Inflammation and tissue remodeling mediator expression during gingivitis: A comparison between experimental, naturally occurring gingivitis, and periodontal health.

BACKGROUND: The aim of this study is to evaluate the immune regulation and tissue remodeling responses during experimental gingivitis (EG) and naturally occurring gingivitis (NG) to provide a comprehensive analysis of host responses. Gingival crevicular fluid (GCF) was obtained from 2 human studies conducted in university settings. METHODS: The EG study enrolling 26 volunteers provided controls for the baseline (Day 0) from healthy disease-free participants, while Day 21 (the end of EG induction of the same group) was used to represent EG. Twenty-six NG participants age-matched with those of the EG group were recruited. GCF samples were analyzed for 39 mediators of inflammatory/immune responses and tissue remodeling using commercially available bead-based multiplex immunoassays. The differences in GI and mediator expression among groups were determined at a 95% confidence level (p ≤ 0.05) by a 2-way analysis of variance (ANOVA) with a post-hoc Tukey's test. RESULTS: Our findings showed that EG had a greater gingival index than NG and was healthy (p < 0.01 of all comparisons). Furthermore, EG showed significantly higher levels of MPO (p < 0.001), CCL3 (p < 0.05), and IL-1B (p < 0.001) than NG. In contrast, NG had increased levels of MIF (p < 0.05), Fractalkine (p < 0.001), angiogenin (p < 0.05), C3a (p < 0.001), BMP-2 (p < 0.001), OPN (p < 0.05), RANKL (p < 0.001), and MMP-13 (p < 0.001) than EG. CONCLUSIONS: Consistent with the findings from chronic (NG) versus acute (EG) inflammatory lesions, these data reveal that NG displays greater immune regulation, angiogenesis, and bone remodeling compared to EG.

Dental Utilization of Refugee Children in Washington State Varies by Demographic Characteristics.

Purpose: To assess factors associated with the dental utilization of refugee children in Washington state who received oral health care. Methods: This study used Medicaid data of newly arrived children who resettled in 2015. Demographics, refugee population density groups, special care needs, dates of dental encounters, and dental claim variables were analyzed using descriptive statistics, analysis of variance (ANOVA), regression analysis, and the Cox proportional-hazard ratios (P<0.05). Results: Among 1,125 children, 78 percent had at least one dental claim. The majority were under six years (37 percent), male (55 percent), and without disabilities (98 percent). On average children started using dental care within 6.0 months (±4.0 standard deviation) of resettlement (median equals 4.4; interquartile range [IQR] equals 2.6 to 10.3). White children had the greatest mean number of dental claims, whereas Black children had the least (P<0.001). Children from the low-volume refugee population density group were significantly less likely to have a dental claim than children from the medium-volume refugee population density group (P<0.001). Compared to 13- to 21-year-olds, children aged zero to seven years and seven to 13 years had a 46.7 percent (95 percent confidence interval [95% CI] equals 24.9 to 72.3 percent) and 54.8 percent (95% CI equals 30.3 to 83.9 percent) significantly increased likelihood of having their first dental claim (P<0.001). Conclusions: A large percentage (78 percent) of children newly resettled in the state of Washington utilized at least one dental service. Age, race, and refugee population density group were significantly associated with utilization within the initial 12 months after resettlement.

Localized microbially induced inflammation influences distant healthy tissues in the human oral cavity.

Variation in human immune response to the same bacterial or viral pathogen is well established in the literature. Variation in immune response to microbial challenge has also been observed within the human oral cavity. Our recent study focused on characterizing observed variations in microbially induced gingival inflammation-resulting in three distinct clinical Inflammatory Responder Types (IRTs): High-IRT, Low-IRT, and Slow-IRT. Here, we applied a high-resolution temporal multiomic analysis during microbially induced inflammation in order to characterize the effects of localized oral inflammation on distant healthy tissues in young healthy adults. Our results highlight a nonlocalized subclinical effect with alterations in proinflammatory host mediators and an ecological shift toward dysbiosis within the subgingival microbiome in an IRT-dependent manner-despite maintained oral hygiene. Our results provide mechanistic insight into how healthy tissues within humans are influenced by distant localized inflammation and may ultimately become susceptible to disease.

