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.

An autochthonous case of cutaneous bacillary angiomatosis not related to major immunosuppression: An emerging or overlooked disease?

Cutaneous bacillary angiomatosis (cBA) is a vascular proliferative disorder due to Bartonella henselae or Bartonella quintana that has been mostly described in people living with HIV. Since cBA is considered to be rare in hosts not affected by major immunosuppression, it could be underdiagnosed in this population. Moreover, antimicrobial treatment of cBA has been poorly validated, thus reporting experiences on this clinical entity is important. We reported a challenging and well-characterized case of an Italian 67-year-old gentleman without a history of major immunocompromizing conditions, although he was affected by conditions that can be associated with impaired immune function. The patient reported herein was diagnosed after a long time since the initiation of symptoms and was successfully treated with combined antibiotic therapy including macrolides and quinolones under the guidance of molecular test results. Physicians should consider cBA as a possible manifestation of Bartonella spp. Infection in patients not suffering from major immunocompromizing conditions. Until evidence-based guidelines are available, molecular tests together with severity and extension of the disease can be useful to personalize the type of treatment and its duration.

Touching Base with Some Mediterranean Diseases of Interest from Paradigmatic Cases at the "Magna Graecia" University Unit of Infectious Diseases: A Didascalic Review.

Among infectious diseases, zoonoses are increasing in importance worldwide, especially in the Mediterranean region. We report herein some clinical cases from a third-level hospital in Calabria region (Southern Italy) and provide a narrative review of the most relevant features of these diseases from epidemiological and clinical perspectives. Further, the pathogenic mechanisms involved in zoonotic diseases are reviewed, focusing on the mechanisms used by pathogens to elude the immune system of the host. These topics are of particular concern for individuals with primary or acquired immunodeficiency (e.g., people living with HIV, transplant recipients, patients taking immunosuppressive drugs). From the present review, it appears that diagnostic innovations and the availability of more accurate methods, together with better monitoring of the incidence and prevalence of these infections, are urgently needed to improve interventions for better preparedness and response.

A Rare Complication of Ascariasis: A Case of Acute Interstitial Nephritis.

Acute interstitial nephritis (AIN) due to helminths is a rare cause of acute kidney injury (AKI). Helminthiases often progresses insidiously, making diagnosis difficult. This was the case of a 72-year-old man, who presented with renal failure, itching and diarrhoea. Urinalysis revealed leukocyturia, microhaematuria and mild proteinuria. A full blood count revealed leucocytosis with eosinophilia. A stool parasitological examination revealed fertilised eggs of Ascaris lumbricoides. Tubulointerstitial nephropathy secondary to A. lumbricoides infection was suspected. A percutaneous renal biopsy was not performed since the patient refused the anti-platelet therapy discontinuation. Mebendazole, albendazole and prednisone therapy was administered. After worm eradiation and discharge, recovery from the parasitosis, absence of pruritus and eosinophilia, and progressive improvement of renal function were observed, strongly suggesting a causal relationship between Ascaris infection and AIN. Parasite infection should be considered in the differential diagnosis of unexplained renal failure because early diagnosis and treatment are necessary to avoid irreversible complications.

Salivary Biomarkers Analysis and Neurobehavioral Assessment in Nurses Working Rotation Shifts: A Pilot Study.

Currently, about one in five workers is employed in night shift work in Europe. Shift work including nighttime hours is essential in several activities, especially the healthcare sector. Importantly, night working may be associated with the occurrence of sleep disorders or work-related stress, both potentially augmenting the risk of errors and accidents at work. This study aims to examine the presence of neurobehavioral alterations that can be a consequence of shift working and concurrent misalignment of the sleep times and circadian rhythms. Nurses (n = 102) employed at a University Hospital located in North-Eastern Sicily, Italy, voluntarily participated in this pilot study. During medical surveillance, morning and evening salivary samples were collected, and seven psychodiagnostics questionnaires were administered to all the subjects. On one hand, the salivary levels of stress-related biomarkers (cortisol and alpha-amylase) and a circadian biomarker (melatonin) were evaluated. On the other hand, several neurobehavioral features were assessed, including depression, anxiety, work-related, and sleep issues. Interestingly, a positive relationship between salivary morning cortisol and depression scale, as well as a negative relationship between salivary morning alpha-amylase and work ability scale, were observed. Based on these results, the integration of subjective questionnaire outcomes and objective salivary biomarker quantification can help to identify workers with increased susceptibility to developing neurobehavioral alterations. This approach may contribute to ameliorating preventive strategies towards sensitive categories, such as nurses working rotation shifts.

