Respuestas del miocardio al estrés biomecánico

El estrés biomecánico del miocardio hace referencia a la situación que se genera cuando, debido a la hipertensión, la hipoxia u otras formas de daño miocárdico, están aumentadas las demandas de trabajo cardíaco y/o se ha perdido miocardio funcionante. Como consecuencia del estrés biomecánico se producen diversas respuestas que afectan a todas las células miocárdicas, en particular a los cardiomiocitos. El resultado final de las mismas son distintas modificaciones fenotípicas que inicialmente son compensadoras (p. ej., hipertrofia), pero que si persiste el estrés pueden mediar la transición de la hipertrofia a la insuficiencia cardíaca (p. ej., apoptosis y fibrosis). Esta revisión se centra en la descripción de las distintas fases de las respuestas miocárdicas al estrés, así como en la consideración de los hallazgos más recientes sobre los mecanismos moleculares implicados en el desarrollo de insuficiencia cardíaca

Myocardial Response to Biomechanical Stress

Biomechanical stress of the myocardium is the situation resulting from hypoxia, hypertension, and other forms of myocardial injury, that invariably lead to increased demands for cardiac work and/or loss of functional myocardium. As a consequence of biomechanical stress a number of responses develop involving all the myocardial cells, namely cardiomyocytes. As a result some myocardial phenotypic changes develop that are initially compensatory (i.e., hypertrophy) but which may mediate the eventual decline in myocardial function that occurs with the transition from hypertrophy to failure in conditions of persistent stress (i.e., apoptosis and fibrosis). This review focuses on the steps involved in the response of the myocardium to biomechanical stress and highlights the most recent developments in the molecular mechanisms involved in the development of heart failure

Entre la carrera eclesiástica y las preocupaciones familiares: correspondencia de un prebendado del siglo XVIII

La correspondencia familiar es una fuente riquísima para conocer aspectos relacionados con la intimidad del hogar, hechos o circunstancias históricas, así como los éxitos y fracasos en la carrera de los individuos; todo ello redactado a modo de confidencia, permitiéndonos conocer rasgos identitarios personales y colectivos. Este artículo analiza bajo esta perspectiva las relaciones familiares de un clérigo y la carrera eclesiástica en relación con elementos políticos que influían en el acceso a las prebendas eclesiásticas y al episcopado durante los últimos años del siglo XVIII.The family correspondence is a rich source to know aspects related to home intimacy, facts or historical circumstances, as well as the successes and failures in the career of the individuals; all written in confidence, allowing us to know personal and collective identity features. This article analyzes the family relationships of a clergyman and the ecclesiastical career in relation to political elements that influenced access to ecclesiastical prebends and the episcopate during the last years of the 18th century

Cambios y permanencias entre las élites intelectuales en el Reino de Navarra. Las Sociedades Económicas de Amigos del País de Pamplona

Pamplona desde finales del siglo XVIII y primeras décadas del XIX fue testigo de varios intentos de constituir una Sociedad Económica de Amigos del País. Aunque estas instituciones han sido ampliamente estudiadas en el presente artículo hemos querido comprobar si hubo alguna continuidad entre las élites intelectuales que las promovieron o, como resultado de los convulsos periodos que se sucedieron, fueron iniciativas aisladas entre sí. Para ello se han cruzado los datos de los individuos que constituyeron las distintas sociedades dejando ver ciertas constantes entre algunos grupos de la nobleza, los comerciantes o el clero, en especial el alto clero. Algunas de las familias que participaron en el ascenso social del fenómeno denominado la Hora navarra consiguieron continuar en puestos políticos y económicos destacados en el nuevo régimen liberal, dejando los que tradicionalmente habían ocupado para entrar en otros nuevos

Tobacco smoking-associated genome-wide DNA methylation changes in the EPIC study.

Epigenetic changes may occur in response to environmental stressors, and an altered epigenome pattern may represent a stable signature of environmental exposure

Physical activity reduces the risk of incident type 2 diabetes in general and in abdominally lean and obese men and women: the EPIC-InterAct Study.

AIMS/HYPOTHESIS: We examined the independent and combined associations of physical activity and obesity with incident type 2 diabetes in men and women. METHODS: The InterAct case-cohort study consists of 12,403 incident type 2 diabetes cases and a randomly selected subcohort of 16,154 individuals, drawn from a total cohort of 340,234 participants with 3.99 million person-years of follow-up. Physical activity was assessed by a four-category index. Obesity was measured by BMI and waist circumference (WC). Associations between physical activity, obesity and case-ascertained incident type 2 diabetes were analysed by Cox regression after adjusting for educational level, smoking status, alcohol consumption and energy intake. In combined analyses, individuals were stratified according to physical activity level, BMI and WC. RESULTS: A one-category difference in physical activity (equivalent to approximately 460 and 365 kJ/day in men and women, respectively) was independently associated with a 13% (HR 0.87, 95% CI 0.80, 0.94) and 7% (HR 0.93, 95% CI 0.89, 0.98) relative reduction in the risk of type 2 diabetes in men and women, respectively. Lower levels of physical activity were associated with an increased risk of diabetes across all strata of BMI. Comparing inactive with active individuals, the HRs were 1.44 (95% CI 1.11, 1.87) and 1.38 (95% CI 1.17, 1.62) in abdominally lean and obese inactive men, respectively, and 1.57 (95% CI 1.19, 2.07) and 1.19 (95% CI 1.01, 1.39) in abdominally lean and obese inactive women, respectively. CONCLUSIONS/INTERPRETATION: Physical activity is associated with a reduction in the risk of developing type 2 diabetes across BMI categories in men and women, as well as in abdominally lean and obese men and women

