Concordance between CDKN2A homozygous deletion and MTAP immunohistochemical loss in fluoroedenite-induced pleural mesothelioma: An immunohistochemical and molecular study on a single-institution series.

Fluoroedenite-induced pleural mesothelioma (FE-induced-PM) is a rare and small subset of PM that shares with its asbestos-induced counterpart the same aggressive biological behavior and poor prognosis, but that differs from it from a pathogenetic point of view as it is associated with exposure to fluoroedenite, a carcinogenic agent that shows similarities with tremolite amphibolic asbestos fibers. Although it has been demonstrated that asbestos-induced PMs frequently harbor CDKN2A homozygous deletion and that the immunohistochemical loss of MTAP may represent a cheap and reliable surrogate marker for this molecular alteration, little is known about the molecular landscape and the reliability of MTAP immunohistochemistry in this peculiar subset of PM. The study herein presented investigated the prevalence of CDKN2A homozygous deletion and its concordance with MTAP immunohistochemical status on a cohort of 10 cases of FE-induced-PM from patients with environmental exposure to FE fibers, who were residents in the small town of Biancavilla (Sicily, Italy) or nearby areas. CDKN2A homozygous deletions were found in 3 out of 10 cases (30%) and all these cases showed concomitant cytoplasmic loss of MTAP with a concordance rate of 100%. Despite the relatively low number of cases included in our series, MTAP immunohistochemistry seemed to represent a reliable immunohistochemical surrogate marker of CDKNA homozygous deletion even in this subset of PMs.

Corrigendum: Time-Trends in Air Pollution Impact on Health in Italy, 1990-2019: An Analysis from the Global Burden of Disease Study 2019.

[This corrects the article DOI: 10.3389/ijph.2023.1605959.].

Decade-long insights: tracking asbestos-related health impacts among formerly exposed workers in Palermo, Italy.

Background: Asbestos is a foremost occupational carcinogen globally. Despite the prohibition under Law 257/1992, Italy persists as one of the European nations most burdened by asbestos-related diseases (ARDs). This research assessed ARD cases in asbestos-exposed workers from the Province of Palermo, Italy, spanning 2010-2021. Methods: Data acquisition utilized the epidemiological dataset from the 'Service of Prevention and Safety on Work Environment' under the Prevention Department of Palermo's Local Health Authority (LHA). Results: Between 2010 and 2021, we identified 245 ARD instances, comprising 163 Asbestosis/Pleural plaques, 41 Lung Cancers, 38 Mesotheliomas, and 3 unspecified cases. Multivariate analysis indicated a notable decline in temporal exposure for mesothelioma (HR=0.933; 95% CI=0.902-0.965) and lung cancer (HR=0.93; 95% CI=0.90-0.978) relative to pleural plaques/asbestosis. Tobacco use displayed a pronounced correlation with lung cancer (smoker HR=64.520 95% CI=13,075-318.390; former smoker HR=20.917 95% CI=4,913-89.048). A significant link was observed between mesothelioma and pleural plaques/asbestosis in those employed in shipbuilding and repair (HR=0.371 95% CI=0.155-0.892). Conclusions: ARDs persist in clinical observations, even following the 1992 cessation of asbestos-related activities, emphasizing an enduring public health challenge. Enhancing prevention strategies is paramount, focusing on amplifying anamnestic and occupational data collection, thereby facilitating superior early diagnosis strategies for these maladies in the occupationally exposed cohort.

Mesothelin methylation, soluble mesothelin related protein levels and inflammation profiling in workers chronically exposed to naturally occurring asbestos fibers.

Exposure to asbestiform fibers, including chrysotile and amphibole, is carcinogenic, causing malignant pleural mesothelioma (MPM) when inhaled. Some populations globally face Naturally Occurring Asbestos (NOA) exposure, leading to MPM cases like in Biancavilla, Italy, from Fluoro-edenite (FE) contamination. Studies show NOA exposure causes epigenetic changes, focusing on mesothelin methylation, an MPM marker, and altered inflammation, emphasizing the health risks of FE and asbestos. This research, conducted from February 2022 to October 2022, studied 125 construction workers from Biancavilla and 125 controls from 40 km away without Biancavilla work history. With at least ten years in construction and no respiratory conditions, participants underwent medical assessments and gave blood samples for analysis, including inflammation markers, mesothelin methylation, and soluble mesothelin-related protein levels. The results showed similar demographics but differing inflammation and methylation levels in exposed workers, suggesting long-term cellular changes. Pearson correlation showed intricate biomarker relationships. Significant inflammatory differences were found between FE exposed and non-exposed workers, indicating potential health impacts from FE. This raises concerns for communities like Biancavilla, emphasizing the importance of extensive epigenetic research for public health.

