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Chronic periodontitis (CP) has a genetic component, particularly its severe forms. Evidence from genome-wide association studies (GWASs) has highlighted several potential novel loci. Here, the authors report the first GWAS of CP among a large community-based sample of Hispanics/Latinos. The authors interrogated a quantitative trait of CP (mean interproximal clinical attachment level determined by full-mouth periodontal examinations) among 10,935 adult participants (mean age: 45 y, range: 18 to 76 y) from the Hispanic Community Health Study / Study of Latinos. Genotyping was done with a custom Illumina Omni2.5M array, and imputation to approximately 20 million single-nucleotide polymorphisms was based on the 1000 Genomes Project phase 1 reference panel. Analyses were based on linear mixed models adjusting for sex, age, study design features, ancestry, and kinship and employed a conventional P < 5 × 10-8 statistical significance threshold. The authors identified a genome-wide significant association signal in the 1q42.2 locus ( TSNAX-DISC1 noncoding RNA, lead single-nucleotide polymorphism: rs149133391, minor allele [C] frequency = 0.01, P = 7.9 × 10-9) and 4 more loci with suggestive evidence of association ( P < 5 × 10-6): 1q22 (rs13373934), 5p15.33 (rs186066047), 6p22.3 (rs10456847), and 11p15.1 (rs75715012). We tested these loci for replication in independent samples of European-American ( n = 4,402) and African-American ( n = 908) participants of the Atherosclerosis Risk in Communities study. There was no replication among the European Americans; however, the TSNAX-DISC1 locus replicated in the African-American sample (rs149133391, minor allele frequency = 0.02, P = 9.1 × 10-3), while the 1q22 locus was directionally concordant and nominally significant (rs13373934, P = 4.0 × 10-2). This discovery GWAS of interproximal clinical attachment level-a measure of lifetime periodontal tissue destruction-was conducted in a large, community-based sample of Hispanic/Latinos. It identified a genome-wide significant locus that was independently replicated in an African-American population. Identifying this genetic marker offers direction for interrogation in subsequent genomic and experimental studies of CP.

Vaishnavi Bhaskar,1 Kathleen A McGraw,2 Kimon Divaris3 1Department of Health Policy and Management, Gillings School of Global Public Health, 2Health Sciences Library, 3Department of Pediatric Dentistry, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Background: Dental caries, the most common childhood chronic disease, disproportionately affects vulnerable parts of the population and confers substantial impacts to children, families, and health systems. Because efforts directed toward oral health promotion and disease prevention are fundamentally superior to dental rehabilitation secondary to disease development, early preventive dental visits (EPDVs) are widely advocated by professional and academic stakeholders. The aim of this comprehensive review was to critically review and summarize available evidence regarding the effectiveness of EPDVs in improving children's oral health outcomes. Materials and methods: A systematic literature search of the PubMed and Embase electronic databases was undertaken to identify peer-reviewed publications investigating the effectiveness of EPDVs on oral health outcomes, including clinical, behavioral, and cost end points up to October 30, 2013. Outcomes of the identified studies were abstracted and summarized independently by two investigators. Results: Four manuscripts met the inclusion criteria and were included in the review. All studies were conducted in the US and employed a retrospective cohort study design using public insurance-claims data, whereas one study matched claims files with kindergarten state dental surveillance data. That study found no benefit of EPDVs in future clinically determined dental caries levels in kindergarten. The other three studies found mixed support for an association of EPDVs with subsequent more preventive and fewer nonpreventive visits and lower nonpreventive service-related expenditures. Selection bias and a problem-driven dental care-seeking pattern were frequently articulated themes in the reviewed studies. Conclusion: The currently available evidence base supporting the effectiveness of EPDVs and the year 1 first dental visit recommendation is weak, and more research is warranted. The benefits of EPDVs before the age of 3 years are evident among children at high risk or with existing dental disease. However, EPDVs may be associated with reduced restorative dental care visits and related expenditures during the first years of life. Keywords: prevention, children, dental visits, anticipatory guidance, dental home, caries

