Urinary Procoagulant Activity in Health and Disease Method Development and Clinical Development

The broad aims of this thesis are to: 1) develop and validate a novel and reliable Urine Tissue Factor (uTF) assay, 2) study uTF function, expression and origin, 3) address factors which might affect uTF measurements in health and renal disorders, 4) re-assess the diagnostic value of uTF levels in cancer, glomerular injuries and inflammatory conditions, 5) examine the hypothesis that uTF levels reflect tumour taken by relating these to disease stage, tumour recurrence and conventional markers of tumour progression and 6) investigate whether uTF levels mirror those of blood mTF activation.Urine and/or blood samples were collected from a total of 1658 subjects covering normal individuals, patients with renal insufficiency, four types of malignant tumours and corresponding benign conditions and glomerulonephritis.The new uTF method is reproducible (intra-assay CV 2.3%, inter-assay CV 8.1%) with very low variation in normal controls and no significant diurnal or day-to-day variation once values were corrected for urine concentration. uTF was expressed on lipid vesicles which are essential for its activity. Cellular TF antigen was localised to the distal and proximal tubules, uTF was stable and levels were not significantly affected by glomerular permeability and filtration, tubular function nor by the presence of contaminants in urine. Patients with malignant tumours, glomerular injury and various inflammatory conditions have significantly higher uTF activity compared to normal subjects or patients with benign non-inflammatory disease. Levels were significantly associated with histological tumour grade, malignant recurrence and other markers of tumour aggressiveness.</p

Is there evidence that e-cigarettes promote an increased risk of dental caries?

Data sources: this study was conducted on a sample of patients who attended the dental clinic at Tufts University School of Dental Medicine, between January 1, 2019 and January 1, 2022. Ethical approval was obtained before commencing the research.Study selection: this cross-sectional study was carried out through an electronic search of electronic records. It includes patients aged over 16 years, both electronic cigarette (e-cigarettes) users and non-users, with recorded caries risk assessments. Patients with a history of recreational drug use or lacking a caries diagnosis were excluded. The Caries Management by Risk Assessment (CAMBRA) was utilized to indicate and classify caries risk.Data extraction and synthesis: descriptive statistics, multivariate and bivariate analyzes were used to assess the relationship between use of e-cigarettes and caries risk level. SPSS software, Version 26 (IBM) was used in the analysis with significance level set at α = 0.05.Results: out of a total of 13,216 patients included in the research, 13,080 (99.3%) self-declared as non-users of e-cigarettes, and 136 (0.69%) were e-cigarette users. There was a statistically significant difference (P &lt; 0.001) in caries risk levels between e-cigarette users (6.6% low, 14.3% moderate, and 79.1% high caries risk level) and control group (14.5% low, 25.9% moderate, and 59.6% high caries risk level).Conclusions: the study provides evidence supporting the notion that e-cigarette users exhibit a high level of caries risk

Electronic nicotine delivery systems (ENDS): a strategy for smoking cessation or a new risk factor for oral health?

Data sources: a search was conducted in PubMed and Cochrane Library databases for articles published in English between January 2012 and October 2022.Study selection: articles were selected using both the term “electronic nicotine delivery system” (ENDS), as per the Medical Subject Heading (MeSH), in conjunction with specific oral domains. In vitro studies, animal models, unregistered clinical trials, and articles with conflicts of interest were excluded.Data extraction and synthesis: clinical and public health studies comparing ENDS users, smokers, and non-smokers in the context of oral-related diseases were included. Results from duplicate articles were not considered.Results: the study indicates a potential carcinogenic effect due to cytogenotoxicity from intrinsic components of ENDS. However, this does not establish ENDS as an independent risk factor for oral cancer. ENDS use may alter the oral microbiome, leading to increased biofilm adhesion and potential associations with caries, periodontal disease, and peri-implantitis. The wide variety of flavors available in the ENDS market is a significant factor influencing initiation and long-term use by young people.Conclusions: ENDS users are susceptible to periodontal disease, caries, soft tissue injuries, and changes in tooth and prosthesis coloration. The chemical components in ENDS can induce cellular changes associated with a potential risk of oral cancer. However, more long-term studies are required to fully understand the impact of ENDS use on oral health

How safe is off-label use of imiquimod in oral lesions?