Acrylamide and Glycidamide Hemoglobin Adducts and Epithelial Ovarian Cancer: A Nested Case-Control Study in Nonsmoking Postmenopausal Women from the EPIC Cohort

Background: Acrylamide was classified as “probably carcinogenic to humans (group 2A)” by the International Agency for Research on Cancer. Epithelial ovarian cancer (EOC) is the fourth cause of cancer mortality in women. Five epidemiological studies have evaluated the association between EOC risk and dietary acrylamide intake assessed using food frequency questionnaires, and one nested case–control study evaluated hemoglobin adducts of acrylamide (HbAA) and its metabolite glycidamide (HbGA) and EOC risk; the results of these studies were inconsistent. Methods: A nested case–control study in nonsmoking postmenopausal women (334 cases, 417 controls) was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Unconditional logistic regression models were used to estimate ORs and 95% confidence intervals (CI) for the association between HbAA, HbGA, HbAA+HbGA, and HbGA/HbAA and EOC and invasive serous EOC risk. Results: No overall associations were observed between biomarkers of acrylamide exposure analyzed in quintiles and EOC risk; however, positive associations were observed between some middle quintiles of HbGA and HbAA+HbGA. Elevated but nonstatistically significant ORs for serous EOC were observed for HbGA and HbAA+HbGA (ORQ5vsQ1, 1.91; 95% CI, 0.96–3.81 and ORQ5vsQ1, 1.90; 95% CI, 0.94–3.83, respectively); however, no linear dose–response trends were observed. Conclusion: This EPIC nested case–control study failed to observe a clear association between biomarkers of acrylamide exposure and the risk of EOC or invasive serous EOC. Impact: It is unlikely that dietary acrylamide exposure increases ovarian cancer risk; however, additional studies with larger sample size should be performed to exclude any possible association with EOC risk

Measured adiposity in relation to head and neck cancer risk in the European Prospective Investigation into Cancer and Nutrition

BACKGROUND: Emerging evidence from cohort studies indicates that adiposity is associated with greater incidence of head and neck cancer (HNC). However, most studies have used self-reported anthropometry which is prone to error. METHODS: Among 363 094 participants in the European Prospective Investigation into Cancer and Nutrition study (EPIC) with measured anthropometry, there were 837 incident cases of HNC. HNC risk was examined in relation to body mass index (BMI) [lean: 30 kg/m²], waist circumference (WC), hip circumference (HC) and waist to hip ratio (WHR) using Cox proportional hazards models. RESULTS: Among men, a BMI < 22.5 kg/m² was associated with higher HNC risk [hazard ratio (HR) 1.62, 95% confidence interval (CI) 1.23 - 2.12)]; BMI was not associated with HNC among women. WC and WHR were associated with greater risk of HNC among women, (WC per 5 cm: HR 1.08, 95% CI 1.02 - 1.15; WHR per 0.1 unit: HR 1.64, 95% CI 1.38 - 1.93). After stratification by smoking status, the association for WHR was present only among smokers (p interaction 0.004). Among men, WC and WHR were associated with HNC only upon additional adjustment for BMI (WC per 5 cm: HR 1.16, 95% CI 1.07 - 1.26; WHR per 0.1 unit: HR 1.42, 95% CI 1.21 - 1.65). CONCLUSION: Central adiposity, particularly among women, may have a stronger association with HNC risk than previously estimated. IMPACT: Strategies to reduce obesity may beneficially impact HNC incidence.The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); ERC- 2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS), PI13/00061 to Granada; , PI13/01162 to EPIC-Murcia), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (14136 to K.T. Khaw, N.J. Wareham; C570/A16491 to R.C. Travis and C8221/A19170 to Tim Key (EPIC-Oxford), Medical Research Council (1000143 to K.T. Khaw, N.J. Wareham, MR/M012190/1 to Tim Key (EPIC-Oxford)) (United Kingdom)

An epidemiological model for prediction of endometrial cancer risk in Europe

Endometrial cancer (EC) is the fourth most frequent cancer in women in Europe, and as its incidence is increasing, prevention strategies gain further pertinence. Risk prediction models can be a useful tool for identifying women likely to benefit from targeted prevention measures. On the basis of data from 201,811 women (mostly aged 30–65 years) including 855 incident EC cases from eight countries in the European Prospective Investigation into Cancer and Nutrition cohort, a model to predict EC was developed. A step-wise model selection process was used to select confirmed predictive epidemiologic risk factors. Piece-wise constant hazard rates in 5-year age-intervals were estimated in a cause-specific competing risks model, five-fold-cross-validation was applied for internal validation. Risk factors included in the risk prediction model were body-mass index (BMI), menopausal status, age at menarche and at menopause, oral contraceptive use, overall and by different BMI categories and overall duration of use, parity, age at first full-term pregnancy, duration of menopausal hormone therapy and smoking status (specific for pre, peri- and post-menopausal women). These variables improved the discriminating capacity to predict risk over 5 years from 71 % for a model based on age alone to 77 % (overall C statistic), and the model was well-calibrated (ratio of expected to observed cases = 0.99). Our model could be used for the identification of women at increased risk of EC in Western Europe. To achieve an EC-risk model with general validity, a large-scale cohort-consortium approach would be needed to assess and adjust for population variation