Search

Emerging evidence suggests comprehensive immune profiling represents a highly promising, yet insufficiently tapped approach to identify potentially prognostic signatures for periodontitis. In this report, we agnostically identified a periodontitis-associated inflammatory expression network with multiple biomarkers identified within gingival crevicular fluid samples from study participants by applying principal component analysis. We identified an IL-17–dominated trait that is associated with periodontal disease and is inversely modified by the level of IL-10. IL-10 mitigated chemokine CXCL5 and CXCL1 expressions in IL-17–stimulated peripheral blood monocytic cells and peripheral blood monocytic cell–derived macrophages. Il10-deficient mice presented more bone loss, which was associated with more Il17 and IL-17–mediated chemokine and cytokine expression at the transcriptional levels in comparison with control wild-type mice in both the Porphyromonas gingivalis–induced experimental murine periodontitis and ligature-induced alveolar bone-loss models. The dampening effect of IL-10 on the excessive signaling of IL-17 appeared to be mediated by innate immune cells populations rather than by gingival epithelial cells, which are the major cell target for IL-17 signaling. Additionally, elevated IL-17 response in Il10-deficient mice specifically elicited an M1-skewing macrophage phenotype in the gingiva that was associated with the advanced bone loss in the ligature model. In summary, IL-17 dominated an inflammatory network characteristic of periodontitis, and IL-10 dampens this excessive IL-17–mediated periodontitis trait.

Rationale & Objective Observational studies have suggested that periodontal disease may be a modifiable risk factor for chronic kidney disease (CKD). The Kidney and Periodontal Disease (KAPD) Study was designed to determine the feasibility of conducting a periodontal disease treatment trial among a high-risk (mostly poor and racial/ethnic minority) population and estimate the magnitude and variability of kidney and inflammatory biomarker levels in response to intensive periodontal treatment. Study Design Single-center, unmasked, intention-to-treat, randomized, controlled, pilot trial with 2:1 allocation to the treatment and comparison groups. Setting & Participants English- and Spanish-speaking individuals aged 20 to 75 years receiving primary care within the San Francisco Community Health Network with evidence of both moderate to severe periodontal disease and CKD. Intervention Immediate intensive nonsurgical periodontal treatment versus rescue treatment for progressive disease at baseline and 4, 8, and 12 months. Outcomes Feasibility and process outcomes. Levels of biomarkers of kidney function, kidney injury, and systemic inflammation obtained at baseline and 4 and 12 months. Results KAPD randomly assigned 51 participants to the immediate (34 participants) or rescue (17 participants) groups. 14% dropped out of the study (4 immediate, 3 rescue) and 80% completed all 4 visits of the 12-month protocol (28 immediate, 13 rescue). Fewer than half the teeth recommended for extraction were extracted and 40% of immediate group visits were outside the protocol window. Bleeding on probing and probing depth improved more in the immediate group than in the rescue group; there was no significant separation in periodontal status. Levels of markers of vascular endothelial and systemic injury declined in both groups. Limitations No true control group. Conclusions This 12-month, pilot, randomized, controlled trial successfully recruited and retained a high-risk population but was less successful observing treatment adherence, treatment effect, and variability of biomarker levels. Although KAPD did not meet all of its goals, important lessons learned can be applied to future studies. Funding National Institute of Diabetes and Digestive and Kidney Disease (Bethesda, MD; grant number 1K23DK093710-01A1) and Harold Amos Medical Faculty Development Program of the Robert Wood Johnson Foundation, Princeton, NJ. Funders had no role in study design; collection, analysis, or interpretation of data; writing the report; or the decision to submit the report for publication. Trial Registration NCT01802216., Graphical abstract

Periodontal medicine is a term used to describe how periodontal infection/inflammation may impact extraoral health. Periodontitis has been linked to over 50 systemic diseases and conditions. As part of the Journal of Dental Research’s Centennial Celebration, this narrative review discusses periodontal medicine research done over the past 100 y, with particular focus on the effects of periodontal disease on 3 pathological conditions: cardiovascular disease, diabetes mellitus, and adverse pregnancy outcomes. We selected 29 total studies that were the “first” of their kind, as they provided novel observations or contributed to shifting paradigms as well as important studies that made strong contributions to progress in understanding relationships to the systemic conditions. These studies were organized in an overview timeline and broken down into timelines by topic: cardiovascular disease ( n = 10), diabetes ( n = 12), and adverse pregnancy outcomes ( n = 7). Overall, the majority of cross-sectional, case-control, and longitudinal studies have revealed positive associations between poor periodontal status and cardiovascular disease, diabetes metabolic control, and a number of adverse pregnancy outcomes, and these associations are upheld in systematic reviews. Findings from randomized controlled trials testing the effects of periodontal therapy on systemic health outcomes were conflicting and inconsistent. While there has been a great deal of progress, we highlight lessons learned and make comments and suggestions on a number of key aspects, including the heterogeneity of case definitions of periodontal disease across studies, accounting for features of the periodontal phenotype that are most relevant to the biological link between periodontitis and systemic outcomes, the role of other comorbid inflammatory conditions, selection of study participants, and timing and intensity of the periodontal intervention.

There is no agnostic GWAS evidence for the genetic control of IL-1β expression in periodontal disease. Here we report a GWAS for “high” gingival crevicular fluid IL-1β expression among 4910 European-American adults and identify association signals in the IL37 locus. rs3811046 at this locus (p = 3.3 × 10−22) is associated with severe chronic periodontitis (OR = 1.50; 95% CI = 1.12–2.00), 10-year incident tooth loss (≥3 teeth: RR = 1.33; 95% CI = 1.09–1.62) and aggressive periodontitis (OR = 1.12; 95% CI = 1.01–1.26) in an independent sample of 4927 German/Dutch adults. The minor allele at rs3811046 is associated with increased expression of IL-1β in periodontal tissue. In RAW macrophages, PBMCs and transgenic mice, the IL37 variant increases expression of IL-1β and IL-6, inducing more severe periodontal disease, while IL-37 protein production is impaired and shows reduced cleavage by caspase-1. A second variant in the IL37 locus (rs2708943, p = 4.2 × 10−7) associates with attenuated IL37 mRNA expression. Overall, we demonstrate that IL37 variants modulate the inflammatory cascade in periodontal disease., IL-1β in gingival crevicular fluid (GCF) is a marker of inflammation in periodontal disease. Here, Offenbacher et al. identify genetic variants in the IL37 locus associated with GCF-IL-1β and show that the IL-1β-increasing allele at rs3811046 leads to an enhanced inflammatory response in vitro and in vivo.

Non-alcoholic fatty liver disease (NAFLD) prevalence is greater among Hispanics/Latinos than other racial/ethnic groups and prevalence is further reported to vary among Hispanic/Latino background groups. Experimental animal and human studies demonstrate associations between periodontitis and NAFLD, not yet reported among Hispanics/Latinos. This study examined periodontitis as a novel risk factor that may contribute to the burden of NAFLD among Hispanics/Latinos.Data came from 11,914 participants of the Hispanic Community Health Study/Study of Latinos. Periodontitis was defined as the extent (none, 30%, ≥30%) of periodontal sites with clinical attachment level (CAL) of ≥3 mm or probing pocket depth (PD) of ≥4 mm. Elevated serum transaminases indicative of suspected NAFLD were defined as having alanine aminotransferase levels (ALT) 40 IU/L or aspartate aminotransferase (AST) 37 IU/L for men and ALT 31 IU/L or AST 31 IU/L for women. Survey-logistic regression models estimated prevalence odds ratios (POR) and 95% confidence intervals (CI) for the association between periodontitis and suspected NAFLD.The overall age-standardized percentage of study participants with 30% of sites with CAL ≥3 mm or PD ≥4 mm was 53.5% and 58.6%, respectively, while participants with ≥30% sites with CAL ≥3 mm or PD ≥4 mm comprised 16% and 5.72%, respectively. The overall age-standardized prevalence (95% CI) of suspected NAFLD was 18.1% (17.1-19.0). For the entire cohort, we observed a dose-response (i.e. graded) association between PD ≥4 mm and the prevalence odds of suspected NAFLD, whereby participants with 30% affected had a crude POR = 1.19 (95% CI: 1.03, 1.38) while participants with ≥30% affected had a crude POR = 1.39 (95% CI: 1.02, 1.90). These crude estimates were attenuated toward the null and rendered non-significant upon covariate adjustment. No differences were found by Hispanic/Latino background group.Previously reported associations between periodontitis and NAFLD were marginal to null in this study of a diverse group of Hispanics/Latinos.

