Epigenetic fingerprint in endometrial carcinogenesis: the hypothesis of a uterine field cancerization.

"Abstract. Transcriptional silencing by CpG island hypermethylation plays a critical role in endometrial carcinogenesis. In a collection of benign, premalignant and malignant endometrial lesions, a methylation profile of a complete gene panel, such steroid receptors (ERα, PR), DNA mismatch repair (hMLH1), tumor-suppressor genes (CDKN2A\/P16 and CDH1\/E-CADHERIN) and WNT pathway inhibitors (SFRP1, SFRP2, SFRP4, SFRP5) was investigated in order to demonstrate their pathogenetic role in endometrial lesions. Our results indicate that gene hypermethylation may be an early event in endometrial endometrioid tumorigenesis. Particularly, ERα, PR, hMLH1, CDKN2A\/P16, SFRP1, SFRP2 and SFRP5 revealed a promoter methylation status in endometrioid carcinoma, whereas SFRP4 showed demethylation in cancer. P53 immunostaining showed weak-focal protein expression level both in hyperplasic lesions and in endometrioid cancer. Non-endometrioid cancers showed very low levels of epigenetic methylations, but strong P53 protein positivity. Fisher exact test revealed a statistically significant association between hMLH1, CDKN2A\/P16 and SFRP1 genes methylation and endometrioid carcinomas and between hMLH1 gene methylation and peritumoral endometrium (p < 0.05). Our data confirm that the methylation profile of the peritumoral endometrium is different from the altered molecular background of benign endometrial polyps and hyperplasias. Therefore, our findings suggest that the methylation of hMLH1, CDKN2A\/P16 and SFRP1 may clearly distinguish between benign and malignant lesions. Finally, this study assessed that the use of an epigenetic fingerprint may improve the current diagnostic tools for a better clinical management of endometrial lesions.

Risk agents related to work and amyotrophic lateral sclerosis: An occupational medicine focus

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by progressive muscular paralysis reflecting degeneration of motor neurons. In recent years, in addition to several studies about genetic mechanisms leading to motor neurons damage, various epigenetic theories have been developed, involving the study of the patients’ work and lifestyle. The work aims at focusing the role of occupational exposure related to ALS by literature data analysis. Articles, selected on the basis of keywords, year of publication and topics, are related to occupational exposure, suggesting an impact on ALS onset. The literature review shows that there are still a lot of biases in the studies design, which actually do not allow to draw unequivocal conclusions

Applications and Current Medico-Legal Challenges of Telemedicine in Ophthalmology

Background: The digital revolution is redesigning the healthcare model, and telemedicine offers a good example of the best cost-effectiveness ratio. The COVID-19 pandemic has catalysed the use of the telemedicine. The aim of this review is to describe and discuss the role and the main applications of telemedicine in the ophthalmic clinical practice as well as the related medico-legal aspects. Methods: 45 original articles and 5 reviews focused on this topic and published in English language from 1997 and 2021 were searched on the online databases of Pubmed, Scopus, Web of Sciences and Embase, by using the following key words: &ldquo;telemedicine&rdquo;, &ldquo;privacy&rdquo;, &ldquo;ophthalmology&rdquo;, &ldquo;COVID-19&rdquo; and &ldquo;informed consent&rdquo;. Results: Telemedicine is able to guarantee patient care using information and communication technologies. Technology creates an opportunity to link doctors with the aim of assessing clinical cases and maintaining high standards of care while performing and saving time as well. Ophthalmology is one of the fields in which telemedicine is most commonly used for patient management. Conclusions: Telemedicine offers benefits to patients in terms of saving time and costs and avoiding physical contact; however, it is necessary to point out significant limitations such as the absence of physical examinations, the possibility of transmission failure and potential violations of privacy and confidentiality

Healthcare Workers and Manual Patient Handling: A Pilot Study for Interdisciplinary Training

Manual patient handling (MPH) is a major occupational risk in healthcare settings. The aim of this study was to propose an MPH training model involving interdisciplinary aspects. A scheduled training program was performed with 60 healthcare workers (HCWs) from a hospital in Naples, Italy, providing training divided into three sections (occupational health&mdash;section one; physical therapy&mdash;section two; psychosocial section&mdash;section three) and lasting six hours. Fifty-two HCWs performed the training session. In section one, a questionnaire about risk perception related to specific working tasks was administered. Section two provided specific exercises for the postural discharge of the anatomical areas most involved in MPH. The last section provided teamwork consolidation through a role-playing exercise. The training program could also be useful for risk assessment itself, as they can examine the perceptions of the specific risk of the various workers and incorrect attitudes and therefore correct any incorrect procedures, reducing exposure to specific risks in the field. This pilot study proposes a training model that explores all aspects related to MPH risk exposure and also underlines the need for standardization of this formative model, which could represent a useful tool for studying the real effectiveness of training in workplaces

5-Fluorouracil induces apoptosis in rat cardiocytes through intracellular oxidative stress

<p>Abstract</p> <p>Background</p> <p>Cardiotoxicity is a major complication of anticancer drugs, including anthracyclines and 5-fluorouracil(5-FU) and it can have detrimental effects both in patients and workers involved in the preparation of chemotherapy.</p> <p>Methods</p> <p>Specifically, we have assessed the effects of increasing concentrations of 5-FU and doxorubicin (DOXO) on proliferation of H9c2 rat cardiocytes and HT-29 human colon adenocarcinoma cells by MTT assay. Cells were treated for 24, 48 and 72 h with different concentrations of the two drugs alone or with 5-FU in combination with 10^-4 M of levofolene (LF).</p> <p>Results</p> <p>5-FU induced a time- and dose-dependent growth inhibition in both cell lines. The 50% growth inhibition (IC:50) was reached at 72 h with concentrations of 4 μM and 400 μM on HT-29 and H9c2, respectively. The addition of LF to 5-FU enhanced this effect. On the other hand, the IC:50 of DOXO was reached at 72 h with concentrations of 0.118 μM on H9c2 and of 0.31 μM for HT-29. We have evaluated the cell death mechanism induced by 50% growth inhibitory concentrations of 5-FU or DOXO in cardiocytes and colon cancer cells. We have found that the treatment with 400 μM 5-FU induced apoptosis in 32% of H9c2 cells. This effect was increased by the addition of LF to 5-FU (38% of apoptotic cells). Apoptosis occurred in only about 10% of HT-29 cells treated with either 5-FU or 5-FU and LF in combination. DOXO induced poor effects on apoptosis of both H9c2 and HT-29 cells (5–7% apoptotic cells, respectively). The apoptosis induced by 5-FU and LF in cardiocytes was paralleled by the activation of caspases 3, 9 and 7 and by the intracellular increase of O²⁻ levels.</p> <p>Conclusions</p> <p>These results suggest that cardiotoxic mechanism of chemotherapy agents are different and this disclose a new scenario for prevention of this complication.</p