Publications by authors named "Kimon Divaris"

86 Publications

A Web-Based Rendering Application for Communicating Dental Conditions.

Healthcare (Basel) 2021 Jul 29;9(8). Epub 2021 Jul 29.

Division of Pediatric and Public Health, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7450, USA.

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.
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http://dx.doi.org/10.3390/healthcare9080960DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393219PMC
July 2021

The bacterial microbiome and metabolome in caries progression and arrest.

J Oral Microbiol 2021 Jun 16;13(1):1886748. Epub 2021 Jun 16.

Division of Diagnostic Sciences, Adams School of Dentistry, University of North Carolina, Chapel Hill, USA.

: This experimental study investigated bacterial microbiome and metabolome longitudinal changes associated with enamel caries lesion progression and arrest. : 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. : Biofilm maturation and caries lesion progression were characterized by an increase in Gram-negative anaerobes, including and was associated caries lesion progression, while a more equal distribution of characterized arrest. Lactate, acetate, pyruvate, alanine, valine, and sugars were more abundant in mature biofilms compared to newly formed biofilms. : 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.
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http://dx.doi.org/10.1080/20002297.2021.1886748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211139PMC
June 2021

Child Nutrition Patterns Are Associated with Primary Dentition Dental Caries.

Pediatr Dent 2021 May;43(3):205-210

Dr. Divaris is a professor, Division of Pediatric and Public Health, Adams School of Dentistry, University of North Carolina-Chapel Hill, Chapel Hill, N.C., USA.

Diet is a well-established, modifiable factor influencing dental caries risk. However, evidence regarding its association with distinct clinical patterns of dental caries is lacking. The purpose of this study was to identify the association of child nutrition patterns with two distinct clinical presentations (subtypes) of childhood dental caries. The study sample comprised 120 children who were patients of a private pediatric dental practice: 30 ages one to three years (mean equals 2.2 years) with anterior carious lesions; 30 ages four to 12 years (mean equals six years) with posterior-only carious lesions; and 60 age-, gender-, and payment method-matched caries-free controls. Participants underwent dental examinations, and their guardians completed a 17-item nutrition frequency questionnaire. A latent profile analysis was used to define distinct dietary patterns and, subsequently, test their association with dental caries subtypes. Dietary patterns were differentiated by consumption frequencies of water and cariogenic solid, soft, and liquid food items; a diet cluster characterized by frequent consumption of fruit juice, cereal bars, and daily vitamins was more common (P<0.05) among one- to three-year-old patients with anterior carious lesions compared to matched caries-free controls. These results affirm the key role of dietary patterns in childhood oral health and demonstrate the influence of fermentable carbohydrates on specific clinical subtypes of caries.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243840PMC
May 2021

An Automated Machine Learning Classifier for Early Childhood Caries.

Pediatr Dent 2021 May;43(3):191-197

Dr. Divaris is a professor, Division of Pediatric and Public Health, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, N.C., USA.

The purpose of the study was to develop and evaluate an automated machine learning algorithm (AutoML) for children's classification according to early childhood caries (ECC) status. Clinical, demographic, behavioral, and parent-reported oral health status information for a sample of 6,404 three- to five-year-old children (mean age equals 54 months) participating in an epidemiologic study of early childhood oral health in North Carolina was used. ECC prevalence (decayed, missing, and filled primary teeth surfaces [dmfs] score greater than zero, using an International Caries Detection and Assessment System score greater than or equal to three caries lesion detection threshold) was 54 percent. Ten sets of ECC predictors were evaluated for ECC classification accuracy (i.e., area under the ROC curve [AUC], sensitivity [Se], and positive predictive value [PPV]) using an AutoML deployment on Google Cloud, followed by internal validation and external replication. A parsimonious model including two terms (i.e., children's age and parent-reported child oral health status: excellent/very good/good/fair/poor) had the highest AUC (0.74), Se (0.67), and PPV (0.64) scores and similar performance using an external National Health and Nutrition Examination Survey (NHANES) dataset (AUC equals 0.80, Se equals 0.73, PPV equals 0.49). Contrarily, a comprehensive model with 12 variables covering demographics (e.g., race/ethnicity, parental education), oral health behaviors, fluoride exposure, and dental home had worse performance (AUC equals 0.66, Se equals 0.54, PPV equals 0.61). Parsimonious automated machine learning early childhood caries classifiers, including single-item self-reports, can be valuable for ECC screening. The classifier can accommodate biological information that can help improve its performance in the future.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278225PMC
May 2021

Human oral mucosa cell atlas reveals a stromal-neutrophil axis regulating tissue immunity.

Cell 2021 Jul 14;184(15):4090-4104.e15. Epub 2021 Jun 14.

Oral Immunity and Inflammation Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address:

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.
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http://dx.doi.org/10.1016/j.cell.2021.05.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8359928PMC
July 2021

Children's oral health-related behaviours and early childhood caries: A latent class analysis.

Community Dent Oral Epidemiol 2021 May 13. Epub 2021 May 13.

