Sources of bias in genomics research of oral and dental traits.

Evidence regarding the genomic basis of oral/dental traits and diseases is a fundamental pillar of the emerging notion of precision health. During the last decade, technological advances have improved the feasibility and affordability of conducting genome-wide association studies (GWAS) and studying the associations of emanating data with both common and rare oral conditions. Most evidence thus far emanates from GWAS of dental caries and periodontal disease that have tested the associations of several million single nucleotide polymorphisms (SNPs) with typically binary, health vs. disease phenotypes. GWAS offer advantages over the previous candidate-gene studies, mainly owing to their agnostic (i.e., unbiased, or hypothesis-free) nature. Nevertheless, GWAS are prone to virtually all sources of random and systematic error. Here, we review common sources of bias in genomics research with focus on GWAS including: type I and II errors, population stratification and heterogeneity, selection bias, adjustment for heritable covariates, appropriate reference panels for imputation, and gene annotation. We argue that valid and precise phenotype measurement is a key requirement, as GWAS sample sizes and thus statistical power increase. Finally, we stress that the lack of diversity of populations with phenotypes and genotypes is a major limitation for the generalizability and ultimate translation of the emerging genomics evidence-base into oral health promotion for all.

Searching Deep and Wide: Advances in the Molecular Understanding of Dental Caries and Periodontal Disease.

During the past decades, remarkable progress has been made in the understanding of the molecular basis of the 2 most common oral diseases, dental caries and periodontal disease. Improvements in our knowledge of the diseases' underlying biology have illuminated previously unrecognized aspects of their pathogenesis. Importantly, the key role of the oral (supragingival and subgingival) microbiome is now well recognized, and both diseases are now best understood as dysbiotic. From a host susceptibility standpoint, some progress has been made in dissecting the "hyperinflammatory" trait and other pathways of susceptibility underlying periodontitis, and novel susceptibility loci have been reported for dental caries. Nevertheless, there is a long road to the translation of these findings and the realization of precision oral health. There is promise and hope that the rapidly increasing capacity of generating multiomics data layers and the aggregation of study samples and cohorts comprising thousands of participants will accelerate the discovery and translation processes. A first key element in this process has been the identification and interrogation of biologically informed disease traits-these "deep" or "precise" traits have the potential of revealing biologically homogeneous disease signatures and genetic susceptibility loci that might present with overlapping or heterogeneous clinical signs. A second key element has been the formation of international consortia with the goals of combining and harmonizing oral health data of thousands of individuals from diverse settings-these "wide" collaborative approaches leverage the power of large sample sizes and are aimed toward the discovery or validation of genetic influences that would otherwise be impossible to detect. Importantly, advancements via these directions require an unprecedented engagement of systems biology and team science models. The article highlights novel insights into the molecular basis of dental caries and chronic periodontitis that have been gained from recent and ongoing studies involving "deep" and "wide" analytical approaches.

The role of oral hygiene in head and neck cancer: results from International Head and Neck Cancer Epidemiology (INHANCE) consortium.

BACKGROUND: Poor oral hygiene has been proposed to contribute to head and neck cancer (HNC) risk, although causality and independency of some indicators are uncertain. This study investigates the relationship of five oral hygiene indicators with incident HNCs. METHODS: In a pooled analysis of 8925 HNC cases and 12 527 controls from 13 studies participating in the International Head and Neck Cancer Epidemiology Consortium, comparable data on good oral hygiene indicators were harmonized. These included: no denture wear, no gum disease (or bleeding), <5 missing teeth, tooth brushing at least daily, and visiting a dentist ≥once a year. Logistic regression was used to estimate the effects of each oral hygiene indicator and cumulative score on HNC risk, adjusting for tobacco smoking and alcohol consumption. RESULTS: Inverse associations with any HNC, in the hypothesized direction, were observed for <5 missing teeth [odds ratio (OR) = 0.78; 95% confidence interval (CI) 0.74, 0.82], annual dentist visit (OR = 0.82; 95% CI 0.78, 0.87), daily tooth brushing (OR = 0.83, 95% CI 0.79, 0.88), and no gum disease (OR = 0.94; 95% CI 0.89, 0.99), and no association was observed for wearing dentures. These associations were relatively consistent across specific cancer sites, especially for tooth brushing and dentist visits. The population attributable fraction for ≤ 2 out of 5 good oral hygiene indicators was 8.9% (95% CI 3.3%, 14%) for oral cavity cancer. CONCLUSION: Good oral hygiene, as characterized by few missing teeth, annual dentist visits, and daily tooth brushing, may modestly reduce the risk of HNC.

