Oxidative stress in occupational exposure to styrene vapors and dangerous chemicals in the shipbuilding industry.

Introduction: In the shipbuilding industry, workers are exposed to a variety of dangerous chemicals, styrene being one of them. The International Agency for Research on Cancer classified styrene as a chemical belonging to group 2A, which means it is probably carcinogenic to humans. This study aimed at evaluating the oxidative stress effects due to occupational exposure to styrene and other chemicals. Materials and methods: Styrene urinary metabolites, such as mandelic acid and phenylglyoxylic acid, and the urinary biomarkers of oxidative stress, i.e., oxidation products of DNA and RNA and of proteins, were measured in a group of 17 workers and compared to the concentrations found in a group of 17 healthy volunteers who had not been exposed to chemicals. Results and discussion: Statistically significant differences were found for 8-oxo-7,8-dihydroguanine (8-oxoGua) and 8-oxo-7,8-dihydro-2'-deoxiguanosine (8-oxodGuo) concentrations that are higher in workers than in the control group. The workers performing the tasks of painting are the most exposed to styrene and show higher concentrations of 8-oxo-7,8-dihydroguanosine (8-oxoGuo). Workers performing the tasks of wood refining and welding are less exposed to styrene but have higher concentrations of 8-oxoGua and 8-oxodGuo. Conclusion: The exposure scenario in shipbuilding is a complex one, in which different xenobiotics are simultaneously present. The oxidative stress effect biomarkers, obtained from the oxidation product of RNA and DNA, are promising, sensitive, but not specific.

Staging of Prostate Cancer: Role of Multiparametric Magnetic Resonance Imaging in Different Risk Classes.

Using multiparametric magnetic resonance imaging, it is now possible to diagnose prostate cancer and categorize its risk. As it can accurately determine the extracapsu- lar extension of the tumor, invasion of seminal vesicles, involvement of lymph nodes, and the potential presence of bone metastases, multiparametric magnetic resonance imaging plays a crucial role not only in the diagnosis but also in the local staging of prostate cancer. The patients with a history of negative biopsy/increasing prostate- specific antigen and the existence of further data supporting its use in biopsy-naive patients and active surveillance are the most blatant indications for multiparametric magnetic resonance imaging in guidelines. The traditional clinical examination, pros- tate-specific antigen tests, and systematic biopsy are all enhanced by multiparametric magnetic resonance imaging, which will miss certain cancers due to insufficient size or changes in tissue density. The use of multiparametric magnetic resonance imaging is expected to rise, and further advances in the method will be crucial for the secure adoption of targeted therapeutic ideas. Here, we give a succinct overview of multipa- rametric magnetic resonance imaging's application to the identification and risk clas- sification of prostate cancer.

Radiomics and Artificial Intelligence for the Diagnosis and Monitoring of Alzheimer's Disease: A Systematic Review of Studies in the Field.

The use of radiomics and artificial intelligence applied for the diagnosis and monitoring of Alzheimer's disease has developed in recent years. However, this approach is not yet completely applicable in clinical practice. The aim of this paper is to provide a systematic analysis of the studies that have included the use of radiomics from different imaging techniques and artificial intelligence for the diagnosis and monitoring of Alzheimer's disease in order to improve the clinical outcomes and quality of life of older patients. A systematic review of the literature was conducted in February 2023, analyzing manuscripts and articles of the last 5 years from the PubMed, Scopus and Embase databases. All studies concerning discrimination among Alzheimer's disease, Mild Cognitive Impairment and healthy older people performing radiomics analysis through machine and deep learning were included. A total of 15 papers were included. The results showed a very good performance of this approach in the differentiating Alzheimer's disease patients-both at the dementia and pre-dementia phases of the disease-from healthy older people. In summary, radiomics and AI can be valuable tools for diagnosing and monitoring the progression of Alzheimer's disease, potentially leading to earlier and more accurate diagnosis and treatment. However, the results reported by this review should be read with great caution, keeping in mind that imaging alone is not enough to identify dementia due to Alzheimer's.

