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Supplementary Tables 1-4 from Changes in CpG Islands Promoter Methylation Patterns during Ductal Breast Carcinoma Progression

Supplementary figures 1-4 from Changes in CpG Islands Promoter Methylation Patterns during Ductal Breast Carcinoma Progression

Aberrant promoter methylation of several known or putative tumor suppressor genes occurs frequently during carcinogenesis, and this epigenetic change has been considered as a potential molecular marker for cancer. We examined the methylation status of nine genes (APC, CDH1, CTNNB1, TIMP3, ESR1, GSTP1, MGMT, THBS1, and TMS1), by quantitative methylation specific PCR. Synchronous preinvasive lesions (atypical ductal hyperplasia and/or ductal carcinoma in situ) and invasive ductal breast carcinoma from 52 patients, together with pure lesions from 24 patients and 12 normal tissues paired to tumor and 20 normal breast distant from tumor were analyzed. Aberrant promoter methylation was detected in both preinvasive and invasive lesions for genes APC, CDH1, CTNNB1, TIMP3, ESR1, and GSTP1. However, hierarchical mixed model and Generalized Estimating Equations model analyses showed that only APC, CDH1, and CTNNB1 promoter regions showed a higher frequency and methylation levels in pathologic samples when compared with normal breast. Whereas APC and CTNNB1 did not show differences in methylation levels or frequencies, CDH1 showed higher methylation levels in invasive tumors as compared with preinvasive lesions (P < 0.04, Mann-Whitney test with permutation correction). The analysis of APC, CDH1, and CTNNB1 methylation status was able to distinguish between normal and pathologic samples with a sensitivity of 67% (95% confidence interval, 60-71%) and a specificity of 75% (95% confidence interval, 69-81%). Our data point to the direct involvement of APC, CDH1, and CTNNB1 promoter methylation in the early stages of breast cancer progression and suggest that they may represent a useful tool for the detection of tumor cells in clinical specimens. (Cancer Epidemiol Biomarkers Prev 2009;18(10):2694–700)

Gastric sleeve stenosis (GSS) is described in 1%-4% of patients.To evaluate the role of endoscopy in the management of stenosis after laparoscopic sleeve gastrectomy using a standardized approach according to the characteristic of stenosis.Retrospective, observational, single-center study on patients referred from several bariatric surgery departments to an endoscopic referral center.We enrolled 202 patients. All patients underwent endoscopy in a fluoroscopy setting, and a systematic classification of the type, site, and length of the GSS was performed. According to the characteristics of the stenosis, patients underwent pneumatic dilatation or placement of a self-expandable metal stent or a lumen-apposed metal stent. Failure of endoscopic treatment was considered an indication for redo surgery, whereas patients with partial or complete response were followed up for 2 years. In the event of a recurrence, a different endoscopic approach was used.We found inflammatory strictures in 4.5% of patients, pure narrowing in 11%, and functional stenosis in 84.5%. Stenosis was in the upper tract of the stomach in 53 patients, whereas medium and distal stenosis was detected in 138 and 11 patients, respectively, and short stenosis in 194 patients. A total of 126 patients underwent pneumatic dilatation, 8 self-expandable metal stent placement, 64 lumen-apposed metal stent positioning, and 36 combined therapy. The overall rate of endoscopy success was 69%.GSS should be considered to be a chronic disease, and the endoscopic approach seems to be the most successful treatment, with a prolonged positive outcome of 69%. Characteristics of the stenosis should guide the most suitable endoscopic approach. (Surg Obes Relat Dis 2022;X:XXX-XXX.) © 2022 American Society for Metabolic and Bariatric Surgery. All rights reserved.

This work analysed the permeation of binary and ternary H-containing mixtures through a SAPO-34 membrane, aiming at investigating how hydrogen influences and its permeation is influenced by the presence of the other gaseous species, such as CO and CH. We considered the behaviour of various gas mixtures in terms of permeability and selectivity at various temperatures (25-300 °C), feed pressures (400-1000 kPa) and compositions by means of an already validated mass transport model, which is based on surface and gas translation diffusion. We found that the presence of CO and CH in the H-containing mixtures influences in a similar way the H permeation, reducing its permeability of about 80% compared to the single-gas value because of their stronger adsorption. On the other hand, H promotes the permeation of CO and CH, causing an increment of their permeability with respect to those as single gases. These combined effects reflected in interesting selectivity values in binary mixture (e.g., CO/H about 11 at 25 °C, H/CH about 9 at 180 °C), which showed the potential of SAPO-34 membranes in treating of H-containing mixtures.