A new periodontitis classification scheme has been adopted, in which forms of the disease previously recognized as "chronic" or "aggressive" are now grouped under a single category ("periodontitis") and are further characterized based on a multi-dimensional staging and grading system. Staging is largely dependent upon the severity of disease at presentation as well as on the complexity of disease management, while grading provides supplemental information about biological features of the disease including a history-based analysis of the rate of periodontitis progression; assessment of the risk for further progression; analysis of possible poor outcomes of treatment; and assessment of the risk that the disease or its treatment may negatively affect the general health of the patient. Necrotizing periodontal diseases, whose characteristic clinical phenotype includes typical features (papilla necrosis, bleeding, and pain) and are associated with host immune response impairments, remain a distinct periodontitis category. Endodontic-periodontal lesions, defined by a pathological communication between the pulpal and periodontal tissues at a given tooth, occur in either an acute or a chronic form, and are classified according to signs and symptoms that have direct impact on their prognosis and treatment. Periodontal abscesses are defined as acute lesions characterized by localized accumulation of pus within the gingival wall of the periodontal pocket/sulcus, rapid tissue destruction and are associated with risk for systemic dissemination.

The purpose of this study was to evaluate the associations between interdental cleaning behavior and the prevalence of caries and periodontal disease and numbers of missing teeth, with data from the National Health and Nutrition Examination Survey (2011 to 2012 and 2013 to 2014). Analysis included the following parameters: interproximal clinical attachment level (iCAL) ≥3 mm, interproximal probing depth (iPD) ≥4 mm, number of coronal and interproximal caries, number of missing teeth, ≥1 surfaces with coronal caries, and periodontal profile classes (PPCs). Chi-square was used for bivariate associations. Associations of interdental cleaning with outcomes were assessed with multiple linear regression and generalized logit regression, adjusting for age, race, sex, diabetes, smoking, education, dental visits, and sugar consumption. Nonusers had a significantly higher percentage of sites with iCAL ≥3 mm and iPD ≥4 mm as compared with individuals who used interdental cleaning devices ( P < 0.0001). Individuals with a higher frequency of cleaning (4 to 7×/wk) had a significantly lower extent of sites with iCAL ≥3 mm as compared with lower-frequency cleaning (1 to 3×/wk; P ≤ 0.05). Interdental cleaning users showed lower numbers of coronal caries, interproximal coronal caries, and missing teeth as compared with nonusers ( P < 0.0001). Nonusers had 1.73-times (95% confidence interval, 1.53 to 1.94) higher odds for having ≥1 surfaces of coronal caries as compared with interdental cleaning users, regardless of the weekly frequency. Individuals were less likely to be in diseased PPCs if they were interdental cleaning users. Low-frequency cleaners (1 to 3×/wk) had significantly greater odds (1.43; 95% confidence interval, 1.08 to 1.88) to have severe disease (PPC-G) versus health (PPC-A) than were high-frequency cleaners (4 to 7×/wk). Interdental cleaning users showed lower levels of periodontal disease and caries and lower numbers of missing teeth. Higher frequency of interdental cleaning was correlated with increased periodontal health. Individuals with severe periodontal disease could show additional oral health benefits by increasing cleaning frequency. The data support the use of interdental cleaning devices as an oral hygiene behavior for promoting health.

Background and Purpose— Periodontal disease is independently associated with cardiovascular disease. Identification of periodontal disease as a risk factor for incident ischemic stroke raises the possibility that regular dental care utilization may reduce the stroke risk. Methods— In the ARIC (Atherosclerosis Risk in Communities) study, pattern of dental visits were classified as regular or episodic dental care users. In the ancillary dental ARIC study, selected subjects from ARIC underwent fullmouth periodontal measurements collected at 6 sites per tooth and classified into 7 periodontal profile classes (PPCs). Results— In the ARIC study 10 362 stroke-free participants, 584 participants had incident ischemic strokes over a 15-year period. In the dental ARIC study, 6736 dentate subjects were assessed for periodontal disease status using PPC with a total of 299 incident ischemic strokes over the 15-year period. The 7 levels of PPC showed a trend toward an increased stroke risk (χ 2 trend P Conclusions— We confirm an independent association between periodontal disease and incident stroke risk, particularly cardioembolic and thrombotic stroke subtype. Further, we report that regular dental care utilization may lower this risk for stroke.

Background Current periodontal disease taxonomies have limited utility for predicting disease progression and tooth loss; in fact, tooth loss itself can undermine precise person-level periodontal disease classifications. To overcome this limitation, the current group recently introduced a novel patient stratification system using latent class analyses of clinical parameters, including patterns of missing teeth. This investigation sought to determine the clinical utility of the Periodontal Profile Classes and Tooth Profile Classes (PPC/TPC) taxonomy for risk assessment, specifically for predicting periodontal disease progression and incident tooth loss. Methods The analytic sample comprised 4,682 adult participants of two prospective cohort studies (Dental Atherosclerosis Risk in Communities Study and Piedmont Dental Study) with information on periodontal disease progression and incident tooth loss. The PPC/TPC taxonomy includes seven distinct PPCs (person-level disease pattern and severity) and seven TPCs (tooth-level disease). Logistic regression modeling was used to estimate relative risks (RR) and 95% confidence intervals (CI) for the association of these latent classes with disease progression and incident tooth loss, adjusting for examination center, race, sex, age, diabetes, and smoking. To obtain personalized outcome propensities, risk estimates associated with each participant's PPC and TPC were combined into person-level composite risk scores (Index of Periodontal Risk [IPR]). Results Individuals in two PPCs (PPC-G: Severe Disease and PPC-D: Tooth Loss) had the highest tooth loss risk (RR = 3.6; 95% CI = 2.6 to 5.0 and RR = 3.8; 95% CI = 2.9 to 5.1, respectively). PPC-G also had the highest risk for periodontitis progression (RR = 5.7; 95% CI = 2.2 to 14.7). Personalized IPR scores were positively associated with both periodontitis progression and tooth loss. Conclusions These findings, upon additional validation, suggest that the periodontal/tooth profile classes and the derived personalized propensity scores provide clinical periodontal definitions that reflect disease patterns in the population and offer a useful system for patient stratification that is predictive for disease progression and tooth loss.

Aim Several papers have considered the potential relationship between periodontitis and lipid parameters. The present systematic review, meta-analysis and meta-regression study focused on investigating whether serum lipid parameter levels were elevated in patients with periodontal disease (PD) (without altered systemic conditions) in comparison with periodontally healthy subjects. Materials and Methods Eligible studies were those with data about serum lipid parameter levels in non-smoking subjects with and without chronic periodontitis, who are generally healthy and not taking any medication for dyslipidemia. Mean differences and 95% confidence intervals for total cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol were obtained from all the selected studies. Results 19 publications were included for meta-analysis. Participants with chronic periodontitis presented significantly higher serum levels of LDL and triglycerides (p=0.003 and p

Background Periodontal disease (PD) is associated with recurrent vascular event in stroke or transient ischemic attack (TIA). In this study, we investigated whether PD is independently associated with aortic arch atheroma (AA). We also explored the relationship PD has with AA plaque thickness and other characteristics associated with atheroembolic risk among patients with stroke or TIA. Finally, we confirmed the association between AA and recurrent vascular event in patients with stroke or TIA. Methods In this prospective longitudinal hospital-based cohort study, PD was assessed in patients with stroke and TIA. Patients with confirmed stroke and TIA (n = 106) were assessed by calibrated dental examiners to determine periodontal status and were followed over a median of 24 months for recurrent vascular events (stroke, myocardial infarction, and death). The extent of AA and other plaque characteristics was assessed by transesophageal echocardiography. Results Within our patient cohort, 27 of the 106 participants had recurrent vascular events (including 16 with stroke or TIA) over the median of 24-month follow-up. Severe PD was associated with increased AA plaque thickness and calcification. The results suggest that PD may be a risk factor for AA. In this cohort, we confirm the association of severe AA with recurrent vascular events. Conclusions In patients with stroke or TIA, severe PD is associated with increased AA plaque thickness, a risk factor for recurrent events. Further studies are needed to confirm this finding and to determine whether treatment of PD can reduce the rate of AA plaque progression and recurrent vascular events.

