Histopathological and immunohistochemical study of periodontal changes in chronic smokers.

Periodontal disease is a chronic inflammatory, multifactorial condition, that, in the absence of an early and adequate treatment, may lead to a progressive damaging of the alveolar tissues that support the teeth (periodontal ligament, cement and alveolar bone) followed by teeth mobility and, subsequently, their loss. Periodontal disease is one of the most common inflammatory disease affecting adult individuals all over the world, being considered a real worldwide pandemic. This disease may influence the progression of certain systemic diseases: diabetes mellitus, cardiovascular diseases, ischemic cardiomyopathy, myocardial infarction, stroke, neurodegenerative diseases, chronic kidney diseases, cancer, etc. The association between smoking and periodontal disease was described in numerous clinical and epidemiological studies, suggesting that products derived from tobacco burning may change the clinical aspects and the disease progression. The present study analyzed microscopically and immunohistochemically 58 periodontal fragments, from 50 patients, chronic smokers, clinically diagnosed with severe periodontitis. There were highlighted major changes in the gingival epithelium (epithelium thickening, acanthosis, intraepithelial edema, infiltrates of neutrophils or lymphocytes, epithelial necrosis), in the periodontal conjunctive tissue (more or less intense inflammatory infiltrates, microhemorrhages, vascular congestion, intense immunohistochemical expression for some matrix metalloproteinases). The periodontal changes may be the expression of both toxic factors present in tobacco smoke and due to the changes caused by tobacco in the microbial flora of the oral cavity.

Preclinical and histological study of boron-containing compounds hydrogels on experimental model of periodontal disease.

Periodontitis is a disease that affects a wide group of people, and there has been an increased interest in the research of finding useful materials that help reduce inflammation and the further loss of tissue. In this study, we have tested a boron-containing compound (BCC) Calcium Fructoborate (CaFB) and Boric Acid (BA) hydrogels on the gingival level on Wistar rats. First, we have induced the periodontal disease at the lower incisors, we have applied the hydrogels and after a week, we have euthanized the rats. Next, the oral soft tissue reaction was clinically and then histologically investigated. Our study has shown good clinical response of the oral tissue, and we have noticed lower levels of inflammation on the experimental groups treated with the BCCs hydrogels. Despite the generally good response of the biological structures to the presence of BA and CaFB on periodontal level, more scientifically proved information is needed to obtain the desired biological responses in all clinical situations.

Health data protection and confidentiality in EU BTC legislation: ethical and safety standards.

PURPOSE: The current paper focuses on the ethical approaches to data protection and confidentiality (DP&C) and the quality and safety (Q&S) requirements in the European Union (EU) blood, tissues and cells (BTC) legislation, namely: Directive 2002∕98∕EC, Directive 2004∕23∕EC, Directive 2005∕61∕EC, Directive 2005∕62∕EC, Directive 2006∕86∕EC, Commission Directive (EU) 2015∕565, SWD(2019) 376 final and the external evaluation SANTE∕2017∕B4∕010. BACKGROUND: In the EU, the ethical requirements for the BTC legal framework focus also on the quality, eligibility, safety, and protection standards. In addition, the SWD(2019) 376 final on the evaluation of the EU BTC legislation released in October 2019 draws attention to the challenges of technology, consent and donation, testing procedures and management of the BTC services. CONTENT: The paper highlights the EU BTC setting standards by examining the particular provisions for the: hemovigilance, eligibility of donors, blood and blood components (BBC), consent, decisions required at the Member States (MS) level, healthcare standards, measures for the blood establishments (BE) and tissue establishments (TE) and particular issues concerning the donation of tissues and/or cells (T&C). CONCLUSIONS: Nevertheless, the intended function of the analysis is to focus on the EU BTC legislation and to enable research responsive to the latest initiatives launched by the European Blood Alliance (EBA) and Nuffield Council on Bioethics (NCB) in the field of the definitions and ethical processes.

Ethical review of patient safety and public health in EU clinical trials legislation: impact of COVID-19 pandemic.

PURPOSE: The study considers the ethical review of the European Union (EU) clinical trials (CTs) legislation, namely the Clinical Trials Regulation (CTR) (EU) 2014∕536, the Directive 2001∕20∕EC and the "Guidance on the management of clinical trials during the COVID-19 (coronavirus) pandemic" (GMCT) (version 3) issued on 28 April 2020 by the European authorities in the field. BACKGROUND: The Directive 2001∕20∕EC focuses the legal provisions for the conduct of CTs by acknowledging the screening role of the Ethics Committees (ECs) and of the national competent authorities (NCA) in the Member States (MS) to protect the CT subject and the personal data. CONTENT: The present article displays the ethical requirements for conducting, monitoring and reporting of the CTs by raising awareness on the: (i) new conceptual framework of the "clinical trial", "low-intervention clinical trial", "non-interventional study" and "ethics committee"; (ii) ethical considerations addressed in Part I and Part II of the assessment report; (iii) evaluation of the coronavirus disease 2019 (COVID-19) pandemic on the current regulatory framework. CONCLUSIONS: The CTR stimulates the EU clinical research and enables an independent control with regard to the respect of the interests of the CT subject.

