[SENTIERI Project: a systematic review on the association between sources of environmental exposure in contaminated sites and health outcomes]. / Progetto SENTIERI: revisione della letteratura scientifica sull'associazione tra fonti di esposizione ambientale in siti contaminati ed esiti di salute.

BACKGROUND: the epidemiological surveillance programme carried out in the Italian Contaminated Sites (SENTIERI Project) is based on an a priori evaluation of the epidemiological evidence of a causal association between environmental exposures and health outcomes. OBJECTIVES: to produce an updated review of the epidemiological evidence (January 2009-May 2020) on the association between environmental exposures and health outcomes predefined and published by the SENTIERI working group. METHODS: a systematic review was conducted on MEDLINE, EMBASE, and Web of Science. Additional searches were conducted on the websites of relevant organizations. The sources of environmental exposure considered were the ones included in SENTIERI Projects (chemicals, petrochemicals and refineries, steel plants, power plants, port area, waste, mines and source of asbestos). RESULTS: a total of 16,817 records were identified and, after the screening process, 14 systematic reviews were identified: two IARC Monograph, two WHO Reports, one WHO/UNEP Report, and 15 observational studies. Living in proximity of contaminated sites was associated with specific diseases (mortality or incidence), with a high heterogeneity across environmental sources. For some exposures, data suggests a gender differential effect for some causes of disease. CONCLUSIONS: compared to a previous evidence evaluation, this systematic review shows a higher number of diseases associated with residential exposure to some contaminated sites (petrochemical facilities, waste, mines, and sources of asbestos). According to the results of this review, the a priori evidence evaluation was updated and used to interpret the epidemiological data of the Sixth SENTIERI Project Report.

[The contaminated sites in the SENTIERI Project: an update of legislative, contamination, and sources of environmental exposure aspects in Italy]. / I siti contaminati del Progetto SENTIERI: aggiornamenti legislativi, caratteristiche della contaminazione e fonti di esposizione ambientale.

In Italy, the problem of contaminated sites was introduced for the first time at a regulatory level with the 'Ronchi Decree' No. 22 of 1997. Subsequently, the regulations that defined most of the contaminated Sites of National Interest (SINs) were Law No. 426 of 09.12.1998 and Law no. 179 of 31.07.2002. Today, the reference directive is the Legislative Decree 152/2006 'Consolidated Environmental Act', which in Part IV, Title V 'Remediation of contaminated sites', dictates the administrative and technical procedures for the remediation of contaminated sites. Over time, there have been numerous regulatory updates that have changed the selection criteria for the SINs, leading some of these to be downgraded to Sites of Regional Interest (SIRs). The SINs in their entirety are managed by the Italian Ministry of the Environment, today called 'of the Ecological Transition', while the pass to the competence of the territorially concerned Regions SIRs regarding the verification and eventual remediation operations. Currently, in Italy there are 42 SINs and 17 SIRs. All the information derived from the various environmental regulations and that found in the context of the remediation procedures made it possible to define the exposure of the population residing in the areas adjacent to the SINs and SIRs as well as the elaboration of sheets containing all the site-specific information.

[SENTIERI - Epidemiological Study of Residents in National Priority Contaminated Sites. Sixth Report]. / SENTIERI - Studio epidemiologico nazionale dei territori e degli insediamenti esposti a rischio da inquinamento. Sesto Rapporto.