Burnout prevalence and correlates amongst Colombian dental students: the STRESSCODE study.

INTRODUCTION: Accumulating evidence amongst dental students indicates an alarming prevalence of stress, which can precipitate the development of burnout--a state of mental or physical exhaustion and disengagement. Understanding individual and educational correlates of burnout is necessary for its prevention. The aims of this study were to determine the prevalence of burnout amongst a large sample of Colombian dental undergraduates and investigate its psychosocial and educational correlates. MATERIALS AND METHODS: Survey data collected from 5647 students participating in the Stress in Colombian Dental Education study were used for this analysis. Burnout was measured using the Maslach Burnout Inventory-Student Survey (MBI-SS). Covariates included participants' socio-demographic characteristics and perceived stress, as well as educational environment factors. Descriptive, bivariate and multivariate methods based on multilevel mixed-effects logistic regression modelling were used for data analysis. RESULTS: Seven per cent of the students surveyed met the criteria for burnout. The prevalence of burnout was higher amongst upper classes, older and married students, those who reported not having passed all required courses and not having dentistry as their first career choice, as well as students in public institutions and those with large class sizes. Moreover, students' perceived stress in the domains of workload and self-efficacy was significantly and positively associated with burnout. CONCLUSIONS: Both personal and educational environment characteristics were found to be associated with burnout. Irrespective of these factors, students' perceived stress with regard to workload and self-efficacy was a strong influence on burnout and its alleviation may be a promising avenue to prevent psychological morbidity.

Multiple Imputation for Partial Recording Periodontal Examination Protocols.

AIM: Partial-mouth recording protocols often result in underestimation of population prevalence and extent of periodontitis. We posit that multiple imputation of measures such as clinical attachment loss for nonselected tooth sites in partial-mouth samples can reduce bias in periodontitis estimates. METHODS: Multiple imputation for correlated site-level dichotomous outcomes in a generalized estimating equations framework is used to impute site-level binary indicators for clinical attachment loss exceeding a fixed threshold in partial-mouth samples. Periodontitis case definitions are applied to the imputed "complete" dentitions, enabling estimation of prevalence and other summaries of periodontitis for partial-mouth samples as if for full-mouth examinations. A multiple imputation-bootstrap procedure is described and applied for point and variance estimation of these periodontitis measures. The procedure is evaluated with pseudo-partial-mouth samples based on random site selection protocols of 28 to 84 periodontal sites repeatedly generated from full-mouth periodontal examinations of 3,621 participants in the 2013 to 2014 National Health and Nutrition Examination Survey (NHANES) survey. RESULTS: Multiple imputation applied to partial-mouth samples overestimated periodontitis mean extent, defined as the number of sites with clinical attachment loss 3 mm or greater, by 9.5% in random site selection protocols with 84 sites and overestimated prevalence by 5% to 10% in all the evaluated protocols. CONCLUSIONS: In the 2013 to 2014 NHANES data, multiple imputation of site-level periodontal indicators provides less biased estimates of periodontitis prevalence and extent than has been reported from estimates based on the direct application of full-mouth case definitions to partial-mouth samples. Multiple imputation provides a promising solution to the longstanding, vexing problem of estimation bias in partial-mouth recording, with potential application to a wide array of case definitions, periodontitis measures, and partial recording protocols. KNOWLEDGE TRANSFER STATEMENT: Partial-mouth sampling, while a resource-efficient strategy for obtaining oral disease estimates, often results in underestimation of periodontitis metrics. Multiple imputation for nonselected periodontal sites produces pseudo-full-mouth data sets that may be analyzed and combined to produce estimates with small bias.

A Polygenic Score Predicts Caries Experience in Elderly Swedish Adults.