An association between periodontitis and nonalcoholic fatty liver disease (NAFLD) has been reported by experimental animal and epidemiologic studies. This study investigated whether circulating levels of serum C-reactive protein (CRP) and a weighted genetic CRP score representing markers of inflammatory burden modify the association between periodontitis and NAFLD. Data came from 2,481 participants of the Study of Health in Pomerania who attended baseline examination that occurred between 1997 and 2001. Periodontitis was defined as the percentage of sites (0%, 3 mg/L. Periodontitis was positively associated with higher prevalence odds of NAFLD, and this relationship was modified by serum CRP levels.

Objective To investigate racial differences in the associations between periodontitis and 10-year self-reported incident tooth loss in a biracial, community-based cohort of US late middle-aged and older adults. Methods Subjects were 3,466 dentate men and women aged 53-74 who underwent dental examinations from 1996 to1998. In 2012-2013, telephone interviewers asked participants about tooth loss in the preceding 10 years. Separate multivariable ordinal logistic regression models were used to calculate proportional odds ratios (OR) and 95% confidence intervals (CI) as estimates of association between periodontitis and tooth loss for Whites and African-Americans (AAs). Results The majority of participants were White (85 percent) and female (57 percent) with 23 teeth on average at enrollment. Approximately half the Whites (56 percent) and AAs (49 percent) had periodontitis. At follow-up, approximately 44 percent of AAs and 38 percent of Whites reported having lost ≥1 tooth. In multivariable models, severe periodontitis (OR = 3.03; 95% CI = 2.42-3.80) and moderate periodontitis (OR = 1.64; 95% CI= 1.39-1.94) were significant risk factors of incident tooth loss among Whites. For AAs, severe but not moderate periodontitis increased the odds of incident tooth loss (OR = 2.22; 95% CI = 1.37-3.59). In the final model, education was inversely associated with incident tooth loss among AAs, while lower income was associated with greater odds of tooth loss among Whites. Conclusions In this population-based cohort, there is racial heterogeneity in the association between periodontitis and tooth loss. Interventions to reduce the impact of periodontitis on tooth loss need to consider these differences.

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.

Objectives Previous studies on a potential association between endodontic infection (EI) and cardiovascular disease (CVD) produced mixed results. Endodontic treatment (ET) may also be linked to cardiovascular risk, as a marker for prior chronic dental infection and subclinical EI in other teeth. We tested the hypothesis that ET is associated with elevated risk of coronary heart disease (CHD), ischemic stroke (IS), heart failure (HF), or venous thromboembolism (VTE). Methods ARIC participants who completed the dental ancillary study exam 4 (1996-1998; n = 6,638) were included in the analyses. Participants were followed through 2013 for CHD, stroke, and HF and 2011 for VTE. Cox-proportional hazards regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for CHD, IS, HF, and VTE across ET classifications adjusting for age, sex, race/center, education, income, smoking, alcohol consumption, BMI, statin use, family history of CHD, physical activity, diet quality, insurance status, last dental visit, dental visit frequency, having a current dentist, and tooth loss due to gum disease. Results Among participants, 21.0% reported a single ET, while 28.5% reported multiple ETs. Over a median of 15.8 years of follow-up, there were 506 incident CHD events, 311 IS events, 739 HF events, and 219 VTE events. There were no significant associations between self-reported history of ET and any of our outcomes (HR (95%CI): CHD = 1.16 (0.87,1.44), IS = 0.77 (0.55,1.09), HF = 1.00 (0.81,1.24), VTE = 0.98 (0.67,1.43)) after adjustment. Conclusions Our results do not support an independent association between ET and development of CHD, IS, HF, or VTE.

AimThe intronic variant rs4252120 in the plasminogen gene (PLG) is known to be associated with aggressive periodontitis (AgP) and atherosclerosis. Here, we examined the chromosomal region spanning PLG for associations with both chronic periodontitis (CP) and AgP. Materials and MethodsThe association of PLG candidate rs4252120 was tested in a German case–control sample of 1,419 CP cases using the genotyping assay hCV11225947 and 4,562 controls, genotyped with HumanOmni BeadChips. The German and Dutch sample of AgP cases (N = 851) and controls (N = 6,836) were genotyped with HumanOmni BeadChips. The North American CP sample (N = 2,681 cases, 1,823 controls) was previously genotyped on the Genome‐Wide Human SNP Array 6.0. Genotypes were imputed (software Impute v2), and association tests were performed using an additive genetic model adjusting for sex and smoking. ResultsRs4252120 was not associated with CP. However, a haplotype block downstream of PLG and not in linkage disequilibrium with rs4252120 (r2 = .08) was associated with both AgP (rs1247559; p = .002, odds ratio [OR] = 1.33) and CP (p = .02, OR = 1.15). That locus was also significantly associated with PLG expression in osteoblasts (p = 6.9 × 10−5). ConclusionsOur findings support a role of genetic variants in PLG in the aetiology of periodontitis.

Denture stomatitis is a common condition manifested by inflammation of the oral mucous membrane beneath a denture. The objective of this study was to compare the transcriptome of human palatal mucosa with chronic oral stomatitis-associated Candida albicans infection to that of healthy oral mucosa.Oral palatal biopsies were obtained from 17 healthy and 15 C. albicans-infected stomatitis subjects for whole transcriptome analyses. The presence of C. albicans was confirmed by cytology and cultivable methods. The clinical severity of the stomatitis was evaluated by the Newton Classification (Class II or III). For transcriptome analyses a false discovery rate (FDR) of0.05 was used, and the effects of age, race, and gender were evaluated by principle component analysis (PCA). Specific differentially expressed genes identified by mRNA array data were confirmed by measurements of salivary protein expression using multiplex analyses.Microarray analysis of mRNA expression indicated that in C. albicans stomatitis there were 3034 genes-in-play that were differentially expressed and met the FDR0.05 criteria. Two hundred thirty five (235) genes were up-regulated2-fold, and 71 genes were down-regulated2-fold. Five of the 6 most significant gene ontology pathways involve inflammation and activation of the immune response with CD28 and CTLA signaling of T cells. There was strong up-regulation of TLR2, CD14, MYD88, IKKA, and NFKB as the dominant toll-like receptor-signaling pathway. The expression of several extracellularly expressed inflammatory protein genes was up-regulated in candidiasis, and 2 were confirmed as up-regulated within the saliva using protein multiplexing analyses.Neutrophil recruitment and activation, epithelial suppression, and T-cell activation appear as major pathways in chronic oral candidiasis. Tissue up-regulation of TLR2 pathways, as well as potential C. albicans binding proteins, was observed, whereas keratin and adhesion molecule synthesis were down-regulated. Several candidate biomarkers to potentially identify the presence of oral candidiasis were differentially expressed in tissues and saliva.

Aim Periodontal disease is a cardiovascular disease (CVD) risk factor but few studies have considered the relationship between periodontal disease and venous thromboembolism (VTE). We hypothesized that periodontal disease is independently associated with increased risk of incident VTE. Materials and methods We used data from 8,092 participants of the Atherosclerosis Risk in Communities (ARIC) study to examine periodontal disease in 1996-1998 and incident VTE through 2011. Periodontal disease was determined using self-reported tooth loss due to gum disease and dental examinations. Cox proportional hazards regression models were used to estimate hazard ratios for VTE and 95% confidence intervals adjusted for relevant confounders. Results and conclusions Participants were on average 62.7 years old at baseline and 13.9% self-reported tooth loss from gum disease. Over a mean of 12.9 years of follow-up, there were 313 incident VTE events. Self-reported tooth loss due to gum disease was associated with 30% higher VTE risk (HR = 1.29 (0.96, 1.73) after adjusting demographic factors, SES, periodontal risk factors, oral hygiene, and access to dental care variables. No statistically significant associations between clinical measures of periodontitis and VTE were observed after adjustment. Further research is needed to elucidate whether a relationship between periodontal disease and VTE exists.

Epigenetic factors are heritable genome modifications that potentially impact gene transcription, contributing to disease states. Epigenetic marks play an important role in chronic inflammatory conditions, as observed in periodontal diseases, by allowing microbial persistence or by permitting microbial insult to play a role in the so-called 'hit-and-run' infectious mechanism, leading to lasting pathogen interference with the host genome. Epigenetics also affects the health sciences by providing a dynamic mechanistic framework to explain the way in which environmental and behavioral factors interact with the genome to alter disease risk. In this article we review current knowledge of epigenome regulation in light of the multifactorial nature of periodontal diseases. We discuss epigenetic tagging in identified genes, and consider the potential implications of epigenetic changes on host-microbiome dynamics in chronic inflammatory states and in response to environmental stressors. The most recent advances in genomic technologies have placed us in a position to analyze interaction effects (eg, between periodontal disease and type 2 diabetes mellitus), which can be investigated through epigenome-wide association analysis. Finally, because of the individualized traits of epigenetic biomarkers, pharmacoepigenomic perspectives are also considered as potentially novel therapeutic approaches for improving periodontal disease status.

