthy adolescents, identifying these biomarkers as risk factors for chronic diseases in adulthood. In addition, other inflammatory markers such as in vitro production of IL-6 and TNF-α have generally shown higher values in adolescents with overweight/obesity than in those with nonoverweight (Wärnberg et al., 2004). Besides AVENA, EVASYON and also HELENA studies (www.helenastudy.com) (a multicentre European project aimed to evaluate the nutritional status of the European adolescents including intervention studies), Madrid CSIC and UAM groups have recently finished a project entitled AFINOS (www.afinos.wordpress.com) aimed to measure the efficacy of physical activity on the prevalence of inflammation risk in adolescents. Prelimiminary results from AFINOS study have shown the indirect role of habitual physical activity measured by accelerometer on inflammatory markers (CRP,C3, C4 and IL-6) through fitness and body fat in an adolescent sample. Further analysis also showed the inverse and joint association of physical activity, cardiorespiratory fitness and muscular fitness on leptin and adiponectin levels, independent of body fat and insulin-resistance. The UAM research group presented the preliminary evidence of physical activity measured by accelerometer in Spanish youth and validated several self-report instruments in Spanish adolescents. UAM has also shown that subjective measures are weakly correlated with objective measures in Spanish adolescents (r≈0.3), while objective instruments such as accelerometers can measure patterns of physical activity and sedentary activity more accurately. However, several self-report instruments such as the PAQ-A, 3-d Bouchard Diary and Recess Physical Activity Recall showed reasonable validity in Spanish youth, and may be administrated to provide additional context about youth’s activity. There are a few studies assessing longitudinal assessments of physical activity in youth but only a handful used objective measures. The UAM group also examined the cross-sectional associations of physical activity with obesity, physical fitness, academic performance, cardiovascular disease risk factors, inflammatory markers and adipocytokines. On the other hand, the UAM group has also assessed sedentary behaviours using objective and subjective instruments to describe these behaviours in Spanish adolescents and investigate the relationships with academic performance and cardiovascular disease risk factors. These findings suggest that physical activity and sedentariness may play a key role on health in childhood, adolescence and later in life. Likewise, the UAM group has investigated the relationships between sport participation and obesity in children and adolescents with Down syndrome. Those findings suggested that involvement in sport activities is associated with a lower level of body fat in this population and

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a call for action was necessary since early ages. The UAM research group has also developed guidelines for schools and physical education teachers and student notebooks for the promotion of an active lifestyle in 14,000 schoolchildren involved in the PERSEO Programme (Ministry of Health and Social Policy, www.perseo.aesan.msps.es). The computer-based tools have been used in several countries as easy and cheap instruments to collect relevant data on health indicators and to provide feedback in children and adolescents for behavioural changes towards a healthy lifestyle. The most famous computer tools related to physical activity and fitness is the FITNESSGRAM programme (www.fitnessgram.net). This programme is encouraged by the famous Cooper Institute (Dallas, TX, USA) and established in the majority of USA primary and secondary schools. The UCA research group has shown that high cardiorespiratory fitness during adolescence has also been associated with healthier cardiovascular profile during these years, and later in life. We showed that high cardiorespiratory fitness during childhood and adolescence is associated with a favourable lipid profile in both overweight and non-overweight children and adolescents, with total and central body fat, features of the metabolic syndrome, insulin resistance, blood pressure and inflammation. Further analysis revealed a significant discriminatory accuracy of cardiorespiratory fitness to identify either a low or high metabolic risk in children. We found similar patterns in adolescents from the U.S. We reported that cardiorespiratory fitness is also associated with a novel CVD risk factors such as homocysteine in Spanish adolescents, yet this result was not confirmed in Swedish youth after controlling for different potential confounders including the methylenetetrahydrofolate reductase (MTHFR) 677C>T genotype. The role of muscular strength in preventing cardiovascular diseases has become increasingly recognized. We showed that muscular strength is independently associated with death from all causes and cancer in men aged 20-82. In adolescents, we observed that muscular strength is associated with metabolic profile. Likewise, we showed that low-grade inflammation, which plays a role in the development of cardiovascular disease, is negatively associated with muscular strength after controlling for potential confounders including cardiorespiratory fitness and body fat. The patterns of these associations seem more relevant in overweight adolescents, suggesting that having high levels of muscular strength may counteract the negative consequences ascribed to body fat. The UCM research group has a long experience in the study of the influence of gene polymorphism on physical activity and fitness phenotypes. This group has shown that certain polymorphisms are associated with endurance or power/strength performance in a number of case (elite athletes)-control studies, healthy non-athletes young adults, diseased young people, as well as elderly. This group has also experience in the field of pharmacogenetics. Moreover, they have also investigated whether elite endurance athletes are genetically predisposed to lower disease risk by comparing a polygenic profile that combined 33 disease risk-related mutations and polymorphisms among non-athletic healthy controls and elite endurance athletes and no significant differences were observed in genotype or allele distributions among groups. Moreover, the computed health-related total genotype score was shown to be similar among groups (23.8+/-1.0 vs. 24.2+/-0.8 in controls and athletes respectively, P=0.553). In a cohort of Swedish youth, this group investigated whether polymorphisms in the UCP3 gene had an influence on plasma homocysteine levels during youth, as well as the putative modifying role of fitness. A significant interaction effect of fitness X rs1800849 polymorphism (P=0.042) was observed. The effect of the rs1800849 polymorphism on homocysteine levels persisted in youth with low fitness, whereas it was abolished in those with moderate or high cardiorespiratory fitness (P>0.1). 3.3. Describe briefly the objectives of the project. Main objectives: 1. To determine the patterns, interrelationships and impact on health indicators of objectively and subjectively measured physical activity, sedentary behaviours and health-related fitness (including fatness) in healthy primary and secondary schoolchildren and in adolescents with Down syndrome along a 3-yr follow-up (STUDY 1). 2.To identify the main psycho-social and environmental determinants of physical activity and sedentary behaviours in healthy primary and secondary schoolchildren and in adolescents with Down syndrome along a 3-yr follow-up (STUDY 1) 3.To investigate genotype-lifestyle interactions in healthy primary and secondary schoolchildren and in adolescents with Down syndrome along a 3-yr follow-up (STUDY 2) 4.To evaluate the effect of physical activity, sedentary behaviours and health-related fitness on traditional and new cardiovascular disease risk factors through the assessment of inflammatory biomarkers in healthy primary and secondary schoolchildren and in adolescents with Down syndrome along a 3-yr follow-up (STUDY 3) 5.To develop an on-line tool to collect epidemiological data on lifestyle and health indicators and test its potential application to school evaluation and formative task to schoolchildren (STUDY 4) Complementary objectives: 1.To evaluate the food intake and hydration habits in the studies cohorts (except for adolescents with Down syndrome) along a 3-yr follow-up. 2.To analyze gender differences in all research phenomena, and when possible differences between native and immigrant populations.

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υ 3.4. For Coordinated projects only, the coordinator must indicate (maximum 2 pages): The global objectives of the coordinated project, the need for coordination, and the added value provided by this coordination Main objective of the coordinated project: To endure effective management of the project overall, enabling and stimulating efficient exchange of information and collaboration between partners Secondary objectives: 1. To ensure proper co-ordination, integration and execution of every sub-study activities on the following levels i.e.

scientific, communication, dissemination, and training. 2. To monitor progress of all sub-study activities, applying remedial actions if required and to organize audits on

progress and quality output. 3. To inform all partners about the project status, including progress reports and to ratify and provide minutes of

meetings of the consortium meetings. 4. To organise the selection of partners (for example, subcontractors) and screening of their competence. 5. To organize every year a meeting of the consortium. The rest of the discussions among partners will be organized

by multi-conference calls. 6. To organise project partner meetings and to implement actions resulting from these meetings, where appropriate

(Consortium meetings). 7. To ensure all research activities are in line with ethical guidelines applied within Spain. 8. To ensure that all partners meet the deadlines for deliverables and reports. The need of coordination In order to get a successful project and achieve the objectives already shown, in our experience it’s essential to count on the best experts in each field involved in the study. CSIC will be the coordinator centre. The project coordinator, senior scientist Ascension Marcos, from CSIC, has a long track record of successful coordination, management and dissemination in various national research projects (AVENA, EVASYON and AFINOS studies). The CSIC group has expertise in the immunonutrition field and the evaluation of its interactions with other related fields as well as in leading projects. Two groups from UAM will be involved in this project. The UAM group has expertise in evaluating the physical activity, especially in adolescents and has also been working for years on disabled subjects. The members of the UCA group are experts in evaluating fitness, especially in children. The UCM group is an expert on the assessment of genetic profiles. Methodological coordination and harmonization workshops related to the evaluation of questionnaries and the measurements of anthropometry, physical activity and fitness will be held up in order to carry out the same methods, both in children and adolescents, as well as in adolescents with SD. Blood samples will be analyzed in one lab placed at CSIC (Institute Frio-ICTAN), except for hemogram which will be analysed in two labs (CSIC and UCA) due to the short spanlife blood cells. The same methodology will be used in both labs. Saliva samples will be analyzed in one lab at UCM (indicar departamento). It should be highlighted that all groups have already collaborated in other co-joint projects. Objectives of each sub-project CSIC SUB-PROJECT: Immunological profile evaluation in healthy schoolchildren and in adolescents with Down syndrome: a 3-yr follow-up study 1. To describe cardiovascular disease risk and inflammatory biomarkers at the baseline and 2 yr later in healthy

schoolchildren and in adolescents with Down syndrome. 2. To examine, in coordination with the UAM sub-project, the effect of physical activity and sedentary patters on

cardiovascular disease risk and inflammatory biomarkers at the baseline and 2 yr later in healthy schoolchildren and in adolescents with Down syndrome.

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3. To examine, in coordination with the UCA sub-project, the effect of physical fitness status on cardiovascular disease risk and inflammatory biomarkers at the baseline and 2 yr later in healthy schoolchildren and in adolescents with Down syndrome.

4. To examine, in coordination with UCM, the interaction between physical activity/fitness and gene polymorphism on cardiovascular disease risk and inflammatory biomarkers in healthy schoolchildren and in adolescents with Down syndrome.

5. Complementary to the main objectives related to physical activity and immunological profile, to describe basic food habit patterns on healthy schoolchildren along the 3-yr follow-up period.

UAM SUB-PROJECT: Physical activity and sedentary behaviour patterns and its determinants in healthy schoolchildren and in adolescents with Down syndrome and its relation with health indicators: a 3-yr follow-up study 1. To describe physical activity and sedentary patterns using subjective (self-reports) and objective (accelerometer)

measures in healthy schoolchildren and in adolescents with Down syndrome over 3-yr. follow-up period. 2. To identify psycho-environmental determinants of physical activity and sedentary behaviour on school children over

3-yr follow-up period. 3. To examine, in coordination with CSIC and UCA sub-project, the relationship between 3-yr of physical

activity/inactivity patterns and several health indicators (health related fitness, cardiovascular risk, inflammatory biomarkers and mental health).

UCA SUB-PROJECT: Health-related physical fitness in healthy schoolchildren and in adolescents with Down syndrome and its relation with health indicator: a 3-yr follow-up study.

1. To describe tracking of health-related fitness in healthy schoolchildren and in adolescents with Down syndrome over a 3-yr follow-up period, and to determine whether basal health-related fitness status predicts health-related fitness along three years.

2. To examine, in coordination with CSIC and UAM sub-projects, the relationship changes of health-related fitness and several health indicators (cardiovascular risk, inflammatory biomarkers and mental health) in healthy schoolchildren and in adolescent with Down syndrome over a 3yr follow-up period.

