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Background: Individuals with low levels of cardiovascular risk factors experience low incidence of subsequent cardiovascular diseases (CVD). The aims of this study were to assess cancer incidence in people with favorable (low) CVD risk profile and its association with educational level (EL). Methods: The MATISS longitudinal cohort comprised 3609 men and 4146 women aged 20-70 years, free of CVD and cancer at baseline with validated non-fatal and fatal CVD and cancer events during a median 17.7 years of follow-up. People at baseline were classified as ‘low risk’ with total cholesterol 2 and no hypertension treatment and no diabetes and no smoking habit and ‘high risk’ (total cholesterol >=240mg/dl or blood pressure >=140/90 mmHg or BMI >=30.0 kg/m 2 or hypertension treatment, diabetes, smoking). EL was classified as low (LEL=elementary school) and middle-high (MHEL=middle/high school/university). Results: 724 cancer and 571 CVD events occurred; 22.7% of participants were ‘low risk’; 77.3% were ‘high risk; 61.5% had LEL. Cancer and CVD incidences increased with age; age-adjusted cancer and CVD incidence were higher in men compared to women (cancer: 68.92 versus 48.95 x 10,000 person-years; CVD: 64.18 versus 29.5 x 10,000 person-years). Incidences of cancer and CVD were higher in LEL (cancer: 83.22 versus 50.35 x 10,000 person-years in men and 51.67 versus 33.59 x 10,000 person-years in women; CVD: 70.07 versus 64.84 x 10,000 person-years in men and 30.72 versus 17.89 x 10,000 person-years in women). Persons with ‘low risk’ profile experienced less cancers and CVD than persons with ‘high risk (cancer: 37.66 versus 72.3 x 10,000 person-years in men and 39.57 versus 50.07 x 10,000 person-years in women; CVD: 18.49 versus 69.75 per 10,000 person-years in men and 20.34 versus 30.7 x 10,000 person-years in women). In analysis by risk profile and EL considered together for both genders rates of both CVD and cancer were highest in those with less education classified as high risk (cancer: 85.2 versus 56.13 x 10,000 person-years in men and 50.97 versus 35.12 x 10,000 person-years in women; CVD: 74.58 versus 69.06 per 10,000 person-years in men and 30.87 versus 22.69 x 10,000 person-years in women). Conclusions: Increasing educational levels and prevalence of low CVD risk profile in the general population may be effective strategies for population-wide CVD and cancer prevention.

HHH syndrome is an autosomal recessive urea cycle disorder caused by alterations in the SLC25A15 gene encoding the mitochondrial ornithine carrier 1, which catalyzes the transport of cytosolic ornithine into the mitochondria in exchange for intramitochondrial citrulline. In this study the functional effects of several SLC25A15 missense mutations p.G27R, p.M37R, p.N74A, p.F188L, p.F188Y, p.S200K, p.R275Q and p.R275K have been tested by transport assays in reconstituted liposomes and complementation of Saccharomyces cerevisiae ORT1 null mutant in arginine-less synthetic complete medium. The HHH syndrome-causing mutations p.G27R, p.M37R, p.F188L and p.R275Q had impaired transport and did not complement ORT1 ∆ cells (except p.M37R slightly after 5days in solid medium). The experimentally produced mutations p.N74A, p.S200K and p.R275K exhibited normal or considerable transport activity and complemented ORT1 ∆ cells after 3days (p.N74A, p.S200K) or 5days (p.R275K) incubation. Furthermore, the experimentally produced p.F188Y mutation displayed a substantial transport activity but did not complement the ORT1 ∆ cells in both liquid and solid media. In view of the disagreement in the results obtained between the two methods, it is recommended that the method of complementing the S . cerevisiae ORT1 knockout strain is used complimentary with the measurement of the catalytic activity, in order to distinguish HHH syndrome-causing mutations from isomorphisms.

Among the members of the mitochondrial carrier family, there are transporters that catalyze the translocation of ornithine and related substrates, such as arginine, homoarginine, lysine, histidine, and citrulline, across the inner mitochondrial membrane. The mitochondrial carriers ORC1, ORC2, and SLC25A29 from Homo sapiens, BAC1 and BAC2 from Arabidopsis thaliana, and Ort1p from Saccharomyces cerevisiae have been biochemically characterized by transport assays in liposomes. All of them transport ornithine and amino acids with side chains terminating at least with one amine. There are, however, marked differences in their substrate specificities including their affinity for ornithine (KM values in the mM to μM range). These differences are most likely reflected by minor differences in the substrate binding sites of these carriers. The physiological role of the above-mentioned mitochondrial carriers is to link several metabolic pathways that take place partly in the cytosol and partly in the mitochondrial matrix and to provide basic amino acids for mitochondrial translation. In the liver, human ORC1 catalyzes the citrulline/ornithine exchange across the mitochondrial inner membrane, which is required for the urea cycle. Human ORC1, ORC2, and SLC25A29 are likely to be involved in the biosynthesis and transport of arginine, which can be used as a precursor for the synthesis of NO, agmatine, polyamines, creatine, glutamine, glutamate, and proline, as well as in the degradation of basic amino acids. BAC1 and BAC2 are implicated in some processes similar to those of their human counterparts and in nitrogen and amino acid metabolism linked to stress conditions and the development of plants. Ort1p is involved in the biosynthesis of arginine and polyamines in yeast.

Objectives To assess geographic and socioeconomic gradients in sodium and potassium intake in Italy.\ud \ud Setting Cross-sectional survey in Italy.\ud \ud Participants 3857 men and women, aged 39–79 years, randomly sampled in 20 regions (as part of a National cardiovascular survey of 8714 men and women).\ud \ud Primary outcome measures Participants’ dietary sodium and potassium intakes were measured by 24 h urinary sodium and potassium excretions. 2 indicators measured socioeconomic status: education and occupation. Bayesian geoadditive models were used to assess spatial and socioeconomic patterns of sodium and potassium intakes accounting for sociodemographic, anthropometric and behavioural confounders.\ud \ud Results There was a significant north-south pattern of sodium excretion in Italy. Participants living in southern Italy (eg, Calabria, Basilicata and Puglia >180 mmol/24 h) had a significantly higher sodium excretion than elsewhere (eg, Val d'Aosta and Trentino-Alto Adige

BACKGROUND: Cardiovascular risk factor research has recently broadened its focus based on new data indicating the benefits of low risk, i.e. favorable levels of all major risk factors. The aims of this study were to assess further the relation of low risk to coronary heart disease risk, and implications for prevention. DESIGN: We conducted a prospective population-based Italian study, of 7438 men and 13 009 women aged 35-69 years, with a mean follow-up of 10.4 years and validated first coronary events. METHODS: Baseline coronary heart disease risk was classified into three categories: low risk; unfavorable but not high risk; and high risk. To analyze the relation of these risk profiles to coronary heart disease incidence, age-adjusted, sex-averaged coronary heart disease incidence was calculated for persons free of coronary heart disease and stroke, stratified as baseline low risk, unfavorable but not high risk or high risk. To assess the independent relationship of individual risk factors to coronary heart disease incidence, multivariate proportional hazards models were computed for combinations of risk factors. RESULTS: Only 2.7% of participants met low risk criteria; 81.4% were high risk. Age-adjusted coronary heart disease incidence for the whole cohort was 37.1 out of 10000 person-years (men 59.0; women 15.3). No coronary heart disease events occurred in low-risk men, only two in low-risk women. For women and men who were not high risk, the age-sex standardized coronary heart disease rate was 62% lower than for high-risk participants. Blood pressure, need for antihypertensive medication, smoking, hyperglycemia, diabetes, total and high-density lipoprotein cholesterol were independently related to coronary heart disease risk. CONCLUSIONS: Favorable levels of all modifiable readily measured risk factors - rare among Italian adults - assure minimal coronary heart disease risk. Population-wide prevention is needed, especially improved lifestyles, to increase the proportion of the population at low risk. © 2006 The European Society of Cardiology.