Influenza immunization of healthcare personnel in the post-COVID-19 pandemic era: Still a lot to do!

Healthcare-associated influenza is frequently encountered in healthcare settings with significant morbidity and mortality among vulnerable patients, absenteeism among healthcare personnel (HCP), and interruption of healthcare services. Numerous investigations indicate that nosocomial outbreaks are often traced to HCP. Despite the international and national endorsements, seasonal influenza vaccine acceptance among HCP continues suboptimal worldwide. Infection control is the major objective for healthcare risk management in order to guarantee patient safety, limit the cost of hospitalization and assurance health management in controlling influenza seasons. Vigilance and anticipation are required as globally we are moving from a reactive COVID-19 pandemic response phase to one of planning for the co-circulation of viral respiratory infections. Declining to understand HCP perception of influenza risk and acceptance of vaccination might have impact patient safety as well as healthcare services.

Absenteeism of Healthcare Personnel in the COVID-19 Era: A Systematic Review of the Literature and Implications for the Post-Pandemic Seasons.

This systematic review aimed to assess COVID-19-associated absenteeism among healthcare personnel (HCP). PubMed was searched on 4 February 2023. Inclusion criteria were the presentation of original data on COVID-19-associated absenteeism among HCP. Exclusion criteria were absenteeism associated with burnout, mental health illness, post-COVID syndrome, or child-care. Nineteen articles were identified; fifteen concerned almost exclusively the first pandemic year. Hospitals accounted for most data. There was heterogeneity across studies in terms of presentation of absenteeism data. Before COVID-19 vaccines became available, COVID-19 was a major driver of HCP absenteeism with excess costs, while the mean duration of absenteeism ranged from 5.82 to 33 days per episode of absence. Determinant factors of absenteeism rates were department of employment, high-risk exposure, age, profession, and work experience of HCP, suspected COVID-19, SARS-CoV-2 testing, SARS-CoV-2 positivity, and return-to-work strategy. Two studies demonstrated that COVID-19 vaccination significantly reduced the burden of absenteeism. Routine testing of asymptomatic HCP and use of personal protective equipment also significantly ameliorated absenteeism. In conclusion, COVID-19 has been a major driver of HCP absenteeism. Research is needed to assess how COVID-19 will impact HCP in the next years, considering the new SARS-CoV-2 variants, the co-circulation of other respiratory viruses, and the newer COVID-19 vaccines. Networks are needed to survey morbidity and absenteeism among HCP in real-time and guide vaccination policies.

Keratinocytes Exposed to Blue or Red Light: Proteomic Characterization Showed Cytoplasmic Thioredoxin Reductase 1 and Aldo-Keto Reductase Family 1 Member C3 Triggered Expression.

Several cell-signaling mechanisms are activated by visible light radiation in human keratinocytes, but the key regulatory proteins involved in this specific cellular response have not yet been identified. Human keratinocytes (HaCaT cells) were exposed to blue or red light at low or high irradiance for 3 days in cycles of 12 h of light and 12 h of dark. The cell viability, apoptotic rate and cell cycle progression were analyzed in all experimental conditions. The proteomic profile, oxidative stress and mitochondrial morphology were additionally evaluated in the HaCaT cells following exposure to high-irradiance blue or red light. Low-irradiance blue or red light exposure did not show an alteration in the cell viability, cell death or cell cycle progression. High-irradiance blue or red light reduced the cell viability, induced cell death and cell cycle G2/M arrest, increased the reactive oxygen species (ROS) and altered the mitochondrial density and morphology. The proteomic profile revealed a pivotal role of Cytoplasmic thioredoxin reductase 1 (TXNRD1) and Aldo-keto reductase family 1 member C3 (AKR1C3) in the response of the HaCaT cells to high-irradiance blue or red light exposure. Blue or red light exposure affected the viability of keratinocytes, activating a specific oxidative stress response and inducing mitochondrial dysfunction. Our results can help to address the targets for the therapeutic use of light and to develop adequate preventive strategies for skin damage. This in vitro study supports further in vivo investigations of the biological effects of light on human keratinocytes.

