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Periodontitis has been associated with an increased risk of and mortality associated with human colorectal cancer (CRC). Current evidence attributes such an association to the direct and indirect effects of virulence factors belonging to periodontal pathogens, to inflammatory mediators and to genetic factors. The aims of the study were to assess the existence of a genetic linkage between periodontitis and human CRC, to identify genes considered predominant in such a linkage, thus named leader genes, and to determine pathogenic mechanisms related to the products of leader genes. Genes linking periodontitis and CRC were identified and classified in order of predominance, through an experimental investigation, performed via computer simulation, employing the leader gene approach. Pathogenic mechanisms relating to leader genes were determined through cross-search databases. Of the 83 genes linking periodontitis and CRC, 12 were classified as leader genes and were pathogenically implicated in cell cycle regulation and in the immune-inflammatory response. The current results, obtained via computer simulation and requiring further validation, support the existence of a genetic linkage between periodontitis and CRC. Cell cycle dysregulation and the alteration of the immuno-inflammatory response constitute the pathogenic mechanisms related to the products of leader genes.

(1) Introduction: The novel respiratory syndrome coronavirus 2 (SARS-CoV-2), also called coronavirus disease 2019 (COVID-19), is rapidly spreading in many countries and represents a public health emergency of international concern. The SARS-CoV-2 transmission mainly occurs from person-to-person via respiratory droplets (direct transmission route), leading to the onset of mild or severe symptoms or even causing death. Since COVID-19 is able to survive also on inanimate surfaces for extended periods, constituting an indirect transmission route, healthcare settings contaminated surfaces should be submitted to specific disinfection protocols. Our review aimed to investigate the existing disinfection measures of healthcare settings surfaces, preventing the nosocomial transmission of SARS-CoV-2. (2) Materials and Methods: We conducted electronic research on PubMed, Scopus, Science Direct, and Cochrane Library, and 120 items were screened for eligibility. Only 11 articles were included in the review and selected for data extraction. (3) Results: All the included studies proposed the use of ethanol at different concentrations (70% or 75%) as a biocidal agent against SARS-CoV-2, which has the capacity to reduce the viral activity by 3 log10 or more after 1 min of exposure. Other disinfection protocols involved the use of chlorine-containing disinfectant, 0.1% and 0.5% sodium hypochlorite, quaternary ammonium in combination with 75% ethanol, isopropyl alcohol 70%, glutardialdehyde 2%, ultraviolet light (UV-C) technology, and many others. Two studies suggested to use the Environmental Protection Agency (EPA)-registered disinfectants, while one article chooses to follow the WST-512-2016 Guidance of Environmental and Surfaces Cleaning, Disinfection and Infection Control in Hospitals. (4) Conclusion: Different surface disinfection methods proved to reduce the viral activity of SARS-CoV-2, preventing its indirect nosocomial transmission. However, more specific cleaning measures, a

Introduction. The administration of several classes of drugs can lead to the onset of gingival overgrowth: Anticonvulsants, immunosuppressants, and calcium channel blockers. Among the anticonvulsants, the main drug associated with gingival overgrowth is diphenylhydantoin. Materials and Methods. In this study, we compared the effects of diphenylhydantoin and gabapentin on 57 genes belonging to the “Extracellular Matrix and Adhesion Molecule” pathway, present in human fibroblasts of healthy volunteers. Results. Both molecules induce the same gene expression profile in fibroblasts as well as a significant upregulation of genes involved in extracellular matrix deposition like COL4A1, ITGA7, and LAMB3. The two treatments also induced a significant downregulation of genes involved in the expression of extracellular matrix metalloproteases like MMP11, MMP15, MMP16, MMP24, and transmembrane receptor ITGB4. Conclusions. Data recorded in our study confirmed the hypothesis of a direct action of these drugs at the periodontium level, inducing an increase in matrix production, a reduction in its degradation, and consequently resulting in gingival hyperplasia.