Objectives The aim of this study was to assess the hypothesis that alcohol consumption is associated with onset of atrial fibrillation (AF) and/or heart failure (HF). Background The connection between ethanol intake and AF or HF remains controversial. Methods The study population was 22,824 AF- or HF-free subjects (48% men, age ≥35 years) randomly recruited from the general population included in the Moli-sani study, for whom complete data on HF, AF, and alcohol consumption were available. The cohort was followed up to December 31, 2015, for a median of 8.2 years (183,912 person-years). Incident cases were identified through linkage to the Molise regional archive of hospital discharges. Hazard ratios were calculated using Cox proportional hazard models and cubic spline regression. Results A total of 943 incident cases of HF and 554 of AF were identified. In comparison with never drinkers, both former and occasional drinkers showed comparable risk for developing HF. Drinking alcohol in the range of 1 to 4 drinks/day was associated with a lower risk for HF, with a 22% maximum risk reduction at 20 g/day, independent of common confounders. In contrast, no association of alcohol consumption with onset of AF was observed. Very similar results were obtained after restriction of the analyses to regular or only wine drinkers or according to sex, age, social status, or adherence to the Mediterranean diet. Conclusions Consumption of alcohol in moderation was associated with a lower incidence of HF but not with development of AF.

Membranes are increasingly replacing the traditional processes in the separation field, allowing the selective removal of components from gas or liquid streams. In this work, the separation performance of zeolite membranes for gas mixtures containing a strongly adsorbed species (i.e., CO2 and water vapor) and a weakly adsorbed one (e.g., H2) was analyzed based on a developed model,1, 2 which considers the interaction between the mass transport mechanisms contributing to the overall diffusion (i.e., surface and gas translation diffusion). As a main result, the predicted H2 permeance drops in mixture with H2O compared to the single gas condition, describing very well the literature experimental values 3 (Figure 1). This reduction occurs because water vapor molecules occupy the adsorption sites, impeding the H2 diffusion. The higher temperatures mitigate this hindering effect, causing an increase of H2 permeance since the H2O adsorption decreases. The H2O/H2 selectivity in 4A was estimated to be about 240 at 25°C. A strong hindering effect was also obtained in case of CO2 mixed with H2 through a NaY membrane, with a CO2/H2 selectivity of about 45 at 25°C. Hence, zeolite membranes are suitable materials for separation of gas mixtures. The presence of a strongly adsorbed species hinders the permeation of the other components and membrane selectivity increases.

Permeation of single gases and mixtures containing CO2, H2 and CO was investigated through NaY and DD3R zeolite membranes. Mass transport was modelled considering the competition between surface and gas translation diffusion.1 In particular, it was demonstrated the importance of gas translation also at a low temperature, in the region where surface diffusion is generally the dominant mechanism. Specifically, the permeation of weakly adsorbed species (i.e., H2) through NaY membrane was well predicted in the whole temperature range experimentally investigated in the literature.2 In fact, this model is able to describe the increase of H2 permeance at low temperatures owing to both surface and gas translation diffusion. Furthermore, a maximum in permeance was predicted at about 450 K, whereas gas translation becomes more important than surface diffusion above 520 K. A previous model, 3 which considered the competition between surface and Knudsen diffusion, showed a discrepancy with the experimental values at low temperatures. In fact, Knudsen diffusion instead of gas translation provides an error in H2 permeance of about 30% at 308 K. On the contrary, the strongly adsorbed species are not dependent on gas translation or Knudsen diffusion, since the surface diffusion is the dominant mechanism in the whole temperature range investigated. The estimated CO2/H2 mixture selectivity value at 303 K by this model in NaY membrane coincides with the experimental value of Kusakabe et al. 308 K.4 In fact, the same selectivity of 28 was obtained. On the other hand, a lower value of about 20 was predicted using Knudsen instead of gas translation. Permeation of light gases through a DD3R zeolite membrane was also evaluated considering the competition between surface and gas translation diffusion. The experimental permeances of H2, CO and CO2 as a function of temperature measured by Kanezashi et al.5 were well described in the whole temperature range considered. A presence of a minimum was predicted for CO2, CO and H2 at 690, 480 and 440 K, respectively. The minimum of H2 was also experimentally observed.5 The CO2 permeation takes place by surface diffusion up to a relatively high temperature. The minimum of CO2 permeance was found between the experimental values at 673 and 773 K (at ca. 690 K). The CO permeation occurs only by surface diffusion up to 400 K, whereas gas translation becomes significant above 450 K. The H2 permeation at 298 K is only owing to surface diffusion, which drastically tends to decrease with increasing temperature. On the other hand, gas translation becomes important with increasing temperature, being higher than surface diffusion above 410 K. The correct description of single gas behavior allowed a prediction of the separation performance through DD3R membranes also for mixtures. In particular, syngas permeation through a DD3R membrane was simulated in a wide range of temperature (273 -813 K) and feed pressure (200 - 1000 kPa). This membrane showed CO2/CO and CO2/H2 selectivity values of about 63 and 56 respectively at 273 K, which decrease to 36 and 18 at 303 K. A reverse H2/CO2 selectivity was predicted above 450 K. An increment of feed pressure did not significantly affect CO2/H2 selectivity, whereas slightly reduced the CO2/CO selectivity. Therefore, NaY and DD3R are good candidates for separation of different gas mixtures. Gas translation competing with surface diffusion successfully predicts the experimental permeation through zeolite membranes for both mixture and single gas at different operating conditions.