Unmasking the Hidden Danger: A Decade-Long Systematic Review of Case-Control Studies on Single Occupational Risks and Prostate Cancer.

The present systematic review addresses the influence of occupational exposures on prostate cancer risk. Eleven studies were analyzed for a range of occupational exposures, including but not limited to firefighting, physical activity, night shift work, chemical exposure, and solar ultraviolet radiation. The results of the review reveal that firefighters exposed to harmful substances, individuals engaged in physically strenuous work, and workers with chronic night shift routines showed an increased likelihood of developing prostate cancer. Moreover, the review identified an increased risk associated with exposure to certain chemicals, including alkylphenolic compounds and benzene-related substances. The evidence underscores the importance of considering the cumulative effect of multiple risk factors in a comprehensive risk assessment. However, the conclusions indicate the necessity for further research to deepen these relationships and develop more effective strategies for the prevention of prostate cancer.

Expression of stathmin in asbestos-like fibers-induced mesothelioma: A preliminary report.

BACKGROUND: Mesothelioma is strongly associated with exposure to asbestos fibers, however, recent studies have also linked exposure to "naturally occurring asbestos" fibers with this disease. Fluoro-edenite, a silicate mineral found in the southeast of Biancavilla (Sicily, Italy), has been identified as a potential risk factor for mesothelioma. Unfortunately, this cancer often has a poor prognosis, and current diagnostic and prognostic biomarkers are inadequate. Histological subtype, gender, and age at diagnosis are the most significant parameters for mesothelioma. Stathmin, a cytosolic protein that regulates cell growth and migration and is overexpressed in many human malignancies, has not yet been linked to mesothelioma survival or clinical-pathological variables. AIM: The aim of this study was to investigate the immunohistochemical expression of stathmin in ten mesothelioma tissue samples with available clinical and follow-up data. MATERIAL AND METHODS: Paraffin-embedded tissue samples from ten mesothelioma patients were processed for immunohistochemical analyses to evaluate stathmin expression. RESULTS: Our findings suggest that stathmin overexpression is associated with shorter overall survival in patients with mesothelioma. Furthermore, stathmin expression was significantly correlated with the survival time of mesothelioma patients. CONCLUSION: Our results suggest that stathmin expression may serve as a potential prognostic biomarker for mesothelioma. This biomarker could be used to promptly identify patients with poor prognosis and to guide clinicians in the selection of treatment options.

Time-Trends in Air Pollution Impact on Health in Italy, 1990-2019: An Analysis From the Global Burden of Disease Study 2019.

Objectives: We explored temporal variations in disease burden of ambient particulate matter 2.5 µm or less in diameter (PM2.5) and ozone in Italy using estimates from the Global Burden of Disease Study 2019. Methods: We compared temporal changes and percent variations (95% Uncertainty Intervals [95% UI]) in rates of disability adjusted life years (DALYs), years of life lost, years lived with disability and mortality from 1990 to 2019, and variations in pollutant-attributable burden with those in the overall burden of each PM2.5- and ozone-related disease. Results: In 2019, 467,000 DALYs (95% UI: 371,000, 570,000) were attributable to PM2.5 and 39,600 (95% UI: 18,300, 61,500) to ozone. The crude DALY rate attributable to PM2.5 decreased by 47.9% (95% UI: 10.3, 65.4) from 1990 to 2019. For ozone, it declined by 37.0% (95% UI: 28.9, 44.5) during 1990-2010, but it increased by 44.8% (95% UI: 35.5, 56.3) during 2010-2019. Age-standardized rates declined more than crude ones. Conclusion: In Italy, the burden of ambient PM2.5 (but not of ozone) significantly decreased, even in concurrence with population ageing. Results suggest a positive impact of air quality regulations, fostering further regulatory efforts.

Immunohistochemical expression of cAMP in fluoroedenite­induced malignant pleural mesothelioma: Preliminary results.