Radiological lung sequelae, functional status and symptoms in older patients 3 and 6 months after hospitalization for COVID-19 pneumonia.

The aim of our study was to assess the lung sequelae and clinical consequences 3 and 6 months after hospitalization for COVID-19 pneumonia in older patients. An observational study was conducted on 55 patients aged 65 years and older. Activities of daily living (ADL) and clinical frailty scale (CFS) were assessed at baseline and after 3 months. Both quantitative assessment at chest high-resolution computed tomography (CT) and semi-quantitative severity score (CTSS) were performed at baseline and after 3 and 6 months. Mean age: 82.3 ± 7.1 years. Male prevalence: 56.4%. After 6 months, ground-glass opacities (GGO) were still detectable in 22% of subjects, while consolidations were no longer appreciable. During follow-up, CTSS reached an overall median score of zero after 6 months. Fibrotic-like changes were found in 40% of subjects with an overall median score of 0 (0-5) points, being more prevalent in males. Patients reporting worsening ADL and CFS were 10.9% and 45.5%, respectively. They were associated with the burden of comorbidities, especially history of heart failure and chronic obstructive pulmonary disease at baseline. Amnesic disorders, exertional dyspnea, and fatigue were the most relevant symptoms reported. No association emerged between persistent or new-onset symptoms and evidence of fibrotic-like changes. The typical chest CT abnormalities of the COVID-19 pneumonia acute phase resolved in most of our older patients. Mild fibrotic-like changes persisted in less than half of the patients, especially males, without significantly affecting the functional status and frailty condition, which instead were more likely associated with pre-existing comorbidities.

Which men with non-malignant pathology at magnetic resonance imaging-targeted prostate biopsy and persistent PI-RADS 3-5 lesions should repeat biopsy?

PURPOSE: To assess predictors of clinically significant (cs) prostate cancer (PCa) in men who had a non-malignant Multiparametric magnetic resonance imaging (mpMRI)-targeted biopsy and persistent Prostate Imaging-Reporting Data System (PI-RADS) 3 to 5 lesions in subsequent mpMRI. MATERIALS AND METHODS: We retrospectively analyzed MRI-targeted biopsy database in three centers. INCLUSION CRITERIA: persistence of at least one PI-RADS ≥3 lesion found negative for cancer in a previous MRI-targeted plus systemic biopsy (baseline biopsy). EXCLUSION CRITERIA: downgrading to PI-RADS 1-2. A logistic regression analysis was performed to estimate the predictors of csPCa. RESULTS: Fifty-seven patients were included. Median interval between biopsies was 12.9(2.43) months. Median age was 68.0(12) years. Median PSA was 7.0(5.45) ng/ml. At follow-up, 24.6%, 54.4%, and 21% of patients had a PI-RADS score 3, 4, and 5 index lesion (IL), respectively. At re-biopsy, 28/57(49.1%) men were found to harbor PCa. Among these, 22(78.6%) had csPCa. csPCa was found outside the IL in only 2 patients. Eleven, 13, and 5 patients with PI-RADS 3, 4, and 5, respectively, had no cancer. Three patients with a PI-RADS 3 lesion had cancer (2 with Gleason score 3+3, 1 with Gleason score 3+4). 14/43 men with a PI-RADS 4/5 lesion harbored Gleason score ≥3+4 PCa. Logistic regression analysis found that PSA (HR 1.281, 95% CI: 1.013-1.619, P = 0.039) and IL size (HR 1.146, 95% CI: 1.018-1.268, P = 0.041) were the predictors of csPCa at re-biopsy. CONCLUSIONS: Patients with non-malignant pathology from PI-RADS ≥3 lesions targeted biopsy should be follow-up with mpMRI, and those with persistent PI-RADS 4 to 5 lesions should repeat MRI-targeted and systematic biopsy.

