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Abstract Waste is part of the agenda of the European Environment and Health Process and included among the topics of the Sixth Ministerial Conference on Environment and Health. Disposal and management of hazardous waste are worldwide challenges. We performed a systematic review to evaluate the evidence of the health impact of hazardous waste exposure, applying transparent and a priori defined methods. The following five steps, based on pre-defined systematic criteria, were applied. 1. Specify the research question, in terms of “Population-Exposure-Comparators-Outcomes” (PECO). Population: people living near hazardous waste sites; Exposure: exposure to hazardous waste; Comparators: all comparators; Outcomes: all diseases/health disorders. 2. Carry out the literature search, in Medline and EMBASE. 3. Select studies for inclusion: original epidemiological studies, published between 1999 and 2015, on populations residentially exposed to hazardous waste. 4. Assess the quality of selected studies, taking into account study design, exposure and outcome assessment, confounding control. 5. Rate the confidence in the body of evidence for each outcome taking into account the reliability of each study, the strength of the association and concordance of results. Fifty-seven papers of epidemiological investigations on the health status of populations living near hazardous waste sites were selected for the evidence evaluation. The association between 95 health outcomes (diseases and disorders) and residential exposure to hazardous waste sites was evaluated. Health effects of residential hazardous waste exposure, previously partially unrecognized, were highlighted. Sufficient evidence was found of association between exposure to oil industry waste that releases high concentrations of hydrogen sulphide and acute symptoms. The evidence of causal relationship with hazardous waste was defined as limited for: liver, bladder, breast and testis cancers, non-Hodgkin lymphoma, asthma, congenital anomalies overall and anomalies of the neural tube, urogenital, connective and musculoskeletal systems, low birth weight and pre-term birth; evidence was defined as inadequate for the other health outcomes. The results, although not conclusive, provide indications that more effective public health policies on hazardous waste management are urgently needed. International, national and local authorities should oppose and eliminate poor, outdated and illegal practices of waste disposal, including illegal transboundary trade, and increase support regulation and its enforcement.

High LDL-cholesterol (LDL-C) characterizes familial hypercholesterolemia (FH) and familial combined hyperlipidemia (FCH). LDL-apheresis, used in these patients to reduce LDL-C levels, has been shown to also affect HDL levels and composition. We studied LDL-apheresis effects on six FH and nine FCH subjects’ serum capacity to modulate cellular cholesterol efflux, an index of HDL functionality, and to load macrophages with cholesterol. Serum cholesterol efflux capacity (CEC) and macrophage cholesterol loading capacity (CLC) were measured before, immediately after, and two days after LDL-apheresis. The procedure reduced total cholesterol (TC), LDL-C, and apoB plasma levels (−69%, −80% and −74%, respectively), parameters only partially restored two days later. HDL-C and apoA-I plasma levels, reduced after LDL-apheresis (−27% and −16%, respectively), were restored to almost normal levels two days later. LDL-apheresis reduced serum aqueous diffusion (AD) CEC, SR-BI-CEC, and ABCA1-CEC. AD and SR-BI were fully restored whereas ABCA1-CEC remained low two days later. Sera immediately and two days after LDL-apheresis had a lower CLC than pre-LDL-apheresis sera. In conclusion, LDL-apheresis transiently reduces HDL-C levels and serum CEC, but it also reduces also serum capacity to deliver cholesterol to macrophages. Despite a potentially negative effect on HDL levels and composition, LDL-apheresis may counteract foam cells formation.

Background : Maxillar atrophy is a prevalent condition associated with diminished bone volume, which precludes the conventional placement of dental implants. Sinus floor lift is a surgical procedure that aims to address this atrophy through the insertion of a graft within the sinus cavity. A multitude of techniques have been documented in the international literature for the management of the sinus bone window, though each approach has its own set of advantages and disadvantages. Methods : The present study is a retrospective analysis of traditional sinus floor lift surgery, comparing the outcomes of two surgical approaches: placement of a collagen membrane over the maxillary lateral bone window with or without bone tacks. The study enrolled a total of 48 consecutive patients. Twenty-four patients underwent sinus floor lift surgery, with the placement of a collagen membrane over the maxillary lateral bone window without bone tacks (control group). The remaining 24 patients underwent the same procedure, but with bone tacks (study group). All patients received an amoxicillin 875 mg + clavulanic acid 125 mg administration for six days and underwent Cone Beam Computed Tomography (CBCT) before the sinus floor lift surgery and six months later before the implant surgery. The parameters measured on the preoperative Cone Beam Computed Tomography (CBCT) scan included residual bone, the preoperative thickness of the lateral bone in the center, and the distance between the lateral wall and the medial wall of the sinus. Only the bone height increment was measured on the postoperative CBCT scan. Postoperative complications and the visual analogue scale (VAS) score were also recorded. A statistical analysis was performed, and the correlation between the parameters was evaluated using Pearson's correlation coefficient. A comparison of the mean of the parameters between the treatment group and the control group was conducted using the t -test. Results and Conclusions : The study group was found to have superior outcomes in terms of bone height increment ( p = 0.001) and VAS after 7 days ( p = 0.11) compared to the control group. The novel application of bone tacks on the collagen membrane over the bone window following sinus elevation surgery was associated with superior outcomes in terms of bone height and reduced pain at seven days, as measured by the VAS, with no postoperative complications.

Objective: The aim of this study was to compare the efficacy of voice therapy combined with standard anti-reflux therapy in reducing symptoms and signs of laryngopharyngeal reflux (LPR)., Methods: A randomised clinical trial was conducted. Fifty-two patients with LPR diagnosed by 24 h multichannel intraluminal impedance-pH monitoring were randomly allocated in two groups: medical treatment (MT) and medical plus voice therapy (VT). Clinical symptoms and laryngeal signs were assessed at baseline and after 3 months of treatment with the Reflux Symptom Index (RSI), Reflux Finding Score (RFS), Voice Handicap Index (VHI) and GRBAS scales., Results: Groups had similar scores at baseline. At 3-month follow-up, a significant decrease in RSI and RFS total scores were found in both groups although it appeared to be more robust in the VT group. G and R scores of the GRBAS scale significantly improved after treatment in both groups, with better results in the VT group. The VHI total score at 3 months improved more in the VT group (VHI delta 9.54) than in the MT group (VHI delta 5.38) (p < 0.001)., Conclusions: The addition of voice therapy to medications and diet appears to be more effective in improving treatment outcomes in subjects with LPR. Voice therapy warrants consideration in addition to medication and diet when treating patients with LPR., (Copyright © 2024 Società Italiana di Otorinolaringoiatria e Chirurgia Cervico-Facciale, Rome, Italy.)

