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Garcia A.M.,University of Valencia | Garcia A.M.,CIBER ISCIII | Ramon-Bou N.,Conselleria de Sanidad | Porta M.,CIBER ISCIII | And 2 more authors.
Journal of Alzheimer's Disease | Year: 2010

The roles of smoking and alcohol on the development of Alzheimer's disease (AD) remain unclear. We performed a case-control study on the effects of both exposures before the age of onset of the disease in the cases (and same reference age for their age-matched controls) on disease risk. Interviews were conducted with population controls (n=246) and relatives of cases (n=176) identified through local Alzheimer's Disease Associations. Logistic regression models were built adjusting by gender, age, residence, education, economic situation, employment, and history of dementia in close relatives. Risk of AD was unaffected by any measure of tobacco consumption. Alcohol consumers showed a lower risk of AD than never consumers (adjusted odds ratio, aOR = 0.53, 95% CI 0.32, 0.88), with differences by gender (women aOR =0.48, 95% CI 0.27, 0.84; men aOR=0.80, 95% CI 0.23, 2.80). Mean daily total consumption of alcohol and time consuming alcohol showed increasingly protective dose-response relationships in women. Lower AD risk was observed in alcohol drinkers of both genders who never smoked (aOR= 0.37, 95% CI 0.21, 0.65). All these associations were independent of the presence of apolipoprotein E4 allele(s) in the cases. Although the sample was small for some analyses addressing these interactions, our results suggest a protective effect of alcohol consumption, mostly in non-smokers, and the need to consider interactions between tobacco and alcohol consumption, as well as interactions with gender, when assessing the effects of smoking and/or drinking on the risk of AD. © 2010 - IOS Press and the authors. All rights reserved.

Van Arensbergen J.,Institute dInvestigacions Biomediques August Pi i Sunyer | Van Arensbergen J.,CIBER ISCIII | Garcia-Hurtado J.,Institute dInvestigacions Biomediques August Pi i Sunyer | Garcia-Hurtado J.,CIBER ISCIII | And 10 more authors.
Genome Research | Year: 2010

The epigenome changes that underlie cellular differentiation in developing organisms are poorly understood. To gain insights into how pancreatic beta-cells are programmed, we profiled key histone methylations and transcripts in embryonic stem cells, multipotent progenitors of the nascent embryonic pancreas, purified beta-cells, and 10 differentiated tissues. We report that despite their endodermal origin, beta-cells show a transcriptional and active chromatin signature that is most similar to ectoderm-derived neural tissues. In contrast, the beta-cell signature of trimethylated H3K27, a mark of Polycomb-mediated repression, clusters with pancreatic progenitors, acinar cells and liver, consistent with the epigenetic transmission of this mark from endoderm progenitors to their differentiated cellular progeny. We also identified two H3K27 methylation events that arise in the beta-cell lineage after the pancreatic progenitor stage. One is a wave of cell-selective de novo H3K27 trimethylation in non-CpG island genes. Another is the loss of bivalent and H3K27me3-repressed chromatin in a core program of neural developmental regulators that enables a convergence of the gene activity state of beta-cells with that of neural cells. These findings reveal a dynamic regulation of Polycomb repression programs that shape the identity of differentiated beta-cells. © 2010 by Cold Spring Harbor Laboratory Press.

Karakosta P.,University of Crete | Alegakis D.,University of Crete | Georgiou V.,University of Crete | Roumeliotaki T.,University of Crete | And 8 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2012