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.

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.

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.

Spike-specific T-cell responses in patients with COVID-19 successfully treated with neutralizing monoclonal antibodies against SARS-CoV-2.

OBJECTIVES: Neutralizing monoclonal antibodies (moAbs) improves clinical outcomes in patients with COVID-19 when administered during the initial days of infection. The action of moAbs may impair the generation or maintenance of effective immune memory, similar to that demonstrated in other viral diseases. We aimed to evaluate short-term memory T-cell responses in patients effectively treated with bamlanivimab/etesevimab, casirivimab/imdevimab, or sotrovimab (SOT). METHODS: Spike (S)-specific T-cell responses were analyzed in 23 patients with COVID-19 (vaccinated or unvaccinated) before and after a median of 50 (range: 28-93) days from moAb treatment, compared with 11 vaccinated healthy controls. T-cell responses were measured by interferon-γ-enzyme-linked immunospot and flow cytometric activation-induced marker assay. RESULTS: No statistically significant difference in S-specific T-cell responses was observed between patients treated with moAb and vaccinated healthy controls. Bamlanivimab/etesevimab and casirivimab/imdevimab groups showed significant increases in cellular responses in paired baseline/postrecovery series, as well as vaccinated patients receiving SOT. In contrast, unvaccinated patients prescribed SOT presented no statistically significant increases in T-cell-responses, suggesting diverse impacts of different moAbs on the evolution of S-specific T-cell responses in vaccinated and unvaccinated patients. CONCLUSION: The moAbs did not hinder short-term memory S-specific T-cell responses in the overall group of patients; however, differences among moAbs must be further investigated both in vaccinated and unvaccinated individuals.

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.

Weight of Clinical and Social Determinants of Metabolic Syndrome in People Living with HIV.

Background. Comorbidities in people living with HIV (PLWH) represent a major clinical challenge today, and metabolic syndrome (MTBS) is one of the most important. Objective. Our objective was to assess the prevalence of MTBS and the role of both clinical/socio-behavioral risk factors for MTBS in a cohort of PLWH. Methods. All PLWH, over 18 years of age, attending all Infectious Disease Units in Calabria Region (Southern Italy) for their routine checks from October 2019-January 2020 were enrolled. MTBS was defined by NCEP-ATP III criteria. Logistic regression analysis was performed to assess factors significantly associated with the main outcome (MTBS). Results. We enrolled 356 PLWH, mostly males (68.5%), with a mean age of 49 years (standard deviation: 12), including 98 subjects with and 258 without MTBS. At logistic regression analysis, a statistically significant association was found between MTBS and alcohol use, osteoporosis, polypharmacy, and a history of AIDS. Conclusions. Identifying and addressing risk factors, including those that are socio-behavioral or lifestyle-related, is crucial to prevent and treat MTBS. Our results suggest the importance of implementing educational/multidimensional interventions to prevent MTBS in PLWH, especially for those with particular risk factors (alcohol abuse, osteoporosis, previous AIDS events, and polypharmacy). Moreover, alcohol consumption or abuse should be routinely investigated in clinical practice.

Similarities, differences, and possible interactions between hepatitis E and hepatitis C viruses: Relevance for research and clinical practice.

Hepatitis E virus (HEV) and hepatitis C virus (HCV) are both RNA viruses with a tropism for liver parenchyma but are also capable of extrahepatic manifestations. Hepatitis E is usually a viral acute fecal-oral transmitted and self-limiting disease presenting with malaise, jaundice, nausea and vomiting. Rarely, HEV causes a chronic infection in immunocompromised persons and severe fulminant hepatitis in pregnant women. Parenteral HCV infection is typically asymptomatic for decades until chronic complications, such as cirrhosis and cancer, occur. Despite being two very different viruses in terms of phylogenetic and clinical presentations, HEV and HCV show many similarities regarding possible transmission through organ transplantation and blood transfusion, pathogenesis (production of antinuclear antibodies and cryoglobulins) and response to treatment with some direct-acting antiviral drugs. Although both HEV and HCV are well studied individually, there is a lack of knowledge about coinfection and its consequences. The aim of this review is to analyze current literature by evaluating original articles and case reports and to hypothesize some interactions that can be useful for research and clinical practice.

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.

Role of the T2Dx magnetic resonance assay in patients with suspected bloodstream infection: a single-centre real-world experience.

