Showing papers in "Frontiers in oral health in 2022"

Oral-Gut Microbiome Axis in the Pathogenesis of Cancer Treatment-Induced Oral Mucositis

Abstract: Oral mucositis (OM) is one of the most common and debilitating oral complications of cancer treatments including chemotherapy, radiotherapy, and hematopoietic stem cell transplantation. It is associated with severe pain and difficulties in chewing, swallowing, and speech. This leads to impairment of basic oral functions and could result in unplanned treatment interruption or modification. As such, OM negatively impacts both patients' quality of life as well as tumor prognostic outcomes. Understanding pathways underlying OM pathogenesis help identify new targets for intervention or prevention. The pathophysiology of OM has been widely studied over past decades with several pathways related to oxidative stress, inflammation, and molecular and cellular signaling being implicated. In this mini-review, we will discuss the emerging role of the oral-gut microbiome axis in the development of OM. Particularly, we will elaborate on how the alterations in the oral and gut microbiota as well as intestinal dysfunction caused by cancer treatments could contribute to the pathogenesis of OM. Further, we will briefly discuss the potential methods for targeting the oral-gut microbiome axis to improve OM outcomes.

Deep Machine Learning for Oral Cancer: From Precise Diagnosis to Precision Medicine

Abstract: Oral squamous cell carcinoma (OSCC) is one of the most prevalent cancers worldwide and its incidence is on the rise in many populations. The high incidence rate, late diagnosis, and improper treatment planning still form a significant concern. Diagnosis at an early-stage is important for better prognosis, treatment, and survival. Despite the recent improvement in the understanding of the molecular mechanisms, late diagnosis and approach toward precision medicine for OSCC patients remain a challenge. To enhance precision medicine, deep machine learning technique has been touted to enhance early detection, and consequently to reduce cancer-specific mortality and morbidity. This technique has been reported to have made a significant progress in data extraction and analysis of vital information in medical imaging in recent years. Therefore, it has the potential to assist in the early-stage detection of oral squamous cell carcinoma. Furthermore, automated image analysis can assist pathologists and clinicians to make an informed decision regarding cancer patients. This article discusses the technical knowledge and algorithms of deep learning for OSCC. It examines the application of deep learning technology in cancer detection, image classification, segmentation and synthesis, and treatment planning. Finally, we discuss how this technique can assist in precision medicine and the future perspective of deep learning technology in oral squamous cell carcinoma.

The Relationships Among Periodontitis, Pneumonia and COVID-19

Abstract: Periodontitis is a chronic inflammatory disease of the supporting structures of the teeth that affects approximately half of adults 30 years and older. There is increasing interest in the direct and indirect relationships between periodontitis and systemic diseases, including respiratory diseases. The aim of this study was to assess the evidence on links among periodontitis, pneumonia, and COVID-19. Oral and periodontal bacteria may be linked to respiratory disease directly by aspiration of pathogens into the lungs causing pneumonia. As SARS-CoV-2 began to spread worldwide in 2020, questions have arisen of how periodontal disease may also be connected to SARS-CoV-2 infection and severity, including potential replication and dissemination of the virus from periodontal pockets. Some proposed mechanisms include the oral cavity acting as a reservoir or point of entry for SARS-CoV-2, overgrowth of periodontal pathogens, and increased production of proinflammatory cytokines. Due to potential links between periodontal disease and respiratory infections like pneumonia and SARS-CoV-2, oral hygiene and management of periodontitis remain essential to help reduce infection and transmission of SARS-CoV-2.

Irrigating Solutions and Activation Methods Used in Clinical Endodontics: A Systematic Review

Abstract: Background Ex vivo and in vitro studies have demonstrated the effectiveness of some irrigation protocols in reducing the bacterial load in the root canal system. However, standardized protocols have not yet been defined for the real clinical context due to many irrigation procedures available. Objective To evaluate the clinical endodontic protocols and limitations of irrigating solutions in the disinfection of the root canal system in patients with apical periodontitis. Methods PubMed, Scopus, Embase, Web of Science, and Cochrane databases were searched for randomized controlled trials (RCT) published until January 2021. Hand searching was also performed. Studies focused on evaluating the effectiveness of irrigating solutions and/or irrigation activation methods in reducing the bacterial load in the root canal system were considered. The Cochrane risk-of-bias tool for randomized trials (RoB2) was used to assess the quality of the studies. Results Four hundred and twenty eight published articles were identified. After removing the duplicate studies and analyzing full texts, seven RCTs were selected. Two studies compared pure NaOCl with some combination of NaOCl with HEDP and MTAD. Two studies analyzed the antibacterial efficacy of NaOCl and chlorhexidine (CHX). Three studies compared conventional needle irrigation with different irrigation activation methods (PUI, XP-endo finisher, F-file activator, EndoVac activator). The review attained a satisfactory methodology. The main results of each included study were described. Discussion Activation methods provide significantly higher biofilm reduction than conventional needle irrigation methods. Combinations of NaOCl with different chelating agents were ineffective in terms of antimicrobial, but it could potentially increase the risk of irrigant extrusion. However, the irrigating protocols were not carefully detailed, especially those regarding the irrigants application time or total volume. The existing literature lacks high-quality studies. The level of evidence is moderate. Conclusions The available data is too heterogeneous to compare and identify the superiority of specific valuable irrigation protocols in each clinical context. Application time, volume, and activation methods should be standardized to determine the optimal irrigating procedures to reduce the bacterial load and ensure higher predictability of the endodontic treatment. Systematic Review Registration (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=218555), PROSPERO registration: CRD42020218555.

