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Background Italy was one of the first countries to be heavily hit by the spread of the new Coronavirus. Longitudinal studies are needed to investigate the real effect of COVID-19 on adult mental health. The Italian Twin Registry carried out a study to investigate, over time, the course of depressive symptoms in the general population. Methods The study relies on data collected just before the beginning (February 2020) and the end (June 2020) of the first lockdown. Symptoms of depression were assessed using the Patient Health Questionnaire, and total scores or categorized depression scores were considered in the analyzes. Results A total of 1690 adult twins were recruited. The study showed a mean depression score of 1.11 immediately before lockdown and 1.20 immediately after, with an overall prevalence of depressive symptoms increasing from 33.6 to 38.9%. Depressive symptoms immediately after the restriction period were associated with Covid-19 symptoms affecting households, financial problems due to the pandemic and poor social support. Independently of the baseline risk of depressive symptoms, we observed an increased risk among younger and less educated people. Compared to the pre-lockdown period, women and middle-aged people also were found to be at greater risk of developing depressive symptoms. Limitations Possible participation bias and residual selection bias. Conclusions The study shows that the COVID-19 pandemic was associated with an increased depressive symptomatology and that, in such health emergency times, the most vulnerable persons are young adults, women, and those living in a socially, culturally, or economically disadvantaged environment.

Comparing twins from same- and opposite-sex pairs can provide information on potential sex differences in a variety of outcomes, including socioeconomic-related outcomes such as educational attainment. It has been suggested that this design can be applied to examine the putative role of intrauterine exposure to testosterone for educational attainment, but the evidence is still disputed. Thus, we established an international database of twin data from 11 countries with 88,290 individual dizygotic twins born over 100 years and tested for differences between twins from same- and opposite-sex dizygotic pairs in educational attainment. Effect sizes with 95% confidence intervals (CI) were estimated by linear regression models after adjusting for birth year and twin study cohort. In contrast to the hypothesis, no difference was found in women (β = −0.05 educational years, 95% CI −0.11, 0.02). However, men with a same-sex co-twin were slightly more educated than men having an opposite-sex co-twin (β = 0.14 educational years, 95% CI 0.07, 0.21). No consistent differences in effect sizes were found between individual twin study cohorts representing Europe, the USA, and Australia or over the cohorts born during the 20th century, during which period the sex differences in education reversed favoring women in the latest birth cohorts. Further, no interaction was found with maternal or paternal education. Our results contradict the hypothesis that there would be differences in the intrauterine testosterone levels between same-sex and opposite-sex female twins affecting education. Our findings in men may point to social dynamics within same-sex twin pairs that may benefit men in their educational careers. CC BY 4.0Correspondence Address: Silventoinen, K.; University of Helsinki, P.O. Box 18, Finland; email: karri.silventoinen@helsinki.fi© 2021 The Authors

Data on the etiological factors underlying the co-occurrence of common adolescent pain with anxiety and depression symptoms are very limited. Opioid prescriptions for adolescent pain problems are on the rise in North America and constitute a risk factor for diversion, misuse, and substance use. In this study, we aimed to investigate the phenotypic and etiological association among pain, depression, and anxiety and to test their link to substance use in adolescents. By taking advantage of the Italian National Twin Registry and of the relatively low incidence of opioid prescriptions in Italy, we applied multivariate modelling analyses to 748 Italian adolescent twins (374 pairs, mean age 16 ± 1.24 years). Twins' responses to the Achenbach Youth Self-Report questionnaire were used to build a composite adolescent pain index and to measure anxiety, depression, and substance use. All monozygotic within-pair correlations were higher than the dizygotic correlations, indicating genetic influences for adolescent pain, anxiety, and depressive problems. A common latent liability factor influenced by genetic and environmental elements shared among pain, depression, and anxiety provided the best fit to explain the co-occurrence of adolescent pain, anxiety, and depression problems. A common phenotypic factor capturing all 3 phenotypes was positively associated (β = 0.19, P < 0.001, confidence interval: 0.10-0.27) with substance use. These findings indicate that several intertwined mechanisms, including genetic factors, can explain a shared liability to common adolescent pain, anxiety, and depression problems. Their association with substance use remains traceable even in societies with relatively low prevalence of opioid prescriptions.

Background: Heart rate (HR), mean arterial pressure (MAP) and carotid intima–media thickness (cIMT) are moderately heritable cardiovascular traits, but the environmental effects on the longitudinal change of their heritability have never been investigated. Methods: 368 Italian and Hungarian twins (107 monozygotic, 77 dizygotic) underwent oscillometric measurement and B-mode sonography of bilateral carotid arteries in 2009/2010 and 2014. Within- -individual/cross-study wave, cross-twin/within-study wave and cross-twin/cross-study wave correlations were estimated, and bivariate Cholesky models were fitted to decompose the total variance at each wave and covariance between study waves into additive genetic, shared and unique environmental components. Results: For each trait, a moderate longitudinal stability was observed, with within-individual/crosswave correlations of 0.42 (95% CI: 0.33–0.51) for HR, 0.34 (95% CI: 0.24–0.43) for MAP, and 0.23 (95% CI: 0.12–0.33) for cIMT. Cross-twin/cross-wave correlations in monozygotic pairs were all significant and substantially higher than the corresponding dizygotic correlations. Genetic continuity was the main source of longitudinal stability, with across-time genetic correlations of 0.52 (95% CI: 0.29–0.71) for HR, 0.56 (95% CI: 0.31–0.81) for MAP, and 0.36 (95% CI: 0.07–0.64) for cIMT. Overlapping genetic factors explained respectively 57%, 77%, and 68% of the longitudinal covariance of the HR, MAP and cIMT traits. Conclusions: Genetic factors have a substantial role in the longitudinal change of HR, MAP and cIMT; however, the influence of unique environmental factors remains relevant. Further studies should better elucidate whether epigenetic mechanisms have a role in influencing the stability of the investigated traits over time.

Context Analysis of a 2-screen program for congenital hypothyroidism (CH) was performed using differential dried-blood spot thyrotropin (bTSH) cutoffs of 10 mU/L at first screening (all infants) and 5 mU/L at second screening (selected infants). Objectives This work aimed to characterize CH infants identified by the second screening and compare infants with bTSH of 5.0 to 9.9 and 10 mU/L or greater on second screening. Design and Patients Maternal and neonatal clinical features were retrospectively analyzed for 119 CH babies detected on the second screen in the Lombardy region of Italy, 2007 to 2014. Results Fifty-two (43.7%) of the 119 CH neonates showed bTSH values ranging from 5.0 to 9.9 mU/L at the second screening (low bTSH group) and 67 (56.3%) bTSH of 10.0 mU/L or greater (high bTSH group). The frequency of thyroid dysgenesis and eutopic gland was similar in both groups, as was the frequency of permanent and transient CH. Moreover, a high frequency of extrathyroidal malformations was found in both groups. The percentage of preterm infants (57.7% vs 23.9%, P Conclusions This study has demonstrated that a lower TSH cutoff at the second screening can detect additional cases of CH and that a second bTSH cutoff of 5.0 mU/L is appropriate for identifying preterm newborns and babies with associated risk factors.

Background The mechanism underlying the association between personality profile and subclinical atherosclerosis is poorly understood. This study explores the association between personality, carotid atherosclerosis and arterial stiffness, and the contribution of genes and environment to this association. Methods Early atherosclerotic traits, including carotid intima-media thickness (CCA-IMT), aortic pulse wave velocity (PWVao) and heart rate, were assessed in 318 adult twins, who also completed a Big Five personality questionnaire. Using the co-twin control approach, the association between intra-pair differences in clinical and personality scores was assessed in dizygotic (DZ) and monozygotic (MZ) twins separately. Results An association between CCA-IMT and extroverted personality, as well as between PWVao and openness to experience was detected. The inverse association between CCA-IMT and extraversion was persistent in DZ and disappeared in MZ twins, suggesting genetic confounding. In contrast, the association between PWVao and openness to experience was of the same magnitude in DZ and MZ twins, thus surviving the adjustment for genetic and shared environmental factors. Conclusions This study highlights that the association between some psychological factors and cardiovascular traits may be partly explained by genetic factors. This result may provide support for the feasibility of prevention programs based on assessing familiarity for personality disorders to detect genetic risk for subclinical cardiovascular disease.

