Biochemical and haematological effects of serum PFOA, ADV and cC6O4 in workers of a chemical company producing fluoropolymers, Italy, 2013-2022.

INTRODUCTION: Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are widely used in the manufacture of fluoropolymers. We evaluated biochemical and haematological effects of three PFAS, serum perfluorooctanoic acid (PFOA), ADV, and cC6O4 in workers of a fluoropolymer company. METHODS: Using data (2013-2022), we fitted random intercept regression models adjusted for several covariates and reciprocal adjustment between the three PFAS. RESULTS: We analysed data of 814 workers (698 men, 116 women), 607 from the chemical plant, 207 from the research centre, for a total of 4912 blood samples (2065 with all three PFAS measured). Median levels of PFOA and ADV were 21.3 and 120 µg/L. Most (65.5%) cC6O4 measurements were below the limits of quantification (which varied over time from 5 to 0.1 µg/L). For PFOA, we observed positive associations with total cholesterol (+1.1% increase per ln(PFOA) increase) and apolipoprotein B (+1.4%) and negative associations with alkaline phosphatase (-1.5%); suggestive associations were also found with RBC (-0.4%), IgA (-1.5%), IgM (-1.4%). ADV was positively associated with total and LDL cholesterol (+1.0% and +1.6% per ln(ADV) increase), apolipoprotein B (+1.0%), GGT (+2.1%), IgM (+1.4%), and WBC (+1.5%) and negatively associated with direct bilirubin (-2.3%) and alpha-2-globulins (-0.7%); suggestive associations were found for indirect bilirubin (-2.0%), oestradiol (-2.1%), ad CRP (+6.0%). For samples with detectable cC6O4 levels we observed higher values of ALP (+2.3%), proteins (+0.5%), IgG (+0.7%) and platelets (+1.6%) and suggestively increased total bilirubin (+3.9%), RBC (+0.6%), and oestradiol (+5.8%). Some associations (total cholesterol, apolipoprotein B, WBC, total bilirubin, and alkaline phosphatase showed reverse time trends in parallel with the strong decrease of serum PFOA and ADV over the study period. DISCUSSION: We found associations of serum PFOA and ADV with lipid metabolism, liver function, and immunoglobulins. The reverse time trends of some endpoints in parallel with decrease of serum PFOA and ADV reinforce causal interpretation of results. cC6O4 showed a different pattern of associations.

Benzene Exposure in Workers From a Waste Oil Regeneration Plant During Ordinary Activities by Air and Biological Monitoring.

BACKGROUND: In the regeneration of waste oil, a strategical technological process for the European Union circular economy action plan, exhausted oils are regenerated to produce high performing oil bases. Aim of this work was to assess the exposure to benzene in plant workers during ordinary activities. METHODS: 59 workers, potentially exposed to benzene, and 9 administrative workers from an Italian plant were monitored for the whole work shift with personal air samplers; urinary benzene (BEN-U) and S-phenyl mercapturic acid (SPMA) were measured by mass spectrometry methods in end-shift urine samples. Different job tasks were identified among workers. RESULTS: Median (minimum-maximum) airborne exposures to benzene were <0.9 (<0.9-6.3) and <0.9 (<0.9-0.9) µg/m3, BEN-U and SPMA levels were 0.094 (<0.015-3.095) µg/L and 0.15 (<0.10-9.67) µg/g crt and 0.086 (0.034-0.712) µg/L and <0.10 (<0.10-3.19) µg/g creatinine in workers and administrative workers, respectively. No differences were found among job tasks and between workers and administrative workers, while higher levels were found in smokers than in non-smokers. For all job tasks, the exposure to benzene was always below occupational limit values. CONCLUSIONS: This study has investigated for the first time the exposure to benzene of workers employed in the re-refining of exhaust oil. The results showed that normal production activities in regenerating used oils do not pose a risk of exposure to benzene in workers.

Metabolomic profiling of Prader-Willi syndrome compared with essential obesity.