Mass Spectrometry-Based Differentiation of Oral Tongue Squamous Cell Carcinoma and Nontumor Regions With the SpiderMass Technology

Abstract: Oral cavity cancers are the 15th most common cancer with more than 350,000 new cases and ~178,000 deaths each year. Among them, squamous cell carcinoma (SCC) accounts for more than 90% of tumors located in the oral cavity and on oropharynx. For the oral cavity SCC, the surgical resection remains the primary course of treatment. Generally, surgical margins are defined intraoperatively using visual and tactile elements. However, in 15–30% of cases, positive margins are found after histopathological examination several days postsurgery. Technologies based on mass spectrometry (MS) were recently developed to help guide surgical resection. The SpiderMass technology is designed for in-vivo real-time analysis under minimally invasive conditions. This instrument achieves tissue microsampling and real-time molecular analysis with the combination of a laser microprobe and a mass spectrometer. It ultimately acts as a tool to support histopathological decision-making and diagnosis. This pilot study included 14 patients treated for tongue SCC (T1 to T4) with the surgical resection as the first line of treatment. Samples were first analyzed by a pathologist to macroscopically delineate the tumor, dysplasia, and peritumoral areas. The retrospective and prospective samples were sectioned into three consecutive sections and thaw-mounted on slides for H&E staining (7 μm), SpiderMass analysis (20 μm), and matrix-assisted laser desorption ionization (MALDI) MS imaging (12 μm). The SpiderMass microprobe collected lipidometabolic profiles of the dysplasia, tumor, and peritumoral regions annotated by the pathologist. The MS spectra were then subjected to the multivariate statistical analysis. The preliminary data demonstrate that the lipidometabolic molecular profiles collected with the SpiderMass are significantly different between the tumor and peritumoral regions enabling molecular classification to be established by linear discriminant analysis (LDA). MALDI images of the different samples were submitted to segmentation for cross instrument validation and revealed additional molecular discrimination within the tumor and nontumor regions. These very promising preliminary results show the applicability of the SpiderMass to SCC of the tongue and demonstrate its interest in the surgical treatment of head and neck cancers.

Association Between Mental Health and Oral Health Status and Care Utilization

Abstract: Studies have shown that mental health and oral health may be correlated, with associations demonstrated between mental health problems and tooth loss, periodontal disease, and tooth decay. The COVID-19 pandemic had alarming implications for individuals' and communities' mental and emotional health. This study examined the associations between mental health status, oral health status, and oral healthcare utilization and highlighted the impact of COVID-19 on mental health. Additionally, this study examines specific sociodemographic factors that may amplify oral health disparities. A nationally representative survey was conducted to capture attitudes, experiences, and behaviors related to oral health, mental health, and unmet oral health needs. Eighteen percent of respondents were categorized as having poor mental health. Visiting the dentist in the last year was more common amongst individuals with good mental health. From the logistic regression model, mental health status, age group, race/ethnicity, education, and last dental visit were all significantly associated with of oral health status. Mental health status, age group, and income groups were all significantly associated with unmet oral health need. Future work should focus on the mental-oral health association, including determining ways to improve oral healthcare utilization and oral health status among people with poorer mental health.

Oral Fungal Infections: Past, Present, and Future

Abstract: Oral fungal infections have afflicted humans for millennia. Hippocrates (ca. 460-370 BCE) described two cases of oral aphthae associated with severe underlying diseases that could well have been oral candidiasis. While oral infections caused by other fungi such as cryptococcosis, aspergillosis, mucormycosis, histoplasmosis, blastomycosis, and coccidioidomycosis occur infrequently, oral candidiasis came to the fore during the AIDS epidemic as a sentinel opportunistic infection signaling the transition from HIV infection to AIDS. The incidence of candidiasis in immunocompromised AIDS patients highlighted the importance of host defenses in preventing oral fungal infections. A greater understanding of the nuances of human immune systems has revealed that mucosal immunity in the mouth delivers a unique response to fungal pathogens. Oral fungal infection does not depend solely on the fungus and the host, however, and attention has now focussed on interactions with other members of the oral microbiome. It is evident that there is inter-kingdom signaling that affects microbial pathogenicity. The last decade has seen significant advances in the rapid qualitative and quantitative analysis of oral microbiomes and in the simultaneous quantification of immune cells and cytokines. The time is ripe for the application of machine learning and artificial intelligence to integrate more refined analyses of oral microbiome composition (including fungi, bacteria, archaea, protozoa and viruses—including SARS-CoV-2 that causes COVID-19). This analysis should incorporate the quantification of immune cells, cytokines, and microbial cell signaling molecules with signs of oral fungal infections in order to better diagnose and predict susceptibility to oral fungal disease.