Adenoid cystic carcinoma (AdCC) is a slow-growing salivary gland malignancy that relapses frequently. AdCCs of the submandibular gland exhibit unique differences in prognosis and treatment response to adjuvant radiotherapy compared to other sites, yet the role of tumor anatomic subsite on gene expression and tumor immune microenvironment (TIME) composition remains unclear. We used 87 samples, including 48 samples (27 AdCC and 21 normal salivary gland tissue samples) from 4 publicly available AdCC RNA sequencing datasets, a validation set of 33 minor gland AdCCs, and 39 samples from an in-house cohort (30 AdCC and 9 normal salivary gland samples). RNA sequencing data were used for single sample gene set enrichment analysis and TIME deconvolution. Quantitative PCR and multiplex immunofluorescence were performed on the in-house cohort. Wilcoxon rank-sum, nonparametric equality-of-medians tests and linear regression models were used to evaluate tumor subsite differences. AdCCs of different anatomic subsites including parotid, submandibular, sublingual, and minor salivary glands differed with respect to expression of several key tumorigenic pathways. Among the three major salivary glands, the reactive oxygen species (ROS)/nuclear factor erythroid 2-related factor 2 (NRF2) pathway signature was significantly underexpressed in AdCC of submandibular compared to parotid and sublingual glands while this association was not observed among normal glands. Additionally, the NRF2 pathway, whose expression was associated with favorable overall survival, was overexpressed in AdCCs of parotid gland compared to minor and submandibular glands. The TIME deconvolution identified differences in CD4 + T cell populations between AdCC of major and minor glands and natural killer (NK) cells among AdCC of minor, submandibular, and parotid glands while plasma cells were enriched in normal submandibular glands compared to other normal gland controls. Our data reveal key molecular differences in AdCC of different anatomic subsites. The ROS and NRF2 pathways are underexpressed in submandibular and minor AdCCs compared to parotid gland AdCCs, and NRF2 pathway expression is associated with favorable overall survival. The CD4 + T, NK, and plasma cell populations also vary by tumor subsites, suggesting that the observed submandibular AdCC tumor-intrinsic pathway differences may be responsible for influencing the TIME composition and survival differences., (© 2024. The Author(s).)

Background: Fluoridation of public water systems is known as a safe and effective strategy for preventing dental caries based on evidence from non-randomized studies. Yet 110 million Americans do not have access to a fluoridated public water system and many others do not drink tap water. This article describes the study protocol for the first randomized controlled trial (RCT) of fluoridated water that assesses its potential dental caries preventive efficacy when delivered in bottles., Methods: waterBEST is a phase 2b proof-of-concept, randomized, quadruple-masked, placebo-controlled, parallel-group trial designed to estimate the potential efficacy of fluoridated versus non-fluoridated bottled water to prevent dental caries incidence in the first 4 years of life. Two hundred children living in eastern North Carolina, USA, and aged 2-6 months at screening are being allocated at random in a 1:1 ratio to receive fluoridated (0.7 mg/L F) or non-fluoridated bottled water sourced from two local public water systems. Throughout the 3.5-year intervention, study water is delivered monthly in 5-gallon bottles to each child's home with instructions to use it whenever the child consumes water as a beverage or in food preparation. Parents are interviewed quarterly to monitor children's water consumption and health. At annual visits, the presence of dental caries is evaluated with a dental screening examination. Clippings from fingernails and toenails are collected to quantify fluoride content as a biomarker of total fluoride intake. The primary endpoint is the number of primary tooth surfaces decayed, missing, or filled due to dental caries measured by the study dentist near the time of the child's fourth birthday. Tooth decay is assessed at the threshold of macroscopic enamel loss. For the primary aim, a least-squares, generalized linear model will estimate efficacy and its one-tailed, upper 80% confidence limit., Discussion: waterBEST is the first evaluation of a randomized intervention of fluoridated drinking water in bottles to prevent dental caries in the primary dentition. This innovative method of delivering fluoridated water has the potential to prevent early childhood caries in a large segment of the US population that currently does not benefit from fluoridated public water., Trial Registration: ClinicalTrials.gov NCT04893681. Registered on March 2022. Last update posted on 10 October 2023. https://clinicaltrials.gov/study/NCT04893681?cond=Dental%20Caries%20in%20Children&term=fluoride&locStr=North%20Carolina,%20USA&country=United%20States&state=North%20Carolina&distance=50&rank=1., (© 2024. The Author(s).)