Caries is a partially heritable disease, raising the possibility that a polygenic score (PS, a summary of an individual's genetic propensity for disease) might be a useful tool for risk assessment. To date, PS for some diseases have shown clinical utility, although no PS for caries has been evaluated. The objective of the study was to test whether a PS for caries is associated with disease experience or increment in a cohort of Swedish adults. A genome-wide PS for caries was trained using the results of a published genome-wide association meta-analysis and constructed in an independent cohort of 15,460 Swedish adults. Electronic dental records from the Swedish Quality Registry for Caries and Periodontitis (SKaPa) were used to compute the decayed, missing, and filled tooth surfaces (DMFS) index and the number of remaining teeth. The performance of the PS was evaluated by testing the association between the PS and DMFS at a single dental examination, as well as between the PS and the rate of change in DMFS. Participants in the highest and lowest deciles of PS had a mean DMFS of 63.5 and 46.3, respectively. A regression analysis confirmed this association where a 1 standard deviation increase in PS was associated with approximately 4-unit higher DMFS (P < 2 × 10-16). Participants with the highest decile of PS also had greater change in DMFS during follow-up. Results were robust to sensitivity analysis, which adjusted for age, age squared, sex, and the first 20 genetic principal components. Mediation analysis suggested that tooth loss was a strong mediating factor in the association between PS and DMFS but also supported a direct genetic effect on caries. In this cohort, there are clinically meaningful differences in DMFS between participants with high and low PS for caries. The results highlight the potential role of genomic data in improving caries risk assessment.

Immune Dysregulation in the Oral Cavity during Early SARS-CoV-2 Infection.

Tissue-specific immune responses are critical determinants of health-maintaining homeostasis and disease-related dysbiosis. In the context of COVID-19, oral immune responses reflect local host-pathogen dynamics near the site of infection and serve as important "windows to the body," reflecting systemic responses to the invading SARS-CoV-2 virus. This study leveraged multiplex technology to characterize the salivary SARS-CoV-2-specific immunological landscape (37 cytokines/chemokines and 11 antibodies) during early infection. Cytokine/immune profiling was performed on unstimulated cleared whole saliva collected from 227 adult SARS-CoV-2+ participants and 37 controls. Statistical analysis and modeling revealed significant differential abundance of 25 cytokines (16 downregulated, 9 upregulated). Pathway analysis demonstrated early SARS-CoV-2 infection is associated with local suppression of oral type I/III interferon and blunted natural killer-/T-cell responses, reflecting a potential novel immune-evasion strategy enabling infection. This virus-associated immune suppression occurred concomitantly with significant upregulation of proinflammatory pathways including marked increases in the acute phase proteins pentraxin-3 and chitinase-3-like-1. Irrespective of SARS-CoV-2 infection, prior vaccination was associated with increased total α-SARS-CoV-2-spike (trimer), -S1 protein, -RBD, and -nucleocapsid salivary antibodies, highlighting the importance of COVID-19 vaccination in eliciting mucosal responses. Altogether, our findings highlight saliva as a stable and accessible biofluid for monitoring host responses to SARS-CoV-2 over time and suggest that oral-mucosal immune dysregulation is a hallmark of early SARS-CoV-2 infection, with possible implications for viral evasion mechanisms.

Multi-ancestry Genome-Wide Association Study of Early Childhood Caries.

Early childhood caries (ECC) is the most common non-communicable childhood disease. It is an important health problem with known environmental and social/behavioral influences that lacks evidence for specific associated genetic risk loci. To address this knowledge gap, we conducted a genome-wide association study of ECC in a multi-ancestry population of U.S. preschool-age children (n=6,103) participating in a community-based epidemiologic study of early childhood oral health. Calibrated examiners used ICDAS criteria to measure ECC with the primary trait using the dmfs index with decay classified as macroscopic enamel loss (ICDAS ≥3). We estimated heritability, concordance rates, and conducted genome-wide association analyses to estimate overall genetic effects; the effects stratified by sex, household water fluoride, and dietary sugar; and leveraged the combined gene/gene-environment effects using the 2-degree-of-freedom (2df) joint test. The common genetic variants explained 24% of the phenotypic variance (heritability) of the primary ECC trait and the concordance rate was higher with a higher degree of relatedness. We identified 21 novel non-overlapping genome-wide significant loci for ECC. Two loci, namely RP11-856F16 . 2 (rs74606067) and SLC41A3 (rs71327750) showed evidence of association with dental caries in external cohorts, namely the GLIDE consortium adult cohort (n=∼487,000) and the GLIDE pediatric cohort (n=19,000), respectively. The gene-based tests identified TAAR6 as a genome-wide significant gene. Implicated genes have relevant biological functions including roles in tooth development and taste. These novel associations expand the genomics knowledge base for this common childhood disease and underscore the importance of accounting for sex and pertinent environmental exposures in genetic investigations of oral health.