Understanding dental caries as a non-communicable and behavioral disease: Management implications

Abstract: New paradigms in caries conceptualization have emerged during the last decades, leading to intense debate and discussion on how to approach the disease, both from a preventive and a therapeutic perspective. Among many new ideas, research discoveries and technologies, one major concept can be highlighted that created a deep frontier between the old and the new paradigm in caries conceptualization; the non-communicable nature of the disease, firmly associated with behaviors and lifestyles. This article synthetizes the conceptual construction of dental caries as a non-communicable disease (NCD) based on the current evidence and discusses the appropriate management of the disease in this context. Dental caries has shifted from being considered transmissible and infectious to an ecological and non-communicable disease. Environmental factors such as frequent sugars intake, disrupt the symbiosis of the dental biofilm leading to a dysbiosis, which favors caries lesion initiation and progression. As an NCD, dental caries shares characteristics with other NCDs such as cardiovascular and chronic respiratory diseases, cancer and diabetes, including long duration and slow progression, not being transmissible from person-to-person, being strongly related to modifiable behavioral risk factors, and affecting preferentially disadvantaged populations with a strong inequality gradient. Given the high prevalence of dental caries, and its consequences on people's health and quality of life, a recognizable conceptual view of caries as a NCD is required to target an effective management. Current understanding of dental caries supports prevention through acting on the modifiable risk factors (behaviors) and involves management based on an interdisciplinary approach. Communicating these modern concepts among researchers, clinicians and policymakers is needed to decrease the global high burden of the disease.

Salvage Surgery in Recurrent Oral Squamous Cell Carcinoma

Abstract: More than half of patients with oral cancer recur even after multimodality treatment and recurrent oral cancers carry a poorer prognosis when compared to other sites of head and neck. The best survival outcome in a recurrent setting is achieved by salvage surgery; however, objective criteria to select an ideal candidate for salvage surgery is difficult to frame, as the outcome depends on various treatment-, tumor-, and patient-related factors. The following is summarizes various tumor- and treatment-related factors that guide our decision-making to optimize oncologic and functional outcomes in surgical salvage for recurrent oral cancers. Short disease-free interval, advanced tumor stage (recurrent and primary), extracapsular spread and positive tumor margins in a recurrent tumor, regional recurrence, and multimodality treatment of primary tumor all portend worse outcomes after surgical salvage. Quality of life after surgical intervention has shown improvement over 1 year with a drastic drop in pain scores. Various trials are underway evaluating the combination of immunotherapy and surgical salvage in recurrent head and neck tumors, including oral cavity, which may widen our indications for salvage surgery with improved survival and preserved organ function.

aMMP-8 Oral Fluid PoC Test in Relation to Oral and Systemic Diseases

Abstract: The manuscript uses the previously published literature and highlights the benefits of active-matrix metalloproteinase (aMMP)-8 chairside/point-of-care (PoC) diagnostic tools as adjunctive measures in oral and systemic diseases. Previous studies suggest that as a biomarker, aMMP-8 is more precise than total MMP-8, MMP-9, MMP-2, MMP-3, MMP-13, MMP-7, MMP-1, calprotectin, myeloperoxidase (MPO), human neutrophil elastase (HNE), tissue inhibitor of matrix metalloproteinase (TIMP)-1, and bleeding of probing (BOP). Therefore, aMMP-8 could be implemented as the needed key biomarker for the new disease classification for both periodontitis and peri-implantitis. With a sensitivity to the tune of 75–85% and specificity in the range of 80–90%, lateral flow aMMP-8 PoC testing is comparable to catalytic protease activity assays for aMMP-8. The test can be further applied to estimate the glycemic status of an individual, to ascertain whether a person is at risk for COVID-19, in managing the oral side effects of radiotherapy carried in head and neck cancers, and in selected cases pertaining to reproductive health. In the future, aMMP-8 could find application as a potential systemic biomarker in diseases affecting the cardiovascular system, cancers, bacteremia, sepsis, diabetes, obesity, meningitis, as well as pancreatitis. The aMMP-8 PoCT is the first practical test in the emerging new dental clinical field, that is, oral clinical chemistry representing oral medicine, clinical chemistry, peri-implantology, and periodontology.

The Microbiome in Periodontitis and Diabetes

Abstract: Objectives To perform a comprehensive and integrative review of the available literature on the potential changes in the microbiome of healthy and individuals with diabetes under periodontal health and disease. Materials and Methods The review was conducted by two independent reviewers. Indexed electronic databases (PubMed/Medline, Cochrane Library, Web of Science and Scopus) were searched, including articles published in English and dated from 5 years ago until December 2021. A manual search also was performed to identify co-related articles. Following the removal of duplicates and eligibility criteria, the articles were included in tables for analysis and described in the manuscript. Results According to this review, diabetes mellitus was associated with significant changes in the subgingival and salivary microbiome, either in its association with periodontitis or in cases of periodontal health. In addition to affecting microbial diversity in terms of taxonomy, metagenomic studies have shown that this endocrine disorder may also be directly related to increased pathogenicity in the oral microbiome. Conclusion Although the reviewed studies demonstrate important differences in the subgingival and salivary microbiome composition because of diabetes mellitus, further studies are needed to clarify the real effects of hyperglycemia on oral microbial profiles and support new diagnostic approaches and innovative treatments.