AIMS Although calculation of the global cardiovascular risk is strongly recommended, limited data are available regarding the use and the utility of this tool in clinical practice. We aimed at answering the following questions in the setting of Italian general practice: how many patients are evaluated via the cardiovascular risk algorithm; what are their characteristics; and what happens after their evaluation. METHODS We used the Health Search/CSD Longitudinal Patient Database. The software used by about 800 participating GPs allows the calculation of the global cardiovascular risk in automatic. The following data were yearly extracted from the database within 2004-2008: age, sex, and recorded diagnosis of the main cardiovascular and other information encompassing smoking habits, blood pressure, total cholesterol, high density lipoprotein cholesterol (i.e., variables used to calculate cardiovascular risk), BMI, physical activity, triglycerides, glucose and creatinine; wherever available, current cardiovascular therapy and the automatically computed global cardiovascular risk were also extracted. RESULTS In 2008, the observed population, aged 35-69 years, numbered 438 922 individuals; 78 617 (17.9%) had at least one calculation of cardiovascular risk; 20 181 patients were re-evaluated at least once: 61.1% among high-risk patients, 43.8% among moderate-risk patients, and 27.2% among low-risk patients. The level of cardiovascular risk measured at baseline increased in 6863 (34%), decreased in 11 791 (58.4%), and did not change in 1527 (7.6%) individuals. Overall, mean cardiovascular risk decreased over 4 years in 2.25% (SD 6.41%; P

Background The great interest in the production of highly pure lactic acid enantiomers comes from the application of polylactic acid (PLA) for the production of biodegradable plastics. Yeasts can be considered as alternative cell factories to lactic acid bacteria for lactic acid production, despite not being natural producers, since they can better tolerate acidic environments. We have previously described metabolically engineered Saccharomyces cerevisiae strains producing high amounts of L-lactic acid (>60 g/L) at low pH. The high product concentration represents the major limiting step of the process, mainly because of its toxic effects. Therefore, our goal was the identification of novel targets for strain improvement possibly involved in the yeast response to lactic acid stress. Results The enzyme S-adenosylmethionine (SAM) synthetase catalyses the only known reaction leading to the biosynthesis of SAM, an important cellular cofactor. SAM is involved in phospholipid biosynthesis and hence in membrane remodelling during acid stress. Since only the enzyme isoform 2 seems to be responsive to membrane related signals (e.g. myo-inositol), Sam2p was tagged with GFP to analyse its abundance and cellular localization under different stress conditions. Western blot analyses showed that lactic acid exposure correlates with an increase in protein levels. The SAM2 gene was then overexpressed and deleted in laboratory strains. Remarkably, in the BY4741 strain its deletion conferred higher resistance to lactic acid, while its overexpression was detrimental. Therefore, SAM2 was deleted in a strain previously engineered and evolved for industrial lactic acid production and tolerance, resulting in higher production. Conclusions Here we demonstrated that the modulation of SAM2 can have different outcomes, from clear effects to no significant phenotypic responses, upon lactic acid stress in different genetic backgrounds, and that at least in one genetic background SAM2 deletion led to an industrially relevant increase in lactic acid production. Further work is needed to elucidate the molecular basis of these observations, which underline once more that strain robustness relies on complex cellular mechanisms, involving regulatory genes and proteins. Our data confirm cofactor engineering as an important tool for cell factory improvement. Electronic supplementary material The online version of this article (doi:10.1186/s12934-014-0147-7) contains supplementary material, which is available to authorized users.

Background Italy has a long tradition of cardiovascular surveys. Due to the decline in the participation rates, in the OEC/HES new exams such as bone densitometry were added; more attention was put to select and train the fieldwork staff; possibility to change the appointment was offered. Methods The OEC/HES was conducted in May 2008-July 2012; 220 men and women aged 35-79 years per 1.5 million persons were randomly selected for a …

International audience; Severe neonatal epilepsies with suppression-burst pattern are epileptic syndromes with either neonatal onset or onset during the first months of life. These disorders are characterized by a typical electroencephalogram pattern-namely, suppression burst, in which higher-voltage bursts of slow waves mixed with multifocal spikes alternate with isoelectric suppression phases. Here, we report the genetic mapping of an autosomal recessive form of this condition to chromosome 11p15.5 and the identification of a missense mutation (p.Pro206Leu) in the gene encoding one of the two mitochondrial glutamate/H + symporters (SLC25A22, also known as "GC1"). The mutation co-segregated with the disease and altered a highly conserved amino acid. Functional analyses showed that glutamate oxidation in cultured skin fibroblasts from patients was strongly defective. Further studies in reconstituted proteo-liposomes showed defective [ 14 C]glutamate uniport and [ 14 C]glutamate/glutamate exchange by mutant protein. Moreover , expression studies showed that, during human development, SLC25A22 is specifically expressed in the brain, within territories proposed to contribute to the genesis and control of myoclonic seizures. These findings provide the first direct molecular link between glutamate mitochondrial metabolism and myoclonic epilepsy and suggest potential insights into the pathophysiological bases of severe neonatal epilepsies with suppression-burst pattern.

The mitochondrial carriers are a family of transport proteins that, with a few exceptions, are found in the inner membranes of mitochondria. They shuttle metabolites, nucleotides, and cofactors through this membrane and thereby connect and/or regulate cytoplasm and matrix functions. ATP-Mg is transported in exchange for phosphate, but no protein has ever been associated with this activity. We have isolated three human cDNAs that encode proteins of 458, 468, and 489 amino acids with 66–75% similarity and with the characteristic features of the mitochondrial carrier family in their C-terminal domains and three EF-hand Ca2+-binding motifs in their N-terminal domains. These proteins have been overexpressed in Escherichia coli and reconstituted into phospholipid vesicles. Their transport properties and their targeting to mitochondria demonstrate that they are isoforms of the ATP-Mg/Pi carrier described in the past in whole mitochondria. The tissue specificity of the three isoforms shows that at least one isoform was present in all of the tissues investigated. Because phosphate recycles via the phosphate carrier in mitochondria, the three isoforms of the ATP-Mg/Pi carrier are most likely responsible for the net uptake or efflux of adenine nucleotides into or from the mitochondria and hence for the variation in the matrix adenine nucleotide content, which has been found to change in many physiopathological situations.