INTRODUCTION ADN OBJECTIVES: The Sixth Report presents the results of the "SENTIERI Project: implementation of the permanent epidemiological surveillance system of populations residing in Italian Sites of Remediation Interest", promoted and financed by the Italian Ministry of Health (Centre for Disease Control and Prevention - CCM Project 2018). The aim of this study is to update the mortality and hospitalization analyses concerning the 6,227,531 inhabitants (10.4% of the Italian population) residing in 46 contaminated sites (39 of national interest and 7 of regional interest). The sites include 316 municipalities distributed as follows: 15 in the North-East (20.3% of the investigated population); 104 in the North-West (12% of the investigated population), 32 in the Centre (12.6% of the investigated population), 165 in the South and Islands (55.5% of the investigated population). Analyses were carried out on the paediatric-adolescent (1,128,396 residents) and youth (665,284 residents) population, and a study on congenital anomalies (CA) was carried out at sites covered by congenital malformation registers. Accompanying the epidemiological assessments, site-specific socioeconomic conditions were examined and an overall estimate of excess risk for populations residing at contaminated sites was drawn up. By means of a systematic review of the scientific literature, the epidemiological evidence on causal links between sources of environmental exposure and health effects was updated to identify pathologies of a priori interest. METHODOLOGY: In the 46 sites included in the SENTIERI Project, mortality (time window: 2013-2017) and hospital admissions (time window: 2014-2018) of the general population of all ages, divided by gender, and of the paediatric-adolescent (0-1 year, 0-14 years, 0-19 years), youth (20-29 years), and overall (0-29 years) age groups, divided by gender, were analysed. In 21 sites, CA diagnosed within the first year of life were studied. Standardised mortality ratios (SMR) and hospitalization ratios (SHR) were calculated with reference to the rates in the regions to which the sites belong. The reference population was calculated net of residents in the sites. CA were studied by calculating the prevalence per 10,000 births and the ratio, multiplied by 100, between the cases observed at the site and those expected on the basis of the prevalences observed in the reference area (region or sub-regional area of belonging, according to the geographical coverage of the registry). The socioeconomic condition studied in the 46 sites is based on the convergence of three deprivation indicators with respect to the reference region: deprivation index at municipal level, deprivation index at census section level, premature mortality indicator (age range 30-69 years) for chronic non-communicable diseases. For the estimation of excess risk for the entire study population, meta-analysis of the mortality and hospitalization risk estimates for each site was carried out and the number of excess deaths estimated for the sites as a whole. The epidemiological evidence was updated through a systematic literature review (January 2009-May 2020), following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. The search was carried out on the search engines MEDLINE, EMBASE and Web of Science; the quality of the studies included in the review was assessed using the AMSTAR 2 checklist for systematic reviews and the NewCastle-Ottawa Scale for observational studies in the case of cohort and case-control studies and a modified version thereof for ecological and cross-sectional studies. The update was based on the selection of 14 systematic reviews, 15 primary studies, 6 monographs/reports from international scientific organisations on health effects due to the presence of environmental exposure sources. RESULTS: Mortality. The a priori causes of interest that occur most frequently in excess are, in descending order: malignant lung cancer, malignant mesothelioma of the pleura, malignant bladder cancer, respiratory diseases, non-Hodgkin lymphomas, malignant liver cancer, all malignant tumours, malignant colorectal cancer, malignant stomach cancer, total mesotheliomas, malignant breast cancer, and asbestosis. Hospitalization. The a priori causes of interest that occur most frequently in excess are represented in descending order by: respiratory diseases, malignant lung cancer, malignant tumours of the pleura, malignant bladder cancer, malignant breast cancer, malignant liver cancer, asthma, malignant colorectal cancer, all malignant tumours, malignant stomach cancer, non-Hodgkin's lymphomas, acute respiratory diseases, leukaemias. The differences observed between mortality and hospitalization can be attributed to the intrinsic characteristics of the diseases (higher or lower lethality, gender differences in incidence), lifestyles, and occupational phenomena. Age classes. Excesses of general mortality were observed in the first year of life at the Manfredonia, Basso Bacino Fiume Chienti, Litorale Domizio Flegreo and Agro Aversano sites; in the 0-1 year and 0-19 year age groups at Casale Monferrato; in the paediatric age group at Serravalle Scrivia and at the Trento Nord site; in the 0-19 year age group at Sassuolo Scandiano; in the young age group (0-29 years) at the two municipalities of Cerchiara and Cassano (Crotone-Cassano-Cerchiara site). With regard to hospitalization due to natural causes, risk excesses in both genders are found in the first year of life in 35% of the sites (Porto Torres industrial areas, Bari-Fibronit, Basso bacino fiume Chienti, Bolzano, Crotone-Cassano-Cerchiara, Cerro al Lambro, Bologna ETR large repair workshop, Gela, Manfredonia, Massa Carrara, Pioltello Rodano, Pitelli, Priolo, Sesto San Giovanni, Trento Nord, and Trieste). These same sites, with the addition of Casale Monferrato, Cengio e Saliceto, Serravalle Scrivia, and Sulcis-Iglesiente-Guspinese (total: 43% of sites), show excesses for all natural causes, in both genders, even in the paediatric-adolescent age group (0-19 years). Among young adults (20-29 years), the analyses show excesses of hospitalization for all natural causes in both genders in the Bolzano, Crotone-Cassano-Cerchiara, Gela, Manfredonia, Pitelli, Priolo, and