Surface-specific efficacy of fluoride varnish in caries prevention in the primary dentition: results of a community randomized clinical trial.

OBJECTIVES: Fluoride varnish (FV) is efficacious in caries prevention although its effects among different tooth surfaces are poorly understood. This study sought to determine the extent to which caries-preventive effects of a community intervention that included FV application among preschool-aged children varied according to primary tooth anatomy and baseline tooth pathology. METHODS: Secondary analysis was undertaken of data from a community-randomized controlled trial among 543 3- to 5-year-old Aboriginal children in 30 Northern Territory Australian communities. Children in intervention communities received community health promotion and FV application once every 6 months. Net caries (d(3)mfs) risk and 95% confidence limits (CL) were estimated for the control and intervention arms, and stratified according to tooth anatomy/location and baseline pathology (sound, enamel opacity, hypoplastic defect or precavitated carious lesion). The intervention's efficacy was quantified using generalized estimating equation modeling accounting for study design and clustering. The assumption of efficacy homogeneity was tested using a Wald χ(2) test with a p < 0.2 criterion and post hoc pairwise comparisons. RESULTS: The intervention resulted in a 25% reduction (relative risk, RR = 0.75; 95% CL = 0.71, 0.80) in the 2-year surface-level caries risk. There was substantial heterogeneity in FV efficacy by baseline surface pathology: RRs were 0.73 for sound, 0.77 for opaque, 0.90 for precavitated, and 0.92 for hypoplastic surfaces. Among sound surfaces, maxillary anterior facials received significantly more benefit (RR = 0.62) compared to pits and fissures (RR = 0.78). CONCLUSION: The intervention had greatest efficacy on surfaces that were sound at baseline. Among those sound surfaces, maxillary anterior facials received most caries-preventive benefit.

Oral health literacy comparisons between Indigenous Australians and American Indians.

OBJECTIVES: To compare oral health literacy (OHL) levels between two profoundly disadvantaged groups, Indigenous Australians and American Indians, and to explore differences in socio-demographic, dental service utilisation, self-reported oral health indicators, and oral health-related quality of life (OHRQoL) correlates of OHL among the above. METHODS: OHL was measured using REALD-30 among convenience samples of 468 Indigenous Australians (aged 17-72 years, 63% female) and 254 female American Indians (aged 18-57 years). Covariates included socio-demography, dental utilisation, self-reported oral health status (OHS), perceived treatment needs and OHRQoL (prevalence, severity and extent of OHIP-14 'impacts'). Descriptive and bivariate methods were used for data presentation and analysis, and between-sample comparisons relied upon empirical contrasts of sample-specific estimates and correlation coefficients. RESULTS: OHL scores were: Indigenous Australians - 15.0 (95% CL=14.2, 15.8) and American Indians--13.7 (95% CL=13.1, 14.4). In both populations, OHL strongly correlated with educational attainment, and was lower among participants with infrequent dental attendance and perceived restorative treatment needs. A significant inverse association between OHL and prevalence of OHRQoL impacts was found among American Indians (rho=-0.23; 95% CL = -0.34, -0.12) but not among Indigenous Australians. CONCLUSIONS: Our findings indicate that OHL levels were comparable between the two groups and lower compared to previously reported estimates among diverse populations. Although the patterns of association of OHL with most examined domains of correlates were similar between the two groups, this study found evidence of heterogeneity in the domains of self-reported OHS and OHRQoL.

Perceived sources of stress amongst Chilean and Argentinean dental students.