The effect of the polyphenol content of the human diet on mortality risk is not yet fully understood. The aim of this study was to evaluate the association of a polyphenol-rich diet with mortality rate and a possible mediation effect by inflammation, in what we believe to be a novel, holistic approach.We analyzed 21 302 participants (10 980 women and 10 322 men, aged ≥35 y) from the Moli-sani cohort. The participants were followed up for a median of 8.3 y. The European Prospective Investigation into Cancer and Nutrition food frequency questionnaire (FFQ) was used for dietary assessment. Flavonol, flavone, flavanone, flavanol, anthocyanin, isoflavone, and lignan intakes were calculated using European Food Information Resource-Bioactive Substances in Food Information Systems and the polyphenol antioxidant content (PAC)-score was constructed to assess the total content of these nutrients in the diet.Participants included in the highest quintile of intake of various polyphenol classes and subclasses presented a significant lower all-cause mortality risk compared with those in the lowest group of consumption (hazard ratio [HR] 1; P 0.05). Cox regression analyses adjusted for potential confounders indicated that participants in higher quintiles of PAC-score had lower all-cause mortality risk (HR1; P 0.05). When cause-specific mortality rates were considered, similar effects were observed for cardiocerebrovascular and cancer mortality (HR1; P 0.05).The polyphenol content of the diet was associated with reduced mortality risk in a Mediterranean population, possibly through an antiinflammatory mechanism.

Evidence indicates that Vitamin D deficiency may be associated with increased risk of cardiovascular disease, although findings on risk of heart failure (HF) are controversial. We investigated the relationship between serum Vitamin D and the incidence of hospitalization for HF in a large prospective cohort of Italian adults.19,092 (49% men, age range 35-99 years) HF-free individuals from the Moli-sani study, with complete data on serum Vitamin D (25-hydroxyvitamin) levels and incident hospitalized HF, were analysed. The cohort was followed up for a median of 6.2 years. Baseline serum Vitamin D levels were categorized in deficient (10 ng/mL), insufficient (10-29 ng/mL), and normal (≥30 ng/mL) Incident cases of hospitalization for HF were identified by linkage with the regional hospital discharge registry. Hazard ratios (HRs) were calculated using Cox-proportional hazard models. The prevalence of normal, insufficient or deficient levels of Vitamin D was 12.2%, 79.6% and 8.2%, respectively. During follow-up, 562 admissions to hospital for HF were identified. The incidence of HF was 1.6%, 2.9% and 5.3%, respectively in subjects with normal, insufficient and deficient levels of Vitamin D. After multivariable analysis, individuals with deficiency of Vitamin D had a higher risk of hospitalization for HF (HR: 1.61, 95%CI: 1.06-2.43) than those with normal levels. Further adjustment for subclinical inflammation did not substantially change the association between Vitamin D deficiency and HF.Deficiency of Vitamin D was associated, independently of known HF risk factors, with an increased risk of hospitalization for HF in an Italian adult population.