Background: The frequency of overweight (OW) and obese (OB) children has increased worldwide, particularly in economically developed countries. No studies have been conducted to verify whether the ...

To disentangle genetic and environmental influences on the development of femoral plaques using a population of adult twins. To evaluate the potential role of shared genetic and environmental factors in the co-occurrence of femoral and carotid plaques. The sample included 566 twins belonging to 164 monozygotic (MZ) and 119 dizygotic (DZ) twin pairs, who underwent peripheral arterial assessment by B-mode ultrasound in different centers. The variance in femoral plaques onset was due to genetic factors and the remaining 50% was explained by common (15%) and unique (35%) environmental factors. Findings on sidedness and number of femoral plaques indicated that also these traits were mainly under genetic control. No effect of common environment was found on plaques composition, and variability of this trait was explained by genetics (64%) and unique environment (36%). Covariation between the liabilities to carotid and femoral plaques was mainly attributed to shared genes (77%), with the remaining 23% explained by individual-specific environmental factors shared by the two districts. Inter-individual differences in plaque onset as well as in their number, sidedness and composition are mainly genetic in origin. The results on the cooccurrence of carotid and femoral plaque underline the genetic role in atherogenesis.

Poster: "ECR 2016 / C-2137 / Vertebral artery diameter and flow: nature or nurture " by: " A. D. Tarnoki 1, D. L. Tarnoki1, L. Littvay1, P. Lucatelli2, C. Fagnani2, C. Baracchini3, G. Pucci4, G. Schillaci4, M. A. Stazi2; 1Budapest/HU, 2Rome/IT, 3Padua/IT, 4Terni/IT"

To compare long-term clinical outcomes in patients with ST-elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (PPCI) using radial and femoral arterial access. The present study was an observational cohort study of patients with STEMI treated consecutively with PPCI between 2004 and 2011 at a single centre. The primary end point was all-cause mortality at a median follow-up of 3 years. Among 2727 patients, 1600 (58.7%) underwent PPCI via the femoral route. The femoral group was older (64.7 vs. 61.7 years; P

The Italian Twin Registry (ITR), established in 2001, is a population-based registry of voluntary twins. To date, it consists of approximately 29,000 twins who gave their consent to participate in the studies proposed by the ITR research group. The database comprises 11,500 monozygotic and 16,700 dizygotic twins resident throughout the country and belonging to a wide age range (from 0 to 95 years, mean 36.8 years). This article provides an overview of the recruitment strategies along with the major phenotypes investigated during an 18 years’ research period. Over the years, several self-reported questionnaire data were collected, together with saliva/blood samples and measurements taken during in-person interviews or outpatient clinical examinations. Mental and behavioral phenotypes as well as atherosclerotic traits were studied in depth across different age groups. A birth cohort of twins was established and followed up. Novel research hypotheses are also being tested in ongoing projects. The ITR is involved in international studies in collaboration with other twin registries and represents a valuable resource for national and international research initiatives regarding a broad spectrum of health-related characteristics.