Sulcis-Iglesiente-Guspinese sites. Among young women only, excesses for all natural causes are also found in Brescia Caffaro, Brindisi, Broni, Casale Monferrato, Crotone-Cassano-Cerchiara, Falconara Marittima, Fidenza, and Massa Carrara. Congenital anomalies. In the 21 sites investigated for CA, 10,126 cases of CA, validated by participating registers, were analysed out of 304,620 resident births. Genital CA is the subgroup for which the greatest number of excesses was observed (in 6 out of 21 sites). The available evidence does not allow a causal link to be established between the excesses observed for specific subgroups of ACs and exposure to industrial sources, but the results suggest further action. The interpretation of the results appears, in fact, particularly complex as the scientific literature on the association between exposure to industrial sources and AC is very limited. Socioeconomic status. The sites in which the indicators converge to show the presence of fragility are: Litorale Vesuviano area, Val Basento industrial areas, Basso Bacino fiume Chienti, Biancavilla, Crotone-Cassano-Cerchiara, Litorale Domizio Flegreo and Agro Aversano, Livorno, Massa Carrara, Trieste. Global impact. Over the period 2013-2017, an estimated 8,342 excess deaths (CI90% 1,875-14,809) or approximately 1,668 excess cases/year, 4,353 excess deaths among males (CI90% 334-8,372) and 3,989 among females (CI90% -1,122;9,101). The pooled excess risk of general mortality is 2% in both genders (pooled SMR 1.02; CI90% 1.00-1.04). The proportion of excess deaths to total observed deaths is almost constant over time, rising from 2.5% in 1995-2002 to 2.6% in 2013-2017. The number of deaths in absolute value is also very similar between the periods analysed. Deaths from all malignant tumours contribute the most by accounting for 56% of the observed excesses, the excess risk of mortality from malignant tumours across all sites, compared to the reference populations, is 4% in the male population (pooled SMR 1.04; CI90% 1.01-1.06) and 3% among the female population (pooled SMR 1.03; CI90% 1.01-1.05). Hospitalization (2014-2018) in the 46 sites as a whole was in excess of 3% for all causes, in both genders, for all major disease groups (males: SHR pooled 1.03; CI90% 1.01-1.04 - females: SHR pooled 1.03; CI90% 1.01-1.05). The results for the pooled estimates at the 46 sites on the general population, both with regard to mortality and hospitalization, are consistent in indicating excess risk in both genders for all the diseases considered and, in particular, for all malignancies. A total of 1,409 paediatric-adolescent deaths and 999 young adult deaths were observed, and the pooled analysis of mortality across the 46 sites showed no critical issues, with pooled estimates for all causes, perinatal morbid conditions and all malignancies falling short of expectations. The analysis of hospitalizations, on the other hand, showed an excess risk of 8% (males: SHR pooled 1.08; CI90% 1.03-1.13 - females: SHR pooled 1.08; CI90% 1.03-1.14) for all causes in the first year of life, and in paediatric-adolescent and juvenile age of 3-4% among males (age 0-19 years: SHR pooled 1.04; CI90% 1.02-1.06 - age 20-29 years: SHR pooled 1.03; CI90% 1.00-1.05) and 5% among females (in both age groups; SHR pooled 1.05; CI90% 1.02-1.08). The pooled analysis of mortality for the a priori identified diseases reported excesses for specific diseases in the group of sites with sources of exposure associated with them. Mortality from total mesotheliomas is three times higher at sites with asbestos present (males:pooled SMR 3.02; CI90% 2.18-3.87 - females: pooled SMR 3.61; CI90% 2.33-4.88) and that from pleural mesotheliomas more than two times higher at the group of sites with asbestos and port areas (males: pooled SMR 2.47; CI90% 1.94-3.00 - females: pooled SMR 2.43; CI90% 1.67-3.19). Lung cancer was in excess by 6% among males (pooled SMR 1.06; CI90% 1.03-1.10) and 7% among females (pooled SMR 1.07; CI90% 1.00-1.13). In addition, there are excess mortalities for colorectal cancer at sites with chemical plants, by 4 % among males (SMR pooled 1.04; CI90% 1.01-1.08) and 3 % among females (SMR pooled 1.03; CI90% 1.00-1.07) and for bladder cancer among the male population of sites with landfills (+6 %: SMR pooled 1.06; CI90% 1.02-1.11). Among the diseases of a priori interest, stomach and soft tissue cancers are at fault as a cause of death among all the sites considered. LITERATURE REVIEW: The update of the epidemiological evidence underlying the Sixth SENTIERI Report has highlighted in the general population a possible association, previously undiscovered, between certain diseases and residence near petrochemical and steel plants, landfills, coal mines and asbestos sources. CONCLUSIONS AND PERSPECTIVES: Despite the fact that this is an ecological study, and the excesses of pathologies with multifactorial aetiology can never be mechanically attributed solely to the environmental pressure factors that exist or existed in the areas studied, the ability to identify the excesses found in the contaminated sites investigated by the SENTIERI Project confirms the validity of this method of assessing the site-specific health profile, based on the use of epidemiological evidence to identify pathologies of interest a priori. In interpreting the data and lending robustness to what has been observed, comparison with the results obtained in previous Reports is essential. The global estimates give an overall picture that shows excess mortality and hospitalization in these populations compared to the rest of the population, and show how, for specific pathologies, comparable effects are produced at sites with similar contamination characteristics. The themes developed in the in-depth chapters broaden the vision and understanding of the complex interactions between environment and health, describe the possibilities offered by new ways of communicating the results, and confirm the modernity of a Project that began way back in 2006, and that could be grafted onto the objectives of the National Recovery and Resilience Plan within the framework of the Operational Programme Health, Environment, Biodiversity and Climate.

