Bone and Phosphate in Relation to Health, Survival and Genetic Factors

In this thesis, we found that a) low bone mineral density was related to increased mortality from chronic obstructive pulmonary disease and b) increased serum phosphate, even at normal levels, was related to fracture risk, low BMD at the lumbar spine and coronary artery calcification. For the latter association, we found evidence of causality, due to the implementation of Mendelian Randomization technique. All our results were more consistent or even unique in men. The genetic analyses on phosphate levels identified 264 loci in the human genome and highlighted the importance of the Major Histocompatibility Complex (6p21.3) also on phosphate levels, as the top hit mapped to the flanking region of the MHC. Interestingly, the same finding has been described in White British and East Asian Japanese populations. Our next step will be the replication in BioBank Japan followed by trans-ethnic meta-analysis and Bayesian fine-mapping

Bone mineral density and chronic lung disease mortality: the Rotterdam study

Context: Low bone mineral density (BMD) has been associated with increased all-cause mortality. Cause-specific mortality studies have been controversial. Objective: The aim of the study was to investigate associations between BMD and all-cause mortality and in-depth cause-specific mortality. Design and Setting: We studied two cohorts from the prospective Rotterdam Study (RS), initiated in 1990 (RS-I) and 2000 (RS-II) with average follow-up of 17.1 (RS-I) and 10.2 (RS-II) years until January 2011. Baseline femoral neck BMD was analyzed in SD values. Deaths were classified according to International Classification of Diseases into seven groups: cardiovascular diseases, cancer, infections, external, dementia, chronic lung diseases, and other causes. Gender-stratified Cox and competing-risks models were adjusted for age, body mass index, and smoking. Participants: The study included 5779 subjects from RS-I and 2055 from RS-II. Main Outcome Measurements: We measured all-cause and cause-specific mortality. Results: A significant inverse association between BMD and all-cause mortality was found in males [expressed as hazard ratio (95% confidence interval)]: RS-I, 1.07 (1.01-1.13), P = .020; RS-II, 1.31 (1.12-1.55), P = .001); but it was not found in females: RS-I, 1.05 (0.99-1.11), P = .098; RS-II, 0.91 (0.74-1.12), P = .362. An inverse association with chronic lung disease mortality was found in males [RS-I, 1.75 (1.34-2.29), P < .001; RS-II, 2.15 (1.05-4.42), P = .037] and in RS-I in females [1.72 (1.16-2.57); P = .008], persisting after multiple adjustments and excluding prevalent chronic obstructive pulmonary disease. A positive association between BMD and cancer mortality was detected in females in RS-I [0.89 (0.80-0.99); P = .043]. No association was found with cardiovascular mortality. Conclusions: BMD is inversely associated with mortality. The strong association of BMD with chronic lung disease mortality is a novel finding that needs further analysis to clarify underlying mechanisms

Genetic Evidence for a Causal Role of Serum Phosphate in Coronary Artery Calcification:The Rotterdam Study

BACKGROUND: Hyperphosphatemia has been associated with coronary artery calcification (CAC) mostly in chronic kidney dis-ease, but the association between phosphate levels within the normal phosphate range and CAC is unclear. Our objectives were to evaluate associations between phosphate levels and CAC among men and women from the general population and assess causality through Mendelian randomization. METHODS AND RESULTS: CAC, measured by electron-beam computed tomography, and serum phosphate levels were assessed in 1889 individuals from the RS (Rotterdam Study). Phenotypic associations were tested through linear models adjusted for age, body mass index, blood pressure, smoking, prevalent cardiovascular disease and diabetes, 25-hydroxyvitamin D, total calcium, C-reactive protein, glucose, and total cholesterol: high-density lipoprotein cholesterol ratio. Mendelian randomiza-tion was implemented through an allele score including 8 phosphate-related single-nucleotide polymorphisms. In phenotypic analyses, serum phosphate (per 1 SD) was associated with CAC with evidence for sex interaction (Pinteraction =0.003) (men β, 0.44 [95% CI, 0.30– 0.59]; P=3×10−9; n=878; women β, 0.24 [95% CI, 0.08– 0.40]; P=0.003; n=1011). Exclusion of hyperphos-phatemia, chronic kidney disease (estimated glomerular filtration rate &lt;60 mL/min per 1.73 m2) and prevalent cardiovascular disease yielded similar results. In Mendelian randomization analyses, instrumented phosphate was associated with CAC (total population β, 0.93 [95% CI: 0.07–1.79]; P=0.034; n=1693), even after exclusion of hyperphosphatemia, chronic kidney disease and prevalent cardiovascular disease (total population β, 1.23 [95% CI, 0.17– 2.28]; P=0.023; n=1224). CONCLUSIONS: Serum phosphate was associated with CAC in the general population with stronger effects in men. Mendelian randomization findings support a causal relation, also for serum phosphate and CAC in subjects without hyperphosphatemia, chronic kidney disease, and cardiovascular disease. Further research into underlying mechanisms of this association and sex differences is needed.</p