Loos, Ruth J F/0000-0002-8532-5087; Kaprio, Jaakko/0000-0002-3716-2455; Huibregtse, Brooke M./0000-0003-0977-7249; de Freitas, Duarte Luis/0000-0001-6642-3370; Aliev, Fazil/0000-0001-8357-4699; Medda, Emanuela/0000-0003-4837-4549; Bartels, Meike/0000-0002-9667-7555; Latvala, Antti/0000-0001-5695-117X; Sund, Reijo/0000-0002-6268-8117; Rebato, Esther/0000-0003-1221-8501; Silventoinen, Karri/0000-0003-1759-3079; Aaltonen, Sari/0000-0002-2873-4263; Nistico, Lorenza/0000-0003-1805-6240; Knafo-Noam, Ariel/0000-0003-0613-1960; van Beijsterveldt, Toos/0000-0002-6617-4201; Harden, Kathryn/0000-0002-1557-6737; Willemsen, Gonneke/0000-0003-3755-0236; Pahlen, Shandell/0000-0003-0753-4155 WOS: 000465255700021 PubMed: 30950584 Objective The objective of this study was to analyze how parental education modifies the genetic and environmental variances of BMI from infancy to old age in three geographic-cultural regions. Methods A pooled sample of 29 cohorts including 143,499 twin individuals with information on parental education and BMI from age 1 to 79 years (299,201 BMI measures) was analyzed by genetic twin modeling. Results Until 4 years of age, parental education was not consistently associated with BMI. Thereafter, higher parental education level was associated with lower BMI in males and females. Total and additive genetic variances of BMI were smaller in the offspring of highly educated parents than in those whose parents had low education levels. Especially in North American and Australian children, environmental factors shared by co-twins also contributed to the higher BMI variation in the low education level category. In Europe and East Asia, the associations of parental education with mean BMI and BMI variance were weaker than in North America and Australia. Conclusions Lower parental education level is associated with higher mean BMI and larger genetic variance of BMI after early childhood, especially in the obesogenic macro-environment. The interplay among genetic predisposition, childhood social environment, and macro-social context is important for socioeconomic differences in BMI. Collaborative Project of Development of Anthropometrical Measures in Twins (Academy of Finland) [266592]; Swedish Research Council through the Swedish Initiative for Research on Microdata in the Social and Medical Sciences Framework Grant [340-2013-5867]; Stockholm County Council (ALF projects)Stockholm County Council; Swedish Heart-Lung FoundationSwedish Heart-Lung Foundation; Swedish Asthma and Allergy Association's Research Foundation; Netherlands Organization for Scientific ResearchNetherlands Organization for Scientific Research (NWO); MagW/ZonMW [904-61-090, 985-10-002, 912-10-020, 904-61-193, 480-04-004, 463-06-001, 451-04-034, 400-05-717, Addiction-31160008, Middelgroot-911-09-032, Spinozapremie-56-464-14192]; Vrije University's Institute for Health and Care Research; European Research Council (ERC)European Research Council (ERC) [230374]; Avera Institute, Sioux Falls, South Dakota; European Network for Genetic and Genomic Epidemiology (ENGAGE) [FP7-HEALTH-F4-2007, 201413]; National Institute of Alcohol Abuse and AlcoholismUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Alcohol Abuse & Alcoholism (NIAAA) [AA-12502, AA-00145, AA-09203]; Academy of Finland Center of Excellence in Complex Disease GeneticsAcademy of Finland [213506, 129680]; Academy of FinlandAcademy of Finland [100499, 205585, 118555, 141054, 265240, 264146, 312073]; Fund of Scientific Research, FlandersFWO; Twins, a nonprofit Association for Scientific Research in Multiple Births (Belgium); Cancer Research UKCancer Research UK [C1418/A7974]; European Union's Seventh Framework Programmes ENGAGE Consortium [HEALTH-F4-2007-201413]; Biobank Standardization and Harmonization for Research Excellence in the European Union [HEALTH-F4-2010-261433]; Kirikkale UniversityKirikkale University [2009/43]; Scientific and Technological Research Council of TurkeyTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [114C117]; Osaka University's International Joint Research Promotion Program; National Institutes of Health (NIH)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01HD068435, R01MH062375]; California Tobacco-Related Disease Research ProgramUniversity of California System [7RT-0134H, 8RT-0107H, 6RT-0354H]; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [1R01ESO15150-01, AA023322, HD081437, R21AG039572]; National Institute on Aging (NIA)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Aging (NIA) [1R01AG13662-01A2]; National Institute on Drug AbuseUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Drug Abuse (NIDA) [DA011015]; Longitudinal Twin Study grant [HD10333]; MSU; National Institute of Mental Health (NIMH)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Mental Health (NIMH) [R01MH081813, R01MH0820-54, R01MH092377-02, R21MH070542-01, R03MH63851-01]; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) [R01HD066040]; MSU Foundation [11-SPG-2518]; NIMHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Mental Health (NIMH) [R01MH58354]; NIH/NIAUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute on Aging (NIA) [R01AG018384, R01AG018386, R01AG022381, R01AG022982]; VA San Diego Center of Excellence for Stress and Mental Health; Cooperative Studies Program of the Office of Research & Development of the US Department of Veterans Affairs (VA); Global Research Network Program of the National Research Foundation (NRF) [2011-220-E00006]; NRF of Korea [NRF-371-2011-1 B00047]; Japan Society for the Promotion of ScienceMinistry of Education, Culture, Sports, Science and Technology, Japan (MEXT)Japan Society for the Promotion of Science [15H05105]; National Health and Medical Research CouncilNational Health and Medical Research Council of Australia [1079102]; ERCEuropean Research Council (ERC) [240994]; [POCI/DES/56834/2004]; [5T32DA017637]; [5T32AG052371] This study was conducted within the Collaborative Project of Development of Anthropometrical Measures in Twins (Academy of Finland Grant 266592). Funding for individual collaborators is as follows. The Child and Adolescent Twin Study in Sweden is supported by the Swedish Research Council through the Swedish Initiative for Research on Microdata in the Social and Medical Sciences Framework Grant 340-2013-5867, grants provided by the Stockholm County Council (ALF projects), the Swedish Heart-Lung Foundation, and the Swedish Asthma and Allergy Association's Research Foundation. The Netherlands Twin Register acknowledges support from the Netherlands Organization for Scientific Research and MagW/ZonMW Grants 904-61-090, 985-10-002, 912-10-020, 904-61-193,480-04-004, 463-06-001, 451-04-034, 400-05-717, Addiction-31160008, Middelgroot-911-09-032, and Spinozapremie-56-464-14192; Vrije University's Institute for Health and Care Research; the European Research Council (ERC; grant 230374); and the Avera Institute, Sioux Falls, South Dakota. Data collection and analyses in Finnish twin cohorts have been supported by the European Network for Genetic and Genomic Epidemiology (ENGAGE; FP7-HEALTH-F4-2007, grant agreement 201413), the National Institute of Alcohol Abuse and Alcoholism (grants AA-12502, AA-00145, and AA-09203 to R. J. Rose), the Academy of Finland Center of Excellence in Complex Disease Genetics (grants 213506 and 129680), and the Academy of Finland (grants 100499, 205585, 118555, 141054, 265240, 264146, and 312073 to J. Kaprio). Since its origin, the East Flanders Prospective Survey has been partly supported by grants from the Fund of Scientific Research, Flanders and Twins, a nonprofit Association for Scientific Research in Multiple Births (Belgium). Gemini was supported by a grant from Cancer Research UK (C1418/A7974). Data collection and research stemming from the Norwegian Twin Registry are supported, in part, by the European Union's Seventh Framework Programmes ENGAGE Consortium (grant agreement HEALTH-F4-2007-201413) and Biobank Standardization and Harmonization for Research Excellence in the European Union (grant agreement HEALTH-F4-2010-261433). Madeira data come from Genetic and Environmental Influences on Physical Activity, Fitness and Health: the Madeira Family Study (project reference: POCI/DES/56834/2004, founded by the Portuguese agency for research [the Foundation for Science and Technology]). S. Y. Oncel and F. Aliev are supported by a Kirikkale University research grant (2009/43) and a Scientific and Technological Research Council of Turkey grant (114C117). K. Silventoinen is supported by Osaka University's International Joint Research Promotion Program. The Boston University Twin Project is funded by grants (R01HD068435 and R01MH062375) from the National Institutes of Health (NIH) to K. J. Saudino. The California Twin Program was supported by the California Tobacco-Related Disease Research Program (7RT-0134H, 8RT-0107H, and 6RT-0354H) and NIH (1R01ESO15150-01). The Carolina African American Twin Study of Aging was funded by a grant from the National Institute on Aging (NIA; 1R01AG13662-01A2) to K. E. Whitfield. The Colorado Twin Registry is funded by National Institute on Drug Abuse grant DA011015 and Longitudinal Twin Study grant HD10333; B. M. Huibregtse is supported by 5T32DA017637 and 5T32AG052371.; The Michigan State University (MSU) Twin Registry has been supported by MSU, as well as by grants R01MH081813, R01MH0820-54, R01MH092377-02, R21MH070542-01, and R03MH63851-01 from the National Institute of Mental Health (NIMH), grant R01HD066040 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and grant 11-SPG-2518 from the MSU Foundation. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of NIMH, NICHD, or NIH. The University of Southern California Twin Study is funded by a grant from NIMH (R01MH58354). The Texas Twin Project is currently funded by grants AA023322 and HD081437 from NIH. The Vietnam Era Twin Study of Aging was supported by NIH/NIA grants R01AG018384, R01AG018386, R01AG022381, and R01AG022982 and, in part, with resources of the VA San Diego Center of Excellence for Stress and Mental Health. The Cooperative Studies Program of the Office of Research & Development of the US Department of Veterans Affairs (VA) has provided financial support for the development and maintenance of the Vietnam Era Twin Registry. The content of this manuscript is solely the responsibility of the authors and does not necessarily represent the official views of NIA/NIH or VA. The National Academy of Sciences-National Research Council Twin Registry acknowledges financial support from NIH grant R21AG039572. The Korean TwinFamily Register was supported by the Global Research Network Program of the National Research Foundation (NRF; 2011-220-E00006). The South Korea Twin Registry is supported by the NRF of Korea (NRF-371-2011-1 B00047). The West Japan Twins and Higher Order Multiple Births Registry was supported by a Grant-inAid for Scientific Research (B) (15H05105) from the Japan Society for the Promotion of Science. This research was facilitated through access to Twins Research Australia, a national resource supported by a Centre of Research Excellence Grant (1079102) from the National Health and Medical Research Council. The Longitudinal Israeli Study of Twins was funded by Starting Grant 240994 from the ERC to A. Knafo-Noam.

ContextNewborn screening program for congenital hypothyroidism (CH) adopting rescreening in at-risk neonates.ObjectivesTo estimate the concordance rate for CH in twin pairs discordant at the first screening; to verify whether long-term follow-up of healthy cotwins belonging to CH discordant pairs may be useful to diagnose thyroid hypofunction during development; to evaluate the importance of genetic and environmental influences on liability to permanent and transient CH.Design and PatientsForty-seven screening discordant twin pairs were investigated. Proband was defined as the twin in the pair with a positive test at the first screening and a confirmed diagnosis of CH.ResultsSeven screening discordant twin pairs became concordant for CH within the first month of life (pairwise concordance of 14.9%) because seven screening negative cotwins showed high TSH values when retested. During long-term follow-up (range, 3 to 21 years), hypothyroidism was diagnosed in two monozygotic screening negative cotwins at the age of 9 months and 12 years, respectively. Furthermore, the twin analysis showed that 95% of liability to transient CH was explained by genetic factors and 5% by environmental (unshared) factors, whereas 64% of phenotypic variance of permanent CH was explained by common environmental factors (shared during the fetal life) and 36% by unshared environmental factors.ConclusionsThis study showed that the introduction of rescreening permits the diagnosis of CH in a greater number of twins. It also showed the importance of long-term follow-up in both twins in the pair, and the role of nongenetic factors in the etiology of permanent CH.