Introduction Edible algae, rich in biologically active components, may influence glycaemic control, lower blood lipids and increase antioxidant activities. The aim of this study was to evaluate the effect of prolonged supplementation with an extract of the brown edible seaweed Ascophyllum nodosum on anthropometric indexes and biomarkers of metabolic risk for cardiovascular disease in human volunteers.

Mediterranean diet (MD) has been associated with lower risk of ischemic cerebro- and cardio-vascular disease, neurological degenerative disease, and breast and colonrectal cancers. Nevertheless, adherence to this pattern has decreased. Food labels are a potentially valid means to encourage towards healthier dietary behavior. This study, conducted on a subsample of 883 subjects enrolled in the Moli-sani Project, evaluated whether food labels reading (LR) is associated with MD adherence. Participants completed a questionnaire on nutrition knowledge, information, and attitudes, with a specific question on food labels reading. Biometric measurements, socio-economic status, education, physical activity, and smoking habits were collected. The European Prospective Investigation into Cancer and Nutrition (EPIC) food frequency questionnaire was used to collect dietary habits, and subsequently evaluated by both the Mediterranean diet score (MDS) and Italian Mediterranean index (IMI), a priori dietary patterns. Food consumption patterns were generated by Principal Components Analysis (PCA), an a posteriori approach. Multivariable odds ratios were calculated to quantify the association of LR categories with dietary habits. LR was significantly associated with greater adherence to both MDS (p = 0.0004) and IMI (p = 0.0019) in a multivariable model. LR participants had 74% (MDS) or 68% (IMI) higher probability to be in the highest level of adherence to Mediterranean diet-like patterns. Moreover, they showed greater adherence to Mediterranean-like food consumption patterns (0.1 vs. −0.2, p < 0.0001) and lower adherence to two Western-like patterns (0.01 vs. 0.2, p = 0.009 and 0.1 vs. 0.2, p = 0.02). These findings support an association between food label use and consuming a Mediterranean-type diet.

Aim: To evaluate the contribution of the 46C>T polymorphism of the Factor XII (FXII) gene to risk for coronary heart disease (CHD) in the West of Scotland Coronary Prevention Study (WOSCOPS) of men with high cholesterol. Background: WOSCOPS is a primary prevention trial that demonstrated the effectiveness of pravastatin in reducing morbidity and mortality from CHD. FXII is a protein of the contact system that plays a key role in both coagulation and fibrinolysis. Elevated activated FXII (FXIIa) levels have been previously associated with CHD. Plasma FXIIa levels are strongly determined by a 46C>T polymorphism in the FXII gene. Results: 441 CHD cases and 990 controls were genotyped. The frequency of TT homozygotes was 8.3% in controls and 11.8% in cases ( P =0.04). When compared with the CC+CT group (after adjustment for age, blood pressure, BMI, fibrinogen and lipid levels) the TT genotype was an independent risk factor for CHD (OR 1.48 95% CI 1.01–2.17), an effect that was only significant in the pravastatin group (OR 1.95 95% CI 1.09–3.47) and not in the placebo group (OR 1.20, 95%CI 0.72–2.02). Compared with risk in the placebo group as a whole (reference group), and after adjustment for other risk factors, men with the CC or CT genotype, but not the TT genotype showed a significant benefit from pravastatin treatment (OR, respectively, 0.61 (0.46–0.81) and 0.56 (0.40–0.79) compared with 1.10 (0.64–1.96). In a subgroup of these men, subjects with the TT genotype had, as expected, baseline levels of FXIIa that were 50% lower than those with the CC genotype, with CT subjects having intermediate levels ( P Conclusions: The TT genotype of the FXII 46C>T polymorphism is associated with a high risk of CHD in men with high cholesterol. We hypothesise that reduced fibrinolysis in these men, as a consequence of lower plasma FXIIa, may be the mechanism leading to higher risk, and that pravastatin treatment may enhance this effect.

