Immunophenotypic and Gene Expression Analyses of the Inflammatory Microenvironment in High-Grade Oral Epithelial Dysplasia and Oral Lichen Planus.

BACKGROUND: Oral lichen planus (OLP) and oral epithelial dysplasia (OED) present diagnostic challenges due to clinical and histologic overlap. This study explores the immune microenvironment in OED, hypothesizing that immune signatures could aid in diagnostic differentiation and predict malignant transformation. METHODS: Tissue samples from OED and OLP cases were analyzed using immunofluorescence/immunohistochemistry (IF/IHC) for CD4, CD8, CD163/STAT1, and PD-1/PDL-1 expression. RNA-sequencing was performed on the samples, and data was subjected to CIBERSORTx analysis for immune cell composition. Gene Ontology analysis on the immune differentially expressed genes was also conducted. RESULTS: In OED, CD8 + T-cells infiltrated dysplastic epithelium, correlating with dysplasia severity. CD4 + lymphocytes increased in the basal layer. STAT1/CD163 + macrophages correlated with CD4 + intraepithelial distribution. PD-1/PDL-1 expression varied. IF/IHC analysis revealed differential immune cell composition between OED and OLP. RNA-sequencing identified upregulated genes associated with cytotoxic response and immunosurveillance in OED. Downregulated genes were linked to signaling, immune cell recruitment, and tumor suppression. CONCLUSIONS: The immune microenvironment distinguishes OED and OLP, suggesting diagnostic potential. Upregulated genes indicate cytotoxic immune response in OED. Downregulation of TRADD, CX3CL1, and ILI24 implies dysregulation in TNFR1 signaling, immune recruitment, and tumor suppression. This study contributes to the foundation for understanding immune interactions in OED and OLP, offering insights into future objective diagnostic avenues.

Racial and ethnic disparities in periodontal health among adults seeking dental care in rural North Carolina communities: A retrospective study.

BACKGROUND: Population studies consistently demonstrate a greater prevalence of chronic diseases, including oral diseases, among underrepresented minorities. This retrospective study aimed to measure and describe the prevalence and extent of periodontitis among adults seeking dental care within an academic practice-based network in rural North Carolina. METHODS: This study used de-identified electronic health record (EHR) data from 2011 to 2017 of adult dentate patients (aged ≥30 years) seeking dental care who received a comprehensive periodontal examination at one of nine networked clinical centers. Periodontitis prevalence was calculated using CDC/AAP case definitions, along with extent (%) scores for periodontal parameters. Comparisons focused on age, sex, race, ethnicity, tobacco use, diabetes status, payer or insurance status, plaque scores, and the number of teeth. RESULTS: EHR data for 10,544 adult patients (60.5% female) indicated 79.8% had some form of periodontitis. This patient population was diverse: 22.6% Black, 4.4% American Indian, and 53.8% White, with 4.8% self-identified as Hispanic. Patients 50 years and older showed greater mean extent scores for clinical attachment levels relative to patients 30 to 49 years. Males exhibited greater periodontitis than females (p = 0.001). Blacks showed significantly (p < 0.001) greater periodontitis prevalence relative to Whites. Hispanics also showed a greater prevalence of periodontitis (p < 0.001) relative to non-Hispanics. Significantly greater periodontitis was also noted for tobacco users (p < 0.001) but not for diabetes or payer status. A multiple logistic regression analysis of periodontitis prevalence confirmed significant associations for periodontitis for age, sex, race, ethnicity, tobacco use, high plaque scores, and the number of teeth (p < 0.001), but not diabetes or payer status. CONCLUSIONS: The data document that racial and ethnic inequalities in periodontal health occur within the population of adults residing in rural communities in North Carolina and seeking dental care.

Randomized Clinical Trial of a Topical Botanical Patch for the Adjunctive Management of Periodontitis.

PURPOSE: This randomized, controlled clinical trial aimed to evaluate the clinical, adjunctive effects of an approved botanical barrier device or patch on probing parameters in patients with periodontitis. MATERIALS AND METHODS: Eighty patients with periodontitis were recruited for this single-blinded trial. Patient demographic data, including gender, age, self-reported smoking status, and history of diabetes or cardiovascular disease, were collected. At baseline, all patients received a full-mouth probing examination followed by scaling and root planing (SRP). Thereafter, patients were randomized to receive either adjunctive botanical patch applications (i.e. at 2-4 treatment sites with baseline pocket depth PD ≥6 mm) or no additional therapy (SRP alone, control). Patients applied botanical patch devices per randomization to treatment sites three times on day 0 and once daily on days 1-6. Study devices were spontaneously shed or removed by the patient at 2-2.5 h after each application. Patients were recalled for probing reexaminations at 1, 2 and 3 months. Statistical analyses focused on intergroup differences in probing parameters and included ANOVA for baseline measures and ANCOVA controlling for baseline measures at 1, 2 and 3 months in the overall population and in subpopulations (e.g. smokers vs nonsmokers). RESULTS: Randomized patient groups were balanced with respect to baseline periodontal status (mean and extent PD) but not smoking, with statistically significantly more smokers clustering in the control group (p = 0.002). For the overall population and the non-smoking subpopulation, statistically significantly improved PD and clinical attachment levels (CAL) were observed with adjunctive botanical patch therapy vs control at 1 and 2 months (p < 0.05) but not 3 months (p = 0.08 for PD). For smokers, no statistically significant intergroup differences in PD or CAL were detected with botanical patch treatment. CONCLUSIONS: The data from this trial indicate short-term improvements in probing parameters with the botanical patch device when used adjunctively with SRP, especially with non-smoking periodontitis patients.