Background: Atmospheric pollution has been recognized as the greatest environmental threat to human health. The population of the Venafro Valley, southern Italy, is exposed to emissions from a Waste-To-Energy (WTE) and a cement plant and potentially also to another WTE located in the neighboring region of Lazio; also, the vehicular atmospheric pollution situation is critical. In order to assess the environmental health risk of residents in eight municipalities of the Venafro Valley, a retrospective residential cohort study during 2006-2019 was carried out., Methods: Four exposure classes were defined by natural-break method, using a dispersion map of nitrogen dioxides (chosen as proxy of industrial pollution). The association between the industrial pollution and cause-specific mortality/morbidity of the cohort was calculated using the Hazard Ratio (HR) through a multiple time-dependent and sex-specific Cox regression adjusting for age, proximity to main roads and socio-economic deprivation index., Results: Results showed, for both sexes, mortality and morbidity excesses in the most exposed class for diseases of the circulatory system and some signals for respiratory diseases. Particularly, mortality excesses in both sexes in class 3 for diseases of the circulatory system [men: HR = 1.37 (1.04-1.79); women: HR = 1.27 (1.01-1.60)] and for cerebrovascular diseases [men: HR = 2.50 (1.44-4.35); women: HR = 1.41 (0.92-2.17)] were observed and confirmed by morbidity analyses. Mortality excesses for heart diseases for both sexes [men-class 3: HR = 1.32 (0.93-1.87); men-class 4: HR = 1.95 (0.99-3.85); women-class 3: HR = 1.49 (1.10-2.04)] and for acute respiratory diseases among women [HR = 2.31 (0.67-8.00)] were observed. Morbidity excesses in both sexes for ischemic heart diseases [men-class 3: HR = 1.24 (0.96-1.61); women-class 4: HR = 2.04 (1.04-4.02)] and in class 4 only among men for respiratory diseases [HR = 1.43 (0.88-2.31)] were also found., Conclusions: The present study provides several not-negligible signals indicating mitigation actions and deserve further investigations. For future studies, the authors recommend enriching the exposure and lifestyle profile using tools such as questionnaires and human biomonitoring., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objective: The aim of this study was to adapt and validate the Italian version of the singing Voice Handicap Index-10 (SVHI-10-IT)., Methods: 99 Italian singers were enrolled in the study. All subjects underwent videolaryngostroboscopic examination and were asked to fill out the self-reported 10-item SVHI-10-IT. Laryngostroboscopic examination was pathological in 56 subjects (study group) (56.6%), while it was normal in the remaining 43 singers (control group) (43.4%). Dimensionality, test retest and internal validity for SVHI-10-IT were performed. Videolaryngostroboscopy was used as gold-standard for external validity., Results: The items of SVHI-10-IT were uni-dimensional and Cronbach's α was 0.853 (95% CI = 0.805-0.892). High and comparable area under curve (AUC:0.93 95% CI = 0.88-0.98) values indicate a good ability of the scale to distinguish between the study and control groups. Based on balanced sensitivity (Se = 83.9%) and specificity (Sp = 86.0%), the optimal cut-off score for a singer's perceived voice handicap was 12., Conclusions: The SVHI-10-IT is a reliable and valid instrument to evaluate the self-reported singing voice handicap among singers. It can also be used as a quick screening tool since a score higher than 12 is indicative of a problematic voice as perceived by singers., (Copyright © 2023 Società Italiana di Otorinolaringoiatria e Chirurgia Cervico-Facciale, Rome, Italy.)

Nonalcoholic fatty liver disease (NAFLD)-associated liver fibrosis is likely related to coronary artery disease (CAD) by the mediation of systemic inflammation. This study aimed at evaluating the predictive value of neutrophil-to-lymphocyte-ratio (NLR) and fibrosis-4 index (FIB-4), indices of inflammation and fibrosis, respectively, on CAD mortality. Data from 1460 CAD patients (1151 males, age: 68 ± 10 years, mean ± SD) were retrospectively analyzed. Over a median follow-up of 26 months (interquartile range (IQR) 12−45), 94 deaths were recorded. Kaplan−Meier survival analysis revealed worse outcomes in patients with elevation of one or both biomarkers (FIB-4 > 3.25 or/and NLR > 2.04, log-rank p-value < 0.001). In multivariate Cox regression analysis, the elevation of one biomarker (NLR or FIB-4) still confers a significant independent risk for mortality (hazard ratio (HR) = 1.7, 95% confidence interval (95% CI): 1.1−2.7, p = 0.023), whereas an increase in both biomarkers confers a risk corresponding to HR = 3.5 (95% CI: 1.6−7.8, p = 0.002). Categorization of patients with elevated FIB-4/NLR could provide valuable information for risk stratification and reduction of residual risk in CAD patients.

Oxidative stress and inflammation are key factors in cardiometabolic diseases. We set out to evaluate the relationship between serum uric acid (UA) and the neutrophil-to-lymphocyte ratio (NLR) with cardiometabolic risk factors in coronary artery disease (CAD) patients, and their additive and multiplicative interactive effects on outcomes (cardiac death/CD and hard events (HE)-death plus reinfarction). A total of 2712 patients (67 ± 11 years, 1960 males) who underwent coronary angiography was retrospectively analyzed and categorized into no-CAD patients ( n =806), stable-CAD patients ( n =1545), and patients with acute myocardial infarction (AMI) ( n =361). UA and NLR were reciprocally correlated and associated with cardiometabolic risk factors. During a mean follow-up period of 27 ± 20 months, 99-3.6% deaths, and 213-7.8% HE were registered. The Kaplan-Meier survival estimates showed significantly worse outcomes in patients with elevated UA or NLR levels. Multivariate Cox regression analysis demonstrated that NLR independently predicted CD and HE. There was no multiplicative interaction between UA and NLR; however, the use of measures of additive interaction evidenced a positive additive interaction between UA and NLR for CD and HE. Although it is clear that correlation does not imply causation, the coexistence of NRL and UA appears to have a synergistic effect, providing further information for the risk stratification of CAD patients., Competing Interests: The authors declare no conflicts of interest.

Geothermal fluids for electricity and heat production have long been exploited in the Mt. Amiata area (Tuscany, Italy). Public concern about the health impact of geothermal plants has been present from the outset. Several factors influence the way people perceive risk; therefore, the objective of the present research is to develop indicators of risk perception and assess indices differences in relation to some questionnaire variables. A cross-sectional survey was conducted in the Amiata area on 2029 subjects aged 18-77. From the questionnaire section about risk perception from environmental hazards, four indicators were developed and analysed. A total of 64% of the subjects considered the environmental situation to be acceptable or excellent, 32% serious but reversible, and 4% serious and irreversible; as the values of the various perception indicators increased, an upward trend was observed in the averages. Risk perception was higher among women and young people, and was associated with higher education. Those who smelled bad odours in their surroundings reported higher risk perception. Furthermore, risk perception was higher in four municipalities. The results represent the basis for further investigations to analyse the link among risk perception indicators, exposure parameters, and health status.