[From the selection of priority pollutants to the analysis of health data in the SENTIERI Project]. / Dalla selezione degli inquinanti prioritari alla lettura dei dati sanitari nel Progetto SENTIERI.

OBJECTIVES: evaluation of mortality and hospitalization of residents in five Italian National Priority Contaminated Sites, studied in the SENTIERI Project, for those pathologies which, on the basis of the assessments of international agencies and bodies, are known to have an aetiological connection with exposure to specific environmental pollutants. DESIGN: ecological study. SETTING AND PARTICIOANTS: resident population in the sites of Trieste and Piombino (steel plants), and Falconara, Livorno, and the industrial area of Milazzo (petrochemical plants and/or refineries). Data extracted from the Sixth SENTIERI Report. MAIN OUTCOME MEASURES: mortality (2013-2017) and hospitalization (2014-2018) for associated causes by exposure to specific pollutants detected in the soil and water matrices. RESULTS: the results obtained do not show common patterns between the excesses found in Trieste and Piombino Sites (steel plants) nor among Livorno, Falconara, and Milazzo (petrochemicals and/or refineries). Livorno and Trieste sites, having a larger population, show the greatest number of excesses. CONCLUSIONS: the proposed approach can be a useful tool, in addition to others, for the study of the health profile of residents in contaminated sites, being also the basis for aetiological epidemiological studies.

[Global evaluation of the mortality and hospitalization in the Italian contaminated sites included in the SENTIERI project]. / Stime globali della mortalità e ospedalizzazione nei siti contaminati italiani inclusi nel progetto SENTIERI.

