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.

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.

Exposure to Respirable Particulate Matter and Its Association with Respiratory Outcomes in Beauty Salon Personnel.

We aimed to assess exposure to respirable particulate matter (PM) of beauty salon personnel, identify its determinants and ascertain the associated respiratory effects. We collected 122 full-day respirable PM samples from 12 beauty salons (floor area ranging from 24 to 550 m3, staff from 4 to 8) in Almaty, Kazakhstan, taking 10 samples from each place using a portable SidePak AM520 monitor. We also assessed lifestyle (smoking, etc.), respiratory symptoms and health-related quality of life (HRQL) of the personnel using questionnaires. Out of 11,831 5-min data points, daily median respirable PM concentrations were highly variable and ranged from 0.013 to 0.666 mg/m3 with 8.5-times difference in the median concentrations between the venue with the highest median (0.29 mg/m3) and the least median (0.034 mg/m3). In a multivariate linear regression modelling, ambient PM2.5 concentration was the strongest predictor of daily median respirable PM concentration (beta 2.12; 95% CI 1.89; 2.39), and R2 of the model was 0.63. We also found a positive association of the median respirable PM with respiratory symptoms and seasonal allergy, but not with HRQL. Short-term respirable PM levels in the beauty salons may be very high, but the median concentrations are mainly determined by the ambient air pollution.

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.

Esophageal cancer and bacterial part of gut microbiota - A multidisciplinary point of view.

There is an urgent need to search for new screening methods that allow early detection of esophageal cancer and thus achieve better clinical outcomes. Nowadays, it is known that the esophagus is not a sterile part of the gastrointestinal tract. It is colonized with various microorganisms therefore a "healthy" esophageal microbiome exists. The dysbiotic changes of esophageal microbiome can lead to the development of esophageal diseases including esophageal cancer. There is a strong consensus in the literature that the intestinal microbiome may be involved in esophageal carcinogenesis. Recently, emphasis has also been placed on the relationship between the oral microbiome and the occurrence of esophageal cancer. According to recent studies, some of the bacteria present in the oral cavity, such as Tannerella forsythia, Streptococcus anginosus, Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, and Fusobacterium nucleatum may contribute to the development of this cancer. Moreover, the oral microbiome of patients with esophageal cancer differs significantly from that of healthy individuals. This opens new insights into the search for a microbiome-associated marker for early identification of patients at high risk for developing this cancer.

Work Ability after Breast Cancer: Study of Healthcare Personnel Operating in a Hospital of South Italy.

Breast cancer (BrC) treatment can produce disabilities that often impact the quality of daily life and impact the social and working relationships of the patient. This paper looked into the remaining work ability in a group of female healthcare personnel (HCPs) with BrC in Southern Italy. Each HCP was subjected to a medical check, routine blood tests, and a questionnaire on the work ability index (WAI). Of 980 (100%) HCWs undergoing health control, 6% (n = 54) had experienced BRC, and only 66.6% (n = 36) agreed to take part in the study. A total of 28 (78%) were on night shifts. The WAI score was quite low in 5 (13.8%) cases, moderate in 10 (27.7%) cases, good in 14 (38.8%) cases, and excellent in 7 (19.5%) HCWs. Among all health figures, in nurses as well as technical staff, lower WAI scores were observed. HCWs reported various comorbidities, which affected WAI score, such as limited mobility in the upper limbs, arm/shoulder pain, numbness, and lymphoedema. The main complication that negatively affects any work activity is the morbidity in the upper limbs. This seems to affect the ability to perform tasks, and the re-entry to work is highlighted on sick leave days.

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.

Immunohistochemical Expression of Serine and Arginine-Rich Splicing Factor 1 (SRSF1) in Fluoro-Edenite-Induced Malignant Mesothelioma: A Preliminary Study.

The Serine and Arginine-Rich Splicing Factor 1 (SRSF1) has a proto-oncogenic function, being associated with angiogenesis and frequently overexpressed in many human malignant neoplasms. Its immunohistochemical expression has never been investigated in malignant pleural mesothelioma (MPM). We evaluated SRSF1 immunoexpression and its possible relation to angiogenesis in a selected cohort of 10 fluoro-edenite(FE)-induced MPM cases. METHODS: Immunohistochemical analyses with an anti-SRSF1 antibody were performed. We interpreted the cases as positive if tumor cell nuclei were stained; a semi-quantitative analysis of the cases was performed by evaluating the intensity of staining and the percentage of tumor positive cells. A microvessel density (MVD) count was also performed. RESULTS: High and low immunoexpressions of SRSF1 were seen in six and four MPMs, respectively. A trend of shorter overall survival was found in FE-induced MPM patients with SRSF1 overexpression. In addition, a significant association between high-MVD and high SRSF1 immunoexpression (p = 0.0476) was found. CONCLUSIONS: SRSF1 appears to be involved in MPM pathogenesis and its immunoexpression may represent a prognostic biomarker capable of identifying subgroups of patients with different prognosis. However, given the preliminary nature of the present study, further investigations on larger series, and additional in vitro studies, are required to validate our findings.