3. To coordinate the development of an on-line tool to collect data from the research and to test its potential application to school evaluation and educative tasks.

UCM SUB-PROJECT: Genetics and physical activity interaction assessment on fitness and health in healthy schoolchildren and in adolescents with Down syndrome: a 3-yr follow-up study 1. To determine, in coordination with CSIC, UAM and UCA sub-projects, whether lifestyle factors (i.e. physical activity

and sedentary behaviours) can attenuate the detrimental effect of certain gene polymorphisms associated with cardiovascular disease risk factors such as total and central body fat, blood pressure, blood lipids and lipoproteins as well as low-grade inflammatory proteins in apparently healthy schoolchildren and in adolescents with Down syndrome.

The coordinated project flow (—) & interactions among the objectives and subprojects (---):

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4. METHODOLOGY AND WORKING PLAN (in the case of coordinated projects this title must include all the subprojects) The UP & DOWN Study is a 3-yr longitudinal study in healthy schoolchildren and adolescents with Down syndrome to observe the impact over time of physical activity and sedentary behaviours on health indicators (physical fitness, metabolic and cardiovascular disease risk factors, new inflammation-immunity biomarkers, mental health and cognitive performance) as well as to identify the psyco-enviromental and genetic determinants of an active lifestyle in these populations. To carry out these aims, the UP and DOWN Study is divided in 4 overall STUDIES: STUDY 1: Longitudinal study of physical activity, sedentary behaviours and health-related fitness in healthy schoolchildren and in adolescents with Down syndrome: determinants and their effects on health (Research) Aims: 1. To assess and describe the patterns of physical activity, sedentary behaviours and health-related fitness in healthy

children and adolescents (primary and secondary schools, respectively) over a 3-yr period. 2. To assess patterns of physical activity, sedentary behaviours and health-related fitness in adolescents with Down

syndrome over a 3-yr period. 3. To evaluate the feasibility, reliability and validity and of physical activity and health-related fitness assessments in

adolescents with Down syndrome. 4. To validate subjective measures of physical activity in Spanish healthy schoolchildren (<12 yr) 5. To identify the psycho-environmental determinants of physical activity, sedentary behaviours and health-related

fitness in healthy schoolchildren, and in adolescents with Down syndrome over a 3-yr period. 6. To evaluate the effect of physical activity, sedentary behaviours and health-related fitness on health indicators such

as hypertension, positive health, stress, anxiety, self-concept, eating disorders, school and cognitive performance over a 3-yr period.

Samples: • 1000 children (CADIZ) = 500 6-7-yr (1st grade) and 500 9-10-yr (4th grade) from primary schools • 1000 adolescents (MADRID) = 500 12-13-yr (7th grade) and 500 14-15 (9th grade) from secondary schools • 200 adolescents (MADRID) with Down syndrome from special schools.

Follow-up: The follow-up on the participants will be over a 3-yr period:

YEAR 2011 2012 2013 QUARTER Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4

TIME-POINT 1 2 3 4 5 6 7 8 9 10 11 12 ASSESSMENTS X X X X X X X X X

Assessments: 1. Physical and sedentary activity by accelerometry (time points 2,6,10) Levels and patterns of physical activity and sedentary activity will be measured by the Actigraph accelerometer. The Actigraph is a small and lightweight uniaxial activity monitor (3.8 x 3.7 x 1.8 cm, 27 g) designed to detect vertical accelerations ranging in magnitude from 0.05 to 2.00 g with a frequency response of 0.25–2.50 Hz. The ActiGraph (previously known as MTI and CSA) has been validated against doubly labelled water and indirect calorimetry in laboratory and free-living conditions with children and adolescents (Freedson et al. 2005). Data will be processed and

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analysed by JAVA software developed to analyze the output from this activity monitor. Participants will wear the monitor on an elastic belt at the lower back to the centre of gravity for 7 consecutive days. 2. Physical activity and sedentary behaviours by self-report (time points 2,3,4,5,6,7,8,9,10) Levels of physical activity will be assessed by self-report through the reliable and validated Spanish version of the PAQ-A/C (Martinez-Gomez et al. 2009a). To classify children and adolescents according to the youth physical activity recommendation, the Spanish version of the PACE+ questionnaire for adolescents will be used (Martinez-Gomez et al. 2009b). Test-retest reliability and validity against objective measures of the PAQ-A/C and 1-item question for the children sample will be addressed in time point 1. Also, several attempts may be performed to validate the PAQ-C/A and PACE questionnaires in adolescents with Down syndrome, even thought there are great limitations to obtain a reasonable validity due to the recall characteristics in this population. The Recess Physical Activity Recall (RPAR) will assess patterns of physical activity during the school recess time (Martinez-Gomez et al. In press). In addition, habitual easy questions will be used to estimate time spent in sedentary behaviours such as TV viewing, computer usage, sitting time, and sleep. 3. Health-related fitness (time points 2,6,10) 20m shuttle run test: The participants perform the test as previously described by Léger et al. (Leger et al. 1988). Participants are required to run between two lines 20 m apart, while keeping pace with audio signals emitted from a pre-recorded CD. The initial speed is 8.5 km/h, and is increased by 0.5 km/h per minute (one minute equals one stage). Participants are instructed to run in a straight line, to pivot on completing a shuttle, and to pace themselves in accordance with the audio signals. The test is finished when the participant fails to reach the end lines concurrent with the audio signals on two consecutive occasions, or when the subject stops because of fatigue. The participants are encouraged to keep running as long as possible throughout the course of the test. The test is performed once and the last completed stage or half-stage at which the subject dropped out is scored. A gymnasium or space large enough to mark out a 20 m track is used to perform the test. Handgrip strength test: To perform this test a hand dynamometer with adjustable grip (TKK 5101 Grip D; Takey, Tokio Japan) will be used. This dynamometer presents a high validity and reliability when compared with calibrated known weights (España-Romero et al. In press). The participant squeeze gradually and continuously for at least two seconds, performing the test with the right and left hands in turn, and with the elbow in full extension as described elsewhere (España-Romero, Ortega Porcel In press). The grip-span of the dynamometer is adjusted according to the hand size for determining the maximum handgrip strength using the equations specifically developed for children (España-Romero et al. 2008) and adolescents (Ruiz et al. 2006). The test is performed twice and the maximum score for each hand is recorded in kilograms. The sum of the scores achieved by left and right hands is used in the analysis. Standing long jump test: From a starting position immediately behind a line, standing with feet approximately shoulder’s width apart, the participant jumps as far forwards as possible on a non-slip hard surface. The test is performed twice and the best score is recorded in centimetres. 4 x 10m shuttle run test: 4 x 10m shuttle run is an adaptation of the 5 x 10m shuttle run test included in the EUROFIT battery (Council of Europe Committee for the Development of Sport 1993) but maintaining the same characteristics. Velocity, agility and coordination are assessed in this test. Participants run 4 x 10m (back and forth) as fast as possible. Body mass index: Participants are barefoot and with t-shirt and short trousers. Weight is measured with an electronic scale (Type SECA 861; range, 0.05 to 130 kg; precision, 0.05 kg), and stature is measured in the Frankfort plane with a telescopic stature-measuring instrument (Type SECA 225; range, 60 to 200 cm; precision, 1 mm). Body mass index (BMI) will be calculated as weight/height squared (kg/m2). Participants will be categorized according to the BMI international cut-off values as underweight, normalweight, overweight, and obesity (Cole et al. 2000; Cole et al. 2007). Skinfolds: Triceps and subscapular skinfold thickness will be measured on the right side of the body with a Holtain caliper (range, 0 to 40 mm; precision, 0.2 mm). Triceps is raised in a vertical fold halfway between the acromion process and the superior head of the radius, in the posterior aspect of the arm, and subscapular about 20 mm below the inferior

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angle of the scapula and 45º to the lateral side of the body. It is performed according to Lohman’s anthropometric standardization reference manual (Lohman et al. 1991). Waist circumference: Waist circumference will be measured with a non-elastic tape (Seca 200; range, 0 to 150 cm; precision, 1 mm), at the level of the natural waist, in a horizontal plane, which is the narrowest part of the torso, as seen from a front view. In some obese participants, it is difficult to identify the waist circumference, therefore this measurement will be performed in the midpoint between the superior iliac spine and the costal edge in the midaxillary line (Nagy et al. 2008). The measurements will be taken at the end of a normal expiration, without the tape compressing the skin. The measurements will be carried out twice, but not consecutively; all the anthropometric variables will be measured in order, and then the same measurements will be once more repeated. The mean of the two measurements will be used in the analyses 4. Dietary patterns (time points 2,6,10) A food-frequency questionnaire (FFQ) will be used to obtain the diet information from the children's parents and adolescents (Royo-Bordonada et al. 2006). The FFQ contains 77 food items divided into the following categories: dairy products, meat and eggs, fish, fruit and vegetables, legumes, potatoes and cereals, nuts, oils and fat, sweets and beverages. For each food item, an average portion size is specified, and participants will be asked how often they have consumed that unit throughout the previous period having nine options for the frequency of intake (ranging from never/almost never to at least six times per day). 5. Determinants: (time points 2,6,10) Environmental determinants of physical activity and sedentary behaviours will be assessed using the European questionnaire developed in the ALPHA project (Spittaels et al. 2009). Likewise, psychological determinants of physical activity and sedentary behaviours such as physical activity stages, family influence, change strategies and self-efficacy will be assessed using questionnaires standardized in previous national (AVENA, EVASYON, AFINOS) and European studies (HELENA, PROCHILDREN, IDEFICS). A questionnaire with easy questions will be also developed to obtain immigration characteristics, socioeconomic (income and parents educational levels) status, family structure, and early life determinants (e.g. birth weight, breast feeding, early menarche). 6. Other health indicators: (time points 2,6,10) Blood pressure: blood pressure will be measured with a validated digital automatic blood pressure monitor (OMRON M6, OMRON HEALTH CARE Co., Ltd., Kyoto, Japan) according to the International Protocol of the European Society of Hypertension. Self-concept: In order to assess self-esteem, the AF-5 (Quiles-Marcos et al. 2009) multidimensional Self-Esteem Scale appraises five personal aspects: academic, social, emotional, family, and physical dimensions. Eating disorders: The SCOFF Eating Disorders Questionnaire is a valid and reliable screening tool for detecting the existence of an eating disorder that includes 5 questions (Rueda Jaimes et al. 2009). The questions focus on some key symptoms of anorexia and bulimia. School performance: School children will be asked to self-report the last grades in several academic subjects: Language, Maths, Sciences, English and Physical Education. Adolescents will report their grades in these subjects on 5 ordinal variables (A, B, C, D, E). The minimum level to pass academic subjects is a grade of D, as compulsory for all secondary schools in Spain according to the Spanish Educational System. Other academic characteristics that might be related to academic performance will be also obtained by questionnaire: school contentment, repeated grades and absenteeism. Cognitive performance: Cognitive performance will be measured by the Spanish version of the ‘SRA Test of Educational Ability or also called TEA test. The TEA is a complete battery that measures intelligence, as a subject’s ability to learn, by means of measuring the three basics school skills: verbal, numeric and reasoning abilities (Thurstone et al. 1998)

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STUDY 2: Longitudinal study of gene-lifestyle interaction and cardiovascular health in healthy schoolchildren and in adolescents with Down syndrome (Research) Aims: 1. To determine whether physical activity and sedentary behaviours can attenuate the detrimental effect of certain

polymorphism of genes associated with cardiovascular disease risk factors such as total and central body fat, blood pressure, blood lipids and lipoproteins or low-grade inflammatory proteins in apparently healthy school children and in adolescents.