Biological processes underlying health and disease are inherently dynamic and are best understood when characterized in a time-informed manner. In this comprehensive review, we discuss challenges inherent in time-series microbiome data analyses and compare available approaches and methods to overcome them. Appropriate handling of longitudinal microbiome data can shed light on important roles, functions, patterns, and potential interactions between large numbers of microbial taxa or genes in the context of health, disease, or interventions. We present a comprehensive review and comparison of existing microbiome time-series analysis methods, for both preprocessing and downstream analyses, including differential analysis, clustering, network inference, and trait classification. We posit that the careful selection and appropriate utilization of computational tools for longitudinal microbiome analyses can help advance our understanding of the dynamic host-microbiome relationships that underlie health-maintaining homeostases, progressions to disease-promoting dysbioses, as well as phases of physiologic development like those encountered in childhood.

Understanding the function of the human microbiome is important but the development of statistical methods specifically for the microbial gene expression (i.e. metatranscriptomics) is in its infancy. Many currently employed differential expression analysis methods have been designed for different data types and have not been evaluated in metatranscriptomics settings. To address this gap, we undertook a comprehensive evaluation and benchmarking of 10 differential analysis methods for metatranscriptomics data. We used a combination of real and simulated data to evaluate performance (i.e. type I error, false discovery rate and sensitivity) of the following methods: log-normal (LN), logistic-beta (LB), MAST, DESeq2, metagenomeSeq, ANCOM-BC, LEfSe, ALDEx2, Kruskal-Wallis and two-part Kruskal-Wallis. The simulation was informed by supragingival biofilm microbiome data from 300 preschool-age children enrolled in a study of childhood dental disease (early childhood caries, ECC), whereas validations were sought in two additional datasets from the ECC study and an inflammatory bowel disease study. The LB test showed the highest sensitivity in both small and large samples and reasonably controlled type I error. Contrarily, MAST was hampered by inflated type I error. Upon application of the LN and LB tests in the ECC study, we found that genes C8PHV7 and C8PEV7, harbored by the lactate-producing Campylobacter gracilis, had the strongest association with childhood dental disease. This comprehensive model evaluation offers practical guidance for selection of appropriate methods for rigorous analyses of differential expression in metatranscriptomics. Selection of an optimal method increases the possibility of detecting true signals while minimizing the chance of claiming false ones., (© The Author(s) 2023. Published by Oxford University Press.)

Streptococcus mutans has been implicated as the primary pathogen in childhood caries (tooth decay). While the role of polymicrobial communities is appreciated, it remains unclear whether other microorganisms are active contributors or interact with pathogens. Here, we integrate multi-omics of supragingival biofilm (dental plaque) from 416 preschool-age children (208 males and 208 females) in a discovery-validation pipeline to identify disease-relevant inter-species interactions. Sixteen taxa associate with childhood caries in metagenomics-metatranscriptomics analyses. Using multiscale/computational imaging and virulence assays, we examine biofilm formation dynamics, spatial arrangement, and metabolic activity of Selenomonas sputigena, Prevotella salivae and Leptotrichia wadei, either individually or with S. mutans. We show that S. sputigena, a flagellated anaerobe with previously unknown role in supragingival biofilm, becomes trapped in streptococcal exoglucans, loses motility but actively proliferates to build a honeycomb-like multicellular-superstructure encapsulating S. mutans, enhancing acidogenesis. Rodent model experiments reveal an unrecognized ability of S. sputigena to colonize supragingival tooth surfaces. While incapable of causing caries on its own, when co-infected with S. mutans, S. sputigena causes extensive tooth enamel lesions and exacerbates disease severity in vivo. In summary, we discover a pathobiont cooperating with a known pathogen to build a unique spatial structure and heighten biofilm virulence in a prevalent human disease., (© 2023. The Author(s).)