Geospatial Analysis of Dental Access and Workforce Distribution in Kenya.

Background and Objective: One of the major factors affecting access to quality oral healthcare in low- and middle-income countries is the under-supply of the dental workforce. The aim of this study was to use Geographical Information System (GIS) to analyse the distribution and accessibility of the dental workforce and facilities across the Kenyan counties. Methods: This was a cross-sectional study targeting dental professionals and their practices in Kenya in 2013. Using QGIS 3.16, these data were overlaid with data on population size and urbanization levels. For access measurement, buffers were drawn around each clinic at distances of 2.5, 5, 10 and 20 km, and the population within each determined. Findings: Nine hundred six dental professionals in 337 dental clinic locations were included in the study. Dentists, community oral health officers (equivalent to dental therapists) and dental technologists comprised 72%, 15% and 12%, respectively. Nairobi county with 100% urbanization and >4000 people/km2 had 43% of the workforce and a dentist to population ratio of 1:9,018. Wajir with an urbanization level of 15% and 12 people/km2 had no dental facility. Overall, 11%, 19%, 35% and 58% of the Kenyan population were within 2.5, 5, 10 and 20 km radius of a dental clinic respectively. Conclusion: Maldistribution of dental workforce in Kenya persists, particularly in less urbanized and sparsely populated areas. GIS map production give health planners a better visual picture of areas that are most in need of health care services based on population profiles.

Integration of a new classification scheme for periodontal and peri-implant diseases through blended learning.

PURPOSE: In recent years, dental education has experienced a general shift toward an increased technology presence in education delivery and learning. This research examines the student-perceived efficacy of a blended learning approach (mixture of online content and face-to-face instruction) in a predoctoral periodontics curriculum to teach a new periodontal classification scheme to dental students in clinical training. METHODS: Participants were recruited from third- and fourth-year predoctoral periodontal classes at the University of Washington School of Dentistry. Students were administered a live lecture introducing the new classification system and given access to an online module with built in case quizzes and interactive activities. Upon completing the module, students were given a post-module survey to assess learning preferences, utilization of various learning methods, and student-perceived efficacy of blended learning. RESULTS: In a study group of 69 predoctoral dental students, the online module was the most preferred (52.2% ranked first) and utilized learning method for students (p < 0.001). Over 80% of students agreed or strongly agreed that they enjoyed using it and found it more effective than traditional lecture alone. Traditional lecture was preferred by 31.9% of students, and no students ranked the assigned reading as their first choice of learning method (p < 0.001). CONCLUSIONS: Our findings demonstrate higher student preference, utilization, and self-perceived efficacy of blended learning as compared to traditional assigned readings and lectures - supporting blended learning as a promising educational approach for predoctoral dental education.

Human enamel thickness and ENAM polymorphism.

The tooth enamel development gene, enamelin (ENAM), showed evidence of positive selection during a genome-wide scan of human and primate DNA for signs of adaptive evolution. The current study examined the hypothesis that a single-nucleotide polymorphism (SNP) C14625T (rs7671281) in the ENAM gene identified in the genome-wide scan is associated with a change in enamel phenotype. African Americans were selected as the target population, as they have been reported to have a target SNP frequency of approximately 50%, whereas non-Africans are predicted to have a 96% SNP frequency. Digital radiographs and DNA samples from 244 teeth in 133 subjects were analysed, and enamel thickness was assessed in relation to SNP status, controlling for age, sex, tooth number and crown length. Crown length was found to increase with molar number, and females were found to have thicker enamel. Teeth with larger crowns also had thicker enamel, and older subjects had thinner enamel. Linear regression and generalized estimating equations were used to investigate the relationship between enamel thickness of the mandibular molars and ENAM SNP status; enamel in subjects with the derived allele was significantly thinner (P=0.040) when the results were controlled for sex, age, tooth number and crown length. The derived allele demonstrated a recessive effect on the phenotype. The data indicate that thinner dental enamel is associated with the derived ENAM genotype. This is the first direct evidence of a dental gene implicated in human adaptive evolution as having a phenotypic effect on an oral structure.