Division of Pediatric and Public Health, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Objective: In this cross-sectional study in a large community-based sample of preschool-age children, we sought to identify distinct clusters of modifiable early childhood oral health-related behaviours (OHBs) and quantify their association with clinical and parent-reported measures of early childhood oral health.

Methods: We relied upon a questionnaire (n = 8033; 11% in Spanish) and clinical oral health data (n = 6404; early childhood caries [ECC] prevalence = 54%] collected in the context of an epidemiologic study of early childhood oral health among 3- to 5-year-old children in North Carolina. Latent class analysis was used to identify clusters of modifiable OHBs based on parents' responses to 6 questionnaire items pertaining to their children's oral hygiene, diet and dental home. The optimal number of clusters was determined based on measures of model fit and interpretability. We examined associations of OHB clusters with clinical and parent-reported child oral health status (ie, ECC prevalence, severity and proportion with untreated disease) using bivariate association tests and multivariable regression modelling with marginal effects estimation accounting for clustered data. We used Mplus v.8.6 (Muthén & Muthén, Los Angeles, CA, USA) and Stata v.16.1 (StataCorp, College Station, TX, USA) for data analyses.

Results: We identified 2 OHB clusters, a favourable (74%) and an unfavourable (26%) one. Children in the favourable OHB cluster had better oral hygiene practices (ie, tooth brushing frequency and fluoridated toothpaste use), lower consumption frequency of sugar-containing snacks and beverages, less frequent reports of night-time bottle-feeding history and a higher likelihood of a dental home. Children in the unfavourable cluster had significantly higher ECC prevalence (57% vs 53%), caries burden (mean dmfs = 9.3 vs 7.6), untreated disease (43% vs 33%) and worse parent-reported oral health status than the favourable cluster.

Conclusions: Our findings demonstrate the importance and utility of clustering common, modifiable ECC risk factors in population studies - health promotion efforts may centre on groups of people rather than individual behavioural risk factors.
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http://dx.doi.org/10.1111/cdoe.12645DOI Listing
May 2021

Double-Blind, Randomized Clinical Trial Comparing One Percent Buffered Versus Two Percent Unbuffered Lidocaine Injections in Children.

Pediatr Dent 2021 Mar;43(2):88-94

Dr. Divaris is a professor, Division of Pediatric and Public Health, Adams School of Dentistry, all at the University of North Carolina at Chapel Hill, Chapel Hill, N.C., USA.

Buffered local anesthetics offer an alternative to conventional, unbuffered anesthetic formulations; however, evidence about their use in children is scant. The purpose of this study was to determine the anesthetic and physiologic differences associated with the use of buffered one percent and unbuffered two percent lidocaine (both with 1:100,000 epinephrine) in children. In this randomized, double-blinded, crossover study, 25 children ages 10 to 12 years old received two inferior alveolar never blocks, at least one week apart, randomized to alternating sequences of two drug formulations: (1) formula A-three mL buffered one percent lidocaine (i.e., including 0.3 mL of 8.4 percent sodium bicarbonate); or (2) formula B-three mL unbuffered two percent lidocaine. Primary outcomes were mean blood lidocaine levels (15 minutes post-injection), timing of clinical signs onset, response to pain on injection, and duration of anesthesia. Analyses relied upon analysis of variance for crossover study designs and a P<0.05 statistical significance criterion. The buffered formulation resulted in significantly lower mean blood lidocaine levels compared to unbuffered-a 63 percent (P<0.05) weight-adjusted relative decrease. The authors found no important differences in pain upon injection, onset, and duration of anesthesia. The buffered local anesthetic formulation showed equal effectiveness with a double-concentration unbuffered formulation while resulting in lower mean blood lidocaine levels-an important gain for the prevention of anesthetic toxicity.
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March 2021

Impact of Tumor Site and Adjuvant Radiotherapy on Survival of Patients with Adenoid Cystic Carcinoma: A SEER Database Analysis.

Cancers (Basel) 2021 Feb 3;13(4). Epub 2021 Feb 3.

Division of Oral and Craniofacial Health Sciences, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7455, USA.

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.
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http://dx.doi.org/10.3390/cancers13040589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913220PMC
February 2021

Influences on dentists' adoption of nonsurgical caries management techniques: A qualitative study.

J Am Dent Assoc 2021 Jun 15;152(6):463-470. Epub 2021 Jan 15.

Background: Nonsurgical caries management techniques (NSCMT) offer a simple, conservative approach to treating caries. Despite evidence supporting and potential advantages of NSCMT, dentists can be reluctant to adopt these techniques. To better understand this phenomenon, the authors interviewed dentists who primarily treat children regarding their thoughts, attitudes, and adoption of 3 NSCMT.

Methods: The 3 NSCMT were fluoride varnish, silver diamine fluoride, and Hall stainless steel crowns. The authors interviewed dentists in North Carolina whose practices were restricted mostly to children. A nonprobabilistic maximum-variation design was used in the sampling. Using a semistructured interview guide, the authors recorded the interviews digitally and analyzed them thematically. The authors stratified the analysis according to years of practice, geographic location, and type of practice. Reporting was based on emerging and recurring themes and insightful quotes.