Fusobacterium nucleatum Subspecies Differ in Biofilm Forming Ability in vitro

Abstract: Development of dysbiosis in complex multispecies bacterial biofilms forming on teeth, known as dental plaque, is one of the factors causing periodontitis. Fusobacterium nucleatum (F. nucleatum) is recognised as a key microorganism in subgingival dental plaque, and is linked to periodontitis as well as colorectal cancer and systemic diseases. Five subspecies of F. nucleatum have been identified: animalis, fusiforme, nucleatum, polymorphum, and vincentii. Differential integration of subspecies into multispecies biofilm models has been reported, however, biofilm forming ability of individual F. nucleatum subspecies is largely unknown. The aim of this study was to determine the single-subspecies biofilm forming abilities of F. nucleatum ATCC type strains. Static single subspecies F. nucleatum biofilms were grown anaerobically for 3 days on untreated or surface-modified (sandblasting, artificial saliva, fibronectin, gelatin, or poly-L-lysine coating) plastic and glass coverslips. Biofilm mass was quantified using crystal violet (CV) staining. Biofilm architecture and thickness were analysed by scanning electron microscopy and confocal laser scanning microscopy. Bioinformatic analysis was performed to identify orthologues of known adhesion proteins in F. nucleatum subspecies. Surface type and treatment significantly influenced single-subspecies biofilm formation. Biofilm formation was overall highest on poly-L-lysine coated surfaces and sandblasted glass surfaces. Biofilm thickness and stability, as well as architecture, varied amongst the subspecies. Interestingly, F. nucleatum ssp. polymorphum did not form a detectable, continuous layer of biofilm on any of the tested substrates. Consistent with limited biofilm forming ability in vitro, F. nucleatum ssp. polymorphum showed the least conservation of the adhesion proteins CmpA and Fap2 in silico. Here, we show that biofilm formation by F. nucleatum in vitro is subspecies- and substrate-specific. Additionally, F. nucleatum ssp. polymorphum does not appear to form stable single-subspecies continuous layers of biofilm in vitro. Understanding the differences in F. nucleatum single-subspecies biofilm formation may shed light on multi-species biofilm formation mechanisms and may reveal new virulence factors as novel therapeutic targets for prevention and treatment of F. nucleatum-mediated infections and diseases.

The Potential Contribution of Dental Foci and Oral Mucositis to Febrile Neutropenia in Patients Treated With Myelosuppressive Chemotherapy for Solid Tumors and Lymphoma

Abstract: Introduction Febrile neutropenia (FN) is a potential life-threatening complication of myelosuppressive chemotherapy, particularly when induced by infection. There is evidence that FN can originate from the oral cavity, but its contribution to FN is largely understudied in patients treated for solid tumors. The aim of this study was to assess the prevalence of FN in these patients and to evaluate its relation with dental foci and oral mucositis. Material and Methods A prospective longitudinal observational study was conducted. Patients diagnosed with solid tumors and lymphoma scheduled to be treated with myelosuppressive chemotherapy with an intermediate risk of developing FN were included. A pre-chemotherapy dental examination was performed and patients were followed during and after chemotherapy regimen. During subsequent hospital visits for chemotherapy administration, the oral cavity was inspected and oral mucositis (OM) was scored using the CTC-AE version 3.0. When patients presented with fever, a comprehensive full body examination including laboratory/microbiological/imaging investigation was performed. Results Eighty-eight patients were included. Pre-chemotherapy, 39 patients (44.3%) were diagnosed with a dental focus. During chemotherapy, 46 patients developed OM (53.4%), of which 15 patients had a maximum score of grade II (ulcerative mucositis). Ten patients developed FN during the follow-up period. Patients with FN more often suffered from ulcerative OM compared to patients without FN; both FN and mucositis risk was associated with the myelotoxicity of chemotherapy. However, no relation could be established between the presence of dental foci prior to chemotherapy and the development of FN (p > 0.05). Conclusion A significant relation was identified between ulcerative OM and FN, but no robust conclusions could be drawn with respect to a relationship between the presence of dental foci and FN.

Oral Complications in Cancer Patients–Medication-Related Osteonecrosis of the Jaw (MRONJ)

Abstract: Medication-Related Osteonecrosis of the Jaw (MRONJ) was first reported in 2003. Despite the progress in the understanding of this oral complication in cancer patients for the past 18 years, there is still discussion about the best way to define MRONJ, prevent the complication, how to diagnose, and the options of treatment available. The initial reports associated MRONJ to bisphosphonates and denosumab, medications that work as bone-modifying agents. Later, other agents such as the antiangiogenics, have also been reported to cause the oral complication, either alone or in combination with antiresorptives. Initially, these medications were prescribed to patients with osteoporosis and cancers patients with bone metastasis. Today, because of the effect of the medications in the bone remodeling system, patients with several other diseases such as giant cell tumors, rheumatoid arthritis, Paget's disease of bone, fibrous dysplasia, osteogenesis imperfecta, are managed with these medications, significantly increasing the population of individuals at risk for developing MRONJ. This mini review focused on the cancer patient. It updates the dental clinician on the recent scientific literature about MRONJ and provides information on how to diagnose and manage patients being treated with these medications, suggests protocols to prevent the development of MRONJ, and present ways to manage those patients who develop the oral complication.

Top 100 Cited Publications in the Field of Temporomandibular Disorders: A Bibliometric Analysis

Abstract: Background The aim of this bibliometric research was to identify and analyze the top 100 cited publications in the field of temporomandibular disorders (TMD) in order to guide any professional level with interest in this topic by mapping the current trends in the field of TMD. Materials and Methods The Clarivate Analytics' Web of Science database was used to find the top 100 most cited papers in the field of TMD, published from the year 2000 to November 18, 2021, with MeSH terms in the search strategy. Data extracted were ranking, title, main author, institution, publication year, a total of citations, citation average per year, the journal the study was published, journal impact factor, and the number of studies that each journal published. Further, also the percentage of the different study designs, the number of studies regarding a specific area within the field of TMD, and the number of studies per country were also calculated. A ranking of authors was also performed. Results The top cited paper was a study on diagnostic criteria for TMD, with 1,287 citations published in 2014 in the Journal of Oral and Facial Pain and Headache which also had most of the top 100 cited publications. Eighty-one percent of the most cited studies were from the USA and Europe and 33% of the included studies were review articles. Conclusion Taken together, since all papers were considered classic, one can draw the conclusion that researchers in 2000 onward in the field of TMD are interested in (a) diagnostic criteria, (b) TMD symptoms and mainly pain-related symptoms, (c) etiology and risk factors of TMD and mainly bruxism, and (d) treatment of TMD. However, topics such as imaging, occlusion, tissue engineering, and disk displacements are presently not as popular.