Environmental noise can induce detrimental health effects such as cardiovascular disease (CVD). The relationship between vehicular traffic noise pollution and CVD was investigated through a retrospective residential cohort study in the city of Pisa. Four exposure classes were defined for noise pollution, using noise propagation maps. The association between noise exposures and cause-specific mortality or hospitalization of the subjects of the cohort was calculated using the hazard ratio (HR) for night and day through a multiple time-dependent and sex-specific Cox regression adjusting for age, the socio-economic deprivation index, and traffic air pollution. Mortality excess for CVD and risk trends for a 1 decibel noise increment were observed among the most exposed women (mortality: HRnight class4 1.15 (1.03-1.28); Trend night 1.007 (1.002-1.012); HRday class4 1.14 (1.02-1.27); Trend day 1.008 (1.003-1.013)), particularly for ischaemic disease (mortality: Trend night 1.008 (0.999-1.017); Trend day 1.009 (0.999-1.018)) and cerebrovascular disease (mortality: HRnight class3 1.23 (1.02-1.48), HRday class3 1.24 (1.03-1.49)). Hospitalization analyses confirm mortality results. A decreased risk for hospitalization was also observed among the most exposed men (HRday class4 0.94 (0.88-1.01), particularly for ischaemic disease (HRnight class4 0.90 (0.80-1.02); HRday class4 0.86 (0.77-0.97)) and cerebrovascular disease (HRnight class4 0.89 (0.78-1.01)). Authors recommend the adoption of prevention measures aimed at mitigating noise and the activation of a monitoring of the risk profile in the Pisa population updating both the residential cohort and health data.

In the province of Lecce (southern Italy), a higher incidence of lung cancer (LC) among men compared to regional and national data was reported. In a sub-area in the center of the province (cluster area), the incidence and mortality for LC was even higher. PROTOS is a case-control study aimed at investigating possible risk factors for LC in the province area. A total of 442 patients with LC and 1326 controls matched by sex and age living in the province of Lecce for at least 10 years were enrolled and georeferenced; they filled in a questionnaire with their personal information and exposures. For each risk factor, an Odds Ratio adjusted for all the other variables was calculated. The risk of LC increased with excessive use of alcohol in women, for those subjects with a family cancer history, for each increase in pack/year of cigarettes, for men more exposed considering the industrial district in the cluster area, and for those using pesticides in agriculture without wearing personal protective equipment. The higher incidence of adenocarcinoma in both sexes suggests that, in addition to cigarette smoking, concurrent exposures to other environmental, occupational, and life-style factors may play a role in increased cancer risk and should be more deeply explored.

Risk perception (RP) evaluation during pregnancy and its relationship with lifestyles are considered useful tools for understanding communities living in high-risk areas and preventing dangerous exposure. It is well known that exposure to pollutants and less-healthy lifestyles may result in increased disease occurrence during life. Our work investigated environmental RP through ad hoc questionnaires administered to 611 mothers within the NEHO birth cohort, recruited in three heavily contaminated areas of Southern Italy. Four different RP indices, an exploratory factorial analysis (EFA), and a latent class analysis were evaluated from questionnaires. The highest values of risk perception index were observed in the Milazzo site (0.64 ± 0.16) and the lowest in the Crotone site (0.5 ± 0.18). EFA revealed four latent factors, including different items describing environmental pollution, and subjects were classified into four latent classes with different RP indices. Significant RP profiles were different among the sites ( p < 0.001). Our results did not demonstrate any association between RP and lifestyles during pregnancy. Improving healthy lifestyle behaviours, particularly in polluted areas, would generate co-benefits by preventing further risk factors. As remediation interventions can take a long time, it needs to improve healthy lifestyles in residents until remediation is completed.

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.

Purpose: Robotic assistance could increase the rate of ileo-colic intra-corporeal anastomosis (ICA) during robotic right colectomy (RRC). However, although robotic ICA can be accomplished with several different technical variants, it is not clear whether some of these technical details should be preferred. An evaluation of the possible advantage of one respect to another would be useful., Methods: We conducted a systematic review of literature on technical details of robotic ileo-colic ICA, from which we performed a meta-analysis of clinical outcomes. The extracted data allowed a comparative analysis regarding the outcome of overall complication (OC), bleeding rate (BR) and leakage rate (LR), between (1) mechanical anastomosis with robotic stapler, versus laparoscopic stapler, versus totally hand-sewn anastomosis and (2) closure of enterocolotomy with manual double layer, versus single layer, versus stapled., Results: A total of 30 studies including 2066 patients were selected. Globally, the side-to-side, isoperistaltic anastomosis, realized with laparoscopic staplers, and double-layer closure for enterocolotomy, is the most common technique used. According to the meta-analysis, the use of robotic stapler was significantly associated with a reduction of the BR with respect to mechanical anastomosis with laparoscopic stapler or totally hand-sewn anastomosis. None of the other technical aspects significantly influenced the outcomes., Conclusions: ICA fashioning during RRC can be accomplished with several technical variants without evidence of a clear superiority of anyone of these techniques. Although the use of robotic staplers could be associated with some benefits, further studies are necessary to draw conclusions.

Chronic arsenic (As) exposure is a critical public health issue. The As metabolism can be influenced by many factors. The objective of this study is to verify if these factors influence As metabolism in four Italian areas affected by As pollution. Descriptive analyses were conducted on 271 subjects aged 20-49 in order to assess the effect of each factor considered on As methylation. Percentages of metabolites of As in urine, primary and secondary methylation indexes were calculated as indicators for metabolic capacity. The results indicate that women have a better methylation capacity (MC) than men, and drinking As-contaminated water from public aqueducts is associated with poorer MC, especially in areas with natural As pollution. In areas with anthropogenic As pollution occupational exposure is associated with a higher MC while smoking with a poorer MC. Dietary habits and genetic characteristics are probably implicated in As metabolism. BMI, alcohol consumption and polymorphism of the AS3MT gene seem not to influence As MC. Arsenic metabolism may be affected by various factors and in order to achieve a comprehensive risk assessment of As-associated disease, it is crucial to understand how these factors contribute to differences in As metabolism.