2. To determine whether physical activity and sedentary behaviours can attenuate the detrimental effect of certain polymorphism of genes associated with cardiovascular disease risk factors such as total and central body fat, blood pressure, blood lipids and lipoproteins or low-grade inflammatory proteins in adolescents with Down syndrome.

Samples:

• Healthy schoolchildren and adolescents with Down syndrome from STUDY 1 (n = 2200) Follow-up: The follow-up of the participants will be over a 3-yr period

YEAR 2011 2012 2013 QUARTER Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4

TIME-POINT 1 2 3 4 5 6 7 8 9 10 11 12 ASSESSMENTS X X X

Assessments: As a first wave measurements, and according to the specific budget, we will genotype 3 SNPs, namely, the rs9939609 polymorphism in the fat mass and obesity associated (FTO) gene, the angiotensin converting enzyme (ACE) 287bp Ins(I)/Del(D) polymorphism (rs1799752), and the Gly482Ser (rs8192678) polymorphism in the peroxisome proliferator-activated receptor γ coactivator 1α (PPARGC1A) gene. Among the obesity-related genes, polymorphisms in the FTO gene are strongly associated with body fat estimates in populations of different ethnic background or age (Cecil et al. 2008, Dina et al. 2007, Frayling et al. 2007). The ACE is a possible candidate gene that may influence both body fatness and blood pressure (Danilczyk et al. 2004). Indeed, the ACE rs1799752 polymorphism is associated with coronary artery disease, being the DD genotype associated with an increased risk for coronary artery disease compared with the individuals carrying the II (Zintzaras et al. 2008). The rs8192678 polymorphism in the PPARGC1A gene is associated with mitochondrial biogenesis and skeletal muscle fiber-type conversion (i.e., II→I) (Lucia et al. 2005), which may trigger the development of metabolic disorders (Arany 2008). Note: Other SNPs might be genotyped whether additional private or public funding is obtained during the study or later.

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STUDY 3: Effects of physical activity and fitness on metabolic and cardiovascular risk related novel biomarkers in healthy schoolchildren and in adolescents with Down syndrome (Research) Aims: 1. To evaluate the effects of physical activity and fitness on early development of metabolic and cardiovascular related

risk novel factors, also associated with the immune function (inflammatory risk factors) in apparently healthy schoolchildren and in adolescents with Down syndrome.

2. To identify children and adolescents at risk of sedentary-related diseases: features of the pre-metabolic syndrome, dyslipidemia, inflammation and early cardiovascular disease risk in apparently healthy schoolchildren and in adolescents with Down syndrome.)..

3. To evaluate the effects of physical activity, fitness and body composition on immunodeficiency status and risk of infections in adolescents with Down syndrome (DS).

Samples: Sub-samples from STUDY 1 samples are as follows: • 200 children (CADIZ) = 100 6-7-yr (1st grade) and 100 9-10-yr (4th grade) from primary schools • 200 adolescents (MADRID) = 100 12-13-yr (7th grade) and 100 14-15 (9th grade) from secondary schools • 100 adolescents (MADRID) with Down syndrome from secondary and special schools.

Follow-up: The follow-up on the participants will be over 3-yr: YEAR 2011 2012 2013

QUARTER Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 TIME-POINT 1 2 3 4 5 6 7 8 9 10 11 12

ASSESSMENTS X X Assessments: Blood sample protocol: Blood collection will be performed upon an empty stomach between 8 and 9 am, after fasting for 10-h. Health state of human volunteers must be optimal for blood sample collection. In all cases, blood will be extracted from the antecubital vein (21.5 mL). Experienced clinical staff will carry out blood collection. Blood samples will be divided into aliquots as follows: 1.5 mL in EDTA tube (for haematological study) and 10 mL in gel containing tube (for serum extraction). To avoid erroneous values due to sample deterioration, blood cell counts and differentials will be analyzed in each city where the samples will be collected (Madrid and Cadiz). Within 1-h of collection, blood will be centrifuged and aliquots of plasma or serum will be stored at -80ºC. Serum samples will be sent to each laboratory in Madrid (CSIC or UCA) at convenient time intervals. Biological markers: Haematology: Total red blood cell count, haemoglobin levels, haematocrit percentage, mean corpuscular volume, mean corpuscular haemoglobin, mean corpuscular haemoglobin concentration, red cell distribution width, total white blood cell count (WBC) and absolute values and percentage of WBC differential counts (lymphocytes, monocytes, neutrophils, eosinophils and basophils) and platelet profile and mean platelet volume by Coulter auto-analyser. Biochemistry: The following biomarkers can identify children and adolescents at metabolic and cardiovascular risk: glucose, triglycerides and total-cholesterol will be analysed by using standard enzymatic-colorimetric methods with kits provided by Roche-Boehringer, adapted to a Hitachi 917 auto-analyser. HDL-cholesterol will be determined after selective centrifugation following a validated method. LDL-cholesterol will be calculated indirectly with the Friedewald formula. Insulin will be determined by means of an enzymo-inmuno-assay. Immunology/Inflammation: C-reactive protein and complement factors C3 and C4 will be measured by nephelometry. Serum IL-6, and TNF-α levels will be analysed by Luminex-100 IS (Integrated System: Luminex Corporation, Austin, TX, USA) using the multiplex assay kit Linco High Sensitivity Human Cytokine Panel Lincoplex (Linco Research, Inc., MO, USA). Leptin, adiponectin and insuline will be determined by Luminex-100 IS (Integrated System: Luminex Corporation, Austin, TX, USA) using the multiplex assay kit Linco Human Gut Hormone panel (Linco Research, Inc., MO, USA). Fibrinogen, visfatin, galectin 3 and Cortisol will be analysed by ELISA

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The present sub-project 3 from the UP&DOWN proposal attempts to be a pioneer study that will provide new useful information about the early development of metabolic and cardiovascular risk related to physical activity/sedentariness and fitness of apparently healthy schoolchildren and of adolescents with DS. Based on the results obtained from this sub-study, a realistic intervention strategy could be conjointly proposed and promoted by stakeholders (researchers and politicians) in order to achieve the goals of understanding the objective influence of physical activity on chronic disease risks in a susceptible youth Spanish population and in adolescents with DS. STUDY 4: Applications development for monitoring and process the data (Develop + Innovation) The last study in this project will develop applications to improve the data adquisition process as well as their analysis. The indicators managed by the application are related to the physical activity, physical condition, body composition and food habits in schoolchildren. Aims: 1. To develop an On-line Data Management System (ODMS). 2. To create an On-line Interface for Data Collection (OIDC). 3. To develop questionnaires for optical reader devices. 4. To create a tool to analyze the data information from the accelerometres. Management: Development of an On-line Data Management System (ODMS): The ODMS will allow each research group to record directly their own data in this on-line platform, minimizing possible inconsistencies between different databases, thus avoiding missing data. This on-line platform will be able to create a whole database, which could be used for statistical analysis software. Creation of an On-line Interface for Data collection (OIDC): This project will allow collect epidemiological data in primary and secondary schools. The development of an on-line tool will help to the data acquisition of lifestyle behaviours and health indicators in Spanish schoolchildren. This tool have 2 possibilities: 1) Teachers and professors will be able to include this information from their students, similarly than a researcher; 2) Children and adolescents will be able to answer questionnaires in electronic versions. In both options, a report may be created for each student to provide educational-feedback with regard his/her health status, unhealthy lifestyle behaviours and several advices. Questionnaires for optical reader devices: This task will help to reduce the overhead in the data collection in this study. The UP&DOWN study will collect a great amount of data from tests and questionnaires administered in children, adolescents and their parents. Development of a tool to analyze the data information from the accelerometers: We will create an easy tool to process the information from the accelerometres. Each accelerometre measurement has 7-d data using a 15-sec epoch. This is approximately 40.320 results per subject, 88.704.000 in 2200 subjects and 266.112.000 results in 2200 subjects during 3 measurements. Hence, it is necessary an easy software to obtain refined variables for describing the patterns of physical activity in these populations. This software will help to obtain physical activity variables such as time at different intensities, weekday vs. weekend day patterns, bouts at different physical activity intensities, differences between weekday periods (before school, school, after school), etc. Assessment and optimization of the developed tools

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The aim of this project is to have useful tools to be used in future research. To achieve this objective, it is mandatory not only to develop, but also to assess the utilization of the developed tools. Thanks to this information, the researchers and pilot studies in schoolchildren can provide feedback to improve the utility of these tools. Execution: The developments will be performed on the following periods:

YEAR 2011 2012 2013 QUARTER Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4

TIME-POINT 1 2 3 4 5 6 7 8 9 10 11 12 MILESTONES X X X X X X

Management of measurements in the UP&DOWN study:

Sample recruitment in the UP&DOWN study: Healthy children and adolescents will be enrolled in the UP&DOWN study from primary and secondary schools in Cadiz and Madrid regions, respectively. Public schools from these regions will be invited to participate in this study. In each region, at least 10 schools will be included to collect the data. In each school centre that decides participating in the UP&DOWN study a total of 50-100 schoolchildren will be assessed over 3- year. Parents/guardians and school supervisors will be informed by letter about the nature and purpose of the study and written consents to participate will be obtained from both the volunteers and their parents/guardians. Adolescents with Down syndrome will be enrolled in the UP&DOWN study from special schools in the Madrid region. Parents/guardians and school supervisors from these adolescents will be also informed by letter about the nature and purpose of the study and written consents to participate will be obtained from both the volunteers and their parents/guardians Viability in the UP&DOWN for sample recruitments: • Children (Cadiz): The UCA members are professors in the Physical Education undergraduate programme who

teach to future physical education teachers of primary schools. MSc and PhD students are commonly PE teachers who may make easier the access to data collection in their PE classes.

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• Adolescents (Madrid): The UCA members are professors in the Physical Activity and Sport Science undergraduate programme who teach to future physical education professors of secondary schools. MSc and PhD students are commonly PE professors who may make easier the access to data collection in their PE classes.

• Adolescents with DS: Several UCA members have experience in contexts related to physical activity and Down syndrome. Also, the UAM group has a specific postgraduate (MSc) programme called “Physical Activity, Persons with Disabilities and Social Integration” where specialists in physical activity are traninned to work with these populations, specially with children and adolescents with intellectual disabilities such as the Down Syndrome.