Introduction: Prader-Willi syndrome (PWS) is a rare disease, which shows a peculiar clinical phenotype, including obesity, which is different from essential obesity (EOB). Metabolomics might represent a valuable tool to reveal the biochemical mechanisms/pathways underlying clinical differences between PWS and EOB. The aim of the present (case-control, retrospective) study was to determine the metabolomic profile that characterizes PWS compared to EOB. Methods: A validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) targeted metabolomic approach was used to measure a total of 188 endogenous metabolites in plasma samples of 32 patients with PWS (F/M = 23/9; age: 31.6 ± 9.2 years; body mass index [BMI]: 42.1 ± 7.0 kg/m2), compared to a sex-, age- and BMI-matched group of patients with EOB (F/M = 23/9; age: 31.4 ± 6.9 years; BMI: 43.5 ± 3.5 kg/m2). Results: Body composition in PWS was different when compared to EOB, with increased fat mass and decreased fat-free mass. Glycemia and HDL cholesterol were higher in patients with PWS than in those with EOB, while insulinemia was lower, as well as heart rate. Resting energy expenditure was lower in the group with PWS than in the one with EOB, a difference that was missed after fat-free mass correction. Carrying out a series of Tobit multivariable linear regressions, adjusted for sex, diastolic blood pressure, and C reactive protein, a total of 28 metabolites was found to be associated with PWS (vs. non-PWS, i.e., EOB), including 9 phosphatidylcholines (PCs) ae, 5 PCs aa, all PCs aa, 7 lysoPCs a, all lysoPCs, 4 acetylcarnitines, and 1 sphingomyelin, all of which were higher in PWS than EOB. Conclusions: PWS exhibits a specific metabolomic profile when compared to EOB, suggesting a different regulation of some biochemical pathways, fundamentally related to lipid metabolism.

Adherence to the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet and exposure to selenium species: A cross-sectional study.

Selenium is a trace element found in many chemical forms. Selenium and its species have nutritional and toxicologic properties, some of which may play a role in the etiology of neurological disease. We hypothesized that adherence to the Mediterranean-Dietary Approach to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) diet could influence intake and endogenous concentrations of selenium and selenium species, thus contributing to the beneficial effects of this dietary pattern. We carried out a cross-sectional study of 137 non-smoking blood donors (75 females and 62 males) from the Reggio Emilia province, Northern Italy. We assessed MIND diet adherence using a semiquantitative food frequency questionnaire. We assessed selenium exposure through dietary intake and measurement of urinary and serum concentrations, including speciation of selenium compound in serum. We fitted non-linear spline-based regression models to investigate the association between MIND diet adherence and selenium exposure concentrations. Adherence to the MIND diet was positively associated with dietary selenium intake and urinary selenium excretion, whereas it was inversely associated with serum concentrations of overall selenium and organic selenium, including serum selenoprotein P-bound selenium, the most abundant circulating chemical form of the metalloid. MIND diet adherence also showed an inverted U-shaped relation with inorganic selenium and particularly with its hexavalent form, selenate. Our results suggest that greater adherence to the MIND diet is non-linearly associated with lower circulating concentrations of selenium and of 2 potentially neurotoxic species of this element, selenoprotein P and selenate. This may explain why adherence to the MIND dietary pattern may reduce cognitive decline.

Cardiogenic Shock Integrated PHenotyping for Event Reduction: A Pilot Metabolomics Analysis.

Cardiogenic shock (CS) portends a dismal prognosis if hypoperfusion triggers uncontrolled inflammatory and metabolic derangements. We sought to investigate metabolomic profiles and temporal changes in IL6, Ang-2, and markers of glycocalyx perturbation from admission to discharge in eighteen patients with heart failure complicated by CS (HF-CS). Biological samples were collected from 18 consecutive HF-CS patients at admission (T0), 48 h after admission (T1), and at discharge (T2). ELISA analytical techniques and targeted metabolomics were performed Seven patients (44%) died at in-hospital follow-up. Among the survivors, IL-6 and kynurenine were significantly reduced at discharge compared to baseline. Conversely, the amino acids arginine, threonine, glycine, lysine, and asparagine; the biogenic amine putrescine; multiple sphingolipids; and glycerophospholipids were significantly increased. Patients with HF-CS have a metabolomic fingerprint that might allow for tailored treatment strategies for the patients' recovery or stabilization.

Ricerca scientifica ed educazione ambientale: l'approccio partecipativo dei progetti MAPS-MI nelle scuole di Milano.