A magnetic resonance imaging-based nomogram for predicting clinically significant prostate cancer at radical prostatectomy.

PURPOSE: To develop a nomogram incorporating clinical and multiparametric magnetic resonance imaging (mpMRI) parameters for the detection of clinically significant prostate cancer (csCaP) at radical prostatectomy (RP). MATERIALS AND METHODS: We retrospectively analyzed all consecutive patients who underwent robotic RP between 2016 and 2020. All patients underwent a 1.5-T mp-MRI according to the PI-RADS-v2 scoring system. RP specimens were examined with the whole-mount technique. csCaP definition: any tumor with a volume larger than 0.5 cm3 or with a Gleason score ≥7. Univariable logistic regression models explored the association between clinical and imaging data and the risk of csCaP. Significant variables (P < 0.05) were selected into multivariable regression models to identify independent predictors. A nomogram was designed to select the significant relevant predictors. The nomogram was internally validated in terms of discrimination and calibration. Receiver operating characteristics of the area under the curve was used to assess the discrimination ability of the nomogram. To assess the predictive performance of mpMRI, the accuracy of the mpMRI-based nomogram was compared with that excluding either PI-RADS score or mpMRI IL size. RESULTS: The analysis involved 393 patients. The median age was 65(9) years. The median prostate specific antigen was 5.81(3.76) ng/ml. 363 had csCaP. PI-RADS v2 score of 4-5, prostate specific antigen density of 0.15 or more, and mpMRI index lesion (IL) size were significantly associated with csCaP in the multivariable regression analyses. Based on these variables, a diagnostic model was developed. The full model yielded an area under the curve of 0.77 (95%CI:0.75-0.80) which was significantly better than those excluding mpMRI findings (P = 0.02) Decision curve analysis showed a slight but significant net benefit associated with the use of the mp-MRI based nomograms compared with those excluding either PI-RADS score (Delta net benefit 0.0278) or mpMRI maximum IL size (Delta net benefit 0.0111). CONCLUSIONS: The nomogram constructed in this study can assist urologists in assessing an individual's risk of csCaP at RP.

Sinus Disease Grading on Computed Tomography Before and After Modulating Therapy in Adult Patients with Cystic Fibrosis.

Objectives: Cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy effects on respiratory function, pulmonary exacerbations and quality of life have been well documented. However, CFTR modulator therapy effects on sinus disease have not been so well reported. A previous study reported that ivacaftor improves appearance of sinus disease on Computed Tomography (CT) in cystic fibrosis (CF) patients with G551D mutation. The aim of this study was to evaluate the effect of CFTR modulator therapy in sinus disease using CT scores in a wider CF patient population. Materials and Methods: Forty-eight adult patients with CF underwent at least one CT sinus examination before CFTR modulator therapy (ivacaftor, lumacaftor, ivacaftor/lumacaftor or elexcaftor/tezacaftor/ivacaftor) and one CT sinus examination one year after CFTR modulator therapy initiation. Two radiologists assessed the images in consensus. The Lund-Mackay score (LM score) and the Sheikh-Lind CT sinus disease severity scoring system (SL score) were used. The 22-item SinoNasal Outcome Test (SNOT-22) questionnaire was evaluated before CFTR modulator therapy and one year after CFTR modulator therapy initiation. Results: CT sinus examination after CFTR modulator therapy showed statistically significant lower mean LM, SL and SNOT-22 scores than CT sinus examination before CFTR modulator therapy (p < 0.001). Conclusion: Evolution of imaging findings on CT during follow-up closely correlate with improved SNOT-22 score one year after CFTR modulator therapy initiation, indicating that CT may be a useful adjunct during follow-up of CF patients under this treatment as an objective measure of sinonasal disease improvement.

Biomonitoring of Exposure to Urban Pollutants and Oxidative Stress during the COVID-19 Lockdown in Rome Residents.