BACKGROUND: T2Dx was approved by the US Food and Drug Administration for the rapid detection of a modified panel of ESKAPE bacterial species or Candida spp. causing bloodstream infection (BSI). PATIENTS AND METHODS: We performed a retrospective, observational study from January 1, 2018 to December 31, 2019 of all hospitalised patients with suspected BSI who underwent assessment using T2Dx in addition to standard blood culture (BC). T2-positive patients (cases) were compared to a matched group of patients with BSI documented only by BC (1:2 ratio) to investigate the possible impact of T2Dx on the appropriateness of empirical antimicrobial therapy and 21-day mortality. RESULTS: In total, 78 T2Dx-analysed samples (49 patients) were analysed. The T2Dx assay result was positive for18 patients and negative for 31 patients. The concordance rates of the T2Bacteria Panel and T2Candida Panel results with those of standard BC were 74.4% and 91.4%, respectively. In the matched analysis, inappropriate empiric antimicrobial therapy administration was significantly less frequent in cases than in comparators (5.5% vs. 38.8%). The 21-day mortality rate was twofold lower in cases than in comparators (22.2% vs. 44.4%), although the difference was not significant. No other analysed variables were significantly different between the two groups. CONCLUSIONS: This study illustrated that T2Dx might be associated with an increase in the appropriateness of empiric antimicrobial therapy in patients with BSI. Further studies are needed to evaluate whether the T2Dx assay can improve patient outcomes.

Prevalence of Antibiotic Resistance Over Time in a Third-Level University Hospital.

This study evaluated the spread and possible changes in resistance patterns of ESKAPE bacteria to first-choice antibiotics from 2015 to 2019 at a third-level university hospital after persuasive stewardship measures were implemented. Isolates were divided into three groups (group 1, low drug-resistant; group 2, multidrug/extremely drug-resistant; and group 3, pan-resistant bacteria) and a chi-squared test (χ2) was applied to determine differences in their distributions. Among the 2,521 isolates, Klebsiella pneumoniae was the most frequently detected (31.1%). From 2015 to 2019, the frequency of isolates in groups 2 and 3 decreased from 70.1% to 48.6% (χ2 = 63.439; p < 0.0001). Stratifying isolates by bacterial species, for K. pneumoniae, the frequency of PDR isolates decreased from 20% to 1.3% (χ2 = 15.885; p = 0.003). For Acinetobacter baumannii, a statistically significant decrease was found in groups 2 and 3: from 100% to 83.3% (χ2 = 27.721; p < 0.001). Also, for Pseudomonas aeruginosa and Enterobacter spp., the frequency of groups 2 and 3 decreased from 100% to 28.3% (χ2 = 225.287; p < 0.001) and from 75% to 48.7% (χ2 = 15.408; p = 0.003), respectively. These results indicate that a program consisting of persuasive stewardship measures, which were rolled out during the time frame of our study, may be useful to control drug-resistant bacteria in a hospital setting.

Quality of Life, Insomnia and Coping Strategies during COVID-19 Pandemic in Hospital Workers. A Cross-Sectional Study.

COVID-19 became a pandemic in a few months, leading to adverse health outcomes, reducing the quality of life, affecting the sleep/wake cycle, and altering coping strategies, especially among hospital personnel. Life quality, insomnia, and coping strategies were thus assessed among hospital personnel during the first wave of the COVID-19 pandemic in Italy. This cross-sectional study was conducted from May to November 2020 through an online survey. There were 558 participants (28.5% males and 71.5% females) enrolled in two different metropolitan areas (in North and South of Italy, respectively). Three standardized questionnaires were administered: European Quality of life-5 Dimensions (EQ-5D), Athens Insomnia Scale (AIS), and Brief COPE. Differences in sociodemographic characteristics and work-related factors were also investigated in order to identify possible predictors through a generalized linear model and logistic regression analysis. Results showed good perceived life quality and high insomnia prevalence. After sample stratification, the statistical analysis highlighted that personal (gender, age, educational level) and work-related factors (employment in COVID wards, remote working) played different roles in predicting quality of life, insomnia, and coping attitude. Active, Planning, and Acceptance were the most frequently adopted coping strategies. Despite women confirming their attitude in reacting to the difficulties, adopting emotion-focused coping strategies, they showed a higher probability to develop insomnia, so a gender perspective should be considered in the health protection of this working category. An integrated approach should be implemented at individual, interpersonal and organizational levels aiming to monitor psychological distress, favor regular sharing and communication between peers, and also allow conciliation of work with family life. At the organizational level, preventive and protective measures adequate to work-related risk to COVID-19 should be adopted.

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.

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.