The accumulated scientific evidence regarding the effects of air pollution on health calls for urgent and effective action to protect the most vulnerable part of the population, such as children and the elderly. In this context, the participatory approach represents a viable option to empower citizens and increase their level of awareness and participation. The involvement of civil society is a potential ally in tackling the still open research challenges. The MAPS-MI 2018-2019 Mapping air pollution in the catchment area of an elementary school of Milan and MAPS-MI 2022-2023 Mobility, environment and participation in the schools of Milan projects are here presented.The main targets of the projects are primary and middle school children, their parents and teachers, with some activities extended to the entire citizenship. Starting from the survey on parents' habits and opinions about mobility and air pollution, to the air quality and personal exposure assessment, and the field-testing and development of an environmental education module, the MAPS-MI approach aims to increase knowledge and awareness about air pollution and to involve stakeholders in experimenting practices towards change. The first results suggest that adopting a participatory approach in the fields of exposure science and environmental epidemiology is a winning choice in terms of quality research, participation and community impact.

Influence of dietary patterns on urinary excretion of cadmium in an Italian population: A cross-sectional study.

INTRODUCTION: Cadmium is a toxic heavy metal with detrimental effects on human health. Apart from smoking and occupational factors, diet is the main source of cadmium. However, the relation between adherence to so-called "healthy" dietary patterns and cadmium exposure has not been investigated in detail. In this study, we aimed at assessing such association in a Northern Italian population. METHODS: Using a cross-sectional study design, we investigated a population of non-smokers aged 30-60 years in the period 2017-2019. Each subject completed a validated food frequency questionnaire (FFQ) in order to estimate adherence to four dietary patterns, namely the Dietary Approach to Stopping Hypertension-DASH diet, Greek Mediterranean Index-GMI, the Italian Mediterranean Index-IMI, and the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet. We collected a fasting morning urinary sample to measure urinary levels of cadmium and cotinine. The association between increasing adherence to dietary patterns and cadmium exposure was evaluated using a cubic spline regression non-linear model and adjusting for relevant confounders (age, sex, body mass index, urinary cotinine levels, intake of fiber, and alcohol). RESULTS: We recruited 137 participants (males/females: 62/75) with median (interquartile range-IQR) age of 47 (IQR: 43-53) years. Median scores for the investigated dietary patterns were 24 (IQR: 21-28), 4 (IQR: 3-6), 4 (IQR: 3-5), and 7.5 (IQR: 6.5-8.5) for DASH, GMI, IMI and MIND diets, respectively. The median urinary cadmium level was 0.21 µg/L (IQR: 0.11-0.34 µg/L). Spline regression analysis showed an inverse linear association between increasing adherence to the DASH and MIND diets and urinary cadmium levels, reaching a plateau at high adherence scores, approximately > 25 and > 9 for DASH and MIND diets, respectively. An increase of cadmium exposure with increasing MIND score also emerged. Conversely, the association was almost null for IMI, and slightly positive for GMI. CONCLUSIONS: The present findings suggest that increasing adherence to the DASH and MIND diets are associated with decreased cadmium levels only at moderate level. Overall, these results indicate that public health strategies, including the decrease of cadmium contamination in healthy foods should be implemented.

Bioavailability Assessment of an Iron Formulation Using Differentiated Human Intestinal Caco-2 Cells.

In recent years, there has been growing interest in exploring alternative and innovative delivery systems to improve the efficacy of iron supplements, satisfying iron needs and lowering side effects. To address this issue, this study aimed at demonstrating the advantages of Ferro Supremo formulation (composed of encapsulated iron, vitamins, and micronutrients), in terms of capacity to improve iron intestinal absorption, in comparison with standard FeSO4. Hence, differentiated Caco-2 cells have been used for assessing the in vitro bioavailability and safety of FS and FeSO4. MTT experiments demonstrated that both FS and FeSO4 are not able to impair the viability of Caco-2 cells. Furthermore, the quantitative and qualitative analysis, conducted by atomic absorption spectrometry and fluorescence determinations, revealed that FS can enter, accumulate in the cytoplasm, and be transported by intestinal cells four times more efficiently than FeSO4. Our findings indicate that this formulation can be considered a valuable and efficiently good choice as food supplements for improving iron deficiency.

Prenatal and childhood exposure to per-/polyfluoroalkyl substances (PFASs) and its associations with childhood overweight and/or obesity: a systematic review with meta-analyses.