Control of mRNA decapping by autoinhibition.

5' mediated cytoplasmic RNA decay is a conserved cellular process in eukaryotes. While the functions of the structured core domains in this pathway are well-studied, the role of abundant intrinsically disordered regions (IDRs) is lacking. Here we reconstitute the Dcp1:Dcp2 complex containing a portion of the disordered C-terminus and show its activity is autoinhibited by linear interaction motifs. Enhancers of decapping (Edc) 1 and 3 cooperate to activate decapping by different mechanisms: Edc3 alleviates autoinhibition by binding IDRs and destabilizing an inactive form of the enzyme, whereas Edc1 stabilizes the transition state for catalysis. Both activators are required to fully stimulate an autoinhibited Dcp1:Dcp2 as Edc1 alone cannot overcome the decrease in activity attributed to the C-terminal extension. Our data provide a mechanistic framework for combinatorial control of decapping by protein cofactors, a principle that is likely conserved in multiple 5' mRNA decay pathways.

Alcohol intake and periodontitis in adults aged ≥30 years: NHANES 2009-2012.

BACKGROUND: Whether an association between alcohol consumption and periodontitis exists is still unclear. This study aimed to assess the association between alcohol consumption and periodontitis. METHODS: 7062 adults 30 years or older who participated in 2009-2010 and 2011-2012 cycles of the National Health and Nutrition Examination Survey (NHANES) were included. Alcohol consumption measurement included self-reported average number of alcoholic drinks per week over the previous 12 months and was categorized into four groups (0, < 1, 1- < 8, and ≥8 drinks per week). Participants were categorized using surveillance case definitions for periodontitis that included both clinical attachment level (CAL) and periodontal probing depth (PD) measurements. The association between alcohol consumption and chronic periodontitis was evaluated by multivariable regression analyses adjusting for age, gender, race/ethnicity, education level, income-to-poverty ratio, smoking, self-rated overall oral health, and HbA1c . RESULTS: The odds ratio (95% confidence interval) of having severe periodontitis was 1.9 (1.2-3) among participants who reported alcohol consumption of ≥8 drinks compared to participants consuming some alcohol but < 1 drink per week on average. Participants who consumed 1- < 8, and ≥8 drinks per week, on average, also had higher mean PD, percentage of sites with PD ≥4 mm, mean CAL, and percentage of sites with CAL ≥3 mm compared to participants reporting consumption of < 1 drink per week. Meanwhile, the odds of having periodontitis, mean PD, extent PD ≥4 mm, mean CAL, and extent CAL ≥3 mm were not significantly different for nondrinkers than for participants who consumed some alcohol but < 1 drink per week on average. CONCLUSIONS: Alcohol consumption was associated with an increase in the likelihood of having periodontitis, particularly severe periodontitis. Consumption of some alcohol, < 1 drink per week on average, was associated with similar odds of having periodontitis compared to consumption of no alcohol.

Application of a Schizosaccharomyces pombe Edc1-fused Dcp1-Dcp2 decapping enzyme for transcription start site mapping.

Changes in the 5' leader of an mRNA can have profound effects on its translational efficiency with little effect on abundance. Sequencing-based methods to accurately map the 5' leader by identifying the first transcribed nucleotide rely on enzymatic removal of the 5' eukaryotic cap structure by tobacco acid pyrophosphatase (TAP). However, commercial TAP production has been problematic and has now been discontinued. RppH, a bacterial enzyme that can also cleave the 5' cap, and Cap-Clip, a plant-derived enzyme, have been marketed as TAP replacements. We have engineered a Schizosaccharomyces pombe Edc1-fused Dcp1-Dcp2 decapping enzyme that functions as a superior TAP replacement. It can be purified from E. coli overexpression in high yields using standard biochemical methods. This constitutively active enzyme is four orders of magnitude more catalytically efficient than RppH at 5' cap removal, compares favorably to Cap-Clip, and the 5' monophosphorylated RNA product is suitable for standard RNA cloning methods. This engineered enzyme is a better replacement for TAP treatment than the current marketed use of RppH and can be produced cost-effectively in a general laboratory setting, unlike Cap-Clip.