Summary The malate-aspartate NADH shuttle in mammalian cells requires the activity of the mitochondrial aspar- tate-glutamate carrier (AGC). Recently, we identified in man two AGC isoforms, aralar1 and citrin, which are regulated by calcium on the external face of the inner mitochondrial membrane. We have now identi- fied Agc1p as the yeast counterpart of the human AGC. The corresponding gene was overexpressed in bacteria and yeast mitochondria, and the protein was reconstituted in liposomes where it was identified as an aspartate-glutamate transporter from its transport properties. Furthermore, yeast cells lacking Agc1p were unable to grow on acetate and oleic acid, and had reduced levels of valine, ornithine and citrulline; in contrast they grew on ethanol. Expression of the human AGC isoforms can replace the function of Agc1p. However, unlike its human orthologues, yeast Agc1p catalyses both aspartate-glutamate exchange and substrate uniport activities. We conclude that Agc1p performs two metabolic roles in Saccharomy- ces cerevisiae . On the one hand, it functions as a uniporter to supply the mitochondria with glutamate for nitrogen metabolism and ornithine synthesis. On the other, the Agc1p, as an aspartate-glutamate exchanger, plays a role within the malate-aspartate NADH shuttle which is critical for the growth of yeast on acetate and fatty acids as carbon sources. These results provide strong evidence of the existence of a malate-aspartate NADH shuttle in yeast.

Summary We describe the identification and functional characterization of two Arabidopsis mitochondrial basic amino acid carriers (BAC), AtmBAC1 and AtmBAC2, which are related to the yeast ornithine (Orn) carrier Ort1p, also known as Arg11p. The arg11 mutant requires arginine (Arg) supplementation because it fails to export sufficient ornithine from the mitochondrion to the cytosol where it is converted to arginine. AtmBAC1 and, to a lesser extent, AtmBAC2 partially replaced the function of Ort1p in yeast arg11. The more efficient putative carrier, AtmBAC1, was expressed in E. coli, purified, and reconstituted into phospholipid vesicles, where it transported the basic l-amino acids arginine, lysine, ornithine and histidine (in order of decreasing affinity). AtmBAC1 recognized l-histidine whereas both yeast Ort1p and the mammalian ortholog ORNT1p do not. Also different from ORNT1p, AtmBAC1 did not transport citrulline. AtmBAC1 appeared to be more stereospecific than the yeast and mammalian ornithine carriers, exhibiting greater preference for the l-forms of arginine, lysine and ornithine. By RT-PCR, both AtmBAC1 and AtmBAC2 transcripts were detected in stems, leaves, flowers, siliques, and seedlings. Expression of AtmBAC1 in seedlings is consistent with its involvement in Arg breakdown in early seedling development, i.e. delivery of Arg to mitochondrial arginase. The Km (0.19 mm) for Arg uptake by AtmBAC1 was close to the value we previously determined for the saturable component of Arg uptake into intact mitochondria from soybean seedling cotyledons.

A cDNA from Arabidopsis thaliana and four related cDNAs from Nicotiana tabacum that we have isolated encode hitherto unidentified members of the mitochondrial carrier family. These proteins have been overexpressed in bacteria and reconstituted into phospholipid vesicles. Their transport properties demonstrate that they are orthologs/isoforms of a novel mitochondrial carrier capable of transporting both dicarboxylates (such as malate, oxaloacetate, oxoglutarate, and maleate) and tricarboxylates (such as citrate, isocitrate, cis-aconitate, and trans-aconitate). The newly identified dicarboxylate-tricarboxylate carrier accepts only the single protonated form of citrate (H-citrate2-) and the unprotonated form of malate (malate2-) and catalyzes obligatory, electroneutral exchanges. Oxoglutarate, citrate, and malate are mutually competitive inhibitors, showing K(i) close to the respective K(m). The carrier is expressed in all plant tissues examined and is largely spread in the plant kingdom. Furthermore, nitrate supply to nitrogen-starved tobacco plants leads to an increase in its mRNA in roots and leaves. The dicarboxylate-tricarboxylate carrier may play a role in important plant metabolic functions requiring organic acid flux to or from the mitochondria, such as nitrogen assimilation, export of reducing equivalents from the mitochondria, and fatty acid elongation.

Saccharomyces cerevisiae ANT1/YPR128c encodes the peroxisomal adenine nucleotide transporter that provides ATP for intra-peroxisomal activation of medium-chain fatty acids. A lacZ reporter construct comprising the ANT1 promoter was shown to be comparatively more highly expressed in a wild-type strain grown on oleic acid, a long-chain fatty acid, than in pip2Delta(oaf1)Delta mutant cells that are defective in fatty acid induction. The ANT1 promoter was demonstrated to contain a deviant oleate response element (ORE) that could bind the Pip2p-Oaf1p transcription factor and confer activation on a basal CYC1-lacZ reporter gene. Expression of Ant1p as well as other enzymes whose genes are known to be regulated by a canonical ORE was found to be increased in cells grown on lauric acid, a medium-chain fatty acid. We concluded that the signal for induction does not differentiate between long- and medium-chain fatty acids. This signal was independent of beta-oxidation or the biogenesis of the peroxisomal compartment where this process occurs, since a pox1Delta strain blocked in the first and rate-limiting step of beta-oxidation as well as various pex mutant cells devoid of intact peroxisomes produced sufficient amounts of Pip2p-Oaf1p for binding OREs in vitro and for expressing an ORE-driven reporter gene. The signal's durability was shown to be related to the concentration of fatty acids in the medium, since a pex6Delta strain expressed an ORE-driven reporter gene at high levels for a longer period than did isogenic wild-type cells. Generation of the signal was also independent of protein synthesis, as demonstrated by cycloheximide treatment.

Sengers syndrome is characterized by congenital cataracts, hypertrophic cardiomyopathy, mitochondrial myopathy, and lactic acidosis, but no abnormalities have been found with routine mitochondrial biochemical diagnostics (the determination of pyruvate oxidation rates and enzyme measurements). In immunoblot analysis, the protein content of the mitochondrial adenine nucleotide translocator 1 (ANT1) was found to be strongly reduced in the muscle tissues of two unrelated patients with Sengers syndrome. In addition, low residual adenine nucleotide translocator activity was detected upon the reconstitution of detergent-solubilized mitochondrial extracts from the patients' skeletal or heart muscle into liposomes. Sequence analysis and linkage analysis showed that ANT1 was not the primary genetic cause of Sengers syndrome. We propose that transcriptional, translational, or posttranslational events are responsible for the ANT1 deficiency associated with the syndrome.

The mitochondrial carriers are a family of transport proteins in the inner membranes of mitochondria. They shuttle substrates, metabolites, and cofactors through this membrane and connect cytoplasm functions with others in the matrix. Glutamate is co-transported with H+ (or exchanged for OH−), but no protein has ever been associated with this activity. Two human expressed sequence tags encode proteins of 323 and 315 amino acids with 63% identity that are related to the aspartate-glutamate carrier, a member of the carrier family. They have been overexpressed in Escherichia coli and reconstituted into phospholipid vesicles. Their transport properties demonstrate that the two proteins are isoforms of the glutamate/H+ symporter described in the past in whole mitochondria. Isoform 1 is expressed at higher levels than isoform 2 in all the tissues except in brain, where the two isoforms are expressed at comparable levels. The differences in expression levels and kinetic parameters of the two isoforms suggest that isoform 2 matches the basic requirement of all tissues especially with respect to amino acid degradation, and isoform 1 becomes operative to accommodate higher demands associated with specific metabolic functions such as ureogenesis.