Oxidative stress and DNA damage in agricultural workers after exposure to pesticides.

BACKGROUND: Recent epidemiological studies on workers describe that exposure to pesticides can induce oxidative stress by increased production of free radicals that can accumulate in the cell and damage biological macromolecules, for example, RNA, DNA, DNA repair proteins and other proteins and/or modify antioxidant defense mechanisms, as well as detoxification and scavenger enzymes. This study aimed to assess oxidative stress and DNA damage among workers exposed to pesticides. METHODS: For this purpose, 52 pesticide exposed workers and 52 organic farmers were enrolled. They were assessed: the pesticide exposure, thiobarbituric acid reactive substances (TBARS), total glutathione (TG), oxidized glutathione levels (GSSG), and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), levels. RESULTS: Correlation between pesticide exposure was positively associated with high TBARS and 8-oxodG levels (p <  0.001). A negative association was founded with TG and GSSG and pesticide exposure. CONCLUSIONS: The present investigation results seem to indicate a mild augment in oxidative stress associated with pesticide exposure, followed by an adaptive response to increase the antioxidant defenses to prevent sustained oxidative adverse effects stress.

Update of in vitro, in vivo and ex vivo fluoro-edenite effects on malignant mesothelioma: A systematic review (Review).

Fluoro-edenite (FE), asbestiform fiber found in Biancavilla (Sicily, Italy), presents various characteristics similar to the asbestos group, in particular two fibrous phases tremolite and actinolite. Indeed, epidemiological studies have shown that FE fibers have similar effects to those of asbestos fibers. Such studies have reported a high incidence of malignant mesothelioma (MM), an aggressive neoplasm of the serosal membranes lining the pleural cavity, in individuals residing there due to FE exposure in Biancavilla related to environmental contamination. Evidence has led to the classification of FE as a Group 1 human carcinogen by the International Agency for Research on Cancer (IARC). The aim of this systematic review is to compare the results achieved in in vitro, in vivo and ex vivo experimental studies involving FE in order to update the current knowledge on the pathogenesis and molecular mechanisms responsible for FE-mediated MM development as well as the availability of effective biomarkers for MM prevention and diagnosis. This review is focused on the pathophysiological mechanisms mediated by inflammation induced by FE fiber exposure and which are responsible for MM development. This review also discusses the discovery of new diagnostic and prognostic biomarkers for the management of this pathology. It is known that the risk of cancer development increases with chronic inflammation, arising from enhanced reactive oxygen species (ROS) and NO• production stimulated by the body to remove exogenous agents, causing DNA damage and enhanced signal transduction that may lead to activation of oncogenes. Studies concerning MM biomarker discovery indicate that several biomarkers have been proposed for MM, but mesothelin is the only Food and Drug Administration (FDA)-approved biomarker for MM, with limitations. In recent studies, in silico analysis to identify selected miRNAs highly deregulated in cancer samples when compared with normal control have been developed. This in silico approach could represent an effort in the field of biomarker discovery for MM.

MacroH2A1 Immunoexpression in Breast Cancer.

MacroH2A1 has two splice isoforms, macroH2A1.1 and macroH2A1.2, that have been studied in several form of cancer. In the literature there are not many scientific papers dealing with the role of macroH2A1 in breast cancer. Breast cancer is the most frequent form of malignancy in females. It tend to metastasize to the bone in ~70% of patients. Despite treatment, new bone metastases will still occur in 30-50% of cases with advanced disease. Overall 5-year survival after the diagnosis of bone metastasis is ~20%. Osteoclasts and osteoblasts of the bone microenvironment are engaged by soluble factors released by neoplastic cells, resulting in bone matrix breakdown. This malfunction enhances the proliferation of the cancer cells, creating a vicious cycle. We investigated immunohistochemical expression of macroH2A1 in primitive breast cancer, focusing on the comparison of metastatic and non-metastatic cases. Furthermore, the immunohistochemical expression of macroH2A1 has been evaluated both in all cases of nodal metastases and in distant metastases. Our data demonstrated that macroH2A1 expression was higher expressed in metastatic breast cancer (77%) vs. non-metastatic breast cancer (32%). Also in analyzed metastases cases, a high macroH2A1 expression was detected: 85 and 80% in nodal and distant metastases cases, respectively. These results supported the fact that macroH2A1 is more highly expressed in breast cancer with worst prognosis.