Low doses of drugs delivered at close, regular intervals are increasingly being used to manage patients with different neoplasms. Despite the good tolerability, treatment-related adverse events still occur following metronomic protocols. The aim of this study was to retrospectively investigate whether polymorphisms of different genes involved in fluoropyrimidine metabolism and 5-fluorouracil (5-FU) degradation rate were associated with the outcome of a low-dose capecitabine schedule. Genotyping of DPYD IVS14+1 G>A, MTHFR C677T, and A1298C single-nucleotide polymorphisms was performed by pyrosequencing technology. A PCR technique was used for genotyping TYMS-TSER. Using peripheral blood mononuclear cells, we also evaluated the 5-FU degradation rate, which determines the net result of all the enzymatic transformation of 5-FU, in terms of the amount of drug consumed by the cells in a time unit. The association of these variables with clinical outcome was evaluated using multivariate logistic regression analysis. Eighty-four patients with metastatic gastrointestinal cancer, who had been treated with a low-dose fluoropyrimidine schedule, as a rescue therapy were included in the study. The TSER 2R/2R genotype was significantly associated with both hematologic (odds ratio=7.90, P=0.002) and gastrointestinal toxicity (odds ratio=3.24, P=0.009). Because DPYD IVS14 G>A single-nucleotide polymorphism was not observed in the cohort, it was excluded from the statistical analysis. No significant association was detected between clinical outcome and both MTHFR polymorphisms and the 5-FU degradation rate. In the advanced setting of cancer care, high attention should be paid toward avoiding toxicity and worsening of quality of life. Although metronomic chemotherapy is generally well tolerated, treatment toxicity nonetheless does occur. Our data suggest a possible role of the TSER 2R/2R polymorphism as a predictive marker of toxicity in patients treated with low-dose capecitabine.

We compared intima–media thickness (IMT) and the prevalence of plaques in the common carotid artery (CCA) and common femoral artery (CFA) in apparently healthy participants. This multicenter study included 322 participants (59.9% female; age 20-78 years, mean 52.1 ± 15.3 years) who underwent Echo-color Doppler examination of the CCA and CFA bilaterally. Prevalence and composition of plaque were recorded. A significant ( P < .01) difference between mean CCA-IMT and mean CFA-IMT was detected (0.70 vs 0.73 mm). Plaque prevalence was significantly higher in the CFA compared to the CCA (40.7% vs 30.4%). Atherosclerotic plaques were found in both CFA and CCA in 46% of the cases, solely in CFA in 38%, and in CCA alone in 17%. The observed difference in plaque prevalence was even greater when only fibrolipid isolated plaques were considered (CFA 39.4% vs CCA 22.1%). In a healthy general population, atherosclerotic plaques were present in the CFA but not in the CCA in over one-third of the cases. Further studies must confirm whether ultrasonography of the CFA might be introduced in the screening protocols for cardiovascular risk assessment.

Morphological and hemodynamic variations of the circle of Willis (CW) may have an important impact on cerebrovascular events. However, the environmental and genetic influence remains unclear. For this reason we studied the variations and hemodynamic parameters of the CW in twins using transcranial color-coded sonography (TCCS). Sixty-four twins, 19 monozygotic (MZ) and 13 dizygotic (DZ) pairs from the Italian Twin Registry (average age 45.0 ± 13.7 years) underwent TCCS and risk factor assessment. We examined CW morphology and recorded peak systolic velocity (PSV), end-diastolic velocity (EDV) and pulsatility index (PI). Raw heritability was determined for hemodynamic parameters, whereas concordance and discordance rates were calculated for CW morphological variants. A normal CW anatomy was observed in the majority of MZ and DZ twins (76.5% and 92.3%, respectively). The most frequent variant was a missing anterior cerebral artery (ACA). There was no significant difference in the prevalence of most CW variants depending on the zigosity. Concordance rates were low regarding the presence of variant CW anatomy both in MZ and DZ groups (0.14 and 0.00, respectively). Women had a significantly higher PI in vertebral arteries (VA) and in the right ACA (p = 0.01, p = 0.02 and p

Aims The elasticity of the internal jugular vein (IJV) is a major determinant of cerebral venous drainage and right atrium venous return. However, the level of genetic determination of IJV dimensions, compliance and distensibility has not been studied yet. Methods 170 adult Caucasian twins (43 monozygotic [MZ] and 42 dizygotic [DZ] pairs) were involved from the Italian twin registry. Anteroposterior and mediolateral diameters of the IJV were measured bilaterally by ultrasonography. Measurements were made both in the sitting and supine positions, with or without Valsalva maneuver. Univariate quantitative genetic modeling was performed. Results Genetic factors are responsible for 30-70% of the measured properties of IJV at higher venous pressure even after adjustment for age and gender. The highest level of inheritance was found in the supine position regarding compliance (62%) and venous diameter during Valsalva (69%). Environmental and measurement-related factors instead are more important in the sitting position, when the venous pressure is low and the venous lumen is almost collapsed. The range of capacity changes between the lowest and highest intraluminal venous pressure (full distension range) are mainly determined by genetic factors (58%). Conclusions Our study has shown substantial heritability of IJV biomechanics at higher venous pressures even after adjustment for age and gender. These findings yield an important insight to what degree the geometric and elastic properties of the vascular wall are formed by genetic and by environmental factors in humans.

Background We aimed at evaluating the impact of genetic and environmental factors on longitudinal changes in aortic pulse wave velocity (aPWV) and aortic augmentation index (aAIx). Method Three hundred and sixty-eight Italian and Hungarian adult twins (214 monozygotic, 154 dizygotic) underwent repeated evaluations of aPWV and aAIx (TensioMed Arteriograph). Within-individual/cross-wave, cross-twin/within-wave and cross-twin/cross-wave correlations were calculated; bivariate Cholesky models were fitted to calculate additive genetic (A), shared environmental (C) and unique environmental (E) components. Results For both aPWV and aAIx, cross-twin correlations in monozygotic pairs (r between 0.35 and 0.56) were all significant and always higher than in dizygotic pairs, both at wave 1 and at wave 2. Heritability and unshared environmental proportion of variance at each wave were substantially time-invariant for aPWV (heritability 0.51, 95% CI 0.36-0.63 at wave 1; 0.49, 95% CI 0.34-0.62 at wave 2), whereas for aAIx, we observed a diminished genetic effect (heritability 0.57, 95% CI 0.45-0.67 at wave 1; 0.37, 95% CI 0.21-0.51 at wave 2). Overlapping genetic factors explained a high proportion (0.88, 95% CI 0.61-1.00) of longitudinal covariance for aPWV, and had a relatively lower impact on aAIx (0.55, 95% CI 0.35-0.70). Genetic correlations of aPWV (r = 0.64, 95% CI 0.42-0.85) and aAIx (r = 0.70, 95% CI 0.52-0.87) between waves were lower than 1, suggesting a potential contribution of novel genetic variance on arterial stiffening. Conclusion Changes in aPWV and aAIx over time are largely genetically determined. Our results might stimulate further studies on genetic and epigenetic factors influencing the process of vascular ageing.

Background The measurement of femoral intima-media thickness (IMT) is underutilized in the clinical practice, although it is a surrogate marker of cardiovascular disease. Materials and methods 388 Hungarian and Italian twins (121 monozygotic, 73 dizygotic pairs) underwent bilateral B-mode sonography of femoral arteries. IMT was measured by semiautomated software, where available, or by calipers. Results Within-pair correlation in monozygotic twins was higher than in dizygotics for each parameter. Age-, sex- and country-adjusted genetic effect accounted for 43.9% (95% confidence interval, CI 21.3%–65.2%) and 47.2% (95% CI, 31.4%–62.6%) of the variance of common and superficial femoral artery IMT, respectively, and unshared environmental effect for 56.1% (95% CI 34.6%–78.5%) and 52.8% (95% CI, 37.2%–68.5%). These results did not change significantly after correcting for body mass index or central systolic blood pressure. Conclusions Genetic factors have a moderate role in the determination of common and superficial femoral IMT; however, the influence of environmental (lifestyle) factors remains still relevant. Environmental factors may have a role in influencing the genetic predisposition for femoral vascular hypertrophy.