Inclusion and exclusion criteria: Before starting the UP&DOWN study, a screening will be performed to all candidates. Several inclusion and exclusion criteria will be defined to homogenize the sample characteristics

Sample 1 (Cadiz) Sample 2 (Madrid) Sample 3 (Madrid)

Children Adolescents Adolescents with SD

Inclusion criteria Inclusion criteria Inclusion criteria - Healthy for physical activity - 6-10 yr in YEAR 1

- Healthy for physical activity - 12-15 yr in YEAR 1

- Healthy for physical activity - 12-15 yr in YEAR 1

Exclusion criteria Exclusion criteria Exclusion criteria

-No signed the informed consent -No signed the informed consent - No signed the informed consent - Intelligent coefficient <35/100

Data collection: A manual of operations will be ready to be followed by all participating research centres. This manual will include the whole set of data collection methodology and a detailed description of all instruments for the core study data. A protocol for data-entry will include specifications aimed at minimising coding errors. Training sessions with all the technical staff involved in the fieldwork from the different research centres will be carried out in order to harmonize data collection. Standardised protocols for the quality control and first round of data cleaning to be applied by all participating centres will be set-up. Central database architecture for centralisation of data from the different participating centres and for the different aspects of the study will be designed. A central protocol for anonymous data cross-linkage will be created. A central analytical plan will be developed. The coordinating group (CSIC) will provide analyses and reports of the UP&DOWN study data in a format decided and approved by all participating centres. Ethical aspects: This project will follow the ethical standards recognized by the Declaration of Helsinki (reviewed in Hong-Kong in September 1989 and in Edinburgh, Scotland in 2000), the EEC Good Clinical Practice recommendations (document 111/3976/88, July 1990), the current Spanish legislation regulating clinical and biomedical research in humans, personal data protection and bioethics (Royal Decree 561/1993 on clinical trials and 14/2007, 3rd July, for Biomedical Research). The study will be submitted by the Ethics Committee of each research group participating in this project and by the Bioethic Committee of the Scientific National Research Council (CSIC). The study will be explained to the participants before starting; both volunteers and parents/tutors will be required to sign an informed consent. Infrastructure and equipment:

19

All of the research groups participating in the proposal have their own infrastructure and equipment that will be also used during the project. The research groups involved in the proposal will provide the available equipment to carry out the present study. CSIC research group: Laboratory for these measurements is currently in use in the CSIC research group by analyzer based on the principles of flow cytometry: Luminex-100 IS plate reader XY Platform (Integrated System: Luminex Corporation, Austin, TX, USA/Linco Research, Inc., MO, USA). Personnel offices include PCs Biochemistry and haematological laboratory. The laboratory of CSIC research group also contains Auto-Analyzer COULTER LH 500 for haematology and Autoanalyser, ELISA (Enzyme Linked Immuno-Sorbent Assay) for other novel risk biomarkers. Working places also include PCs. UAM research group: - Laboratory of Physical Activity assessments and Exercise Physiology - Personnel offices - 200 Actigraph GTM1 Accelerometers and software for analysis - Health-related fitness assessment instruments - Skinfold caliper (Caliper Holtain; Holtain Ltd., Walles, UK) - Bioelectrical impedance analyser: Bioelectrical impedance will be determined using AKERN 101 equipment (AKERN Srl., Firenze, Italy). - Statistical Software (SPSS, MedCald) UCA research group: - Laboratory of Physical Activity assessments and Exercise Physiology - Personnel offices - Health-related field fitness test assessment instruments (1 equipment for the ALPHA health-related fitness test battery) - Statistical Softwares (SPSS) UCM research group: Laboratory for genetic analysis of DNA polymorphisms is currently in use in the UCM research group by analyzer on the principles of nucleic acids analysis: Robotic workstation for automated isolation of nucleics acids MagNa Pure Compact, 2 thermal cyclers Eppendorf personal, thermal cycler Mastercycler gradient for DNA amplification, 1 system for real-time PCR Ligthcycler 1.5, 1 Genetic analyzer ABI 310 DNA sequencer, 1 Spectrophotometer Nanodrop 2000 for DNA quantification. This laboratory also contains accessory devices for these purposes as refrigerated centrifuges or photo documentation system for DNA visualization. Human recourses requirements: The UP&DOWN study is a large scale educational-lifestyle and health evaluation project involving several research groups from different Spanish cities and more than two thousand of children and adolescents who will be exhaustively evaluated along three years. In this context, resources and funding will be needed according to the expenses this study will cause. Every research group involved in the project will need human resources to develop the multiple tasks proposed, which include the assessments of a large sample (n=2200) followed-up during 3 years with a exhaustive evaluation protocol and a sub-sample (n=500) with blood sample parameters. Most of the partners involved in the proposal must also deploy an important number of persons-month since they are involved in other educational and research activities. Participants in the UP&DOWN study mainly need the participation of young researchers in order to perform the fieldwork. Thus, university graduates in diverse scientific specialities and technical worker will be required. Human resources is the main need for a successfully project development. According to the UP&DOWN study objectives the requested personnel to be contracted during the UP&DOWN study as are follows (tasks are detailed into the chronogram model): CSIC group:

20

- 1 techinical lab worker

UAM group:

- 3 university graduated (half time, 18,5 h/week) UCA group:

- 2 univesity graduated (half time, 18,5 h/week) List of milestones:

STUDY 1 STUDY 2

M1.1 Description of patterns of physical activity, sedentary behaviours and health-related fitness in children, adolescents and in adolescents with Down syndrome

M1.2 Report of valid and reliable methods for assessing physical activity and health-related assessments in Spanish school children and in adolescents with Down syndrome

M1.3 Report of the psycho-environmental determinants of physical activity, sedentary behaviours and health-related fitness in school children and adolescents, and in adolescents with Down syndrome

M1.4 Identification of adolescents at risk of unhealthy behaviours

M2.1 Reports linking polymorphism of genes associated with cardiovascular disease risk factors and physical activity and sedentary behaviours in apparently healthy children and adolescents

M2.2 Reports linking polymorphism of genes associated with cardiovascular disease risk factors and physical activity and sedentary behaviours in adolescents with Down syndrome.

STUDY 3 STUDY 4 M3.1 Report linking metabolic and cardiovascular related risk novel factors with physical activity levels, fitness and behaviours in children and adolescents M3.2 Identification of children and adolescents at risk of sedentary-related diseases according novel biomarkers determination in children and adolescents M3.3 Report of the effects of physical activity, fitness and body composition on immunodeficiency status and risk of infections in adolescents with Down syndrome (DS).

M4.1 Evaluation of the Online Data Management System (ODMS) in a research centre M4.2 Assessment of the Online Interface for Electronic Questionnaires (OIEQ) in a school M4.3 Data collection using questionnaires for optical reader devices M4.4 Development of a tool to analyze the data information from the accelerometers M4.5 Assessment and improvement of the developed tools

21

CHRONOGRAM MODEL This chronogram must indicate the persons involved in the project, including those contracted with project funds.

TASK Centre Persons Year 1 Year 2 Year 3STUDY 1, STUDY 2 & STUDY 3 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12

Phase I: Preparatory tasks x x x Initial coordination meeting All All x Primary School contacts management (Cadiz) UCA All x x Secondary School contacts management (Madrid) UAM O.Veiga, C.Tejero x x Special Education School contacts management (Madrid) UAM A.Villagra, M. Díaz x x

Pilot proof of assessment protocols for children UCA All Evaluator´s Training for children UCA All Pilot proof of assessment protocols for adolescents UAM JM.Moya,

J.Campo

Evaluator´s training for adolescents UAM All x x Pilot proof of assessment protocols for DS adolescents UAM M.Diaz, A. Sanz x x

Evaluator´s training for DS adolescents UAM M.Diaz, A. Sanz x x Modification on assessments protocol for children UCA All x Modification on assessments protocol for adolescent UAM O.Veiga, JM.

Moya, J. Campo x

Modification on assessment protocol for DS adolescent UAM A.Villagra, M.Diaz,

A.Sanz x

Research Team Coordination Meeting All All x

22

TASK Centre Persons Year 1 Year 2 Year 3

STUDY 1, STUDY 2 & STUDY 3 1 2 3 4 5 6 7 8 9 10

11

12 1 2 3 4 5 6 7 8 9 1

011

12 1 2 3 4 5 6 7 8 9 1

0 11

12

Phase II: First cohort data collection x x x x x x x x x x x x

Accelerometry data collection on children UCA UCA PA Graduates 1 & 2 (+ FPI)

x x x x

Fitness data collection on children UCA All UCA members x x x x

General information and mental health data collection on children

UCA UCA PA Graduates 1 & 2 (+ FPI)

x x x x

Psycho-environmental determinants data collection on children UCA

UCA PA Graduates 1 & 2 (+ FPI)

x x x x

Saliva samples data collection on children UCA All UCA

Members x x x x

Blood sample data collection on children UCA

Health specialist worker

x x x x

PA and food habits data collection on children (questionnaire): Year 1/Measure 1

UCA UCA PA Graduates 1 & 2 (+ FPI)

x x x x

Recording of first cohort data of fitness, PA determinants and mental health(children)

UCA UCA PA Graduates 1 & 2 (+ FPI)

x x x x x x

Debugging of accelerometry data (children) UAM

O.Veiga; UAM PA Graduates 1,2 and 3

x x x x x x

Recording of first cohort data of accelerometry data (children)

UAM UAM PA Graduates 1,2 and 3

x x x x x x

Genotyping saliva samples (children) UCM All UCM members x x x x x x

Haematological analysis of blood samples (children) UCA

Subcontracted external laboratory

x x x x

23

TASK Centre Persons Year 1 Year 2 Year 3

STUDY 1, STUDY 2 & STUDY 3 1 2 3 4 5 6 7 8 9 10

11

12 1 2 3 4 5 6 7 8 9 1

011

12 1 2 3 4 5 6 7 8 9 1

0 11

12

Phase II: First cohort data collection x x x x x x x x x x x x Biochemical analysis of blood samples (children) CSIC Support/Laborat

ory Technician x x x x Immunological analysis of blood samples (children) CSIC Support/Laborat

ory Technician x x x x PA and food habits data collection on children (questionnaire)- Year 1/Measure 2

UCA UCA PA Graduates 1 & 2 (+ FPI)

x x

Record PA and food habits data: Years 1/Measure 2

UCA UCA PA Graduates 1 & 2 (+ FPI)

x x

PA and food habits data collection on children (questionnaire)- Year 1/Measure 3

UCA UCA PA Graduates 1 & 2 (+ FPI)

x x

Record PA and food habits data: Year 1/Measure 3

UCA UCA PA Graduates 1 & 2 (+ FPI)

x x

PA and food habits data collection on children (questionnaire)- Year 1/Measure 4

UCA UCA PA Graduates 1 & 2 (+ FPI)

x x

Record PA and food habits data: Year 1/Measure 4

UCA UCA PA Graduates 1 & 2 (+ FPI)

x x

Accelerometry data collection on adolescents & DS UAM

UAM PA Graduates 1,2 and 3 (+ FPI)

x x x x

Fitness data collection on adolescents & DS UAM

UAM PA Graduates 1,2 and 3 (+ FPI)

x x x x

24

TASK Centre Persons Year 1 Year 2 Year 3

STUDY 1, STUDY 2 & STUDY 3 1 2 3 4 5 6 7 8 9 10

11

12 1 2 3 4 5 6 7 8 9 1

0 11

12 1 2 3 4 5 6 7 8 9 1

0 11

12

Phase II: First cohort data collection x x x x x x x x x x x x

General information and mental health data collection on adolescents

UAM UAM PA Graduates 1,2 and 3 (+ FPI)

x x x x

Psycho - environmental determinants data collection on adolescents UAM All UAM

members x x x x

Saliva samples collection on adolescents & DS

UAM UAM PA Graduates 1,2 and 3 (+ FPI)

x x x x

Blood sample data collection on adolescents & DS

UAM Health specialist worker

x x x x

PA and food habits data collection on adolescents (questionnaire): Years 1/Measure 1

UAM All UAM Members x x x x

Recording of first cohort data of fitness, PA determinants and mental health (adolescents)

UAM UAM PA Graduates 1,2 and 3 (+ FPI)

x x x x

Debugging of accelerometry data (adolescents & DS) UAM

UAM PA Graduates 1,2 and 3 (+ FPI)

x x x x

Research Team Coordination Meeting AllAll team members x

Recording of first cohort data of accelerometry data (adolescents)