Results: Factors most likely to promote the adoption of NSCMT were related to clinical practice, family preference, patient safety, and provider philosophy. Barriers to adoption included previous practitioner negative experiences using the techniques, high-risk caries population, and perceived likelihood of negative outcomes. Characteristics of the practice environment, patient population, communication with families, and financial considerations were influential in the clinician's determination as to whether to use these techniques.

Conclusions: These findings provide valuable insight into practitioners' influences, motivations, and clinical decision making in the adoption and use of management and treatment approaches for carious lesions in the pediatric population.

Practice Implications: The primary factors and barriers identified in this study are possible targets for education and quality improvement programs aimed at increasing NSCMT use.
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http://dx.doi.org/10.1016/j.adaj.2020.10.001DOI Listing
June 2021

Cohort Profile: ZOE 2.0-A Community-Based Genetic Epidemiologic Study of Early Childhood Oral Health.

Int J Environ Res Public Health 2020 11 1;17(21). Epub 2020 Nov 1.

Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina-Chapel Hill, NC 27599-7400, USA.

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% ( = 3872) were African American, 22% white, and 20% ( = 1611) were Hispanic/Latino. Seventy-nine percent ( = 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.
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http://dx.doi.org/10.3390/ijerph17218056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7663650PMC
November 2020

Access to preventive care services and stage at diagnosis in head and neck cancer.

Head Neck 2020 10 3;42(10):2841-2851. Epub 2020 Jul 3.

Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

Background: Decreased access to preventive care services has been proposed as a mechanism for the association between low socioeconomic status (SES) and advanced stage at diagnosis in patients with head and neck squamous cell carcinoma (HNSCC).

Methods: Retrospective analysis of patients diagnosed with HNSCC in North Carolina between 2002 and 2006.

Results: A total of 1108 patients with HNSCC were included in the study. In the multivariable analysis, use of annual routine dental services (OR 0.7, 95% CI 0.5-0.9) and colonoscopy in the past 10 years (OR 0.7, 95% CI 0.5-0.9) were associated with lower odds of advanced T stage at diagnosis. Having no insurance (OR 1.8, 95% CI 1.1-2.9), an income <$20 000 (OR 1.6 95% CI 1.03-2.6), and >10 pack-years tobacco use (OR 1.5, 95% CI 1.04-2.2) were associated with advanced T stage at diagnosis.

Conclusion: Use of preventive care services and SES independently predict stage at diagnosis in HNSCC.
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http://dx.doi.org/10.1002/hed.26326DOI Listing
October 2020

Importance of Genetic Studies of Cardiometabolic Disease in Diverse Populations.

Circ Res 2020 06 4;126(12):1816-1840. Epub 2020 Jun 4.

Department of Epidemiology, Gillings School of Global Public Health (K.L.Y, H.M.H., C.A., S.-A.M.L., M.G., K.D., K.E.N.), University of North Carolina at Chapel Hill.

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.
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http://dx.doi.org/10.1161/CIRCRESAHA.120.315893DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7285892PMC
June 2020

Biologically informed stratification of periodontal disease holds the key to achieving precision oral health.

J Periodontol 2020 10 25;91 Suppl 1:S50-S55. Epub 2020 Jun 25.

Comprehensive Oral Health, Adams School of Dentistry, University of North Carolina, Chapel Hill, NC.

Medicine and dentistry need to treat the individual not the "average patient." This personalized or precision approach to health care involves correctly diagnosing and properly classifying people to effectively customize prevention, diagnosis, and treatment. This is not a trivial undertaking. Achieving precision health requires making sense of big data, both at the population level and at the molecular level. The latter can include genetic, epigenetic, transcriptomic, proteomic, metabolomic data, and microbiome data. This biological information can augment established clinical measurements and supplement data on socioeconomic status, lifestyle, behaviors, and environmental conditions. Here, the central thesis is that, with sufficient data and appropriate methods, it is possible to segregate symptom-based and phenotypically based categories of patients into clinically and biologically similar groups. These groups are likely to have different clinical trajectories and benefit from different treatments. Additionally, such groups are optimal for investigations seeking to unveil the genomic basis of periodontal disease susceptibility. Analysis of these complex data to produce actionable and replicable health and disease categories requires appropriately sophisticated bioinformatics approaches and thorough validation in diverse patient samples and populations. Successful research programs will need to consider both population-level and well-controlled deep phenotyping approaches. Biologically informed stratification of periodontal disease is both feasible and desirable. Ultimately, this approach can accelerate the development of precision health through improvements in research and clinical applications.
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http://dx.doi.org/10.1002/JPER.20-0096DOI Listing
October 2020

Trends and determinants of drinking water practices among North Carolina children.

J Public Health Dent 2020 09 3;80(3):250-253. Epub 2020 Apr 3.

Division of Pediatric and Public Health, Adams School of Dentistry, University of North Carolina, Chapel Hill, NC, USA.

Objectives: To identify trends and determinants of drinking water practices [bottled (BW) versus community water (CW) consumption] among families of pediatric patients presenting to an academic dental institution over 15 years.

