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Oral potentially malignant disorders (OPMDs) are a heterogeneous group of oral lesions with a variable risk of malignant transformation to oral squamous cell carcinoma. The current OPMDs malignant transformation screening depends on conventional oral examination (COE) and is confirmed by biopsy and histologic examination. However, early malignant lesions with subtle mucosal changes are easily unnoticed by COE based on visual inspection and palpation. Optical techniques have been used to determine the biological structure, composition, and function of cells and tissues noninvasively by analyzing the changes in their optical properties. The oral epithelium and stroma undergo persistent structural, functional, and biochemical alterations during malignant transformation, leading to variations in optical tissue properties; optical techniques are thus powerful tools for detecting OPMDs malignant transformation. The optical imaging methods already used to detect OPMDs malignant transformation in vivo include autofluorescence imaging, narrowband imaging, confocal reflectance microscopy, and optical coherence tomography. They exhibit advantages over COE in detecting biochemical or morphologic changes at the molecular or cellular level in vivo; however, limitations also exist. This article comprehensively reviews the various real-time in vivo optical imaging methods used in the adjunctive diagnosis of OPMDs malignant transformation. We focus on the principles of these techniques, review their clinical application, and compare and summarize their advantages and disadvantages. Finally, we conclude with a discussion of current challenges and future directions of this field.

This living systematic review aims to summarize evidence on the prevalence of oral signs and symptoms in patients with COVID-19. The review was reported per the PRISMA checklist, and the literature search was conducted in 6 databases and in gray literature. Studies published in any language mentioning oral symptoms and signs in patients with COVID-19 were included. The risk of bias was assessed by the Joanna Briggs Institute appraisal tools. The certainty of evidence was evaluated through GRADE assessment. After a 2-step selection, 40 studies were included: 33 cross-sectional and 7 case reports. Overall, 10,228 patients (4,288 males, 5,770 females, and 170 unknown) from 19 countries were assessed. Gustatory impairment was the most common oral manifestation, with a prevalence of 45% (95% CI, 34% to 55%; I2 = 99%). The pooled eligible data for different taste disorders were 38% for dysgeusia and 35% for hypogeusia, while ageusia had a prevalence of 24%. Taste disorders were associated with COVID-19 (odds ratio [OR], 12.68; 95% CI, 6.41 to 25.10; I2 = 63%; P < 0.00001), mild/moderate severity (OR, 2.09; 95% CI, 1.25 to 3.49; I2 = 66%; P = 0.005), and female patients (OR, 1.64; 95% CI, 1.23 to 2.17; I2 = 70%; P = 0.0007). Oral mucosal lesions presented multiple clinical aspects, including white and erythematous plaques, irregular ulcers, small blisters, petechiae, and desquamative gingivitis. Tongue, palate, lips, gingiva, and buccal mucosa were affected. In mild cases, oral mucosal lesions developed before or at the same time as the initial respiratory symptoms; however, in those who required medication and hospitalization, the lesions developed approximately 7 to 24 d after onset symptoms. Therefore, taste disorders may be common symptoms in patients with COVID-19 and should be considered in the scope of the disease’s onset and progression. Oral mucosal lesions are more likely to present as coinfections and secondary manifestations with multiple clinical aspects (PROSPERO CRD42020184468).

Chronic oral infection/inflammation is cross-sectionally associated with metabolic syndrome (MetS) in adults, but there are few longitudinal studies and studies on childhood oral infections and adult MetS risk. We investigated whether childhood clinical parameters indicative of oral infection/inflammation were associated with adulthood MetS and its components. A total of 755 children aged 6, 9, and 12 y underwent a clinical oral examination in 1980 as part of the Cardiovascular Risk in Young Finns Study. Oral health measures included bleeding on probing (BOP), periodontal probing pocket depth, caries, fillings, and visible plaque. Metabolic parameters were determined at baseline and during follow-up. MetS was diagnosed ( n = 588, 77.9%) in the adulthood at 21 y (in 2001), 27 y (in 2007), and 31 y (in 2011) after the oral assessment, when the participants were 27 to 43 y old. Regression analyses were adjusted for childhood age, sex, body mass index, and family income, as well as adulthood smoking and education level. In adulthood, MetS was diagnosed in 11.9% (2001), 18.7% (2007), and 20.7% (2011) of participants at the 3 follow-ups. Childhood caries and fillings were associated with increased risk of adult MetS (risk ratio [95% CI], 1.25 [0.90 to 2.45] and 1.27 [1.02 to 1.99]) and with increased systolic blood pressure (1.78 [1.01 to 4.26] and 2.48 [1.11 to 4.12]) and waist circumference (2.25 [1.02 to 4.99] and 1.56 [1.01 to 3.25]), whereas BOP and visible plaque were associated with plasma glucose (1.97 [1.08 to 3.60] and 1.88 [1.00 to 3.53]). Severity of BOP ( P = 0.015) and caries ( P = 0.005) and teeth with plaque ( P = 0.027) were associated with number of MetS components. No such trends were seen with probing pocket depth. Childhood oral infection/inflammation was associated with adverse metabolic parameters and MetS in adulthood.