UAM UAM PA Graduates 1,2 and 3 (+ FPI)

x x x x x x

Genotyping saliva samples (adolescents & DS) UCM All members

UCM x x x x x x

Haematological analysis of blood samples (adolescents & DS) CSIC

Subcontracted to external laboratory

x x x x x

Biochemical analysis of blood samples (adolescents & DS) CSIC Support/Laborat

ory Technician x x x x x x

Immunological analysis of blood samples (adolescents & DS) CSIC Support/Laborat

ory Technician x x x x x x

25

TASK Centre Persons Year 1 Year 2 Year 3

STUDY 1, STUDY 2 & STUDY 3 1 2 3 4 5 6 7 8 9 10

11

12 1 2 3 4 5 6 7 8 9 1

0 11

12 1 2 3 4 5 6 7 8 9 1

0 11

12

Phase II: First cohort data collection x x x x x x x x x x x x

PA and food habits data collection on adolescents (questionnaire)- Years 1/Measure 2

UAM UAM PA Graduates 1,2 and 3 (+ FPI)

x x

Record PA and food habits data adolescents: Year 1/Measure 3 UAM CSIC

UAM Graduates + Support Technician CSIC

x x

PA and food habits data collection on adolescents (questionnaire)- Years 1/Measure 3

UAM UAM PA Graduates 1,2 and 3 (+ FPI)

x x

Record PA and food habits data: Years 1/Measure 3

UAM CSICUAM Graduates + Support Technician CSIC

x x

PA and food habits data collection on adolescents (questionnaire)- Years 1/Measure 4

UAM UAM PA Graduates 1 and 2 (+ FPI)

x x

Record PA and food habits data on adolescents: Year 1/Measure 4

UAM CSIC UAM Graduates + Support Technician CSIC

x x

Preliminary Analysis of Accelerometer Data Cohort 1

UAM O.Veiga, C Cordente, A Villagra

x x x x x x

Preliminary Analysis of PA Self-reported Data Cohort 1 UAM JM Moya, A Acha

J Campo x x x x x x Preliminary Analysis of Health Related Fitness Data Cohort 1 UCA J Castro J Mora J

Ruiz x x x x x x Preliminary Analysis of Psycho-Environmental Determinants of Cohort1 UAM C Tejero, M Diez,

JM Moya, A Sanz x x x x x x Preliminary Analysis of Metal Health Indicators of Cohort 1 UCA J Conde JAL Diaz

R Ortega x x x x x x Preliminary Analysis Biochemical parameters CSIC A Marcos, LE Díaz x x x x x x Preliminary Analysis of immunological parameters CSIC A Marcos, E Nova

J Romeo x x x x x x Preliminary Global Analysis Data Cohort 1 All All members x x x x x x

26

TASK Centre Persons Year 1 Year 2 Year 3STUDY 1, STUDY 2 and STUDY 3 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12

Phase III: Second cohort data collection x x x x x x x x x x x x

Accelerometry data collection on children UCA

UCA PA Graduates 1 & 2 (+FPI)

x x x

Fitness data collection on children UCA All UCA members x x x General information and mental health data collection on children UCA UCA PA Graduates

1 & 2 (+FPI) x x x Psyco-eviromental determinants data collection on children UCA UCA PA Graduates

1 & 2 (+FPI)

x x x

Saliva samples collection on children UCA All UCA Members x x x Blood sample data collection on children UCA Health specialist

worker

x x x

PA and food habits data collection on children (questionnaire): Years 1/Measure 1

UCA UCA PA Graduates 1 & 2 (+FPI)

x x x

Recording of first cohort data of fitness, PA determinants and mental health(children)

UCA UCA PA Graduates 1 & 2 (+ FPI)

x x x x x x

Debugging of accelerometry data (children) UAM O.Veiga; UAM PA

Graduates

x x x x x x

Recording of first cohort data of accelerometry data (children) UAM UAM PA Graduates

1,2 and 3

x x x x x x

Genotyping saliva samples (children) UCM All UCM members x x x x x x PA and food habits data collection on children (questionnaire)- Years 1/Measure 2

UCA UCA PA Graduates 1 & 2 (+ FPI)

x x

Record PA and food habits data: Year 1/Measure 3

UCA/CSIC

UCA PA Graduates 1 & 2 (+ FPI)

x x

PA and food habits data collection on children (questionnaire)- Years 1/Measure 3

UCA UCA PA Graduates 1 & 2 (+ FPI)

x x

Record PA and food habits data: Year 1/Measure 3 UCA UCA PA Graduates

1 & 2 (+ FPI)

x x

PA and food habits data collection on children (questionnaire)- Years UCA UCA PA Graduates

1 & 2 (+ FPI)

x x

27

TASK Centre Persons Year 1 Year 2 Year 3 STUDY 1, STUDY 2 and STUDY 3 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12

Phase III: Second cohort data collection x x x x x x x x x x x x 1/Measure 4

Record PA and food habits data: Year 1/Measure 4 UCA UCA PA Graduates

1 & 2 (+ FPI)

x x

Accelerometry data collection on adolescents & DS UAM UAM PA Graduates

1,2 and 3 (+ FPI) x x x

Fitness data collection on adolescents UAM UAM PA Graduates

1,2 and 3 (+ FPI) x x x

General information and mental health data collection on adolescents UAM UAM PA Graduates

1,2 and 3 (+ FPI)

x x x

Psycho-environmental determinants data collection on adolescents UAM All UAM members

x x x

Saliva samples collection on adolescents & DS UAM UAM PA Graduates

1,2 and 3 (+ FPI)

x x x

Blood sample data collection on adolescents & DS UAM Health specialist

worker

x x x

PA and food habits data collection on adolescents (questionnaire): Years 1/Measure 1

UAM All UAM Members

x x x x x

Research Team Coordination Meeting All All team members x Recording of first cohort data of fitness, PA determinants and mental health (adolescents)

CSIC Support/Laboratory Technician

x x x x

Debugging of accelerometry data (adolescents & DS) UAM UAM PA Graduates

1,2 and 3 (+ FPI)

x x x x

Recording of first cohort data of accelerometry data (adolescents) UAM UAM PA Graduates

1,2 and 3 (+ FPI)

x x x x x PA and food habits data collection on adolescents (questionnaire)- Years 1/Measure 2

UAM UAM PA Graduates 1,2 and 3 (+ FPI) x x

Record PA and food habits data adolescents: Year 1/Measure 2

UAM CSIC

UAM Graduates + Support Technician CSIC

x x

28

TASK Centre Persons Year 1 Year 2 Year 3 STUDY 1, STUDY 2 and STUDY 3 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12

Phase III: Second cohort data collection x x x x x x x x x x x x PA and food habits data collection on adolescents (questionnaire)- Year 2/Measure 3

UAM UAM PA Graduates 1,2 and 3 (+ FPI) x x

Record PA and food habits data: Year 2/Measure 3

UAM CSIC

UAM Graduates + Support Technician CSIC

x x

PA and food habits data collection on adolescents (questionnaire)- Year 2/Measure 4

UAM UAM PA Graduates 1,2 and 3 (+ FPI) x x

Record PA and food habits data: Year 1/Measure 4

UAM CSIC

UAM PA Graduates + Support Technician CSIC

x x

Preliminary Analysis of Accelerometer Data Cohort 2 UAM O.Veiga, C

Cordente, A Villagra x x x x x x

Preliminary Analysis of PA Self-reported Data Cohort 2 UAM JM Moya, A Acha J

Campo

x x x x x x

Preliminary Analysis of Health Related Fitness Data Cohort 2

UCA

J Castro J Mora J Ruiz

x x x x x x

Preliminary Analysis of Psycho-Environmental Determinants of Cohort 2

UAM C Tejero, M Díez, JM Moya, A Sanz

x x x x x x

Preliminary Analysis of Mental Health Indicators of Cohort 2 UCA J Conde JL Diaz R

Ortega

x x x x x x

Preliminary Analysis Biochemical parameters CSIC A Marcos, LE Díaz x x x x x x Preliminary Analysis of immunological parameters CSIC A Marcos, E Nova J

Romeo

x x x x x x

Preliminary Global Analysis Data Cohort 2 All All members x x x x x x

29

TASK Centre Persons Year 1 Year 2 Year 3 STUDY 1, STUDY 2 and STUDY 3 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12

Phase IV: Third cohort data collection x x x Accelerometry data collection on children UCA UCA PA Graduates

1 & 2 (+ FPI)

x x x

Fitness data collection on children UCA All UCA members x x x General information and mental health data collection on children UCA UCA PA Graduates

1 & 2 (+ FPI)

x x x

Psycho-environmental determinants data collection on children UCA UCA PA Graduates

1 & 2 (+ FPI)

x x x

Saliva samples collection on children UCA All UCA Members x x x Blood sample data collection on children UCA Health specialist

worker

x x x

PA and food habits data collection on children (questionnaire): Years 3/Measure 1

UCA UCA PA Graduates 1 & 2 (+ FPI)

x x x

Recording of first cohort data of fitness, PA determinants and mental health(children)

UCA UCA PA Graduates 1 & 2 (+ FPI)

x x

Debugging of accelerometry data (children) UAM O.Veiga; UAM PA

Graduates

x x

Recording of first cohort data of accelerometry data (children) UAM UAM PA Graduates

1,2 and 3

x x

Haematological analysis of blood samples (children) UCA Subcontracted

external laboratory

x x x

Biochemical analysis of blood samples (children) CSIC Support/Laboratory

Technician

x x

Immunological analysis of blood samples (children) CSIC Support/Laboratory

Technician

x x

Accelerometry data collection on adolescents & DS UAM UAM PA Graduates

1,2 and 3 (+ FPI)

x x x

Fitness data collection on adolescents & DS UAM UAM PA Graduates

1,2 and 3 (+ FPI)

x x x

General information and mental health data collection on adolescents UAM UAM PA Graduates

1,2 and 3 (+ FPI)

x x x

30

TASK Centre Persons Year 1 Year 2 Year 3 STUDY 1, STUDY 2 and STUDY 3 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12

Phase IV: Third cohort data collection x x x Psyco-eviromental determinants data collection on adolescents UAM All UAM members

x x x

Blood sample data collection on adolescents & DS UAM Health specialist

worker

x x x

PA and food habits data collection on adolescents (questionnaire): Years 3/Measure 1

UAM All UAM Members

x x x

Research Team Coordination Meeting All All team members x Recording of first cohort data of fitness, PA determinants and mental health (adolescents)

CSIC Support/Laboratory Technician

x x x

Debugging of accelerometry data (adolescents & DS) UAM UAM PA Graduates

1,2 and 3 (+ FPI)

x x x

Recording of first cohort data of accelerometry data (adolescents & DS)

UAM UAM PA Graduates 1,2 and 3 (+ FPI)

x x x

Haematological analysis of blood samples (adolescents & DS) UAM UAM PA Graduates

1,2 and 3 (+ FPI)

x x x

Biochemical analysis of blood samples (adolescents & DS) UCM All UCM members

x x x

Immunological analysis of blood samples (adolescents & DS) CSIC Subcontracted to

external laboratory x x x

31

TASK Centre Persons Year 1 Year 2 Year 3 STUDY 1, STUDY 2 & STUDY 3 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12

Phase V: Longitudinal data analysis & final report writing x x x x x x Longitudinal analysis of PA data children (accelerometry) UAM O.Veiga, C

Cordente, Villagra

x x x x x

Longitudinal analysis of PA data on adolescents (accelerometry) UAM

O.Veiga, C Cordente, A Villagra

x x x x x

Longitudinal analysis of PA data on DS adolescents (accelerometry)