Data sources: a comprehensive search was conducted on PubMed and Embase, adhering to the principles outlined in the PRISMA Extension for Scoping Reviews (PRISMA-ScR). The search strategy was subsequently registered on PROSPERO. Study selection: articles were chosen based on an analysis of titles and abstracts, with no restrictions on publication date, language, or participant age. In vitro studies, animal studies, and literature reviews were excluded from consideration. Data extraction and synthesis: clinical trials in humans, case reports, or case series that reported the use of imiquimod for treating conditions in the oral or labial mucosa were included in this study. Results from duplicate articles were excluded from the analysis. Results: out of a total of 601 references initially identified, only 28 studies were included in the review. These studies were classified based on the use of imiquimod into three groups: potentially malignant disorders and oral cancer, lesions related to HPV, and autoimmune conditions. In all cases presented in the article, there is an occurrence of both local and systemic side effects. Conclusions: the study elucidated the off-label use of imiquimod in oral pathologies, whether potentially malignant, cancerous, autoimmune, or associated with HPV infection. However, it was observed that further research is warranted for the development of a specific formulation for the oral mucosa, ensuring the drug’s sustained presence at its active site of action without interference from saliva and minimizing potential side effects.</p

Impacts of smoking on oral health—what is the role of the dental team in smoking cessation?

Data sources: electronic searches were conducted on databases (PubMed, EMBASE, and Google Scholar). In addition, websites of national organisations (US Food and Drug Administration, National Cancer Institute, Centres for Disease Control and Prevention, American Dental Association, Office of Disease Prevention and Health Promotion, National Institute on Drug Abuse, Agency for Healthcare Research and Quality) were also searched.Study selection: to achieve the objectives of the study, systematic reviews, controlled clinical trials, and observational studies published between October 2021 and February 2022 were considered.Data extraction and synthesis: this narrative review included articles which investigated the role of Dentistry professionals and their impact on smoking cessation and the effects resulting from tobacco use on oral health.Results: the review revealed that smokers have a significantly higher likelihood of developing oral cancer (95% CI: 3.19–6.77) compared to non-smokers. Passive smokers also have an increased risk (1.51 times) of developing oral cancer (95% CI: 1.20–1.91). Additionally, smokers have an 80% increased risk of periodontitis (RR = 1.82; 95% CI: 1.43–2.31), an 85% worsened periodontal condition (RR = 1.85; 95% CI: 1.5–2.2), and a 36.6% increase in caries prevalence (OR = 1.84; 95% CI: 1.64–2.07). Smoking is also associated with a higher potential for dental implant failure in a dose-dependent manner. Brief educational interventions by the dental team resulted in a smoking cessation rate of 74/1000 individuals versus 27/1000 individuals in the control group. When combined with pharmacological therapy, these interventions may lead to an additional 50 to 70% increase in long-term smoking abstinence.Conclusions: smoking is strongly linked to an increased risk of oral cancer, dental caries, implant failure, and periodontal disease. Dental teams play a vital role in identifying and addressing oral pathologies related to smoking and providing necessary care for smoking cessation. Brief educational interventions, either alone or in combination with pharmacotherapy, offer valuable approaches for the dental team to support smoking cessation. However, establishing a comprehensive training and continuing education program is crucial to integrate dental professionals into a multidisciplinary smoking cessation program

COVID-19 Vaccines: Bioethical Consideration

15 páginasLa pandemia de la covid-19 ha tenido impactos inconmensurables en la economía, la educación y la socialización, además de la pérdida de millones de vidas. Por lo tanto, se ha acelerado el desarrollo de un número sin precedentes de candidatos a vacunas contra la covid-19 para controlar la pandemia. A su vez, la autorización para su uso de emergencia por parte de la Organización Mundial de la Salud permitió el inicio de la inmunización de la población a través de vacunas que aún se encuentran en ensayos clínicos. Aquí presentamos una perspectiva de los preceptos bioéticos de autonomía, no maleficencia, beneficencia y justicia en el contexto del uso de emergencia de vacunas contra la covid-19. Además, se enfatiza la importancia de la vigilancia en todas las etapas del desarrollo de la vacuna con el fin de detectar efectos adversos y asegurar el cumplimiento de los preceptos bioéticos.The COVID-19 pandemic produced immeasurable impacts on the economy, education, and socialization, besides the loss of mi-llions of lives. Thus, there has been an accelerated development of an unprecedented number of COVID-19 vaccine candidates to control the pandemic. The World Health Organization’s emergency use authorization of COVID-19 vaccines still in clinical trial allowed immunizing the population. This paper presents a perspective of the bioethical precepts of autonomy, non-maleficence, beneficence, and justice in the emergency use of COVID-19 vaccines. Furthermore, it emphasizes the importance of surveillance at all stages of vaccine development to detect adverse effects and ensure compliance with bioethical precepts