Periodontal diseases are Gram-negative anaerobic infections that can occur in women of childbearing age (18 to 34 years). In the present investigation we sought to determine whether the prevalence of maternal periodontal infection could be associated with preterm low birth weight (PLBW), controlling for known risk factors and potential covariates. A case-control study of 124 pregnant or postpartum mothers was performed. PLBW cases were defined as a mother with a birth of less than 2,500 g and one or more of the following: gestational age

This paper was prepared by the Research, Science and Therapy Committee of the American Academy of Periodontology. It is intended to provide information for the dental profession and other interested parties. The purpose of this paper is to provide a general overview of oral reconstructive and corrective procedures used in periodontal therapy. It is not intended to be a comprehensive review of this subject.

BACKGROUND This study uses multiple, contemporary methodologies to expand our knowledge of the temporal relationship between host-microbial interactions and clinical signs of gingivitis. METHODS Subgingival plaque and crevicular fluid samples were collected from 31 systemically healthy adults with naturally occurring plaque-induced gingivitis. Professional prophylaxis was administered and participants were followed over 7 weeks. Microbial characterization was performed using a bead-based hybridization assay and cytokine analysis using bead-based flow cytometry. RESULTS The provision of sequential interventions, oral hygiene instruction, and subsequent professional prophylaxis brought about significant reduction of plaque and resolution of gingivitis at all post baseline time points (P

BACKGROUND This paper focuses on the Periodontal Profile Class (PPC) System that may be more informative and representative of periodontitis phenotypes than current case definitions of periodontitis. This study illustrates the unique aspects of the PPC compared with other periodontal indices for studying associations between periodontal disease and prevalent systemic conditions. METHODS We computed odds ratios and 95% confidence intervals to compare associations between periodontal disease and prevalent systemic conditions using our new PPC and two traditional indices. We used the Bayesian Information Criterion (BIC) to determine the fit of the model and the magnitude of the contribution attributable to periodontal disease beyond traditional risk factors. The Atherosclerosis Risk in Communities (ARIC) Study (1996-1998) results were compared with results from the combined National Health and Nutrition Examination Survey 2009-2014 datasets. RESULTS In the ARIC Study, high gingival inflammation, tooth loss, severe tooth loss, and severe disease PPC components were significantly associated with diabetes, coronary heart disease (CHD), high-sensitivity C-reactive protein, and interleukin (IL)-6, while only severe disease was associated with stroke. Severe disease was associated with CHD using the Centers for Disease Control/American Academy of Periodontology index, and the European Periodontal index was associated with CHD and IL-6. CONCLUSIONS The addition of the PPC to traditional variables associated with prevalent diabetes, stroke, CHD, and systemic measures of inflammation resulted in very strong improvement of the overall models, while the traditional indices were less likely to be associated and, if present, the associations were weaker. The PPC system provides specific insight into the individuals and periodontal characteristics of the phenotype that are associated with systemic conditions that may be useful in designing treatment interventions.

Background This paper focuses on Periodontal Profile Class (PPC), a component of the Periodontal Profile Phenotype (P3 ) System that may be more representative of the periodontitis phenotype than current case definitions of periodontitis. Data illustrate the unique aspects of the PPC compared with other commonly used periodontal classification indices. Methods Latent Class Analysis (LCA) identified discrete classes of individuals grouped by tooth-level clinical parameters. The analysis defined seven distinct periodontal profile classes (PPC A through G) and seven distinct tooth profile classes (TPC A through G). This LCA classification was an entirely data-derived agnostic process without any preconceived presumptions of what constituted disease. Results Comparing the PPC with the Centers for Disease Control/American Academy of Periodontology (CDC/AAP) and European indices, the PPC is unique in that it contains four disease classes not traditionally used. Less than half of individuals classified as Healthy by both the CDC/AAP and European indices were Healthy using the PPC. About 25% of those classified as Severe by CDC/AAP and European indices were PPC-Severe. The remainder spread out over the High Gingival Index, Posterior Disease, Tooth Loss, and Severe Tooth Loss phenotypes. Conclusions The PPC classification provides a significant departure from the traditional clinical case status indices that have been used, but has resulted in clinical phenotypes that are quite familiar to most clinicians who take notice of the distribution of missing teeth, areas of recession, diminished periodontal support, and other aspects of the dentition while conducting a periodontal examination. The mutually exclusive categories provided by the PPC system provide periodontal clinical summaries that can be an important component of precision dentistry.

Purpose To determine the prevalence of third molars in the US population and to report the differences in prevalence of visible third molars in the most recent National Health and Nutrition Examination Survey (NHANES) population of 2011 through 2012 by participant, jaw, and demographics. Materials and Methods The number of visible third molars in the NHANES data was assessed in nonclinical settings by trained, calibrated dental hygienists by decade of age beginning in the 20- to 29-year-old cohort through the 70- to 79-year-old cohort. Cross-sectional analyses of third molar data were conducted by the authors from the NHANES databases of 2001 through 2002, 2009 through 2010, and 2011 through 2012 to compare data for similarity of outcomes on third molar prevalence in the US population. Outcomes on third molar prevalence also were assessed from the NHANES of 2011 through 2012 by participant, jaw, and demographics: gender, race or ethnicity (Caucasian, African American, other), and education (less than high school, high school graduate, some college, college graduate). Results Data on the mean number of third molars from NHANES of 2001 through 2002, 2009 through 2010, and 2011 through 2012 were similar. The number of visible third molars in the NHANES of 2011 through 2012 decreased progressively from a mean of 1.48 in the 20- to 29-year-old cohort to 0.81 in the 60- to 69-year-old cohort, No visible third molars were observed in 47% of the 20- to 29-year-old cohort compared with 53% in the 50- to 59-year-old cohort. Participants who were male, non-Caucasian, and had less than a high school education were more likely to have a visible third molar in all age cohorts. No data were collected by NHANES examiners to determine why third molars were absent. Conclusion Third molar prevalence did not appear to differ in the US population during the first decade of the 21st century. Numbers of visible third molars, prevalent in young adults, decreased progressively through each successive age cohort. Demographic differences exist for prevalence of third molars in the US population.

Objective To assess whether partial-mouth protocols (PRPs) result in biased estimates of the associations between smoking, alcohol, obesity and diabetes with periodontitis. Methods Using a sample (n = 6129) of the 1996–1998 Atherosclerosis Risk in Communities study, we used measures of probing pocket depth and clinical attachment level to identify moderate-severe periodontitis. Adjusting for confounders, unconditional binary logistic regression estimated prevalence odds ratios (POR) and 95% confidence limits. Specifically, we compared POR for smoking, alcohol, obesity and diabetes with periodontitis derived from full-mouth to those derived from 4-PRPs (Ramfjord, National Health and Nutrition Examination survey-III, modified-NHANES-IV and 42-site-Random-site selection-method). Finally, we conducted a simple sensitivity analysis of periodontitis misclassification by changing the case definition threshold for each PRP. Results In comparison to full-mouth PORs, PRP PORs were biased in terms of magnitude and direction. Holding the full-mouth case definition at moderate-severe periodontitis and setting it at mild-moderate-severe for the PRPs did not consistently produce POR estimates that were either biased towards or away from the null in comparison to full-mouth estimates. Conclusions Partial-mouth protocols result in misclassification of periodontitis and may bias epidemiologic measures of association. The magnitude and direction of this bias depends on choice of PRP and case definition threshold used.