UAM O.Veiga, C Cordente, A Villagra

x x x x x

Longitudinal analysis of Health-Related Fitness Data on children UCA J Castro J Mora J

Ruiz

x x x x x

Longitudinal analysis of Health-Related Fitness Data on adolescents UCA J Castro J Mora J

Ruiz

x x x x x

Longitudinal analysis of Health-Related Fitness Data DS Adolescents UCA J Castro J Mora J

Ruiz

x x x x x

Longitudinal analysis of PA self-report habits in children UAM JM Moya, A Acha

J Campo

x x x x x

Longitudinal analysis of PA self-report habits in adolescents UAM JM Moya, A Acha

J Campo

x x x x x

Longitudinal analysis of PA psycho-environmental determinants in children UAM C Tejero, M Díez,

JM Moya, A Sanz

x x x x x

Longitudinal analysis of PA psycho-environmental determinants in adolescents

UAM C Tejero, M Díez, JM Moya, A Sanz

x x x x x

Longitudinal analysis of metal health indicator in children UCA J Conde JL Diaz R

Ortega

x x x x x

Longitudinal analysis of metal health indicator adolescents UCA J Conde JL Diaz R

Ortega

x x x x x

Longitudinal analysis of food and hydration habits in children CSIC S Gómez B

Zapatera

x x x x x

Longitudinal analysis of food and hydration habits in adolescents CSIC S Gómez B

Zapatera

x x x x x

32

TASK Centre Persons Year 1 Year 2 Year 3 STUDY 1, STUDY 2 & STUDY 3 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12

Phase V: Longitudinal data analysis & final report writing x x x x x x

Analysis of attenuating PA effect of gene polymorphism

UCM-UAM

All members UCM -UAM

x x x x x

Analysis of attenuating PA on effect of gene polymorphism

UCM-UAM

All members UCM -UAM

x x x x x

Analysis of attenuating on fitness effect of gene polymorphism

UCM-UCA All members UCM -UCA

x x x x x

Analysis of attenuating fitness on effect of gene polymorphism

UCM-UCA All members UCM -UCA

x x x x x

Analysis of PA effect on development of cardiovascular disease risk factors in children

CSIC-UAM

O.Veiga, C Cordente, D Martínez

x x x x x

Analysis of PA effect on development of cardiovascular risk factors in adolescents

CSIC-UAM

O.Veiga, C Cordente, D Martínez, J Romeo

x x x x x

Analysis of PA effect on development of cardiovascular risk factors in DS adolescents

CSIC-UAM

O.Veiga, C Cordente, D Martínez, J Romeo

x x x x x

Analysis of PA effect development of inflammation biomarkers in children

CSIC-UAM

O.Veiga, C Cordente, D Martínez, J Romeo

x x x x x

Analysis of PA effect on development of inflammation biomarkers in adolescents

CSIC-UAM

O.Veiga, C Cordente, D Martínez, J Romeo

x x x x X

Analysis of PA on effect on development of inflammation biomarkers in DS adolescents

CSIC-UAM

O.Veiga, C Cordente, D Martínez, J Romeo

x x x x X

Analysis of fitness status on development of cardiovascular risk factors children

CSIC-UCA

O.Veiga, C Cordente, D Martínez, J Romeo

x x x x X

33

TASK Centre Persons Year 1 Year 2 Year 3 STUDY 1, STUDY 2 & STUDY 3 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12

Phase V: Longitudinal data analysis & final report writing x x x x x x Analysis of fitness status on development of cardiovascular risk factors adolescents

CSIC-UCA

A Marcos E Nova J Ruiz J Castro

x x x x X

Analysis of fitness status on development of cardiovascular risk factors DS adolescents

CSIC-UCA

A Marcos E Nova J Ruiz J Castro

x x x x X

Analysis of fitness status on development of inflammation biomarkers children

CSIC-UCA

A Marcos E Nova J Ruiz J Castro

x x x x X

Analysis of fitness status on development of inflammation biomarkers adolescents

CSIC-UCA

A Marcos E Nova J Ruiz J Castro

x x x x X

Analysis of fitness status on development of inflammation biomarkers DS Adolescents

CSIC-UCA

A Marcos E Nova J Ruiz J Castro

x x x x x

Writing final reports All All members x x x x x Writing initial scientific papers All All members x x x x x

34

35

TASK Centre Persons Year 1 Year 2 Year 3

STUDY 4 1 2 3 4 5 6 7 8 9 10

11

12 1 2 3 4 5 6 7 8 9 1

011

12 1 2 3 4 5 6 7 8 9 1

0 11

12

Phase I: Preparatory tasks x x x Preparing the technical specifications of the ODMS All All x x x Preparing the technical specifications of the OIDC

UCA, UAM, CSIC All x x x

Preparing the technical specifications of the questionaires for optical reader devices

UCA,UAM,CSIC All x x x

Preparing the technical specifications of the accelerometry analyzer

UAM O.Veiga; UAM Graduates 1,2 and 3 x x x

Phase II: Developments x x x x x x x x x

ODMS development UCA Subcontracted external company x x x x x

OIDC development UCA Subcontracted external

company x x x x x Development of the questionnaires for optical reader devices and computer versions

UCA Subcontracted external company x x

Development of accelerometry analyzer

UCA UAM

Subcontracted external company x x

Phase III: Optimization x x x x x x

ODMS optimization UCA Subcontracted external company

x Pilot study of OIDC in children UCA all x x Pilot study of OIDC in adolescents UAM/CSIC all x x

OIDC development UAM Subcontracted external

company/ O.Veiga; UAM Graduates 1,2 & 3

x

OIDC optimization UCA Subcontracted external company x x x x

PA Graduates: Graduates on Physical Activiy and Sport Sciences contracted with the Research Project Funds FPI: FPI fellowship

5. BENEFITS DERIVED FROM THE PROJECT, DIFUSION AND EXPLOTATION OF RESULTS (maximum 1 page) Benefits The main benefits obtained from the UP&DOWN study are as follows: - Information on the growth/deterioration in a 3-year follow-up of lifestyles such as physical activity, academic performance and dietary patterns during schooling period (age ranged 6-17 years) and in adolescents with Down syndrome. - Information on the growth/deterioration of health indicators such as fitness, obesity, cognitive performance, stress, anxiety, hypertension, metabolic syndrome and immuno-inflammation during schooling period (age ranged 6-17 years) and in adolescents with Down syndrome. - Information on the effect of physical activity on health indicators in schooling period (age ranged 6-17 years) and in adolescents with Down syndrome. - Identification of lifestyle behaviours that can attenuate the detrimental effect of certain polymorphism of genes associated with chronic diseases in apparently healthy schoolchildren and in adolescents with Down syndrome. - Development of an epidemiological on-line tool to collect data on lifestyle behaviours and health indicators in Spanish schoolchildren. - Development of an educational on-line tool to report feedbacks and advices in Spanish schoolchildren with regard to their lifestyle behaviours and health indicators. - Training for graduate students involved in postgraduate courses and PhD students. - Option to continue the study the next 3 years between 2014-2016 (2013 I+D+I) - Development of the WHO Global Strategy on Diet, Physical Activity and Health, NAOS Strategy (Spanish Ministry of Health and Social Policy) and the A+D Integral Plan for Physical activity and Sport (Spanish National Sports Council) Diffusion plan & explotation of the results. Scientific diffusion: A communication and dissemination plan for exploitation and dissemination of the project results will be planned by the UP&DOWN consortium from the beginning of the project including the following issues: - Scientific papers and meetings: The research groups involved in the UP&DOWN study have experience and interest in publishing their scientific articles in impact factor journals and in presenting their results in national and international scientific meetings. The most relevant results from the UP&DOWN study will be written and submitted to scientific and educational journals indexed in Journal Citation Reports (JCR). - Website: An official UP&DOWN website will be created during the first 3 months, which will be closely coordinated by the CSIC group and all the research groups will be connected throughout this way. Each research group will provide a link from their own sites to the official site and links will also be established from the websites of our Institutions, namely the supporting ones. The website will be maintained by CSIC, for at least 3 years after the completion of the project, but it is plausible and desirable to maintain the website for 3 more years after the end of the project to facilitate information about papers within the scientific field. Preliminary results of academic and scientific papers, meetings, workshops, conferences, symposiums, awards, etc. derived from the UP&DOWN study will be shown into the website in a free status. - International Workshop: The coordinator research group will submit an application to the call scheduled for 2013 Subprogramme for Complementary Actions by Basic Research Projects for the organization of an International Workshop to disseminate the UP&DOWN findings. The CSIC group has a wide experience on this issue because organizes bi-annually International Courses and Workshops: www.immunonutritionworkshop.com Social diffusion: - The results from the UP&DOWN study will be also disseminated among the general population. To this end, informative guides will be written by the consortium of this project with the support of the Spanish National Sports Council, Spanish Food Security and Nutrition Agency from the Spanish Ministry of Health and Social Policy), Institute of Nutrition and Eating Disorders and the Sport Medicine Centre from Ministry of Health (Madrid Region). This information will reach parents/tutors/ and school teachers in order to facilitate them tools to encourage children and adolescents to practice the best levels of physical activity to achieve the most beneficial health effects, and consequently tackle the high risk indexes of chronic diseases, which nowadays is a flagstone for Health and Social Policy. - CSIC Press releases, UCA Press releases, UAM Press releases, UCM Press releases, School centres (primary, secondary and special) involved in the UP&DOWN study, CSD website, AESAN website Institute of Nutrition and Eating Disorders. Ministry of Health and Social Policy. Madrid Region website, Sport Medicine Centre from Ministry of Health. Madrid Region website.

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6. BACKGROUND OF THE GROUP (maximum 2 pages)

The CSIC-Immunonutriton research group headed by Prof. Ascension Marcos has participated in one EU FP projects (HELENA Study) and has coordinated several multi-centre Spanish projects related to adolescent nutritional status, eating disorders and obesity, funded by the Foundation for Health Research from Ministry of Health and Consumption (AVENA Study), Ministry of Education and Science (AFINOS Study), and Alicia Koplowitz Foundation (ANABEL study). In these projects CSIC has been responsible for the nutrition-related immunological and inflammatory assessment for subclinical detection of malnutrition and cardiovascular diseases, interventions in overweight and obese adolescents in primary care centres using a multidisciplinary approach including physiological treatment as well as diet education and physical activity motivation, and evolution of biomarkers during follow-up studies in bulimia and anorexia nervosa adolescents. Staff involved in the subproject: Ascension Marcos (PhD), Esther Nova (PhD), Javier Romeo (PhD), Sonia Gomez-Martinez (PhD), Esperanza L Diaz (PhD), Tamara Pozo (MSc), David Martinez-Gomez (MSc). Last 5 JCR publications related to the topic involved: • Romeo J, Wärnberg J, García-Mármol E, Rodríguez-Rodríguez M, Diaz LE, Gomez-Martínez S, Cueto B, López-Huertas

E, Cepero M, Boza JJ, Fonollá J, Marcos A. Daily consumption of milk enriched with fish oil, oleic acid, minerals and vitamins reduces cell adhesion molecules in healthy children. Nutr Metab Cardiovasc Dis. [Epub ahead of print].

• Martinez-Gomez D, Gomez-Martinez S, Puertollano MA, Nova E, Wärnberg J, Veiga OL, Martí A, Campoy C, Garagorri JM, Azcona C, Vaquero MP, Redondo-Figuero C, Delgado M, Martínez JA, Garcia-Fuentes M, Moreno LA, Marcos A; EVASYON Study Group. Design and evaluation of a treatment programme for Spanish adolescents with overweight and obesity. The EVASYON Study. BMC Public Health. 2009;9:414.