Summary Objective Multiple twin studies have demonstrated the heritability of anthropometric and metabolic traits. However, assessment of body composition parameters by bioimpedance analysis (BIA) has not been routinely performed in this setting. Design A cross-sectional study. Setting Study subjects were recruited and assessed at twin festivals or at major university hospitals in Italy, Hungary, and the United States to estimate the influence of genetic and environmental components on body composition parameters in a large, wide age range, international twin cohort by using bioelectrical impedance analysis. Subjects 380 adult twin pairs (230 monozygotic and 150 dizygotic pairs; male:female ratio, 68:32; age years 49.1±15.4; mean±standard deviation; age range 18–82) were included in the analysis. Results Heritability was calculated for weight (82%; 95% confidence interval [CI]: 78–85), waist and hip circumferences (74%; 95%CI: 68–79), body fat percentage (74%; 95%CI: 69–79), fat-free mass (74%; 95%CI: 69–79) and body mass index (79%; 95%CI: 74–83). The completely environmental model showed no impact of shared environmental effects on the variance, while unshared environmental effects were estimated as between 18% and 26%. Conclusions BIA findings provide additional evidence to the heritability of anthropometric attributes related to obesity and indicate the practical value of this simple method in supporting efforts to prevent obesity-related adverse health events.

Summary Background An association between reduced lung function and increased cardiovascular risk has been reported, but the underlying mechanisms are unknown. The aim of this study was to assess the heritability of lung function and to estimate its genetic association with arterial stiffness. Methods 150 monozygotic and 42 dizygotic healthy Hungarian and American Caucasian twin pairs (age 43 ± 17 years) underwent spirometry (forced vital capacity/FVC/, forced expiratory volume in 1 s/FEV 1 /; MIR Minispir, USA); and their brachial and central augmentation indices (AIx), and aortic pulse wave velocity (PWV) were measured by oscillometric Arteriograph (TensioMed Ltd, Budapest, Hungary). Phenotypic correlations and bivariate Cholesky decomposition models were applied. Results Age-, sex-, country- and smoking-adjusted heritability of FEV 1 , percent predicted FEV 1 , FVC and percent predicted FVC were 73% (95% confidence interval /CI/: 45–85%), 28% (95% CI: 0–67%), 68% (95% CI: 20–81%) and 45% (95% CI: 0–66%), respectively. Measured and percent predicted FVC and FEV 1 values showed no significant phenotypic correlations with AIx or aortic PWV, except for phenotypic twin correlations between measured FEV 1 , FVC with brachial or aortic augmentation indices which ranged between −0.12 and −0.17. No genetic covariance between lung function and arterial stiffness was found. Conclusions Lung function is heritable and the measured FVC and FEV are phenotypically, but not genetically, associated with augmentation index, a measure of wave reflection. This relationship may in turn reveal further associations leading to a better mechanistic understanding of vascular changes in various airway diseases.

The Italian Twin Register has been in place for more than 10 years. Since its establishment, it has been focusing, on the one hand, on a continuous update of the existing information, and on the other hand, on new phenotypes and sample collection. Demographic data on about 140,000 twins have been updated using the municipality registries. The Italian Twin Register has been carrying out several new studies during the last few years. A birth cohort of twins, Multiple Births Cohort Study, has been started and the enrolment is ongoing. For this cohort, data on pregnancy and birth are collected, and periodical follow-ups are made. DNA is being collected for the twins and their parents. In the area of behavioral genetics, most efforts have been directed to psychological well being assessed with self-reported tools. Research on age-related traits continues with studies on arteriosclerosis development, early biomarkers in mild cognitive impairment, and the relation between lifestyle habits and mutagen sensitivity. The Italian Twin Register biobanking has grown in its size and in its know-how in terms of both technical issues and ethical procedures implementation. Furthermore, attitudes toward biobank-based research, together with willingness and motivation for donation, are being investigated. A valuable key resource for the Italian Twin Register is the possibility of linking twin data with disease registries. This approach has been yielding several important results, such as the recent study on the heritability of type 1 diabetes.

Aims The elasticity of the internal jugular vein (IJV) is a major determinant of cerebral venous drainage and right atrium venous return. However, the level of genetic determination of IJV dimensions, compliance and distensibility has not been studied yet. Methods 170 adult Caucasian twins (43 monozygotic [MZ] and 42 dizygotic [DZ] pairs) were involved from the Italian twin registry. Anteroposterior and mediolateral diameters of the IJV were measured bilaterally by ultrasonography. Measurements were made both in the sitting and supine positions, with or without Valsalva maneuver. Univariate quantitative genetic modeling was performed. Results Genetic factors are responsible for 30–70% of the measured properties of IJV at higher venous pressure even after adjustment for age and gender. The highest level of inheritance was found in the supine position regarding compliance (62%) and venous diameter during Valsalva (69%). Environmental and measurement-related factors instead are more important in the sitting position, when the venous pressure is low and the venous lumen is almost collapsed. The range of capacity changes between the lowest and highest intraluminal venous pressure (full distension range) are mainly determined by genetic factors (58%). Conclusions Our study has shown substantial heritability of IJV biomechanics at higher venous pressures even after adjustment for age and gender. These findings yield an important insight to what degree the geometric and elastic properties of the vascular wall are formed by genetic and by environmental factors in humans.

Objective: Evaluation of the interaction between alcohol intake and cofactors [hepatitis B virus (HBV), hepatitis C virus (HCV), body mass index] and coffee consumption on the risk of cirrhosis. Design: Seven hundred and forty-nine consecutive patients with chronic liver disease referring to units for liver or alcohol diseases in Italy during a 6-months period. Teetotalers were excluded. The odds ratios (OR) for cirrhosis were evaluated using chronic hepatitis cases as the control group. Results: An alcohol intake of more than 3 units/day resulted associated with the likelihood of cirrhosis both in males (OR 4.3; 95% CI=2.5–7.3) and in females (OR 5.7; 95% CI=2.3–14.5). A multiplicative interaction on the risk of cirrhosis between risky alcohol intake and HBsAg or HCV-Ab/HCV-RNA positivity was observed. A reduction of cirrhosis risk was observed in subjects consuming more than 3 alcohol units/day with increasing coffee intake. The OR for the association with cirrhosis decreased from 2.3 (95% CI=1.2–4.4) in subjects drinking 0–2 cups of coffee/day to 1.4 (95% CI=0.6–3.6) in those drinking more than 2 cups/day. Conclusions: In subjects with an alcohol intake >3 units/day the coexistence of HBV or HCV multiplies the risk of cirrhosis. Coffee represents a modulator of alcoholic cirrhosis risk.

Aim To determine the reasons for large standard deviation of bronchodilator response (BDR) and establish whether there is a potential heritable component in healthy subjects. Methods 67 monozygotic and 42 dizygotic adult twin pairs were assessed for bronchodilator response (% change in FEV1 after inhaling 400 μg salbutamol). Univariate quantitative genetic modeling was performed. Results Multiple regression modeling showed a significant association between BDR and sex and baseline FEV1 (P < 0.05), while no association was found with smoking habits, body mass index, or age. Within pair correlation in monozygotic twins was modest (0.332), but higher than in dizygotic twins (0.258). Age-, sex-, and baseline FEV1- adjusted genetic effect accounted for 14.9% (95% confidence interval, CI 0%-53.1%) of the variance of BDR, shared environmental effect for 18.4% (95% CI 0%-46.8%), and unshared environmental effect for 66.8% (95% CI 46.8%-88.7%). Conclusion Our twin study showed that individual differences in BDR can be mostly explained by unshared environmental effects. In addition, it is the first study to show low, insignificant hereditary influences, independently from sex, age, and baseline FEV1.