Introduction: Environmental pollution has been progressively becoming one of the main risk factors to human diseases. In particular, populations living in high-contaminated sites are particularly exposed to environmental toxicants, with consequent increased risks to human health. In Italy, there are currently ongoing three epidemiological etiological studies aimed at evaluating the association between exposure to inorganic and organic chemicals and presence of biological markers of early effects in population living in three National Priority Contaminated Sites (NPCSs). Specifically, the correlations concern preclinical indicators of liver disease in Priolo NPCS, thyroid diseases in Milazzo-Valle del Mela NPCS and cardiovascular risk and kidney damage in Crotone NPCS., Methods and Analysis: Overall, approximately 1300 subjects of both sexes will be enrolled in the three NPCSs according to specific inclusion criteria. For each subject, serum and urine specimens are collected, on which the determination of biological markers of exposure and early effects for the selected outcomes are performed. Individual information on environmental and occupational exposure, medical history, diet and life habits is obtained through questionnaires provided by web platform. In Milazzo-Valle del Mela and Crotone NPCSs, not invasive instrumental and imaging examinations are performed in order to evaluate further risk factors of thyroid carcinoma and cardiovascular disease, respectively., Ethics and Dissemination: The protocol studies have been approved by the Ethics Committees responsible for the three involved NPCSs: the Ethics Committee 'Catania 2' for the NPCS of Priolo (21 July 2017, n. 500/2017/CECT2), the Ethics Committee of the University Hospitals of Messina for the NPCS of Milazzo-Valle del Mela (19 February 2018, n.2/2018); the Ethics Committee of the Region of Calabria for the NPCS of Crotone (20 July 2017, n. 174). Results will be disseminated among policy-makers, citizens, stakeholders and scientific community through the organisation of conferences and events, and the publication on international peer/reviewed journals., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

In the present research, we evaluated the health effects of exposure to the municipal waste incinerator (MWI) in Pisa, Italy, through a population-based cohort design. The individual exposure pattern in the area was estimated through CALPUFF dispersion models of NO χ (developed by Atmospheric Studies Group Earth Tech, Lowell, Massachusetts), used as pollution proxies of the MWI and the relevant industrial plant, and through land-use regression for NO χ due to traffic pollution. Using Cox regression analysis, hazard ratios (HR) were estimated adjusting for exposure to other sources of pollution, age, and socioeconomic deprivation. An adjusted linear trend of HR (HRt) over the categories of exposure, with the relative 95% CI and p-value, was also calculated. Mortality and hospital discharge were studied as impact outcomes. Mortality analysis on males showed increased trends of mortality due to natural causes (HRt p < 0.05), the tumor of the lymphohematopoietic system (HRt p = 0.01), cardiovascular diseases (HRt p < 0.01); in females, increased trends for acute respiratory diseases (HRt p = 0.04). Morbidity analysis showed a HRt for lymphohematopoietic system tumor in males (HRt p = 0.04). Some of the excesses are in agreement with previous evidence on the health effects of MWIs, although the observation in males but not in females, suggests a cautious interpretation. Confounding due to other sources of exposure cannot be ruled out. The evidence was considered important in the decision-making process of the waste cycle.

Exposure to air pollution has been shown to increase the risk of developing chronic respiratory diseases. The largest crude oil first treatment plant in Italy emits harmful polluting substances. This cross-sectional study assesses the occurrence of respiratory symptoms in a sample of the adult population living near the plant. A proximal and a reference area were defined in order to recruit 200 subjects. Each subject performed a spirometry test and completed a questionnaire. Associations between the distance from the plant and selected respiratory outcomes were assessed (distance-based approach). The prevalence of outcomes between a proximal and a reference area (area-based approach) were also compared. Odds ratios were adjusted for potential confounders. Living near the plant was associated with a higher prevalence of respiratory symptoms, with significant associations for severe dyspnoea equivalent to the halving of risk as the distance of residence from the plant increased by 1 km (adjusted odds ratio (OR) 0.48, confidence interval at the 95% probability level (95% CI): 0.25⁻0.92). Several signals emerged for respiratory allergic symptoms. The area-based approach generally confirmed the results obtained with the distance-based approach. This is the first study to be carried out on a crude oil first treatment plant aimed at assessing the association with the occurrence of respiratory symptoms. These findings contribute to the evidence supporting the need for a space⁻time surveillance system in the investigated area.

Arsenic is ubiquitous and has a potentially adverse impact on human health. We compared the distribution of concentrations of urinary inorganic arsenic plus methylated forms (uc(iAs+MMA+DMA)) in four Italian areas with other international studies, and we assessed the relationship between uc(iAs+MMA+DMA) and various exposure factors. We conducted a human biomonitoring study on 271 subjects (132 men) aged 20-44, randomly sampled and stratified by area, gender, and age. Data on environmental and occupational exposure and dietary habits were collected through a questionnaire. Arsenic was speciated using chromatographic separation and inductively coupled mass spectrometry. Associations between uc(iAs+MMA+DMA) and exposure factors were evaluated using the geometric mean ratio (GMR) with a 90% confidence interval by stepwise multiple regression analysis. The 95th percentile value of uc(iAs+MMA+DMA) for the whole sample (86.28 µg/L) was higher than other national studies worldwide. A statistical significant correlation was found between uc(iAs+MMA+DMA) and occupational exposure (GMR: 2.68 [1.79-4.00]), GSTT gene (GMR: 0.68 [0.52-0.80]), consumption of tap water (GMR: 1.35 [1.02-1.77]), seafood (GMR: 1.44 [1.11-1.88]), whole milk (GMR: 1.34 [1.04-1.73]), and fruit/vegetables (GMR: 1.37 [1.03-1.82]). This study demonstrated the utility of uc(iAs+MMA+DMA) as a biomarker to assess environmental exposure. In a public health context, this information could be used to support remedial action, to prevent individuals from being further exposed to environmental arsenic sources., Competing Interests: The authors declare no conflict of interest.

The effects of noise on students' health, well-being, and learning are of growing concern among both the general public and policy-makers in Europe. Several studies have highlighted the consequences of noise on children's learning and performance at school. This study investigates the relationship between noise judgment in school goers aged 11-18 and noise measurements aimed at evaluating their exposure at school. For this purpose, a questionnaire was administered to 521 individuals in 28 classrooms in eight schools of four cities in Italy, with different environmental characteristics. Using a Likert-type scale, a selected set of responses related to noise generated an Annoyance Index (AI) score for each student and a classroom median score (MAI). From the noise data acquired, a global noise score (GNS) was assigned to each classroom. A higher AI was found in industrialized areas and among younger students. No significant differences in noise judgment were found by gender. A significant inverse correlation was described between MAI and GNS, thus the better the acoustic quality of the classrooms, the less the perceived noise and annoyance. The results show that noise perception and consequent disturbance are highly correlated with classroom acoustics, and confirm that annoyance represents the most widespread subjective response to noise., Competing Interests: The authors declare no conflict of interest.