Chronic oral diseases are rarely studied together, especially with an emphasis on their common risk factors. This study examined the association of added sugar consumption on "chronic oral disease burden" among adolescents, with consideration of obesity and systemic inflammation pathways through structural equation modeling. A cross-sectional study was conducted of a complex random sample of adolescent students enrolled at public schools in Sao Luis, Brazil ( n = 405). The outcome was chronic oral disease burden, a latent variable based on the presence of probing depth ≥4 mm, bleeding on probing, caries, and clinical consequences of untreated caries. The following hypotheses were tested: 1) caries and periodontal diseases among adolescents are correlated with each other; 2) added sugar consumption and obesity are associated with chronic oral disease burden; and 3) chronic oral disease burden is linked to systemic inflammation. Models were adjusted for socioeconomic status, added sugar consumption, oral hygiene behaviors, obesity, and serum levels of interleukin 6 (IL-6). All estimators of the latent variable chronic oral disease burden involved factor loadings ≥0.5 and P values

Dental diseases are now viewed as a consequence of a deleterious shift in the balance of the normally stable resident oral microbiome. It is known that frequent carbohydrate consumption or reduced saliva flow can lead to caries, and excessive plaque accumulation increases the risk of periodontal diseases. However, when these "disease drivers" are present, while some individuals appear to be susceptible, others are more tolerant or resilient to suffering from undesirable changes in their oral microbiome. Health-maintaining mechanisms that limit the effect of disease drivers include the complex set of metabolic and functional interrelationships that develop within dental biofilms and between biofilms and the host. In contrast, "positive feedback loops" can develop within these microbial communities that disrupt resilience and provoke a large and abrupt change in function and structure of the ecosystem (a microbial "regime shift"), which promotes dysbiosis and oral disease. For instance, acidification due to carbohydrate fermentation or inflammation in response to accumulated plaque select for a cariogenic or periopathogenic microbiota, respectively, in a chain of self-reinforcing events. Conversely, in tolerant individuals, health-maintaining mechanisms, including negative feedback to the drivers, can maintain resilience and promote resistance to and recovery from disease drivers. Recently studied health-maintaining mechanisms include ammonia production, limiting a drop in pH that can lead to caries, and denitrification, which could inhibit several stages of disease-associated positive feedback loops. Omics studies comparing the microbiome of, and its interaction with, susceptible and tolerant hosts can detect markers of resilience. The neutralization or inhibition of disease drivers, together with the identification and promotion of health-promoting species and functions, for example, by pre- and probiotics, could enhance microbiome resilience and lead to new strategies to prevent disease.

The Global Burden of Disease 2015 study aims to use all available data of sufficient quality to generate reliable and valid prevalence, incidence, and disability-adjusted life year (DALY) estimates of oral conditions for the period of 1990 to 2015. Since death as a direct result of oral diseases is rare, DALY estimates were based on years lived with disability, which are estimated only on those persons with unmet need for dental care. We used our data to assess progress toward the Federation Dental International, World Health Organization, and International Association for Dental Research's oral health goals of reducing the level of oral diseases and minimizing their impact by 2020. Oral health has not improved in the last 25 y, and oral conditions remained a major public health challenge all over the world in 2015. Due to demographic changes, including population growth and aging, the cumulative burden of oral conditions dramatically increased between 1990 and 2015. The number of people with untreated oral conditions rose from 2.5 billion in 1990 to 3.5 billion in 2015, with a 64% increase in DALYs due to oral conditions throughout the world. Clearly, oral diseases are highly prevalent in the globe, posing a very serious public health challenge to policy makers. Greater efforts and potentially different approaches are needed if the oral health goal of reducing the level of oral diseases and minimizing their impact is to be achieved by 2020. Despite some challenges with current measurement methodologies for oral diseases, measurable specific oral health goals should be developed to advance global public health.

Professor Robert J. Genco made extraordinary research advances in immunology, periodontology, and microbiology research, pioneering major advances in oral science. In addition to his extraordinary research advancements in oral biology, his pioneering advances in oral science leadership at the local/university, national, and international levels are recognized worldwide, as are his educational advancements. In his era, he is truly the “father” of oral science.

Indigenous populations around the world experience a disproportionate burden in terms of oral diseases and conditions. These inequalities are likely due to a complex web of social determinants that includes poverty, historical consequences of colonialism, social exclusion, government policies of assimilation, cultural annihilation, and racism in all its forms (societal, institutional). Despite documented oral health disparities, prevention interventions have been scarce in Indigenous communities. This review describes oral health interventions and their outcomes conducted for Indigenous populations of the United States, Canada, Brazil, Australia, and New Zealand. The review includes research published since 2006 that are available in English in electronic databases, including MEDLINE. A total of 13 studies were included from the United States, Canada, Brazil, and Australia. The studies reviewed provide a wide range of initiatives, including interventions for prevention and treatment of dental disease, as well as interventions that improve oral health knowledge, behaviors, and other psychosocial factors. Overall, 6 studies resulted in improved oral health in the study participants, including improvements in periodontal health, caries reduction, and oral health literacy. Preferred intervention methodologies included community-based research approaches, culturally tailored strategies, and use of community workers to deliver the initiative. Although these studies were conducted with discrete Indigenous populations, investigators reported similar challenges in research implementation. Recommendations for future work in reducing oral health disparities include addressing social determinants of health in various Indigenous populations, training future generations of dental providers in cultural competency, and making Indigenous communities true partners in research.