Despite advances in understanding of the biology of malignant pleural mesothelioma (MPM), the prognosis of this malignancy remains poor. Although asbestos still remains the main pathogenic agent of MPM, other asbestos­like fibers such as fluoro­edenite (FE) fibers, induce MPM. Notable incidence and mortality rates of MPM have been found in Biancavilla, Italy, where FE fibers have been extracted from building materials for >50 years. Cyclic adenosine monophosphate (cAMP) is a secondary messenger that plays a key role in several physiological and pathological mechanisms regulating protein kinase A (PKA) and the CREB pathway. Hyperactivation of the cAMP/PKA/CREB pathway is involved in many neoplastic processes, including tumor cell proliferation, invasion and metastatic spread. The present study investigated immunohistochemical expression of cAMP in patients with FE­induced MPM, which included six males and four females with an age range of 50­93 years. There was high immunoexpression of cAMP in 5 out of 10 tumors while the remaining 5 cases showed low immunoexpression. In addition, there was a correlation between cAMP overexpression and decreased survival times (mean overall survival times, 7.5 months in high expression group vs. 18 months in low expression group).

Small RNA-Seq Transcriptome Profiling of Mesothelial and Mesothelioma Cell Lines Revealed microRNA Dysregulation after Exposure to Asbestos-like Fibers.

Environmental exposure to fibers of respirable size has been identified as a risk for public health. Experimental evidence has revealed that a variety of fibers, including fluoro-edenite, can develop chronic respiratory diseases and elicit carcinogenic effects in humans. Fluoro-edenite (FE) is a silicate mineral first found in Biancavilla (Sicily, Italy) in 1997. Environmental exposure to its fibers has been correlated with a cluster of malignant pleural mesotheliomas. This neoplasm represents a public health problem due to its long latency and to its aggression not alerted by specific symptoms. Having several biomarkers providing us with data on the health state of those exposed to FE fibers or allowing an early diagnosis on malignant pleural mesothelioma, still asymptomatic patients, would be a remarkable goal. To these purposes, we reported the miRNA transcriptome in human normal mesothelial cell line (MeT-5A) and in the human malignant mesothelioma cell line (JU77) exposed and not exposed to FE fibers. The results showed a difference in the number of deregulated miRNAs between tumor and nontumor samples both exposed and not exposed to FE fibers. As a matter of fact, the effect of exposure to FE fibers is more evident in the expression of miRNA in the tumor samples than in the nontumor samples. In the present paper, several pathways involved in the pathogenesis of malignant pleural mesothelioma have been analyzed. We especially noticed the involvement of pathways that have important functions in inflammatory processes, angiogenesis, apoptosis, and necrosis. Besides this amount of data, further studies will be designed for the selection of the most significant miRNAs to test and validate their diagnostic potential, alone or in combination with other protein biomarkers, in high-risk individuals' liquid biopsy to have a noninvasive tool of diagnosis for this neoplasm.

Alterations in Pregnenolone and Testosterone Levels in Male Shift Workers.

Steroid hormone levels are closely related to the endogenous circadian rhythm induced by sleep-wake and dark-light cycles. Shift work that disrupts the circadian rhythm may influence the levels of steroid hormones. The association between shift work and alterations in female sex steroid hormone levels has been studied, but little is known about testosterone and its precursor pregnenolone levels in male shift workers. The present study investigated serum pregnenolone and testosterone levels in a group of shift and daytime male workers. All participants were sampled at the beginning of the morning shift. Lower levels of serum pregnenolone and total testosterone were found in the shift workers compared to the daytime workers. Variations in pregnenolone levels may have consequences for well-being, and they might produce consequences for the levels of hormones downstream of the steroid hormone cascade, such as testosterone. The low levels of testosterone found in shift workers demonstrate the perturbative effect of shift work on testosterone serum levels, which may be independent and/or related to pregnenolone synthesis.

COVID-19 vaccination refusal and suspension of work among healthy healthcare personnel in Italy: A cross-sectional study of their knowledge and attitudes toward vaccinations.

Despite the initial optimistic projections from various countries and the evidence that vaccination against coronavirus disease 2019 (COVID-19) reduces the associated hospitalization rates and mortality, vaccine hesitancy and refusal among healthcare personnel (HCP) became a major public health concern globally. The aim of this survey was to estimate the knowledge about the Italian Vaccination Plan for HCP and attitudes about occupational vaccinations for HCP among Italian HCP who refused COVID-19 vaccination and were suspended from work. A total of 52 HCP participated in the study. Nurses were the prevalent profession among vaccination refusers. About COVID-19, 24 (26.2%) of all responders have been involved in COVID-19 care and 21 (40.4%) had a history of COVID-19. None had received influenza and pneumococcus vaccination in the past. Knowledge of vaccinations recommended for HCP was high, ranging from 75% to 98% by vaccine. Instead, all HCP were against any mandatory vaccination policy for all HCP. Finally, most HCP questioned the expected benefits and safety of vaccines in general, raised issues of mistrust of information provided for authorities and of compliance with their HCP' vaccination recommendations. Our study indicates good knowledge of occupational vaccinations but strong anti-vaccination beliefs among Italian HCP who refused COVID-19 vaccination and were suspended from work.