A randomized controlled trial to compare group motivational interviewing to very brief advice for the effectiveness of a workplace smoking cessation counseling intervention.

BACKGROUND: Studies show that smokers have a lower work performance due to time spent smoking, increased fatigue perception and are more absent from work due to smoking-related diseases. The workplace could represent an important location to promote smoking cessation. METHODS: This study is a multi-center, controlled trial for smoking cessation counseling at the participants' workplace, where 656 randomized participants received four sessions of group motivational interviewing or four sessions of very brief advice and were followed up for 52 weeks. RESULTS: The Continuous Quit Rate (CQR) was higher for the smoking cessation counseling group than for the very brief advice group during weeks 9 to 12 (17.5% vs. 3.6%) weeks 9 to 24 (13.4% vs. 3.4%) and weeks 9 to 52 (10.3% vs. 3.1%). CONCLUSIONS: This study demonstrated that motivational interviewing is an efficacious smoking cessation approach for smokers at their workplace. The short-term and long-term cessation rate of the intervention of the smoking cessation counseling group exceeded that of very brief advice.

Night shift work in resident physicians: does it affect mood states and cognitive levels?

BACKGROUND: The effects of night shift work on health status have been widely studied. Night workers seem to smoke more, eat badly and show a low propensity to physical activity. Night work can be associated with an increase in cardiovascular and gastrointestinal disorders, alterations in immune response, diabetes, aging, hormonal imbalance, and premature death; alteration of circadian rhythm is also regarded as a risk factor for breast cancer and neuropsychiatric disorders. Moreover, several studies have highlighted the effects of sleep deprivation on clinical performance, quality of care and personal safety of healthcare personnel. No studies have investigated the effects of night work on Italian resident physicians and compared its effect across specialties. This study aims to assess the prevalence of sleep disorders, possible cognitive impairment and mood states, in relation to night shift work among resident physicians. METHODS: 80 resident physicians, attending the postgraduate training into an Hospital located in the South of Italy, were divided into 4 areas (medical, surgical, services and anaesthesia). They were recruited from July 2017 to June 2018 and participated to a survey consisting of 4 questionnaires to investigate the presence of sleep deprivation and sleep quality (Epworth Sleepiness Scale, Pittsburgh Sleep Quality Index), their cognitive status (Mini Mental State examination) and mood profiles (Profile of Mood States, POMS). Analysis of variance was used for comparison of questionnaires scores across specialties. RESULTS: Authors reported no sleep deprivation, no sleep disorders and their outcomes, no changes in intellectual efficiency and no cognitive impairment in this population, neither in the areas performing night shifts nor in those involving only day shifts. Mood states measured by POMS showed a borderline level of Anger-Hostility (A) value among the residents of the medical area and services, and an increase slightly beyond the physiological levels of the T-score 50 of Fatigue-Inertia (F) always in the same groups. An increase in the Vigour-Activity (V) value beyond T-score 50 levels was also observed among residents of all the areas considered. CONCLUSIONS: Emotional involvement could be attributed to the gap between high professional demand and lack of experience and knowledge among trainees. Tutors should help their students in order to identify earlier changes in the mood. Improvement in the organization of the trainee's activity could reduce the emotional overload.

Defense and protection mechanisms in lung exposed to asbestiform fiber: the role of macrophage migration inhibitory factor and heme oxygenase-1.

Fluoro-edenite (FE), an asbestiform fiber, is responsible for many respiratory pathologies: chronic obstructive diseases, pleural plaques, fibrosis, and malignant mesothelioma. Macrophage migration inhibitory factor (MIF) is one of the first cytokines produced in response to lung tissue damage. Heme oxygenase-1 (HO-1) is a protein with protective effects against oxidative stress. It is up regulated by several stimuli including pro-inflammatory cytokines and factors that promote oxidative stress. In this research, the in vivo model of sheep lungs naturally exposed to FE was studied in order to shed light on the pathophysiological events sustaining exposure to fibers, by determining immunohistochemical lung expression of MIF and HO-1. Protein levels expression of HO-1 and MIF were also evaluated in human primary lung fibroblasts after exposure to FE fibers in vitro. In exposed sheep lungs, MIF and HO-1 immunoexpression were spread involving the intraparenchymal stroma around bronchioles, interstitium between alveoli, alveolar epithelium and macrophages. High MIF immunoexpression prevails in macrophages. Similar results were obtained in vitro, but significantly higher values were only detected for HO-1 at concentrations of 50 and 100 µg/mL of FE fibers. MIF and HO-1 expressions seem to play a role in lung self-protection against uncontrolled chronic inflammation, thus counteracting the strong link with cancer development, induced by exposure to FE. Further studies will be conducted in order to add more information about the role of MIF and HO-1 in the toxicity FE-induced.