In recent years, the study of genetic defects arising from inborn errors in immunity has resulted in the discovery of new genes involved in the function of the immune system and in the elucidation of the roles of known genes whose importance was previously unappreciated. With the recent explosion in the field of genomics and the increasing number of genetic defects identified, the study of naturally occurring mutations has become a powerful tool for gaining mechanistic insight into the functions of the human immune system. In this concise perspective, we discuss emerging evidence that inborn errors in immunity constitute real-life models that are indispensable both for the in-depth understanding of human biology and for obtaining critical insights into common diseases, such as those affecting oral health. In the field of oral mucosal immunity, through the study of patients with select gene disruptions, the interleukin-17 (IL-17) pathway has emerged as a critical element in oral immune surveillance and susceptibility to inflammatory disease, with disruptions in the IL-17 axis now strongly linked to mucosal fungal susceptibility, whereas overactivation of the same pathways is linked to inflammatory periodontitis.

Although several epidemiologic studies reported plausible and potentially causal associations between oral infections and cardiometabolic diseases (CMDs), controversy still lingers. This might be due to unrecognized confounding from metabolic inflammation and genetics, both of which alter the immune responses of the host. Low-grade inflammation termed metainflammation is the hallmark of obesity, insulin resistance, type 2 diabetes, and CMDs. According to the common soil theory, the continuum of obesity to CMDs is the same pathology at different time points, and early metainflammations, such as hyperglycemia and obesity, display many adverse cardiometabolic characteristics. Consequently, adipose tissue is now considered a dynamic endocrine organ that expresses many proinflammatory cytokines such as TNF- α, IL-6, plasminogen activator inhibitor 1, and IL-1 β. In metainflammation, IL-1 β and reactive oxygen species are generated, and IL-1 β is a pivotal molecule in the pathogenesis of CMDs. Note that the same cytokines expressed in metainflammation are also reported in oral infections. In metabolic inflammation and oral infections, the innate immune system is activated through pattern recognition receptors—which include transmembrane receptors such as toll-like receptors (TLRs), cytosolic receptors such as nucleotide-binding oligomerization domain–like receptors, and multiprotein complexes called inflammasome. In general, TLR-2s are presumed to recognize lipoteichoic acid of Gram-positive microbes—and TLR-4s, lipopolysaccharide of Gram-negative microbes—while nucleotide-binding oligomerization domain–like receptors detect both Gram-positive and Gram-negative peptidoglycans on the bacterial cell walls. However, a high-fat diet activates TLR-2s, and obesity activates TLR-4s and induces spontaneous increases in serum lipopolysaccharide levels (metabolic endotoxemia). Moreover, genetics controls lipid-related transcriptome and the differentiation of monocyte and macrophages. Additionally, genetics influences CMDs, and this creates a confounding relationship among oral infections, metainflammation, and genetics. Therefore, future studies must elucidate whether oral infections can increase the risk of CMDs independent of the aforementioned confounding factors.

The objective of this study was to verify whether oral conditions (tooth loss, periodontal disease, dental caries) are negatively associated with health-related quality of life (HRQoL) in adults. A search was carried out on PubMed, EMBASE, Web of Science, Scopus, SciELO, and LILACS databases until the end of July 2016 with no date restrictions. Quantitative observational studies written in English were included and data extraction was performed independently by 2 reviewers. HRQoL was investigated as the outcome, and tooth loss, periodontal diseases, and dental caries were exposures. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used and the quality of the selected studies was assessed by using the Joanna Briggs Institute Meta-Analysis of Statistics assessment and review instrument (JBI-MAStARI). Twenty-one studies were included. The sample sizes ranged from 88 to 15,501 subjects; 20 studies were cross-sectional designs, while 1 was a case-control study. Case definitions of the exposures were different across the studies, mainly for tooth loss, which was defined according to 11 different criteria. Fifteen studies were of “high” and 6 of “medium” quality. Eight HRQoL instruments were identified, and the most frequent was the EuroQol ( n = 8). Ten of 16 studies reported a negative impact of tooth loss on HRQoL. Four of 7 studies reported that periodontal disease impairs HRQoL, and 1 study showed that periodontal disease is positively associated with HRQoL. All studies that assessed dental caries reported a negative association between this condition and HRQoL. Despite the different definitions and measures of tooth loss and dental caries, the majority of the available evidence reported a negative impact of these conditions on HRQoL. Mixed and inconclusive findings were observed for the association between periodontal disease and HRQoL. Longitudinal prospective studies are suggested to improve the strength of the findings.

Oral diseases such as dental caries, edentulism (tooth loss), periodontal disease (PD), and oral cancer currently constitute an increased major public health burden across the globe, with significant differences between countries. One of the main drivers of caries, edentulism, and PD is the excessive intake of sugars. Here, we aimed to quantify the global sugar-related dental health and cost burden in the year 2010. This study used a health-econometrical model to calculate the disease burden as well as the direct and indirect costs attributable to the intake of free sugars (mono- and disaccharides [MDS]). To this end, several databases from the Institute for Health Metrics and Evaluation (IHME), Organisation for Economic Co-operation and Development (OECD), Food and Agriculture Organization (FAO), and World Bank were used. In total, the corresponding disease burden in 168 countries and economic burden in 31 OECD countries were quantified. In 2010, the consumption of MDS was associated with a global dental disease burden of 4.1 million disability-adjusted life years (DALYs; 95% uncertainty interval [UI]: 2.1 to 7.4 million DALYs), with 2.7 million DALYs from MDS-related caries and 1.4 million DALYs from PD. In terms of economic costs, MDS-related dental diseases were associated with a global financial burden of 172 billion US dollars (USD; 95% UI: 91 to 295 billion USD), the largest share of which (151 billion USD) was incurred in OECD countries. Overall, 26.3% (95% UI: 13.3% to 47.5%) of the total global oral disease burden was attributed to the consumption of MDS. The present study emphasizes the need to further address the role of free sugars in oral health and nutrition policy. Although the largest share of the economic burden was accounted for by OECD countries, emerging economies should address this challenge early on in national public health policies if they are to avoid disease and the prospect of increased cost burdens.