A Review Into the Effects of Pamidronic Acid and Zoledronic Acid on the Oral Mucosa in Medication-Related Osteonecrosis of the Jaw

Abstract: Medication-related osteonecrosis of the jaw (MRONJ) is a growing problem without an effective treatment, presenting as necrotic bone sections exposed via lesions in the overlying soft tissue. There is currently a lack of clarity on how the factors involved in MRONJ development and progression contribute to disease prognosis and outcomes. Bisphosphonates (BPs), the most common cause of MRONJ, affect bone remodeling, angiogenesis, infection, inflammation and soft tissue toxicity, all of which contribute to MRONJ development. This article reviews the cellular mechanisms through which BPs contribute to MRONJ pathology, with a focus on the effects on cells of the oral mucosa. BPs have been shown to reduce cell viability, reduce proliferation, and increase apoptosis in oral keratinocytes and fibroblasts. BPs have also been demonstrated to reduce epithelial thickness and prevent epithelial formation in three-dimensional tissue engineered models of the oral mucosa. This combination of factors demonstrates how BPs lead to the reduced wound healing seen in MRONJ and begins to uncover the mechanisms through which these effects occur. The evidence presented here supports identification of targets which can be used to develop novel treatment strategies to promote soft tissue wound healing and restore mucosal coverage of exposed bone in MRONJ.

Probiotics for Oral Candidiasis: Critical Appraisal of the Evidence and a Path Forward

Abstract: Oropharyngeal Candidiasis (OPC) is a mucosal fungal infection that is prevalent among patients with compromised immunity. The success of probiotics in treating chronic diseases with a microbial etiology component at other mucosal sites (i.e., gastro-intestinal, genitourinary and alveolar mucosae) has inspired research into the use of probiotics in the treatment of OPC. A growing body of research in vitro and in animal models indicates that some probiotic species and strains have inhibitory activities against Candida albicans growth, morphological switching, and biofilm formation. However, recent review and meta-analysis studies reveal a dearth of human randomized, controlled clinical trials on the efficacy of probiotics to treat or prevent OPC, while the majority of these have not based their selection of probiotic strains or the type of administration on sound pre-clinical evidence. In this mini-review, we assess the state of the field, outline some of the difficulties in translating lab results to clinical efficacy, and make recommendations for future research needed in order to move the field forward.

Oral health associated with incident diabetes but not other chronic diseases: A register-based cohort study

Abstract: Introduction Oral infectious diseases are common chronic oral diseases characterized by a chronic inflammatory condition. We investigated chronic oral diseases as potential risk factors for systemic chronic diseases, diabetes mellitus, connective tissue diseases, seropositive rheumatoid arthritis, ulcerative colitis, and Crohn's disease, as well as severe psychotic and other severe mental disorders. Methods The cohort comprised 68,273 patients aged ≥ 29 years with at least one dental visit to the Helsinki City Health Services between 2001 and 2002. The cohort was linked to the data on death (Statistics Finland), cancer (Finnish Cancer Registry), and drug reimbursement (Finnish Social Insurance Institution) and followed until death or the end of 2013. The outcomes of interest were the incidences of chronic diseases measured starting with special refund medication, which means Social Insurance Institution partly or fully reimburses medication costs. Outcomes of interest were diabetes mellitus, connective tissue diseases, seropositive rheumatoid arthritis, ulcerative colitis and Crohn's disease, and severe mental disorders. Results The mean follow-up time was 9.8 years. About 25% of the study population had periodontitis, 17% caries, over 70% apical periodontitis, and 9% <24 teeth at the start of follow-up. Diabetes was the only chronic systemic condition associated with oral health variables. Having 24 to 27 teeth was associated with a higher incidence rate ratio (IRR) (1.21, 95% confidence interval 1.09–1.33) compared to having 28 or more teeth; the IRR for having 23 or less was 1.40 (1.22–1.60). Having periodontitis (1.10, 1.01–1.20), caries (1.12, 1.01–1.23), or apical periodontitis (1.16, 1.04–1.30) is also associated with a higher risk of diabetes. Conclusion Our epidemiological 10 years follow-up study suggests that the association exists between chronic oral diseases and diabetes, warranting close collaboration among patient's healthcare professionals.

Impact of COVID-19 on Periodontitis and Peri-Implantitis: A Narrative Review

Abstract: COVID-19 is reported as one of the most widespread diseases in the world. An extraordinary number of articles and manuscripts have focused on the inflammatory cascade and sequelae, showing the important roles of cytokines and renin-angiotensin levels and possible links to other pathologies. Nowadays, interest regarding the possible correlation between COVID-19 and periodontal and Peri-implant diseases is increasing. This mini-review aims to collect data regarding the possible correlation between COVID-19 and periodontitis or Peri-implantitis through the analysis of articles published in the last 3 years. The following keywords were used: ([periodontitis OR periodontal disease] AND [COVID-19]); ([Peri-implantitis OR mucositis] AND [COVID-19 OR Sars-CoV-2]). The inclusion criteria were studies on COVID-19 or SARS-CoV-2 and periodontitis or Peri-implantitis, and studies on the molecular and cellular aspect of COVID-19 in periodontal or Peri-implant tissues. The search revealed 484 articles in total (PubMed 208 and Scopus 276). After a screening of titles and abstracts, 47 articles were included in the full-text analysis. Two articles comprised the Peri-implant group: a short communication and a review. Regarding the periodontal group, 45 articles were selected and analyzed according to the type of study, population, and aim. Of these, 10 articles were clinical studies, and the other 35 were hypotheses, reviews, letters to the editor, or commentaries. In conclusion, according to the data extracted, a mutual correlation between COVID-19 and periodontitis can be stated; however, data linked to Peri-implantitis are still missing, and future clinical studies are still needed.