INTRODUCTION: The prevalence of high levels of stress as well as its multilevel consequences is well documented amongst students in the health sciences, and particularly in dentistry. However, investigations of perceived stress amongst Spanish-speaking student groups are sparse. This study aimed to (i) describe the translation, adaptation and psychometric properties of a Spanish version of the Dental Environment Stressors questionnaire and (ii) to examine the perceived sources of stress and their associations with the students' study year and gender in two dental schools in Latin America. MATERIALS AND METHODS: All students officially registered in the dental schools of the University of San Sebastian (USS) in Chile and the Catholic University of Cordoba (CUC) in Argentina were invited to participate in the study. The DES30 questionnaire was adapted in Spanish using translation/back-translation, an expert bilingual committee, and consensus building. Cronbach's alpha was used to measure the instrument's internal consistency, and iterated principal factor analysis with promax rotation was employed to explore its underlying factor structure. Descriptive, bivariate and multivariate methods were used to examine the patterns of association between individual stressors, factor scores and students' characteristics. RESULTS: Three hundred and four students comprised the study's analytical sample, with two-thirds of those being female. The DES30-Sp demonstrated good internal consistency (Cronbach's α = 0.89). A four-factor solution emerged and included 'academic workload', 'clinical training', 'time constraints' and 'self-efficacy beliefs' factors. 'Fear of failing a course or a year', 'examinations and grades' and 'lack of time for relaxation' were amongst the top individual-item stressors reported by students in both schools. Amongst this group of undergraduate dental students, those in Argentina, in higher study year, and females reported higher perceived stress. CONCLUSIONS: Increased workload, time constraints and some aspects of clinical training were the top stressors of approximately 300 Chilean and Argentinean dental undergraduates. Some variations between schools, males and females and study years were noted. The Spanish version of the DES30 questionnaire performed well, but future studies should evaluate the instrument's properties in larger and more diverse dental student populations.

Plasmin-Mediated Fibrinolysis in Periodontitis Pathogenesis.

The hemostatic and inflammatory systems work hand in hand to maintain homeostasis at mucosal barrier sites. Among the factors of the hemostatic system, fibrin is well recognized for its role in mucosal homeostasis, wound healing, and inflammation. Here, we present a basic overview of the fibrinolytic system, discuss fibrin as an innate immune regulator, and provide recent work uncovering the role of fibrin-neutrophil activation as a regulator of mucosal/periodontal homeostasis. We reason that the role of fibrin in periodontitis becomes most evident in individuals with the Mendelian genetic defect, congenital plasminogen (PLG) deficiency, who are predisposed to severe periodontitis in childhood due to a defect in fibrinolysis. Consistent with plasminogen deficiency being a risk factor for periodontitis, recent genomics studies uncover genetic polymorphisms in PLG, encoding plasminogen, being significantly associated with periodontal disease, and suggesting PLG variants as candidate risk indicators for common forms of periodontitis.

Longitudinal Microbiome Changes in Supragingival Biofilm Transcriptomes Induced by Orthodontics.

INTRODUCTION: Common oral diseases are known to be associated with dysbiotic shifts in the supragingival microbiome, yet most oral microbiome associations with clinical end points emanate from cross-sectional studies. Orthodontic treatment is an elective procedure that can be exploited to prospectively examine clinically relevant longitudinal changes in the composition and function of the supragingival microbiome. METHODS: A longitudinal cohort study was conducted among 24 adolescent orthodontic patients who underwent saliva and plaque sampling and clinical examinations at time points: before fixed appliance bonding and at 1, 6, and 12 wk thereafter. Clinical indices included bleeding on probing (BOP), mean gingival index (GI), probing depths (PDs), and plaque index (PI). To study the biologically (i.e., transcriptionally) active microbial communities, RNA was extracted from plaque and saliva for RNA sequencing and microbiome bioinformatics analysis. Longitudinal changes in microbiome beta diversity were examined using PERMANOVA tests, and the relative abundance of microbial taxa was measured using Kruskal-Wallis tests, Wilcoxon rank-sum tests, and negative binomial and zero-inflated mixed models. RESULTS: Clinical measures of oral health deteriorated over time-the proportion of sites with GI and PI ≥1 increased by over 70% between prebonding and 12 wk postbonding while the proportion of sites with PD ≥4 mm increased 2.5-fold. Streptococcus sanguinis, a health-associated species that antagonizes cariogenic pathogens, showed a lasting decrease in relative abundance during orthodontic treatment. Contrarily, caries- and periodontal disease-associated taxa, including Selenomonas sputigena, Leptotrichia wadei, and Lachnoanaerobaculum saburreum, increased in abundance after bonding. Relative abundances of Stomatobaculum longum and Mogibacterium diversum in prebonding saliva predicted elevated BOP 12 wk postbonding, whereas Neisseria subflava was associated with lower BOP. CONCLUSIONS: This study offers insights into longitudinal community and species-specific changes in the supragingival microbiome transcriptome during fixed orthodontic treatment, advancing our understanding of microbial dysbioses and identifying targets of future health-promoting clinical investigations. KNOWLEDGE TRANSFER STATEMENT: Bonding braces was associated with subsequent changes in the oral microbiome characterized by increases in disease-associated species, decreases in health-associated species, and worsened clinical measures of oral health.