Methods: Electronic health record data were obtained for all first-time routine-care patients ages 0-16 presenting to UNC-Chapel Hill's Pediatric Dentistry Clinics from 2002 to 2016, including families' primary drinking water source and patient demographics (e.g., age, gender, residence, insurance status). Data analyses included descriptive and bivariate methods and multivariable modeling using a P < 0.05 statistical significance criterion.

Results: BW consumption has increased over time, from 17 percent in 2004 to 42 percent in 2016 (n = 2,920; P < 0.05). Medicaid-enrolled children [prevalence ratio (PR) = 2.1; 95% confidence interval (CI) = 1.8-2.4] and residents of rural counties (PR = 1.3, 95% CI = 1.1-1.5) were significantly more likely to consume BW versus CW.

Conclusions: BW consumption among NC children has been increasing and is most prevalent among low-income families and in rural areas.
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http://dx.doi.org/10.1111/jphd.12366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541412PMC
September 2020

Drinking Water Practices Among Latino Families in North Carolina: A qualitative study.

J Dent Hyg 2020 Feb;94(1):14-20

The purpose of this study was to understand the beliefs, experiences and practices regarding drinking water among the North Carolina (NC) Latino community, and to gather information on what would make effective messages to promote fluoridated community water (CW) consumption among Latino families. Phone interviews were conducted with Latino stakeholders, consisting of parents of young children and key community informants (n=15). The interviews were audio-recorded, and transcripts were analyzed qualitatively using Atlas. ti.8 software. Major themes emerging from the interviews included: poor characteristics of CW misconceptions and lack of knowledge about CW fluoridation and safety, ingrained culture/upbringing that devalued CW consumption, and reasons for consuming CW. Participants suggested that effective efforts to promote fluoridated CW consumption among the NC Latino community should be implemented in a variety of formats and involve a collaborative approach between Spanish-speaking health professionals and community workers. Successful promotion of fluoridated CW consumption among NC Latino communities requires engagement of both health professionals and community stakeholders. Effective interventions aimed to promote fluoridated CW consumption need to be widespread, informative, persuasive, credible, culturally sensitive, and interactive.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325707PMC
February 2020

Development of a Greek Oral health literacy measurement instrument: GROHL.

BMC Oral Health 2020 01 15;20(1):14. Epub 2020 Jan 15.

Department of Community and Preventive Dentistry, School of Dentistry, National and Kapodistrian University of Athens, Athens, Greece.

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.
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http://dx.doi.org/10.1186/s12903-020-1000-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6964004PMC
January 2020

Genomics of periodontal disease and tooth morbidity.

Periodontol 2000 2020 02;82(1):143-156

Department of Pediatric Dentistry, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

In this review we critically summarize the evidence base and the progress to date regarding the genomic basis of periodontal disease and tooth morbidity (ie, dental caries and tooth loss), and discuss future applications and research directions in the context of precision oral health and care. Evidence for these oral/dental traits from genome-wide association studies first emerged less than a decade ago. Basic and translational research activities in this domain are now under way by multiple groups around the world. Key departure points in the oral health genomics discourse are: (a) some heritable variation exists for periodontal and dental diseases; (b) the environmental component (eg, social determinants of health and behavioral risk factors) has a major influence on the population distribution but probably interacts with factors of innate susceptibility at the person-level; (c) sizeable, multi-ethnic, well-characterized samples or cohorts with high-quality measures on oral health outcomes and genomics information are required to make decisive discoveries; (d) challenges remain in the measurement of oral health and disease, with current periodontitis and dental caries traits capturing only a part of the health-disease continuum, and are little or not informed by the underlying biology; (e) the substantial individual heterogeneity that exists in the clinical presentation and lifetime trajectory of oral disease can be identified and leveraged in a precision medicine framework or, if unappreciated, can hamper translational efforts. In this review we discuss how composite or biologically informed traits may offer improvements over clinically defined ones for the genomic interrogation of oral diseases. We demonstrate the utility of the results of genome-wide association studies for the development and testing of a genetic risk score for severe periodontitis. We conclude that exciting opportunities lie ahead for improvements in the oral health of individual patients and populations via advances in our understanding of the genomic basis of oral health and disease. The pace of new discoveries and their equitable translation to practice will largely depend on investments in the education and training of the oral health care workforce, basic and population research, and sustained collaborative efforts..
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http://dx.doi.org/10.1111/prd.12320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6972532PMC
February 2020

Advances in precision oral health.

Periodontol 2000 2020 02;82(1):268-285

Division of Comprehensive Oral Health, Adams School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.