Since 2006, epidemiological surveillance of populations living in Italian contaminated sites has been ongoing (SENTIERI Project). Updated global estimates of mortality (2013-2017) and hospitalization (2014-2018) are reported. The excess deaths (observed-expected) for the main groups of diseases were calculated for all the 46 sites together. Through a random-effect meta-analysis of the standardized mortality and hospitalization rates (SMR/SHR), the pooled SMR/SHR for all the sites and their groupings were estimated. In the 46 sites, 8,342 exceeding deaths (1,668/year) were estimated, 4,353 in males and 3,989 in females, resulting in an excess risk of 2% in both genders. The risk of hospitalization for all causes was in excess of 3%. These excesses are mainly attributable to malignant tumours. In subgroups of sites, exceeding SMRs were observed for all mesotheliomas and pleural mesotheliomas, lung and colorectal cancers in both genders. SHR for all causes were observed in excess in the first year of life (+8%), in the group 0-19 and 20-29 years (+3-5%); no excesses of mortality were observed in the group 0-29 years.

Optimized office lighting advances melatonin phase and peripheral heat loss prior bedtime.

Improving indoor lighting conditions at the workplace has the potential to support proper circadian entrainment of hormonal rhythms, sleep, and well-being. We tested the effects of optimized dynamic daylight and electric lighting on circadian phase of melatonin, cortisol and skin temperatures in office workers. We equipped one office room with an automated controller for blinds and electric lighting, optimized for dynamic lighting (= Test room), and a second room without any automated control (= Reference room). Young healthy participants (n = 34) spent five consecutive workdays in each room, where individual light exposure data, skin temperatures and saliva samples for melatonin and cortisol assessments were collected. Vertical illuminance in the Test room was 1177 ± 562 photopic lux (mean ± SD) , which was 320 lux higher than in the Reference room (p < 0.01). Melanopic equivalent daylight (D65) illuminance was 931 ± 484 melanopic lux in the Test room and 730 ± 390 melanopic lux in the Reference room (p < 0.01). Individual light exposures resulted in a 50 min earlier time of half-maximum accumulated illuminance in the Test than the Reference room (p < 0.05). The melatonin secretion onset and peripheral heat loss in the evening occurred significantly earlier with respect to habitual sleeptime in the Test compared to the Reference room (p < 0.05). Our findings suggest that optimized dynamic workplace lighting has the potential to promote earlier melatonin onset and peripheral heat loss prior bedtime, which may be beneficial for persons with a delayed circadian timing system.

Ecological meta-analytic study of kidney disease in Italian contaminated sites.

INTRODUCTION: Environmental heavy metals exposure has been associated with kidney disease. There is also some evidence that exposure to solvents may be a risk factor for kidney disease. We estimated the risk of hospitalization for kidney diseases (ICD-9 580-586) and chronic kidney disease (CDK, ICD-9 585) in residents in thirty-four Italian National Priority Contaminated Sites (NPCSs) polluted by heavy metals. METHODS: Random-effects model meta-analyses of SHR (Standard Hospitalization Ratio) computed for each NPCS was performed for all the NPCSs together, and separately, according to the presence/absence of selected industrial activities (petrochemical/refinery and steel plants), and the presence/absence of solvents contamination. RESULTS: Pooled SHRs of overall NPCSs were in excess in both genders. Statistically significant excesses were found for CKD in both genders, and for kidney diseases in females, residing in NPCSs with the combined presence of heavy metals and solvents contamination. The pooled SHRs for CKD and kidney diseases were not statistically significant in excess in NPCSs with petrochemical/refinery and steel plants, and only petrochemical/refinery plants. CONCLUSIONS: The results are suggestive of a possible kidney disease risk in population living in the above-mentioned NPCSs. Epidemiological surveillance and remediation actions in these areas are recommended.

Residential proximity to an industrial incinerator and risk of soft-tissue sarcoma, 1999-2014.