Introduction and Hypothesis: Intracranial Atherosclerotic Stenosis (ICAS) is associated with 8-10% of all strokes in the U.S. Although there is evidence in the Asian population that inflammation plays a role in ICAS, it has not been shown in the U.S. population. We hypothesized that midlife sensitivity C-reactive protein (hs-CRP), a marker of inflammation, is associated with late-life ICAS in the U.S. population. Methods: The Atherosclerosis Risk in Communities (ARIC) study recruited participants from four U.S. communities between 1987-1989. In the ancillary Dental ARIC study, dentate subjects from ARIC undergoing full-mouth examination also had blood samples obtained to measure the serum inflammatory marker, hs-CRP (1996-1998). High sensitivity ELISA assay that had been validated against nephelometry, was used to measure hs-CRP. Of this cohort, a subset (N=909) underwent high resolution 3T magnetic resonance angiogram at a follow-up visit (2011-2013). All images were analyzed in a centralized lab and ICAS was graded as no stenosis/3 mg/l), and ICAS. Results: A total of 909 subjects (mean age 62±6, 45% male, 81% Caucasian and 19% African-American), underwent assessment of hs-CRP and ICAS. Compared with the reference group (hs-CRP 50% ICAS, on univariate (Crude OR 1.3 95% CI: 0.9-2.0) or multivariable analysis (Adjusted OR 1.3, 95% CI: 0.9-2.0). Elevated hs-CRP (>3mg/l) was significantly associated with >50% ICAS in both univariate (Crude OR 1.6, 95% CI:1.1-2.3) and adjusted model (Adjusted OR 1.6, 95% CI:1.1-2.4). Conclusions: In this US population-based community study, we report a significant and independent association between inflammatory marker hs-CRP and ICAS. Further studies are required to test if anti-inflammatory drugs or diet prevents ICAS.

We evaluated whether first-trimester high-sensitivity C-reactive protein (hsCRP), a suggested marker of pregnancy-associated hyperglycemia, predicts third-trimester impaired glucose tolerance (IGT) in a secondary analysis of a prospective cohort of nondiabetic singletons enrolled at26 weeks gestation.We measured the association between hsCRP collected at14 weeks among women classified as IGT (gestational diabetes screening results, 135 to200 mg/dL) and those among normoglycemic women. Multivariable modeling estimated the association between log hsCRP and IGT, adjusted for maternal body mass index (BMI).Among 300 women, 13% (39 of 300) had IGT. The hsCRP was positively associated with glucose (P = .005). Compared with normoglycemic women, women with IGT had higher log hsCRP (0.87 ± 0.66 vs 0.67 ± 0.60, P = .04), but the association was not significant in adjusted models (adjusted odds ratio 1.20, 95% confidence interval 0.65-2.21). The hsCRP did not predict third-trimester IGT in this analysis when BMI is considered.Early identification of women at risk of IGT remains a priority, but the contribution of maternal BMI appears greater than hsCRP.

Background Non-alcoholic fatty liver disease (NAFLD) affects 20-30% of adults with risk factors like obesity and insulin resistance putatively acting through chronic low-grade inflammation. Because periodontitis elicits low-grade inflammation, we hypothesized that it could contribute to NAFLD occurrence. Objective To investigate epidemiologic associations between periodontitis and the incidence of NAFLD among 2,623 participants of the Study of Health in Pomerania Methods Periodontitis at baseline was defined as the percentage of sites (0%, 1-30%, ≥30%) with 1) clinical attachment level (CAL) ≥3mm; 2) probing pocket depth (PD) ≥4mm. Incident NAFLD was defined as a significant increase in liver echogenicity on ultrasound relative to the kidneys, with the diaphragm indistinct OR the echogenic walls of the portal veins invisible Results After a median 7·7 years of follow-up, 605 incident NAFLD cases occurred at a rate of 32·5 cases per 1,000 person-years. Relative to participants without CAL ≥3mm, NAFLD incidence was elevated slightly in participants with 1

Background While evidence is increasingly consistent with a positive association between periodontitis and cancer risk, most studies have relied on self-reported periodontitis. In this study, we prospectively evaluated the association of periodontal disease severity with cancer risk in black and white older adults in a cohort study that included a dental examination. Methods Included were 7466 participants in the Atherosclerosis Risk in Communities study cohort who at visit 4 (1996-1998) reported being edentulous or underwent the dental examination. Probing depth and gingival recession were measured at six sites on all teeth; these measurements were used to define periodontal disease severity. Incident cancers (n = 1648) and cancer deaths (n = 547) were ascertained during a median of 14.7 years of follow-up. All statistical tests were two-sided. Results An increased risk of total cancer (hazard ratio [HR] = 1.24, 95% confidence interval [CI] = 1.07 to 1.44, Ptrend = .004) was observed for severe periodontitis (>30% of sites with attachment loss >3 mm) compared with no/mild periodontitis ( 3 mm), adjusting for smoking and other factors. Strong associations were observed for lung cancer (HR = 2.33, 95% CI = 1.51 to 3.60, Ptrend < .001), and elevated risks were noted for colorectal cancer for severe periodontitis, which were significant among never smokers (HR = 2.12, 95% CI = 1.00 to 4.47). Associations were generally weaker, or not apparent among black participants, except for lung and colorectal cancers, where associations were similar by race. No associations were observed for breast, prostate, or hematopoietic and lymphatic cancer risk. Conclusions This study provides additional evidence that cancer risk, especially for lung and colorectal cancer, is elevated in individuals with periodontitis. Additional research is needed to understand cancer site-specific and racial differences in findings.

Objectives The long-term success of dental implants is established by literature. Although clinically well defined, the complex genetic pathways underlying osseointegration have not yet been fully elucidated. Furthermore, patients with osteopenia/osteoporosis are considered to present as higher risk for implant failure. Porous tantalum trabecular metal (PTTM), an open-cell porous biomaterial, is suggested to present enhanced biocompatibility and osteoconductivity. The goal of this study was to evaluate the expression patterns of a panel of genes closely associated with osteogenesis and wound healing in osteopenic patients receiving either traditional titanium (Ti) or PTTM cylinders to assess the pathway of genes activation in the early phases of osseointegration. Material and methods Implant cylinders made of Ti and PTTM were placed in osteopenic volunteers. At 2- and 4 weeks of healing, one Ti and one PTTM cylinder were removed from each subject for RT-PCR analysis using osteogenesis PCR array. Results Compared to Ti, PTTM-associated bone displayed upregulation of bone matrix proteins, BMP/TGF tisuperfamily, soluble ligand and integrin receptors, growth factors, and collagen genes at one or both time points. Histologically, PTTM implants displayed more robust osteogenesis deposition and maturity when compared to Ti implants from the same patient. Conclusions Our results indicate that PTTM properties could induce an earlier activation of genes associated with osteogenesis in osteopenic patients suggesting that PTTM implants may attenuate the relative risk of placing dental implants in this population.

Introduction: Prior epidemiological studies have shown that periodontal disease (PD), also referred to as gum disease, is an independent risk factor for ischemic stroke. We assessed the hypothesis that users of regular dental care may have a lower risk for incident ischemic stroke and specific stroke subtype when compared with users of episodic dental care. Methods: In this prospective, longitudinal community-based cohort study, participants without prior stroke were assessed for dental care utilization represented by patient-reported responses to questionnaires. The pattern of dental care utilization was classified as regular use (every year), episodic use (as needed), or no use (never). Episodic visits, or visits as needed, are considered signs of inadequate utilization of dental care. These participants were followed for incident ischemic strokes. Ischemic stroke diagnoses were defined as sudden onset of neurological deficit(s) lasting ≥24 hours along with neuroimaging confirmation. Strokes were further classified according to etiologic subtype as thrombotic, lacunar, or cardioembolic stroke subtype according to criteria adopted from the National Survey of Stroke. Results: Of 11,242 participants (mean age±SD=62.8±5.6, 56% female, 78% white and 22% African-American) assessed for dental care utilization at the fourth ARIC visit (1996-1998). Over a 15-year follow-up period a total of 583 participants had incident ischemic stroke events, of who 19% were lacunar, 29% were cardioembolic and 45% were of the thrombotic stroke subtype. After adjustment for confounders (race/center, age, gender, BMI, hypertension, diabetes, LDL level, smoking, and education), regular dental care utilization was associated with lower risk for ischemic stroke overall compared with episodic dental users (adjusted HR 0.77, 95% CI 0.63-0.94). Regular dental care specifically lowered the risk of thrombotic stroke subtype (adjusted HR 0.75, 95% CI 0.56-0.99). Conclusions: Results from this prospective cohort study demonstrates an independent association between regular dental care utilization with a lower ischemic stroke risk. Further, we report the highest impact of regular dental care in lowering risk of the thrombotic stroke subtype.