The relationship of activated factor XII (FXIIa) and FXII 46CT genotype to coronary atherosclerosis and endothelial function was examined in 192 randomly sampled subjects from the general population and 190 type 1 diabetic subjects (mean age 38+/-4 years). Coronary artery calcification (CAC) was measured using Electron beam CT. von Willebrand factor (vWF), a marker of endothelial function, and FXIIa were measured by ELISA. Endothelial nitric oxide production was quantified as the forearm blood flow response to intra-brachial infusion of bradykinin and N(G) monomethyl-L-arginine (L-NMMA). A higher FXIIa was independently associated with higher triglycerides (P0.001), BMI (P=0.001), alcohol consumption (P=0.003) and vWF (P0.001) in non-diabetic subjects and with insulin dose (P=0.009), total cholesterol (P=0.02) and alcohol (P0.001) in diabetic subjects. Diabetic subjects had lower FXIIa (1.55 ng/ml) than non-diabetic subjects (1.92 ng/ml, P0.001). Higher FXIIa was associated with lower response to bradykinin (P=0.048) and to L-NMMA (P=0.029). FXIIa was positively associated with CAC (odds ratio=1.57 for every 1 ng/ml higher FXIIa, P=0.005) but not independently of other risk factors (odds ratio=1.1 on adjustment). 46CT genotype explained 18% of the variance in FXIIa (P0.001) but was not associated with CAC (P=0.6). We conclude that plasma FXIIa is under strong genetic control but also reflects plasma triglycerides and endothelial activation or dysfunction. FXIIa appears unlikely to be directly atherogenic but may be a useful marker of coronary atherosclerosis because of its association with these other factors. Type 1 diabetes is associated with lower levels of FXIIa despite a greater prevalence of atherosclerosis.

Mushrooms are known to be a major food source of selenium, a mineral associated with diabetes prevalence. This study aimed to evaluate the relationship between mushroom and dietary selenium intakes and blood glucose levels in a free-living adult Italian population.A total of 6879 men and 6891 women (aged 53.1±11.0years) with neither diabetes nor on special diets were analyzed from the population randomly recruited for the Moli-sani study. The European Prospective Investigation into Cancer and Nutrition (EPIC) food frequency questionnaire was used for dietary assessment. Fasting blood glucose (FBG) levels were measured from fasting serum samples, and diabetes prevalence was determined according to American Diabetes Association diagnostic criteria.In men, an increase of one (30-g) portion/week in mushroom consumption was associated with a 0.43-0.55mmol/L increase in FBG at different levels of adjustment (P0.05). In both men and women, dietary selenium was positively associated with blood glucose in both unadjusted and fully adjusted models (P0.05 for all). Both mushroom and dietary selenium intakes were independently associated with blood glucose on multivariate analyses. In addition, high intakes of both were associated with higher diabetes prevalence in men and women (OR1, P0.05).The association of mushroom and selenium intakes with FBG suggests that mushroom and selenium might each independently increase the risk of diabetes. However, prospective studies are now necessary to confirm this hypothesis.

The role of fibrinogen in cardiovascular disease has been extensively studied, and meta-analyses have definitively confirmed that high levels of fibrinogen are associated with an increased risk of the disease. In recent years, several polymorphisms have been identified in the fibrinogen chain genes that contribute to determine the levels of fibrinogen in the general population. The fibrinogen β-chain gene has been more extensively studied because the β-chain synthesis is the limiting step in the production of mature fibrinogen. Overall, the studies show an association between β-fibrinogen chain polymorphisms and the levels of fibrinogen. In contrast, the majority of the studies did not find any relation with the risk of cardiovascular disease. The individual responses to gender or to environmental stimuli such as smoking, physical exercise, or infections may be genetically determined, and genetic variability underlies changes in biological reactions that contribute to differences in cardiovascular risk. In the future, gene-environment interactions should be considered in evaluating the relevance of genetic variations on the risk of cardiovascular disease.

An extracellular, constitutive, and nonglucose repressed β-glucosidase from a yeast strain of Debaryomyces hansenii was purified and immobilized using a one-step procedure on hydroxyapatite (HTP). Analysis of purified enzyme gave two bands both on SDS gel electrophoresis, native gel electrophoresis, and capillary electrophoresis. The two bands on SDS gels were positive for carbohydrate staining. Their apparent molecular mass was estimated to be 122 and 96 kDa with carbohydrates, and 109 and 81 kDa after carbohydrate removal, respectively. Amino acid analysis of electroblotted bands revealed that the n -terminus was blocked in both cases. Gel slices corresponding to the two bands, as obtained after native gel electrophoresis, were found to be reactive when incubated separately with p-nitro-phenyl-β- d -glucopyranoside (pNPG) as substrate. The Km of the two forms coeluted from HTP in the same fractions was 3.68 ± 0.06 m m . The optimum pH was 5. The immobilized enzyme exhibited a lower activity than the purified free enzymes, but both were much more stable than the enzymes in cell-free supernatant. The two enzyme isoforms in the mixture were only active against few glycosides with β-linkage configuration. Since the HTP-bound enzyme was found to be active, stable, easily separable from the substrate, and reusable, it could be potentially used in its immobilized form for the release of specific-bound aroma in wine and fruit juices.

