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Personalized medicine, and particularly gender medicine, is becoming essential in daily medical practice. This narrative review aims to assess sex and gender differences in occupational risks among workers. We point out that female workers are more exposed to biological risks (i.e., 70% of healthcare workers during the COVID-19 pandemic were women), but also seem to be more protected against microorganisms (i.e., for HBV vaccination: OR 1.21, p = 0.0023); with regard to physical risks, women are more susceptible to radiations (the estimated incidence of solid tumors for 0.1 Gy of exposure is 0.013% in females and 0.008% in males), while men are more susceptible to heat (infertility prevalence was 22.7% in exposed workers vs 3.0% in controls); female video terminal workers are more susceptible to both computer vision syndrome (aOR 2.57 and aOR 2.35) and musculoskeletal symptoms (OR 3.6). From a psychological point of view, women are more at risk for work-related stress and burnout, as well as workplace mobbing (65% of affected workers are women) and verbal violence, while physical violence was more common among men. In conclusion, important sex and gender differences are present with regard to occupational risks and hazards, thus showing the necessity to improve medical surveillance and to allow occupational physicians to personalize health surveillance.

Background: Alcohol consumption is prohibited in some categories of workers due to its temporary and longterm effects. The purpose of this study is to review and evaluate the use of carbohydrate-deficient transferrin (CDT) as a biomarker to screen alcohol consumption in workers. Methods: A systematic review was performed, searching three databases, PubMed, Scopus and Isi Web of Knowledge, up to December 2021, screening for studies that used CDT as a biomarker in workers. A quality assessment was performed on the included studies. Results: Seven studies met the inclusion criteria, accounting for more than 3200 workers from five different countries; in the samples observed, a positive percentage of CDT was found in the single studies between 7 and 24%. The large interval could be due to the differences in populations in the included studies; furthermore, not all workers are prohibited from drinking on the job. Four out of the seven studies also included questionnaires on alcohol consumption assessment. Finally, included articles were stratified by occupational hazards and by industrial sector. Interestingly, different methods of analysis and different cut-offs were used by the different authors. Conclusions: The use of CDT as a biomarker of alcohol consumption has high specificity. However, further studies are needed to be able to strongly validate the use of CDT for screening purposes in the working population to detect alcohol abuse.

Glioblastoma (GBM), the most commonly occurring primary tumor arising within the central nervous system, is characterized by high invasiveness and poor prognosis. In spite of the improvement in surgical techniques, along with the administration of chemo- and radiation therapy and the incessant investigation in search of prospective therapeutic targets, the local recurrence that frequently occurs within the peritumoral brain tissue makes GBM the most malignant and terminal type of astrocytoma. In the current study, we investigated both GBM and peritumoral tissues obtained from 55 hospitalized patients and the expression of three molecules involved in the onset of resistance/unresponsiveness to chemotherapy: O6-methylguanine methyltransferase (MGMT), breast cancer resistance protein (BCRP1), and A2B5. We propose that the expression of these molecules in the peritumoral tissue might be crucial to promoting the development of early tumorigenic events in the tissue surrounding GBM as well as responsible for the recurrence originating in this apparently normal area and, accordingly, for the resistance to treatment with the standard chemotherapeutic regimen. Notably, the inverse correlation found between MGMT expression in peritumoral tissue and patients' survival suggests a prognostic role for this protein.

The analysis of a lymphoblastoid cell line (5106), derived from a rare individual of normal intelligence with an unmethylated full mutation of the FMR1 gene, allowed us to reconstruct the chain of molecular events leading to the FMR1 inactivation and to fragile X syndrome. We found that lack of DNA methylation of the entire promoter region, including the expanded CGG repeat, correlates with methylation of lysine 4 residue on the N-tail of histone H3 (H3-K4), as in normal controls. Normal levels of FMR1 mRNA were detected by real-time fluorescent RT-PCR (0.8-1.4 times compared with a control sample), but mRNA translation was less efficient (-40%), as judged by polysome profiling, resulting in reduced levels of FMRP protein (approximately 30% of a normal control). These results underline once more that CGG repeat amplification per se does not prevent FMR1 transcription and FMRP production in the absence of DNA methylation. Surprisingly, we found by chromatin immunoprecipitation that cell line 5106 has deacetylated histones H3 and H4 as well as methylated lysine 9 on histone H3 (H3-K9), like fragile X cell lines, in both the promoter and exon 1. This indicates that these two epigenetic marks (i.e. histone deacetylation and H3-K9 methylation) can be established in the absence of DNA methylation and do not interfere with active gene transcription, contrary to expectation. Our results also suggest that the molecular pathways regulating DNA and H3-K4 methylation are independent from those regulating histone acetylation and H3-K9 methylation.

The fragile X syndrome is caused by a >200 CGG repeat expansion within the FMR1 gene promoter, with consequent DNA hypermethylation and inactivation of its expression. To further clarify the mechanisms that suppress the activity of the mutant gene and the conditions that may permit its reactivation, we investigated the acetylation and methylation status of three different regions of the FMR1 gene (promoter, exon 1 and exon 16) of three fragile X cell lines, using a chromatin immunoprecipitation (ChIP) assay with antibodies against acetylated-H3/H4 histones and against dimethylated lysine residues K4 and K9 of histone H3 (H3-K4 and H3-K9). We then coupled the ChIP assay with real-time PCR, obtaining absolute quantification of immunoprecipitated chromatin. Basal levels of histone acetylation and H3-K4 methylation were much higher in transcriptionally active wild-type controls than in inactive fragile X cell lines. Treatment of fragile X cell lines with the DNA demethylating drug 5-aza-2-deoxycytidine (5-azadC), known to reactivate the FMR1 gene, induced a decrease of H3-K9 methylation, an increase of H3 and H4 acetylation and an increase of H3-K4 methylation. Treatment with acetyl-L-carnitine (ALC), a compound that reduces the in vitro expression of the FRAXA fragile site without affecting DNA methylation, caused an increase of H3 and H4 acetylation. However, H3-K4 methylation remained extremely low, in accordance with the observation that ALC alone does not reactivate the FMR1 gene. Our experiments indicate that H3-K4 methylation and DNA demethylation are the main epigenetic switches activating the expression of the FMR1 gene, with histone acetylation playing an ancillary role.