Ethical assessment of the EU health policy under the Directive 2011∕24∕EU: approaching patients' rights and cross-border healthcare.

PURPOSE: The purpose of the present article is to discuss the ethical challenges of the European Union (EU) health legislation framing the patients' rights and the cross-border healthcare (CBHC). BACKGROUND: The paper reviews the EU main legislation in the field, namely the Directive 2011∕24∕EU (CBHC Directive) of the European Parliament and of the Council of 9 March 2011, on the application of patients' rights in CBHC. CONTENT: The aim of the study is to analyze the patients' rights and the CBHC, enhancing the healthcare support and coordination under this regulatory framework. An exploratory and descriptive analysis will be conducted based on these legal provisions by focusing the ethical choices, the ethical duty, the ethical reasons and the patients' rights. An introductory literature overview will be provided and an analysis of the recent data reports published by the European Commission (EC) on the application of the CBHC Directive will be detailed. Therefore, six main themes emerged: (i) the protection of the patients' rights; (ii) the examination of the ethical challenges to address the EU public health issues; (iii) the monitoring of the data reports on the operation of the CBHC Directive; (iv) the reimbursement of costs of CBHC; (v) the European reference networks (ERNs); (vi) the eHealth network and the health technology assessment (HTA). CONCLUSIONS: The paper reviews the existing legal framework aimed to support the Member States (MS) in achieving a harmonized implementation of the CBHC Directive. Hence, particular ethical issues will be developed under this regulatory framework.

Histological and immunohistochemical aspects of the atrophic dental pulp modifications of abutment teeth.

BACKGROUND: Reducing the thickness of hard dental tissues through the preparation of teeth for fixed prosthodontics represents an aggression for the dentin-pulp complex and may cause changes in dental pulp tissues, by means of acute or chronic inflammation, or by asymptomatic, atrophic modifications. AIM: The aim of the study was to histological and immunohistochemical evaluate samples of dental pulp selected from previously prepared teeth, which had been functioning as abutment teeth for some years. PATIENTS, MATERIALS AND METHODS: The starting point of the study was a statistical study conducted on a batch of 276 patients, of which 64 needed to change the fixed prosthetic restorations. Some of the existing abutment teeth were extracted, others presented previously performed root canal treatments and others required endodontic treatment. RESULTS: Of the 21 samples taken, 12 showed atrophic pulp modifications, represented by low cellularity, collagen fibrosis, vascular congestion, and pulpal calcifications. CONCLUSIONS: Certain irreversible atrophic changes can be observed in abutment teeth's pulps, a fact that justifies the need of performing pre-prosthetic endodontic treatment.

Ethical approach to the genetic, biometric and health data protection and processing in the new EU General Data Protection Regulation (2018).

PURPOSE: The main purpose of the present paper is to analyze the rules for processing of special categories of personal data (genetic data, including biological samples, biometric and health data) in the light of the new General Data Protection Regulation (GDPR), thus contributing to overview the health status and the biomedical state of the data subject. BACKGROUND: Over the last two decades, debating the European Union's (EU) major legislation with regard to personal data and patients' rights became relevant for the scientific research. The paper assesses the basic legal provisions with regard to the genetic, biometric and data concerning health considered as "sensitive data", while safeguarding the ethical standards of the scientific research. The present article investigates the ethical and legal approaches to processing personal data in the understanding of the new regulatory guidelines regarding the data protection, here including the health status and the rights of a data subject. CONCLUSIONS: The protection of natural persons with regard to the processing of genetic, biometric and health data and the free movement of such data are reinforced in the new GDPR entered into force in May 2016 and applied from 25 May 2018. The new legal context elucidates: the special categories of personal data ("sensitive data"), the "consent" and the research exemption by explicitly recognizing the "pseudonymised" data. Although the new guidelines revisit the EU data protection reform, it also grants the EU Member States the right to maintain or introduce further limitations to the processing of such data.

Ethical governance of the medical research: clinical investigation and informed consent under the new EU Medical Devices Regulation (2017∕745).