Stress and burnout in postgraduate dental education.

INTRODUCTION: High levels of stress and burnout have been documented among dental students and practicing dentists, but evidence among dental residents and postgraduate students is lacking. MATERIALS AND METHODS: Ninety-nine postgraduate students enrolled in clinical, non-clinical and PhD programmes in the Athens University School of Dentistry completed the Graduate Dental Environment Stress (GDES) questionnaire and the Maslach Burnout Inventory. Perceived stress was measured in two domains, academic (GDES-A) and clinical (GDES-C) and burnout was measured using the scales of emotional exhaustion (EE), depersonalisation (DP) and personal accomplishment (PA). Analyses relied on descriptive, univariate and multivariate methods based on ANOVA and generalised linear models. RESULTS: Participants' mean age was 30 years; two-thirds were women and practised dentistry independently of their graduate studies. Residents in clinical programmes reported significantly higher levels of perceived stress compared to non-clinical and PhD students (P<0.05). There were no gender differences in perceived stress. Forty per cent of respondents were burnout 'cases' on the EE scale, while this proportion was 38% for reduced PA and smaller, 13% for DP. Perceived stress was positively correlated with all burnout dimensions, whereas independent dental practice and higher age had a protective effect. CONCLUSIONS: High rates of burnout manifestations were detected among this sample of Greek postgraduate dental students. Perceived stress correlated with burnout and was more pronounced among those enrolled in clinical residency compared to non-clinical and PhD programmes.

Phenotype Harmonization in the GLIDE2 Oral Health Genomics Consortium.

Genetic risk factors play important roles in the etiology of oral, dental, and craniofacial diseases. Identifying the relevant risk loci and understanding their molecular biology could highlight new prevention and management avenues. Our current understanding of oral health genomics suggests that dental caries and periodontitis are polygenic diseases, and very large sample sizes and informative phenotypic measures are required to discover signals and adequately map associations across the human genome. In this article, we introduce the second wave of the Gene-Lifestyle Interactions and Dental Endpoints consortium (GLIDE2) and discuss relevant data analytics challenges, opportunities, and applications. In this phase, the consortium comprises a diverse, multiethnic sample of over 700,000 participants from 21 studies contributing clinical data on dental caries experience and periodontitis. We outline the methodological challenges of combining data from heterogeneous populations, as well as the data reduction problem in resolving detailed clinical examination records into tractable phenotypes, and describe a strategy that addresses this. Specifically, we propose a 3-tiered phenotyping approach aimed at leveraging both the large sample size in the consortium and the detailed clinical information available in some studies, wherein binary, severity-encompassing, and "precision," data-driven clinical traits are employed. As an illustration of the use of data-driven traits across multiple cohorts, we present an application of dental caries experience data harmonization in 8 participating studies (N = 55,143) using previously developed permanent dentition tooth surface-level dental caries pattern traits. We demonstrate that these clinical patterns are transferable across multiple cohorts, have similar relative contributions within each study, and thus are prime targets for genetic interrogation in the expanded and diverse multiethnic sample of GLIDE2. We anticipate that results from GLIDE2 will decisively advance the knowledge base of mechanisms at play in oral, dental, and craniofacial health and disease and further catalyze international collaboration and data and resource sharing in genomics research.

Distinct Microbial Signatures between Periodontal Profile Classes.