BACKGROUND: Per-/polyfluoroalkyl substances (PFASs) are persistent organic pollutants and suspected endocrine disruptors. OBJECTIVE: The aim of this work was to conduct a systematic review with meta-analysis to summarise the associations between prenatal or childhood exposure to PFASs and childhood overweight/obesity. METHODS: The search was performed on the bibliographic databases PubMed and Embase with text strings containing terms related to prenatal, breastfeeding, childhood, overweight, obesity, and PFASs. Only papers describing a biomonitoring study in pregnant women or in children up to 18 years that assessed body mass index (BMI), waist circumference (WC), or fat mass in children were included. When the estimates of the association between a PFAS and an outcome were reported from at least 3 studies, a meta-analysis was conducted; moreover, to correctly compare the studies, we developed a method to convert the different effect estimates and made them comparable each other. Meta-analyses were performed also stratifying by sex and age, and sensitivity analyses were also performed. RESULTS: In total, 484 and 779 articles were retrieved from PubMed and Embase, respectively, resulting in a total of 826 articles after merging duplicates. The papers included in this systematic review were 49: 26 evaluating prenatal exposure to PFASs, 17 childhood exposure, and 6 both. Considering a qualitative evaluation, results were conflicting, with positive, negative, and null associations. 30 papers were included in meta-analyses (19 prenatal, 7 children, and 4 both). Positive associations were evidenced between prenatal PFNA and BMI, between PFOA and BMI in children who were more than 3 years, and between prenatal PFNA and WC. Negative associations were found between prenatal PFOS and BMI in children who were 3 or less years, and between PFHxS and risk of overweight. Relatively more consistent negative associations were evidenced between childhood exposure to three PFASs (PFOA, PFOS, and PFNA) and BMI, in particular PFOS in boys. However, heterogeneity among studies was high. CONCLUSION: Even though heterogeneous across studies, the pooled evidence suggests possible associations, mostly positive, between prenatal exposure to some PFASs and childhood BMI/WC; and relatively stronger evidence for negative associations between childhood exposure to PFASs and childhood BMI.

Follicular steroidogenesis in random start protocols for oocyte cryopreservation.

PURPOSE: Random start protocols are commonly used for oocyte cryopreservation in women with cancer. However, albeit generally reassuring, available evidence is still insufficient to rule out a sub-optimal cycle outcome. This study aimed to compare follicular steroidogenesis between women initiating the random start protocol in the luteal phase and those initiating in the follicular phase. METHODS: Consecutive women with cancer scheduled for oocyte cryostorage were prospectively recruited. We excluded those requiring a concomitant letrozole assumption. All women received a standardized protocol with recombinant FSH and GnRH antagonists. At the time of oocyte retrieval, follicular fluids were pooled, and a sample was collected and frozen at -80 °C. All samples were assayed concomitantly after thawing by liquid chromatography-tandem mass spectrometry. The concentration of 15 different steroid hormones was determined. RESULTS: Seventy-one women were recruited. Thirty-three initiated the ovarian stimulation in the luteal phase, while the remaining 38 initiated in the follicular phase. Baseline characteristics were generally similar. Cycle outcome did also not differ; the median (interquartile range) number of frozen mature oocytes was 9 (5-14) and 10 (5-21), respectively (p = 0.42). None of the 15 tested steroid hormones differed. CONCLUSIONS: The endocrine microenvironment surrounding oocytes is not markedly influenced by the phase of the menstrual cycle at the initiation of ovarian stimulation. This result further supports the validity of random start protocols.

Metabolomic profiles in night shift workers: A cross-sectional study on hospital female nurses.

Background and aim: Shift work, especially including night shifts, has been found associated with several diseases, including obesity, diabetes, cancers, and cardiovascular, mental, gastrointestinal and sleep disorders. Metabolomics (an omics-based methodology) may shed light on early biological alterations underlying these associations. We thus aimed to evaluate the effect of night shift work (NSW) on serum metabolites in a sample of hospital female nurses. Methods: We recruited 46 nurses currently working in NSW in Milan (Italy), matched to 51 colleagues not employed in night shifts. Participants filled in a questionnaire on demographics, lifestyle habits, personal and family health history and work, and donated a blood sample. The metabolome was evaluated through a validated targeted approach measuring 188 metabolites. Only metabolites with at least 50% observations above the detection limit were considered, after standardization and log-transformation. Associations between each metabolite and NSW were assessed applying Tobit regression models and Random Forest, a machine-learning algorithm. Results: When comparing current vs. never night shifters, we observed lower levels of 21 glycerophospholipids and 6 sphingolipids, and higher levels of serotonin (+171.0%, 95%CI: 49.1-392.7), aspartic acid (+155.8%, 95%CI: 40.8-364.7), and taurine (+182.1%, 95%CI: 67.6-374.9). The latter was higher in former vs. never night shifters too (+208.8%, 95%CI: 69.2-463.3). Tobit regression comparing ever (i.e., current + former) and never night shifters returned similar results. Years worked in night shifts did not seem to affect metabolite levels. The Random-Forest algorithm confirmed taurine and aspartic acid among the most important variables in discriminating current vs. never night shifters. Conclusions: This study, although based on a small sample size, shows altered levels of some metabolites in night shift workers. If confirmed, our results may shed light on early biological alterations that might be related to adverse health effects of NSW.