BACKGROUND: exposure to dioxins has been associated with an increased risk of soft-tissue sarcoma (STS). In a study relating to 1989-1998, a significant excess of STS was found in the population living within a 2-kilometre radius of an industrial incinerator located inside a Mantua industrial site. In the years 1974-1991, the incinerator burned hazardous chlorine-containing waste that resulted in the emission of dioxins. After 1991, it was exclusively fed with organic synthetic products not containing chlorine. OBJECTIVES: the aim of this case-control study was to estimate the STS risk, for 1999-2014, in the population living in four Mantua districts located in the proximity of the industrial incinerator, compared to subjects resident in the remaining parts of Mantua province, regarded as non-exposed. METHODS: the cases analysed were subjects with a first-incident diagnosis of STS between 1999 and 2014 resident at diagnosis in Mantua Province. Cases were selected using the 2013 criteria from the WHO classification. Cases of Kaposi sarcoma, PEComas and STS occurring in a previously irradiated field were excluded. For each case of soft-tissue sarcoma, four controls were randomly selected from all individuals resident in Mantua Province included in the Regional Health Service database in the years of incidence of each case (calendar year), and individually matched for gender and year of birth. Residential and occupational history (for employment in an oil refinery, and petrochemical and chemical plants) was reconstructed for all study subjects (cases and controls) since 1961. Subjects were considered exposed if they had lived in the four Mantua districts most affected by the incinerator emissions, on the basis of an atmospheric dispersion model and a dioxins biomonitoring survey. Four analyses were performed according to variously defined residential time windows. Odds ratios and corresponding 95% confidence intervals (95%CI) were calculated using conditional regression models adjusted for occupational history. RESULTS: 391 cases (203 males and 188 females) and 1,564 controls were included. The number of exposed cases and controls in the four analyses were 8 and 55, 8 and 60, 15 and 68, and 15 and 73, respectively. An increased STS risk was not observed in any of the analyses. CONCLUSIONS: in this study, no increased risk of STS was observed in subjects who had lived, in the study's time window, in the Mantua districts most affected by the incinerator emissions. The most likely interpretation of the present finding is a real STS risk reduction for subjects resident in the most recent decades in the Mantua districts most affected by the incinerator emissions, due to the cessation of burning chlorine-containing waste in the incinerator, development of some remediation plans, and implementation of new industrial procedures.

Incidence of Thyroid Cancer in Italian Contaminated Sites.

Some human literature suggests a possible role of endocrine disruptors (EDs) exposure in thyroid cancer (TC) development. We investigated TC incidence in selected Italian National Priority Contaminated Sites (NPCS) with documented presence of EDs considered thyroid carcinogens. Adjusted Standardized Incidence Ratios (SIRs), with their 90% confidence intervals, were computed by gender, and age-specific groups (aged 15-39 years, and 40 years or over) for each NPCS in the period 2006 to 2013. In the age group of 15-39 years, a significant excess of TC risk was found in two NPCSs in males; non-significant excess risks were observed in four NPCSs in males, and in five in females. In the age group of 40 years and over, significant excess risks were found in six NPCSs in males and in seven NPCSs in females; non-significant excess risks were identified in two NPCSs in males and females. The findings of several excesses in incidence, mainly observed in adults aged 40 years or over, are suggestive of a possible adverse effect associated with residence in NPCSs, even if a role of other factors cannot be excluded, due to the adoption of an ecological study design. Future analytical studies are needed to clarify if EDs are a TC risk factor for individuals living in NPCSs.

Human organoids: a new dimension in cell biology.

Organoids derived from stem cells or tissues in culture can develop into structures that resemble the in vivo anatomy and physiology of intact organs. Human organoid cultures provide the potential to study human development and model disease processes with the same scrutiny and depth of analysis customary for research with nonhuman model organisms. Resembling the complexity of the actual tissue or organ, patient-derived human organoid studies may accelerate medical research, creating new opportunities for tissue engineering and regenerative medicine, generating knowledge and tools for preclinical studies, including drug development and testing. Biologists are drawn to this system as a new "model organism" to study complex disease phenotypes and genetic variability among individuals using patient-derived tissues. The American Society for Cell Biology convened a task force to report on the potential, challenges, and limitations for human organoid research. The task force suggests ways to ease the entry for new researchers into the field and how to facilitate broader use of this new model organism within the research community. This includes guidelines for reproducibility, culturing, sharing of patient materials, patient consent, training, and communication with the public.

Spatial distribution of kidney disease in the contaminated site of Taranto (Italy).