Waste is part of the agenda of the European Environment and Health Process and included among the topics of the Sixth Ministerial Conference on Environment and Health. Disposal and management of hazardous waste are worldwide challenges. We performed a systematic review to evaluate the evidence of the health impact of hazardous waste exposure, applying transparent and a priori defined methods. The following five steps, based on pre-defined systematic criteria, were applied. 1. Specify the research question, in terms of "Population-Exposure-Comparators-Outcomes" (PECO)., Population: people living near hazardous waste sites; Exposure: exposure to hazardous waste; Comparators: all comparators; Outcomes: all diseases/health disorders. 2. Carry out the literature search, in Medline and EMBASE. 3. Select studies for inclusion: original epidemiological studies, published between 1999 and 2015, on populations residentially exposed to hazardous waste. 4. Assess the quality of selected studies, taking into account study design, exposure and outcome assessment, confounding control. 5. Rate the confidence in the body of evidence for each outcome taking into account the reliability of each study, the strength of the association and concordance of results.Fifty-seven papers of epidemiological investigations on the health status of populations living near hazardous waste sites were selected for the evidence evaluation. The association between 95 health outcomes (diseases and disorders) and residential exposure to hazardous waste sites was evaluated. Health effects of residential hazardous waste exposure, previously partially unrecognized, were highlighted. Sufficient evidence was found of association between exposure to oil industry waste that releases high concentrations of hydrogen sulphide and acute symptoms. The evidence of causal relationship with hazardous waste was defined as limited for: liver, bladder, breast and testis cancers, non-Hodgkin lymphoma, asthma, congenital anomalies overall and anomalies of the neural tube, urogenital, connective and musculoskeletal systems, low birth weight and pre-term birth; evidence was defined as inadequate for the other health outcomes. The results, although not conclusive, provide indications that more effective public health policies on hazardous waste management are urgently needed. International, national and local authorities should oppose and eliminate poor, outdated and illegal practices of waste disposal, including illegal transboundary trade, and increase support regulation and its enforcement.

Introduction: The limited scientific knowledge on the relationship between exposure and health effects in relation to geothermal activity motivated an epidemiologic investigation of Tuscan geothermal area., Aim: This study aims at describing mortality of populations living in Tuscan municipalities in the period 2003-2012., Method: Sixteen municipalities were included in the study area: eight in the northern and eight in the southern area. Mortality data come from the Regional Mortality Registry of Tuscany. Fifty-four causes of death, considered of interest for population health status or consistent with "Project SENTIERI" criteria, are analyzed., Results: Results show a worse mortality profile in the southern area, especially in males, for whom excesses of all cancers and some causes of cancer emerge, while in the northern area an excess of cerebrovascular diseases among females merits attention. Further and more appropriate studies are needed to clarify the etiology of some diseases and to better assess a potential cause-effect relationship.

The health impact on populations residing in industrially contaminated sites (CSs) is recognized as a public health concern especially in relation to more vulnerable population subgroups. The aim of this study was to estimate the risk of congenital anomalies (CAs) in Italian CSs. Thirteen CSs covered by regional CA registries were investigated in an ecological study. The observed/expected ratios (O/E) with 90% confidence intervals (CI) for the total and specific subgroups of CAs were calculated using the regional areas as references. For the CSs with waste landfills, petrochemicals, and refineries, pooled estimates were calculated. The total number of observed cases of CAs was 7085 out of 288,184 births (prevalence 245.8 per 10,000). For some CSs, excesses for several CA subgroups were observed, in particular for genital and heart defects. The excess of genital CAs observed in Gela (O/E 2.36; 90% CI 1.73-3.15) is consistent with findings from other studies. For CSs including petrochemical and landfills, the pooled risk estimates were 1.10 (90% CI 1.01-1.19) and 1.07 (90% CI 1.02-1.13), respectively. The results are useful in identifying priority areas for analytical investigations and in supporting the promotion of policies for the primary prevention of CAs. The use of short-latency effect indicators is recommended for the health surveillance of the populations residing in CSs.

Introduction: The association between reproductive health outcomes and exposure to municipal solid waste incinerators (MSWIs) is inconclusive. This study investigates the association between exposure to a MSWI and various reproductive outcomes (preterm birth, low birth weight, small for gestational age, and sex ratio), taking into account other sources of pollution (industrial plants, highway, major roads with high traffic flows) and maternal factors, including the socioeconomic status., Methods: PM10 concentration maps were used for the exposure assessment to the MSWI and to other sources of pollution in the study area. Information on resident births and maternal covariates were selected from the delivery certificates referred to the period 2001-2010. Mothers' addresses were geocoded in order to attribute the individual level of exposure. Odds ratios (ORs) with a 95% confidence interval (CI) adjusted for maternal covariates and exposure to other pollution sources were calculated., Results: A total of 3153 newborns to 2401 mothers residing in area during the study period were analyzed. A risk of preterm birth associated with increased exposure was detected (OR = 1.61; 95% CI: 0.88-2.94; p test for trend 0.098). When newborns to primiparous women were considered an OR of 2.18 (95% CI: 1.05-4.53) and a significant trend were observed (p = 0.033). No significant results for the other investigated outcomes were observed., Conclusions: The study detected a slight association between exposure at MSWI and preterm births. The results are in agreement with those of a previous multi-site study with similar design, and they strengthen the recommendation to consider gestational age in studies and surveillance in areas with MSWIs and similar sources of pollution.