PURPOSE: The paper focuses on the ethical appraisal of the clinical investigations (CIs) and the informed consent within the new European Union (EU) legislation on medical devices (MDs). The Regulation (EU) 2017∕745 of the European Parliament and of the Council was adopted on 5 April 2017 and entered into force on 25 May 2017, repealing the Council Directives concerning Medical Devices 93∕42∕EEC and the Active Implantable Medical Devices 90∕385∕EEC. BACKGROUND: For the past thirty years, the EU legislation on MDs has been updated by several directives: Council Directive 90∕385∕EEC on Active Medical Devices (1990); Council Directive 93∕42∕EEC on Medical Devices (1993) and Council Directive 98∕79∕EC on In vitro Medical Devices (1998) aiming to frame the MDs market development. CONTENT: From the ethical perspective, the present article investigates the new rules concerning the CIs of the MDs for human use and accessories for such devices conducted in the EU by highlighting new regulatory aspects: (1) the framework of the clinical evaluation and CI; (2) the relevant definitions; (3) the ethical principles related to CIs; (4) the informed consent; (5) the role of the national ethics committees. CONCLUSIONS: Although the new guidelines enable an extension of the definition of "medical device" and the harmonization of the rules for "the placing on market and putting into service of the medical devices", it also regulates the MDs industry to ensure clinical benefits for patients and high standards of quality and safety.

The immunoexpression of EGFR, HER2 and HER3 in malignant serous ovarian tumors.

The expression of epidermal growth factor (EGF) receptors is common in human carcinomas and the proteins are used as therapeutics targets. In this study, we analyzed the immunoexpression of EGFR, HER2 (EGFR2) and HER3 (EGFR3) in 41 cases of serous borderline ovarian tumors and carcinomas, in relation to the degree of differentiation and tumor stage. The quantification of the results was done using the final staining score (FSS), which took into account the number of labeled cells and the intensity of immunoreactions. For all the receptors, the FSS values corresponding to the high-grade serous carcinomas were significantly superior compared with low-grade carcinomas and borderline tumors. Also, the FSS values associated with advanced stages ovarian tumors were significantly superior compared to those in the initial stages. In this study, we found positive linear correlations between the values associated with the expression of EGF receptors. The relation of EGFR, HER2 and HER3 immunoexpression with the lesion subtype, tumor grade and stage, designates the EGF receptors system as possible therapeutic target in ovarian serous tumors.

The evaluation of p16 and Ki67 immunoexpression in ameloblastomas.

In this study, we investigated the p16 and Ki67 immunoexpression in 19 ameloblastomas in order to highlight some correlations of these markers with the aggressive variants of tumors. The p16 immunoreaction was present in 90.9% of cases; the highest scores are present in the typical follicular and in the intraluminal unicystic variant, at the opposite pole being the granular cells variant. In these cases, the maximum reaction was observed at the level of the stellated reticulum cells while the lowest reaction was present at the level of cubico-cylindrical peripheral cells of the neoplastic islands. The Ki67 immunoreaction was present in all cases, the highest scores being present in the typical follicular variant, opposite being the ameloblastoma with granular cells cases and that with acanthomatous differentiation type. The immunostained cells were located predominantly at the periphery of the tumoral islands but also in the stellated reticulum cells in the central area. The p16 and Ki67 markers may be useful for distinguishing different types of ameloblastomas in terms of aggressiveness.

VEGF, CD105 and α-SMA immunoexpression study in lips squamous cell carcinomas and associated dysplastic lesions.

This study analyzes the microvascular density (MVD) for CD105+ and α-SMA+ vessels and VEGF immunoexpression for 35 oral squamous cell carcinomas and for the associated dysplastic lesions of the lips. CD105+ MVD was superior in the advancing edge compared to the intratumoral area, no matter the analyzed clinico-pathological parameters (gender, age, differentiation degree, tumor stage) (p<0.05), MVD being significantly higher in poorly differentiated carcinomas (p<0.05). α-SMA+ MVD was also superior in the advancing edge compared to the intratumoral area (p<0.05), MVD values being significantly higher in well and moderately differentiated carcinomas (p<0.05). CD105+ MVD and α-SMA+ MVD were significantly lower compared to the analyzed tumor area (p<0.05), in the dysplastic lesions. VEGF score showed significantly higher values in well to moderately differentiated carcinoma and in the tumor area versus dysplastic associated lesions (p<0.05). CD105+ MVD and VEGF are markers able to characterize the angiogenic phenotype of carcinomas and of the dysplastic lesions of the lips, while α-SMA+ MVD quantification is useful in assessing the vascular maturity degree.