Bone health and coronary artery calcification: The Rotterdam Study

Objectives: Vascular calcification has been associated inconsistently to low bone mineral density and fractures. The aims of the present study were to investigate the associations between coronary artery calcification (CAC) and BMD change, BMD and fracture risk in elderly subjects of the population-based Rotterdam Study. Methods: BMD was assessed through dual-energy X-ray absorptiometry and CAC through Electron-Beam Computed Tomography in 582 men and 694 women. We investigated the associations between BMD change (6.4 years follow-up) and CAC at follow-up and between BMD and CAC (measured simultaneously). In sensitivity analyses we stratified analyses for estradiol levels in women. The association between CAC and fracture risk (9 years follow-up) was tested through competing-risks models. Models were sex-stratified and adjusted for age, body mass index, smoking, bisphosphonate use and age at menopause. Results: There was no association between BMD change and CAC in men. In women, each 1% increase in annual BMD loss was significantly associated with higher follow-up CAC [β = 0.22 (0.06-0.38), p. =. 0.006; prevalence ratio: 4%]. Stratified analyses showed significant associations between BMD loss and follow-up CAC only in women with lower estradiol levels. We found no association between CAC and fracture risk and no association between BMD and CAC cross-sectionally. Conclusions: BMD loss was associated with higher follow-up CAC in women, which might be related to low estrogen levels. No association between CAC and BMD or fracture risk was found. Further studies are required to elucidate the mechanisms that might underlie the association between BMD change and coronary calcification in women

Serum 25-hydroxyvitamin D3 is associated with advanced glycation end products (AGEs) measured as skin autofluorescence: The Rotterdam Study

Advanced glycation end products (AGEs) accumulate in tissues with aging and may influence age-related diseases. They can be estimated non-invasively by skin autofluorescence (SAF) using the AGE Reader™. Serum 25-hydroxyvitamin D3 (25(OH)D3) may inhibit AGEs accumulation through anti-oxidative and anti-inflammatory properties but evidence in humans is scarce. The objective was to investigate the association between serum 25(OH)D3 and SAF in the population-based cohort study. Serum 25(OH)D3 and other covariates were measured at baseline. SAF was measured on average 11.5 years later. Known risk factors for AGE accumulation such as higher age, BMI, and coffee intake, male sex, smoking, diabetes, and decreased renal function were measured at baseline. Linear regression models were adopted to explore the association between 25(OH)D3 and SAF with adjustment for confounders. Interaction terms were tested to identify effect modification. The study was conducted in the general community. 2746 community-dwelling participants (age ≥ 45 years) from the Rotterdam Study were included. Serum 25(OH)D3 inversely associated with SAF and explained 1.5% of the variance (unstandardized B = − 0.002 (95% CI[− 0.003, − 0.002]), standardized β = − 0.125), independently of known risk fa

Serum phosphate levels are related to all-cause, cardiovascular and COPD mortality in men