• Wärnberg J, Gomez-Martinez S, Romeo J, Díaz LE, Marcos A. Nutrition, inflammation, and cognitive function. Ann N Y Acad Sci. 2009;1153:164-75.

• Nova E, Lopez-Vidriero I, Varela P, Casas J, Marcos A. Evolution of serum biochemical indicators in anorexia nervosa patients: a 1-year follow-up study.J Hum Nutr Diet. 2008;21(1):23-30.

• Diaz LE, Cano P, Jimenez-Ortega V, Nova E, Romeo J, Marcos A, Esquifino AI. Effects of moderate consumption of distilled and fermented alcohol on some aspects of neuroimmunomodulation. Neuroimmunomodulation. 2007;14:200-5.

The UAM research group headed by Dr. Oscar L. Veiga had expertise on physical activity and health, and determinants of physical activity and sedentary behaviour. The members of this group have been participating in the Spanish PERSEO program (www.perseo.aesan.msps.es) and in other national projects funding by the Spanish Ministries of Education (AFINOS Study) and Health (EVASYON Study). They have collaborations with international groups at Iowa State University (ISU); Michigan State University (MSU); Karolinska Institutet (Sweden) and the University of Porto (Portugal). UAM has also participated in several books related to physical activity and Down syndrome in early ages, and collaborations in this field are with associations such as Special Olympics (www.specialolympics.es), Telefonica, APIFAD and Autonomous Region of Madrid. Staff involved in the subproject: Oscar L Veiga (PhD), Ariel Villagra (PhD), Juan del-Campo (PhD), Carlos Cordente (PhD), Mario Diaz (PhD), Carlos M Tejero (PhD), Jose Mª Moya (PhD), Aitor Acha (BSc) and Alberto Sanz (BSc). Last 5 JCR publications related to the topic involved: • Martínez-Gómez D, Calabro MA, Welk GJ, Marcos A, Veiga OL. Reliability and validity of a school recess physical activity

recall in Spanish youth. Pediatr Exerc Sci. In press. • Martínez-Gómez D, Welk GJ, Puertollano MA, del-Campo J, Moya JM, Marcos A, Veiga OL, and the AFINOS Study

Group. Associations of physical activity with muscular fitness in adolescents. Scand J Med Sci Sports. [Epub ahead of print].

• Veiga OL, Gómez-Martínez S, Martinez-Gomez D, Villagra A, Calle ME, Marcos A; AFINOS Study Group. Physical activity as a preventive measure against overweight, obesity, infections, allergies and cardiovascular disease risk factors in adolescents: AFINOS Study protocol. BMC Public Health. 2009:9:475.

• Martínez-Gómez D, Wärnberg J, Welk GJ, Sjöström M, Veiga OL, Marcos A. Validity of the Bouchard activity diary in Spanish adolescents. Public Health Nutr. 2010;13(2):261-268

• Martínez-Gómez D, Welk GJ, Calle ME, Marcos A, Veiga OL; and the AFINOS Study Group. Preliminary evidence of physical activity levels measured by accelerometer in Spanish adolescents. The AFINOS Study. Nutr Hosp. 2009;24(2):212-218.

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The group of University of Cadiz (GALENO, CTS-158) headed by Dr. Jose Castro-Piñero will lead the subproject on health-related physical fitness. This group has large experience in the assessment of (i) physical fitness using own developed standardized methods, now used across the world, after involvement in EU-projects like ALPHA (www.thealphaproject.eu/); (ii) the relation between physical activity, fitness and cardiovascular risk factors in young ages which has been studied extensively in the AVENA study (http://www.estudioavena.es/) the European Youth Heart Study (EYHS), and the EU-funded HELENA study (http://www.helenastudy.com/). The group is active in several National (Spanish) projects and International and National networks. The table below describes the projects and groups that some of the members from the UCA group has already been working with. This study will reinforce the UCA’s existing National collaborations, as well as will serve as a potential platform to increase the group’s possibilities to establish a fruitful and successful research network in the field of fitness and cardiovascular health in young people. Staff involved in the subproject: José Castro Piñero (PhD), Jesús Mora Vicente (MD, PhD), José Luis González Montesinos (PhD), Julio Conde Caveda (PhD), Francisco B Ortega (PhD) and Jonatan R Ruiz (PhD). Last 5 JCR publications related to the topic involved: • Castro-Piñero J, Artero EG, España-Romero V, Ortega FB, Sjöström M, Suni J, Ruiz JR. Criterion-related validity of field-

based fitness tests in youth: a systematic review. Brit J Sports Med, 2009; Apr 12. [Epub ahead of print]. • Castro-Piñero J, González-Montesinos JL, Mora J, Keating XD, Girela-Rejón MJ, Sjöström M, Ruiz JR. Percentile values

for muscular strength field tests in children aged 6 to 17 years; influence of weight status. J Strength Cond Res. 2009;23(8):2295-310.

• Ruiz JR, Castro-Piñero J, Artero EG, Ortega FB, Sjöström M, Suni J, Castillo MJ. Predictive Validity of Health-Related Fitness in Youth: A Systematic Review. Brit J Sports Med 2009; 43: 909-23.

• Castro-Piñero J, Ortega FB, Mora J, Sjöström M, Ruiz JR. Criterion related validity of 1/2 mile run-walk test for estimating VO2peak in children aged 6-17 years. Int J Sports Med 2009; 30(5): 366-7.

• Lobelo F, Pate RR, Dowda M, Liese AD, Ruiz JR. Validity of Cardiorespiratory Fitness Criterion-Referenced Standards for Adolescents. Med Sci Sports Exerc. 2009;41(6):1222-1229

The group of UCM headed by Dr. Fernando Bandrés will lead the subproject on gene-lifestyle interactions. This research group has a wide experience in genotype-phenotype studies funded by the Spanish Council of Sports (CSD) and Ministry of Health (FIS) with similar topics than the current UP&DOWN study. In these studies, the UCM group has analyzed polymorphisms related to physical fitness, lifestyle behaviours and health risks in apparently healthy (children, adolescents, adults, older adults) and unhealthy individuals (anorexia, cancer, cystic fibrosis, etc). The main findings obtained from these studies have been published in high impact factor journal indexed in JCR. Staff involved in the subproject: Fernando Bandrés (MD, PhD), Catalina Santiago (MD, PhD) and Felix Gómez-Gallego (MD, Phd). Last 5 JCR publications related to the topic involved: • Santiago C, Rodríguez-Romo G, Gómez-Gallego F, González-Freire M, Yvert T, Verde Z, Naclerio F, Altmäe S, Esteve-

Lanao J, Ruiz JR, Lucia A. Is there an association between ACTN3 R577X polymorphism and muscle power phenotypes in young, non-athletic adults? Scand J Med Sci Sports. 2009 Oct 5. [Epub ahead of print]

• Santiago C, Ruiz JR, Buxens A, Artieda M, Arteta D, Gonzalez-Freire M, Rodríguez-Romo G, Altmäe S, Lao JI, Gómez-Gallego F, Lucia A. Trp64Arg polymorphism in ADRB3 gene is associated with elite endurance performance. Br J Sports Med. 2009 Jun 23. [Epub ahead of print]

• Gomez-Gallego F, Santiago C, González-Freire M, Yvert T, Muniesa CA, Serratosa L, Altmäe S, Ruiz JR, Lucia A. The C allele of the AGT Met235Thr polymorphism is associated with power sports performance. Appl Physiol Nutr Metab. 2009;34(6):1108-11.

• Gómez-Gallego F, Ruiz JR, Buxens A, Artieda M, Arteta D, Santiago C, Rodríguez-Romo G, Lao JI, Lucia A. The -786 T/C polymorphism of the NOS3 gene is associated with elite performance in power sports. Eur J Appl Physiol. 2009;107(5):565-9.

• Santiago C, Ruiz JR, Muniesa CA, González-Freire M, Gómez-Gallego F, Lucia A. Does the polygenic profile determine the potential for becoming a world-class athlete? Insights from the sport of rowing. Scand J Med Sci Sports. 2009 Apr 20. [Epub ahead of print]

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6.2 PUBLIC AND PRIVATE GRANTED PROJECTS AND CONTRACTS OF THE RESEARCH GROUP Indicate the project and contract grants during the last 5 years (2005-2009) (national, regional or international)

Title of the project or contract

Relationship with this

proposal (1)

Principal Investigator

Budget

Funding agency and project

reference

Project period (2)

EURO Valoración de biomarcadores inmunológicos en niños con asma. Efecto de los probióticos.

2 Ascensión Marcos 72.000 DANONE 2005-2006C

Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA)

1 COORDINADOR: Luis Moreno Subproyecto Madrid: Ascensión Marcos

5.000.000 (Madrid-486.000)

COMUNIDAD EUROPEA. VI PROGRAMA MARCO. FOOD-

CT-2005-007034

2005-2008C

Utilidad de la cerveza en la recuperación del metabolismo mineral, hormonal e inmunológico de deportistas tras realizar un esfuerzo físico.

3 COORDINADOR: Manuel Castillo Subproyecto Madrid: Ascensión Marcos

67.980 ASOCIACION CERVECEROS DE ESPAÑA.

2005-2006C

Evaluación de la relación entre la inmunocompetencia y el patrón de colonización microbiana intestinal en la enfermedad celiaca. Inmunomodulación por potenciales probióticos.

2 COORDINADOR: Yolanda Sanz Subproyecto Madrid: Ascensión Marcos

29.500 PROYECTOS INTRAMURALES DE FRONTERA (CSIC) Ref:

200570F0093

2005-2007C

Evaluación del efecto de un complemento nutricional sobre la regulación intestinal y la función inmune.

2 Ascensión Marcos 37.753 PHERGAL 2006-2007C

Desarrollo, aplicación y evaluación de la eficacia de un programa terapéutico para adolescentes con sobrepeso y obesidad: educación integral nutricional y de actividad física. (EVASYON)

1 COORDINADOR: Ascensión Marcos Subproyecto Madrid: Ascensión Marcos

320.000 (Subproyecto

Madrid: 113.000)

FIS Ref: PI051574 2006-2009C

Actividad física como agente activador del sistema inmune e inhibidor del proceso inflamatorio y los factores de riesgo cardiovascular (AFINOS)

1 Ascensión Marcos 50.000 Ministerio de Educación y Ciencia

2007-2010 C

Estudio de las propiedades inmunomoduladoras de bacterias probióticas de posible utilidad terapéutica o preventiva en la enfermedad celiaca

3 Ascensión Marcos 14.400 CSIC 2007 C

Papel de la nutrición y la genética materna sobre la programación del desarrollo del tejido adiposo fetal. Búsqueda de marcadores de riesgo de obesidad en etapas precoces de la vida (PREOBE)

2 COORDINADOR: Cristina Campoy Subproyecto Madrid: Ascensión Marcos

58.000 Junta de Andalucía 2007-2010 C

Investigación científica dirigida al desarrollo de una nueva generación de alimentos para el control de peso y prevención de la obesidad (PRONAOS)

2 COORDINADOR: PULEVA BIOTECH Subproyecto Madrid: Ascensión Marcos

578.000 CDTI 2008-2011 C

39

Clasificación de la población en diferentes segmentos y estudio de las necesidades nutricionales de cada uno de ellos” (AL-ANDSALUD).