A human biomonitoring (HBM) survey in four areas affected by natural or anthropogenic arsenic pollution was conducted in Italy within the framework of the SEpiAs project. A questionnaire, including the exploration of risk perception (RP) regarding environmental hazards and access to and trust in information, was administered to 282 subjects stratified by area, gender and age. The survey was designed to investigate how populations living in polluted areas could adopt prevention-oriented habits, fostered by the awareness of existing risks and, in addition, how increased knowledge of RP and information flows could support researchers in identifying recommendations, and presenting and disseminating HBM results. This study characterizes the four areas in terms of RP and access to and trust in environmental information, and provides insights into the influence of RP and environmental information on food consumption. For the data analysis, a combined random forest (RF) and logistic regression approach was carried out. RF was applied to the variables derived from the questionnaire in order to identify the most important in terms of the aims defined. Associations were then tested using Fisher's exact test and assessed with logistic regression in order to adjust for confounders. Results showed that the perception of and personal exposure to atmospheric and water pollution, hazardous industries and waste, hazardous material transportation and waste was higher in geographical areas characterized by anthropogenic pollution. Citizens living in industrial areas appeared to be aware of environmental risks and had more confidence in environmental non-governmental organizations (NGOs) than in public authorities. In addition, they reported an insufficient circulation of information. Concerning the influence of RP and environmental information on food consumption, a high perception of personal exposure to atmospheric pollution and hazardous industries was associated with a lower consumption of local fish. In conclusion, different RPs and information flow patterns were observed in areas with arsenic of natural origin or in industrial contexts. These findings may be useful for targeted risk communication plans in support of risk-management strategies., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Arsenic-induced health effects may be associated with critically shortened telomeres. However, few data are available on the effects of arsenic exposure on telomere length. The aim of this study was to investigate the effects of chronic arsenic exposure on leukocyte telomere length (LTL) as well as the contribution of common polymorphisms in genes implicated in arsenic metabolism (GSTT1 and GSTM1) and DNA repair (hOGG1 and XRCC1). A group of 241 healthy subjects was enrolled from four areas of Italy known to be affected by natural or anthropogenic arsenic pollution. Urine samples were tested for inorganic As (iAs), monomethylarsinic (MMA) and dimethylarsinic acid (DMA). LTL was evaluated by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Genotyping was carried out by PCR-RFLP on leukocyte DNA. In multiple linear regression analysis, LTL was significantly and inversely correlated with age (β = -0.231, P = 0.006) and showed a certain trend toward significance with iAs urinary concentration (log10 iAs, β = -0.106, P = 0.08). The genotype distribution showed significant associations between GSTT1 and the As concentration (log10 iAs, P = 0.01) and metabolite patterns (log10 DMA, P = 0.05) in the urine. However, GST genes did not interact with arsenic exposure in the modulation of LTL. Conversely, the combined presence of a higher level of iAs + MMA + DMA ≥ 19.3 μg/l (F = 6.0, P interaction = 0.01), Asi ≥ 3.86 (F = 3.9, P interaction = 0.04) μg/l, iAs + MMA + DMA ≥ 15 μg/l (F = 4.2, P interaction = 0.04) and hOGG1 Cys allele was associated with a significantly lower LTL. An interaction between XRCC1 Arg399Gln and arsenic exposure was also observed (all P interaction = 0.04). These findings suggest that telomere shortening may represent a mechanism that contributes to arsenic-related disease. The interaction of hOGG1 and XRCC1 DNA repair polymorphisms and exposure enhances telomeric DNA damage. Future studies are warranted to understand better the epidemiologic impact of arsenic on telomere function as well as to identify the subgroups of exposed subjects who need better health surveillance., (© The Author 2016. Published by Oxford University Press on behalf of the UK Environmental Mutagen Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Modulation of frontal midline theta (fmθ) is observed during error commission, but little is known about the role of theta oscillations in correcting motor behaviours. We investigate EEG activity of healthy partipants executing a reaching task under variable degrees of prism-induced visuo-motor distortion and visual occlusion of the initial arm trajectory. This task introduces directional errors of different magnitudes. The discrepancy between predicted and actual movement directions (i.e. the error), at the time when visual feedback (hand appearance) became available, elicits a signal that triggers on-line movement correction. Analysis were performed on 25 EEG channels. For each participant, the median value of the angular error of all reaching trials was used to partition the EEG epochs into high- and low-error conditions. We computed event-related spectral perturbations (ERSP) time-locked either to visual feedback or to the onset of movement correction. ERSP time-locked to the onset of visual feedback showed that fmθ increased in the high- but not in the low-error condition with an approximate time lag of 200 ms. Moreover, when single epochs were sorted by the degree of motor error, fmθ started to increase when a certain level of error was exceeded and, then, scaled with error magnitude. When ERSP were time-locked to the onset of movement correction, the fmθ increase anticipated this event with an approximate time lead of 50 ms. During successive trials, an error reduction was observed which was associated with indices of adaptations (i.e., aftereffects) suggesting the need to explore if theta oscillations may facilitate learning. To our knowledge this is the first study where the EEG signal recorded during reaching movements was time-locked to the onset of the error visual feedback. This allowed us to conclude that theta oscillations putatively generated by anterior cingulate cortex activation are implicated in error processing in semi-naturalistic motor behaviours.

Preterm children have an increased risk of neurodevelopmental impairments which include psychomotor and language retardation. The objectives of the present retrospective cohort study were to examine the effects of an individually adapted, home-based, and family-centred early developmental habilitation program on neurodevelopmental and behavioural outcomes of very preterm children compared with a standard follow-up at 2 years' corrected age. Enrolled infants were retrospectively assigned to the intervention group (61 subjects) or to the control group (62 subjects) depending on whether they had or had not carried out a home-based family-centred early developmental habilitation program focused on environmental enrichment, parent-guided environmental interaction, and infant development. Developmental outcome was assessed for both groups at 24 months' corrected age using the Bayley Scales of Infant Development 2nd Edition. Intervention significantly improved both cognitive and behavioural outcomes. In addition, males had significantly lower scores than females either before or after treatment. However, the treatment was effective in both genders to the same extent. In conclusion, a timely updated environment suitable to the infant's developmental needs could provide the best substrate where the parent-infant relationship can be practised with the ultimate goal of achieving further developmental steps., Competing Interests: The authors declare that there is no conflict of interests regarding the publication of this paper.

Objectives: Adverse effects of waste management represent a public health issue. Mortality meta-analysis in Italian National Priority Contaminated Sites (NPCSs) with industrial waste landfills or illegal dumps is presented., Methods: 24 NPCSs include industrial waste landfills or illegal dumps. Class 1 (10 NPCSs with industrial waste landfills) and Class 2 (14 NPCSs with illegal dumps) were categorized. Random-effects model meta-analyses of Standardized Mortality Ratios non-adjusted (SMRs) and adjusted for Deprivation (DI-SMRs) computed for each CS (1995-2002) were performed for overall 24 NPCSs and the two classes. The North- Southern gradient was considered., Results: 24 CSs pooled-SMRs are significantly increased in both genders for cancer of liver (men: SMR=1.13; women: SMR=1.18), bladder (men: SMR=1.06; women: SMR=1.11), and for cirrhosis (men: SMR=1.09; women: SMR=1.13). In Class 2 the increase is confirmed in both genders for liver and bladder cancers and for cirrhosis and in men only for lung cancer. Congenital anomalies and adverse perinatal conditions are not increased., Conclusion: The results are consistent with the hypothesis of adverse health effects of non-adequately managed hazardous waste. Causal interpretation is not allowed, but the meta-analytic approach provides more confidence in the findings.