Progestin-primed ovarian stimulation for fertility preservation in women with cancer: A comparative study.

BACKGROUND: In women scheduled for cancer treatment, oocytes cryopreservation is a well-established procedure. Random start protocols have been a substantial improvement in this setting, allowing to prevent delay in the initiation of cancer treatments. However, there is still the need to optimize the regimen of ovarian stimulation, to make treatments more patient-friendly and to reduce costs. METHODS: This retrospective study compares two periods (2019 and 2020), corresponding to two different ovarian stimulation regimens. In 2019, women were treated with corifollitropin, recombinant FSH and GnRH antagonists. Ovulation was triggered with GnRH agonists. In 2020, the policy changed, and women were treated with a progestin-primed ovarian stimulation (PPOS) protocol with human menopausal gonadotropin (hMG) and dual trigger (GnRH agonist and low dose hCG) Continuous data are reported as median [Interquartile Range]. To overcome expected changes in baseline characteristics of the women, the primary outcome was the ratio between the number of mature oocytes retrieved and serum anti-mullerian hormone (AMH) in ng/ml. RESULTS: Overall, 124 women were selected, 46 in 2019 and 78 in 2020. The ratio between the number of mature oocytes retrieved and serum AMH in the first and second period was 4.0 [2.3-7.1] and 4.0 [2.7-6.8], respectively (p = 0.80). The number of scans was 3 [3-4] and 3 [2-3], respectively (p<0.001). The total costs of the drugs used for ovarian stimulation were 940 € [774-1,096 €] and 520 € [434-564 €], respectively (p<0.001). CONCLUSIONS: Random start PPOS with hMG and dual trigger represents an easy and affordable ovarian stimulation protocol for fertility preservation in women with cancer, showing similar efficacy and being more friendly and economical.

Kinetics of Excretion of the Perfluoroalkyl Surfactant cC6O4 in Humans.

cC6O4 is a new-generation perfluoroalkyl surfactant used in the chemical industry for the synthesis of perfluoroalkyl polymers. It was introduced as a less biopersistent substitute of traditional perfluoroalkyl surfactants such as PFOA, but its kinetics in humans was never investigated. This work is aimed to investigate the kinetics of elimination of cC6O4 in exposed workers. Eighteen male individuals occupationally exposed to cC6O4 in the production of fluoropolymers volunteered for the study. Blood and urine samples were collected from the end of a work-shift for the following 5 days off work. Serum and urinary cC6O4 were measured by LC-MS/MS. Seventy-two samples with serum cC6O4 ranging from 0.38 to 11.29 µg/L were obtained; mean levels were 3.07, 2.82, 2.67 and 2.01 µg/L at times 0, 18, 42 and 114 h. Two hundred and fifty-four urine samples with cC6O4 ranging from 0.19 to 5.92 µg/L were obtained. A random-intercept multiple regression model was applied to serum data and a half-life of 184 (95% CI 162-213) h for a first-order kinetics elimination was calculated; a mean distribution volume of 80 mL/kg was also estimated. Pearson's correlation between ln-transformed serum and daily urine concentrations was good, with r ranging from 0.802 to 0.838. The amount of cC6O4 excreted daily in urine was about 20% of the amount present in serum. The study allowed calculating a half-life for cC6O4 in blood of about 8 days in humans, supporting its much shorter biopersistence in comparison with legacy PFAS. The good correlation between urine and serum cC6O4 suggests urine as a possible non-invasive matrix for biomonitoring. The amount of cC6O4 excreted daily in urine suggests urine as the sole elimination route.