2 COORDINADOR: GRUPO SOS, COPAV Subproyecto Madrid:

Ascensión Marcos

375.000 CDTI 2009-2012 C

Beneficios nutricionales del aceite de oliva. PRO-OLIVE. 3 COORDINADOR: GRUPO SOS Subproyecto Madrid:

Ascensión Marcos

336.000 CDTI 2009-2012

40

Title of the project or contract

Relationship with this

proposal (1)

Principal Investigator

Budget

Funding agency and project

reference

Project period (2)

EUROS Proyectos para la integración de las tecnologías de la información y la comunicación en el proceso de enseñanza-aprendizaje

2 Emilio J. López Caballero 2,000 Universidad de Alcalá 2006-2007 C

La evaluación de capacidades motrices, estilos de vida y valores en la población escolar, y su repercusión en la elaboración de programas sociales y educativos en Argentina, Brasil y España

1 Roberto Velázquez Buendía

17,825 UAM-Grupo Santander 2006-2008 C

Desarrollo, aplicación y evaluación de la eficacia de un programa terapéutico para adolescentes con sobrepeso y obesidad: educación integral nutricional y de actividad física. (EVASYON)

1 Ascensión Marcos Sánchez 113,050 Fondo de Investigaciones Sanitarias

2006-2010 C

Evaluación de la actividad física, condición física, antropometría y composición corporal, y su relación con patologías relacionadas con los estilos de vida sedentario. AFINOS Study

1 Hernán Ariel Villagra Astudillo

27,126 Ministerio de Ciencia y Tecnología

2006-2009 C

El proceso de comunicación docente en educación física y su influencia sobre la adopción de hábitos de actividad físico-deportiva y de estilos de vida saludables entre la población escolar

1 Juan Luís Hernández Álvarez

31,500 Ministerio de Ciencia y Tecnología

2007-2010 C

Elaboración de material informativo y didáctico de promoción de la actividad física en el ámbito escolar, para su uso en el Programa PERSEO

1 Oscar L Veiga 12,000 AESAN 2007 C

Elaboración de guías de promoción de la actividad física para su uso en el Programa PERSEO de promoción de la alimentación saludable y la actividad física en el ámbito escolar.

1 Oscar L Veiga 12,000 AESAN 2007 C

Evaluación de indicadores morfológicos, condición física y hábitos de vida saludables en la población infanto-juvenil en zonas socioeconómicas muy desfavorables y de grave desnutrición

1 Hernán Ariel Villagra Astudillo

23,000 AECI 2008 C

Sensibilización en centros educativos sobre las personas con discapacidad y mayores como prevención contra la discriminación. Progress

1 Hernán Ariel Villagra Astudillo

400.000 Unión Europea VP/2007/006/594

2007-2013 C

Hacia la accesibilidad universal y el diseño para todos en recintos deportivos: el caso de los estadios de fútbol de 1ª división en España

3 Juan Luis Paramio Salcines 12,850 CSD 2008 C

Formación investigadora basada en proyectos aplicados. Sensibilización e inclusión social de personas con discapacidad, niños y jóvenes de alto riesgo social, y trastornos de la alimentación

1 Hernán Ariel Villagra Astudillo

10,500 UAM-Grupo Santander 2009-2010 C

41

Title of the project or contract

Relationship with this

proposal (1)

Principal Investigator

Budget

Funding agency and project

reference

Project period (2)

EUROS

Batería de tests para la valoración de la condición física en diferentes grupos de población. BATESTAN (Batería de Tests Andalucía). Propuesta unificadora

1 Jesús Mora Vicente

6.050 Centro Andaluz de Medicina del Deporte. Junta de Andalucía

2005-2006 C

HELENA: "Healthy lifestyle in Europe by nutrition in adolescence" 1 Luis Moreno Aznar 5.000.000 Sexto Programa Marco. Unión Europea

2006-2008 C

IDEFICS: " Identification and prevention of dietary- and lifestyle-induced health effects in children and infants”

1 Wolfgang Ahrens 12.000.000 Sexto Programa Marco. Unión Europea

2006-2011

Assessing Levels of Physical Activity. ALPHA Project 1 Michael Sjöstrom 1.697.889 Public Health Executive Agency (PHEA). Unión Europea

2007-2009 C

Physical activity, fitness, cardiovascular risk factors and gene-lifestyle interactions in youths

1 Jonatan R Ruiz 13.000 Fundación Karolinska Institutet

2008-2009

The European Youth Heart Study – a collaborative effort; Analyses of longitudinal objective data on physical activity habits and influence of CVD risk factors will make interventions more effective!

1 Jonatan R Ruiz 25.000 Fundación Karolinska Institutet

2008-2010 C

Physical activity, fitness, cardiovascular risk factors and gene-lifestyle interactions in young Swedish people. A longitudinal sub-study of the European Youth Heart Study

1 Jonatan R Ruiz 136.000 Fundación Karolinska Institutet

2009-2010 C

Propuesta y evaluación de un programa de Educación Física en una población diabética adulta

2 Jesús Mora Vicente

4.000 Excma. Diputación de Cádiz 2006-2006 C

Condición física en la mujer: Nuevo indicador de envejecimiento biológico y potente predictor de morbilidad y mortalidad por todas las causas. Validación de un protocolo de evaluación de la condición física y prescripción individualizada de ejercicio

3 Manuel J Castillo Garzón

6.500 Consejo Superior de Deportes. Ministerio de Educación, Cultura y Deporte.

2004-2005 C

Utilidad de la cerveza en la recuperación del metabolismo mineral, hormonal e inmunológico de deportistas tras realizar un esfuerzo físico

3 Manuel J Castillo Garzón

68.000 Asociación Española de Cerveceros

2005-2006 C

Laboratorio ergonómico para el desarrollo y validación de un protocolo integral de valoración de la calidad de vida en poblaciones adultas y mayores. (Acrónimo: ERGOLAB).

3 Manuel J Castillo Garzón

266.000 Ministerio de Educación y Ciencia

2005-2008 C

Sistema de detección de apoyos vía radio 3 José Luís González Montesinos

3.500 Universidad de Cádiz. OTRI 2007-2007 C

42

Desarrollo de un instrumento de evaluación de los patrones temporales en el baile flamenco mediante un sistema de detección de apoyos

3 José Luis González Montesinos

6.000 Consejería de Cultura de la Junta de Andalucia

2007-2008 C

Efectos del entrenamiento de los músculos respiratorios sobre indicadores de rendimiento en deportistas mujeres de alto nivel de resistencia aeróbica

3 Jesús Mora Vicente

42.700 Consejería de Turismo Ocio y Deporte Junta de Andalucía

2007-2008 C

Valoración y preparación física en la población flamenca andaluza 3 José Luis González Montesinos

8.100 Agencia Andaluza para el Desarrollo del Flaenco

2008-2009 C

Desarrollo de un nuevo sistema de restricción de flujo ventilatorio y estudio de sus efectos en el entrenamiento de músculos inspiratorios en atletas.

3 José Luis González Montesinos

25.000 Consejo Superior de Deportes Duración 1 año desde la

fecha de concesión

S

43

Title of the project or contract

Relationship with this

proposal (1)

Principal Investigator

Budget

Funding agency and project

reference

Project period (2)

EUROS Bases fisiológicas y genéticas de la superioridad de los corredores de fondo africanos: aplicaciones para el entrenamiento de los corredores españoles y la detección de talentos en nuestro país

1 Alejandro Lucía Mulas 13.900 Consejo Superior de Deportes C

Farmacogenética de citocromo P450 2D6: Estudio de sensibilidad a neurolépticos en pacientes psiquiátricos 2 Félix Gómez Gallego 11.700 Universidad Europea de

Madrid C

Estudio de diversos polimorfismos genéticos en enfermos de McArdle: Influencia en la intolerancia al ejercicio de estos pacientes. 1 Alejandro Lucía Mulas 13.400 Universidad Europea de

Madrid C

Bases genéticas de la dependencia a tabaco y su relación con patologias asociadas: implicaciones del citocromo P450 2A6 2 Catalina Santiago Dorrego 6.000 Universidad Europea de

Madrid C

Estudio de genotipos de citocromoP450 2C9 (CYP2C9) y vitamina K epoxido reductasa (VKORC1) como determinantes de hipersensibilidad al acenocumarol (sintrom).

2 Zoraida Verde Rello 6.000 Universidad Europea de Madrid C

Bases genéticas del alto rendimiento en remo (categoría de peso ligero masculino) 2 Alejandro Lucía Mulas 20.130 Consejo Superior de Deportes C

Polimorfismos genéticos y anorexia nerviosa. Aplicaciones de marcadores genéticos a la respuesta a la actividad física 1 Catalina Santiago Dorrego 6.000

Cátedra Real Madrid – Universidad Europea de

Madrid C

Efectos del ejercicio físico en niños con fibrosis quística. Factores genéticos moduladores 1 Félix Gómez Gallego 6.000

Cátedra Real Madrid – Universidad Europea de

Madrid C

Prescripción de un programa de ejercicio físico intrahospitalario para niños con fibrosis quística: Efectos sobre su capacidad funcional y estado de salud general.

1 Alejandro Lucía Mulas 151.000 Fondo de Investigaciones

Sanitarias. Instituto de Salud Carlos III. Ministerio de

Sanidad y Consumo C

44

(1) Write 0, 1, 2 or 3 according to: 0 = Similar project; 1 = Very related; 2 = Low related; 3 = Unrelated. (2) Write C or S if the project has been funded or it is under evaluation, respectively.

7. TRAINING CAPACITY OF THE PROJECT AND THE GROUP (In the case of Coordinated Projects this issue must be filled by each partner) This title must be filled only in case of a positive answer to the corresponding question in the application form. Justify that the group is able to receive fellow students (from the Suprograma de Formación de Investigadores) associated to this project and describe the training capacity of the group. In the case of coordinated projects, each subproject requesting a FPI fellowship must fill this issue.

The UAM research group members are active professors in the Physical Education and Physical activity and Sport Science University graduate programmes for training to future primary and secondary teachers. The Department of Physical Education, Sport and Human Movement includes 2 research laboratories: 1) Physical activity, Body Composition and Physical Performance Lab; 2) Multimedia Lab for Human Movement and Teaching in Physical Education. Nowadays, UAM training capacity includes two posgraduate programmes. Firtly, the Innovation, Assessment and Quality in Physical Education programme. Secondly, the Physical Activity, Persons with Disabilities and Social Integration programme. The last one is one of the few in Europe and the first national postgraduate programme in this topic and training graduated students in physical activity skills to work with physical and mental disabilities persons -mainly children and adolescents populations. In this programme relevant public health institutions that daily work with these populations (Special Olimpics, FEMADI, Deporte & Desafio, Comité Paraolímpico Español, FUAM, Federación Madrileña de Deporte para Sordos, Fundación Real Madrid) participate. After obtaining the MSc, postgraduate students may be involved in PhD programmes through projects from the Department. Ongoing projects include National and International studies (Portugal, France, South America), as well as collaborations with European and USA research groups.

The UCA research group has extensive training capacity since they are involved in teaching postgraduate programmes at the University of Cadiz (Masters of Teaching in Primary and Seconday, Vocational Training, Teaching of Foreign Languages, and PhD in Health and Sport from the Medical School of Physical Education and Sport), as well as other Spanish, South American and European Universities. Also, several team members have conducted PhD thesis (some with European mention). Nowadays, UCA has many doctoral students who are integrated into the group, some fellows in training (FPU or simililar) associated with different projects .

45

References: - Andreasen CH, Stender-Petersen KL, Mogensen MS, Torekov SS, Wegner L, Andersen G, Nielsen AL, Albrechtsen

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