The progress in phenotype descriptions, measurements, and analyses has been remarkable in the last 50 years. Biomarkers (proteins, carbohydrates, lipids, hormones, various RNAs and cDNAs, microarrays) have been discovered and correlated with diseases and disorders, as well as physiological responses to disease, injury, stress, within blood, urine, and saliva. Three-dimensional digital imaging advanced how we “see” and utilize phenotypes toward diagnosis, treatment, and prognosis. In each example, scientific discovery led to inform clinical health care. In tandem, genetics evolved from Mendelian inheritance (single gene mutations) to include Complex Human Diseases (multiple gene-gene and gene-environment interactions). In addition, epigenetics blossomed with new insights about gene modifiers (e.g., histone and non-histone chromosomal protein methylation, acetylation, sulfation, phosphorylation). We are now at the beginning of a new era using human and microbial whole-genome sequencing to make significant healthcare decisions as to risk, stratification of patients, diagnosis, treatments, and outcomes. Are we as clinicians, scientists, and educators prepared to expand our scope of practice, knowledge base, integration into primary health care (medicine, pharmacy, nursing, and allied health science professions), and clinical approaches to craniofacial-oral-dental health care? The time is now.

Scientific opportunities have never been better than today! The completion of the Human Genome project has sparked hope and optimism that cures for debilitating conditions can be achieved and tailored to individuals and communities. The availability of reference genome sequences and genetic variations as well as more precise correlations between genotype and phenotype have facilitated the progress made in finding solutions to clinical problems. While certain craniofacial and oral diseases previously deemed too difficult to tackle have benefited from basic science and technological advances over the past decade, there remains a critical need to translate the fruits of several decades’ worth of basic and clinical research into tangible therapies that can benefit patients. The fifth Annual Fall Focused Symposium, “Translational Genetics – Advancing Fronts for Craniofacial Health”, was created by the American Association for Dental Research (AADR) to foster its mission to advance interdisciplinary research that is directed toward improving oral health. The symposium showcased progress made in identifying molecular targets that are potential therapeutics for common and rare dental diseases and craniofacial disorders. Speakers focused on translational and clinical applications of their research and, where applicable, on strategies for new technologies and therapeutics. The critical needs to transfer new knowledge to the classroom and for further investment in the field were also emphasized. The symposium underscored the importance of basic research, chairside clinical observations, and population-based studies in driving the new translational connections needed for the development of cures for the most common and devastating diseases involving the craniofacial complex.

Investigators have examined children’s dental utilization in various settings ( e.g., dental offices, emergency departments, operating rooms), but no studies have examined inpatient hospitalizations for non-traumatic dental conditions (NTDCs). The authors examined NTDC-related hospitalization trends in the United States and identified the relationship between complex chronic condition (CCCs) and NTDC-related inpatient hospitalizations. We analyzed data from the U.S. Nationwide Inpatient Sample (2000-2010) for children ages 3 to 17 years (N = 3,030,970). The predictor variable was number of CCCs (0/1/2+). The outcome variable was whether the child had a NTDC-related hospitalization (no/yes). Covariate-adjusted multivariable logistic regression models were used to estimate prevalence odds ratios (PORs). From 2000 to 2010, there were 17,993 NTDC-related hospitalizations (0.59%) and a slight increase in NTDC-related hospitalizations ( p = .049). This increase was not significant in the final regression model. There was no difference in odds of NTDCs for children with 0 or 1 CCCs (POR = 1.08; 95%CI = 0.99, 1.18), but children with 2+ CCCs had significantly greater odds (POR = 1.61; 95%CI = 1.42, 1.83), as did non-White, publicly insured, and lower income children. NTDC-related hospitalizations for children did not increase from 2000 to 2010. Children with 2+ CCCs had the greatest odds of being hospitalized for NTDCs, which highlights the need to develop preventive interventions targeting children with 2+ CCCs.

Signaling by extracellular purines such as ATP and adenosine has implications for dental research on multiple levels, with the association of purinergic signaling with inflammation, mechanical strain, and pain making the system particularly relevant for the specific challenges in the oral cavity. Oral tissues express a variety of G-protein-coupled P2Y receptors for ATP and P1 receptors for adenosine in addition to ionotropic P2X receptors for ATP. When these receptors are combined with the plethora of extracellular enzymes capable of manipulating extracellular agonist levels, a complex system for regulating oral health emerges, and recent findings have begun to identify a key role for purinergic signaling in oral pathophysiology. For example, the manipulation of extracellular ATP levels by P. gingivalis reduces inflammasome activation and apoptosis linked to P2X7 receptor activation. Release of ATP by periodontal ligaments may link mechanical strain to bone remodeling. Activation of P2X receptors is implicated in dental pain, and receptor antagonists represent important targets for new analgesics. Altered levels of adenosine receptors in periodontal disease also suggest a role for nucleosides in dental signaling. The intricacies of the purinergic signaling system make it well-suited for the unique concerns of dental research, and future findings will doubtless confirm this importance.