Integration of multi-omics data is a challenging but necessary step to advance our understanding of the biology underlying human health and disease processes. To date, investigations seeking to integrate multi-omics (e.g., microbiome and metabolome) employ simple correlation-based network analyses; however, these methods are not always well-suited for microbiome analyses because they do not accommodate the excess zeros typically present in these data. In this paper, we introduce a bivariate zero-inflated negative binomial (BZINB) model-based network and module analysis method that addresses this limitation and improves microbiome-metabolome correlation-based model fitting by accommodating excess zeros. We use real and simulated data based on a multi-omics study of childhood oral health (ZOE 2.0; investigating early childhood dental caries, ECC) and find that the accuracy of the BZINB model-based correlation method is superior compared to Spearman's rank and Pearson correlations in terms of approximating the underlying relationships between microbial taxa and metabolites. The new method, BZINB-iMMPath, facilitates the construction of metabolite-species and species-species correlation networks using BZINB and identifies modules of (i.e., correlated) species by combining BZINB and similarity-based clustering. Perturbations in correlation networks and modules can be efficiently tested between groups (i.e., healthy and diseased study participants). Upon application of the new method in the ZOE 2.0 study microbiome-metabolome data, we identify that several biologically-relevant correlations of ECC-associated microbial taxa with carbohydrate metabolites differ between healthy and dental caries-affected participants. In sum, we find that the BZINB model is a useful alternative to Spearman or Pearson correlations for estimating the underlying correlation of zero-inflated bivariate count data and thus is suitable for integrative analyses of multi-omics data such as those encountered in microbiome and metabolome studies.

In this cross-sectional, community-based study among a multi-ethnic sample of preschool-age children in North Carolina, United States, we sought to quantify the association between guardians' self-reported oral health and their children's oral health and determine whether race/ethnicity and education level modify these associations. We used questionnaire (n = 7852) responses about caregivers' and their children's oral health and clinical examination-derived (n = 6243) early childhood caries (ECC) status defined at the ICDAS ≥ 3 caries lesion detection threshold. We used multi-level mixed-effects generalized linear models to examine the associations between the guardians' reported oral health and their children's reported and clinically determined oral health among the entire sample and within strata of race/ethnicity, guardians' education, and children's dental home. The guardians' and their children's reported fair/poor oral health (FPOH) were 32% and 15%, respectively, whereas 54% of the children had ECC and 36% had unrestored disease. The guardians' FPOH was strongly associated with their children's FPOH (average marginal effect (AME) = +19 percentage points (p.p.); 95% CI = 17-21), and this association was most pronounced among Hispanics, lower-educated guardians, and children without a dental home. Similar patterns, but smaller-in-magnitude associations, were found for the guardians' FPOH and their children's clinically determined ECC (AME = +9 p.p.; 95% CI = 6-12) and unrestored disease (AME = +7 p.p.; 95% CI = 4-9). The study's findings support a strong association between guardians' and their children's reported and clinically determined oral health and implicate ethnicity, education, and having a dental home as factors possibly modifying the magnitude of these associations.

Background: HIV infection and its management confer a substantial health burden to affected individuals and have been associated with increased risk of oral and dental diseases. In this study, we sought to quantify HIV-associated differences in the prevalence and severity of dental caries in the primary and permanent dentition of 4-11-year-old Nigerian Children., Methods: We used clinical, laboratory, demographic, and behavioral data obtained from an ongoing cohort study of age-matched HIV-infected (HI, n = 181), HIV-exposed-but-uninfected (HEU, n = 177), and HIV-unexposed-and-uninfected (HUU, n = 186) children. Measures of dental caries experience (i.e., prevalence and severity) were based on dmft/DMFT indices recorded by trained and calibrated clinical examiners. Differences in primary and permanent dentition caries experience between HI, HEU, and HUU were estimated using multivariable logistic and negative binomial regression modeling., Results: HI children had significantly higher caries experience (33%) compared to HEU (15%) and HUU (22%) children. This difference persisted in fully adjusted analyses [odds ratio (OR) = 1.6; 95% confidence interval (CI) = 1.0-2.6], was most pronounced in the permanent dentition (OR = 3.4; 95% CI = 1.2-9.5), and mirrored differences in caries severity. While molars were predominantly affected in both primary and permanent dentitions, caries lesion patterns differed between dentitions. Caries severity was significantly associated with hypoplastic primary teeth, gingival inflammation, and lower CD4 counts., Conclusions: We found that the higher prevalence and severity of dental caries among HI children was driven by increased burden of permanent dentition caries compared to their uninfected counterparts. The dentition-specific associations identified in this study highlight the need to design and implement age-specific caries prevention strategies. These may include intensified oral hygiene regimens aimed at mitigating the cariogenic impact of hyposalivation among HI children. Similarly, the long-lasting impacts of developmental defects of the enamel in the primary and permanent dentitions must not be ignored., (© 2022. The Author(s).)

