Interaction between genes and lifestyle factors on obesity.

Obesity originates from a failure of the body-weight control systems, which may be affected by changing environmental influences. Basically, the obesity risk depends on two important mutually-interacting factors: (1) genetic variants (single-nucleotide polymorphisms, haplotypes); (2) exposure to environmental risks (diet, physical activity etc.). Common single-nucleotide polymorphisms at candidate genes for obesity may act as effect modifiers for environmental factors. More than 127 candidate genes for obesity have been reported and there is evidence to support the role of twenty-two genes in at least five different populations. Gene-environment interactions imply that the synergy between genotype and environment deviates from either the additive or multiplicative effect (the underlying model needs to be specified to appraise the nature of the interaction). Unravelling the details of these interactions is a complex task. Emphasis should be placed on the accuracy of the assessment methods for both genotype and lifestyle factors. Appropriate study design (sample size) is crucial in avoiding false positives and ensuring that studies have enough power to detect significant interactions, the ideal design being a nested case-control study within a cohort. A growing number of studies are examining the influence of gene-environmental interactions on obesity in either epidemiological observational or intervention studies. Positive evidence has been obtained for genes involved in adiposity, lipid metabolism or energy regulation such as PPARgamma2 (Pro12Ala), beta-adrenoceptor 2 (Gln27Glu) or uncoupling proteins 1, 2 and 3. Variants on other genes relating to appetite regulation such as melanocortin and leptin receptors have also been investigated. Examples of some recently-identified interactions are discussed

Mediterranean diet as the ideal model for preventing non-alcoholic fatty liver disease (NAFLD)

The prevalence of nonalcoholic fatty liver disease (NAFLD) has dramatically increased in the 2–3 last decades and it represents the most frequent global cause of liver disease, affecting 25% to 45% of adults in most studies (1). The worldwide elevation in the population rates of NAFLD has come in parallel with rising unprecedented pandemics of obesity and diabetes. There is no specific medication for NAFLD and dietary/lifestyle modifications are the main foundations for the treatment of NAFLD. They are also very likely to be effective for its primary prevention. In this context, a dietary pattern that meets most requirements to become the ideal model for the prevention of NAFLD is the traditional Mediterranean diet (2). In addition to the potential for preventing NAFLD, the Mediterranean diet has sufficiently demonstrated its great ability to improve cardiovascular health. The accrual of prospective and well conducted studies showing cardiovascular benefits associated with better adherence to a high-quality food pattern is superior for the traditional Mediterranean food pattern than for any other dietary pattern (3)

A traditional mediterranean diet effectively reduces inflammation and improves cardiovascular health

Chrysohoou et al. fifteen years ago, showed in an elegant analysis nested within the ATTICA study [1] that a dietary score reflecting adherence to the traditional Mediterranean diet (MedDiet) was inversely associated with plasma biomarkers of low-grade inflammation. Specifically, participants in the highest tertile of adherence to the MedDiet presented 20% lower levels of highly-sensitive C reactive protein (hs-CRP), 17% lower levels of interleukin-6 (IL-6), and 14% lower white blood cell counts. This was an observational study that could be affected by residual confounding and other potential imperfections. However, another similar study, this time nested within the Nurses Cohort in the USA [2], assessed hs-CRP, IL-6, E-selectin, soluble intercellular cell adhesion molecule 1, and soluble vascular cell adhesion molecule 1 and found that better adherence to the MedDiet was also associated with a reduction in inflammatory biomarker concentrations, with relative reductions of 24% in hs-CRP, 16% in IL-6, and 13% in E-selectin concentrations [2]. These well conducted observational studies were subsequently confirmed by a randomized clinical trial (the pilot study of the PREDIMED (PREvención con DIeta MEDiterránea) trial) where we were able to show that an intervention with 2 MedDiets maintained during 3 months was able to reduce hs-CRP, IL-6 (in both cases) and adhesion molecules compared to a low-fat diet [3]. However, hs-CRP was reduced only when the MedDiet was supplemented with polyphenol-rich extra-virgin olive oil, but not with nuts

Bifurcations and Slow-Fast Analysis in a Cardiac Cell Model for Investigation of Early Afterdepolarizations

In this study, we teased out the dynamical mechanisms underlying the generation of arrhythmogenic early afterdepolarizations (EADs) in a three-variable model of a mammalian ventricular cell. Based on recently published studies, we consider a 1-fast, 2-slow variable decomposition of the system describing the cellular action potential. We use sweeping techniques, such as the spike-counting method, and bifurcation and continuation methods to identify parametric regions with EADs. We show the existence of isolas of periodic orbits organizing the different EAD patterns and we provide a preliminary classification of our fast-slow decomposition according to the involved dynamical phenomena. This investigation represents a basis for further studies into the organization of EAD patterns in the parameter space and the involved bifurcations

Incidence of Hypertension in a Cohort of Spanish University Graduates:The SUN Study