Introduction Chronic kidney disease (CKD) remains a prevalent public health problem that disproportionately affects minorities and the poor, despite intense efforts targeting traditional risk factors. Periodontal diseases are common bacterial plaque-induced inflammatory conditions that can respond to treatment and have been implicated as a CKD risk factor. However there is limited evidence that treatment of periodontal disease slows the progression of CKD. Methods/design We describe the protocol of the Kidney and Periodontal Disease (KAPD) study, a 12-month un-blinded, randomized, controlled pilot trial with two intent-to-treat treatment arms: 1. immediate intensive non-surgical periodontal treatment or 2. rescue treatment with delayed intensive treatment. The goals of this pilot study are to test the feasibility of conducting a larger trial in an ethnically and racially diverse, underserved population (mostly poor and/or low literacy) with both CKD and significant periodontal disease to determine the effect of intensive periodontal treatment on renal and inflammatory biomarkers over a 12-month period. Results To date, KAPD has identified 634 potentially eligible patients who were invited to in-person screening. Of the 83 (13.1%) of potentially eligible patients who attended in-person screening, 51 (61.4%) were eligible for participation and 46 enrolled in the study. The mean age of participants is 59.2 years (range 34 to 73). Twenty of the participants (43.5%) are Black and 22 (47.8%) are Hispanic. Discussion Results from the KAPD study will provide needed preliminary evidence of the effectiveness of non-surgical periodontal treatment to slow CKD progression and inform the design future clinical research trials.

Introduction: Epidemiological studies have shown that serum inflammatory markers are independently associated with ischemic stroke. We assessed the hypothesis that specific inflammatory mediator is associated with specific ischemic stroke subtypes in the Atherosclerosis Risk in Communities (ARIC) study. Methods: In the ARIC study, serum inflammatory mediators were assessed in a cohort of subjects without prior stroke. They included high sensitivity C-reactive protein (hs-CRP), interleukin 1ra (IL-1ra), and Intercellular Adhesion Molecule 1(sICAM1) and were followed for all vascular events. All stroke events were adjudicated and classified into stroke subtypes by standard definitions. Multivariable Cox proportional hazards models were used to study the relationship between elevated inflammatory markers (upper quartile compared with lower three quartiles) and ischemic stroke, as well as stroke subtypes (cardioembolic, lacunar or thrombotic). Results: At the fourth ARIC study visit, serum inflammatory mediators were assessed in a cohort of 5663 subjects (mean age±SD=62.3±5.6, 55% female, 83% white and 17% African-American). Over a 15-year follow-up, 237 (4.2%) subjects had incident ischemic stroke of which 47% were thrombotic, 26% were cardioembolic, and 20% were of the lacunar stroke subtype. After adjustment for Race/Center, Age, Gender, BMI, Hypertension, Diabetes, LDL Level, Smoking (3-levels), Pack Years, Education (3-levels), hs-CRP (adjusted HR 1.45, 95% CI 1.08-1.96), IL-1ra (adjusted HR 1.90, 95% CI 1.09-3.28) and sICAM1(adjusted HR 1.33, 95% CI 1.0-1.78) were associated with overall ischemic stroke. This was driven by associations between hs-CRP and thrombotic stroke (adjusted HR 1.73, 95% CI 1.14-2.61), IL-1ra and cardioembolic stroke (adjusted HR 3.42, 95% CI 1.23-9.53), and sICAM-1 and lacunar stroke (adjusted HR 1.92, 95% CI 1.05-3.50). Conclusions: Results from this prospective show an independent association between serum inflammatory mediators and incident ischemic stroke. These associations appear to be attributed to the association between specific inflammatory mediator and individual stroke subtype. These results shed light to the mechanism by which inflammatory mediators contribute to stroke risk.

Introduction: Gum, or periodontal disease (PD) is a risk factor for cardiovascular disease. We assessed the graded association of PD levels with incident ischemic stroke as well as the etiological stroke subtypes in the Atherosclerosis Risk in Communities (ARIC) study. Methods: PD was assessed by full-mouth periodontal measurements from 6 sites per tooth, in subjects without prior stroke and categorized into periodontal profile class (PPC). A Latent Class Analysis was used to identify 7 distinct PPCs using the entire cohort that included tooth level periodontal measurements and tooth loss. Stroke diagnoses were based on computer derived diagnosis medical record review and imaging confirmation. Classification required evidence of sudden onset of neurological deficit(s) lasting ≥24 hours. Strokes were classified according to etiology as thrombotic, lacunar, and cardioembolic subtypes. Results: At the fourth ARIC visit (1996-1998), a cohort of 6711 subjects (mean age±SD=62.3±5.6, 55% female, 81% white and 19% African-American) were assessed for PD. A total of 299 incident ischemic strokes (47% thrombotic, 26% cardioembolic and 20% lacunar) occurred over a 15-year period. The seven levels of PPC showed a graded association with incident ischemic stroke as noted in the figure. Participants with mild PD (adjusted HR 1.9 95% CI 1.2-3.0), moderate PD group (adjusted HR 2.1 95% CI 1.2-3.5) and severe PD (adjusted HR 2.2 95% CI 1.3-3.8) had an increased risk of incident ischemic stroke, compared with participants without PD after adjustment for confounders (age, race, gender, BMI, hypertension, diabetes, LDL cholesterol, smoking and education). There were class specific associations noted between PD with cardioembolic and thrombotic stroke subtypes. Conclusions: A graded association was noted between incident ischemic stroke and increasing levels of PPC. Further, we report class specific associations between PD with cardioembolic and thrombotic stroke subtypes.

Observational studies consistently support a relationship between poor oral health and systemic diseases like cardiovascular disease and diabetes mellitus. The purpose of this study was to identify current practices and perceived barriers among North Carolina dentists regarding the incorporation of oral-systemic evidence into the delivery of patient care. A survey questionnaire was developed, pilot tested, revised, and mailed to 1,350 licensed dentists in North Carolina. The response rate was 49 percent. Bivariate analysis was used to compare practice behaviors and barriers among age, gender, practice type, and setting categorizations using the chi-square test. Respondents were predominantly male (77 percent), in solo practice (59.4 percent), and in urban or suburban settings (74 percent). Half (50 percent) reported updating medical histories at every patient visit. Younger dentists were significantly (p

Periodontal disease (PD) has been shown to be associated with incident stroke. We investigated whether PD is independently associated with recurrent vascular events and certain inflammatory markers in stroke/transient ischemic attack (TIA) patients. In this prospective, longitudinal, hospital-based cohort study, PD was assessed in stroke/TIA patients. High periodontal disease (HPD) was defined as the highest tertile of extent (% of sites) with an attachment loss of 5 mm or more. Serum interleukin-6 (IL-6), high-sensitivity C-reactive protein, and soluble intracellular adhesion molecule 1 (s-ICAM) were measured. The patients were followed for recurrent vascular events—stroke, TIA, myocardial infarction, and vascular death. In the 106 patients who were evaluated, 40 (38%) showed HPD and 27 (26%) had recurrent vascular events over a median of 24 months (range, 12-24 months). HPD patients had higher levels of IL-6 ( P = .01) and s-ICAM ( P = .03). HPD was associated with recurrent vascular events before (log-rank P = .01; hazard ratio [HR], 2.6; 95% confidence interval [CI], 1.2-5.7) and after adjustment for significant confounders—age and stroke status (HR, 2.5; 95% CI, 1.1-5.5; P = .03); adjustment for possible confounders—age, male, years of education, and cardioembolic strokes (HR, 2.8; 95% CI, 1.2-6.5; P = .02); and adjustment for propensity score that accounted for all potential measured confounders (HR, 2.8; 95% CI, 1.2-6.5; P = .02). There is an independent association between HPD and recurrent vascular events in stroke/TIA patients. HPD is also associated with higher serum levels of IL-6 and s-ICAM.

Aim Investigate short-term effects of power brushing following experimental induction of biofilm overgrowth in periodontal disease states. Materials and Methods Overall, 175 subjects representing each of five biofilm–gingival interface (BGI) periodontal groups were enrolled in a single-blind, randomized study. After stent-induced biofilm overgrowth for 21 days subjects received either a manual or a power toothbrush to use during a 4 weeks resolution phase. At baseline and during induction and resolution, standard clinical parameters were measured. Subclinical parameters included multikine analysis of 13 salivary biomarkers and 16s Human Oral Microbe Identification Microarray (HOMIM) probe analysis of subgingival plaque samples. Results All groups exhibited significantly greater reductions in bleeding on probing (BOP) (p = 0.002), gingival index (GI) (p = 0.0007), pocket depth (PD) (p = 0.04) and plaque index (p = 0.001) with power brushing compared to manual. When BGI groups were combined to form a shallow PD (PD ≤ 3 mm) and a deep PD group (PD > 4 mm) power brushing reduced BOP and GI in subjects with both pocket depths. Power brushing significantly reduced IL-1β levels at resolution while changes in bacterial levels showed non-significant trends between both brushing modalities. Conclusions Short-term changes in select clinical parameters and subclinical salivary biomarkers may be useful in assessing efficacy of power brushing interventions in a spectrum of periodontal disease states.