Since its start as a database of ‘possible twins’, the Italian Twin Register has developed remarkably in terms of twin approach and recruitment, data-management tools, the cohorts enrolled, and the breadth of information gathered, making the Italian Twin Register a valuable resource for genetic epidemiological research. The Italian Twin Register is a random population of twins at both the national level and within targeted geographical areas or birth cohorts. Further, the Register is linked with disease records and has recently implemented a web-based method for volunteer twin recruitment specifically designed to promote the Register and to disseminate information on genetic epidemiology. To date, approximately 9000 twins have joined the Italian Twin Register, the majority of whom (approximately 70%) represent young adults aged 20 at time of enrolment. Although the total number of twins recruited to date is far below the expected figure initially predicted, the newly established standardized procedures guarantee an increase of around 2000 twins each year. Following the collaboration between the Italian Twin Register and the main Italian nonprofit association for blood donors, twin DNA sampling and storage has recently accelerated contributing to the large amount of phenotypic data collected. The Italian Twin Register is currently involved in both population and clinical based studies on various complex pheno-types and diseases, some conducted within large European consortia.

Background & Aims: Data on the potential of circulating tumor cells (CTC) count in predicting overall survival (OS) in patients with colorectal cancer are timely and worthy of interest. This study aimed to evaluate the prognostic role of CTC count in both localized and metastatic colorectal cancer patients.Methods: Consecutive patients with histological diagnosis of colorectal cancer were enrolled. CTC count was performed, by using a quantitative immunofluorescence method, at baseline (T0) and 1 month following start of chemotherapy (T1). A CTC count

Summary Background and aims Carotid intima-media thickness (IMT) and arterial stiffness parameters, including aortic augmentation index (AIx) and pulse wave velocity (PWV), are independent predictors of stroke and cardiovascular disease. Genetic effects on these traits were never explored in a Mediterranean country. The present study aims to quantify the contribution of genes, environment and age to carotid IMT and aortic Aix and PWV. Methods and results The twin design was used. A total of 348 adult twins from the Italian Twin Register underwent measurements of carotid IMT and aortic PWV and AIx in three university hospitals located in Rome, Padua and Perugia. Carotid IMT was measured by B-mode ultrasound, aortic PWV and AIx by Arteriograph. Genetic modelling was performed to decompose total variance of traits into genetic, shared and unshared environmental and age components. For each phenotype, the best-fitting model included additive genetic, unshared environmental and age effects. For IMT, heritability was 0.32 (95% confidence interval (CI): 0.25–0.38), unshared environmental component was 0.25 (0.18–0.32) and age contribution was 0.44 (0.39–0.49). For AIx and PWV, heritabilities were 0.42 (0.29–0.55) and 0.49 (0.35–0.62), unshared environmental components were 0.31 (0.22–0.44) and 0.37 (0.26–0.51) and age contributions were 0.27 (0.16–0.39) and 0.14 (0.06–0.24), respectively. Conclusion This study shows substantial genetic and unshared environmental influences on carotid intima-media thickness and arterial stiffness and confirms the relevant role of age in the aetiology of these traits. Further support is provided for prevention and health promotion strategies based on modifiable factors.

Background Thyroid autoantibodies (ThyAb) and subclinical hypothyroidism occur more frequently in pregnant women with insulin-dependent diabetes mellitus than in healthy pregnant women. Few studies have investigated the presence of ThyAb in women with gestational diabetes mellitus (GDM), and no significant association between diabetes in pregnancy and thyroid function has been reported. Objective To assess the thyroid biochemical profile and estimate the prevalence of ThyAb in a group of pregnant women at increased risk of GDM due to family and personal risk factors, and to investigate the relationship between a positive family history of diabetes or thyroid diseases and the eventual presence of ThyAb during pregnancy. Methods Oral glucose tolerance, serum ThyAb and thyroid function were evaluated in 181 pregnant women with increased risk for GDM (study group). Seventeen healthy pregnant women without risk factors for GDM and with a normal glucose tolerance were recruited as controls. Results The women who developed GDM showed a mean free thyroxine concentration significantly lower than that observed in the healthy pregnant women and in those with impaired gestational glucose tolerance and normal glucose tolerance. Twenty-nine of the 181 women in the study group (16%) were ThyAb positive. However, the risk of being ThyAb positive during pregnancy was three times greater in the women with positive family history of both diabetes mellitus and thyroid disease than in those with no family history of these conditions. Conclusions This study showed that women with increased risk of GDM, mostly those with family history of diabetes mellitus and thyroid disease, also have an increased risk of being ThyAb positive during pregnancy. It also highlighted the importance of evaluating thyroid function in pregnant women with impaired glucose tolerance, in view of their increased risk of subclinical hypothyroidism.

Purpose: To evaluate the impact on Italian teenagers' knowledge and attitudes of an experimental program in sex education. Methods: The program consisted of five workshops in five public secondary schools in Rome. The impact of the program was evaluated with three questionnaires designed for this study. A pretest evaluated baseline knowledge, a posttest measured the gain in knowledge, and a third questionnaire estimated retention of information 4–6 months later. Three hundred seventy-six students attending secondary school participated in the program. Thirteen questions were selected for the analysis, and improvement was measured by the difference between pretest and posttest scores. Results: Ninety-six percent of the sample was in favor of sex education programs in schools. The students had an average 50% gain in the percentage of correct answers following the course. The mean score based on the number of correct answers to questions showed a baseline value of 5.00, a posttest value of 11.80, and a test value 4–6 months later of 10.7. Results showed students' positive attitude toward school sex education courses, low baseline knowledge, and a good ability to learn. Conclusions: In Italy there is a need for collaboration between schools and local health services to promote knowledge and prevention in reproductive health among teenagers.

Obesity, blood pressure and arterial stiffness are heritable traits interconnected to each other but their possible common genetic and environmental etiologies are unknown.We studied 228 monozygotic and 150 dizygotic twin pairs aged 18-82 years from Italy, Hungary and the United States, of which 45 monozygotic and 38 dizygotic pairs were discordant for body mass index (BMI; intrapair difference (Δ) in BMI ≥ 3 kg/m(2)). Blood pressure components and arterial stiffness were measured by TensioMed Arteriograph.Hypertension was more prevalent among obese than non-obese individuals (55% vs. 29%, p0.001). Age-, sex- and country-adjusted heritability estimates were high for hemodynamic measures (45%-58%) and BMI (78%). According to bivariate Cholesky decomposition, phenotypic correlations between BMI and blood pressure components (r = -0.15 to 0.24, p0.05) were largely explained by additive genetic factors (65%-77%) with the remaining explained by the unique environment. When controlling for genetic factors within all monozygotic pairs, ΔBMI was significantly correlated with Δbrachial systolic blood pressure (SBP) and diastolic blood pressure (DBP), Δmean arterial pressure, and Δaortic SBP (r = 0.15-0.17, p0.05). For the same measures, heavier co-twins of BMI-discordant monozygotic pairs had significantly higher values than their leaner counterparts (p0.05).Blood pressure components are moderately correlated with BMI, largely because of shared genetic factors. However, for the association of BMI with brachial SBP and DBP, aortic SBP and mean arterial pressure, acquired, modifiable factors were also found to be important.

