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Abstract Background Telomere shortening in blood leukocytes has been associated with increased morbidity and death from cardiovascular disease and cancer, but determinants of shortened telomeres, a molecular feature of biological aging, are still largely unidentified. Traffic pollution has been linked with both cardiovascular and cancer risks, particularly in older subjects. Whether exposure to traffic pollution is associated with telomere shortening has never been evaluated. Methods We measured leukocyte telomere length (LTL) by real-time PCR in blood DNA from 77 traffic officers exposed to high levels of traffic pollutants and 57 office workers (referents). Airborne benzene and toluene, as tracers for traffic exposure, were measured using personal passive samplers and gas-chromatography/flame-ionization detector analysis. We used covariate-adjusted multivariable models to test the effects of the exposure on LTL and obtain adjusted LTL means and 95% Confidence Intervals (CIs). Results Adjusted mean LTL was 1.10 (95%CI 1.04-1.16) in traffic officers and 1.27 in referents (95%CI 1.20-1.35) [p < 0.001]. LTL decreased in association with age in both traffic officers (p = 0.01) and referents (p = 0.001), but traffic officers had shorter LTL within each age category. Among traffic officers, adjusted mean relative LTL was shorter in individuals working in high (n = 45, LTL = 1.02, 95%CI 0.96-1.09) compared to low traffic intensity (n = 32, LTL = 1.22, 95%CI 1.13-1.31) [p < 0.001]. In the entire study population, LTL decreased with increasing levels of personal exposure to benzene (p = 0.004) and toluene (p = 0.008). Conclusion Our results indicate that leukocyte telomere length is shortened in subjects exposed to traffic pollution, suggesting evidence of early biological aging and disease risk.

Background: The rapid growth of the digital economy has transformed various labor markets, including the food sector. The transient nature and the peculiar work environments of food delivery workers raise concerns about occupational safety and health (OSH). This study aims to better understand these issues by conducting a comprehensive exploratory survey on OSH among food delivery riders in Milan, Italy., Methods:  The study employed structured interviews based on a validated questionnaire developed through a literature review, expert interviews, and input from riders and health and safety professionals. The survey was performed from July to November 2022 by interviewing riders at their main gathering points., Results: We interviewed 240 riders, 97% males, 81% less than 35 years old, and 83% with extra-European origin. Delivery was performed mainly by traditional bicycles (40%) and e-bikes (46%), with 44% working seven days per week and 23% working more than 8 hours daily. Road accidents were reported by 39% of riders, influenced by type of vehicle, fatigue, and number of daily deliveries. Physical and verbal assaults (12% and 28%, respectively) were reported, as well as health-related issues, particularly musculoskeletal disorders., Conclusions: The findings underscore food delivery riders' complex challenges, emphasizing the need for targeted interventions. The study calls for collaborative efforts between policymakers, employers, OSH professionals, and stakeholders to enhance OSH standards and promote decent working conditions, aligning with the 2030 Agenda for Sustainable Development.

Glyphosate, an herbicide largely used in various contexts, can have adverse effects on human health. Although it is currently the most applied pesticide worldwide, few studies evaluated the extent of human exposure via biomonitoring. To expand such information, biological monitoring of exposure to glyphosate was conducted. The study has a before-and-after design to demonstrate the immediate impact of short-term interventions. Accordingly, the urine concentrations of glyphosate and its main biodegradation product (amino-methylphosphonic acid- AMPA) were measured before and the day after the single herbicide application in 17 male winegrowers. Urine samples were analyzed by high performance liquid chromatography coupled with a triple quadrupole mass spectrometer equipped with an electrospray ionization source. Glyphosate and AMPA were not detectable in pre-application urine samples (limit of quantification for glyphosate (LOQ G ) was 0.1 μg/L; limit of quantification for AMPA (LOQ AMPA ) was 0.5 μg/L). After application, glyphosate urinary levels were above LOQ G in all workers. The median, min, and max values were 2.30, 0.51, and 47.2 μg/L, respectively. The same values were found for 50 %, 5 % and 95 % percentiles. After assigning numerical values, such as one half the LOQ, to each of the non-detects, the "z" of Wilcoxon matched-pairs signed-ranks test was -3.62 (p = 0.0003), suggesting the pre-application values being significantly lower than the post-application urinary glyphosate concentration. A similar analysis was not feasible with AMPA urinary levels, which were detectable only in 3 workers, after application. 12 (71 %) workers were significantly exposed to glyphosate, but adherence to the adoption of personal protective equipment was good: 14 (82 %) workers used gloves, 13 (76 %) used overalls and 13 (76 %) facial masks. Our data show that glyphosate can be absorbed by the workers after a single application and confirms the usefulness of biomonitoring in exposed workers. Further studies are needed in larger working populations and with multiple glyphosate applications, as well as to evaluate the correlations of glyphosate urine levels with exposure questionnaire data, in order to assess the actual relevance of risk and protection factors., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

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.

