Computational Analyses Reveal Deregulated Clock Genes Associated with Breast Cancer Development in Night Shift Workers.

Breast cancer (BC) is the leading cause of cancer death among women worldwide. Women employed in shift jobs face heightened BC risk due to prolonged exposure to night shift work (NSW), classified as potentially carcinogenic by the International Agency for Research on Cancer (IARC). This risk is linked to disruptions in circadian rhythms governed by clock genes at the cellular level. However, the molecular mechanisms are unclear. This study aimed to assess clock genes as potential BC biomarkers among women exposed to long-term NSW. Clock gene expression was analysed in paired BC and normal breast tissues within Nurses' Health Studies I and II GEO datasets. Validation was performed on additional gene expression datasets from healthy night shift workers and women with varying BC susceptibility, as well as single-cell sequencing datasets. Post-transcriptional regulators of clock genes were identified through miRNA analyses. Significant alterations in clock gene expression in BC compared to normal tissues were found. BHLHE40, CIART, CLOCK, PDPK1, and TIMELESS were over-expressed, while HLF, NFIL3, NPAS3, PER1, PER3, SIM1, and TEF were under-expressed. The downregulation of PER1 and TEF and upregulation of CLOCK correlated with increased BC risk in healthy women. Also, twenty-six miRNAs, including miR-10a, miR-21, miR-107, and miR-34, were identified as potential post-transcriptional regulators influenced by NSW. In conclusion, a panel of clock genes and circadian miRNAs are suggested as BC susceptibility biomarkers among night shift workers, supporting implications for risk stratification and early detection strategies.

Polyphenols: a route from bioavailability to bioactivity addressing potential health benefits to tackle human chronic diseases.

Chronic pathologies or non-communicable diseases (NCDs) include cardiovascular diseases, metabolic syndrome, neurological diseases, respiratory disorders and cancer. They are the leading global cause of human mortality and morbidity. Given their chronic nature, NCDs represent a growing social and economic burden, hence urging the need for ameliorating the existing preventive strategies, and for finding novel tackling therapies. NCDs are highly correlated with unhealthy lifestyle habits (such as high-fat and high-glucose diet, or sedentary life). In general, lifestyle approaches that might improve these habits, including dietary consumption of fresh vegetables, fruits and fibers, may contrast NCD symptoms and prolong life expectancy of affected people. Polyphenols (PPLs) are plant-derived molecules with demonstrated biological activities in humans, which include: radical scavenging and anti-oxidant activities, capability to modulate inflammation, as well as human enzymes, and even to bind nuclear receptors. For these reasons, PPLs are currently tested, both preclinically and clinically, as dietary adjuvants for the prevention and treatment of NCDs. In this review, we describe the human metabolism and bioactivity of PPLs. Also, we report what is currently known about PPLs interaction with gastro-intestinal enzymes and gut microbiota, which allows their biotransformation in many different metabolites with several biological functions. The systemic bioactivity of PPLs and the newly available PPL-delivery nanosystems are also described in detail. Finally, the up-to-date clinical studies assessing both safety and efficacy of dietary PPLs in individuals with different NCDs are hereby reported. Overall, the clinical results support the notion that PPLs from fruits, vegetables, but also from leaves or seeds extracts, are safe and show significant positive results in ameliorating symptoms and improving the whole quality of life of people with NCDs.

Effects of pesticide exposure on the expression of selected genes in normal and cancer samples: Identification of predictive biomarkers for risk assessment.

Pesticides pivotal in controlling pests, can represent a threat for human health. Regulatory agencies constantly monitor their harmful effects, regulating their use. Several studies support a positive association between long-term exposure to pesticides and chronic pathologies, such as cancer. Geno-toxicological biomonitoring has proven to be valuable to assess genetic risks associated with exposure to pesticides, representing a promising tool to improve preventive measures and identify workers at higher risk. In this study, a differential gene expression analysis of 70 candidate genes deregulated upon pesticide exposure, was performed in 10 GEO human gene expression DataSets. It was found that six genes (PMAIP1, GCLM, CD36, SQSTM1, ABCC3, NR4A2) had significant AUC predictive values. Also, CD36 was upregulated in non-transformed cell samples and healthy workers, but downregulated in cancer cells. Further validation in larger groups of workers will corroborate the importance of the identified candidates as biomarkers of exposure/effect.

Sleep disorders, stress coping strategies and neurobehavioral aspects: an outlook on the impact of covid­19 in first­year resident physicians.