Background: The number of elderly persons with cardiovascular disease (CVD) is rapidly increasing, mainly due to worldwide aging population. All CVD risk scores consider age as risk factor but most of them assume that the etiological role of other established risk factors is similar at all ages. This analyses aimed to assess the predictive role of cardiovascular risk factors in elderly persons. Methods: We considered 10,979 men and 16,533 women aged 35-74 years from cohorts in North, Centre and South of Italy with 10 years median follow-up time for fatal and non fatal coronary and cerebrovascular events (819 in men and 467 in women) validated according to MONICA criteria. In all cohorts risk factors were assessed by using standardized procedures. Two age groups were defined: adult 35-54 years of age (6,353 men and 10,358 women) and elderly 55-74 years (4,626 men and 6,175 men). Cox models were implemented including age, systolic blood pressure (SBP), total (TC) and HDL cholesterol (HDL-C), smoking, diabetes (DM - fasting blood glucose >=126 mg/dl or under glucose treatment) and hypertension treatment (HT). For continuous variables, hazard ratios (HR) were reported at 1 standard deviation higher level and for dichotomized variables, yes vs no. Results: For adult men SBP resulted having a stronger impact on CVD risk than for elderly even if not statistically significant: adult HR 1.32, 95% confidence interval 1.18-1.48, vs elderly HR 1.25, 1.15-1.36; similar results for TC (HR 1.47 vs 1.25), smoking (HR 1.91, vs 1.52), DM (HR 1.76 vs 1.56), HT (HR 2.30 vs 1.25). HDL-C resulted not significantly associated with CVD risk in elderly men. Among adult women a stronger impact was found than in elderly for SBP (HR 1.59 vs 1.26), HDL-C (0.65 vs 0.84), smoking (2.43 vs 1.99), and HT (2.34 vs 1.45); the opposite for TC (1.19 vs 1.27). DM resulted not significantly associated with CVD risk in adult women. Age resulted having a stronger impact in elderly persons both in men and women (HR 1.22, 1.07-1.39, vs 1.44, 1.29-1.61; 1.45, 1.17-1.80, vs 1.63, 1.42-1.86 respectively). Conclusions: SBP and HT resulted having a pronounced lower impact on CVD risk in elderly than in adult as well as HDL-C for men; age shows a stronger impact in elderly than in adult. Further analyses are recommended to study the reliability of risk scores based on age-specific risk models, evaluating the introduction of different risk factors and considering survival probability derived from data in elderly population.

Background: Strategies aiming at reducing dietary sodium are being implemented in many countries based on evidence-based knowledge supporting their cost-effectiveness for reduction of cardiovascular and other chronic diseases. From 2009 to 2011 a Preventive Program of the Italian Ministry of Health has been implemented in Italy including the agreement with bread makers’ associations for the gradual reduction of the salt content in bread, public information campaigns, and the evaluation of population current dietary sodium intakes. This analyses aim to monitor dietary intake of sodium and potassium in representative samples of the Italian adult population before and after the Preventive Program. Methods: Data from random samples of persons aged 35-79 years and resident in Italian central regions were collected from October 2009 to September 2010 (299 men and 280 women) and from April to July 2012 (205 men and 210 women). Determinations of sodium and potassium were assessed in a centralized laboratory. Information on the consumption of high salt content food were collected through a questionnaire. Comparisons between mean levels and prevalences were performed using t-test and chi-squared test respectively. Results: In men, mean level of sodium chloride per day resulted 185 mmol (95% confidence interval: 177-193 mmol) in 2009-2010 samples and 161 mmol (152-169 mmol) in 2012 samples (p Conclusions: Presented data show that average daily sodium intake in central Italy is still largely higher than that recommended but a significant improvement of mean level of sodium intake and consumption of bread without salt resulted. This results fully justify and encourage the preventive initiatives for reduction of sodium intake and its monitoring in the general population.

Aims: We assess the external validation, on a “new” set of subjects, of the CAMUNI 20-year risk score, developed in a northern Italian population. Although an external validation analysis is recommended before adopting a score in clinical practice, it is rarely performed in long-term prediction equations as it requires similar long-term follow-up procedures in different cohort studies. Methods: The CAMUNI risk score was developed to estimate the 20-year risk of first coronary or ischemic stroke event, fatal or non-fatal, in 5247 (2574 men) 35-69 subjects free of CVD at baseline enrolled in late 1980s-early 1990s in Brianza, northern Italy (derivation set). The score is based on two gender-specific Cox models, including age, total- and HDL-cholesterol, systolic blood pressure, anti-hypertensive treatment, cigarette smoking and diabetes. As validation set, we considered 5307 (2418 men) subjects enrolled in the Rome area in the same time span (MATISS Study). Both the derivation and the validation cohorts shared the same procedures for baseline risk assessment and follow-up procedures, including MONICA definition of acute events. We evaluated the performance of the CAMUNI score in the validation set; the Framingham CVD risk score was used for comparison. The absolute predicted risk from both scores was re-calibrated to the 20-year risk observed in the validation set. We report the calibration slope as a measure of calibration; a value different from 1 is suggestive of a different strength in predictor effects. The Area Under the ROC-curve (AUC) measured the discrimination ability; the AUC in the validation set was compared to the value in the derivation set, corrected for over-optimism. Results: The 20-year Kaplan-Meier risk of event was 16.1% (derivation set; 315 events) and 13.2% (validation set; 238 events) in men, and 6.1% (123 events) and 5.6% (119 events) in women. The calibration slope for the CAMUNI score did not significantly differ from 1 in men (1.1; 95% confidence interval 0.9; 1.2) nor in women (1.0; 0.8;1.2). The Framingham score performed equally well in men (1.1; 0.9; 1.2) but worse in women (1.3; 1.1;1.6). In the derivation set, the over-optimism corrected AUC for the CAMUNI model was 0.737 (men) and 0.801 (women); the corresponding figures in the validation set were 0.732 (95% CI: 0.727-0.738) in men, and 0.801 (0.794-0.808) in women. The Framingham score performed less well in men (0.722; 0.717-0.727) and in women (0.705; 0.699-0.711). Conclusions: Based on these preliminary results, the CAMUNI 20-year risk score seems to be appropriate for long-term risk prediction in Italy and, more generally, in low-incidence populations.

A methodology is proposed that can predict, with a systemic approach, the status of the economic, social, cultural and administrative components of an urban centre in normal growth and in seismic crisis. This is essential to evaluate the ability of a city to fulfill its functions after a disaster. In the model, the following sub-systems are considered as part of the urban system: Social, Residential, Cultural, Health, Education, Energy, Economic, Administrative and Emergency. Each one of the above sub-systems includes many elements at risk and is influenced by the other sub-systems. As an application example we look at Crotone municipality, South Italy, where data on active faults, soil, buildings, infrastructures, lifelines, and population have been extensively collected in the past, within the PIC-Urban II project. Damage scenarios are proposed for earthquakes with different return periods. The functionality of the considered sub-systems is also evaluated

Pulsed light technology (PLT) is an innovative method for the purification and sterilization of food items using very high power, short duration pulses of light emitted by inert-gas flash lamps. This technology was approved by the FDA in 1996, and has recently been widely investigated to assess possible commercial applications. In this chapter, the theoretical and technical principles of PLT are introduced and the main topics of PLT are discussed, including the development of the device, the mechanisms of microbial inactivation, the parameters that are critical to the process, and optimization criteria. Finally, the results of a number of experimental studies of the effects of PLT on microorganisms and food properties are reported. These results confirm that PLT is a rapid, low-energy technique for food microbial inactivation that inflicts little thermal damage, but also indicate that it should be limited to the treatment of very transparent foods, or to surface treatments of foods and food packages.