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/m 2 ), 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/m 2 )., 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Rigamonti, Polledri, Favero, Caroli, Bondesan, Grugni, Mai, Cella, Fustinoni and Sartorio.)

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.

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., (© 2023. The Author(s).)

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., (© 2023. BioMed Central Ltd., part of Springer Nature.)

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 FeSO 4 . Hence, differentiated Caco-2 cells have been used for assessing the in vitro bioavailability and safety of FS and FeSO 4 . MTT experiments demonstrated that both FS and FeSO 4 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 FeSO 4 . Our findings indicate that this formulation can be considered a valuable and efficiently good choice as food supplements for improving iron deficiency.

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., Competing Interests: The authors of this manuscript have the following competing interests: E.S. received honoraria for presentations at meetings from Gedeon-Richter and Merck-Serono. He is also handling two grants of research from Ferring. None of the remaining authors reported any conflict of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Filippi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: This study aimed to evaluate older people's experience of a COVID-19 partial lockdown (16 March-11 May 2020) in Lausanne, Switzerland., Setting and Participants: Community-dwelling participants of the Lausanne cohort (Lc65+) in 2020, aged 71-86 years (n=2642)., Design and Outcome: This cross-sectional study was nested within the Lc65+ longitudinal study. A specific COVID-19 questionnaire was sent on 17 April 2020 to evaluate participants' experience of the lockdown (outcome). Multinomial logistic regression models were used to determine the sociodemographic, living environment, health and social factors associated., Results: Out of 2642 participants, 67.8% described the lockdown as 'somewhat' difficult (reference group), 21.5% as 'not at all' difficult (positive) and 10.7% as 'very or extremely' difficult (negative). The relative risk of a positive experience was higher in participants living alone (relative risk ratio, RRR=1.93, 95% CI 1.52 to 2.46) or in a house (RRR=1.49, 1.03 to 2.16); lower in those who reported fear of falling (RRR=0.68, 0.54 to 0.86), functional difficulties (RRR=0.78, 0.61 to 0.99), feeling of loneliness (RRR=0.67, 0.49 to 0.91), unfamiliarity with communication technologies (RRR=0.69, 0.52 to 0.91), usual social support (RRR=0.71, 0.50 to 0.93), previous participation in group activities (RRR=0.74, 0.59 to 0.92) and among women (RRR=0.75, 0.59 to 0.95). The relative risk of a negative experience was higher in participants with fear of falling (RRR=1.52, 1.07 to 2.15), and lower in those who had a terrace/garden (RRR=0.66, 0.44 to 0.99) and owned a dog (RRR=0.32, 0.11 to 0.90)., Conclusions: Only one in 10 participants experienced the lockdown as very or extremely difficult. Specific interventions targeting vulnerability factors, such as fear of falling, could lessen the impact of any future similar situation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

cC 6 O 4 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 cC 6 O 4 in exposed workers. Eighteen male individuals occupationally exposed to cC 6 O 4 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 cC 6 O 4 were measured by LC-MS/MS. Seventy-two samples with serum cC 6 O 4 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 cC 6 O 4 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 cC 6 O 4 excreted daily in urine was about 20% of the amount present in serum. The study allowed calculating a half-life for cC 6 O 4 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 cC 6 O 4 suggests urine as a possible non-invasive matrix for biomonitoring. The amount of cC 6 O 4 excreted daily in urine suggests urine as the sole elimination route.

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Borroni, Frigerio, Polledri, Mercadante, Maggioni, Fedrizzi, Pesatori, Fustinoni and Carugno.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Frigerio, Carosi, Ferrante, Sala, Polledri, Fustinoni, Ambrosi, Chiodini, Mantovani, Morelli and Arosio.)