Dental anxiety affects up to 21% of children and 80% of adults and is associated with lifelong dental avoidance. Animal assisted activity (AAA) is widely used to reduce anxiety and pain in medical settings and has promise in dentistry. The primary objective of this study was to evaluate caregiver and patient perceptions of canine AAA in orthodontics. A cross-sectional survey consisting of pre-tested and validated questions was conducted ( n = 800) including orthodontic patients ( n = 352 minors, n = 204 adults) and parents/caregivers ( n = 244) attending university orthodontic clinics. In this study, AAA and dog therapy were not used or tested for dental anxiety management. More than a third of orthodontic patients (37%) had moderate or greater anxiety related to care. Participants believed that therapy animals would make dental experiences more enjoyable (75%) and reduce anxiety (82%). There was little to no concern expressed regarding cleanliness (83%), allergies (81%), and safety (89%) with a therapy animal in dental settings. Almost half of the participants would preferentially select an orthodontic office offering AAA. In light of the COVID-19 pandemic, we assessed whether perceptions of AAA changed before and after the shutdown of dental offices, with no significant differences. Across patients and caregivers, the responses support the use of AAA in orthodontic settings with minimal concerns.

Background: Parents'/guardians' perceptions of their children's oral health are useful proxies of their clinically determined caries status and are known to influence dental care-seeking behavior. In this study, we sought to examine (1) the social and behavioral correlates of fair/poor child oral health reported by guardians and (2) quantify the association of these reports with the prevalence of early childhood caries (ECC), unrestored caries lesions and toothaches. Methods: We used guardian-reported child oral health information (dichotomized as fair/poor vs. excellent/very good/good) obtained via a parent questionnaire that was completed for n = 7,965 participants (mean age = 52 months; range = 36-71 months) of a community-based, cross-sectional epidemiologic study of early childhood oral health in North Carolina between 2016 and 2019. Social, demographic, oral health-related behavioral data, and reports on children's history of toothaches (excluding teething) were collected in the same questionnaire. Unrestored ECC (i.e., caries lesions) was measured via clinical examinations in a subset of n = 6,328 children and was defined as the presence of one or more tooth surfaces with an ICDAS ≥ 3 caries lesion. Analyses relied on descriptive and bivariate methods, and multivariate modeling with average marginal effect (A.M.E.) estimation accounting for the clustered nature of the data. Estimates of association [prevalence ratios (PR) and adjusted marginal effects (AME) with 95% confidence intervals (CI)] were obtained via multilevel generalized linear models using Stata's svy function and accounting for the clustered nature of the data. Results: The prevalence of fair/poor oral health in this sample was 15%-it increased monotonically with children's age, was inversely associated with parents' educational attainment, and was higher among Hispanics (21%) and African Americans (15%) compared to non-Hispanic whites (11%). Brushing less than twice a day, not having a dental home, and frequently consuming sugar-containing snacks and beverages were significantly associated with worse reports ( P < 0.0005). Children with fair/poor reported oral health were twice as likely to have unrestored caries lesions [prevalence ratio (PR) = 2.0; 95% confidence interval (CI) = 1.8-2.1] and 3.5 times as likely to have experienced toothaches [PR = 3.5; 95% CI = 3.1-3.9] compared to those with better reported oral health. Conclusions: Guardian reports of their children's oral health are valuable indicators of clinical and public health-important child oral health status. Those with fair/poor guardian-reported child oral health have distinguishing characteristics spanning socio-demographics, oral-health related practices, diet, and presence of a dental home., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Imes, Ginnis, Shrestha, Simancas-Pallares and Divaris.)