Background: Craniofacial morphogenesis is the result of an intricate multistep network of tightly controlled spatial and temporal signalling that involves several molecules and transcription factors organized into highly coordinated pathways. Any alteration in even one step of this delicate process can lead to congenital malformations such as cleft palate. One of the first steps in embryonal orofacial development is the migration of cells from the neural crests to the branchial arches. Next, the cells have to proliferate, differentiate, move and connect to each other in order to correctly form the palate. Cell contraction, promoted by the interaction of non-muscle myosin II and actin A, is a crucial step in morphogenesis and is regulated by ROCK1 protein. Methods: A family-based association study was carried out in order to verify whether or not genetic variants of ROCK1 were associated with non-syndromic cleft palate (nsCP). Two cohorts from Italy and Iran, a total of 189 nsCP cases and their parents were enrolled. Results: The rs35996865-G allele was under-transmitted in cases of nsCP [P =.006, odds ratio (OR) = 0.63 (95% CI 0.45-0.88)]. Conclusion: This investigation reveals for the first time data supporting a role for ROCK1 in nsCP aetiology.

Introduction: The gold-standard method for diagnosis of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or COVID-19) foresees the examination of respiratory tract swabs by real-time reverse-transcription polymerase chain reaction (rRT-PCR). Another group of diagnostic tests, developed to overcome the limitations of RT-PCR, includes the serological assays, which have the purpose of detecting the antibody response to SARS-CoV-2 infection (IgM and IgG titers). The aim of this review was to establish the diagnostic capability of the existing serological tests in the detection of SARS-CoV-2 infection. Materials and Methods: Electronic research was conducted in PubMed, Scopus, Science Direct and Cochrane Library, and only 10 articles, testing 10 different types of serological assays, met the inclusion criteria and were consequently submitted to quality assessment and data extraction. Quantitative data about the sensitivity, specificity, positive/negative predictive value and IgM/IgG titer provided by each antibody test were reported in our review. Results: Almost all the serological tests used in the included items were recorded to ensure high sensitivity and specificity, identifying the presence of IgM and IgG antibodies against SARS-CoV-2 in patients with certain COVID-19 diagnosis (confirmed by RT-PCR) and in participants with suspected infection (SARS-CoV-2 clinical diagnosis and/or RT-PCR negative subjects). Conclusions: Serological tests may represent reliable diagnostic tools in the detection of SARS-CoV-2 infection, and they could be implemented complementary to real-time RT-PCR.

Introduction: Osseointegration are often suffering from oral conditions, especially, the micro gap at the implant-abutment connection represents a site for bacterial plaque aggregation, leading to increased inflammatory cells and causing peri-implantitis. Aim: The aim of this narrative review was to describe the different kinds of implant-abutment connections and their ability to reduce bacterial leakage and thus prevent peri-implantitis. Materials and methods: The following databases were consulted: Pubmed, Scopus, Cochrane Library, and Research gate and a total of 528 articles were found. After reading the abstract and titles, 473 items were excluded. The remaining articles (n = 55) were assessed for full-text eligibility. Thirty-three studies were included in the review. Results and Conclusions: We selected 22 clinical trials and 11 reviews, examining a total sample of 2110 implants. From the review, it was clear that there exists a relationship between the implant-abutment interface and bacterial leakage. All the connections presented an amount of micro-gap and bacterial micro-leakage, though conical and mixed connection systems seemed to behave better. Moreover, both connections seemed to have a better load distribution and the mixed system also had anti-rotational properties which are very useful during the positioning of the prosthesis.

Background. One of the most important aims of an endodontic treatment is to obtain the complete removal or reduction of root canal remaining filling material: Smear layer, bacteria, intra-canal medicaments. To meet this requirement, several irrigation activation techniques have been proposed. Our systematic review examined studies which analyzed the XP-endo Finisher (XPF) instrument efficacy in removing root canal debris during initial endodontic treatment or retreatment, comparing it with the efficacy of other irrigation activation protocols, such as passive ultrasonic irrigation (PUI), laser activation procedure (Er:YAG), and Self-Adjusting File system (SAF). Methods. A systematic review was conducted using PubMed, Chocrane Library, and Scopus databases, identifying 51 items. Thirty-four articles were excluded based on title, abstract, full text, and language. Seventeen randomized controlled trials were selected and consequently submitted to quality assessment and data collection. Results. Conventional needle irrigation (CNI) is the less effective irrigation technique, but it is still unclear whether XPF is able to guarantee greater debris removal than the PUI technique. Er:YAG laser has been proven to be more effective in apical third than XPF instrument. Conclusions. Further investigations are needed in order to establish which final irrigation activation procedure could reach the maximum root canal debris reduction.