Hypertension is a major public health problem. However, no estimates of age- and sex-specific incidences are available for the Spanish population. Our objective was to estimate the incidence of hypertension in a cohort of university graduates in Spain. We followed up 5648 individuals aged 25-65 years who were initially free of hypertension, diabetes, and cardiovascular disease for a median of 30 months. New diagnoses of hypertension were identified using mailed questionnaires. We validated the self-reported diagnosis of hypertension. In 18 250 person-years of follow-up, we identified 248 new cases of hypertension. The unadjusted incidences of hypertension in women and men were 8.2 per 1000 person-years (95% CI, 6.7-10.1) and 21.8 per 1000 person-years (95% CI, 18.6-25.4), respectively. The cumulative probability of receiving a medical diagnosis of hypertension by the age of 65 years was 50% among women and 72% among men. In conclusion, we have provided new evidence confirming that hypertension is one of the most important public health problems in Spain

Uniform semiclassical wave function for coherent 2D electron flow

We find a uniform semiclassical (SC) wave function describing coherent branched flow through a two-dimensional electron gas (2DEG), a phenomenon recently discovered by direct imaging of the current using scanned probed microscopy. The formation of branches has been explained by classical arguments, but the SC simulations necessary to account for the coherence are made difficult by the proliferation of catastrophes in the phase space. In this paper, expansion in terms of "replacement manifolds" is used to find a uniform SC wave function for a cusp singularity. The method is then generalized and applied to calculate uniform wave functions for a quantum-map model of coherent flow through a 2DEG. Finally, the quantum-map approximation is dropped and the method is shown to work for a continuous-time model as well.Comment: 9 pages, 7 figure

Determinants of the adherence to an "a priori" defined Mediterranean dietary pattern

Background: A prospective cohort study with university level participants was initiated to study the effect of Mediterranean diet on health. Aims: The objective of this study was to identify possible lifestyle and socioeconomic variables associated with the consumption of a Mediterranean dietary pattern (MDP). Method: This analysis includes 1587 males and 2260 females. MDP was defined “a priori” by summing the standardized residuals of nutrients and foods after adjusting a regression model using total energy intake as the independent variable. Multiple regression and non-parametric locally weighted regression models were adjusted with the relative adherence to the MDP as the dependent variable in males and females. Results: Women were more compliant than men with the MDP (Coefficient regression (b) = 4.1; Confidence Interval (CI) 95 % = 3.2 to 4.9). The compliance with the MDP was significantly poorer among younger participants both in men and women (p < 0.001 in men and in women). Participants who were more physically active were more likely to fulfill the traditional MDP (p = 0.01 in men and p < 0.001 in women). Conclusions: Our findings provide evidence supporting the progressive departure from the traditional MDP in younger and highly educated subjects of the Mediterranean area. A more active life-style is associated with a better compliance with the MDP

Prevención cardiovascular y de la osteoporosis con terapia hormonal sustitutiva

Se recomienda actualmente que todo médico -sea cual sea su especialidad- aproveche la oportunidad que supone la atención clínica a cualquier mujer postmenopáusica o que se halle en torno a la menopausia para aconsejarle acerca de los beneficios y riesgos que supone la terapia hormonal sustitutiva (THS) con estrógenos y progesterona. Una vez que sea adecuadamente informada de estos beneficios y riesgos, debe ser la propia mujer quien decida si va a iniciar o no esta terapia, teniendo en cuenta no sólo su propio perfil de riesgo sino también sus preferencias. Los beneficios más claros se refieren a la reducción del riesgo de osteoporosis y de fracturas, así como al control y prevención de algunos síntomas frecuentes en la menopausia. Para prevenir la osteoporosis se requiere un uso continuado de IaTHS. También existen cada vez más argumentos que sugieren una reducción del riesgo de un primer episodio coronario. No obstante, no hay pruebas de que laTHS sea útil en la prevención secundaria de la cardiopatía isquémica o aporte alguna protección frente a los accidentes cerebrovasculares. Las desventajas más importantes de la THS se refieren a un mayor riesgo de hiperplasia de endometrio y de cáncer endometrial cuando se usan estrógenos solos, sin combinarlos con progestágenos. También existe un pequeño incremento del riesgo de cáncer de mama cuando se prolonga la THS, también cuando se asocian progestágenos

Daily physical activity and macronutrient distribution of low-calorie diets jointly affect body fat reduction in obese women.

Inadequate dietary patterns and sedentary lifestyles are believed to be important factors in predisposing people to obesity. This study analyzed the potential interaction between habitual physical activity and the carbohydrate (CHO)-fat distribution in 2 hypocaloric diets and the impact of such interplay on body composition changes. Forty healthy obese women, 20–50 years old, were randomly assigned to a high- or low-CHO energy-restricted diet, which was low or high in fat, respectively, during 10 weeks. Baseline and final measurements were performed to assess dietary habits, resting metabolic rate, and body composition changes. Physical activity was measured with a triaxial accelerometer and with a questionnaire. There were no significant differences in anthropometric and metabolic variables between both dietary groups at baseline. However, there was a positive correlation between total free-living physical activity and arm muscle preservation after 10 weeks (r = 0.371; p = 0.024). Interestingly, an interaction between macronutrient (CHO–fat distribution) intake and physical activity was found, since less-active subjects with a high-CHO–low-fat diet showed a greater fat loss than those more active with a lower-CHO–high-fat diet, whereas more-active subjects with a high-CHO–low-fat diet showed a smaller fat loss than those receiving a low-CHO–high-fat diet. Physical activity and the macronutrient content of energyrestricted diets, when designed to promote body fat mass reduction, should be considered together to better predict the outcome