Microbial protection and virulence in periodontal tissue as a function of polymicrobial communities: symbiosis and dysbiosis.

This review discusses polymicrobial interactions with the host in both health and disease. As our ability to identify specific bacterial clonal types, with respect to their abundance and location in the oral biofilm, improves, we will learn more concerning their contribution to both oral health and disease. Recent studies examining host- bacteria interactions have revealed that commensal bacteria not only protect the host simply by niche occupation, but that bacterial interactions with host tissue can promote the development of proper tissue structure and function. These data indicate that our host-associated polymicrobial communities, such as those found in the oral cavity, co-evolved with us and have become an integral part of who we are. Understanding the microbial community factors that underpin the associations with host tissue that contribute to periodontal health may also reveal how dysbiotic periodontopathic oral communities disrupt normal periodontal tissue functions in disease. A disruption of the oral microbial community creates dysbiosis, either by overgrowth of specific or nonspecific microorganisms or by changes in the local host response where the community can now support a disease state. Dysbiosis provides the link between systemic changes (e.g. diabetes) and exogenous risk factors (e.g. smoking), and the dysbiotic community, and can drive the destruction of periodontal tissue. Many other risk factors associated with periodontal disease, such as stress, aging and genetics, are also likely to affect the microbial community, and more research is needed, utilizing sophisticated bacterial taxonomic techniques, to elucidate these effects on the microbiome and to develop strategies to target the dysbiotic mechanisms and improve periodontal health.

Effect of implant surface and grafting on implants placed into simulated extraction sockets: a histologic study in dogs.

PURPOSE: To study bone healing at implant sites in simulated extraction sockets with 1-mm marginal defects and compare healing around a turned surface (T) to that around a porous oxide surface prepared by anodic oxidation (AO) with or without the use of an autogenous bone graft. MATERIALS AND METHODS: All mandibular premolars and first molars were extracted from 10 mongrel dogs. After 9 weeks, four sites were prepared on both sides of all mandibles. Each osteotomy was widened in the coronal 5 mm to create a marginal defect of 1 mm around the implants. Autogenous bone was collected during the drilling procedure. The sites were randomized to receive implants with a T or an AO surface, with or without bone grafting. The animals were sacrificed 4 months after implant placement for histologic analysis. RESULTS: Clinically, all sites healed with complete bone fill. The combination of an AO implant and a bone graft resulted in a significantly greater percentage of bone-to-implant contact (BIC) (P < .05) versus all other groups. The highest point of BIC was achieved with the AO group, which was significantly greater than the lowest group (T). No significant differences between groups were found when the apical 4 mm (non-gap areas) were compared (P = .65). CONCLUSIONS: Studies have demonstrated that bone can fill in a marginal defect around a titanium implant with varied histologic BIC, depending on implant surface type and defect dimensions. Based upon this animal study using 10 mongrel dogs, marginal circumferential defects of 1 mm showed significantly higher BIC values for implants that were prepared by AO compared to implants with a turned surface. The addition of autogenous bone grafts further enhanced the degree of BIC.

Evaluation of the use of ultrasound within a power toothbrush to dislodge oral bacteria using an in vitro Streptococcus mutans biofilm model.