Unlabelled: Assessing the skeletal response to enzyme replacement therapy (ERT) in Gaucher disease (GD) is problematic. We investigated the reliability of (99m)Tc-sestamibi scintigraphy in monitoring changes in bone marrow involvement induced by ERT., Methods: In 52 GD patients, the efficacy of ERT on bone marrow disease was monitored using at least 2 sequential (99m)Tc-sestamibi scans; 17 patients were receiving ERT at enrollment, and 35 were ERT-naïve. We elaborated a dose-response model by statistical analysis based on linear mixed models., Results: Patients whose marrow disease improved had received a significantly higher ERT dose per month than patients who did not improve. Significantly more patients reached near-disappearance of marrow disease if their disease burden at enrollment had been lower and the duration of clinical signs shorter. The response of the marrow scintigraphic score was more pronounced in ERT-naïve patients. No relevant effect of ERT on marrow disease was observed until platelet count and splenomegaly had improved., Conclusion: Although based on localized evaluation, changes in the (99m)Tc-sestamibi score closely correlated with the main determinants of ERT, with a definite dose-response relationship. The threshold at which ERT induced any improvement in bone marrow disease was 35-36 U/kg/mo; in ERT-naïve patients, the scintigraphic score declined by 1 unit after ERT at 28 U/kg/mo.

High LDL-cholesterol (LDL-C) characterizes familial hypercholesterolemia (FH) and familial combined hyperlipidemia (FCH). LDL-apheresis, used in these patients to reduce LDL-C levels, has been shown to also affect HDL levels and composition. We studied LDL-apheresis effects on six FH and nine FCH subjects' serum capacity to modulate cellular cholesterol efflux, an index of HDL functionality, and to load macrophages with cholesterol. Serum cholesterol efflux capacity (CEC) and macrophage cholesterol loading capacity (CLC) were measured before, immediately after, and two days after LDL-apheresis. The procedure reduced total cholesterol (TC), LDL-C, and apoB plasma levels (-69%, -80% and -74%, respectively), parameters only partially restored two days later. HDL-C and apoA-I plasma levels, reduced after LDL-apheresis (-27% and -16%, respectively), were restored to almost normal levels two days later. LDL-apheresis reduced serum aqueous diffusion (AD) CEC, SR-BI-CEC, and ABCA1-CEC. AD and SR-BI were fully restored whereas ABCA1-CEC remained low two days later. Sera immediately and two days after LDL-apheresis had a lower CLC than pre-LDL-apheresis sera. In conclusion, LDL-apheresis transiently reduces HDL-C levels and serum CEC, but it also reduces also serum capacity to deliver cholesterol to macrophages. Despite a potentially negative effect on HDL levels and composition, LDL-apheresis may counteract foam cells formation.

Background: Myeloperoxidase (MPO) is a marker of plaque vulnerability and a mechanistic bridge between inflammation and cardiovascular disease, and thus is a suitable target for therapeutic strategy against cardiovascular disease., Methods: Since hypercholesterolemia is associated with atherosclerosis and inflammation, we tested whether MPO serum levels were up-regulated in Familial Hypercholesterolemia (FH) and whether acute reduction of total cholesterol (TC) would also reduce MPO concentration. FH subjects undergoing LDL-apheresis (LDL-A) treatment are a paradigmatic clinical model where TC rapidly plunges from extremely high to extremely low levels after selective LDL removal, and then spontaneously rebounds to baseline conditions. This clinical setting allows multiple intra-patient observations at different plasma TC concentrations. We measured MPO levels in serum by ELISA tests, and in peripheral leukocytes by immunofluorescence, to learn whether they were affected by the changes in TC levels. Serum MPO was measured before and serially up to the 14th day following LDL-A., Results: In both serum and peripheral leukocytes, MPO concentrations were i) higher than in sex- and age-matched healthy controls (p < 0.01); ii) decreased with TC reduction; iii) parallel with TC time course; iv) correlated with plasma TC. At regression analysis, plasma TC was the only variable considered that influenced MPO serum levels (β 0.022 ± 0.010, p < 0.0001)., Conclusions: In FH the MPO serum levels were modulated through changes in the TC concentrations carried out by LDL-A. Further study is needed to determine whether reduced MPO levels obtained by LDL-A could have any therapeutic impact.

Unlabelled: Early assessment of the efficacy of treatment is important in patients with breast cancer, whose routine adjuvant regimen frequently includes chemotherapy. Irrespective of the exact mechanisms involved in induction, the common early phenotypic marker of apoptosis is the expression on the outer cell membrane surface of phosphatidylserine, which avidly binds annexin V. (99m)Tc-labeled annexin V has been proposed for in vivo scintigraphic detection of apoptosis, albeit with contradicting results. This study was performed to define the time course of apoptosis induced by the chemotherapeutic agent paclitaxel in a model of virus-induced murine breast cancer., Methods: The RIII virus induces an estrogen-dependent, slow-growing breast cancer; BALB-c/cRIII female mice with breast tumors averaging 10 mm were studied, both in baseline conditions and at various times after the intravenous administration of paclitaxel (equivalent to a human dose of 20 mg/70 kg of body weight). The biodistribution of (99m)Tc-annexin V was evaluated at baseline and then at 1, 3, 6, and 24 h after paclitaxel administration. Apoptotic and antiapoptotic markers were also evaluated in tumor samples obtained at the same time points: DNA breaks (terminal deoxynucleotidyl transferase biotin-dUTP nick-end labeling [TUNEL]), active caspase-3, apoptosis-inducing factor, and Bcl-2 protein., Results: Baseline uptake of (99m)Tc-annexin V in breast tumors was about 2-fold higher than the uptake in normal breast tissue (demonstrating some ongoing apoptosis); tracer uptake increased at 1 and 3 h after paclitaxel administration (to almost double the baseline value) and then declined to levels even lower than baseline. Although no activation of the apoptosis-inducing factor mechanism was detected, a peak in TUNEL-positive tumor cells was reached 3 h after paclitaxel administration (to more than 6-fold the baseline level). The antiapoptotic marker Bcl-2 exhibited a biphasic pattern, with a maximum drop at 3 h, followed by return toward baseline levels at 6 h., Conclusion: These results define the time course of various biologic events taking place in this model of murine breast cancer after a proapoptotic insult (single-dose paclitaxel). Although confirming that in vivo uptake of (99m)Tc-annexin V reflects the degree of apoptosis, the study also suggests that the apoptotic response to antitumor therapy may differ from tumor type to tumor type. Therefore, contradicting results previously reported may depend on an inadequate time window chosen for imaging with (99m)Tc-annexin V.