The COVID-19 pandemic had a profound impact on the physical and mental health of healthcare professionals. The present study explored the relationship between sleep disorders, stress, coping strategies and neurobehavioral aspects among young physicians during the second wave of the COVID-19 pandemic. Through a multi-assessment approach, this cross-sectional study collected sociodemographic and occupational data from first-year resident doctors in southern Italy. Subjective sleep quality, chronotype, work-related stress, coping approach and mood state were assessed by administering validated questionnaires during face-to-face interviews. Among the 258 resident physicians enrolled in the study, ~25% complained of poor sleep quality, mainly male subjects [odds ratio (OR), 2.52]. Alcohol consumption resulted as a risk factor for poor sleep quality (OR, 1.97). None of the participants reported work-related stress showing, on the contrary, a high score for the vigor factor in the profile of mood state, in particular in subjects with previous working experience with COVID patients and prevention (P<0.040 and P<0.035, respectively). Women were more likely to adopt coping strategies that involved the search for social support, confirming their tendency to manage stressful situations through emotion-focused mechanisms. The set of these results represents a sight on the attitude of young physicians in their approach to facing the COVID-19 pandemic, in its second wave. The pandemic has turned the spotlight on the importance of prevention and early diagnosis of physical health and mental well-being. Further studies are performed to monitor long-term consequences on health status.

Well-Being and Safety in the Workplace.

The workplace represents a critical and time-consuming exposure setting in which workers are continuously exposed to the heterogeneity of hazards, including physical, biological, chemical, and organizational risk factors [...].

Role-Playing Between Environmental Pollutants and Human Gut Microbiota: A Complex Bidirectional Interaction.

There is a growing interest in the characterization of the involvement of toxicant and pollutant exposures in the development and the progression of several diseases such as obesity, diabetes, cancer, as well as in the disruption of the immune and reproductive homeostasis. The gut microbiota is considered a pivotal player against the toxic properties of chemicals with the establishment of a dynamic bidirectional relationship, underlining the toxicological significance of this mutual interplay. In fact, several environmental chemicals have been demonstrated to affect the composition, the biodiversity of the intestinal microbiota together with the underlining modulated metabolic pathways, which may play an important role in tailoring the microbiotype of an individual. In this review, we aimed to discuss the latest updates concerning the environmental chemicals-microbiota dual interaction, toward the identification of a distinctiveness of the gut microbial community, which, in turn, may allow to adopt personalized preventive strategies to improve risk assessment for more susceptible workers.

Work Performance, Mood and Sleep Alterations in Home Office Workers during the COVID-19 Pandemic.

The sudden burst of the COVID-19 pandemic has changed the work environment in favor of remote working, affecting the perception of work quality, satisfaction and performance. This crisis has also influenced workers' mood, sleep quality and general perception of everyday life. Our main purpose in this study was to give empirical contributions about home office workers experiencing remote working during the pandemic by assessing mood spectrum variations, sleep disturbances and the general impact of pandemic in everyday life. This cross-sectional study was performed between November and December 2020 through an online questionnaire. Participants were office workers performing remote work from workstations settled at home. The questionnaire investigated sociodemographic characteristics, health factors, perception of remote working, mood spectrum, sleep quality and pandemic context perception. The sample consisted of 94 respondents: 63 women and 31 men; the mean age was 50.4 years. Study population showed great satisfaction for remote working performance and online services for video connections. Only one third of the participants reported higher levels of irritability and loneliness and 16% of women complained of nightmares. Most of participants stated that the pandemic importantly affected daily life (85.1%). Half of female subjects with children <18 years stated that children's age influenced their work performance. Since the pandemic is still an ongoing issue, the lesson learnt is that local government actions are needed to assist home office workers through tailored programs to support families. Given the central role of women in childcare, female workers would mainly benefit from social support accordingly to their parental tasks and remote work organization.

Assessment of Mancozeb Exposure, Absorbed Dose, and Oxidative Damage in Greenhouse Farmers.