The concept of precision dentistry as it relates to precision medicine is relatively new to the field of oral health. Precision dentistry is a contemporary, multifaceted, data-driven approach to oral health care that uses individual characteristics to stratify similar patients into phenotypic groups. The objective is to provide clinicians with the information that will allow them to improve treatment planning and a patient's response to treatment. Providers that use a precision oral health approach would move away from using an "average treatment" for all patients with a particular diagnosis and move toward more specific treatments for patients within each diagnostic subgroup. Precision dentistry requires a method or a model that places each individual in a subgroup where each member is the same as every other member in relation to the disease of interest. Precision dentistry is a paradigm shift that requires a new way of thinking about diagnostic categories. This approach uses patients' risk factor data (including, but not limited to, genetic, environmental, and health behavioral), rather than expert opinion or clinical presentation alone, to redefine traditional categories of health and disease. We review aspects of current efforts to allow precision dentistry to be realized and focus on one of the major innovations that may help precision dentistry to be practiced by periodontists, the World Workshop Model. Another approach is the Periodontal Profile Class system. These two approaches represent examples of supervised and unsupervised learning systems, respectively. This review compares and contrasts these two learning systems for their ability to classify patients into homogeneous disease and risk groups, as well as their feasibility at achieving the objective of enabling precision dentistry. We conclude that: (a) the World Workshop Model concept of stages and grades works as expected, in that periodontal status appears to be more serious in each successive stage. In addition, the seriousness and the complexity of the disease are greater as the grade increases within each stage. Stages and grades are important for precision dentistry because they consider the risk of future disease and the prognosis, and enable practitioners to use more signs, symptoms, and other associated factors when placing a patient in a diagnostic category; (b) the assignment of stages and grades using unsupervised learning systems is superior to using supervised learning systems for the prediction of 10-year tooth loss and 3-year attachment loss progression. In addition, the unsupervised learning approach (Periodontal Profile Class stages) results in stronger associations between the periodontal phenotypes and systemic diseases and conditions (prevalent diabetes, C-reactive protein, and incident stroke). This probably occurs because an unsupervised learning model produces more data-driven, mutually exclusive, homogeneous groups than a supervised learning model.
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http://dx.doi.org/10.1111/prd.12314DOI Listing
February 2020

Biologically Defined or Biologically Informed Traits Are More Heritable Than Clinically Defined Ones: The Case of Oral and Dental Phenotypes.

Adv Exp Med Biol 2019 ;1197:179-189

Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA.

The genetic basis of oral health has long been theorized, but little information exists on the heritable variance in common oral and dental disease traits explained by the human genome. We sought to add to the evidence base of heritability of oral and dental traits using high-density genotype data in a well-characterized community-based cohort of middle-age adults. We used genome-wide association (GWAS) data combined with clinical and biomarker information in the Dental Atherosclerosis Risk In Communities (ARIC) cohort. Genotypes comprised SNPs directly typed on the Affymetrix Genome-Wide Human SNP Array 6.0 chip with minor allele frequency of >5% (n = 656,292) or were imputed using HapMap II-CEU (n = 2,104,905). We investigated 30 traits including "global" [e.g., number of natural teeth (NT) and incident tooth loss], clinically defined (e.g., dental caries via the DMFS index, periodontitis via the CDC/AAP and WW17 classifications), and biologically informed (e.g., subgingival pathogen colonization and "complex" traits). Heritability (i.e., variance explained; h) was calculated using Visscher's Genome-wide Complex Trait Analysis (GCTA), using a random-effects mixed linear model and restricted maximum likelihood (REML) regression adjusting for ancestry (10 principal components), age, and sex. Heritability estimates were modest for clinical traits-NT = 0.11 (se = 0.07), severe chronic periodontitis (CDC/AAP) = 0.22 (se = 0.19), WW17 Stage 4 vs. 1/2 = 0.15 (se = 0.11). "High gingival index" and "high red complex colonization" had h > 0.50, while a periodontal complex trait defined by high IL-1β GCF expression and Aggregatibacter actinomycetemcomitans subgingival colonization had the highest h = 0.72 (se = 0.32). Our results indicate that all GWAS SNPs explain modest levels of the observed variance in clinical oral and dental measures. Subgingival bacterial colonization and complex phenotypes encompassing both bacterial colonization and local inflammatory response had the highest heritability, suggesting that these biologically informed traits capture aspects of the disease process and are promising targets for genomics investigations, according to the notion of precision oral health.
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http://dx.doi.org/10.1007/978-3-030-28524-1_13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328987PMC
November 2019

Dental Caries Risk Varies Among Subgroups of Children with Special Health Care Needs.

Pediatr Dent 2019 Sep;41(5):378-384

Dr. Divaris is an associate professor, Department of Pediatric Dentistry, at the Adams School of Dentistry, and an associate professor, Department of Epidemiology, at the Gillings School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, N.C., USA.

Currently, caries risk assessment tools consider all children with special health care needs in tandem. The purpose of this study was to test this assumption by examining caries risk among and within five distinct groups of children, most with special health care needs (CSHCN): (1) autism (ASD); (2) congenital heart disease (CHD); (3) cerebral palsy (CP); (4) Down syndrome (DS); and (5) a control (non-CSHCN) group. A retrospective longitudinal cohort of 150 patients (30 per group) from a private pediatric dental practice was assembled, and information on caries diagnoses and 21 postulated caries risk factors from clinical records was extracted. Bivariate tests and multivariable Poisson regression modeling were used to estimate the caries incidence rate (IR), ratio (IRR), and 95 percent confidence interval (CI). CSHCN had a higher caries burden and caries risk (IR equals 0.049 per person per year) compared to the control group (IR equals 0.033). Caries risk was nearly double among CHD (IRR equals 1.9 [95 percent CI equals 0.72 to 5.2] versus controls) compared to DS (IRR equals 1.04 [95 percent CI equals 0.38 to 2.9]). Visible cavities or fillings was the only significant risk factor, yet it did not alter the between-CSHCN group (i.e., CHD greater than DS, controls) caries risk heterogeneity. Children with special health care needs comprise a heterogeneous group that must be treated in a precise, diagnosis-specific manner in caries risk assessment. Caries experience in the primary dentition was the only significant predictor of permanent dentition caries incidence. (Pediatr Dent 2019;41(5):378-84).
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September 2019

Genome-wide analysis of dental caries and periodontitis combining clinical and self-reported data.