BACKGROUND: The objective of this study is to evaluate the effects of traffic on human health comparing biomonitoring data measured during the COVID-19 lockdown, when restrictions led to a 40% reduction in airborne benzene in Rome and a 36% reduction in road traffic, to the same parameters measured in 2021. METHODS: Biomonitoring was performed on 49 volunteers, determining the urinary metabolites of the most abundant traffic pollutants, such as benzene and PAHs, and oxidative stress biomarkers by HPLC/MS-MS, 28 elements by ICP/MS and metabolic phenotypes by NMR. RESULTS: Means of s-phenylmercaputric acid (SPMA), metabolites of naphthalene and nitropyrene in 2020 are 20% lower than in 2021, while 1-OH-pyrene was 30% lower. A reduction of 40% for 8-oxo-7,8-dihydroguanosine (8-oxoGuo) and 8-oxo-7,8-dihydro-2-deoxyguanosine (8-oxodGuo) and 60% for 8-oxo-7,8-dihydroguanine (8-oxoGua) were found in 2020 compared to 2021. The concentrations of B, Co, Cu and Sb in 2021 are significantly higher than in the 2020. NMR untargeted metabolomic analysis identified 35 urinary metabolites. Results show in 2021 a decrease in succinic acid, a product of the Krebs cycle promoting inflammation. CONCLUSIONS: Urban pollution due to traffic is partly responsible for oxidative stress of nucleic acids, but other factors also have a role, enhancing the importance of communication about a healthy lifestyle in the prevention of cancer diseases.

Phthalate Exposure and Biomarkers of Oxidation of Nucleic Acids: Results on Couples Attending a Fertility Center.

Phthalates are substances used as plasticizing agents and solvents that can increase the risk of infertility and that appear to induce oxidative stress. The aim of the study was to show the possible relationship between urinary concentrations of phthalates metabolites, namely MEP, MBzP, MnBP, MEHP, MEHHP, and MnOP and biomarkers of nucleic acids oxidation, methylation, or protein nitroxidation. The oxidative stress biomarkers measured in human urine were 8-oxo-7,8-dihydroguanine, 8-oxo-7,8-dihydroguanosine, 8-oxo-7,8-dihydro-2'-deoxyguanosine, 3-nitrotyrosine, and 5-methylcytidine. Two hundred and seventy-four couples were enrolled, undergoing an assisted reproduction technology (ART) treatment, urine samples were analyzed in HPLC/MS-MS, and then two sub-groups with urinary concentration > 90th or <10th percentile were identified, reducing the sample size to 112 subjects. The levels of oxidative stress biomarkers were measured in both groups, reduced to 52 men and 60 women. A statistically significantly difference for 8-oxoGuo and 3-NO2Tyr between men and women, with higher levels in men, was found. The levels of oxidative stress biomarkers were directly correlated with some phthalate concentrations in both sexes.

Interventional Radiology's Osteoid Osteoma Management: Percutaneous Thermal Ablation.

Osteoid osteoma (OO) is one of the most common benign bone tumors with specific clinical and radiological characteristics. Analgesic therapy and surgical treatment have been considered the only therapy for a long time. Recently, safe and effective new therapeutic options have been introduced, among which percutaneous thermal ablation techniques. This review aims to describe the recent updates in the field of percutaneous thermal ablation techniques in the treatment of OO, assessing the outcomes in terms of efficacy, complications, and recurrence rate.

Endovascular management of vascular renal injuries: outcomes and comparison between traumatic and iatrogenic settings.