A Metabolomics-Based Investigation of the Effects of a Short-Term Body Weight Reduction Program in a Cohort of Adolescents with Obesity: A Prospective Interventional Clinical Study.

Metabolomics applied to assess the response to a body weight reduction program (BWRP) may generate valuable information concerning the biochemical mechanisms/pathways underlying the BWRP-induced cardiometabolic benefits. The aim of the present study was to establish the BWRP-induced changes in the metabolomic profile that characterizes the obese condition. In particular, a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) targeted metabolomic approach was used to determine a total of 188 endogenous metabolites in the plasma samples of a cohort of 42 adolescents with obesity (female/male = 32/10; age = 15.94 ± 1.33 year; body mass index standard deviation score (BMI SDS) = 2.96 ± 0.46) who underwent a 3-week BWRP, including hypocaloric diet, physical exercise, nutritional education, and psychological support. The BWRP was capable of significantly improving body composition (e.g., BMI SDS, p < 0.0001), glucometabolic homeostasis (e.g., glucose, p < 0.0001), and cardiovascular function (e.g., diastolic blood pressure, p = 0.016). A total of 64 metabolites were significantly reduced after the intervention (at least p < 0.05), including 53 glycerophospholipids (23 PCs ae, 21 PCs aa, and 9 lysoPCs), 7 amino acids (tyrosine, phenylalanine, arginine, citrulline, tryptophan, glutamic acid, and leucine), the biogenic amine kynurenine, 2 sphingomyelins, and (free) carnitine (C0). On the contrary, three metabolites were significantly increased after the intervention (at least p < 0.05)-in particular, glutamine, trans-4-hydroxyproline, and the octadecenoyl-carnitine (C18:1). In conclusion, when administered to adolescents with obesity, a short-term BWRP is capable of changing the metabolomic profile in the plasma.

Effects of the therapy shift from cortisone acetate to modified-release hydrocortisone in a group of patients with adrenal insufficiency.

Objective: Patients with adrenal insufficiency (AI) may be exposed to supraphysiological glucocorticoids levels during standard treatment with cortisone acetate (CA) or immediate-release hydrocortisone (IR-HC). Recent studies, predominantly including patients in IR-HC treatment, suggested that modified-release hydrocortisone (MRH) provide a more physiological cortisol rhythm, improving metabolic control and quality of life. Our primary aim was to assess clinical and biochemical modifications in patients shifted from CA to MRH. Design/Methods: We designed a retrospective longitudinal study, enrolling 45 AI patients (22 primary and 23 secondary AI) treated exclusively with CA thrice daily, shifted to MRH once daily; 29/45 patients concluded at least 18-months follow-up (MRH-group). We recruited 35 AI patients continuing CA as a control group (CA-group). Biochemical and clinical data, including metabolic parameters, bone quality, and symptoms of under- or overtreatment were collected. In 24 patients, a daily salivary cortisol curve (SCC) performed before and one month after shifting to MRH was compared to healthy subjects (HS). Results: No significant changes in glycometabolic and bone parameters were observed both in MRH and CA-groups during a median follow-up of 35 months. A more frequent decrease in blood pressure values (23.1% vs 2.8%, p=0.04) and improvement of under- or overtreatment symptoms were observed in MRH vs CA-group. The SCC showed a significant steroid overexposure in both CA and MRH-groups compared to HS [AUC (area under the curve) = 74.4 ± 38.1 nmol×hr/L and 94.6 ± 62.5 nmol×hr/L respectively, vs 44.1 ± 8.4 nmol×hr/L, p<0.01 for both comparisons], although SCC profile was more similar to HS in MRH-group. Conclusions: In our experience, patients shifted from CA to equivalent doses of MRH do not show significant glycometabolic modifications but blood pressure control and symptoms of over-or undertreatment may improve. The lack of amelioration in glucose metabolism and total cortisol daily exposure could suggest the need for a dose reduction when shifting from CA to MRH, due to their different pharmacokinetics.

Selenium exposure and urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine: Major effects of chemical species and sex.