Precise classification of periodontal disease has been the objective of concerted efforts and has led to the introduction of new consensus-based and data-driven classifications. The purpose of this study was to characterize the microbiological signatures of a latent class analysis (LCA)-derived periodontal stratification system, the Periodontal Profile Class (PPC) taxonomy. We used demographic, microbial (subgingival biofilm composition), and immunological data (serum IgG antibody levels, obtained with checkerboard immunoblotting technique) for 1,450 adult participants of the Dental Atherosclerosis Risk in Communities (ARIC) study, with already generated PPC classifications. Analyses relied on t tests and generalized linear models with Bonferroni correction. Men and African Americans had higher systemic antibody levels against most microorganisms compared to women and Caucasians (P < 0.05). Healthy individuals (PPC-I) had low levels of biofilm bacteria and serum IgG levels against most periodontal pathogens (P < 0.05). Subjects with mild to moderate disease (PPC-II to PPC-III) showed mild/moderate colonization of multiple biofilm pathogens. Individuals with severe disease (PPC-IV) had moderate/high levels of biofilm pathogens and antibody levels for orange/red complexes. High gingival index individuals (PPC-V) showed moderate/high levels of biofilm Campylobacter rectus and Aggregatibacter actinomycetemcomitans. Biofilm composition in individuals with reduced periodontium (PPC-VI) was similar to health but showed moderate to high antibody responses. Those with severe tooth loss (PPC-VII) had significantly high levels of multiple biofilm pathogens, while the systemic antibody response to these microorganisms was comparable to health. The results support a biologic basis for elevated risk for periodontal disease in men and African Americans. Periodontally healthy individuals showed a low biofilm pathogen and low systemic antibody burden. In the presence of PPC disease, a microbial-host imbalance characterized by higher microbial biofilm colonization and/or systemic IgG responses was identified. These results support the notion that subgroups identified by the PPC system present distinct microbial profiles and may be useful in designing future precise biological treatment interventions.

Metabolomics Insights in Early Childhood Caries.

Dental caries is characterized by a dysbiotic shift at the biofilm-tooth surface interface, yet comprehensive biochemical characterizations of the biofilm are scant. We used metabolomics to identify biochemical features of the supragingival biofilm associated with early childhood caries (ECC) prevalence and severity. The study's analytical sample comprised 289 children ages 3 to 5 (51% with ECC) who attended public preschools in North Carolina and were enrolled in a community-based cross-sectional study of early childhood oral health. Clinical examinations were conducted by calibrated examiners in community locations using International Caries Detection and Classification System (ICDAS) criteria. Supragingival plaque collected from the facial/buccal surfaces of all primary teeth in the upper-left quadrant was analyzed using ultra-performance liquid chromatography-tandem mass spectrometry. Associations between individual metabolites and 18 clinical traits (based on different ECC definitions and sets of tooth surfaces) were quantified using Brownian distance correlations (dCor) and linear regression modeling of log2-transformed values, applying a false discovery rate multiple testing correction. A tree-based pipeline optimization tool (TPOT)-machine learning process was used to identify the best-fitting ECC classification metabolite model. There were 503 named metabolites identified, including microbial, host, and exogenous biochemicals. Most significant ECC-metabolite associations were positive (i.e., upregulations/enrichments). The localized ECC case definition (ICDAS ≥1 caries experience within the surfaces from which plaque was collected) had the strongest correlation with the metabolome (dCor P = 8 × 10-3). Sixteen metabolites were significantly associated with ECC after multiple testing correction, including fucose (P = 3.0 × 10-6) and N-acetylneuraminate (p = 6.8 × 10-6) with higher ECC prevalence, as well as catechin (P = 4.7 × 10-6) and epicatechin (P = 2.9 × 10-6) with lower. Catechin, epicatechin, imidazole propionate, fucose, 9,10-DiHOME, and N-acetylneuraminate were among the top 15 metabolites in terms of ECC classification importance in the automated TPOT model. These supragingival biofilm metabolite findings provide novel insights in ECC biology and can serve as the basis for the development of measures of disease activity or risk assessment.

What Child Oral Health-Related Behaviors Can First-time Mothers Actualize? A Pragmatic Prospective Study.