Management of High-Pressure Injection Hand Injuries: A Multicentric, Retrospective, Observational Study.

Hand injuries after high-pressure injection are a medical emergency. These events occur frequently in workers during industrial cleaning, painting, and lubrication, and may have devastating consequences, leading to eventual amputation and poor functional outcomes. The authors have investigated the evolution, management, and outcome. Medical records of occupational medicine units and hand surgery units were collected in order to spot the high-pressure gear accident cases. Records were analyzed by dividing the subjects into two groups: those treated within 6 h and after 6 h of the trauma. A follow-up was carried out at least 1 year after treatment; the post-treatment outcomes were assessed. Of the 71 (100%) subjects, 26 (37%) were treated ≤6 h and 45 (63%) >6 h. A total of 28% (n = 20) underwent amputation. In 61% of cases, accidents had occurred in the iron and steel sector. High viscosity materials with a delayed treatment beyond 6 h seemed to determine compartmental syndrome and following amputation. A significantly better outcome was reported among subjects treated ≤6 h compared to those treated >6 h, 20% (n = 7) versus 26% (n = 9), respectively. Early management of this type of injury is crucial. The results of this study may contribute to providing guidelines to occupational physicians in order to best manage this type of emergency.

Exposure to Toxic Heavy Metals Can Influence Homocysteine Metabolism?

BACKGROUND: Homocysteine is a sulfur amino acid whose metabolism is activated in two pathways: remethylation to methionine, which requires folate and vitamin B12, and transsulfuration to cystathionine, which needs pyridoxal-5'-phosphate. High homocysteine level increases the risk of developing heart disease, stroke, peripheral vascular diseases, and cognitive impairment. Some evidence showed that exposure to these metals increased plasma homocysteine levels. METHODS: A systematic review was carried out to clarify the relationship between homocysteine blood levels and exposure to toxic heavy metals (Lead, Cadmium, Mercury, and Chromium). RESULTS: The results of this systematic review indicate that exposure to Pb, Cr, Cd, and Hg is connected with nonphysiological homocysteine levels or vitamin B12 and folate serum concentrations. CONCLUSIONS: These findings reinforce the importance of involvement in exposure to heavy metals in homocysteine metabolism. This supports the role of blood metals as potential upstream modifiable risk factors to prevent the development of other established risk factors as hyperhomocysteinemia.

Abnormal Plasma Cell Disorders in Refinery Waste Workers.

A monoclonal gammopathy of undetermined significance (MGUS) may develop into a multiple myeloma or a correlated lymphoproliferative malignancy with a progress rate of 1% per year. The immune status, occupational-environmental risk factors, and hereditary factors may influence the risk of developing MGUS. We investigated the prevalence of MGUS in 77 refinery waste workers. They were all males, averagely aged 36, with a mean working history of 18.5 years and working in the dump for about 4.2 years. After analyzing the results of standard serum electrophoresis migrations, 16% of cases (n = 12) showed levels beyond the normal ranges. In all 12 samples we observed an increase of gamma component: 67%, IgG; 17%, IgM; 8%, IgA; 8%, oligoclonal. Workers were exposed to hazardous refinery waste. After the biological monitoring of urine samples for metals and t,t-muconic acid, no extra-range values were observed. The multivariate analysis shows, however, that cigarette smoking and residence near industrial sites are significantly (p < 0.001) associated with a high risk of MGUS development; while no association was found with occupational exposure. Additional attention might be paid in particular to these conditions in epidemiological studies and further larger, prospective, population-based researches appear warranted to evaluate the strength of any positive association.

Fibulin-3 immunoexpression in malignant mesothelioma due to fluoro-edenite: a preliminary report.

An increased standardized incidence and mortality rate were reported due to malignant mesothelioma (MM) in Biancavilla. Environmental investigations showed the presence of an asbestiform fiber: fluoro-edenite (FE). MM develops with a latency of 20-60 years from exposure and specific and sensitive biomarkers are urgently needed. For this purpose, we evaluated Fibulin-3 (Fb-3) immunoexpression in human cases of MM related to FE exposure and its prognostic role. Immunohistochemical analysis of Fb-3 was carried out in eight MM patients resident in Biancavilla and the analysis showed evidence of environmental exposure to FE fibers. Six MM cases (3 epithelioid and 3 biphasic) showed a high immunoexpression of Fb-3 in neoplastic cells with nuclear and cytoplasmic localization. One epithelioid and one biphasic subtype did not show Fb-3 immunostaining. The results demonstrate the implication of Fb-3 in MM due to FE exposure and may possibly suggest its potential role as a diagnostic and prognostic marker.