PURPOSE: To investigate in vitro the use of ultrasound in a power toothbrush to aid in the removal of dental plaque biofilm without bristle contact. METHODS: Dental plaque was modeled using Streptococcus mutans biofilm adherent to hydroxyapatite disks. Treatment arms included positive and negative controls, disks with and without biofilm, respectively. Power toothbrush modes of action tested included a toothbrush with sonic and ultrasonic action (ULT), the same toothbrush with only sonic action (ULN), a sonic toothbrush (SON) and a rotating/oscillating toothbrush (OSC). The active element of the toothbrushes (bristles or point of ultrasound emission) was immersed in toothpaste slurry and held 3 mm away from the disk surface. Treatment included activation of the toothbrush mode of action for 5 seconds. Control disks were exposed to the same fluid environment but not exposed to a power toothbrush. After treatment, biofilm present on the disks was stained using a red dental plaque disclosing solution. Photographs were then taken and the presence of biofilm assessed using digital image analysis. For each disk a normalized pixel volume, related to the presence of biofilm corrected for lighting, was determined. Statistical testing was done with a one-way ANOVA and a Bonferroni post hoc test. RESULTS: Normalized pixel volumes (mean +/- standard deviation) were 0.428 (0.010) for the negative control and 1.022 (0.040) for the positive control. Normalized pixel volumes for the power toothbrush modes of action were 0.641 (0.075) for ULT, 0.972 (0.027) for ULN, 0.921 (0.010) for SON and 0.955 (0.025) for OSC. Statistical analysis showed a significant treatment effect (P<0.001). All power toothbrush modes of action exhibited some biofilm removal without bristle contact in this in vitro assay. Of the modes of action tested, the combined sonic and ultrasonic mode of action (ULT) removed the greatest amount of biofilm from the disk surfaces. The same toothbrush when tested with (ULT) and without (ULN) ultrasound showed a greater amount of biofilm removed when ultrasound was present.

16-Aza-ent-beyerane and 16-Aza-ent-trachylobane: potent mechanism-based inhibitors of recombinant ent-kaurene synthase from Arabidopsis thaliana.

The secondary ent-beyeran-16-yl carbocation (7) is a key branch point intermediate in mechanistic schemes to rationalize the cyclic structures of many tetra- and pentacyclic diterpenes, including ent-beyerene, ent-kaurene, ent-trachylobane, and ent-atiserene, presumed precursors to >1000 known diterpenes. To evaluate these mechanistic hypotheses, we synthesized the heterocyclic analogues 16-aza-ent-beyerane (12) and 16-aza-ent-trachylobane (13) by means of Hg(II)- and Pb(IV)-induced cyclizations onto the Delta12 double bonds of tricyclic intermediates bearing carbamoylmethyl and aminomethyl groups at C-8. The 13,16-seco-16-norcarbamate (20a) was obtained from ent-beyeran-16-one oxime (17) by Beckmann fragmentation, hydrolysis, and Curtius rearrangement. The aza analogues inhibited recombinant ent-kaurene synthase from Arabidopsis thaliana (GST-rAtKS) with inhibition constants (IC50 = 1 x 10-7 and 1 x 10-6 M) similar in magnitude to the pseudo-binding constant of the bicyclic ent-copalyl diphosphate substrate (Km = 3 x 10-7 M). Large enhancements of binding affinities (IC50 = 4 x 10-9 and 2 x 10-8 M) were observed in the presence of 1 mM pyrophosphate, which is consistent with a tightly bound ent-beyeranyl+/pyrophosphate- ion pair intermediate in the cyclization-rearrangement catalyzed by this diterpene synthase. The weak inhibition (IC50 = 1 x 10-5 M) exhibited by ent-beyeran-16-exo-yl diphosphate (11) and its failure to undergo bridge rearrangement to kaurene appear to rule out the covalent diphosphate as a free intermediate. 16-Aza-ent-beyerane is proposed as an effective mimic for the ent-beyeran-16-yl carbocation with potential applications as an active site probe for the various ent-diterpene cyclases and as a novel, selective inhibitor of gibberellin biosynthesis in plants.

Synergistic use of ultrasound and sonic motion for removal of dental plaque bacteria.

Proving that an idea has merit for further investigation is one of the earliest steps in product development. This proof of concept can be effectively studied in a dynamic, multidisciplinary environment where ideas can be quickly tested in a manner related to final product use. In this article, the authors demonstrate the fecundity of a multidisciplinary environment by reviewing their early work that shows that ultrasound could be added to a power toothbrush to enhance the removal of dental plaque bacteria. They hypothesized that sonic brush head motion would generate bubbles in a dentifrice so that ultrasound beamed into that slurry would cause those bubbles to expand and contract in a manner that would dislodge the plaque bacteria adherent to the tooth surfaces. In this work, Streptococcus mutans bacteria adherent to various surfaces was used as a model of dental plaque on human teeth. Prototype power toothbrushes were created using commercially available and custom components so that the ultrasound and sonic processes could be individually modified and applied. Research demonstrated that the combination of sonic and ultrasound processes could synergistically remove S mutans biofilm. This finding established the proof of concept that eventually led to the development of a power toothbrush that uses both ultrasound and sonic activity.