Mancozeb (MNZ) is a fungicide commonly employed in many countries worldwide. This study assesses MNZ absorption dynamics in 19 greenhouse farmers, specifically following dermal exposure, aiming to verify the efficacy of both preventive actions and protective equipment. For data collection, a multi-assessment approach was used, which included a survey to record study population features. MNZ exposure was assessed through the indirect measurement of ethylene thiourea (ETU), widely employed as an MNZ biomarker. The ETU concentration was measured with the patch method, detecting environmental ETU trapped in filter paper pads, applied both on skin and working clothes, during the 8 h work shift. Urine and serum end-of-shift samples were also collected to measure ETU concentrations and well-known oxidative stress biomarkers, respectively, namely reactive oxygen metabolites (ROMs), advanced oxidation protein products (AOPPs), and biological antioxidant potential (BAP). It was observed that levels of ETU absorbed and ETU excreted were positively correlated. Additionally, working clothes effectively protected workers from MNZ exposure. Moreover, following stratification of the samples based on the specific working duty (i.e., preparation and spreading of MNZ and manipulation of MNZ-treated seedlings), it was found that the spreading group had higher ETU-related risk, despite lower chronic exposure levels. AOPP and ROM serum levels were higher in MNZ-exposed subjects compared with non-exposed controls, whereas BAP levels were significantly lower. Such results support an increase in the oxidative stress upon 8 h MNZ exposure at work. In particular, AOPP levels demonstrated a potential predictive role, as suggested by the contingency analysis results. Overall, this study, although conducted in a small group, confirms that ETU detection in pads, as well as in urine, might enable assessment of the risk associated with MNZ exposure in greenhouse workers. Additionally, the measurement of circulating oxidative stress biomarkers might help to stratify exposed workers based on their sensitivity to MNZ. Pivotally, the combination of both ETU measurement and biological monitoring might represent a novel valuable combined approach for risk assessment in farmhouse workers exposed to pesticides. In the future, these observations will help to implement effective preventive strategies in the workplace for workers at higher risk, including greenhouse farmers who are exposed to pesticides daily, as well as to clarify the occupational exposure levels to ETU.

Chronic Pesticide Exposure in Farm Workers Is Associated with the Epigenetic Modulation of hsa-miR-199a-5p.

The increasing use of pesticides in intensive agriculture has had a negative impact on human health. It was widely demonstrated how pesticides can induce different genetic and epigenetic alterations associated with the development of different diseases, including tumors and neurological disorders. Therefore, the identification of effective indicators for the prediction of harmful pesticide exposure is mandatory. In this context, the aim of the study was to evaluate the modification of hsa-miR-199a-5p expression levels in liquid biopsy samples obtained from healthy donors and farm workers with chronic exposure to pesticides. For this purpose, the high-sensitive droplet digital PCR assay (ddPCR) was used to detect variation in the expression levels of the selected microRNA (miRNA). The ddPCR analyses revealed a significant down-regulation of hsa-miR-199a-5p observed in individuals exposed to pesticides compared to control samples highlighting the good predictive value of this miRNA as demonstrated by statistical analyses. Overall, the obtained results encourage the analysis of miRNAs as predictive biomarkers of chronic pesticide exposure thus improving the current strategies for the monitoring of harmful pesticide exposure.

Role of gut microbiome on immunotherapy efficacy in melanoma.

The gut microbiota is considered a key component in many aspects of cancer pathophysiology and response to therapy. In particular, in recent years intriguing evidences has been emerging regarding the role of the intestinal microbiota in the response to immunotherapy and in promoting the development of adverse events, such as colitis. For this reason, studies are being carried out both on pre-clinical models and on humans to study how to predict the response to immunotherapy through the study of the microbiota or how to improve its clinical response through modulation. Promising data have recently been reported through modulation by probiotics or prebiotics, and in particular by fecal microbiota transplantation. The aim of this review is to analyze the evidence regarding the role of the microbiota in immunotherapy with a particular focus on melanoma.

Factors Affecting Perceived Work Environment, Wellbeing, and Coping Styles: A Comparison between Physicians and Nurses during the COVID-19 Pandemic.

The COVID-19 pandemic is a current emergency worldwide. All the consequent changes in sanitary systems have negatively affected the work-life balance. In particular, healthcare workers suffered from anxiety, stress, and depression, mostly nurses compared to physicians. To handle this situation, the adoption of different coping strategies has played a strategic role in psychophysical wellbeing. Our main goal is to the assess the perception of work environment and wellbeing (EQ-5D questionnaire), as well as to analyze possible differences in coping styles between physicians and nurses (brief COPE questionnaire). The arising differences were compared between the two groups, and associations with variables were assessed through a bivariate correlation analysis. This cross-sectional study was conducted from November to December 2020 through an online survey. A total of 172 respondents (117 physicians and 55 nurses), of which 102 were women and 70 were men, accepted to join the study. Our results showed that physicians referred a higher perception of wellbeing, and nurses reported an increased perception of work activity and efficiency, along with an unchanged economic status. The most frequently adopted coping strategies were Active and Planning (self-sufficient coping). Physicians showed a greater tendency to use avoidant coping strategies. More-experienced nurses and physicians were less prone to adopt socially supported coping strategies, emphasizing the need for novel organizational measures at the social dimension that favored sharing and interaction between peers. Future research should aim to further investigate the relationship between the perception of work environment and coping strategies in order to identify risk factors to be prevented by promoting adequate measures at an organizational level.