Population-based data on coronary events are generally lacking for large areas, such as at the nation-wide level. While mortality data are currently and exhaustively collected in all developed countries and in a few developing countries, incidence and prevalence are often available only for certain subgroups of the population under study.We propose to estimate population-based incidence and prevalence of coronary events through a mathematical method using mortality and survival data as input, and to forecast coronary event occurrence using an age, period and cohort approach. The method reconstructs incidence and prevalence of major coronary events in Italy from 1970 to 1997 and projects trends up to the year 2007 using survival data on coronary events from the Area Friuli-MONICA (MONItoring of CArdiovascular diseases) register.Major coronary event incidence has been decreasing since 1977 for men and since 1974, for women. Conversely, major coronary event prevalence increased up to the end of the 1980s for men and up to the early 1980s for women, and it has been declining thereafter. Major coronary event prevalence results from three main effects: increasing survival, population ageing, and incidence trend.Availability of national population data, collection of population-based survival data from the MONICA registers and appropriate statistical and mathematical methods help to estimate and project incidence and prevalence trends for major coronary events. This information is essential to plan and implement actions aimed at improving medical care services, and to evaluate the impact of public health interventions as well as spontaneously changing habits. Incidence, prevalence, mortality, projections, ischaemic heart disease, coronary events

In Saccharomyces cerevisiae, the genes ODC1 and ODC2 encode isoforms of the oxodicarboxylate carrier. They both transport C5-C7 oxodicarboxylates across the inner membranes of mitochondria and are members of the family of mitochondrial carrier proteins. Orthologs are encoded in the genomes of Caenorhabditis elegans and Drosophila melanogaster, and a human expressed sequence tag (EST) encodes part of a closely related protein. Information from the EST has been used to complete the human cDNA sequence. This sequence has been used to map the gene to chromosome 14q11.2 and to show that the gene is expressed in all tissues that were examined. The human protein was produced by overexpression in Escherichia coli, purified, and reconstituted into phospholipid vesicles. It has similar transport characteristics to the yeast oxodicarboxylate carrier proteins (ODCs). Both the human and yeast ODCs catalyzed the transport of the oxodicarboxylates 2-oxoadipate and 2-oxoglutarate by a counter-exchange mechanism. Adipate, glutarate, and to a lesser extent, pimelate, 2-oxopimelate, 2-aminoadipate, oxaloacetate, and citrate were also transported by the human ODC. The main differences between the human and yeast ODCs are that 2-aminoadipate is transported by the former but not by the latter, whereas malate is transported by the yeast ODCs but not by the human ortholog. In mammals, 2-oxoadipate is a common intermediate in the catabolism of lysine, tryptophan, and hydroxylysine. It is transported from the cytoplasm into mitochondria where it is converted into acetyl-CoA. Defects in human ODC are likely to be a cause of 2-oxoadipate acidemia, an inborn error of metabolism of lysine, tryptophan, and hydroxylysine.

The nuclear genome of Saccharomyces cerevisiae encodes 35 members of a family of membrane proteins. Known members transport substrates and products across the inner membranes of mitochondria. We have localized two hitherto unidentified family members, Odc1p and Odc2p, to the inner membranes of mitochondria. They are isoforms with 61% sequence identity, and we have shown in reconstituted liposomes that they transport the oxodicarboxylates 2-oxoadipate and 2-oxoglutarate by a strict counter exchange mechanism. Intraliposomal adipate and glutarate and to a lesser extent malate and citrate supported [14C]oxoglutarate uptake. The expression of Odc1p, the more abundant isoform, made in the presence of nonfermentable carbon sources, is repressed by glucose. The main physiological roles of Odc1p and Odc2p are probably to supply 2-oxoadipate and 2-oxoglutarate from the mitochondrial matrix to the cytosol where they are used in the biosynthesis of lysine and glutamate, respectively, and in lysine catabolism.

The tricarboxylate carrier was purified to homogeneity from liver mitochondria of European eel at the silver and the yellow stage and functionally reconstituted into liposomes. Unexpectedly, the molecular activity of the tricarboxylate carrier obtained from silver eel was about twofold higher than that of the same protein from yellow eel, although eels at the silver stage stop feeding. Parallel changes were found in the activities of the lipogenic enzymes in silver eels. This suggests a functional coordination between all these proteins sequentially involved in hepatic lipogenesis. Cardiolipin added to proteoliposomes strongly stimulated the activity of the purified tricarboxylate carrier from yellow eels, whereas it slightly reduced the activity of the same protein from silver eels. The higher activity of the tricarboxylate carrier from silver eels could therefore be ascribed, at least in part, to a different composition of the lipid domain surrounding the carrier protein, possibly in response to the hormonal alterations accompanying metamorphosis from yellow to silver stage.

The genome of Saccharomyces cerevisiae encodes 35 members of a family proteins thattransport metabolites and substrates across the inner membranes of mitochondria. They includethree isoforms of the ADP/ATP translocase and the phosphate and citrate carriers. At the startof our work, the functions of the remaining 30 members of the family were unknown. We areattempting to identify these 30 proteins by overexpression of the proteins in specially selectedhost strains of Escherichia coli that allow the carriers to accumulate at high levels in the formof inclusion bodies. The purified proteins are then reconstituted into proteoliposomes wheretheir transport properties are studied. Thus far, we have identified the dicarboxylate,succinate-fumarate and ornithine carriers. Bacterial overexpression and functional identification, togetherwith characterization of yeast knockout strains, has brought insight into the physiologicalsignificance of these transporters. The yeast dicarboxylate carrier sequence has been used toidentify the orthologous protein in Caenorhabditis elegans and, in turn, this latter sequencehas been used to establish the sequence of the human ortholog.

The tricarboxylate carrier from eel liver mitochondria was purified by chromatography on hydroxyapatite and Matrix Gel Blue B and reconstituted into liposomes by removal of the detergent with Amberlite. Optimal transport activity was obtained by using a phospholipid concentration of 11.5 mg/ml, a Triton X- 114/phospholipid ratio of 0.9, and ten passages through the same Amberlite column. The activity of the carrier was influenced by the phospholipid composition of the liposomes, being increased by cardiolipin and phosphatidylethanolamine and decreased by phosphatidylinositol. The reconstituted tricarboxylate carrier catalyzed a first-order reaction of citrate/citrate or citrate/malate exchange. The maximum transport rate of external [14C]citrate was 9.0 mmol/min per g of tricarboxylate carrier protein at 25 degrees C and this value was virtually independent of the type of substrate present in the external or internal space of the liposomes. The half-saturation constant (Km) was 62 microM for citrate and 541 microM for malate. The activation energy of the citrate/citrate exchange reaction was 74 kJ/mol from 5 to 19 degrees C and 31 kJ/mol from 19 to 35 degrees C. The rate of the exchange had an external pH optimum of 8.