Sonic tooth brushing reduces gingival overgrowth in renal transplant recipients.

Cyclosporine (CSA) is a commonly used immunosuppressive medication in pediatric transplantation. Drug-induced gingival overgrowth (DIGO) is a frequent side effect associated with CSA use and can impair the patient's ability to achieve good oral hygiene. This study tested the hypothesis that sonic tooth brushing and oral hygiene instruction can reduce the occurrence or severity of DIGO in CSA-treated pediatric renal transplant recipients. Twenty-three pediatric renal transplant patients with DIGO were randomly allocated to treatment or control groups. The treatment group received oral hygiene instruction and use of a sonic toothbrush, while the control group continued their usual home care with manual brushes. Dental impressions and photographs of all subjects were taken at baseline and every 3 months for a year. The casts and photographs were evaluated by a dental panel to compare the DIGO levels from baseline until the end of the study. After 12 months the control group had significantly more severe DIGO than did the sonic tooth brushing and oral hygiene instruction group (OR=4.5, 95%CI=1.2-16.0, P=0.03). Of the risk factors considered, only male gender was significantly associated with worse outcome (OR=6.1, 95%CI=2.3-16.1, P=0.03). The use of a powered toothbrush, together with oral hygiene instruction, may be an important component of health maintenance for pediatric transplant patients on CSA.

Evidence that TRPC1 contributes to calcium-induced differentiation of human keratinocytes.

External calcium ion concentration is a major regulator of epidermal keratinocyte differentiation in vitro and probably also in vivo. Regulation of calcium-induced differentiation changes is proposed to occur via an external calcium-sensing, signaling pathway that utilizes increases in intracellular calcium ion concentration to activate differentiation-related gene expression. Calcium ion release from intracellular stores and calcium ion influx via store-operated calcium-permeable channels are key elements in this proposed signaling pathway; however, the channels involved have not yet been identified. The present report shows that human gingival keratinocytes (HGKs) also undergo calcium-induced differentiation in vitro as indicated by involucrin expression and morphological changes. Moreover, TRPC1, which functions as a store-operated calcium channel in a number of cell types, including epidermal keratinocytes, is expressed in both proliferating and differentiating HGKs. Transfection of HGKs with TRPC1 siRNA disrupted expression of TRPC1 mRNA and protein compared with transfection with scrambled TRPC1 siRNA. Cells with disrupted TRPC1 expression showed decreased calcium-induced differentiation as measured by involucrin expression or morphological changes, as well as decreased thapsigargin-induced calcium ion influx, and a decreased rate of store calcium release. These results indicate that TRPC1 is involved in calcium-induced differentiation of HGKs likely by supporting a store-operated calcium ion influx.

Adjunctive periodontal therapies.

In general, systemic and local chemotherapeutic treatments offer a variety of options as adjuncts to traditional mechanical therapy, but they should not be used routinely for every patient. In fact, initial debridement to disrupt the biofilm and remove calculus prior to drug treatment may enhance results. Dentists will need to use their clinical judgment based on disease nature and severity to make treatment decisions, with the knowledge that these therapies may be best utilized in the few localized persistent lesions present following thorough scaling and root planing.

Periodontal disease pathogenesis: genetic risk factors and paradigm shift.

Periodontitis is a widespread disease caused by oral bacteria and their interaction with lifestyle and genetic risk factors. The focus of periodontal research has expanded over the past few years to include significant progress in the understanding of genetic processes provided by the Human Genome Project. This presentation summarizes recent views on periodontal pathogenesis and the genetic risk factors involved in the disease. Additionally, it describes the paradigm shift in periodontal care, which is evolving from a repair-based to a wellness-based model.

Clinical effects of scaling and root planing on untreated teeth.