PURPOSE: To evaluate the efficacy of endovascular treatment for vascular renal injuries (VRIs) like bleeding, pseudoaneurysm and artero-venous fistula (AVF) and to compare patients with blunt trauma (T-VRIs) with those with iatrogenic damage (I-VRIs). METHODS: We retrospectively assessed 49 renal artery embolizations performed to treat T-VRIs (26.5%) and I-VRIs (73.5%). Different embolic materials were used based on the type of lesion. Technical success was defined as the complete occlusion of target arteries with no further visualization of VRIs. Clinical success was defined if no recurrence was present and if renal function (difference between creatinine after and before treatment <0.5 mg/dl) was preserved after 1 month. RESULTS: Angiography showed bleeding in 27 patients, pseudoaneurysm in 29 and an AVF in 6. Embolic agents used were coils in 39 procedures, coils with sponge in four and others in six. Technical success was 100% while clinical success was 85.7% due to seven patients with recurrence. The group I-VRIs showed a higher rate of clinical success than the group T-VRIs (94.4% vs 61.5%; p < 0.05). Moreover, the group I-VRIs had a higher incidence of pseudoaneurysms and AVFs compared with the group T-VRIs (69.4% vs 30.8% and 16.7% vs 0%; p < 0.05). CONCLUSION: Endovascular treatment for VRIs showed satisfactory results and no patient had a worsening of renal function. I-VRIs had better clinical success and more frequently appeared as pseudoaneurysms compared to T-VRIs: probably iatrogenic injury is localized and pseudoaneurysm is easily identifiable and treatable with endovascular treatment.

A Case-Control Study on the Effects of Plasticizers Exposure on Male Fertility.

Male infertility is a serious concern for public health, and the possible role of exposure to plasticizers such as phthalates and bisphenol A in contributing to the condition is widely debated. We have herein enrolled 155 infertility cases attending an infertility center and 211 controls (fathers of a spontaneously conceived newborn) to investigate this issue. The urinary levels of seven phthalates and BPA were analyzed through HPLC/MS/MS. All data were statistically elaborated considering information about clinical situation, life habits, occupational activity, and, for cases, semen parameters (volume, sperm concentration, total count of spermatozoa, and sperm motility). Results showed significantly higher urinary concentrations for all the phthalates in cases compared to controls, except for monoethylphthalate and BPA. In total, 90.07% of cases had sperm motility lower than the WHO reference value (2010), while 53.69%, 46.31%, and 16.56% had sperm total number, concentration, and volume, respectively, out of the reference range. Regarding the possible source of exposure, the use of scents seems to be a significant source of DEP (diethylphthalate). When considering occupational settings, industrial workers, dental technicians, artisans, and farmers using chemicals showed higher risk (OR = 2.766, 95% CI 1.236-6.185), particularly in relation to DnBP (di-n-butyl phthalate) and DEHP (di-ethyl-hexyl phthalate) exposure. No clear quantitative correlation between specific plasticizers and sperm parameters could be demonstrated but these findings call for future studies about the risks associated with exposure to their mixture.

Female Reproductive Health and Exposure to Phthalates and Bisphenol A: A Cross Sectional Study.

The xenoestrogenicity of some plasticisers (phthalates and bisphenol A) is documented in the literature and may pose a risk to female reproductive health. The aim of this study was to assess exposure to six phthalates. This was achieved by measuring their respective metabolites (mono-ethylphthalate (MEP); mono-n-butylphthalate (MnBP); mono-n-ottylphthalate (MnOP); and monobenzylphthalate (MBzP)), as well as the sum of two of the diethyl-hexyl phthalate metabolites-(∑DEHP) and bisphenol A (BPA) in a female population with infertility problems, and by conducting a correlation analysis between infertility factors, work activities, and lifestyle habits, in order to formulate a causal hypothesis. A cross-sectional epidemiological study was carried out and women under 43 years of age were recruited from an assisted reproduction technology (ART) center; the sample of 186 women was given a specific questionnaire and a spot urine sample was collected. Phthalate metabolites and urinary BPA were analyzed by HPLC/MS/MS. The results showed significantly higher mean values for MEP in women with recurrent pregnancy loss (RPL) (820.5 ± 1929.5 µg/g of creatinine) and idiopathic infertility (230.0 ± 794.2 µg/g of creatinine) than in women with other infertility factors (76.9 ± 171.8 µg/g of creatinine). Similarly, for MnOP levels, women with idiopathic infertility (2.95 ± 3.44 µg/g of creatinine) showed significantly higher values than women with the other infertility factors taken together (1.35 ± 2.05 µg/g of creatinine). Women with tubal factors of infertility, RPL, and endocrine dysfunctions show higher values of DEHP (p = 0.032). Considering occupations, women working in commerce showed more than twice as much urinary BPA levels (1.10 ± 0.48 µg/g of creatinine) compared to women working in other industries (0.45 ± 0.35 µg/g of creatinine). The presence of significantly higher values of certain phthalates, DEHP in particular, especially in women with RPL and idiopathic infertility, suggests a possible involvement of these compounds as competing factors in reproductive issues. The study of sources of exposure suggested that the working activity in trade, as a casher in particular, represents a major one for BPA (p = 0.015).