Hyperphosphatemia has been associated with increased mortality in chronic kidney disease but the nature of such a relation in the general population is unclear. To investigate the association between phosphate (P) levels and all-cause and cause-specific mortality, we assessed two cohorts from the Rotterdam Study, with follow-up of 14.5 (RS-I) and 10.9 (RS-II) years until January 2012 with availability of fasting phosphate levels. Deaths were classified according to International Classification of Diseases into 7 groups: cardiovascular, cancer, infections, external, dementia, chronic lung diseases and other causes. Sex-stratified Weibull and competing-risks models were adjusted for age, BMI and smoking. Hazard ratios are expressed per 1 mg/dL increase in phosphate levels. The total number of participants included 3731 (RS-I, 2154 women) and 2494 (RS-II, 1361 women) subjects. The main outcome measures were all-cause and cause-specific mortality. A significant positive association was found between phosphate and all-cause mortality in men (pooled HR (95% CI): 1.46 (1.26–1.69)) but not in women (0.90 (0.77–1.05)). In men, higher phosphate increased the risk for cardiovascular mortality (1.66 (1.29–2.14)), other causes (1.67 (1.16–2.40)) and chronic lung disease mortality (1.94 (1.02–3.72)), the latter driven by mortality due to chronic obstructive pulmonary disease (COPD) (4.44 (2.08–9.49)). No relations were found for mortality due to infections, cancer, dementia or external causes. In conclusion, serum P is associated with increased all-cause, cardiovascular and COPD mortality in men but not women. The association with COPD mortality is novel and needs further research on underlying mechanisms

Concurso de cuento científico ¡Imagino la ciencia y te la cuento!

Este libro es una muestra del desarrollo del “Evento de Divulgación Tecnológica” EDT, denominado 2° Concurso de Cuento Científico ¡Imagino la Ciencia y te la Cuento!, donde se evidencia la apropiación de las habilidades lingüísticas, comunicativas y competencias lectoras, dentro de los lineamientos STEAM y habilidades para el siglo XXI; como resultado se obtiene la creatividad e imaginación de los niños de 16 instituciones educativas beneficiarias de la estrategia de Tecnoacademia Itinerante Boyacá, quienes, desde su perspectiva y diferentes vivencias, expresan el gusto por la lectura y la escritura, materializada en la construcción de cuentos que fueron leídos por un equipo de profesionales interdisciplinario y donde fueron seleccionados algunos cuentos y dibujos para esta publicación.El primer niño que fue a la luna -- El gran descubrimiento -- Hacia el futuro -- Un amor entre dos mundos -- La aventura de mis sueños -- La felicidad siempre nos espera -- Valiente valentina -- Un sueño perdido -- El científico loco -- El extraterrestre que quería vivir en la tierra -- El mejor líder -- Arkade un juego sin fin -- Experimento d-037 – Robotsing -- El viejo científico -- Fiesta en la luna -- El guardián del bosque -- 20 años de silencio -- Niveles de organización -- De los seres vivos -- Doña Lila y doña Justa -- Proyecto de inclusiòn -- Tecnoacademia “Pintando protejo la naturaleza”na123 página

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Estos dos volúmenes constituyen una contribución al desarrollo de la comparatística que se realiza, principalmente, desde América Latina. El primer volumen está organizado en tres partes y consta de 22 artículos, mientras que el segundo reúne 24 capítulos.UCR::Vicerrectoría de Docencia::Artes y Letras::Facultad de Letras::Escuela de Filología, Lingüística y LiteraturaUCR::Vicerrectoría de Docencia::Ciencias Básicas::Sistema de Educación General::Escuela de Estudios GeneralesUCR::Vicerrectoría de Investigación::Sistema de Estudios de Posgrado::Artes y Letras::Maestría Académica en Literatura FrancesaUCR::Vicerrectoría de Investigación::Sistema de Estudios de Posgrado::Artes y Letras::Maestría Académica en Literatura LatinoamericanaUCR::Vicerrectoría de Docencia::Artes y Letras::Facultad de Letras::Escuela de Lenguas Moderna