Human differences in disease phenotype and treatment responses are well documented. Technological advances now allow healthcare providers to improve the prevention and treatment of chronic diseases by stratifying patient populations. Although personalized medicine has great promise, it has, so far, been primarily applied in oncology. Wider adoption requires changes in the healthcare system and in clinical decision-making, and early applications of personalized medicine appear to require strong clinical utility and sufficient value to drive adoption. Personalized medicine is likely to enter dentistry as patients start to demand it and as new drugs are developed for pathways common to oral diseases.

Chronic graft- vs.-host disease (cGVHD) is a complication of allogeneic hematopoietic stem cell transplantation (alloHSCT). Oral cGVHD is manifested by mucosal, salivary, and/or sclerotic changes that have been linked to pain and poor quality of life. Our aim was to describe the demographic, clinical, and laboratory markers of oral cGVHD in alloHSCT patients (N = 187) enrolled in a cGVHD cross-sectional study at the NIH (#NCT00331968). We propose a meaningful and reproducible measure of disease defined by a cut-off point reflecting clinical minimally detectable change (0-2 = no oral cGVHD, 3-15 = oral cGVHD) on the 15-point NIH cGVHD clinician assessment scale. Forty-four patients had oral cGVHD. Oral cGVHD was associated with a quiescent or de novo type of cGVHD onset (p = 0.05), higher cGVHD severity (p = 0.033), lower albumin (p = 0.0008), higher total complement (p = 0.012), greater bother from foods or oral ulcers and greater mouth pain, and sensitivity (p < 0.0001). Multivariable logistic regression modeling with albumin, mouth pain, and total complement was 74.3% predictive of oral cGVHD and 80.2% predictive of non-oral cGVHD. We propose the use of >2 points on the NIH scale as a reproducible definition of clinically significant oral cGVHD, which may be useful in clinical settings or as eligibility criterion or as an endpoint in clinical trials.

Cigarette smoke (CS) causes considerable morbidity and mortality by inducing cancer, chronic lung and vascular diseases, and oral disease. Despite the well-recognized risks associated with smoking, the habit remains unacceptably prevalent. Several toxins present in CS have immunomodulatory effects. CS also contains trace amounts of microbial cell components, including bacterial lipopolysaccharide. These and other CS constituents induce chronic inflammation at mucosal surfaces and modify host responses to exogenous antigens. The effects of CS on immunity are far-reaching and complex; both pro-inflammatory and suppressive effects may be induced. The net effect of CS on immunity depends on many variables, including the dose and type of tobacco, the route and chronicity of exposure, and the presence of other factors at the time of immune cell stimulation, such as Toll receptor ligands or other inflammatory mediators. CS impairs innate defenses against pathogens, modulates antigen presentation, and promotes autoimmunity. CS also impairs immunity in the oral cavity and promotes gingival and periodontal disease and oral cancer. The recognition of specific mechanisms by which CS affects host immunity is an important step toward elucidating mechanisms of tobacco-induced disease and may identify novel therapeutic approaches for the management of diseases that afflict smokers. Abbreviations: AP-1, activator protein-1; CD, cluster of differentiation; COPD, chronic obstructive pulmonary disease; HLA, human leukocyte antigen; IFNγ, interferon gamma; IL, interleukin; LPS, lipopolysaccharide; MAPK, mitogen-activated protein kinase; NF-κB, nuclear factor kappa-B; RAGE, receptors for advanced glycation end-products; ROS, reactive oxidative species; RORγτ, retinoic acid receptor-related orphan receptor transcription factor; STAT, signal transducer and activator of transcription; T-bet, T-box transcription factor; Th, T-helper; TLR, Toll-like receptors; TNFα, Tumor necrosis factor alpha; and TSLP, thymic stromal lymphopoeitin.

The development of new medical formulations (NMF) for reconstructive therapies has considerably improved the available treatment options for individuals requiring periodontal repair or oral implant rehabilitation. Progress in tissue engineering and regenerative medicine modalities strongly depends on validated pre-clinical research. Pre-clinical testing has contributed to the recent approval of NMF such as GEM 21S® and INFUSE® bone grafts for periodontal and oral regenerative therapies. However, the selection of a suitable pre-clinical model for evaluation of the safety and efficacy of a NMF remains a challenge. This review is designed to serve as a primer to choose the appropriate pre-clinical models for the evaluation of NMF in situations requiring periodontal or oral reconstruction. Here, we summarize commonly used pre-clinical models and provide examples of screening and functional studies of NMF that can be translated into clinical use.

Oral manifestations of diseases caused by bioterrorist agents could be a potential data source for biosurveillance. This study had the objectives of determining the oral manifestations of diseases caused by bioterrorist agents, measuring the prevalence of these manifestations in emergency department reports, and constructing and evaluating a detection algorithm based on them. We developed a software application to detect oral manifestations in free text and identified positive reports over three years of data. The normal frequency in reports for oral manifestations related to anthrax (including buccal ulcers-sore throat) was 7.46%. The frequency for tularemia was 6.91%. For botulism and smallpox, the frequencies were 0.55% and 0.23%. We simulated outbreaks for these bioterrorism diseases and evaluated the performance of our system. The detection algorithm performed better for smallpox and botulism than for anthrax and tularemia. We found that oral manifestations can be a valuable tool for biosurveillance.