Chest X-ray Score and Frailty as Predictors of In-Hospital Mortality in Older Adults with COVID-19.

BACKGROUND: The purpose of this study was to evaluate the prognostic impact of chest X-ray (CXR) score, frailty, and clinical and laboratory data on in-hospital mortality of hospitalized older patients with COVID-19. METHODS: This retrospective study included 122 patients 65 years or older with positive reverse transcription polymerase chain reaction for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and with availability to CXRs on admission. The primary outcome of the study was in-hospital mortality. Statistical analysis was conducted using Cox regression. The predictive ability of the CXR score was compared with the Clinical Frailty Scale (CFS) and fever data using Area Under the Curve (AUC) and net reclassification improvement (NRI) statistics. RESULTS: Of 122 patients, 67 died during hospital stay (54.9%). The CXR score (HR: 1.16, 95% CI, 1.04-1.28), CFS (HR: 1.27; 95% CI, 1.09-1.47), and presence of fever (HR: 1.75; 95% CI, 1.03-2.97) were significant predictors of in-hospital mortality. The addition of both the CFS and presence of fever to the CXR score significantly improved the prediction of in-hospital mortality (NRI, 0.460; 95% CI, 0.102 to 0.888; AUC difference: 0.117; 95% CI, 0.041 to 0.192, p = 0.003). CONCLUSIONS: CXR score, CFS, and presence of fever were the main predictors of in-hospital mortality in our cohort of hospitalized older patients with COVID-19. Adding frailty and presence of fever to the CXR score statistically improved predictive accuracy compared to single risk factors.

Occupational Exposure in Industrial Painters: Sensitive and Noninvasive Biomarkers to Evaluate Early Cytotoxicity, Genotoxicity and Oxidative Stress.

This study aimed to identify sensitive and noninvasive biomarkers of early cyto-genotoxic, oxidative and inflammatory effects for exposure to volatile organic compounds (VOCs) in shipyard painters. On 17 (11 spray and 6 roller) painters (previously characterized for VOCs exposure to toluene, xylenes, ethylbenzene, ethyl acetate) and on 18 controls, we performed buccal micronucleus cytome (BMCyt) assay; Fpg-comet assay on lymphocytes; detection of urinary 8-oxoGua (8-oxo-7,8-dihydroguanine), 8-oxodGuo (8-oxo-7,8-dihydro-2'-deoxyguanosine) and 8-oxoGuo (8-oxo-7,8-dihydroguanosine), and cytokines release on serum. We found induction of cyto-genotoxicity by BMCyt assay and inflammatory effects (IL-6 and TNFα) in roller painters exposed to lower VOC concentrations than spray painters. In contrast, in both worker groups, we found direct and oxidative DNA damage by comet assay (with slightly higher oxidative DNA damage in roller) and significant increase of 8-oxoGuo and decrease of 8-oxodGuo and 8-oxoGua in respect to controls. The cyto-genotoxicity observed only on buccal cells of roller painters could be related to the task's specificity and the different used protective equipment. Although limited by the small number of subjects, the study shows the usefulness of all the used biomarkers in the risk assessment of painters workers exposed to complex mixtures.