Selenium is an element present in trace amounts and different chemical forms. It may exert both beneficial and adverse effects on cellular redox status and on the generation of reactive oxygen species. 8-oxo-7,8-dihydro-2'deoxyguanosine (8-oxodG) is an oxidized derivative of deoxyguanosine, and a sensitive biomarker of oxidative stress and genotoxicity. The present study assessed the extent to which selenium status was associated with urinary 8-oxodG concentrations in a Northern Italian population. We recruited healthy, non-smoking blood donors living in the Reggio Emilia province during 2017-2019. We measured urinary 8-oxodG concentrations and used restricted cubic spline regression analyses to investigate the association between selenium status (estimated using food frequency questionnaires, urinary concentrations, and serum concentrations of selenium and selenium species) and 8-oxodG/g creatinine. Among 137 participants aged 30-60 years, median urinary selenium and 8-oxodG concentrations were 22.02 µg/L and 3.21 µg/g creatinine, respectively. Serum samples and selenium speciation analyses were available for 104 participants. Median total serum selenium levels and dietary intake were 116.5 µg/L and 78.7 µg/day, respectively. In spline regression analysis, there was little association between dietary, serum, or urinary selenium with 8-oxodG concentrations. In sex-specific analyses, urinary selenium showed a positive association with the endpoint among males. For single selenium species, we observed positive associations with urinary 8-oxodG for serum organic selenium species, and negative associations for inorganic selenium forms. In the most adjusted analysis, urinary 8-oxodG concentrations showed a strong positive association with selenomethione-bound selenium (Se-Met) and a negative association with inorganic tetravalent selenium, selenite. In sex-specific analyses, these associations were considerably stronger in males than in females. Overall, study findings indicate that selenium species exhibited very different patterns of associations with the biomarker of oxidative stress, and that these associations also depended on sex. Background exposure to Se-Met appears to be strongly and positively associated with oxidative stress.

Historical Trend of Exposure to Perfluoroalkyl Surfactants PFOA, ADV, and cC6O4 and its Management in Two Perfluoroalkyl Polymers Plants, Italy.

OBJECTIVES: Perfluoroalkyl acid surfactants are used in the chemical industry for the synthesis of perfluoroalkyl polymers. In one Italian fluoropolymer plant and in the research and innovation center, two major perfluoroalkyl surfactants have been historically used: PFOA and ADV and a third, cC6O4 substituted PFOA from mid-2013. This work is summarizing occupational exposure to these chemicals in the period 2004-2021, assessed by biological monitoring. Moreover, taking advantage of the phasing out of PFOA, the elimination kinetics of PFOA in humans is investigated. METHODS: Workers exposed to PFOA (from beginning of the sixties to 2013), ADV (since 1996), and/or cC6O4 (since 2012) in the production of fluoropolymers, in the synthesis, research, and analysis, were periodically surveyed from 2004, measuring the concentration of perfluoroalkyl acid surfactants in serum. Workers of the same plants, not directly exposed, were surveyed as well. Applying the first-order kinetics model, the half-life of PFOA was calculated. RESULTS: 809 Workers were investigated with measurements of PFOA (n = 3692), ADV (n = 4288) and cC6O4 (n = 2272) in serum. In the production plant, median PFOA ranged from 1900 to 14 µg/l from 2004 to 2021; median ADV ranged from 434 to 86 µg/l from 2011 to 2021. For cC6O4 the detection percentage ranged from 9 to 47%; in detected samples median cC6O4 ranged from 3 to 16 µg/l in the period 2013-2021. Adopted mitigation measurements included: the phasing out of PFOA, the improvement of the plastomer and elastomer post-treatments; the reinforcement of the staff involved in prevention. Decreasing trends were observed for all chemicals along years (P value for linear trend of means < 0.01). For PFOA, a half-life of 3.16 (95% CI 2.98-3.37) years was calculated. CONCLUSIONS: In the study plants, several initiatives to reduce exposure and the risk associated with perfluoroalkyl surfactants were undertaken; results of biomonitoring show that they were effective, with a 5- to 136-fold reduction in the concentration of perfluoroalkyl compounds in the serum of workers.

Biological monitoring and personal exposure to traffic-related air pollutants of elementary school-age children living in a metropolitan area.