Several studies have reported positive associations between oral infections and systemic diseases. The purpose of the present study was to evaluate the effects of oral symptoms on mortality from cardiovascular disease (CVD) and pneumonia. Using data from a cohort study in Japan, we analyzed 4,139 individuals aged 40–79 years. The baseline questionnaire included the following items related to oral symptoms: ‘sensitive teeth’, ‘difficulty in chewing tough food substances’, ‘bleeding gums’, and ‘mouth feels sticky’. We used the Cox proportional hazard model to estimate hazard ratios (HRs) and 95% confidence intervals (95%CIs) for mortality, after adjustments for lifestyle, socio-economic factors, and history of diseases. Persons complaining that their ‘mouth feels sticky’ had a two-fold higher risk of pneumonia (HR = 2.1; 95%CI, 1.2–3.6), while those complaining of ‘sensitive teeth’ had a lower risk of CVD (HR = 0.4; 95%CI, 0.2–0.9). Some oral symptoms may be predictors of mortality from pneumonia and CVD.

Contains fulltext : 51068.pdf (Publisher’s version ) (Closed access) Several families of enzymes are responsible for the degradation of extracellular matrix (ECM) proteins during the remodeling of tissues. An important family of such enzymes is that of the matrix metalloproteinases (MMPs). To control MMP-mediated ECM breakdown, tissue inhibitors of metalloproteinases (TIMPs) are able to inhibit MMP activity. A disturbed balance of MMPs and TIMPs is found in various pathologic conditions, such as cancer, rheumatoid arthritis, and periodontitis. The role of MMPs in pathology has been extensively described in the literature. The main focus of this review lies in the biological functions of TIMPs and their occurrence in disease, especially in the head and neck area. Their biological functions and their role in diseases like oral cancers and periodontitis, and in the development of cleft palate, will be discussed. Finally, the diagnostic and therapeutical opportunities of TIMPs will be evaluated.

Vesiculo-erosive diseases of the oral mucosa pose a major challenge in oral medicine, because they are chronic, painful, and interfere with the daily activities and quality of life of the patients, including disturbing eating, drinking, talking, and personal relationships. Many are autoimmune diseases, and corticosteroid therapy is currently central to their treatment. These diseases present with inflammation and alterations to epithelial integrity, through cell and/or humoral immunity-mediated attack on epithelial-connective tissue targets. Until recently, despite their serious adverse effects, it was necessary to prescribe systemic corticosteroids to control severe erosive oral diseases. Now, however, many of these diseases can be controlled by high-potency topical corticosteroids, which have proved to be highly efficacious and to cause fewer adverse effects compared with systemic corticosteroids. Nevertheless, although topical corticosteroids are still the most widely used drugs in the practice of oral medicine, the scientific body of evidence for their use in the oral cavity is virtually non-existent, and therefore many of the protocols followed are, of necessity, drawn from experience of their use in a dermatological setting. This review aims to set out the key aspects of the use of topical corticosteroids in oral medicine. The issues covered include the indications and basic rules for their use, the types of corticosteroids, the drug selection, and the specific formulations.

Although topical corticosteroids (TCs) are the most widely used drugs in oral medicine, and specifically in the treatment of vesiculo-erosive oral mucosal disease, there are few evidence-based data for the correct use of these drugs. In this review, we outline the most widely used protocols, the most common reasons for treatment failure, and the adverse effects documented in the literature.

The present article reviews, in detail, the current knowledge of the oral and dental aspects of chronic renal failure (CRF). Worldwide, increasing numbers of persons have CRF; thus, oral health care staffs are increasingly likely to provide care for patients with such disease. Chronic renal failure can give rise to a wide spectrum of oral manifestations, affecting the hard or soft tissues of the mouth. The majority of affected individuals have disease that does not complicate oral health care; nevertheless, the dental management of such individuals does require that the clinician understand the multiple systems that can be affected. The clinician should also consider the adverse side-effects of drug therapy and appropriate prescribing, in view of compromised renal clearance.

Oral infections and cardiovascular diseases share common biological and behavioral risk factors. Psychosocial determinants could act as a link between general health behavior and dental health behavior. Our objective was to study optimism and life satisfaction as determinants of general and dental health behavior and to evaluate whether these are connected with cardiovascular risk factors and dental diseases. The 1966 Northern Finland Birth Cohort (N = 12,058) is a general population birth cohort. In a postal questionnaire, respondents (N = 8690) were asked about their health behavior and dental status. Cardiovascular risk factors were assessed in health examinations (N = 6033). Generalized linear regression models were used in analysis. The results showed that health orientation increases with strengthening life satisfaction and optimism. Dental health behavior and general health behavior were associated with both cardiovascular risk factors and self-reported dental diseases, which support the assumption that they share a common behavioral background.