Liquid biopsy represents a great promise for its potential to detect cancer before clinical signs occur. It represents a very advantageous tool, as it is rapid and minimally invasive in monitoring cancer: in particular its main applications should concern the early diagnosis of cancer, the prognostic evaluation, the assessment of treatment response and the evaluation of recurrences. In relation to HNSCC compared to other cancer anatomic locations, the impact of liquid biopsy in the clinical setting is still limited: the study of CTCs and ctDNA has been increased in order to identify precise correlations between the tumor burden and biomarkers levels and to assess how these levels vary during and after treatments. However, in order to do this, it is necessary to overcome the pro- blem of tumor heterogeneity, by identifying the main mutations un- derlying head and neck cancers: in this regard an appropriate addition to the TNM staging system would be the inclusion of the molecular typing of the tumor, which would help to personalize therapies, de- creasing the risk of overtreatment or undertreatment [94,95]. Despite the numerous analyzed biomarkers in these studies, we can consider as reliable only a limited number of these: for that concern CTCs the only standardized and reliable method that could be applied to HNSCC is the detection of EPCAM, while in relation to ctDNA, the main genetic alterations that can be correlated to head and neck can- cers are those related to EGFR, RAS and TP53 genes, or viral DNA de- tection (HPV). Finally, despite the several methods and technologies for CTCs and ctDNA detection, there is still a lack of standardized methods. In ad- dition, there are no studies evaluating the influence that different therapies and different types of cancer may have on the detection of CTCs and ctDNA: the heterogeneity of the sample populations, the different therapeutic protocols and the different stages of the tumors included in the clinical trials still

Introduction: In the different branches of dentistry, the use of laser to solve different clinical situations is increasing due to numerous advantages that have been studied in literature since the 70s. Leucoplakia and hyperkeratosis can benefit from laser-assisted treatment. In most cases biopsy sampling, histological examination and, if no malignant cells are present, the follow-up is needed. However, even if the lesion is free of dysplasia patients often ask to eliminate these white spots that are always a cause of concern. Aim: From these numerous requests comes the idea of setting up a laser-assisted protocol as less invasive as possible to be offered to patients. The aim of the study is to find a laser-assisted protocol for the surgical excision of leucoplakia and hyperkeratosis that can both improve the clinical aspect of the lesion and be sustainable for patients. The null hypothesis has been identified in the following statement: the treatment is effective and efficient at the same time; where effectiveness was tested with the following criteria: size of the lesion, tactile perception, discomfort, pain; and efficiency with the following criteria: pain and discomfort perceived during the treatment. Materials and methods: To collect all data, a specially designed medical record was used. The diode laser was used with a pulsed mode and the maximum power corresponds to 1.8 W. No anaesthesia was used. Before laser-assisted treatment, the fibre was activated and was used with a contact overflowing. Results: Our results show a decrease in the size of the lesion statistically significant. No pain was referred during treatment, except for a slight burning sensation. Conclusion: In conclusion we can state that the treatment is both efficient and effective

When exposed to stress, the human body suppresses the parasympathetic nervous system and simultaneously activates the sympathetic nervous system, in order to resist to this condition and acquire energy. Materials and methods. FM5 Sensory® is an innovative technological device that integrates simultaneously: 1) photonic beams emitted by an LED system, 2) acoustic WiFi for listening to musical binaural frequencies and 3) inhaled aro-matherapy with interchangeable disposable diffuser. Aim was to evaluate the cortisol levels in urine collected for 24 hours before and after treatment for 30 minutes in six patients. Results. There was a small not statistical significant drop of urinary cortisol after treatment. Discussion and conclusion. Literature reports show that lighting is able to affect the mood of elderly people. Here a trend is reported although no statistical difference was detected. Additional studies with wide samples are mandatory to verify the real effect of LED therapy on cortisol.

Aims: To select a core list of standard outcomes for diabetes to be routinely applied internationally, including patient-reported outcomes. Methods: We conducted a structured systematic review of outcome measures, focusing on adults with either type 1 or type 2 diabetes. This process was followed by a consensus-driven modified Delphi panel, including a multidisciplinary group of academics, health professionals and people with diabetes. External feedback to validate the set of outcome measures was sought from people with diabetes and health professionals. Results: The panel identified an essential set of clinical outcomes related to diabetes control, acute events, chronic complications, health service utilisation, and survival that can be measured using routine administrative data and/or clinical records. Three instruments were recommended for annual measurement of patient-reported outcome measu