Evaluation of Cardiovascular Activity and Emotional Experience in Healthcare Workers (HCWs) Operating in COVID-19 Wards.

The new 2019 coronavirus or SARS-CoV-2 has been the first biological agent to generate, in this millennium, such a global health emergency as to determine the adoption of public health measures. During this sanitary emergency, the emotional experience of healthcare workers (HCWs) has been hugely tested by several factors. In fact, HCWs have been exposed to greatly tiring physical, psychological and social conditions. The authors investigated the cardiocirculatory activity of a group of HCWs as well as how they perceived stress while working in COVID-19 wards. In particular, every HCW underwent a medical check, an electrocardiographic base exam, systolic and diastolic pressure measurement, and cardio frequency measurement. Furthermore, each HCW was provided with a cardiac Holter device (HoC) and a pressure Holter (Hop). Some psychological factors were considered in order to quantify the stress perceived by each HCW while at work through the administration of two questionnaires: the "Social Stigma towards Patients due to COVID Scale (SSPCS)" and the "Professional Quality of Life Scale (ProQOL)". The HoC and HoP analysis results for HCWs working in COVID-19 OU wards showed significant variations in cardiocirculatory activity. From the analysis of the SSPCS questionnaire answers, it is clear that all of them showed a sense of duty towards their patients. The analysis of the ProQOL questionnaire answers showed that the prevailing attitude is fear; however, HCWs did not absolutely discriminate against those who had COVID-19 nor did they refuse to help those in need. Continuous monitoring of these employees, also carried out through occupational medicine surveillance, allows for the detection of critical conditions and the implementation of actions aimed at preventing chronic processes.

Dysregulation of microRNAs and tRNA-derived ncRNAs in mesothelial and mesothelioma cell lines after asbestiform fiber exposure.

Experimental evidence demonstrated that fluoro-edenite (FE) can develop chronic respiratory diseases and elicit carcinogenic effects. Environmental exposure to FE fibers is correlated with malignant pleural mesothelioma (MPM). An early diagnosis of MPM, and a comprehensive health monitoring of the patients exposed to FE fibers are two clinical issues that may be solved by the identification of specific biomarkers. We reported the microRNA (miRNA) and transfer RNA-derived non coding RNA (tRNA-derived ncRNA) transcriptome in human normal mesothelial and malignant mesothelioma cell lines exposed or not exposed to several concentration FE fibers. Furthermore, an interactive mesothelioma-based network was derived by using NetME tool. In untreated condition, the expression of miRNAs and tRNA-derived ncRNAs in tumor cells was significantly different with respect to non-tumor samples. Moreover, interesting and significant changes were found after the exposure of both cells lines to FE fibers. The network-based pathway analysis showed several signaling and metabolic pathways potentially involved in the pathogenesis of MPM. From papers analyzed by NetME, it is clear that many miRNAs can positively or negatively influence various pathways involved in MPM. For the first time, the analysis of tRNA-derived ncRNAs molecules in the context of mesothelioma has been made by using in vitro systems. Further studies will be designed to test and validate their diagnostic potential in high-risk individuals' liquid biopsies.

Vaccination policies for healthcare personnel: Current challenges and future perspectives.

Healthcare personnel (HCP) are at occupational risk for acquisition of several vaccine-preventable diseases and transmission to patients. Vaccinations of HCP are justified to confer them immunity but also to protect susceptible patients and healthcare services from outbreaks, HCP absenteeism and presenteeism. Mandatory vaccination policies for HCP are increasingly adopted and achieve high and sustainable vaccination rates in short term. In this article we review the scientific evidence for HCP vaccination. We also address issues pertaining to vaccination policies for HCP and present the challenges of implementation of mandatory versus voluntary vaccination policies. Finally, we discuss the issue of mandatory vaccination of HCP against COVID-19.