The objectives of this analysis were to determine the prevalence of oral mucosal lesions (OML) among adults in Southern China and to determine possible associations between OML and reported tobacco-smoking and alcohol-drinking habits. The sample consisted of 1573 35- to 44-year-old and 1515 65- to 74-year-old Chinese from both urban and rural areas of Guangdong Province. The subjects were interviewed by trained interviewers and underwent a clinical examination of the oral mucosa performed according to WHO guidelines. A specially prepared color atlas of OML was used for lesion recognition and confirmation during the survey. Among the 35- to 44-year-old subjects, the overall prevalence of OML was found to be 13% in urban men, 6% in urban women, 15% in rural men, and 4% in rural women. The corresponding figures for the 65- to 74-year-olds were 22%, 12%, 26%, and 19%. Tongue lesions and white lesions were relatively common, but denture-related lesions were not. No malignancies or erythroplakia was observed. Age and gender were found to relate to the occurrence of OML. In elderly men, smoking was significantly (p < 0.05) associated with some white lesions and tongue lesions, and alcohol drinking was also associated with some white lesions. In conclusion, tongue lesions and white lesions were relatively common in men, but pre-cancerous lesions were not prevalent.

The world we live in contains unimaginable numbers of bacteria, and these and other single-celled creatures represent the major diversity of life on our planet. During the last decade or so, the complexity and intimacy of the interactions which occur between bacteria and host eukaryotic cells during the of infection have begun to emerge. The study of such interactions is the subject of the new discipline of cellular microbiology. This intimacy of bacteria/host interactions creates a major paradox. The average human being is 90% bacteria in terms of cell numbers. These bacteria constitute the commensal or normal microflora and populate the mucosal surfaces of the oral cavity, gastrointestinal tract, urogenital tract, and the surface of the skin. In bacterial infections, much of the pathology is due to the release of a range of bacterial components ( e.g., modulins such as Hpopotysaccharide, peptidoglycan, DNA, molecular chaperones), which induce the synthesis of the local hormone-like molecules known as pro-inflammatory cytokines, However, such components must also be constantly released by the vast numbers of bacteria constituting the normal microflora and, as a consequence, our mucosae should constantly be in a state of inflammation. This is patently the case, and a hypothesis is forwarded to account for this ''commensal paradox", namely, that our commensal bacteria and mucosal surfaces exist in a state of bio-communism, forming a unified "tissue" in which interactions between bacteria and epithelia are finely balanced to ensure bacterial survival and prevent the induction of damaging inflammation. Evidence is emerging that bacteria can produce a variety of proteins which can inhibit the synthesis/release of inflammatory cytokines. The authors predict that such proteins are simply one part of an extensive signaling system which occurs between bacteria and epithelial cells at mucosal surfaces such as those found in the oral cavity.

Perceived oral health status has been shown to be associated with a variety of single clinical and self-reported indicators of oral health and oral health-related behaviors. A behavioral model is utilized which hypothesizes that perceived condition of natural teeth is predicted by multiple factors, including individual demographic and enabling characteristics, other health perceptions and orientations, actual levels of diseases and conditions, and self-defined need for treatment. The data are from the clinical examination and adult questionnaire of Phase 1 (1988-1991) of the Third National Health and Nutrition Examination Survey, which is based on a stratified multistage probability sample to produce nationally representative data for the civilian, non-institutionalized US population. Multivariate hierarchical regressions were used to assess perceived condition of natural teeth in two groups of dentate adults (those with a dental visit during the past 12 months, and those with a less recent dental visit). Self-defined treatment need made a significant, non-trivial contribution after other variables had been controlled. In both subpopulation models, the perception of general health and epidemiological indicators of oral health status were also significant factors. Socio-economic indicators did not contribute significantly in either regression. Understanding components of overall perceptions of oral health moves us closer to understanding oral health behaviors and oral-health-related quality of life.

Most physiological processes in mammals display circadian rhythms that are driven by the endogenous circadian clock. This clock is comprised of a central component located in the hypothalamic suprachiasmatic nucleus and subordinate clocks in peripheral tissues. Circadian rhythms sustain 24-hour oscillations of a large number of master genes controlling the correct timing and synchronization of diverse physiological and metabolic processes within our bodies. This complex regulatory network provides an important communication link between our brain and several peripheral organs and tissues. At the molecular level, circadian oscillations of gene expression are regulated by a family of transcription factors called “clock genes”. Dysregulation of clock gene expression results in diverse human pathological conditions, including autoimmune diseases and cancer. There is increasing evidence that the circadian clock affects tooth development, salivary gland and oral epithelium homeostasis, and saliva production. This review summarizes current knowledge of the roles of clock genes in the formation and maintenance of oral tissues, and discusses potential links between “oral clocks” and diseases such as head and neck cancer and Sjögren’s syndrome.

Previous studies among older adults have demonstrated that oral disease frequently leads to dysfunction, discomfort, and disability. This study aimed to assess variations in the social impact of oral conditions among six strata of people aged 65 years and older: residents of metropolitan Adelaide and rural Mt Gambier, South Australia; residents of metropolitan Toronto-North York and non-metropolitan Simcoe-Sudbury counties, Ontario, Canada; and blacks and whites in the Piedmont region of North Carolina (NC), United States. Subjects were participants in three oral epidemiological studies of random samples of the elderly populations in the six strata. Some 1,642 participants completed a 49-item Oral Health Impact Profile (OHIP) questionnaire which asked about impacts caused by problems with the teeth, mouth, or dentures during the previous 12 months. The percentage of dentate people reporting impacts fairly often or very often was greatest among NC blacks for 41 of the OHIP items. Two summary variables of social impact were used as dependent variables in bivariate and multivariate least-squares regression analyses. Among dentate people, mean levels of social impact were greatest for NC blacks and lowest for NC whites, while people from South Australia and Ontario had intermediate levels of social impact (P < 0.01). Missing teeth, retained root fragments, root-surface decay, periodontal pockets, and problem-motivated dental visits were associated with higher levels of social impact (P < 0.05), although there persisted a two-fold difference in social impact across the six strata after adjustment for those factors. Among edentulous people, there was no statistically significant variation in social impact among strata. The findings suggest that there are social and cultural factors influencing oral health and its social impact, and that those factors differ most between dentate blacks and whites in NC.