BACKGROUND: Exposure to heavy metals has been associated with kidney disease. We investigated the spatial distribution of kidney disease in the industrially contaminated site of Taranto. METHODS: Cases were subjects with a first hospital discharge diagnosis of kidney disease. Cases affected by specific comorbidities were excluded. Standardized Hospitalization Ratios (SHRs) were computed for low/high exposure area and for modeled spatial distribution of cadmium and fine particulate matter. RESULT: Using the high/low exposure approach, in subjects aged 20-59 years residing in the high exposure area a significant excess of hospitalization was observed in males and a non-significant excess in females. No excesses were observed in subjects aged 60 years and over. The analysis by the modeling approach did not show a significant association with the greatest pollution impact area. CONCLUSION: Due to the excesses of hospitalization observed in the high/low exposure approach, a continuing epidemiological surveillance of residents and occupational groups is warranted.

Incidence of Breast, Prostate, Testicular, and Thyroid Cancer in Italian Contaminated Sites with Presence of Substances with Endocrine Disrupting Properties.

The aim of the present study was to investigate the incidence of breast (females), prostate, testicular, and thyroid cancer in the Italian National Priority Contaminated Sites (NPCSs), served by cancer registries, where the presence of endocrine disruptors (EDs), reported to be linked to these tumours, was documented. Evidence of carcinogenicity of EDs present in NPCSs was assessed based on evaluation by international scientific institutions and committees. Standardized Incidence Ratios (SIRs) were computed for each NPCS and cancer site between 1996 and 2005. Excess incidence of one or more cancer site studied was found in twelve out of fourteen NPCSs. Significantly increased SIRs were found for breast cancer in eight NPCSs, for prostate cancer in six, for thyroid cancer (both gender) in four, and for testicular cancer in two. Non-significantly increased SIRs were found in five NPCSs for testicular cancer and in two for thyroid cancer (males). In a small number of instances a significant deficit was reported, mainly for thyroid and prostate cancer. Although increased incidence of one or more cancer sites studied were found in several NPCSs, the ecological study design and the multifactorial aetiology of the considered tumours do not permit concluding causal links with environmental contamination. Regarding the observation of some excesses in SIRs, continuing epidemiological surveillance is warranted.

Comprehensive Analysis of the 16p11.2 Deletion and Null Cntnap2 Mouse Models of Autism Spectrum Disorder.

Autism spectrum disorder comprises several neurodevelopmental conditions presenting symptoms in social communication and restricted, repetitive behaviors. A major roadblock for drug development for autism is the lack of robust behavioral signatures predictive of clinical efficacy. To address this issue, we further characterized, in a uniform and rigorous way, mouse models of autism that are of interest because of their construct validity and wide availability to the scientific community. We implemented a broad behavioral battery that included but was not restricted to core autism domains, with the goal of identifying robust, reliable phenotypes amenable for further testing. Here we describe comprehensive findings from two known mouse models of autism, obtained at different developmental stages, using a systematic behavioral test battery combining standard tests as well as novel, quantitative, computer-vision based systems. The first mouse model recapitulates a deletion in human chromosome 16p11.2, found in 1% of individuals with autism. The second mouse model harbors homozygous null mutations in Cntnap2, associated with autism and Pitt-Hopkins-like syndrome. Consistent with previous results, 16p11.2 heterozygous null mice, also known as Del(7Slx1b-Sept1)4Aam weighed less than wild type littermates displayed hyperactivity and no social deficits. Cntnap2 homozygous null mice were also hyperactive, froze less during testing, showed a mild gait phenotype and deficits in the three-chamber social preference test, although less robust than previously published. In the open field test with exposure to urine of an estrous female, however, the Cntnap2 null mice showed reduced vocalizations. In addition, Cntnap2 null mice performed slightly better in a cognitive procedural learning test. Although finding and replicating robust behavioral phenotypes in animal models is a challenging task, such functional readouts remain important in the development of therapeutics and we anticipate both our positive and negative findings will be utilized as a resource for the broader scientific community.

Incidence of soft tissue sarcomas in an Italian area affected by illegal waste dumping sites.