Although the decrease in pyruvate secretion by brewer's yeasts during fermentation has long been desired in the alcohol beverage industry, rather little is known about the regulation of pyruvate accumulation. In former studies, we developed a pyruvate under-secreting sake yeast by isolating a strain (TCR7) tolerant to ethyl α-transcyanocinnamate, an inhibitor of pyruvate transport into mitochondria. To obtain insights into pyruvate metabolism, in this study, we investigated the mitochondrial activity of TCR7 by oxigraphy and (13) C-metabolic flux analysis during aerobic growth. While mitochondrial pyruvate oxidation was higher, glycerol production was decreased in TCR7 compared with the reference. These results indicate that mitochondrial activity is elevated in the TCR7 strain with the consequence of decreased pyruvate accumulation. Surprisingly, mitochondrial activity is much higher in the sake yeast compared with CEN.PK 113-7D, the reference strain in metabolic engineering. When shifted from aerobic to anaerobic conditions, sake yeast retains a branched mitochondrial structure for a longer time than laboratory strains. The regulation of mitochondrial activity can become a completely novel approach to manipulate the metabolic profile during fermentation of brewer's yeasts.

Background: The effects of systolic blood pressure (SBP), serum total cholesterol (TC), fasting plasma glucose (FPG), and body mass index (BMI) on the risk of cardiovascular diseases (CVD) have been established in epidemiological studies, but consistent estimates of effect sizes by age and sex are not available. Methods: We reviewed large cohort pooling projects, evaluating effects of baseline or usual exposure to metabolic risks on ischemic heart disease (IHD), hypertensive heart disease (HHD), stroke, diabetes, and, as relevant selected other CVDs, after adjusting for important confounders. We pooled all data to estimate relative risks (RRs) for each risk factor and examined effect modification by age or other factors, using random effects models. Results: Across all risk factors, an average of 123 cohorts provided data on 1.4 million individuals and 52,000 CVD events. Each metabolic risk factor was robustly related to CVD. At the baseline age of 55-64 years, the RR for 10 mmHg higher SBP was largest for HHD (2.16; 95% CI 2.09-2.24), followed by effects on both stroke subtypes (1.66; 1.39-1.98 for hemorrhagic stroke and 1.63; 1.57-1.69 for ischemic stroke). In the same age group, RRs for 1 mmol/L higher TC were 1.44 (1.29-1.61) for IHD and 1.20 (1.15-1.25) for ischemic stroke. The RRs for 5 kg/m 2 higher BMI for ages 55-64 ranged from 2.32 (2.04-2.63) for diabetes, to 1.44 (1.40-1.48) for IHD. For 1 mmol/L higher FPG, RRs in this age group were 1.18 (1.08-1.29) for IHD and 1.14 (1.01-1.29) for total stroke. For all risk factors, proportional effects declined with age, were generally consistent by sex, and differed by region in only a few age groups for certain risk factor-disease pairs. Conclusion: Our results provide robust, comparable and precise estimates of the effects of major metabolic risk factors on CVD and diabetes by age group.

Background: Chronic kidney disease (CKD) independently increases the risk of death and cardiovascular disease (CVD) in the general population. However, the relationship between estimated glomerular filtration rate (eGFR) and CVD/death risk in a general population at low risk of CVD has not been explored so far. Design: Baseline and longitudinal data of 1465 men and 1459 women aged 35-74 years participating to the MATISS study, an Italian general population cohort, were used to evaluate the role of eGFR in the prediction of all-cause mortality and incident CVD. Methods: Bio-bank stored sera were used to evaluate eGFR at baseline. Serum creatinine was measured on thawed samples by means of an IDMS-calibrated enzymatic method. eGFR was calculated by the CKD-EPI formula. Results: At baseline, less than 2% of enrolled persons had eGFR < 60 mL/min/1.73m 2 and more than 70% had a 10year cardiovascular risk score < 10%. In people 60 or more years old, the first and the last eGFR quintiles (

Background: From 2008 to 2012 an Health Examination Survey (HES)-Osservatorio Epidemiologico Cardiovascolare (OEC) has been implemented in Italy with the aim of assessing cardiovascular (CV) risk factors, prevalence of risk conditions and CV diseases for the Italian adult population. Methods: Random samples of general population stratified by age and sex were examined in all Italian regions (participation rate 56%). Risk factor were collected using standardized procedures and methods; biochemical tests were assayed in a central laboratory; a questionnaire investigates behaviours and CVD history; a ECG read in Minnesota code was used to define previous myocardial infarction. Comparisons between men and women were assessed using t-test for means and chi-squared test for prevalence. Results: Data of 4371 men and 4339 women ages 35-79 years were analysed. Majority of risk factors mean levels resulted higher in men than in women: systolic blood pressure (SBP) was 134 mmHg and 129 mmHg (p=140 mmHg or DBP>=90 mmHg or in treatment (p=200 mg/dl or in treatment for (p2 ) (p=30 kg/m 2 ) resulted similar in men and women: 25% and 27% respectively (p=0.0818). Prevalence of myocardial infarction was 2.1% in men and 0.7% in women (p Conclusions: At present obesity and smoking are still a priority in public health. In combination with other information sources, the OEC can contribute greatly to plan community actions and health services at national and regional level.

Background: Health Interview Survey (HIS) collects only self-reported height and weight to estimate obesity prevalence. Because of self-reporting, estimated obesity prevalence could be too low. From 2008 to 2012 an Health Examination Survey/Osservatorio Epidemiologico Cardiovascolare (HES/OEC) has been implemented in Italy with the aim of assessing cardiovascular (CV) risk factors, prevalence of risk conditions and CV diseases for the Italian adult population. Differences in measured and self-reported main anthropometric measures are described. Methods: Random samples of general population stratified by age and sex were examined in all Italian regions (participation rate 56%). Self-reported height and weight were requested to participants just after the welcome at the screening center. Height and weight were then measured using standardized procedures and methods. BMI was categorized in 3 groups: normal (BMI=30 kg/m2). Comparisons between measured and reported height, weight, and calculated BMI in men and women were assessed using t-test for means and chi-squared test for prevalence for paired samples. Results: Data from 2,583 men and 2,575 women aged 35-79 years were analysed. In men, measured height was lower than self-reported (-2.1 cm.), measured weight resulted higher than self-reported (+0.3 kg.); as a consequence BMI calculated on measured data resulted higher than that based on self-reported data (+0.8 kg/m2). Prevalence of obesity was higher for measured data than for self-reported (+7.1%). In men, difference between measured and self-reported height resulted higher in obese category than in the overweight or normal groups (-2.6 cm.), as well as for weight (+1.6 kg.). Similar results were registered in women: measured height was lower than self-reported (-3.6 cm.), measured weight resulted higher than self-reported (+0.8 kg.); as a consequence BMI calculated on measured data resulted higher than that based on self-reported data (+1.6 kg/m2). Prevalence of obesity was higher for measured data than for self-reported (+9.2%). Difference between measured and self-reported height resulted higher in obese category than in the overweight or normal groups (-5.0 cm.), as well as for weight (1.8 kg.). Both in men and women differences increased by age-group. Conclusions: Our results confirm how important is to produce standardised measures, also to adjust and correct self-reported height and weight, in order to have a reliable picture of obesity in the population. At present obesity is still a priority in public health and is one of the main indicator to plan community actions for cardiovascular disease prevention in the population.