Lysozyme is an enzyme that hydrolyzes bacterial peptidoglicans. For this reason, it is used in cheese manufacturing in order to prevent a defect of long-ripened hard cheese called "late blowing" due to the outgrowth of spores of Clostridium tyrobutyricum and Clostridium butyricum. Moreover, germination of Listeria monocytogenes spores into vegetative cells is also sensitive to lysozyme. The enzyme can be an allergenic molecule, and for this reason there are concerns about its use in food industry. The immunological and clinical response of consumption of lysozyme-containing cheese has been evaluated in 25 egg-sensitive subjects with or without lysozyme sensitization.A total of 25 egg-sensitive subjects were enrolled in this study. All the subjects were already treated for egg-sensitization and presented a positive skin prick test. All the subjects had a body mass index ≤ 25 kg/m(2) and were in the age range of 20-50 years. Each subject was studied twice and received randomly 30 g of Grana Padano (containing lysozyme) or TrentinGrana cheese (lysozyme-free) of two different aging periods: 16 or 24 months. A washout period of 1 week between each cheese intake was adopted. Blood samples were taken in fasting conditions and 1 hour after cheese intake and IgA, total IgE, and lysozyme-, ovomucoid-, and ovalbumin-specific IgE were measured.No adverse reactions were observed in both groups of patients after cheese samples were given. Lysozyme did not determine any variation of specific IgE compared with basal level. In lysozyme-sensitive patients a significant relationship between IgA and lysozyme-specific IgE was observed when lysozyme-containing cheese was given, confirming that lysozyme can pass the gut barrier.Neither adverse events nor immunological responses were observed after ingestion of cheese containing lysozyme. However, the immunological properties of peptides deriving from cheese protein hydrolysis need to be clarified, as does the effect of lysozyme on bacterial proteolytic activity.

To categorize healthy food groups into categories of low-antioxidant (LAC) or high-antioxidant vitamins and phytochemicals content (HAC) and comparatively associate them with metabolic risk factors for cardiovascular disease (CVD).A total of 6879 women (55±12 years) and 6892 men (56 ± 12 years) were analyzed from the Moli-sani cohort, randomly recruited from the general population. The European Prospective Investigation into Cancer and Nutrition Food Frequency Questionnaire was used for dietary assessment. The antioxidant content of each food group was evaluated using Istituto Nazionale di Ricerca per gli Alimenti e la Nutrizione and United States Department of Agriculture (USDA) food composition tables. Healthy foods, according to a Mediterranean dietary pattern, were categorized into HAC or LAC; total food antioxidant content (FAC) score was constructed for a comparative evaluation of the consumption of these two groups.In men, an increase in FAC score, which represents an increased consumption of HAC with respect to LAC foods, was associated with a decrease in systolic blood pressure, diastolic blood pressure and C-reactive protein (CRP) (β=-0.5, P=0.02, β=-0.3, P=0.02 and β=-0.03, P=0.03, respectively). Logistic regression analyses showed that in men 15% (30 units) increase in FAC score was associated with 6% decrease in the likelihood of having hypertension (odds ratio (OR)=0.94, 95% confidence interval (CI) 0.91-0.98) and 3% decrease in the likelihood of having a high CRP risk level (OR=0.97, 95% CI 0.94-0.99). No significant associations were observed in women.A possible greater protective role of healthy HAC as compared with healthy LAC foods on hypertension and inflammation was detected in men. These results stress the importance of studying healthy foods according to their content in antioxidant vitamins and phytochemicals, in primary prevention of CVD.