To assess the impact of third molar removal on the periodontal status of adjacent second molars and teeth more anterior in the mouth in patients with mild symptoms of pericoronitis.Healthy patients with mild symptoms of pericoronitis affecting at least 1 mandibular third molar were recruited for a study approved by the institutional review board. The subset analyzed in this study had all 4 third molars removed. Data were collected at enrollment and at least 3 months after surgery. Full-mouth periodontal probing was conducted at 6 sites per tooth. A probing depth of at least 4 mm (PD4+) was considered an indicator for periodontal pathology. The presence of a PD4+ on the distal of second molars (D2Ms) or anterior to the D2Ms, the number of PD4+s, and extent scores (percentage of PD4+s of all possible probing sites) were assessed at the patient and jaw levels. The association between patients' pre- and postsurgical periodontal status was assessed using the McNemar exact test. The level of significance was set at .05.The median age of the 69 patients was 21.8 years (interquartile range, 20.2 to 25.2 yr). Forty-five percent were men, and 57% were Caucasian. Significantly more patients (88%) had at least 1 D2M PD4+ at enrollment compared with after surgery (46%; P.01). D2M extent scores decreased from 31.5 at enrollment to 11 after surgery. Significantly more patients (61%) had at least 1 PD4+ anterior to the D2M at enrollment compared with after surgery (29%; P.01). Extent scores anterior to the D2M decreased from 2.0 at enrollment to 0.6 after surgery.Removal of third molars in patients with mild pericoronitis symptoms improved the periodontal status of the D2Ms and teeth more anterior in the mouth.

To assess the relationship between the presence or absence of visible third molars and outcomes for periodontal inflammatory disease.Obstetric subjects, at enrollment in an institutional review board-approved, multisite study, Maternal Oral Therapy to Reduce Obstetric Risk (N = 1,798), were divided into 2 groups, those with no visible third molars (n = 692) and those with at least 1 visible third molar (n = 1,106), the predictor variables for this study. The principal outcome variables were the patient-level periodontal status of the first/second molars: mean periodontal probing depths, mean attachment levels, and mean extent scores. Periodontal disease severity also was assessed by criteria from the Oral Conditions and Pregnancy trial and the Centers for Disease Control and Prevention/American Academy of Periodontology. Outcomes according to the presence or absence of third molars were compared with χ(2) statistics and multivariable analyses. Significance was set at P.05.Significantly more subjects had at least 1 third molar (62%) as compared with subjects with no visible third molar (38%) (P.01). Ethnic characteristics of the 2 groups were similar. Overall, more subjects were white (61%), with most identifying their ethnicity as Latino. African-American subjects were well represented (37%). Subjects with a visible third molar were more likely to be significantly older, to be receiving medical assistance, and to have used tobacco before pregnancy. If subjects had at least 1 visible third molar, the mean first/second molar probing depths, attachment levels, and scores for bleeding on probing were significantly greater even after adjustment for covariates. On the basis of either Oral Conditions and Pregnancy criteria or Centers for Disease Control and Prevention/American Academy of Periodontology criteria, subjects were significantly more likely to have moderate or severe periodontal disease if a third molar was detected.If at least 1 visible third molar was detected in subjects in the Maternal Oral Therapy to Reduce Obstetric Risk study at enrollment as compared with no detected third molars, periodontal outcomes were significantly worse.

It is estimated that over 26% of people, ages 65–74 in the US are edentulous.1 The number of edentulous people and people with significant number of missing teeth is even worse in the developing world. It is known that edentulism is a comorbidity to several systemic and oral diseases such as osteoporosis, hypertension, atherosclerosis, diabetes, cancer, etc. 2–7 However, the underlying molecular mechanism that may lead an edentulous individual to be at risk for these diseases is not known. Several biological changes occur after loss of natural teeth. These include reduction on masticatory efficiency, altered neuronal/physiolocal sensation, psycological effects, alveolar bone remodeling, and changes on microflora composition. Complete and partial edentulism clearly reduces mechanical chewing function and esthetics. Edentulism and its comobidities have a bidirectional relationship, in other words, each condition worsens the other. While current treatment modalities for edentulism, such as dental implant therapy, are aimed at improving function and esthetics for patients, the systemic and oral co-morbidities of edentulism, including diabetes, osteoporosis, as well as a lack of sufficient remaining alveolar bone, challenge the immediate and long-term success of dental implant therapy. Recently there has been an incorporation of porous tantalum metal into titanium dental implants. This new type of dental implant may improve dental implant therapy in certain populations. This article therefore aims to review the basic science development, advantages and cautions, as well as possible clinical applications of the new tantalum metal implants.

BACKGROUND: The goal of this study is to use bioinformatics tools to explore identification and definition of distinct periodontal and tooth profile classes (PPCs/TPCs) among a cohort of individuals by using detailed clinical measures at the tooth level, including both periodontal measurements and tooth loss. METHODS: Full-mouth clinical periodontal measurements (seven clinical parameters) from 6,793 individuals from the Dental Atherosclerosis Risk in Communities Study (DARIC) were used to identify PPC. A custom latent class analysis (LCA) procedure was developed to identify clinically distinct PPCs and TPCs. Three validation cohorts were used: NHANES (2009 to 2010 and 2011 to 2012) and the Piedmont Study population (7,785 individuals). RESULTS: The LCA method identified seven distinct periodontal profile classes (PPCs A to G) and seven distinct tooth profile classes (TPCs A to G) ranging from health to severe periodontal disease status. The method enabled identification of classes with common clinical manifestations that are hidden under the current periodontal classification schemas. Class assignment was robust with small misclassification error in the presence of missing data. The PPC algorithm was applied and confirmed in three distinct cohorts. CONCLUSIONS: The findings suggest PPC and TPC using LCA can provide robust periodontal clinical definitions that reflect disease patterns in the population at an individual and tooth level. These classifications can potentially be used for patient stratification and thus provide tools for integrating multiple datasets to assess risk for periodontitis progression and tooth loss in dental patients.

Purpose The purpose of this study was to compare the prevalence of third molars from the US National Health and Nutrition Examination Survey (NHANES) and the Swedish survey. Materials and Methods This cross-sectional study involved the comparison of the only published data on third molar prevalence. The number of visible third molars in the NHANES of 2011 through 2012 were assessed in nonclinical settings by trained, calibrated dental hygienists and reported by age decade (approximately 5,000 patients). Similar data were reported for the Swedish population with data collected in clinical settings (approximately 700 patients). The primary outcome variable was the number of third molars (0 to 4); the predictor variables were age cohorts (20 to 29 through 70 to 79 yr). Outcome data were reported with descriptive statistics. Results In the youngest cohort (20 to 29 yr), having no visible third molars was more likely in the US population than in the Swedish population (47 vs 2%, respectively). By 50 to 59 years, outcomes for no third molars were similar in the United States and Sweden (53 and 57%, respectively). Conclusion The presence or absence of third molars reported from the US and Swedish populations presented contrasting patterns, particularly in the younger cohorts. More comprehensive and detailed data are required in future surveys as population studies on third molars become more important for clinicians and other stakeholders.

Purpose Multifactorial etiological factors contribute to denture stomatitis (DS), a type of oral candidiasis; however, unlike other oral candidiasis, DS can occur in a healthy person wearing a denture. In this study, we therefore attempt to explore the association between candida, denture, and mucosal tissue using 1) exfoliative cytology, 2) the candidal levels present in saliva, on mucosal tissues and on denture surfaces, and 3) the salivary flow rate and xerostomic symptoms.