Objectives: Waste management in the Campania region has been characterised, since the 1980s, by widespread uncontrolled and illegal practices of waste dumping, generating concerns over the health implications. The objective of this study was to evaluate possible adverse health effects of such environmental pressure., Methods: The health effects of waste-related environmental exposures in Campania were assessed in a correlation study on nine causes of death (for the years 1994-2001) and 12 types of congenital anomaly (CA) (1996-2002) in 196 municipalities of the provinces of Naples and Caserta. Poisson regression was used to analyse the association between health outcomes and environmental contamination due to waste, as measured through a composite index, adjusting for deprivation., Results: Statistically significant excess relative risks (ERR, %) in high-index compared with low-index (unexposed) municipalities were found for all-cause mortality (9.2 (95% CI 6.5 to 11.9) in men and 12.4 (9.5 to 15.4) in women and liver cancer (19.3 (1.4 to 40.3) in men and 29.1 (7.6 to 54.8) in women). Increased risks were also found for all cancer mortality (both sexes), stomach and lung cancer (in men). Statistically significant ERRs were found for CAs of the internal urogenital system (82.7 (25.6 to 155.7)) and of the central nervous system (83.5 (24.7 to 169.9))., Conclusion: Although the causal nature of the association is uncertain, findings support the hypothesis that waste-related environmental exposures in Campania produce increased risks of mortality and, to a lesser extent, CAs.

Background: Gaucher disease is the first lysosomal storage disease for which specific therapy became available. Over 4800 patients have been treated with enzyme replacement therapy. Analysis of Gaucher disease registry data has outlined the clinical heterogeneity of the disease and the different responses to treatment from patient to patient, and for different organs. This variability in clinical response justifies the development of a severity score index to assess disease activity, stage and prognosis, and to quantify the effects of treatment., Design and Methods: The new scoring system proposed here, the "Gaucher Disease Severity Score Index - Type I" (GauSSI-I), is based on the clinical experience of the authors and an extensive literature review, including data from the International Gaucher Registry. In particular for skeletal disease, all the available scoring systems have been reviewed and compared in order to provide a skeletal scoring system that allows use of any of the different methods on an equivalent basis., Results: The new scoring system, GauSSI-I, was developed. Six specific domains, in which different items were scored according to their impact on morbidity, were characterized. GauSSI-I was evaluated in 53 type I Gaucher patients treated with imiglucerase, and it was compared to the Zimran score, the only severity index score so far available., Conclusions: The GauSSI-I is a reliable method for staging the severity of adult type I Gaucher disease, and it is more sensitive than the Zimran score for monitoring the response to treatment.

The possible adverse health effects associated with the residence in the neighbourhood of toxic dump sites have been the object of many epidemiological studies in the last two decades;some of these reported increases of various health outcomes. The present study reports the cluster analysis of mortality and malformations at municipality level, standardized by socioeconomic deprivation index, in an area of the Campania Region characterized by a widespread illegal practice of dumping toxic and urban waste. Clusters have been observed with significant excess of mortality by lung, liver, gastric, kidney and bladder cancers and of prevalence of total malformations and malformations of limb, cardiovascular and urogenital system. The clusters are concentrated in a sub-area where most of the illegal practice of dumping toxic waste has taken place

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality in industrialized countries. It is characterized by a progressive airflow limitation resulting from an abnormal inflammatory response of the lungs to inhaled gases and particles. Since oxidative stress is thought to play a role in COPD, and since increased oxidative stress is associated with chromosomal instability in several diseases, we investigated whether such relationship also exists in COPD. Whole blood lymphocytes from 49 COPD patients and 48 age- and sex-matched controls were cultivated in vitro and cytogenetic damage was evaluated by micronucleus (MN) and sister-chromatid-exchange (SCE) assays. In patients with COPD, MN frequency was not significantly different from that of controls. Similarly, SCE frequency did not differ in the two groups suggesting no disturbance in DNA replication. Unlike other diseases characterized by oxidative stress, COPD does not appear to be associated with DNA damage.

Unlabelled: Gaucher's disease is a lysosomal storage disorder due to a genetically transmitted deficiency of the enzyme glucocerebrosidase. In the most common form of the disease (type 1), accumulation of glucosylceramide in the reticuloendothelial cells of liver, spleen, and bone marrow leads to visceromegaly, anemia, thrombocytopenia, and osteopenia. Skeletal manifestations secondary to infiltration of the bone marrow by Gaucher's cells are detectable by radiography only in advanced stages. Imaging of bone marrow involvement can be performed indirectly by magnetic resonance techniques or by bone marrow scintigraphy with radiocolloids. However, both procedures lack specificity because the normal bone marrow, rather than the pathologic process, is imaged. The aim of this study was to assess the reliability of (99m)Tc-sestamibi scintigraphy for direct evaluation of bone marrow involvement., Methods: Seventy-two patients with type 1 and 2 patients with type 3 Gaucher's disease (35 males, 39 females) were enrolled in the study. The mean age +/- SD was 31.9 +/- 16.5 y (range, 3-76 y), and the average duration of the disease manifestations when performing scintigraphy was 12.95 y (median, 10.5 y; range, 0-44 y). Forty-three of 74 patients had never received enzyme replacement therapy (ERT), whereas 31 patients were already being treated with ERT. (99m)Tc-Sestamibi was injected intravenously (6-8 MBq/kg of body weight) and imaging was recorded at the lower limbs 30 min after injection, at the plateau of tracer accumulation in the involved bone marrow. The scans were evaluated visually, assigning a semiquantitative score based on the extension and intensity of uptake in the bone marrow of the lower limbs (0 = no uptake; 8 = maximum uptake). The scintigraphic score was entered into complex statistical analysis, which included a series of clinical and blood chemistry parameters defining overall severity of the disease., Results: (99m)Tc-Sestamibi scintigraphy showed that 71 of 74 patients had some degree of bone marrow involvement. The scintigraphic score was highly correlated with an overall clinical severity score index (SSI) and with various parameters contributing to the SSI, either positively or negatively. The highest correlation of the scintigraphic score was found with an overall biochemical marker of disease severity (serum chitotriosidase). ERT-naive patients showed high correlation of the scintigraphic score with the clinical SSI, with a radiographically based score, and with serum chitotriosidase. In the ERT-treated patients, the scintigraphic score was correlated with the clinical SSI, with hepatomegaly, and with hemoglobin., Conclusion: (99m)Tc-Sestamibi uptake reliably identifies bone marrow infiltration by Gaucher's cells. The scintigraphic score is helpful for defining the severity of bone marrow involvement and for comparing patients. (99m)Tc-Sestamibi scintigraphy, which provides topographic information about the sites involved by the disease, is highly correlated with other parameters of disease severity and appears to correlate with response to ERT.