OBJECTIVE: The aim of this report is to examine whether scaling and root planing (SRP) in one area of the mouth may affect periodontal improvement in untreated areas in the same patient, possibly through systemic effects of treatment. MATERIAL AND METHODS: Twenty patients diagnosed with generalized aggressive periodontitis were randomized into treatment (n=11) and no treatment (n=9) groups. Within the treatment group, three quadrants were treated by SRP at week 0, 3, 12, and 24, while a single experimental quadrant remained untreated throughout the study. The outcome for all teeth was assessed using clinical parameters, subtraction radiography, and pathogenic bacteria levels in the subgingival flora over the 24-week study period. RESULTS: Compared with sites in no treatment patients, the treated sites in the treated patients showed a 1 mm decrease in probing depth (PD) (p<0.01) and a 0.5 mm increase in bone height (p<0.01) by 24 weeks. In untreated sites within treated subjects, however, PDs tended to improve (p=0.09) but at a reduced rate compared with treated sites. The levels of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, and Tannerella forsythensis (Bacteroides forsythus) remained unchanged in untreated sites while levels of Prevetolla intermedia and Treponema denticola tended to decrease as compared with controls but did not reach significance. CONCLUSIONS: This study indicates that untreated sites in treated periodontitis patients show a trend towards clinical improvement and exhibit reductions in some but not all periodontopathic bacterial species tested.

Advanced surgical techniques to enhance implant success in the maxilla.

While less emphasis has traditionally been placed on aesthetics in order to focus on successful osseointegration, increased success rates provided by contemporary endosseous root-form dental implants have improved postoperative peri-implant hard and soft tissue structures. The criteria for the evaluation of implant success should, therefore, include lack of pain, mobility, radiolucency, bone loss, infection, or paresthesia, as well as acceptability and stable aesthetics. This article discusses surgical means to preserve or restore hard and soft tissues around dental implants to achieve ideal and predictable outcomes.

Periodontitis vaccine decreases local prostaglandin E2 levels in a primate model.

Interleukin-1beta, tumor necrosis factor alpha, prostaglandin E2 (PGE2), and Porphyromonas gingivalis-specific immunoglobulin G levels in gingival crevicular fluid were measured in primates immunized with a P. gingivalis vaccine followed by ligature-induced periodontitis. Only PGE2 levels were dramatically suppressed (P < 0.0001) in immunized animals versus controls. A significant correlation (P < 0.027) was also found between PGE2 levels and decreased bone loss scores. This study presents the first evidence of a potential mechanism involved in periodontitis vaccine-induced suppression of bone loss in a nonhuman primate model and offers insight into the role of PGE2 in periodontal destruction.

Clinical application of spiral tomography in anterior implant placement: case report.

BACKGROUND: Placement of endosseous dental implants in edentulous areas of the anterior maxilla poses a unique challenge due to variations in the amount of residual alveolar bone. Implant position becomes crucial in cases demanding high esthetic results but possessing minimal ridge width or in cases requiring augmentation. Recent advances in spiral tomography have allowed for more precise planning and placement of endosseous implants in these challenging areas. METHODS: The purpose of this report is to describe a series of clinical cases in which spiral tomography was utilized in the planning and placement of endosseous dental implants. Two cases will be described utilizing initial spiral tomographic radiographs for implant planning and surgical guide fabrication, followed by post-insertion tomography to evaluate the results of implant position and inclination. RESULTS: Preimplant spiral tomograms revealed that the initial prosthetic trajectory through the proposed incisal edge of each tooth replacement would result in a final osteotomy site that would compromise the overall thickness of the facial cortical plate. After adjusting for magnification and distortion factors, new prosthetic/surgical trajectories were fabricated into the surgical guide, and this information was utilized to prepare the final implant osteotomy site. This adjustment resulted in 2 mm of residual crestal facial bone postimplant insertion, which became wider at more apical measurements. These findings were verified in the postimplant serial tomograms. CONCLUSIONS: Spiral tomography was a valuable adjunct in the treatment planning phases of endosseous dental implant placement especially in cases with minimal crestal width, high esthetic demands, or where exact implant placement is critical for successful treatment outcomes.