Vacinas contra a covid-19: consideração bioética

The COVID-19 pandemic produced immeasurable impacts on the economy, education, and socialization, besides the loss of millions of lives. Thus, there has been an accelerated development of an unprecedented number of COVID-19 vaccine candidates to control the pandemic. The World Health Organization’s emergency use authorization of COVID-19 vaccines still in clinical trial allowed immunizing the population. This paper presents a perspective of the bioethical precepts of autonomy, non-maleficence, beneficence, and justice in the emergency use of COVID-19 vaccines. Furthermore, it emphasizes the importance of surveillance at all stages of vaccine development to detect adverse effects and ensure compliance with bioethical precepts.La pandemia de la covid-19 ha tenido impactos inconmensurables en la economía, la educación y la socialización, además de la pérdida de millones de vidas. Por lo tanto, se ha acelerado el desarrollo de un número sin precedentes de candidatos a vacunas contra la covid-19 para controlar la pandemia. A su vez, la autorización para su uso de emergencia por parte de la Organización Mundial de la Salud permitió el inicio de la inmunización de la población a través de vacunas que aún se encuentran en ensayos clínicos. Aquí presentamos una perspectiva de los preceptos bioéticos de autonomía, no maleficencia, beneficencia y justicia en el contexto del uso de emergencia de vacunas contra la covid-19. Además, se enfatiza la importancia de la vigilancia en todas las etapas del desarrollo de la vacuna con el fin de detectar efectos adversos y asegurar el cumplimiento de los preceptos bioéticos.A pandemia ocasionada pela covid-19, além da perda de milhões de vidas, vem trazendo consequências incomensuráveis para a economia, a educação e a socialização. Portanto, vem sendo acelerado o desenvolvimento de um número sem precedentes de candidatos a vacinas contra a covid-19 para controlar a pandemia. Por sua vez, a autorização para seu uso emergencial por parte da Organização Mundial da Saúde permitiu o início da imunização da população por meio de vacinas que ainda se encontram em ensaios clínicos. Aqui, apresentamos uma perspectiva dos princípios bioéticos de autonomia, não maleficência, beneficência e justiça no contexto do uso emergencial de vacinas contra covid-19. Além disso, é enfatizada a importância da vigilância em todas as etapas do desenvolvimento da vacinação a fim de detectar efeitos adversos e assegurar o cumprimento dos princípios bioéticos

Impaired Fibrinolysis in Angiographically Documented Coronary Artery Disease

Impaired fibrinolysis may predispose to coronary artery disease (CAD). Hypofibrinolysis due to high levels of plasminogen activator inhibitor-1 (PAI-1) has been reported in CAD. A novel regulator of fibrinolytic activity, thrombin activatable fibrinolysis inhibitor (TAFI), has attracted attention in recent years. It acts by blocking the formation of a ternary complex of plasminogen, fibrin, and tissue plasminogen activator (t-PA). Previously ambiguous results regarding TAFI levels have been reported in CAD. We measured plasma levels of PAI-1 and TAFI antigen in 123 patients with age ranging from 40 to 65 years who had been submitted to coronary angiography and assessed the association of these markers with the extent of stenosis in three groups: angiographically normal artery (NAn), mild to moderate atheromatosis (MA), and severe atheromatosis (SA). Plasma levels of PAI-1 were increased in patients with severe atheromatosis compared to mild/moderate atheromatosis or to normal patients (66.60, 40.50, and 34.90 ng/mL, resp.; P < 0.001). For TAFI no difference was found between different groups. When patients were grouped in only two groups based on clinical cut-off point for intervention (stenosis less than or above 70%) we found increased plasma levels for PAI-1 (37.55 and 66.60 ng/mL, resp.; P < 0.001) and decreased plasma levels for TAFI (5.20 and 4.53 μg/mL, resp.; P = 0.04) in patients with stenosis above 70%. No difference was found in PAI-1 or TAFI levels comparing the number of affected vessels. Conclusion. As evidenced by a raised level of PAI-1 antigen, one can suggest an impaired fibrinolysis in stable CAD, although no correlation with the number of affected vessels was found. Curiously, a decreased plasma level of total TAFI levels was observed in patients with stenosis above 70%. Further studies measuring functional TAFI are required in order to elucidate its association with the extent of degree of atheromatosis