Nat Commun 2019 06 24;10(1):2773. Epub 2019 Jun 24.

Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, 15219, USA.

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.
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http://dx.doi.org/10.1038/s41467-019-10630-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6591304PMC
June 2019

Traumatic dental injuries in preschool-age children: Prevalence and risk factors.

Clin Exp Dent Res 2019 04 30;5(2):151-159. Epub 2019 Jan 30.

Department of Pediatric Dentistry, School of Dentistry University of North Carolina-Chapel Hill Chapel Hill North Carolina USA.

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,  = 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.
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http://dx.doi.org/10.1002/cre2.165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6483041PMC
April 2019

Self-Efficacy and Academic Performance in Colombian Dental Students.

J Dent Educ 2019 Jun 25;83(6):697-705. Epub 2019 Mar 25.

Ana C. Mafla, DDS, MSPH, is Research Associate Professor, School of Dentistry, Universidad Cooperativa de Colombia, Pasto, Colombia; Kimon Divaris, DDS, PhD, is Associate Professor, Department of Pediatric Dentistry, School of Dentistry, and Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill; Harvey M. Herrera-López, Psy MEd, MA, PhD, is Associate Professor, Department of Psychology, Universidad de Nariño, Pasto, Colombia; and Marc W. Heft, DMD, MA, PhD, is University Term Professor and Director, Department of Oral and Maxillofacial Surgery, College of Dentistry, University of Florida.

Favorable self-efficacy beliefs have been theorized to predict better academic performance, but this association has been untested in dental education. To address this knowledge gap, the aim of this study was to determine the relationship between students' self-efficacy and academic performance in a Colombian dental school. This cross-sectional study was conducted in 2016 with dental students in all five years at the Universidad Cooperativa de Colombia, Pasto, Colombia. Prior to application for the measurement of self-efficacy, the psychometric properties of the Academic Behaviors Self-Efficacy Scale (ABSS) were examined using confirmatory factor analysis (CFA). Participants' semester grade point average was used as a measure of academic performance. Of the total 390 students, 320 participated (82% participation rate). A three-factor model for ABSS with the dimensions of communication, attention, and excellence emerged from the CFA, demonstrating optimal fit indices: χ =468.912; p<0.01; NNFI=0.994; CFI=0.996; RMSEA=0.031 (90% CI 0.021, 0.037); SRMR=0.070; AIC=344.912. Self-efficacy was positively associated with academic performance (rho=0.259; p<0.001). This association was statistically significant only among women (rho=0.361; p<0.001) and those in low SES strata (1-2: rho=0.310; p<0.001) and was highest among students with a heavy (>15 credits) academic course load (rho=0.306; p=0.001). The ABSS demonstrated adequate psychometric properties. Academic self-efficacy was positively associated with academic performance, and this association was most pronounced among women students, those in low SES strata, and those taking a heavy course load.
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http://dx.doi.org/10.21815/JDE.019.079DOI Listing
June 2019

The Supragingival Biofilm in Early Childhood Caries: Clinical and Laboratory Protocols and Bioinformatics Pipelines Supporting Metagenomics, Metatranscriptomics, and Metabolomics Studies of the Oral Microbiome.

Methods Mol Biol 2019 ;1922:525-548

Center for Gastrointestinal Biology and Disease, Division of Gastroenterology and Hepatology, and UNC Microbiome Core, Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill, NC, USA.

Early childhood caries (ECC) is a biofilm-mediated disease. Social, environmental, and behavioral determinants as well as innate susceptibility are major influences on its incidence; however, from a pathogenetic standpoint, the disease is defined and driven by oral dysbiosis. In other words, the disease occurs when the natural equilibrium between the host and its oral microbiome shifts toward states that promote demineralization at the biofilm-tooth surface interface. Thus, a comprehensive understanding of dental caries as a disease requires the characterization of both the composition and the function or metabolic activity of the supragingival biofilm according to well-defined clinical statuses. However, taxonomic and functional information of the supragingival biofilm is rarely available in clinical cohorts, and its collection presents unique challenges among very young children. This paper presents a protocol and pipelines available for the conduct of supragingival biofilm microbiome studies among children in the primary dentition, that has been designed in the context of a large-scale population-based genetic epidemiologic study of ECC. The protocol is being developed for the collection of two supragingival biofilm samples from the maxillary primary dentition, enabling downstream taxonomic (e.g., metagenomics) and functional (e.g., transcriptomics and metabolomics) analyses. The protocol is being implemented in the assembly of a pediatric precision medicine cohort comprising over 6000 participants to date, contributing social, environmental, behavioral, clinical, and biological data informing ECC and other oral health outcomes.
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http://dx.doi.org/10.1007/978-1-4939-9012-2_40DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6628198PMC
June 2019

Measurement of Early Childhood Oral Health for Research Purposes: Dental Caries Experience and Developmental Defects of the Enamel in the Primary Dentition.