INTRODUCTION: First-time pregnant women are considered to be receptive to health information, rendering the prenatal period an opportune time to provide helpful information on the importance of child-related oral health. However, little is known about pregnant women's knowledge of child oral health-related behaviors (COHBs) during pregnancy and their implementation after birth. We sought to address this knowledge gap by a prospective investigation of intended and actualized oral health behaviors among first-time pregnant women. METHODS: We examined relationships between intended and actualized COHBs and their correlations with changes in oral health knowledge, health literacy, general self-efficacy, and dental neglect in a cohort of first-time pregnant clients at Women, Infants, and Children sites in North Carolina-participants of a large community-based study. The COHBs were related to diet (i.e., frequency of fruit juice and sweet snacks consumption and nighttime bottle-feeding) and oral hygiene practices (e.g., performance of daily oral hygiene and use of fluoridated toothpaste). Analyses relied on descriptive statistics and bivariate tests (Student's t and McNemar's). Data were collected from 48 participants (White, 44%; African American, 40%; Native American, 17%) at baseline and again at least 12 months after the birth of their first child. RESULTS: On average, most mothers actualized 3 of 5 COHBs (range, 1 to 4). Significant differences between before and after birth were noted for frequency of sweet snacks consumption and putting the baby in bed with a bottle. No correlation was found between knowledge, literacy, self-efficacy, neglect, and sociodemographic characteristics and COHB actualization. CONCLUSION: Our findings suggest that first-time mothers in the studied population are likely to implement some but not all positive intended COHBs during pregnancy. Interventions are needed to assist women in implementing these practices. We support that, for prenatal interventional efforts to reap positive benefits, messaging should be personalized and include specific guidance on how to implement these recommendations. KNOWLEDGE TRANSFER STATEMENT: A knowledge gap exists in our understanding of the relationship between first-time mothers' intended and actualized child oral health behaviors, with implications in the optimal timing of infant and early childhood oral health messaging. Our findings suggest that first-time mothers are likely to implement some but not all positive behaviors that they intended to adopt during pregnancy. Interventions are needed to assist women in implementing these practices.

Heritability of periodontitis: A systematic review of evidence from animal studies.

OBJECTIVE: The aim of this study was to quantify the heritability of periodontitis via a systematic appraisal of the existing evidence derived from animal studies. DESIGN: A search was conducted through the electronic databases MEDLINE, Embase, LILACS, Cochrane Library, Open Grey, Google Scholar and ResearchGate, complemented by a hand search, for studies reporting measures of heritability of periodontitis. After full-text reading, 7 studies conducted on animal models met the inclusion criteria. Six studies carried out experimental periodontitis models in mice, while one study assessed bone loss in dry skulls of baboons with known pedigrees. RESULTS: Heritability of 'naturally-occurring bone loss' (3 studies, non-experimental conditions) was estimated at 0.39 (95% confidence interval: 0.13-0.64) with virtually no heterogeneity (I2 = 0%, p = 0.97). Heritability of experimental periodontitis in mice (6 studies) was 0.43 (0.28-0.58) with considerable heterogeneity (I2 = 96%, p < 0.01). There was no evidence of publication bias. CONCLUSIONS: Over a third of the phenotypic variance of periodontitis in animal studies is due to genetic factors, somewhat higher than the estimate from human studies. It can be argued that, under the strictly-controlled experimental conditions of laboratory-induced periodontitis, the relative role of heritable factors predisposing to periodontitis and bone loss may be stronger compared with human studies.

The Era of the Genome and Dental Medicine.

Understanding the "code of life" and mapping the human genome have been monumental and era-defining scientific landmarks-analogous to setting foot on the moon. The last century has been characterized by exponential advances in our understanding of the biological and specifically molecular basis of health and disease. The early part of the 20th century was marked by fundamental theoretical and scientific advances in understanding heredity, the identification of the DNA molecule and genes, and the elucidation of the central dogma of biology. The second half was characterized by experimental and increasingly molecular investigations, including clinical and population applications. The completion of the Human Genome Project in 2003 and the continuous technological advances have democratized access to this information and the ability to generate health and disease association data; however, the realization of genomic and precision medicine, to practically improve people's health, has lagged. The oral health domain has made great strides and substantially benefited from the last century of advances in genetics and genomics. Observations regarding a hereditary component of dental caries were reported as early as the 1920s. Subsequent breakthroughs were made in the discovery of genetic causes of rare diseases, such as ectodermal dysplasias, orofacial clefts, and other craniofacial and dental anomalies. More recently, genome-wide investigations have been conducted and reported for several diseases and traits, including periodontal disease, dental caries, tooth agenesis, cancers of the head and neck, orofacial pain, temporomandibular disorders, and craniofacial morphometrics. Gene therapies and gene editing with CRISPR/Cas represent the latest frontier surpassed in the era of genomic medicine. Amid rapid genomics progress, several challenges and opportunities lie ahead. Importantly, systematic efforts supported by implementation science are needed to realize the full potential of genomics, including the improvement of public and practitioner genomics literacy, the promotion of individual and population oral health, and the reduction of disparities.