Urinary Oxidative Stress Biomarkers in Workers of a Titanium Dioxide Based Pigment Production Plant.

Titanium dioxide is produced or imported into the EU for over one million tons/year. The International Agency for Research on Cancer (IARC) classification is 2B, a possible inhalation carcinogen for humans. This study evaluates urinary biomarkers of oxidative stress in workers of a plant producing TiO2 pigment powder, having 0.25 µm average particle size and an ultrafine fraction, compared to unexposed subjects. Urine samples were collected from forty workers before and after the shift, from six employees of the same company and eighteen volunteers from the same geographical area. Titanium and other metals concentrations were measured by ICP-MS, while DNA, RNA, and protein oxidation products by HPLC/MS-MS. A statistically significant increase was found for the urinary concentration of Al, Cd, Cr, Cu, Fe, Mn, Pb, Ti, and Zr, and for all biomarkers of oxidative stress in post-shift workers' urine samples. Urinary concentrations after the working shift were higher than for employees and volunteers pooled together for Cd, Mn, and Zr, and for the oxidative stress biomarkers 8-oxoGuo, 8-oxodGuo, and 3NO2Tyr. Biomonitoring studies on dose and effect biomarkers for TiO2 occupational exposure provide information useful for protecting workers' health even in conditions that comply with health and safety standards, highlighting reversible effects of chronic exposure at very low doses.

Direct and Oxidative DNA Damage in a Group of Painters Exposed to VOCs: Dose - Response Relationship.

Volatile organic compounds (VOCs) are present in several working activities. This work is aimed at comparing oxidative stress and DNA damage biomarkers to specific VOCs in the occupational exposure of painters. Dose-response relationships between biomarkers of oxidative stress and of dose were studied. Unmetabolized VOCs and their urinary metabolites were analyzed. Urinary Methylhyppuric acids (MHIPPs, xylenes metabolite), Phenylglyoxylic and Mandelic acid (PGA, MA ethylbenzene metabolites), S-Benzylmercapturic acid (SBMA, toluene metabolite), and S-Phenylmercapturic acid (SPMA, benzene metabolite) were quantified at the end of work-shift. Oxidative stress was determined by: urinary excretion of 8-oxodGuo, 8-oxoGua and 8-oxoGuo and direct/oxidative DNA damage in blood by Fpg-Comet assay. Multivariate linear regression models were used to assess statistical significance of the association between dose and effect biomarkers. The regressions were studied with and without the effect of hOGG1 and XRCC1 gene polymorphisms. Statistically significant associations were found between MHIPPs and both 8-oxoGuo and oxidative DNA damage effect biomarkers measured with the Comet assay. Oxidative DNA damage results significantly associated with airborne xylenes and toluene, whilst 8-oxodGuo was significantly related to urinary xylenes and toluene. Direct DNA damage was significantly associated to SBMA. XRCC1 wild-type gene polymorphism was significantly associated with lower oxidative and total DNA damage with respect to heterozygous and mutant genotypes. The interpretation of the results requires some caution, as the different VOCs are all simultaneously present in the mixture and correlated among them.

Occupational exposure to volatile organic compounds affects microRNA profiling: Towards the identification of novel biomarkers.