An ever-growing burden of scientific evidence links air pollution to different aspects of human health even at very low concentrations; the impact increases for those living in urban environments, especially the youngest and the elderly. This study investigated the exposure to air pollution of urban school children of Milan, Italy, by personal and biological monitoring, in the frame of the MAPS-MI project. A total of 128 primary school children (7-11 years) were involved in a two-season monitoring campaign during spring 2018 and winter 2019. Personal exposure to airborne VOCs and eBC, and biological monitoring of urinary benzene (BEN-U) and methyl-tert-butyl ether (MTBE-U) were performed. Time-activity patterns, environmental tobacco smoke (ETS), spatial, and meteorological information were evaluated as determinants in mixed effects regression analysis. Children personal exposure was mostly quantifiable with median (5th-95th percentile) levels 1.9 (0.8-7.5) µg/m3 for eBC, and 1.1 (<0.6-3.4) and 0.8 (0.3-1.8) µg/m3 for benzene and MTBE, respectively; with values 2-3-fold higher in winter than in spring. In urine, median (5th-95th) BEN-U and MTBE-U levels were 44.9 (25.7-98.6) and 11.5 (5.0-35.5) ng/L, respectively. Mixed effect regression models explained from 72 to 93 % of the total variability for air pollutants, and from 58 to 61 % for biomarkers. Major contributors of personal exposure were season, wind speed, mobility- or traffic-related variables; biomarkers were mostly predicted by airborne exposure and ETS. Our results suggest that traffic-mitigation actions, together with parents' educational interventions on ETS and commuting mode, should be undertaken to lower children exposure to air pollution.

Assessing Smoking Habits, Attitudes, Knowledge, and Needs among University Students at the University of Milan, Italy.

BACKGROUND: College campuses and universities are valuable settings for smoking prevention programs targeting young adults. AIM: To investigate smoking habits, electronic cigarette (e-cig) and heated tobacco product (HTP) use, exposure to passive smoke, compliance with smoking bans on campus, attitudes toward the anti-smoking policies, and educational needs among students at the University of Milan, Italy. METHODS: A validated questionnaire was web-submitted to 64,801 students in the period May-July 2021. For each item, the frequency was calculated and χ2 test with Bonferroni correction was used to compare differences among the 10 faculties of the University. RESULTS: 7162 students participated in the survey, while 6605 questionnaires were included in this report (62% female, 84% aged 18-25 years). Sixty-four percent of participants were never smokers, 19% were smokers, 2.8% were e-cig or HTP users, 3.7% were dual smokers, 10% were former smokers, and 66% reported routinely spending free time with smokers. Almost all students were aware of the dangers of active and passive smoking of cigarettes, while about 20% did not have an opinion on the dangers of e-cigs/HTPs. Only 49% were aware of the smoking ban in the outdoor areas of the university. Students from the faculties of Law and Political, Economic, and Social Sciences smoked more frequently and were more frequently exposed to passive smoke than other students. Medicine students were the most aware of the dangers of passive smoking and using e-cigs/HTPs. CONCLUSIONS: This is the first study in Italy involving the entire student population of a university and highlighting differences among faculties in terms of active and passive smoking and opinions. The results suggest that prevention campaigns addressed to students should consider their specific study curricula and give information tailored to the different educational needs to efficiently support health promotion.

Heme Biosynthetic Gene Expression Analysis With dPCR in Erythropoietic Protoporphyria Patients.

Background: The heme biosynthesis (HB) involves eight subsequent enzymatic steps. Erythropoietic protoporphyria (EPP) is caused by loss-of-function mutations in the ferrochelatase (FECH) gene, which in the last HB step inserts ferrous iron into protoporphyrin IX (PPIX) to form heme. Aim and method: The aim of this work was to for the first time analyze the mRNA expression of all HB genes in peripheral blood samples of patients with EPP having the same genotype FECH c.[215dupT]; [315-48T > C] as compared to healthy controls by highly sensitive and specific digital PCR assays (dPCR). Results: We confirmed a decreased FECH mRNA expression in patients with EPP. Further, we found increased ALAS2 and decreased ALAS1, CPOX, PPOX and HMBS mRNA expression in patients with EPP compared to healthy controls. ALAS2 correlated with FECH mRNA expression (EPP: r = 0.63, p = 0.03 and controls: r = 0.68, p = 0.02) and blood parameters like PPIX (EPP: r = 0.58 p = 0.06). Conclusion: Our method is the first that accurately quantifies HB mRNA from blood samples with potential applications in the monitoring of treatment effects of mRNA modifying therapies in vivo, or investigation of the HB pathway and its regulation. However, our findings should be studied in separated blood cell fractions and on the enzymatic level.