Background Agenesis of corpus callosum has been associated with several defects of the mitochondrial respiratory chain and the citric acid cycle. We now report the results of the biochemical and molecular studies of a patient with severe neurodevelopmental disease manifesting by agenesis of corpus callosum and optic nerve hypoplasia. Methods and results A mitochondrial disease was suspected in this patient based on the prominent excretion of 2-hydroxyglutaric acid and Krebs cycle intermediates in urine and the finding of increased reactive oxygen species content and decreased mitochondrial membrane potential in her fibroblasts. Whole exome sequencing disclosed compound heterozygosity for two pathogenic variants in the SLC25A1 gene, encoding the mitochondrial citrate transporter. These variants, G130D and R282H, segregated in the family and were extremely rare in controls. The mutated residues were highly conserved throughout evolution and in silico modeling investigations indicated that the mutations would have a deleterious effect on protein function, affecting either substrate binding to the transporter or its translocation mechanism. These predictions were validated by the observation that a yeast strain harbouring the mutations at equivalent positions in the orthologous protein exhibited a growth defect under stress conditions and by the loss of activity of citrate transport by the mutated proteins reconstituted into liposomes. Conclusions We report for the first time a patient with a mitochondrial citrate carrier deficiency. Our data support a role for citric acid cycle defects in agenesis of corpus callosum as already reported in patients with aconitase or fumarate hydratase deficiency.

Transmembrane threonine fluxes (i.e., uptake, diffusion, and carrier-mediated excretion) all contribut-ing to threonine production by a recombinant strain of Corynebacterium glutamicum, were analyzed and quantitated. A threonine-uptake carrier that transports threonine in symport with sodium ions was identified. Under production conditions (i.e., when internal threonine is high), this uptake system catalyzed predominantly threonine/threonine exchange. Threonine export via the uptake system was excluded. Threonine efflux from the cells was shown to comprise both carrier-mediated excretion and passive diffusion. The latter process was analyzed after inhibition of all carrier-mediated fluxes. Threonine diffusion was found to proceed with a first-order rate constant of 0.003 min–1 or 0.004 μl min–1 (mg dry wt.)–1, which corresponds to a permeability of 8 × 10–10 cm s–1. According to this permeability, less than 10% of the efflux observed under optimal conditions takes place via diffusion, and more than 90% must result from the activity of the excretion carrier. In addition, the excretion carrier was identified by (1) inhibition of its activity by amino acid modifying reagents and (2) its dependence on metabolic energy in the form of the membrane potential. Activity of the excretion system depended on the membrane potential, but not on the presence of sodium ions. Threonine export in antiport against protons is proposed.

Aim: Risk charts and risk score, based on the global absolute risk, are key tools for CVD risk assessment. When applied to the population from which they derive, they provide the best estimate of CVD risk. That is why the CUORE Project has among its objectives the assessment of the Italian population’s cardiovascular risk, identifying the model for the prediction of coronary and cerebrovascular events in 10 years.Methods: Data fromdifferent cohorts enrolled in the North, Centre and South of Italy between the 1980s and the 1990s were used. From the 7,056 men and 12,574 women aged 35-69 years, free of cardiovascular disease at base-line and followed up for a mean time of 10 years for total and cause-specific mortality and non fatal cerebrovascular and coronary events, 894 major cardiovascular events (596 coronary and 298 cerebrovascular) were identified and validated. To assess 10-year cardiovascular risk, the risk score and risk chart were developed for men and women separately, considering the first major coronary or cerebrovascular event as the endpoint.Results: The risk score is applied tomen andwomen aged 35-69 years and includes age, systolic blood pressure, total cholesterol, HDL-cholesterol, smoking habit, diabetes and hypertension treatment using continuous values when possible. The risk chart is applied to persons aged 40-69 years and includes the same risk factors as risk score, except for HDL-cholesterol and hypertension treatment, and uses categorical values for all variables.Conclusions: The risk score and risk chart are easy-to-use tools which enable general practitioners and specialists to achieve an objective evaluation of the absolute global cardiovascular risk of middle-aged persons in primary prevention.

Background: Cardiovascular diseases (CVD) and cancer together cause more than 70% of all deaths. Both the pathologies are caused by the interaction of environmental, behavioral and genetic risk factors. For some recognized CVD risk factors (e.g. smoking and obesity) recent studies found a relation also with several cancers. It’s rare to find studies including both CVD and cancer, fatal and non fatal events. Aim: To pool data from CVD longitudinal study and cancer register to investigate possible common risk factors and verify if cardiovascular favourable risk profile is protective also for cancer in order to implement common preventive strategies at population and individual level. Methods: Men and women (ages 20–75 years) data from the Italian Progetto CUORE cohorts and from the Cancer Register implemented in the area of Latina, were pooled. Risk factors were measured and collected using the same standardized procedures and methodologies: body mass index (BMI), diabetes, metabolic syndrome (MS) (ATP-III definition), total and HDL cholesterol, triglycerides, systolic and diastolic blood pressure, smoking habit, alcohol consumption, educational level. In women, menopausal status and parity were included. Follow-up was conducted until December 2004 for both CVD and cancer, fatal and non fatal events. All Cox regression Hazard Ratios (HR) were adjusted by age, gender, educational level, and study. Results: In 9752 persons (5153 women and 4599 men without cardiovascular events and cancer at baseline) 628 cancer events in men and 531 in women, 504 cardiovascular events in men and 274 in women were identified during a median f-u of 18 years. Smoking resulted significantly associated with cancer risk, also when adjusted by BMI, alcohol, and MS in men (current smokers HR=1.74). In women, MS was positively associated with cancer risk, but not significantly. Persons with favorable risk profile (no smoking, BMI2 , Total Cholesterol Conclusions: There are important common risk factors for cardiovascular diseases and cancers. People with favourable risk profile live longer and cost less to the Heath System. This could be a first step to identify and implement common preventive actions at population and individual level in order to reduce both cardiovascular and cancer diseases.