Toxicology and Microbiota: How Do Pesticides Influence Gut Microbiota? A Review.

In recent years, new targets have been included between the health outcomes induced by pesticide exposure. The gastrointestinal tract is a key physical and biological barrier and it represents a primary site of exposure to toxic agents. Recently, the intestinal microbiota has emerged as a notable factor regulating pesticides' toxicity. However, the specific mechanisms related to this interaction are not well known. In this review, we discuss the influence of pesticide exposure on the gut microbiota, discussing the factors influencing gut microbial diversity, and we summarize the updated literature. In conclusion, more studies are needed to clarify the host-microbial relationship concerning pesticide exposure and to define new prevention interventions, such as the identification of biomarkers of mucosal barrier function.

Women's health and night shift work: Potential targets for future strategies in breast cancer (Review).

Breast cancer is the leading cause of cancer-associated amongst women worldwide. Several studies have shown that individual, environmental and occupational factors can serve an important role in the onset of breast cancer; although the majority of studies have demonstrated this association, and several studies have investigated the biological pathways, it is impossible to describe with certainty the causal relationship that involve circadian rhythm disruption and melatonin dysregulation with the oncogenic processes. Over the years, due to the introduction of more effective screening tools, an increase in the incidence of breast cancer as well as a decrease in the age at diagnosis has been witnessed. Subsequently, an increasing number of individuals have obtained care at a younger age, which has meant that after surgery and chemotherapy, these workers have had to return to work. In light of these paradigmatic changes, the aim of the present review was to identify potential targets for future organisational strategies that should be adopted in the workplace by occupational physicians, both for prevention and for the return-to-work process of working women who have suffered from breast cancer.

Donor program for fecal microbiota transplantation: A 3-year experience of a large-volume Italian stool bank.

BACKGROUND: Due to the increasing rise of C. difficile infection, stool banks and donor programs have been launched to grant access to fecal microbiota transplantation (FMT). Our aim is to describe characteristics and outcomes of the donor program at our stool bank. METHODS: Donor candidates underwent a four-step selection process, including a clinical interview, blood and stool testing, a further questionnaire and a direct stool testing the day of each donation. From March 2020, specific changes to this process were introduced to avoid the potential transmission of COVID-19. We evaluated the rate of excluded candidates at each step of the screening, as well as the number of total fecal aliquots provided by qualified donors. RESULTS: Overall, 114 donor candidates were evaluated. Seventy-five candidates declined to join the program for logistic or personal issues, three were excluded after the questionnaire and seven for positive stool exams. Finally, 29 (25%) subjects qualified as stool donors, and provided 70 stool samples. Fifteen samples were excluded after direct molecular stool testing. A total of 127 aliquots was finally obtained. CONCLUSIONS: Donor recruitment for FMT is a challenging process, and only a small rate of candidates are eligible as donors.

Sleep Quality and Mood State in Resident Physicians during COVID-19 Pandemic.

Since the novel coronavirus (SARS-CoV-2) has spread worldwide, healthcare workers-resident physicians in particular-have been hugely involved in facing the COVID-19 pandemic, experiencing unprecedented challenges in fighting the disease. We aimed to evaluate the prevalence of poor sleep quality, daytime sleepiness, and alterations in mood state profiles in this category. This cross-sectional study, conducted in 2020, enrolled 119 subjects from a university hospital in southern Italy. Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), and Profile of Mood States (POMS) questionnaires were administered to physicians divided into four areas: anesthesiology, medicine, service, and surgery. In the overall sample, approximately 45% reported poor sleep quality, although only nine subjects (8%) reported an ESS score that suggested excessive daytime sleepiness. Alterations in mood profiles were also observed; the Vigor and Fatigue factors were the most altered. In particular, anesthesiologists seem to be the most affected category, showing a profound decrease in Vigor with a concomitant increase in Fatigue. Considering the possible consequences of the COVID-19 pandemic, preventive measures should be adopted, especially those aimed at facilitating a better turnover of physicians, optimizing the working schedule, and improving the organization of work.

Fecal microbiota transplantation for recurrent C. difficile infection in patients with inflammatory bowel disease: experience of a large-volume European FMT center.