Methods Mol Biol 2019 ;1922:511-523

Department of Pediatric Dentistry, UNC School of Dentistry, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA.

Epidemiological investigations of early childhood oral health rely upon the collection of high-quality clinical measures of health and disease. However, ascertainment of valid and accurate clinical measures presents unique challenges among young, preschool-age children. The paper presents a clinical research protocol for the conduct of oral epidemiological examinations among children, implemented in ZOE 2.0, a large-scale population-based genetic epidemiologic study of early childhood caries (ECC). The protocol has been developed for the collection of information on tooth surface-level dental caries experience and tooth-level developmental defects of the enamel in the primary dentition. Dental caries experience is recorded using visual criteria modified from the International Caries Detection and Assessment System (ICDAS), and measurement of developmental defects is based upon the modified Clarkson and O'Mullane Developmental Defects of the Enamel Index. After a dental prophylaxis (toothbrushing among all children and flossing as needed), children's teeth are examined by trained and calibrated examiners in community locations, using portable dental equipment, compressed air, and uniform artificial light and magnification conditions. Data are entered directly onto a computer using a custom Microsoft Access-based data entry application. The ZOE 2.0 clinical protocol has been implemented successfully for the conduct of over 6000 research examinations to date, contributing phenotype data to downstream genomics and other "omics" studies of ECC and DDE, as well as traditional clinical and epidemiologic dental research.
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http://dx.doi.org/10.1007/978-1-4939-9012-2_39DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6642073PMC
June 2019

Protocols, Methods, and Tools for Genome-Wide Association Studies (GWAS) of Dental Traits.

Methods Mol Biol 2019 ;1922:493-509

Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina-Chapel Hill, Chapel Hill, NC, USA.

Oral health and disease are known to be influenced by complex interactions between environmental (e.g., social and behavioral) factors and innate susceptibility. Although the exact contribution of genomics and other layers of "omics" to oral health is an area of active research, it is well established that the susceptibility to dental caries, periodontal disease, and other oral and craniofacial traits is substantially influenced by the human genome. A comprehensive understanding of these genomic factors is necessary for the realization of precision medicine in the oral health domain. To aid in this direction, the advent and increasing affordability of high-throughput genotyping has enabled the simultaneous interrogation of millions of genetic polymorphisms for association with oral and craniofacial traits. Specifically, genome-wide association studies (GWAS) of dental caries and periodontal disease have provided initial insights into novel loci and biological processes plausibly implicated in these two common, complex, biofilm-mediated diseases. This paper presents a summary of protocols, methods, tools, and pipelines for the conduct of GWAS of dental caries, periodontal disease, and related traits. The protocol begins with the consideration of different traits for both diseases and outlines procedures for genotyping, quality control, adjustment for population stratification, heritability and association analyses, annotation, reporting, and interpretation. Methods and tools available for GWAS are being constantly updated and improved; with this in mind, the presented approaches have been successfully applied in numerous GWAS and meta-analyses among tens of thousands of individuals, including dental traits such as dental caries and periodontal disease. As such, they can serve as a guide or template for future genomic investigations of these and other traits.
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http://dx.doi.org/10.1007/978-1-4939-9012-2_38DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6613560PMC
June 2019

The building blocks of precision oral health in early childhood: the ZOE 2.0 study.

J Public Health Dent 2020 03 19;80 Suppl 1:S31-S36. Epub 2018 Dec 19.

Department of Oral and Craniofacial Health Sciences, School of Dentistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Improving children's oral health is a long-standing area of priority and sustained efforts by many stakeholders. Despite these efforts, dental caries, particularly early childhood caries (ECC), persists as a clinical and dental public health problem with multilevel consequences. Despite recent successes in the non-restorative management of dental caries, remarkably little has been done in the domain of ECC prevention. There is promise and expectation that meaningful improvements in early childhood oral health and ECC prevention can be made via the advent of precision medicine in the oral health domain. We posit that precision dentistry, including genomic influences, may be best examined in the context of well-characterized communities (versus convenience clinical samples) and the impact of contextual factors including geography and social disadvantage may be explainable via mechanistic (i.e., biological) research. This notion is aligned with the population approach in precision medicine, which calls for the latter to be predictive, preventive, personalized, and participatory. The article highlights research directions that must be developed for precision dentistry and precision dental public health to be realized. In this context, we describe the rationale, activities, and early insights gained from the ZOE 2.0 study - a large-scale, community-based, genetic epidemiologic study of early childhood oral health. We anticipate that this long-term research program will illuminate foundational domains for the advancement of precision dentistry and precision dental public health. Ultimately, this new knowledge can help catalyze the development of effective preventive and therapeutic modalities via actions at the policy, community, family, and person level.
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http://dx.doi.org/10.1111/jphd.12303DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6584604PMC
March 2020

Sexual orientation-related oral health disparities in the United States.