Microbiome data are becoming increasingly available in large health cohorts, yet metabolomics data are still scant. While many studies generate microbiome data, they lack matched metabolomics data or have considerable missing proportions of metabolites. Since metabolomics is key to understanding microbial and general biological activities, the possibility of imputing individual metabolites or inferring metabolomics pathways from microbial taxonomy or metagenomics is intriguing. Importantly, current metabolomics profiling methods such as the HMP Unified Metabolic Analysis Network (HUMAnN) have unknown accuracy and are limited in their ability to predict individual metabolites. To address this gap, we developed a novel metabolite prediction method, and we present its application and evaluation in an oral microbiome study. The new method for predicting metabolites using microbiome data (ENVIM) is based on the elastic net model (ENM). ENVIM introduces an extra step to ENM to consider variable importance (VI) scores, and thus, achieves better prediction power. We investigate the metabolite prediction performance of ENVIM using metagenomic and metatranscriptomic data in a supragingival biofilm multi-omics dataset of 289 children ages 3-5 who were participants of a community-based study of early childhood oral health (ZOE 2.0) in North Carolina, United States. We further validate ENVIM in two additional publicly available multi-omics datasets generated from studies of gut health. We select gene family sets based on variable importance scores and modify the existing ENM strategy used in the MelonnPan prediction software to accommodate the unique features of microbiome and metabolome data. We evaluate metagenomic and metatranscriptomic predictors and compare the prediction performance of ENVIM to the standard ENM employed in MelonnPan. The newly developed ENVIM method showed superior metabolite predictive accuracy than MelonnPan when trained with metatranscriptomics data only, metagenomics data only, or both. Better metabolite prediction is achieved in the gut microbiome compared with the oral microbiome setting. We report the best-predictable compounds in all these three datasets from two different body sites. For example, the metabolites trehalose, maltose, stachyose, and ribose are all well predicted by the supragingival microbiome., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Xie, Cho, Lin, Pillai, Heimisdottir, Bandyopadhyay, Zou, Roach, Divaris and Wu.)

The importance of visual aids in communicating clinical examination findings or proposed treatments in dentistry cannot be overstated. Similarly, communicating dental research results with tooth surface-level precision is impractical without visual representations. Here, we present the development, deployment, and two real-life applications of a web-based data visualization informatics pipeline that converts tooth surface-level information to colorized, three-dimensional renderings. The core of the informatics pipeline focuses on texture (UV) mapping of a pre-existing model of the human primary dentition. The 88 individually segmented tooth surfaces receive independent inputs that are represented in colors and textures according to customizable user specifications. The web implementation SculptorHD, deployed on the Google Cloud Platform, can accommodate manually entered or spreadsheet-formatted tooth surface data and allows the customization of color palettes and thresholds, as well as surface textures (e.g., condition-free, caries lesions, stainless steel, or ceramic crowns). Its current implementation enabled the visualization and interpretation of clinical early childhood caries (ECC) subtypes using latent class analysis-derived caries experience summary data. As a demonstration of its potential clinical utility, the tool was also used to simulate the restorative treatment presentation of a severe ECC case, including the use of stainless steel and ceramic crowns. We expect that this publicly available web-based tool can aid clinicians and investigators deliver precise, visual presentations of dental conditions and proposed treatments. The creation of rapidly adjustable lifelike dental models, integrated to existing electronic health records and responsive to new clinical findings or planned for future work, is likely to boost two-way communication between clinicians and their patients.