Mechanisms of immune evasion by head and neck cancer stem cells

Abstract: Different mechanisms are involved in immune escape surveillance driven by Oral and Head and Neck Cancer Stem Cells (HNCSCs). The purpose of this review is to show the most current knowledge regarding the main impact of HNCSCs on tumor evasion through immunosuppression, CSCs phenotypes and environmental signals, highlighting strategies to overcome immune evasion. The main results drive the participation of cell surface receptors and secreted products and ligands, the crosstalk between cells, and genetic regulation. The reduction in CD8+ T cell recruitment and decreased effector of anti-PD-1 therapy by cells expressing BMI1 is a key event; Natural Killer cell ligands and cytokines needed for its activation and expansion are crucial to control tumor growth and to target CSCs by immunotherapy; CSCs expressing ALDH1 are related to increased expression of PD-L1, with a positive link between DNMT3b expression; CD276 expression in CSCs can act as a checkpoint inhibitor and together with Activator Protein 1 (AP-1) activation, they create continuous positive feedback that enables immune evasion by suppressing CD8+ T cells and prevent immune cell infiltration in head and neck cancer. These data demonstrate the relevance of the better understanding of the interaction between HNCSCs and immune cells in the tumor microenvironment. The ultimate clinical implication is to ground the choice of optimized targets and improve immune recognition for ongoing treatments as well as the response to approved immunotherapies.

Fluoride Intake Through Dental Care Products: A Systematic Review

Abstract: Fluoride (F) is added to many dental care products as well as in drinking water to prevent dental decay. However, recent data associating exposure to F with some developmental defects with consequences in many organs raise concerns about its daily use for dental care. This systematic review aimed to evaluate the contribution of dental care products with regard to overall F intake through drinking water and diet with measurements of F excretion in urine used as a suitable biomarker. According to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using keywords related to chronic exposure to F in the human population with measurements of F levels in body fluids, 1,273 papers published between 1995 and 2021 were screened, and 28 papers were finally included for data extraction concerning daily F intake. The contribution of dental care products, essentially by toothbrushing with kinds of toothpaste containing F, was 38% in the mean regardless of the F concentrations in drinking water. There was no correlation between F intake through toothpaste and age, nor with F levels in water ranging from 0.3 to 1.5 mg/L. There was no correlation between F intake and urinary F excretion levels despite an increase in its content in urine within hours following exposure to dental care products (toothpastes, varnishes, or other dental care products). The consequences of exposure to F on health are discussed in the recent context of its suspected toxicity reported in the literature. The conclusions of the review aim to provide objective messages to patients and dental professionals worried about the use of F-containing materials or products to prevent initial caries or hypomineralized enamel lesions, especially for young children.

Quality Assessment of PBM Protocols for Oral Complications in Head and Neck Cancer Patients: Part 1

Abstract: Radiotherapy and chemotherapy are frequently employed in head and neck cancer (HNC) patients causing significant side effects that impair life quality and prognosis. Photobiomodulation (PBM) has become a growing approach to managing such oral complications. Despite its proven efficacy and absence of contraindications, there is still a lack of universally accepted disease-specific PBM protocols.A narrative review was conducted to identify the current proposals relating to the use of PBM to treat complications of oncological treatments in HNC patients.An electronic search in PubMed and Scopus databases was performed with the following keywords: ("photobiomodulation" OR "PBM" OR "laser therapy" OR "LLLT" OR "laser") AND ("head and neck cancer" OR "oral cancer") AND ("mucositis" OR "oral mucositis" OR "dysgeusia" OR "oedema" OR "xerostomia" OR "dermatitis" OR "trismus") until October 2021.A total of 35 papers were included in the narrative review. Oral mucositis was the most studied complication, and advisable protocols are conceivable. Although there is a growing interest in PBM to manage of xerostomia, radiodermatitis, pain, and trismus, literature is still scarce to propose a universally feasible protocol.PBM therapy could significantly prevent or reduce the severity of many side effects related to cancer therapies. More research is needed to obtain recommendations over the preferable parameters.

Particle Size Analysis in Aerosol-Generating Dental Procedures Using Laser Diffraction Technique

Abstract: The global outbreak of coronavirus disease 2019 (COVID-19) has raised concerns about the risk of airborne infection during dental treatment. Aerosol-generating dental procedures (AGDP) produce droplets and aerosols, but the details of the risks of COVID-19 transmission in AGDP are not well-understood. By discriminating between droplets and aerosols, we devised a method to measure particle size using laser diffraction analysis and evaluated aerosols generated from dental devices for providing a basis for proper infection control procedures. The droplets and aerosols generated from dental devices were characterized by multimodal properties and a wide range of droplet sizes, with the majority of droplets larger than 50 μm. AGDP emitted few aerosols smaller than 5 μm, which are of concern for pulmonary infections due to airborne transmission. In addition, the use of extraoral suction was found to prevent the spread of aerosols from high-speed dental engines. This study suggests that the risk of aerosol infections is considerably limited in regular dental practice and that current standard precautions, such as mainly focusing on protection against droplet and contact infections, are sufficient. While several cases of airborne transmission of COVID-19 in general clinics and emergency hospitals have been reported, cluster outbreaks in dental clinics have not yet been reported, which may indicate that AGDP does not pose a significant threat in contributing to the spread of SARS-CoV-2.