Inflammatory bowel disease (IBD) is a risk factor for C. difficile infection (CDI), which, in turn, complicates the clinical course of IBD. Fecal microbiota transplantation (FMT) is safe and effective in patients with IBD and recurrent CDI (rCDI). In our study, patients with IBD and rCDI received FMT by colonoscopy and were followed-up for 8 weeks. The primary outcome was negative C. difficile toxin 8 weeks after FMT. Eighteen patients with IBD were enrolled. Eight patients received sequential FMT either for pseudomembranous colitis or failure of single fecal infusion. At 8-week follow-up the C. difficile toxin was negative in 17 patients, and most (83%) experienced also improvement of IBD disease activity. Overall, we did not observe any serious adverse event.FMT appears to be highly effective and safe in patients with IBD and rCDI and is likely not only to eradicate CDI but also to improve disease activity of IBD.

Genetic and Epigenetic Alterations Induced by Pesticide Exposure: Integrated Analysis of Gene Expression, microRNA Expression, and DNA Methylation Datasets.

Environmental or occupational exposure to pesticides is considered one of the main risk factors for the development of various diseases. Behind the development of pesticide-associated pathologies, there are both genetic and epigenetic alterations, where these latter are mainly represented by the alteration in the expression levels of microRNAs and by the change in the methylation status of the DNA. At present, no studies have comprehensively evaluated the genetic and epigenetic alterations induced by pesticides; therefore, the aim of the present study was to identify modifications in gene miRNA expression and DNA methylation useful for the prediction of pesticide exposure. For this purpose, an integrated analysis of gene expression, microRNA expression, and DNA methylation datasets obtained from the GEO DataSets database was performed to identify putative genes, microRNAs, and DNA methylation hotspots associated with pesticide exposure and responsible for the development of different diseases. In addition, DIANA-miRPath, STRING, and GO Panther prediction tools were used to establish the functional role of the putative biomarkers identified. The results obtained demonstrated that pesticides can modulate the expression levels of different genes and induce different epigenetic alterations in the expression levels of miRNAs and in the modulation of DNA methylation status.

Association between oxidative stress biomarkers and PON and GST polymorphisms as a predictor for susceptibility to the effects of pesticides.

Low levels of pesticides persist in the environment and can affect the health of exposed subjects. Oxidative stress is considered as one of the mechanisms responsible for the adverse effects on human health and some molecules may represent useful biomarkers for the evaluation of this physiological balance. This study investigated the role of these biomarkers, such as advanced oxidation protein products (AOPP), advanced glycation end­products (AGE) and reactive oxygen metabolites (ROMs) in relation to genetic polymorphisms of paraoxonase (PON)1, PON2, glutathione S­transferase pi 1 (GSTP1), glutathione S­transferase theta 1 (GSTT1) and glutathione S­transferase mu 1 (GSTM1). An increase in the levels of these biomarkers is usually inversely associated with the depletion of the biological antioxidant potential (BAP). The results revealed a statistically significant difference in the sex­dependent variation of AGE, BAP, AOPP and ROM protein levels. Furthermore, an association between the PON2 S331C gene polymorphism and the serum levels of AOPP, ROMs and BAP was found. Thus, compared with AGE, the levels of AOPP and ROMs provided a more sensitive biomarker, with an improved association with the PON2 genotype. Such an association strengthen the importance of PON in the occurrence of oxidative stress. According to these results, an individual's genetic background may be taken into account for the health surveillance of individuals occupationally exposed to pesticides, in order to define a cluster of highly susceptible workers so as to guarantee greater protection.

MicroRNAs alteration as early biomarkers for cancer and neurodegenerative diseases: New challenges in pesticides exposure.

This review summarizes the current knowledge linking cancer and neuro-degenerative diseases to dysregulation of microRNA network following pesticide exposure. Most findings revealed differential miRNA expression targeting biomolecules and pathways involved in various neoplastic localizations and neurodegenerative diseases. A growing body of evidence in recent literature indicates that alteration of specific miRNAs can represent an early biomarker of disease following exposure to chemical agents, including pesticides. Different miRNAs seem to regulate cell proliferation, apoptosis, migration, invasion, and metastasis via many biological pathways through modulation of the expression of target mRNAs. The evaluation of miRNA expression levels may be used to develop new non-invasive strategies for the prediction and prognosis of many diseases, including cancer. However, the application of miRNAs as diagnostic and therapeutic biomarkers in the clinical field is extremely challenging.