The oral mucosa remains an understudied barrier tissue. This is a site of rich exposure to antigens and commensals, and a tissue susceptible to one of the most prevalent human inflammatory diseases, periodontitis. To aid in understanding tissue-specific pathophysiology, we compile a single-cell transcriptome atlas of human oral mucosa in healthy individuals and patients with periodontitis. We uncover the complex cellular landscape of oral mucosal tissues and identify epithelial and stromal cell populations with inflammatory signatures that promote antimicrobial defenses and neutrophil recruitment. Our findings link exaggerated stromal cell responsiveness with enhanced neutrophil and leukocyte infiltration in periodontitis. Our work provides a resource characterizing the role of tissue stroma in regulating mucosal tissue homeostasis and disease pathogenesis., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aim : This in vivo experimental study investigated bacterial microbiome and metabolome longitudinal changes associated with enamel caries lesion progression and arrest. Methods : We induced natural caries activity in three caries-free volunteers prior to four premolar extractions for orthodontic reasons. The experimental model included placement of a modified orthodontic band on smooth surfaces and a mesh on occlusal surfaces. We applied the caries-inducing protocol for 4- and 6-weeks, and subsequently promoted caries lesion arrest via a 2-week toothbrushing period. Lesions were verified clinically and quantitated via micro-CT enamel density measurements. The biofilm microbial composition was determined via 16S rRNA gene Illumina sequencing and NMR spectrometry was used for metabolomics. Results : Biofilm maturation and caries lesion progression were characterized by an increase in Gram-negative anaerobes, including Veillonella and Prevotella. Streptococcus was associated caries lesion progression, while a more equal distribution of Streptococcus, Bifidobacterium, Atopobium, Prevotella, Veillonella, and Saccharibacteria (TM7) characterized arrest. Lactate, acetate, pyruvate, alanine, valine, and sugars were more abundant in mature biofilms compared to newly formed biofilms. Conclusions : These longitudinal bacterial microbiome and metabolome results provide novel mechanistic insights into the role of the biofilm in caries progression and arrest and offer promising candidate biomarkers for validation in future studies., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Adenoid cystic carcinoma (ACC) is a rare salivary gland tumor, displaying aggressive behavior with frequent recurrence and metastasis. Little information exists regarding the impact of clinicopathological parameters and adjuvant radiotherapy (aRT) on ACC disease specific (DSS) and overall survival (OS). We extracted demographic, treatment, and survival information of 1439 patients with major or minor intraoral salivary gland ACC from the Surveillance, Epidemiology, and End Results (SEER) database. The associations between tumor characteristics and aRT with OS and DSS were estimated using hazard ratios (HR) and 95% confidence intervals (CI). Submandibular gland ACCs had the worst prognosis (adjusted DSS HR = 1.48; 95% CI = 0.99-2.20, compared to parotid), and this difference was more pronounced among patients with advanced-stage tumors (adjusted DSS HR = 1.93; 95% CI = 1.13-3.30). aRT was associated with increased overall survival only among stage III submandibular ACC patients (HR = 0.64; 95% CI = 0.42-0.98) and had no benefit in any other group. In conclusion, submandibular gland ACC carries a worse prognosis than other gland subsites and may benefit from aRT. The different outcomes between submandibular gland and other major or minor gland ACCs warrant further mechanistic investigation.

Early childhood caries (ECC) is an aggressive form of dental caries occurring in the first five years of life. Despite its prevalence and consequences, little progress has been made in its prevention and even less is known about individuals' susceptibility or genomic risk factors. The genome-wide association study (GWAS) of ECC ("ZOE 2.0") is a community-based, multi-ethnic, cross-sectional, genetic epidemiologic study seeking to address this knowledge gap. This paper describes the study's design, the cohort's demographic profile, data domains, and key oral health outcomes. Between 2016 and 2019, the study enrolled 8059 3-5-year-old children attending public preschools in North Carolina, United States. Participants resided in 86 of the state's 100 counties and racial/ethnic minorities predominated-for example, 48% ( n = 3872) were African American, 22% white, and 20% ( n = 1611) were Hispanic/Latino. Seventy-nine percent ( n = 6404) of participants underwent clinical dental examinations yielding ECC outcome measures-ECC (defined at the established caries lesion threshold) prevalence was 54% and the mean number of decayed, missing, filled surfaces due to caries was eight. Nearly all (98%) examined children provided sufficient DNA from saliva for genotyping. The cohort's community-based nature and rich data offer excellent opportunities for addressing important clinical, epidemiologic, and biological questions in early childhood.

Genome-wide association studies have revolutionized our understanding of the genetic underpinnings of cardiometabolic disease. Yet, the inadequate representation of individuals of diverse ancestral backgrounds in these studies may undercut their ultimate potential for both public health and precision medicine. The goal of this review is to describe the imperativeness of studying the populations who are most affected by cardiometabolic disease, to the aim of better understanding the genetic underpinnings of the disease. We support this premise by describing the current variation in the global burden of cardiometabolic disease and emphasize the importance of building a globally and ancestrally representative genetics evidence base for the identification of population-specific variants, fine-mapping, and polygenic risk score estimation. We discuss the important ethical, legal, and social implications of increasing ancestral diversity in genetic studies of cardiometabolic disease and the challenges that arise from the (1) lack of diversity in current reference populations and available analytic samples and the (2) unequal generation of health-associated genomic data and their prediction accuracies. Despite these challenges, we conclude that additional, unprecedented opportunities lie ahead for public health genomics and the realization of precision medicine, provided that the gap in diversity can be systematically addressed. Achieving this goal will require concerted efforts by social, academic, professional and regulatory stakeholders and communities, and these efforts must be based on principles of equity and social justice.