Editorial: The Use of Bioactive Materials in Caries Management

Abstract: Looking to discuss the global policies, guidelines, and relevant information on utilizing SDF for caries management, Gao et al . provide an overview of SDF use in different countries and allow dental professionals to obtain a general idea about SDF use worldwide. The authors concluded that at least two ongoing regional-wide large-scale oral health programs using SDF as one of the components to manage dental caries in young children (one in Hong Kong and one in Mongolia). Because SDF treatment does not require caries removal, it is simple, non-invasive, and inexpensive. Thus, SDF is a valuable strategy for caries management in young children, older adults, and patients with special needs. In addition, to reduce the risk of bacteria or virus transmission in dental settings, using SDF as a non-aerosol-producing procedure should be emphasized under the COVID-19 outbreak.We hope that this work set will stimulate further research on the development of bioactive materials for dental applications by providing an overview of the latest and most exciting advances in emerging approaches for bioactivity. In addition, this topic may help readers to understand the basics and latest developments in this field.The authors declare no conflict of interest.

Transparency of COVID-19-Related Research in Dental Journals

Abstract: Objective We aimed to assess the adherence to transparency practices (data availability, code availability, statements of protocol registration and conflicts of interest and funding disclosures) and FAIRness (Findable, Accessible, Interoperable, and Reusable) of shared data from open access COVID-19-related articles published in dental journals available from the Europe PubMed Central (PMC) database. Methods We searched and exported all COVID-19-related open-access articles from PubMed-indexed dental journals available in the Europe PMC database in 2020 and 2021. We detected transparency indicators with a validated and automated tool developed to extract the indicators from the downloaded articles. Basic journal- and article-related information was retrieved from the PMC database. Then, from those which had shared data, we assessed their accordance with FAIR data principles using the F-UJI online tool (f-uji.net). Results Of 650 available articles published in 59 dental journals, 74% provided conflicts of interest disclosure and 40% funding disclosure and 4% were preregistered. One study shared raw data (0.15%) and no study shared code. Transparent practices were more common in articles published in journals with higher impact factors, and in 2020 than in 2021. Adherence to the FAIR principles in the only paper that shared data was moderate. Conclusion While the majority of the papers had a COI disclosure, the prevalence of the other transparency practices was far from the acceptable level. A much stronger commitment to open science practices, particularly to preregistration, data and code sharing, is needed from all stakeholders.

Porphyromonas gingivalis Infection Induces Lipopolysaccharide and Peptidoglycan Penetration Through Gingival Epithelium

Abstract: Periodontal diseases initiate on epithelial surfaces of the subgingival compartment, while the gingival epithelium functions as an epithelial barrier against microbial infection and orchestrates immune responses. Porphyromonas gingivalis is a major pathogen of periodontal diseases and has an ability to penetrate the epithelial barrier. To assess the molecular basis of gingival epithelial barrier dysfunction associated with P. gingivalis, we newly developed a three-dimensional multilayered tissue model of gingival epithelium with gene manipulation. Using this novel approach, P. gingivalis gingipains including Arg- or Lys-specific cysteine proteases were found to specifically degrade junctional adhesion molecule 1 and coxsackievirus and adenovirus receptor in the tissue model, leading to increased permeability for lipopolysaccharide, peptidoglycan, and gingipains. This review summarizes the strategy used by P. gingivalis to disable the epithelial barrier by disrupting specific junctional adhesion molecules.

Clinical laboratory diagnostics in dentistry: Application of microbiological methods

Abstract: Diagnosis and treatment in dentistry are based on clinical examination of the patients. Given that the major oral diseases are of microbial biofilm etiology, it can be expected that performing microbiological analysis on samples collected from the patient could deliver supportive evidence to facilitate the decision-making process by the clinician. Applicable microbiological methods range from microscopy, to culture, to molecular techniques, which can be performed easily within dedicated laboratories proximal to the clinics, such as ones in academic dental institutions. Periodontal and endodontic infections, along with odontogenic abscesses, have been identified as conditions in which applied clinical microbiology may be beneficial for the patient. Administration of antimicrobial agents, backed by microbiological analysis, can yield more predictable treatment outcomes in refractory or early-occurring forms of periodontitis. Confirming a sterile root canal using a culture-negative sample during endodontic treatment may ensure the longevity of its outcome and prevent secondary infections. Susceptibility testing of samples obtained from odontogenic abscesses may facilitate the selection of the appropriate antimicrobial treatment to prevent further spread of the infection.