The study aimed to estimate the pain related to first trimester abortion under local and general anaesthesia. One hundred and eighty-one women undergoing abortion of first trimester under local anaesthesia and 198 under general anaesthesia were interviewed 1 h after the end of the procedure. About 50% of all women described their experience as less painful than expected. Over 50% of the women described the pain during the procedure as mild or moderate according to the verbal rating scale. The step-up logistic regression analyses identified four important variables: time interval less than 2 min from local anaesthesia injection to the beginning of the procedure (RR = 3), lack of choice between local and general anaesthesia (RR = 1.9), history of frequent use of analgesics (RR = 1.9) and nulliparity (RR = 1.7). These data indicate that skillfully performed abortion with local anaesthesia is a procedure tolerated by most women. Moreover, because it carries lower risk of complications and costs less, its use should be encouraged.The World Health Organization has urged a reduction in the number of first-trimester induced abortions performed under general anesthesia. To determine the implications of this recommendation for pain control, 181 women undergoing first-trimester abortion under local anesthesia and 198 aborted under general anesthesia at University Hospital in Rome, Italy, were interviewed 1 hour after the procedure. Pain intensity was assessed through both the visual analogue and verbal rating scales. Women who selected or were assigned to general anesthesia tended to be younger (mean age, 27 years) and nulliparous. Over 50% of local anesthesia patients described their pain during the procedure as mild or moderate, 30% rated it severe, and 18% characterized it as distressing but time-limited. 60 minutes after the abortion, pain scores were higher in the general anesthesia group. Logistic regression analysis identified four significant predictors of pain: time interval less than 2 minutes from local anesthetic injection to the beginning of the procedure (relative risk (RR), 3.0), lack of choice between general or local anesthesia (RR, 1.9), history of frequent use of analgesics (RR, 1.9), and nulliparity (RR, 1.7). 91% of general anesthesia and 73% of local anesthesia patients stated they would recommend their method of anesthesia to a friend undergoing abortion. These findings suggest that local anesthesia, less costly and with a lower risk of complications than general anesthesia, is feasible for pain control, especially if administered 2-5 minutes before the procedure begins.

Previous studies in twins indicate that non-shared environment, beyond genetic factors, contributes substantially to individual variation in mutagen sensitivity; however, the role of specific causative factors (e.g. tobacco smoke, diet) was not elucidated. In this investigation, a population of 22 couples of monozygotic twins with discordant smoking habits was selected with the aim of evaluating the influence of tobacco smoke on individual response to DNA damage. The study design virtually eliminated the contribution of genetic heterogeneity to the intra-pair variation in DNA damage response, and thus any difference in the end-points investigated could directly be attributed to the non-shared environment experienced by co-twins, which included as main factor cigarette smoke exposure. Peripheral lymphocytes of study subjects were challenged ex vivo with γ-rays, and the induction, processing, fixation of DNA damage evaluated through multiple approaches. Folate status of study subjects was considered significant covariate since it is affected by smoking habits and can influence radiosensitivity. Similar responses were elicited by γ-rays in co-twins for all the end-points analysed, despite their discordant smoking habits. Folate status did not modify DNA damage response, even though a combined effect of smoking habits, low-plasma folic acid level, and ionising radiation was observed on apoptosis. A possible modulation of DNA damage response by duration and intensity of tobacco smoke exposure was suggested by Comet assay and micronucleus data, but the effect was quantitatively limited. Overall, the results obtained indicate that differences in smoking habits do not contribute to a large extent to inter-individual variability in the response to radiation-induced DNA damage observed in healthy human populations.

Background and Purpose— Few family studies reported moderate genetic impact on the presence and scores of carotid plaques. However, the heritability of carotid plaque characteristics remains still unclear. Twin studies more reliably estimate the relative contribution of genes to these traits in contrast to family study design. Methods— One hundred ninety-two monozygotic and 83 dizygotic adult twin pairs (age 49±15 years) from Italy, Hungary, and the United States underwent B-mode and color Doppler ultrasound of bilateral common, internal, and external carotid arteries. Results— Age-, sex-, and country-adjusted heritability was 78% for the presence of carotid plaque (95% CI, 55%–90%), 74% for plaque echogenicity (hypoechoic, hyperechoic, or mixed; 95% CI, 38%–87%), 69% for plaque size (area in mm 2 in longitudinal plane; < or >50 percentile; 95% CI, 16%–86%), 74% for plaque sidedness (unilateral or bilateral; 95% CI, 25%–90%), 74% for plaque numerosity (95% CI, 26%–86%), 68% (95% CI, 40%–84%), and 66% (95% CI, 32%–90%) for the presence of plaque in carotid bulbs and proximal internal carotid arteries. No role of shared environmental factors was found. Unique environmental factors were responsible for the remaining variance (22%–34%). Controlling for relevant covariates did not change the results significantly. Conclusions— The heritability of ultrasound characteristics of carotid plaque is high. Unshared environmental effects account for a modest portion of the variance. Our findings should stimulate the search for genes responsible for these traits.

Central blood pressure and aortic stiffness have been consistently reported as strong cardiovascular risk factors. Twin studies by comparing identical with nonidentical twins produce information on the relative contribution of genes and environment.One hundred and fifty-four monozygotic (MZ) and 42 dizygotic (DZ) twin pairs (age 43 ± 17 years) from Hungary and the United States underwent brachial and central augmentation index (AIx), brachial and central pressure, and aortic pulse wave velocity (PWV) measurements with the invasively validated Arteriograph device. Bivariate Cholesky decomposition models were applied.Age-adjusted, sex-adjusted and country-adjusted heritability was 60.0% for central SBP [95% confidence interval (CI), 44.8-69.6%], 50.1% for aortic PWV (95%CI, 26.0-66.8%), 48.7% for aortic AIx (95%CI, 1.7-74.0%), 46.8% for brachial AIx (95%CI, 1.1-73.8%), 46.7% for central pulse pressure (PP) (95%CI, 12.4-61.4%), and 30.0% for brachial PP (95%CI, 0.0-53.4%). Central SBP and PP had strong bivariate correlations with brachial (r = 0.461 and 0.425) and central AIx (r = 0.457 and 0.419), as well as with aortic PWV (r = 0.341 and 0.292, all P0.001). Brachial PP had a weak correlation with brachial AIx (r = -0.118, P0.05), central AIx (r = -0.122, P0.05), and none with aortic PWV (r = 0.08, P = n.s.). Genetic factors explained a moderate phenotypic correlation between central PP, SBP, brachial SBP and aortic PWV.Central systolic and PPs, brachial PP, AIx, aortic PWV are moderately heritable. A moderate genetic covariance among aortic PWV and central PP, central SBP and brachial SBP was found.

In the past 5 years, four knowledge, attitude and practice (KAP) surveys on family planning have been organized by the Unit of Population Survey Methodology of the Istituto Superiore di Sanita' (National Institute of Health). These surveys show that during the past 20 years, use of reliable contraceptives in Italy has increased, particularly in the North, encouraged by the more open attitude toward sexual behavior, following legalization of the provision of information on contraception and abortion upon request, and other social and cultural changes. In 1989 and 1991, 25% of women in Central and Southern Italy were using the pill or an IUD. However, the percentage of women not using contraceptives was still high (26% in 1989, and 19% in 1991) and withdrawal was the most widely used method (31% and 33%). The data show large regional differences. The main reasons for not using contraception, in the 1989 study, were fear of side-effects and ignorance, especially in the youngest and oldest women. Those least likely to use modern contraception were the young, the ill-educated and the nulliparous women. Lack of information seems to be the main problem in Italy. In fact, the 5044 women interviewed showed a medium level of knowledge of contraception, with only 63% who could identify correctly the fecund period in the menstrual cycle. However, their attitude toward the use of modern contraception was positive; 65% of the women interviewed said they would recommend the Pill or an IUD to a friend, and 10% of them would recommend condoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Background Endometriosis is a common gynecologic disease characterized by the ectopic growth of endometrial tissue. In industrialized countries, it affects approximately 10% of women of reproductive age. Its etiology is unclear, but a multifactorial origin is considered to be most plausible. Environmental organochlorinated persistent pollutants, in particular dioxins and polychlorinated biphenyls (PCBs), have been hypothesized to play a role in the disease etiopathogenesis. However, results of studies carried out on humans are conflicting. Objective We evaluated the exposure to organochlorinated persistent pollutants as a risk factor for endometriosis. Methods We conducted a case–control study in Rome on 158 women comprising 80 cases and 78 controls. In all women, serum concentrations of selected non-dioxin-like PCBs (NDL-PCBs) and dioxin-like PCBs (DL-PCBs), 1,1-dichloro-2,2,-bis(4-chlorophenyl)-ethene (p,p′-DDE), and hexachlorobenzene (HCB) were determined by ion-trap mass spectrometry. DR-CALUX bioassay was employed to assess the 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity equivalent (TEQ) concentrations of polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and DL-PCBs. Results We found an increased risk of endometriosis for DL-PCB-118 [odds ratio (OR) = 3.79; 95% confidence interval (CI), 1.61–8.91], NDL-PCB-138 (OR = 3.78; 95% CI, 1.60–8.94), NDL-PCB-153 (OR = 4.88; 95% CI, 2.01–11.0), NDL-PCB-170 (OR = 3.52; 95% CI, 1.41–8.79), and the sum of DL-PCBs and NDL-PCBs (OR = 5.63; 95% CI, 2.25–14.10). No significant associations were observed with respect to HCB or to the sum of PCDDs, PCDFs, and DL-PCBs given as total TEQs. Conclusions The results of this study show that an association exists between increased PCB and p,p′-DDE serum concentrations and the risk of endometriosis.