Context: Maternal thyroid dysfunction, especially in early pregnancy, may lead to pregnancy complications and adverse birth outcomes. Few population-based prospective studies have evaluated these effects and results are discrepant. Objective: We examined the association of thyroid function and autoimmunity in early pregnancy with adverse pregnancy and birth outcomes. Setting and Participants: The study used data from the prospective mother-child cohort "Rhea" study in Crete, Greece. A total of 1170 women with singleton pregnancies participated in this analysis. Maternal serum samples in the first trimester of pregnancy were tested for thyroidhormones (TSH, free T4, and free T3) and thyroid antibodies (thyroid peroxidase antibody and thyroglobulin antibody). Multivariable log-Poisson regression models were used adjusting for confounders. Main Outcome Measures: Outcomes included gestational diabetes, gestational hypertension/preeclampsia, cesarean section, preterm delivery, low birth weight, and small-for-gestational-age neonates. Results: The combination of high TSH and thyroid autoimmunity in early pregnancy was associated with a 4-fold increased risk for gestational diabetes [relative risk (RR) 4.3, 95% confidence interval (CI) 2.1- 8.9)] and a 3-fold increased risk for low birth weight neonates (RR 3.1,95%CI 1.2- 8.0) after adjustment for several confounders. Women positive for thyroid antibodies without elevated TSH levels in early pregnancy were at high risk for spontaneous preterm delivery (RR 1.7, 95% CI 1.1-2.8), whereas the combined effect of high TSH and positive thyroid antibodies did not show an association with preterm birth. Conclusions: High TSH levels and thyroid autoimmunity in early pregnancy may detrimentally affect pregnancy and birth outcomes. Copyright © 2012 by The Endocrine Society.

Herrero-Gonzalez J.E.,Institute Municipal dInvestigacio Medica
Actas Dermo-Sifiliograficas | Year: 2010

Dermatitis herpetiformis is an autoimmune blistering disease that appears as a cutaneous manifestation of gluten intolerance. It is one of a group of disorders that have gluten sensitivity in common, including celiac disease and gluten ataxia. Patients with dermatitis herpetiformis present with a pruritic papulovesicular rash on extensor surfaces and on the buttocks. Immunological studies demonstrate the presence of specific immunoglobulin (Ig) A antiendomysial and antitransglutaminase antibodies. The finding of granular deposits of IgA along the dermal-epidermal junction is pathognomonic of dermatitis herpetiformis. Treatment of dermatitis herpetiformis is based on a life-long, strict gluten-free diet, which improves all clinical aspects of gluten sensitivity, and dapsone, a drug that is only effective for the skin manifestations. © 2010 Elsevier España, S.L. y AEDV. Todos los derechos reservados.

Gonzalez-Macias J.,University of Cantabria | Gonzalez-Macias J.,Charles III University of Madrid | Vila J.,Institute Municipal dInvestigacio Medica | Diez-Perez A.,Charles III University of Madrid | Diez-Perez A.,Autonomous University of Barcelona
Bone | Year: 2012

Purpose: To assess the ability of the Spanish version of the WHO fracture risk assessment tool (FRAX®) to predict the observed incident fractures in the ECOSAP Study cohort. Methods: 5201 women, aged 65 or older, were enrolled in a three-year, prospective study by a non-randomized sampling of consecutive cases in 58 primary care centers in Spain. Participants completed an osteoporosis and fracture risk questionnaire and attended follow-up visits every 6. months. All radiologically or surgically confirmed low-trauma, non-spinal fractures were collected. The individual 10-year absolute risks of hip and major osteoporotic fractures were calculated with the FRAX® algorithms for Spain without the inclusion of the bone mineral density (BMD) measurements. Calibration was evaluated by comparing the three-year estimated (E) fractures predicted with FRAX® with the number of observed (O) fractures, and their discriminative ability for the probability of new fractures with the area under the receiving operating characteristic (ROC) curves. Results: Fifty (0.96%) women sustained an incident hip fracture, and 201 (3.81%) women presented with major osteoporotic fractures (hip, forearm or humerus). The E/O ratios for hip and major osteoporotic fractures were 1.10 and 0.66 respectively. Clinical vertebral fractures were not collected; therefore, the E/O ratio for major fractures should be expected to be lower. The difference between E and O cases reached statistical significance (χ 2, p<0.001). Areas under the ROC curves were 0.640 and 0.615 for hip and major osteoporotic fractures respectively. Conclusions: The Spanish FRAX® underestimates the risk for major osteoporotic fractures. The estimated risk for hip fractures was similar to the observed fractures; however the algorithm had only modest discriminative ability. These results should be interpreted in the context of the relatively low number of observed fractures, especially at the hip. © 2011 Elsevier Inc.

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