In the framework of a project aimed at finding novel predictive biomarkers of VOCs exposure-related diseases, the effect of exposure to ethylbenzene, toluene, and xylene has been analyzed in a group of painters (spray- and roller-painters) working in the shipyard industry. Airborne levels of solvents were higher in spray- than in roller-painters, and comparable to the Occupational Exposure Limits (OELs), particularly for toluene and xylene. The urinary concentration of each volatile organic compound (VOC) and of the corresponding metabolites were also concurrently measured. A set of oxidative stress biomarkers, i.e., the products of DNA and RNA oxidation, RNA methylation, and protein nitration, were measured, and found significantly higher at the end of the work shift. MicroRNA (MiRNA) expression was analyzed in the VOC-exposed workers and in a control group, finding 56 differentially expressed (DE) miRNAs at a statistically significant level (adjusted p ≤ 0.01). The Receiver-Operating Characteristic curves, computed for each identified miRNA, showed high sensitivity and specificity. A pathway analysis in the Kyoto Encyclopedia of Genes and Genomes (KEGG) showed that miRNA-1, which was found downregulated in exposed workers, is involved in the lung cancer oncogenesis. A subset of 10 miRNAs (out of the 56 DE) was selected, including those with the highest correlation to the urinary dose biomarkers measured at the end of work-shift. Multivariate ANOVA analysis showed a statistically significant correlation between the urinary dose biomarkers (both the VOCs urinary concentration and the VOCs' metabolite concentration), and the identified miRNA subset, indicating that the exposure to low VOC doses may be sufficient to activate the miRNA response. Four miRNAs belonging to the subset strongly related to the VOCs and VOCs' metabolites concentration were individuated, miR-589-5p, miR-941, miR-146b-3p and miR-27a-3p, with well-known implications in oxidative stress and inflammation processes.

Cross Sectional Study on Exposure to BPA and Phthalates and Semen Parameters in Men Attending a Fertility Center.

Among the possible risk factors for male reproduction, exposure to phthalates and alkylphenols is widely documented. This study evaluated the possible association between chemical exposure and the quality of the seminal fluid of 105 subjects in a fertility clinic. The urinary levels of seven phthalate metabolites (monoethylphthalate, MEP; monobenzylphthalate, MBzP; mono n-butylphthalate, MnBP; mono-(2-ethylhexyl) phthalate, MEHP; mono(2-ethyl-5-hydroxyhexyl) phthalate, MEHHP; mono-n-octylphthalate, MnOP; mono-isononylphthalate, MiNP) and bisphenol A (BPA), were analysed by high performance liquid chromatography/tandem mass spectrometry HPLC/MS/MS. The regression analysis showed that the semen volume was positively associated with MnBP, MnOP and BPA levels while was negatively associated with MiNP levels. The sperm concentration had a significant inverse relationship with MEP levels. A negative association was found between the use of plastic containers for food storage (p = 0.037) and semen volume (3.06 vs. 2.30 mL as average values, never vs daily). A significant positive correlation emerged (p < 0.005) between the consumption of canned food and the levels of BPA (2.81 vs. 0.14 µg/g creat as average values, daily vs. never) and between the use of perfumes and levels of MEP (389.86 vs. 48.68 µg/g creat, as average values, daily vs. never). No further statistically significant associations were found, even considering the working activity. Some evidence emerged about the possible link between exposure and seminal fluid quality: further case/control or prospective studies will allow us to confirm this causality hypothesis.

Distortion product otoacoustic emission sensitivity to different solvents in a population of industrial painters.

Objective: To evaluate the ototoxic effect of the exposure to different organic solvents and noise using distortion product otoacoustic emissions (DPOAEs).Design: The exposure to different solvents was evaluated by measuring, before and at the end of the work-shift, the urinary concentrations of solvent metabolites used as dose biomarkers. The urinary concentrations of DNA and RNA oxidation products were also measured as biomarkers of oxidative damage. The simultaneous exposure to noise was also evaluated. DPOAEs and pure tone audiometry (PTA) were used as outcome variables, and were correlated to the exposure variables using mixed effect linear regression models.Study sample: Seventeen industrial painters exposed to a solvent mixture in a naval industry. A sample size of 15 was estimated from previous studies as sufficient for discriminating small hearing level and DPOAE level differences (5 dB and 2 dB, respectively) at a 95% confidence level.Results: Statistically significant associations were found between the DPOAE level and the urinary dose biomarkers and the oxidative damage biomarkers. DPOAE level and the logarithm of the metabolite concentration showed a significant negative correlation.Conclusions: DPOAE are sensitive biomarkers of exposure to ototoxic substances and can be effectively used for the early detection of hearing dysfunction.