Drug-induced gingival overgrowth may occur after a chronic administration of three classes of systemic drugs: Anticonvulsants, immunosuppressants, and calcium channel blockers. This study aimed to investigate how cyclosporin A and mycophenolate mophetil (immunosuppressive drugs) could interfere with human gingival fibroblasts functions, leading to gingival enlargement. Human gingival fibroblasts derived fromthe tissue of a 60-year-old female were cultured in aDMEMEmedium. A stock solution with 1 mg/mL of mycophenolate and 1 mg/mL of cyclosporine were prepared and dissolved in a DMEM medium to prepare a serial dilution at the concentrations of 5000, 2000, 1000, 500, and 100 ng/mL, for both treatments. Cell viability was measured using the PrestoBlueTM Reagent Protocol. Quantitative real-time RT-PCR was performed in order to analyze the expression of 57 genes coding for gingival fibroblasts "Extracellular Matrix and Adhesion Molecules". Mycophenolate and cyclosporine had no effect on fibroblast cell viability at 1000 ng/mL. Both the treatments showed similar effects on the expression profiling of treated cells: Downregulation of most extracellular matrix metalloproteases genes (MMP8, MMP11, MMP15, MMP16, MMP24) was assessed, while CDH1, ITGA2, ITGA7, LAMB3, MMP12, and MMP13 were recorded to be upregulated in fibroblasts treated with immunosuppressive drugs. It has been demonstrated that gingival overgrowth can be caused by the chronic administration of cyclosporin A and mycophenolate mophetil. However, given the contrasting data of literature, further investigations are needed, making clear the possible effects of immunosuppressive drugs on fibroblasts.

Introduction. Several biomaterials are used in periodontal tissue engineering in order to obtain a three-dimensional scaffold, which could enhance the oral bone regeneration. These novel biomaterials, when placed in the affected area, activate a cascade of events, inducing regenerative cellular responses, and replacing the missing tissue. Natural and synthetic polymers can be used alone or in combination with other biomaterials, growth factors, and stem cells. Natural-based polymer chitosan is widely used in periodontal tissue engineering. It presents biodegradability, biocompatibility, and biological renewability properties. It is bacteriostatic and nontoxic and has hemostatic and mucoadhesive capacity. The aim of this systematic review is to obtain an updated overview of the utilization and effectiveness of chitosan-based scaffold (CS-bs) in the alveolar bone regeneration process. Materials and Methods. During database searching (using PubMed, Cochrane Library, and CINAHL), 72 items were found. The title, abstract, and full text of each study were carefully analyzed and only 22 articles were selected. Thirteen articles were excluded based on their title, five after reading the abstract, twenty-six after reading the full text, and six were not considered because of their publication date (prior to 2010). Quality assessment and data extraction were performed in the twelve included randomized controlled trials. Data concerning cell proliferation and viability (CPV), mineralization level (M), and alkaline phosphatase activity (ALPA) were recorded from each article Results. All the included trials tested CS-bs that were combined with other biomaterials (such as hydroxyapatite, alginate, polylactic-co-glycolic acid, polycaprolactone), growth factors (basic fibroblast growth factor, bone morphogenetic protein) and/or stem cells (periodontal ligament stem cells, human jaw bone marrow-derived mesenchymal stem cells). Values about the proliferation of cementoblasts (CB) and

Background: Gingival hyperplasia could occur after the administration of cyclosporine A. Up to 90% of the patients submitted to immunosuppressant drugs have been reported to suffer from this side effect. The role of fibroblasts in gingival hyperplasia has been widely discussed by literature, showing contrasting results. In order to demonstrate the effect of cyclosporine A on the extracellular matrix component of fibroblasts, we investigated the gene expression profile of human fibroblasts after cyclosporine A administration. Materials and methods: Primary gingival fibroblasts were stimulated with 1000 ng/mL cyclosporine A solution for 16 h. Gene expression levels of 57 genes belonging to the “Extracellular Matrix and Adhesion Molecules” pathway were analyzed using real-time PCR in treated cells, compared to untreated cells used as control. Results: Expression levels of different genes were significantly de-regulated. The gene CDH1, which codes for the cell adhesion protein E-cadherin, showed up-regulation. Almost all the extracellular matrix metalloproteases showed down-regulation (MMP8, MMP11, MMP15, MMP16, MMP24, MMP26). The administration of cyclosporine A was followed by down-regulation of other genes: COL7A1, the transmembrane receptors ITGB2 and ITGB4, and the basement membrane constituents LAMA2 and LAMB1. Conclusion: Data collected demonstrate that cyclosporine inhibits the secretion of matrix proteases, contributing to the accumulation of extracellular matrix components in the gingival connective tissue, causing gingival overgrowth. Patients affected by gingival overgrowth caused by cyclosporine A need to be further investigated in order to determine the role of this drug on fibroblasts.