J Public Health Dent 2019 12 2;79(1):18-24. Epub 2018 Oct 2.

Department of Pediatric Dentistry, University of North Carolina at Chapel Hill School of Dentistry, Chapel Hill, NC, 27599, USA.

Objective: Recent reports have documented health disparities according to sexual orientation and used the minority stress model as a framework for understanding their origins. To date, however, sexual orientation-related disparities in the oral health domain have not been evaluated. Accordingly, this study sought to investigate potential health disparities in objectively-assessed and subjective reports of oral heath among lesbian, gay, and bisexual adults relative to the heterosexual community-dwelling US population.

Methods: We used three consecutive cycles (2009-2014) of National Health and Nutrition Examination Survey (NHANES) data for men and women aged 18-59 years. We examined clinical measures of dental caries, tooth loss, chronic periodontitis, and oral human papillomavirus (HPV) as well as subjective reports of oral health status and use of dental services.

Results: Clinical measures of oral disease did not differ according to sexual orientation; however, bisexual adults were more likely to rate their oral health unfavorably (41%) than heterosexual adults (27%). Gay men reported "bone loss around teeth" more frequently (35%) than heterosexual (11%) and bisexual (10%) men. Bisexual individuals were more likely to confront barriers to accessing dental care (30%) versus heterosexual adults (19%).

Conclusions: While clinical measures of oral health did not substantially differ between sexual orientation strata, subjective measures of oral health were worse among gay, lesbian, and bisexual adults versus heterosexual adults. Further study of the psychosocial construction of oral health among sexual minorities is warranted.
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http://dx.doi.org/10.1111/jphd.12290DOI Listing
December 2019

Meta-analysis of genome-wide association studies of aggressive and chronic periodontitis identifies two novel risk loci.

Eur J Hum Genet 2019 01 14;27(1):102-113. Epub 2018 Sep 14.

Department of Periodontology and Synoptic Dentistry, Institute of Health, Institute for Dental and Craniofacial Sciences, Charité-University Medicine Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.

Periodontitis is one of the most common inflammatory diseases, with a prevalence of 11% worldwide for the severe forms and an estimated heritability of 50%. It is classified into the widespread moderate form chronic periodontitis (CP) and the rare early-onset and severe phenotype aggressive periodontitis (AgP). These different disease manifestations are thought to share risk alleles and predisposing environmental factors. To obtain novel insights into the shared genetic etiology and the underlying molecular mechanisms of both forms, we performed a two step-wise meta-analysis approach using genome-wide association studies of both phenotypes. Genotypes from imputed genome-wide association studies (GWAS) of AgP and CP comprising 5,095 cases and 9,908 controls of North-West European genetic background were included. Two loci were associated with periodontitis at a genome-wide significance level. They located within the pseudogene MTND1P5 on chromosome 8 (rs16870060-G, P = 3.69 × 10, OR = 1.36, 95% CI = [1.23-1.51]) and intronic of the long intergenic non-coding RNA LOC107984137 on chromosome 16, downstream of the gene SHISA9 (rs729876-T, P = 9.77 × 10, OR = 1.24, 95% CI = [1.15-1.34]). This study identified novel risk loci of periodontitis, adding to the genetic basis of AgP and CP.
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http://dx.doi.org/10.1038/s41431-018-0265-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6303247PMC
January 2019

Genome-wide association meta-analysis of coronary artery disease and periodontitis reveals a novel shared risk locus.

Sci Rep 2018 09 12;8(1):13678. Epub 2018 Sep 12.

Charité - University Medicine Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute for Dental and Craniofacial Sciences, Department of Periodontology and Synoptic Dentistry, Berlin, Germany.

Evidence for a shared genetic basis of association between coronary artery disease (CAD) and periodontitis (PD) exists. To explore the joint genetic basis, we performed a GWAS meta-analysis. In the discovery stage, we used a German aggressive periodontitis sample (AgP-Ger; 680 cases vs 3,973 controls) and the CARDIoGRAMplusC4D CAD meta-analysis dataset (60,801 cases vs 123,504 controls). Two SNPs at the known CAD risk loci ADAMTS7 (rs11634042) and VAMP8 (rs1561198) passed the pre-assigned selection criteria (P < 0.05; P < 5 × 10; concordant effect direction) and were replicated in an independent GWAS meta-analysis dataset of PD (4,415 cases vs 5,935 controls). SNP rs1561198 showed significant association (PD[Replication]: P = 0.008 OR = 1.09, 95% CI = [1.02-1.16]; PD [Discovery + Replication]: P = 0.0002, OR = 1.11, 95% CI = [1.05-1.17]). For the associated haplotype block, allele specific cis-effects on VAMP8 expression were reported. Our data adds to the shared genetic basis of CAD and PD and indicate that the observed association of the two disease conditions cannot be solely explained by shared environmental risk factors. We conclude that the molecular pathway shared by CAD and PD involves VAMP8 function, which has a role in membrane vesicular trafficking, and is manipulated by pathogens to corrupt host immune defense.
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http://dx.doi.org/10.1038/s41598-018-31980-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6135769PMC
September 2018
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