Background: Despite cardiovascular diseases (CVD) are the leading causes of death and hospitalization in nearly all countries in Europe, there are paucity, weak quality and comparability of data. The periodic Health Examination Survey (HES) represents in Italy the major source of information on CVD at national level thanks to the adoption of standardized methodologies throughout the country. The aim is to present differences in trends of CVD prevalence by gender in the Italian adult population from 1998 to 2008. Methods: Randomized population samples stratified by age and sex were examined. In 1998, 9,712 men and women aged 35–74 years were enrolled in all Italian regions; ongoing screening started in 2008 is enrolling 9,020 persons. A standardized questionnaire investigates cardiovascular disease and pharmacological treatments. The anamnesis is positive when clinical diagnosis has been made by a physician. Electrocardiograms read in Minnesota code are also performed and used to define previous myocardial infarction. Results: Data are from 12 regions in the North, Center, and South of Italy: 3,704 men and women in 1998 and 3,479 persons in 2008 are compared. In men, prevalence of cerebrovascular events decreases from 1.5% (95% confidence interval: 1.0-1.9%) in 1998 to 0.6 (0.3–0.9%) in 2008; in women, prevalence results stable: 0.9% in 1998 (0.5–1.3%) and 0.7% in 2008 (0.4–1.1%). Prevalence of myocardial infarction results stable both in men and women: in 1998, 1.9% in men (1.4–2.4%) and 0.6% in women (0.3–0.9%), and in 2008, 2.0% (1.4-2.7%) and 0.6% (0.3-0.9%) respectively; angina pectoris results stable as well: in 1998, 2.2% in men (1.7-2.8%) and 3.9% in women (3.1-4.6%), and in 2008, 3.2% (2.5-4.0%) and 4.5% (3.6-5.4%) respectively. Prevalence of by-pass or angioplasty surgery increases in men: 2.4% (1.8-3.0%) in 1998, and 4.5% (3.6-5.4%) in 2008; in women increasing is not significant: from 0.2% (0.0-0.4%) in 1998 to 0.7% (0.3-1.1%) in 2008. Stratifying data by geographical area (North, Center, South and Island) all comparisons become not significant; in men only, cerebrovascular decreasing and by-pass or angioplasty surgery increasing trends tend to be confirmed in all three areas. Conclusions: Trends between 1998 and 2008 decrease in cerebrovascular events and increase in prevalence of by-pass or angioplasty surgery, especially in men. Stable prevalence resulted for myocardial infarction and angina pectoris. Cerebrovascular decreasing trend is in line with smoking prevalence and mean of blood pressure decreasing in the country. Further analyses considering data from all Italian regions are needed to confirm results.

Background: The Italian National Prevention Plan 2005–2008 included a 10-year cardiovascular risk assessment (10-CR) for the general population aged 35–69 years using the CUORE-Project risk score. GPs were encouraged to collect data on risk factors, perform a 10-CR and send these data to the Cardiovascular Risk Observatory (CRO). Aim: The aim of this study is to show updated data of the ongoing surveillance system of the 10-CR in the Italian adult population, a first step to implement primary preventive actions at individual level. Methods: A training plan for GPs was launched by the Ministry of Health. Data were collected using the cuore.exe software, easily and freely downloadable by GPs from the CUORE-Project website ( www.cuore.iss.it ). The CRO provides a web-platform to analyze and compare data on 10-CR and risk factors at both regional and national level. In the subgroup of persons examined at least twice a year, variations in continuous risk factors mean levels and categorical risk factors prevalences between baseline and follow-up and their 95% confidence intervals (C.I.) were calculated using methods for matched pair samples. Results: By October 2011, more than 3,000 GPs downloaded cuore.exe ; 146,322 CR assessments on 137,773 persons were sent to CRO. CR mean was 3.0% in women, 8.4% in men; 30% of men and 65% of women were at lower risk (CR Conclusions: Data demonstrate that 10-CR assessment can be an effective first step to implement preventive actions in primary care. The individual risk score is becoming a useful tool for GPs to assess their patients’ CR and promote primary prevention by focusing attention on the adoption of healthy lifestyles. These encouraging data can be used to support health policy decision processes.

This paper describes a mathematical procedure to determine the lethality in a continuous sterilization system for foods containing large particles. A computer program to predict the temperature distribution within the flowing particles and heat lethality was developed using finite difference equations. The convective heat transfer coefficient between fluid and particles was experimentally estimated by means of a model system consisting of an immobile potato cube surrounded by a continuously flowing fluid. To verify this approach, a tubular heating-holding pilot plant was used for processing potato cubes in a NaCl solution. A biological validation of the mathematical model was carried out by inoculating the potato cubes with yeast cells and comparing the experimentally measured lethality values with those calculated using the computer program. Quite a good agreement was obtained between the model predictions and the experimental findings.

The epidemic dimensions of non-dialysis chronic kidney disease (CKD) and the associated elevated cardiovascular risk as well as the high costs of renal replacement therapy have made the identification of CKD patients and the quantification of CKD-related comorbidities a key priority in the strategies of public health agencies worldwide. Information on the CKD prevalence at a national level is still lacking in Italy, although these data are critical for planning preventive strategies and increasing the awareness of CKD as a major chronic disease. In 2008 the CARHES (CArdiovascular risk in Renal Patients of the Italian Health Examination Survey) study was started. The study - a joint venture between the Italian Society of Nephrology, the Italian Society of Cardiologists, and the National Health Institute-Cardiovascular Disease Prevention Project - will integrate the previously collected information on the cardiovascular risk profile of the adult Italian population provided by the Health Examination Survey (HES) with epidemiological data on CKD. The initial results on approximately half of the prospective sample of 9020 subjects aged 35-79 years suggest a lower CKD prevalence than that reported in other countries. The final results will allow to estimate the level of CKD in Italy and hopefully increase the awareness of this high-risk chronic disease among Italian physicians and health authorities.

The Italian national prevention plan 2005-2008 included 10-year cardiovascular risk (10-CR) assessment of the general population aged 35-69 years using the CUORE project risk score. General practitioners (GPs) were encouraged to collect data on risk factors and 10-CR and to contribute to the Cardiovascular Risk Observatory (CRO). The aim is to demonstrate feasibility and effectiveness of 10-CR assessment as a first step to implement primary preventive actions at the individual level.Data were collected using CUORE.EXE software, easily and freely downloadable by GPs from the CUORE project website (www.cuore.iss.it). CRO provides a web platform to analyse and compare data on 10-CR and risk factors at regional and national levels with the aim of supporting health policy decision processes.From January 2007 to May 2010, 2,858 GPs downloaded cuore.exe; 139,269 CR assessments on 117,345 persons were sent to CRO. CR mean was 3.0% in women, 8.3% in men; 30% of men and 65% of women were at lower risk (CR 3%), 9.2% of men and 0.4% of women were at high risk (CR ≥ 20%). Among those with at least two risk assessments (n = 5,948), 8% (95% CI 7-9%) shifted to a lower risk class after 1 year. Systolic blood pressure mean levels decreased by 1.6 mmHg (95% CI 1.2-2.1 mmHg), diastolic blood pressure by 0.9 mmHg (95% CI 0.5-1.3 mmHg), total cholesterol by 5.6 mg/dl (95% CI 4.3-6.8 mg/dl), and smokers prevalence by 3.5% (95% CI 2.5-4.6%); high-density lipoprotein cholesterol increased in women by 1 mg/dl (95% CI 0.5-1.4 mg/dl).Data demonstrate that 10-CR assessment can be the first step to implement preventive actions in primary care.

Autism spectrum disorder (ASD) is a severe, complex neurodevelopmental disorder characterized by impairments in reciprocal social interaction and communication, and restricted and stereotyped patterns of interests and behaviors. Recent evidence has unveiled an important role for calcium (Ca(2+)) signaling in the pathogenesis of ASD. Post-mortem studies of autistic brains have pointed toward abnormalities in mitochondrial function as possible downstream consequences of altered Ca(2+) signaling, abnormal synapse formation, and dysreactive immunity. SLC25A12, an ASD susceptibility gene, encodes the Ca(2+)-regulated mitochondrial aspartate-glutamate carrier, isoform 1 (AGC1). AGC1 is an important component of the malate/aspartate shuttle, a crucial system supporting oxidative phosphorylation and adenosine triphosphate (ATP) production. Here, we review the physiological roles of AGC1, its links to calcium homeostasis, and its involvement in autism pathogenesis.