Revisiting Fluoride in the Twenty-First Century: Safety and Efficacy Considerations

Abstract: Over 100 years of scientific literature is available which describes the long relationship between dentistry and the many possible applications of fluoride anion (F−) as successful therapeutic strategies. To date, systemic introduction of fluoride via water, milk and salt fluoridation, and fluoride-containing tablets, has been employed. Post-eruption topical fluoride products have also been introduced, such as fluoridated toothpaste, along with fluoride-containing rinses and varnishes. Importantly, a recent addition to the available armamentarium of fluoride therapeutics now exists in the form of metal ion-fluorido adducts, most especially silver(I)-diammine fluoride (SDF). In view of its high level of therapeutic success, very recently this agent was added to the World Health Authority's (WHO's) list of essential medicines available for the treatment and prevention of tooth decay. Overall, this current state of affairs merits a major review of all these fluoride-containing therapeutic compounds, together with their risks and benefits, both individually and collectively. In this study, a simple graphical tool has been developed for the rapid “on-site” evaluation of fluoride intake with respect to a range of oral healthcare products and body mass index is presented as a gauge of safety for the risk of fluoride toxicity in individual patients. This exposition commences with (a) an account of the history and value of fluoride therapeutics in clinical dentistry, including applications of monofluorophosphate and stannous fluoride; (b) an evaluation of the toxicological activities of fluoride, together with a summary of any reports, albeit very rare ones, arising from its clinically-driven overuse; (c) a history of the development, molecular structure, mechanisms of action, and therapeutic applications of SDF, including a summary of any possible toxic activities and effects arising from silver(I) ion rather than fluoride itself; and (d) the establishment of a working relationship between fluoride exposure and toxicity, with special reference to the instigation of newly-developed tabular/graphical reference guidelines for use by dental clinicians who employ fluoride-rich products in their practices. Particular attention is given to the oral care and treatment options of pediatric patients. In conclusion, applications of this unique monitoring tool may serve as a valuable toxicity guide for dental practitioners.

Site- and Time-Dependent Compositional Shifts in Oral Microbiota Communities

Abstract: Objectives The oral microbiota plays a significant role in oral health. The present study aims to characterize variations in the oral microbiota relative to the collection site, the dynamics of biofilm accumulation, and inherent inter-individual differences. Methods Whole stimulated saliva and tooth biofilm samples from the 16 defined tooth regions were collected after 1, 2, or 3 days without oral hygiene (accumulation time) in six healthy adults with no signs of active caries or periodontal disease. The routines and conditions before and between sample collections were carefully standardized. Genomic DNA was extracted, and the V3-V4 regions of the 16S rRNA gene were amplified by PCR and sequenced on an Illumina MiSeq platform. Sequences were quality controlled, amplicon sequence variants (ASVs) were clustered, and taxonomic allocation was performed against the expanded Human Oral Microbiome Database (eHOMD). Microbial community profiles were analyzed by multivariate modeling and a linear discriminant analysis (LDA) effect size (LEfSe) method. Results The overall species profile in saliva and tooth biofilm differed between participants, as well as sample type, with a significantly higher diversity in tooth biofilm samples than saliva. On average, 45% of the detected species were shared between the two sample types. The microbiota profile changed from the most anterior to the most posterior tooth regions regardless of whether sampling was done after 1, 2, or 3 days without oral hygiene. Increasing accumulation time led to higher numbers of detected species in both the saliva and region-specific tooth biofilm niches. Conclusion The present study confirms that the differences between individuals dominate over sample type and the time abstaining from oral hygiene for oral microbiota shaping. Therefore, a standardized accumulation time may be less important for some research questions aiming at separating individuals. Furthermore, the amount of DNA is sufficient if at least two teeth are sampled for microbiota characterization, which allows a site-specific characterization of, for example, caries or periodontitis.

Antimicrobial peptides: Defending the mucosal epithelial barrier

Abstract: The recent epidemic caused by aerosolized SARS-CoV-2 virus illustrates the importance and vulnerability of the mucosal epithelial barrier against infection. Antimicrobial proteins and peptides (AMPs) are key to the epithelial barrier, providing immunity against microbes. In primitive life forms, AMPs protect the integument and the gut against pathogenic microbes. AMPs have also evolved in humans and other mammals to enhance newer, complex innate and adaptive immunity to favor the persistence of commensals over pathogenic microbes. The canonical AMPs are helictical peptides that form lethal pores in microbial membranes. In higher life forms, this type of AMP is exemplified by the defensin family of AMPs. In epithelial tissues, defensins, and calprotectin (complex of S100A8 and S100A9) have evolved to work cooperatively. The mechanisms of action differ. Unlike defensins, calprotectin sequesters essential trace metals from microbes, which inhibits growth. This review focuses on defensins and calprotectin as AMPs that appear to work cooperatively to fortify the epithelial barrier against infection. The antimicrobial spectrum is broad with overlap between the two AMPs. In mice, experimental models highlight the contribution of both AMPs to candidiasis as a fungal infection and periodontitis resulting from bacterial dysbiosis. These AMPs appear to contribute to innate immunity in humans, protecting the commensal microflora and restricting the emergence of pathobionts and pathogens. A striking example in human innate immunity is that elevated serum calprotectin protects against neonatal sepsis. Calprotectin is also remarkable because of functional differences when localized in epithelial and neutrophil cytoplasm or released into the extracellular environment. In the cytoplasm, calprotectin appears to protect against invasive pathogens. Extracellularly, calprotectin can engage pathogen-recognition receptors to activate innate immune and proinflammatory mechanisms. In inflamed epithelial and other tissue spaces, calprotectin, DNA, and histones are released from degranulated neutrophils to form insoluble antimicrobial barriers termed neutrophil extracellular traps. Hence, calprotectin and other AMPs use several strategies to provide microbial control and stimulate innate immunity.