A number of studies have provided evidence of a significant familial aggregation for both asthma and hay fever, and have reported a substantial comorbidity between the two conditions. However, far fewer, especially in Italy, have aimed at clarifying the origins of such comorbidity. The main aims of the present study were (a) to estimate heritability of asthma and hay fever, (b) to measure the association between asthma and hay fever at the individual level, and (c) to assess the extent to which genetic and environmental factors, shared by the two conditions, mediate this association. The twin method was used. The study sample was derived from the Italian Twin Registry, and included 392 twin pairs aged 8 to 17 years. Data collection was performed through parent self-administered questionnaire. Bivariate structural equation twin modeling was applied to asthma and hay fever. Genetic factors accounted for 92% and 78% of the variance in liability to asthma and hay fever, respectively, with the remaining contributions due to unique environmental influences. The within-individual association between asthma and hay fever was substantial. The genetic correlation between the two conditions was .58, whereas no evidence of overlapping unique environmental effects was found. In conclusion, this study showed a high heritability of asthma and hay fever in the Italian child and adolescent population. It also indicated that asthma and hay fever share, to a large extent, a common genetic background, and environmental factors are not relevant to explain the comorbidity.

Femoral atherosclerosis, a major cause of peripheral artery disease, has been associated with higher cardiovascular risk in lower extremity peripheral arterial disease patients. The purpose of our study was to assess the effects of the heritable components of atherosclerotic plaque formation in the femoral artery. 161 Hungarian and Italian twin pairs (n = 322, 75 Hungarian and 86 Italian pairs from Padua, Perugia and Terni; 83 monozygotic /MZ/, 78 dizygotic /DZ/; mean age 50 ± 13 years) recruited from the Hungarian and Italian Twin Registries underwent B-mode sonography of bilateral common and superficial femoral arteries (CFA, SFA). Concordance rates between members of the MZ and DZ pairs were calculated, and compared by Chi-square test. Rough heritability was analysed by Falconer formula. Plaques were identified in 24% and 6% of patients in CFA and SFA, respectively. Significantly higher concordance rate was found in MZ twins compared to DZ pairs regarding the presence of plaques in CFA (rMZ = 0.869 vs. rDZ = 0.696) and SFA (rMZ = 0.622 vs. rDZ = 0.403) on left or right side, which indicated a 34% and 44% rough heritability, respectively. Femoral atherosclerotic plaque formation in CFA and SFA is moderately genetically determined. Further studies should elucidate whether offsprings of families at high risk for femoral atherosclerosis may benefit from early ultrasound screening.

Objective: To identify risk factors for permanent and transient congenital hypothyroidism (CH). Design: A population-based case-control study was carried out by using the network created in Italy for the National Register of Infants with CH. Methods: Four controls were enrolled for each new CH infant; 173 cases and 690 controls were enrolled in 4 years. In order to distinguish among risk factors for permanent and transient CH, diagnosis was re-evaluated 3 years after enrolment when there was a suspicion of transient CH being present. Familial, maternal, neonatal and environmental influences were investigated. Results: An increased risk for permanent CH was detected in twins by a multivariate analysis (odds ratio (OR) = 12.2, 95% confidence interval (CI): 2.4–62.3). A statistically significant association with additional birth defects, female gender and gestational age >40 weeks was also confirmed. Although not significant, an increased risk of CH was observed among infants with a family history of thyroid diseases among parents (OR = 1.9, 95% CI: 0.7–5.2). Maternal diabetes was also found to be slightly associated with permanent CH (OR = 15.7, 95% CI: 0.9–523) in infants who were large for gestational age. With regard to transient CH, intrauterine growth retardation and preterm delivery were independent risk factors for this form of CH. Conclusion: This study showed that many risk factors contribute to the aetiology of CH. In particular, our results suggested a multifactorial origin of CH in which genetic and environmental factors play a role in the development of the disease.

Objective: To determine whether genetic amniocentesis performed in the second trimester of pregnancy is associated with the risk of preterm delivery. Study design: Case–control study performed in several departments of obstetrics and gynaecology of nine European countries. Three thousand and ninety-one preterm births and 5298 controls randomly selected from singleton births born at term during 1994–1997 were analysed. Logistic regression models were used to compare preterm births altogether and, separately, spontaneous preterm delivery and induced preterm delivery. Results: An increased risk of preterm delivery was found in women having second trimester genetic amniocentesis after taking account of other risk factors and confounding variables (odds ratios (OR)=1.59, 95% confidence intervals (95% CI): 1.31–1.92). The association was statistically significant and similar for spontaneous preterm delivery and induced preterm delivery. Conclusion: The study shows an association between preterm delivery and genetic amniocentesis. In view of the wide use of amniocentesis, further research on the etiologic role of this prenatal diagnostic technique is needed.

In the last decade a high frequency of other congenital anomalies has been reported in infants with congenital hypothyroidism (CH) detected by neonatal screening. In the present study the occurrence of additional congenital malformations (CM) in the population of CH infants detected in Italy between 1991 and 1998 (n = 1420) was investigated. In Italy all of the centers in charge of screening, treatment, and follow-up of CH adhere to the Italian National Registry of infants with CH. In this study a high prevalence of additional CM (8.4%), more than 4-fold higher than that reported in the Italian population (1-2%), was found in the population of CH infants. Cardiac anomalies represented the most frequent malformations associated with CH, with a prevalence of 5.5%. However, a significant association between CH and anomalies of nervous system, eyes, and multiple CM was also observed. In conclusion, the significantly higher frequency of extrathyroidal congenital malformations reported in the CH infants than in the general population represents a further argument supporting the role of a genetic component in the etiology of CH. Investigations of the molecular mechanisms underlying developmental events of formation of thyroid and other organs represent critical steps in the knowledge of CH etiology.

This study explores the reproductive attitudes, contraceptive use, demand for family planning and related topics of a representative sample of the female population of reproductive age resident in a Refugee Camp in the Gaza Strip. A cluster sample of 841 resident women of reproductive age (15–49 years) was interviewed in their homes. Univariate and multivariate statistical analyses were performed using BMDP software. 98% of the interviewees favour family planning and 88% plan to use a contraceptive in the future. However, 52% of the women at risk do not use any contraception because of their husband's opposition, fear of side effects or lack of knowledge. The risk of having seven or more children is positively associated with a woman's low educational level and husband's desire for more than seven children. Despite favourable attitudes regarding family planning, there is ignorance and the prevalence of contraception use is low. There is a gap between fertility preference and achievement.