Background: Cardiovascular disease and malignancies account for more than 70% of all causes of mortality and morbidity in Italy. There is a subtle balance between genetic determinants and lifestyle, that often defines the line between health and sickness. So far studies aiming at identifying risk factors have mainly come from Northern Europe and the USA. It was to understand this balance between genetics and environmental determinants better, and to tailor appropriate preventive strategies for Italian and other Southern European populations, that theMoli-sani project was launched, transforming a small Italian region into a large scientific laboratory: the “Molise lab”.Methods: Each participant receives a thorough medical check-up at no cost to either him/her or the national health service, resulting in thousands of hours of free public health care. With a completely computerized system, Moli-sani is a “paperless” study, in which researchers and participants communicate using recently developed technologies such as mobile phone text messages (SMS). The newly established biological data bank (the “MoliBank”) will be one of the largest in Europe. Results: Early results of 8000 participants so far show a slightly worrying pattern of risk factors for a Mediterranean population. The prevalence of obesity, hypertension and metabolic syndrome is growing at rates close to those of other Western countries. Hypertension and, to a lesser extent, high blood glucose levels, are under-diagnosed and underestimated by patients, and appropriate therapy appears under-used and not very successful. However, cholesterol management appears more efficient.Conclusions: Paying particular attention towards innovation and new technologies, theMoli-sani project has placed itself at the cutting edge of a new paradigm crossing research and prevention.

Aim We aimed at investigating the association between T-wave axis deviation, metabolic syndrome (MetS), its components and estimated risk of cardiovascular disease (CVD) at 10 years in an adult Italian population. Methods 11,143 women (54 ± 11 years) and 9742 men (55 ± 11 years) were analyzed from the Moli-sani cohort, randomly recruited from the general population. MetS was defined using the ATPIII criteria. T-wave axis deviation was measured from the standard 12-lead resting electrocardiogram. CVD risk in ten years was estimated by the CUORE score. Results 29% of men and 27% of women with MetS showed borderline or abnormal T-wave as compared to 24% and 17% without MetS ( p Among components of MetS, elevated waist and blood pressure were strongly associated with T-wave axis deviation, whereas glucose, HDL and triglycerides were only marginally. The odds of having borderline or abnormal T-wave axis deviation in multivariable regression analysis, was 1.38 (95% CI:1.25–1.53) in MetS men and 1.68 (95% CI:1.51–1.87) in MetS women compared to those without. Further adjustment for MetS components completely abolished the associations. Abnormal T-wave axis deviation was associated with an increased risk of CVD in 10 years in men (OR = 4.4; 95% CI:1.10–17.9). Conclusion T-wave axis deviation is strongly associated with components of the MetS, in particular high waist circumference and blood pressure and with an increased CVD risk, particularly in men. ECG monitoring to identify T-wave axis deviation in obese, hypertensive or MetS subjects can be an early indicator of vascular disease and help in reducing cardiac events.

Background: Guidelines for primary prevention recommend calculation of lifetime risk for cardiovascular disease (CVD) in addition to short-time risk. We aimed at evaluating the distribution of CVD lifetime risk and the percentage of Italians having low short-term, but high lifetime, risk. Design: Cross-sectional general population-based cohort study. Methods: We included 8,403 (46% men) cardiovascular disease-free individuals aged 35–50 years, among those randomly recruited in the framework of the MOLI-SANI cohort. Participants were stratified into three groups: low short-time (10-year) (≤3% and non diabetic)/low lifetime, low short-time/high lifetime, and high short-time risk. Short-time risk was evaluated by the equation provided by the Italian CUORE project. Lifetime risk was evaluated using the algorithm derived from the Framingham cohort. Results: High short-time risk was prevalent in 16% population (32% of men and 2% of women). Among individuals with low short-time risk, 80% had high lifetime risk (82% men and 78% women). The proportion of individuals with very low lifetime risk due to all optimal risk factors was 4.1% only (1.5% men and 6.3% women). Conclusions: A large proportion of Italian adults not qualified for CVD primary prevention because of their very low short-time predicted CVD risk, are in fact at high risk to develop a CVD event in their lifetime; therefore population-based approaches should be sought to modify the overall distribution of individual risk factors. These findings offer helpful information for policy makers involved in contrasting the burden of CVD, especially in women and young men.

Is it possible to reduce the false-positive diagnostic statements in young athlete ECG screening? Roger Abacherli, Richard Kobza, David Hadley, Johann-Jakob Schmid, Franz Frey, Paul Erne, Victor Froelicher SCHILLER AG, Biomed, Research and Signal Processing, Baar, Switzerland Division of Cardiology, Cantonal Hospital Luzern, Switzerland Cardea Associate, Inc., Woodinville, WA, USA Swiss Army, Ittigen, Switzerland Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA, USA Veterans Affairs, Palo Alto Health Care System, Palo Alto, CA, USA