Nanoparticles are normally considered to be of a size no greater than 100 nm, and the exploitation of their unique attributes to combat infection has increased markedly over the past decade. The potential of nanoparticles to control the formation of biofilms within the oral cavity, as a function of their biocidal, anti-adhesive, and delivery capabilities, is now coming under close scrutiny. Possible uses as constituents of prosthetic device coatings, as topically applied agents, and within dental materials are being explored. The latest insights into the application of nanoparticles in the control of oral infections, including their use in photodynamic therapy, will be discussed in this review. In particular, the use of nanoparticulate silver, copper, zinc, silicon, and their oxides will be considered in relation to their effects on bacterial populations. The recent interest in the applications of nanoparticulate polymers and calcium phosphates will also be assessed. Particular attention will be paid to the toxicity issues surrounding the potential impact of nanoparticles on oral and other tissues.

Previous studies examined the serum immunoglobulin levels in relation to coronary artery disease (CAD). We hypothesized that the salivary immunoglobulins might better estimate oral infections in this relationship. Multivariate logistic regression analyses utilizing the data from 256 angiographically confirmed CAD patients and 250 non-CAD individuals that controlled for age, sex, smoking, diabetes, total/HDL cholesterol ratio, hypertension, and education revealed the trends that salivary IgA was positively and salivary IgG was inversely associated with CAD. The odds ratios (OR) of each increasing quartile of salivary IgA were 1.00 (first and second quartiles combined), 1.97, and 1.37 ( p-value for trend = 0.06), while those for salivary IgG were 1.00, 0.77, 0.60, and 0.51 ( p-value for trend = 0.02). Additionally, salivary IgA correlated positively with C-reactive protein and Asymptotic Dental Score (dental infection score), while IgG was inversely associated with these inflammation markers. Salivary IgA warrants further studies to confirm its role in the risk assessment of CAD.

Oral lichen planus (OLP) is a common inflammatory condition of the oral mucous membranes which affects between one and two percent of the general population. In accordance with the protracted clinical course of OLP and its association with known auto-immune diseases, the level of self-tolerance is questionable and possibly diminished in patients with this disorder. Normal suppressor T lymphocyte function is reputedly an essential element in the maintenance of self-tolerance, and deficient cell-mediated suppressor activity is implicated in the pathogenesis of auto-immune diseases. For assessment of in vitro cell-mediated suppressor activity in OLP, peripheral blood mononuclear cells (PBMC) from ten patients with OLP and from 11 control subjects were activated with the plant mitogen concanavalin A (Con A), followed by co-culture with autologous responder cells. The ability of irradiated Con A-activated cells to suppress the proliferation of Con A-stimulated responder cells was determined. Con A-induced suppressor activity of PBMC in the OLP patients was significantly less than that in control subjects (p = 0.001). Results of the present investigation complement previous in vitro findings which provided indirect evidence of deficient cell-mediated suppressor activity in OLP, particularly a decreased proportion of circulating CD4+CD45RA+ lymphocytes and reduced Con A-stimulated PBMC proliferation. The depressed Con A-induced suppressor activity of PBMC in the OLP patients provides direct evidence of deficient in vitro cell-mediated suppressor function in OLP, and suggests that defective cell-mediated suppressor circuits and reduced self-tolerance maybe involved in the pathogenesis of this disorder.

Genetic information is encoded not only by the linear sequence of DNA, but also by epigenetic modifications of chromatin structure that include DNA methylation and covalent modifications of the proteins that bind DNA. These “epigenetic marks” alter the structure of chromatin to influence gene expression. Methylation occurs naturally on cytosine bases at CpG sequences and is involved in controlling the correct expression of genes. DNA methylation is usually associated with triggering histone deacetylation, chromatin condensation, and gene silencing. Differentially methylated cytosines give rise to distinct patterns specific for each tissue type and disease state. Such methylation-variable positions (MVPs) are not uniformly distributed throughout our genome, but are concentrated among genes that regulate transcription, growth, metabolism, differentiation, and oncogenesis. Alterations in MVP methylation status create epigenetic patterns that appear to regulate gene expression profiles during cell differentiation, growth, and development, as well as in cancer. Environmental stressors including toxins, as well as microbial and viral exposures, can change epigenetic patterns and thereby effect changes in gene activation and cell phenotype. Since DNA methylation is often retained following cell division, altered MVP patterns in tissues can accumulate over time and can lead to persistent alterations in steady-state cellular metabolism, responses to stimuli, or the retention of an abnormal phenotype, reflecting a molecular consequence of gene-environment interaction. Hence, DNA epigenetics constitutes the main and previously missing link among genetics, disease, and the environment. The challenge in oral biology will be to understand the mechanisms that modify MVPs in oral tissues and to identify those epigenetic patterns that modify disease pathogenesis or responses to therapy.