Background: Oral health literacy is an important construct for both clinical and public health outcomes research. The need to quantify and test OHL has led to the development of measurement instruments and has generated a substantial body of recent literature. A commonly used OHL instrument is REALD-30, a word recognition scale that has been adapted for use in several languages. The objective of this study was the development and testing of the Greek language oral health literacy measurement instrument (GROHL)., Methods: Data from 282 adult patients of two private dental clinics in Athens, Greece were collected via in-person interviews. Forty-four words were initially considered and tested for inclusion. Item response theory analysis (IRT) and 2-parameter logistic models assessing difficulty and discriminatory ability were used to identify an optimal scale composition. Internal consistency was examined using Cronbach's alpha and test-retest reliability was measured using intraclass correlation coefficient (ICC) in a subset of 20 participants over a two-week period. Convergent validity was tested against functional health literacy screening (HLS) items, dental knowledge (DK), oral health behaviors (OHBs), oral health-related quality of life (OHRQoL; OHIP-14 index), as well as self-reported oral and general health status., Results: From an initial item pool of 44 items that were carried forward to IRT, 12 were excluded due to no or little variance, 10 were excluded due to low item-test correlation, and 2 due to insignificant contribution to the scale, i.e., difficulty parameter estimate with p > 0.05. The twenty remaining items composed the final index which showed favorable internal consistency (alpha = 0.80) and test-retest reliability (ICC = 0.95). The summary score distribution did not depart from normality (p = 0.32; mean = 11.5; median = 12; range = 1-20). GROHL scores were positively correlated with favorable oral hygiene behaviors and dental attendance, as well as HLS, DK and education level., Conclusion: The GROHL demonstrated good psychometric properties and can be used for outcomes research in clinical and public health settings.

Dental caries and periodontitis account for a vast burden of morbidity and healthcare spending, yet their genetic basis remains largely uncharacterized. Here, we identify self-reported dental disease proxies which have similar underlying genetic contributions to clinical disease measures and then combine these in a genome-wide association study meta-analysis, identifying 47 novel and conditionally-independent risk loci for dental caries. We show that the heritability of dental caries is enriched for conserved genomic regions and partially overlapping with a range of complex traits including smoking, education, personality traits and metabolic measures. Using cardio-metabolic traits as an example in Mendelian randomization analysis, we estimate causal relationships and provide evidence suggesting that the processes contributing to dental caries may have undesirable downstream effects on health.

This study examined the prevalence, socio-demographic correlates, and clinical predictors of traumatic dental injuries (TDIs) in the primary dentition among a community-based sample of preschool-age children. The sample comprised 1,546 preschool-age children (mean age 49 [range: 24-71] months) in North Carolina public preschools, enrolled in a population-based investigation among young children and their parents in North Carolina. Information on socio-demographic, extraoral, and intraoral characteristics was collected and analyzed with bivariate and multivariate methods, including logistic regression modeling and marginal effects estimation. The prevalence of dental trauma was 47% and 8% of TDI cases were "severe" (pulp exposure, tooth displacement, discolored or necrotic tooth, or tooth loss). In bivariate analyses, overjet and lip incompetence were significantly associated with TDI. Overjet remained positively associated with severe trauma in multivariate analysis, OR  = 1.4, 95% confidence interval (CI) [1.2, 1.6], corresponding to an absolute 1.3%, 95% CI [0.7, 1.8], increase in the likelihood of severe trauma, per millimeter of overjet. Children with increased overjet (>3 mm) were 3.8, 95% CI [2.0, 7.4], times as likely to have experienced severe TDI compared with those with ≤3 mm. Overjet is a strong risk factor for TDIs in the primary dentition. Incorporating and operationalizing this information may help TDI prevention and related anticipatory guidance for families of preschool-age children., Competing Interests: None declared.