The aim of the present study was to investigate the possible association between occurrence of soft tissue sarcomas (STS) and residence in an Italian area affected by illegal practices of dumping and setting fire to both hazardous and solid urban wastes. Standardized incidence ratios (SIRs) were computed separately for STS and some specific STS subtypes. The analysis was performed for the total population and for specific age groups, namely, children, adolescents, and adults. In adults, no significant increase in STS was found other than for gastrointestinal stromal tumors in males. A nonsignificant increase in incidence of STS was observed for male children and female adolescents. The results of the present study do not allow conclusions for a causal association. In the absence of previous epidemiological studies on this issue, further investigations are needed.

Guglielmo Riva (1627-1677) and the end of hepatocentrism: a 17th-century painting.

During the seventeenth century, the description of the lymphatic system provided a decisive contribution to resolving the misconceptions of Galenic physiology concerning the production of blood in the liver. The transition from a liver-centered (hepatocentrism) to a heart-centered model (cardiocentrism) was fundamental in the history of medicine, since it allowed the role of the liver and of the heart in the bodily processes to be more correctly identified. The modification of the medical knowledge on the liver and its functions during that period is well represented in a 17th-century painting,"ll Fegato" ("The Liver"), probably belonging to the "anatomical museum" of the Roman surgeon Giovanni Guglielmo Riva (1627-1677). In particular, this Italian physician significantly contributed to the discovery of the lymphatic system and to the study of the hematopoiesis. Thus, this painting as well as the figure of Guglielmo Riva would deserve a major consideration in the history of medicine and of hepatology in particular.

Ecological studies of cancer incidence in an area interested by dumping waste sites in Campania (Italy).

Cancer incidence was investigated in an area which has been affected by the illegal practices of dumping hazardous waste and setting fire to mismanaged waste. For the 35 municipalities of this area that are served by a Cancer Registry, municipal standardized incidence ratios (SIR) and hierarchical Bayesian estimators (BIR) were computed. Moreover, municipal spatial clustering and a Poisson regression by municipality index of waste-related exposure were performed for 10 cancer types. Increased municipality SIRs were found for some cancer types. The BIRs confirmed the increases for liver cancer in two municipalities. Statistically significant clusters were detected for liver, lung, leukaemia and soft tissue sarcomas. In the regression analysis, testis cancer showed significant trend with the index of waste-related exposure (RR = 1.18).

No evidence of increased risk of soft tissue sarcomas in the neighborhood of a steel foundry in Verona.

The aim of the present study was to evaluate the possible association between occurrence of soft tissue sarcomas in Verona (Italy) and residence near a steel foundry, whose emissions of dioxin-like compounds may be relevant. Exposure to total suspended particulate (TSP) emitted from the plant as estimated by ADMS-urban dispersion model was used as an indirect index of exposure to dioxin-like compounds. Verona municipality was divided in six subareas according to the decreasing levels of estimated TSP exposure, and soft tissue sarcomas cases were mapped according to residence at time of diagnosis. Standardized incidence ratios were computed. No statistically significant departures between observed and expected cases were detected as illustrated by trend-test results.

Multidrug-resistant commensal Escherichia coli in children, Peru and Bolivia.

Using a rapid screening method, we investigated the prevalence of fecal carriage of antimicrobial drug-resistant Escherichia coli in 3,174 healthy children from 4 urban settings in Peru and Bolivia. High resistance rates were observed for ampicillin (95%), trimethoprim-sulfamethoxazole (94%), tetracycline (93%), streptomycin (82%), and chloramphenicol (70%). Lower resistance rates were observed for nalidixic acid (35%), kanamycin (28%), gentamicin (21%), and ciprofloxacin (18%); resistance to ceftriaxone and amikacin was uncommon (<0.5%). In a random sample of 1,080 resistant E. coli isolates, 90% exhibited a multidrug-resistance (MDR) phenotype. The 2 most common MDR phenotypes (ampicillin/tetracycline/trimethoprim-sulfamethoxazole and ampicillin/tetracycline/trimethoprim-sulfamethoxazole/chloramphenicol) could be transferred en bloc in conjugation experiments. The most common acquired resistance genes were blaTEM, tet(A), tet(B), drfA8, sul1, sul2, and catI. These findings underscore the magnitude of the problem of antimicrobial drug resistance in low-resource settings and the urgent need for surveillance and control of this phenomenon.