Purpose To establish a relationship between visible third molars (M3s) and increased periodontal probing depths on teeth other than M3s and to examine the hypothesis that the presence of M3s and/or increased probing depths and local inflammation associated with M3s was associated with increased levels of serum inflammatory markers. Patients and Methods The data from three previous population studies (Dental Atherosclerosis Risk In Communities [DARIC], Oral Conditions and Pregnancy [OCAP], and National Health and Nutrition Estimates Study [NHANES III]) and the third molar clinical trials of young adults (White et al) are summarized. A secondary analysis determined whether the presence or absence of visible M3s was associated with an increased prevalence of clinical signs of periodontal disease using adjusted logistic regression models. In addition, serum samples collected from the OCAP, DARIC, and White studies were used to measure the markers of systemic inflammation, C-reactive protein, interleukin-6, and soluble intracellular adhesion molecule-1. Results In young adults, asymptomatic M3s were associated with an increase in periodontal probing depths of at least 4 mm on second molars and an increase in probing depth of at least 2 mm in 24% of subjects after 2 years. Retention of asymptomatic M3s for 6 years led to a significant increase in the number of subjects with a probing depth of 4 mm or more in non-M3 regions of the mouth. Findings from the DARIC, OCAP, and NHANES III further confirmed the association between the M3 probing depth and periodontal inflammation on non–M3s. Retention of M3s in the presence of periodontal inflammation was associated with significant increases in the serum interleukin-6, soluble intracellular adhesion molecule-1, and C-reactive protein levels. Conclusion Patients deciding to retain M3s should consider the potential long-term effects on their periodontal status and the potential for the retained M3s to serve as a chronic source of inflammation that stresses their systemic health.

Although associations between periodontal and systemic health have been well established, there is little evidence regarding dental hygienists' knowledge of the oral-systemic connection. The purpose of this study was to determine the knowledge levels of North Carolina dental hygienists regarding oral-systemic connections and their attitudes and confidence about incorporating this knowledge into clinical practice. A survey was developed, pilot tested, revised, and mailed to 1,665 licensed dental hygienists in North Carolina. After three mailings, the response rate was 62 percent, with 52 percent (N=859) meeting the inclusion criteria. The majority (>80 percent) of the respondents correctly identified risk factors for diabetes and cardiovascular disease (CVD), but were less knowledgeable about risk factors for osteoporosis and adverse pregnancy outcomes. Most knew that there is strong evidence linking periodontal disease with CVD (77 percent) and diabetes (70 percent). The majority felt that dental hygienists should be trained to identify risk factors for oral-systemic disease (94 percent) and to actively manage patients with systemic disease (78 percent). Eighty-eight percent felt that dental and medical professionals should be taught to practice collaboratively. These dental hygienists had a high level of knowledge in some areas of oral-systemic disease but could improve their confidence levels and knowledge through expanded content in their educational programs and continuing education. Inter-professional education and collaboration would also assist in integration of knowledge into clinical practice.

Objective Diabetes has been linked with more severe periodontal disease and with coronary heart disease (CHD). The purpose of this study was to determine if periodontal infection was a significant modifier in the risk that diabetes poses for increased carotid artery intimal–medial wall thickness (IMT) and more advanced atheroma lesions as reflected in atherosclerotic plaque calcification measured by acoustic shadowing. Methods and results Comparisons for analyses of cardiovascular outcomes were performed based upon periodontitis and diabetes status. Periodontitis was measured using pocket depth and attachment loss at six sites per tooth. Cross-sectional data on 6048 persons aged 52–74 years were obtained from the Dental Atherosclerosis Risk in Communities Study. Participants without diabetes ( n =5257) were compared to those with diabetes ( n =791). Dependent variables were thick IMT (>1mm), presence of acoustic shadowing, and prevalent CHD. All models were adjusted for the following covariates: gender, age, race/center, LDL and HDL cholesterol, BMI, triglycerides, hypertension, smoking, income and education. For multivariate model building, all non-normally distributed variables were transformed and multivariable logistic regression analyses were performed to evaluate the relationship between periodontal infection, diabetes, and cardiovascular outcomes. Individuals with diabetes and with severe periodontitis were found to be significantly more likely to have IMT>1mm [OR=2.2, (1.4–3.5)], acoustic shadowing [OR=2.5, (1.3–4.6)], and CHD [OR=2.6, (1.6–4.2)] compared to those without diabetes or periodontal disease. Conclusion Results from this study suggest that among people with diabetes, periodontal disease may increase the likelihood of subclinical atherosclerotic heart disease and CHD.

Purpose To assess the prevalence of caries experience and periodontal pathology on third molar teeth compared with first and second molars and teeth more anterior from subjects who had data collected over time in a longitudinal clinical study. Patients and Methods Healthy subjects with 4 asymptomatic third molars and data for at least 4 years after enrollment were included in these analyses. The presence or absence of caries experience on the occlusal surface of the third molars and any surface of the first or second molars was assessed using a visual-tactile caries examination. Full mouth periodontal probing, 6 sites per tooth, was conducted as a measure of clinical periodontal status. The primary outcome measures were at least 1 periodontal probing depth of at least 4 mm versus none, and caries experience versus no caries experience. The prevalence of caries experience and periodontal pathologic findings at follow-up and the relationship of the occurrence between the third molars and teeth more anterior in the mouth were examined using McNemar's statistics. Results The follow-up was a median of 6.9 years (interquartile range 4.6 to 7.7 years) for 179 subjects, with a mean age of 29 years. More subjects were female (54%) and white (80%). At follow-up, 85% of the subjects had caries experience detected on the first or second molars, and only 50% had a third molar affected. In contrast, at follow-up, the presence of at least 1 periodontal probing depth of at least 4 mm was marginally more prevalent on the third molars than on the first or second molars (56% and 50%, respectively). Fewer subjects had third molars free of caries experience and periodontal pathology at follow-up compared with at enrollment (28% versus 38%, respectively). Conclusions The prevalence of both third molar caries experience and third molar periodontal pathology increased from baseline to the follow-up examination. At follow-up, the prevalence of caries experience was greater on the first or second molars than on the third molars, and periodontal pathology were greater on the third molars than on the more anterior teeth.

Maternal periodontal disease is found inor = 40% of pregnant women and is associated with adverse pregnancy outcomes. Vitamin D deficiency may play a role in periodontal disease and tooth loss, and insufficient vitamin D status is common among pregnant women. The objective of this study is to examine the relationship between maternal vitamin D status and periodontal disease.A case-control study was conducted. Cases were defined as pregnant women with clinical moderate to severe periodontal disease; controls were pregnant women who were periodontally healthy. Maternal data were chart abstracted and serum was collected between 14 and 26 weeks of gestation. Serum 25-hydroxyvitamin D (25[OH]D) levels were measured using liquid chromatography-tandem mass spectrometry. Median serum 25(OH)D levels and prevalence of vitamin D insufficiency (defined as75 nmol/l) were compared between cases and controls. The odds ratio and 95% confidence interval for moderate to severe periodontal disease among women with vitamin D insufficiency was calculated using multivariable logistic regression, adjusting for maternal race, season of blood draw, and other potential confounders.A total of 117 cases were compared to 118 controls. Cases had lower median 25(OH)D levels than controls (59 versus 100 nmol/l; P0.001) and were more likely to have vitamin D insufficiency (65% versus 29%; P0.001). The adjusted odds ratio (95% confidence interval) for moderate to severe periodontal disease among women with vitamin D insufficiency was 2.1 (0.99 to 4.5).Vitamin D insufficiency (serum 25[OH]D75 nmol/l) is associated with maternal periodontal disease during pregnancy. Vitamin D supplementation represents a potential therapeutic strategy to improve maternal oral health.

Purpose To assess the relationship between visible third molars and the periodontal status of teeth more anterior in the mouth from reports that included periodontal probing data for all teeth. Materials and Methods Each of 4 reports that included periodontal probing data, 6 probing sites for all teeth, including third molars collected by trained, clinician examiners, were briefly summarized. The design, strengths, and weaknesses of each of the 4 studies were compared and summarized. A Forest plot was used to combine the findings from the 4 studies comparing the mean second molar probing depth differences in mm by the presence of at least 1 visible third molar or no visible third molar. Results A review of the data from 4 reports, 1 from middle-age adults and 3 from young adults, suggested an association between the visible presence of a third molar and increased periodontal probing depths on teeth more anterior in the mouth, predominately the first and second molars. Coupled with the probing depth around the third molars, the result was an expanded surface area at the biofilm–gingival interface. Conclusions Although all those with retained third molars are not at increased risk, the summary data we have reported suggest that those with a visible third molar are more likely to have greater periodontal probing depths overall, particularly on second molars, and a greater surface area of the biofilm–gingival interface compared with those with no visible third molar.