Background: The number of pediatric patients affected by HIV still remains high, mainly in developing countries, where the main cause of infection is vertical transmission from the mother. Even today, a large number of these children do not have access to treatment, and, without proper care, they die in the first few years of life. Objective: The aim of our review was to assess the prevalence of oral hard and soft tissue lesions in HIV-positive pediatric patients by identifying the most common manifestations and the overall impact that they may have on the children’s quality of life. Study design: A systematic review of the articles in the English language in PubMed and Scopus was conducted in March 2019 in order to identify the main epidemiological and cross-sectional studies on the topic. Results: Oral diseases are still one of the most common manifestations in HIV-positive pediatric patients, and they often represent the first form in which immunosuppression shows itself. An analysis of the literature shows that candidiasis is the most common oral lesion found in HIV-positive children. A significant incidence of gingivitis and gingival disease is also evident, though not strictly correlated to HIV infection. However, thanks to the introduction of new antiretroviral therapies, the incidence of HIV-related oral lesions is decreasing. Conclusions: An HIV-positive children care program should also include dental protocols, as oral disease negatively influences the quality of life, affecting both functional and social aspects.

Background: Oral squamous cell carcinoma (OSCC) accounts for more than 90% of oral epithelial malignancies and often arises from precursor lesions, whose diagnosis is based on biopsy and histopathology. In vivo reflectance confocal microscopy (RCM) images the vital tissues at microscopic resolution, well correlating with conventional histopathology, but it is poorly investigated in oral oncology. The present work aims to describe RCM cytoarchitectural findings in oral mucosae affected by OSCC and its precursors. Materials and Methods: A series of clinically suspected oral lesions underwent RCM imaging before conventional biopsy and histopathological assessment in order to identify features suggestive of tumoral changes. Sensitivity (SE), specificity (SP), positive and negative predictive values (PPV and NPV) of RCM compared to histopathology were calculated. Results: Totally, 30 sites in 20 patients were considered and clinically classified into 16 “leukoplakia”/“ traumatism”, nine erosive-ulcerative lesions, three verrucous lesions, and two healthy mucosae, as control. The histopathological “positivity,” due to the presence of various degrees of dysplasia and/or neoplasia, was found in 11 lesions; the RCM “positivity” was referred to nine lesions reporting the RCM detection of polymorphism, multinucleated cells, irregular cellular maturation, altered nuclear/cytoplasm ratio, and abnormal blood vessels. After excluding three verrucous lesions from the RCM analysis, due to the low laser penetration through the hyperkeratotic layers, the results well correlated with histopathology, reporting 1.000 (SE), 0.933 (SP), 0.909 (PPV), and 1.000 (NPV). Conclusion: RCM can reveal dysplastic/neoplastic signs occurring in oral lesions, thus supporting their diagnostic pathway.

AIMS To select a core list of standard outcomes for diabetes to be routinely applied internationally, including patient-reported outcomes. METHODS We conducted a structured systematic review of outcome measures, focusing on adults with either type 1 or type 2 diabetes. This process was followed by a consensus-driven modified Delphi panel, including a multidisciplinary group of academics, health professionals and people with diabetes. External feedback to validate the set of outcome measures was sought from people with diabetes and health professionals. RESULTS The panel identified an essential set of clinical outcomes related to diabetes control, acute events, chronic complications, health service utilisation, and survival that can be measured using routine administrative data and/or clinical records. Three instruments were recommended for annual measurement of patient-reported outcome measures: the WHO Well-Being Index for psychological well-being; the depression module of the Patient Health Questionnaire for depression; and the Problem Areas in Diabetes scale for diabetes distress. A range of factors related to demographic, diagnostic profile, lifestyle, social support and treatment of diabetes were also identified for case-mix adjustment. CONCLUSIONS We recommend the standard set identified in this study for use in routine practice to monitor, benchmark and improve diabetes care. The inclusion of patient-reported outcomes enables people living with diabetes to report directly on their condition in a structured way.