Adjunctive Treatment of Periodontal Disease with Self-Adhesive Hydrogel Wound Dressing: Case Series.

UNLABELLED: Periodontal disease (periodontitis) is a common inflammatory condition affecting the deep, supporting tissues around teeth. While specific bacteria in plaque biofilm initiate the disease process, host immuno-inflammatory responses are responsible for the majority of tissue destruction. Conventional methods for controlling periodontitis include mechanical removal of the biofilm-with or without surgical access-and the adjunctive use of chemotherapeutics (antimicrobials or host modulators). PerioPatch™ is an approved device product that has been developed as an oral adhesive barrier for promoting healing in inflamed oral/gingival tissues and reducing pain, irritation, and the symptoms of inflammation. In this case series, which documented the adjunctive benefits of PerioPatch therapy in patients with chronic periodontitis, 9 patients who presented with generalized moderate to severe chronic periodontitis were treated with scaling and root planing plus adjunctive PerioPatch devices. Patients applied the devices to identified areas with periodontal pocketing (≥ 6 mm at baseline) twice daily at Day 1, then once daily for Days 2 to 7. Three of the patients additionally applied devices to the treatment sites on Days 15 to 21. Patients were evaluated for changes in probing parameters at 4 to 6 weeks. RESULTS: Clinical examinations performed at baseline and post-treatment indicated consistent pocket depth reductions (mean 2.8 mm) and resolution of bleeding on probing (94%). Patients complied with the application schedule and reported no adverse effects. The authors conclude that within the confines of this case series, the PerioPatch is a novel but simple device that can be used adjunctively with scaling and root planing for the management of chronic periodontitis.

Dentists' knowledge and opinions of oral-systemic disease relationships: relevance to patient care and education.

Population studies consistently support associations between poor oral (periodontal) health and systemic diseases such as cardiovascular disease (CVD) and diabetes. The aim of this study was to assess the knowledge of dentists and document their opinions regarding the evidence on oral-systemic disease relationships. A survey consisting of 39 items was developed and mailed to 1,350 licensed dentists in North Carolina. After three mailings, 667 dentists (49%) meeting inclusion criteria responded. The respondents were predominantly male (76.3%), in solo practice (59.5%), and in non-rural settings (74%). More than 75% of these dentists correctly identified risk factors like diet, genetics, smoking, obesity, and physical inactivity for CVD and diabetes. The majority rated the evidence linking periodontal disease with CVD and diabetes as strong (71% and 67%, respectively). These dentists were most comfortable inquiring about patients' tobacco habits (93%), treating patients with diabetes (89%) or CVD (84%) and concurrent periodontal disease, and discussing diabetes-periodontal disease risks with patients (88%). Fewer respondents were comfortable asking patients about alcohol consumption (54%) or providing alcohol counseling (49%). Most agreed that dentists should be trained to identify risk factors (96%) or actively manage systemically diseased patients (74%). Over 90% agreed that medical and dental professionals should be taught to practice more collaboratively. These data indicate that these dentists were knowledgeable about oral-systemic health associations, had mixed comfort levels translating the evidence into clinical practice, but expressed support for interprofessional education to improve their readiness to actively participate in their patients' overall health management.

Factors associated with the clinical response to nonsurgical periodontal therapy in people with type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a growing health problem worldwide. People with T2DM are at risk of experiencing periodontitis and likely require treatment. Using data from the national multicenter Diabetes and Periodontal Therapy Trial (DPTT), the authors assessed patient-based characteristics associated with the clinical response to nonsurgical therapy. METHODS: The DPTT investigators randomly assigned adults with T2DM (hemoglobin A1c [HbA1c] ≥ 7 percent and < 9 percent) and moderate to advanced periodontitis to receive immediate or delayed therapy (scaling and root planing, oral hygiene instruction, chlorhexidine rinse). The investigators assessed probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), and medical conditions at baseline, three months and six months. Six-month changes in mean PD, CAL and BOP defined the treatment response. Complete data were available for 473 of 514 DPTT participants. The authors used multiple regression models to evaluate participant-level factors associated with the response. RESULTS: More severe baseline PD, CAL and BOP were associated with greater improvements in these same measurements (P < .0001). Hispanic participants experienced greater improvements in PD and CAL than did non-Hispanic participants (P < .0001). Obese participants (those with a body mass index > 30 kilograms per square meter) experienced greater reductions in PD and BOP than did participants who were not obese (P < .001). Age, sex, HbA1c values, diabetes duration, and smoking were not associated with change in any outcome (P > .1). CONCLUSIONS: In patients with T2DM, baseline disease severity was associated with the clinical response to nonsurgical periodontal therapy. Body mass index and Hispanic ethnicity-but not glycemic control, diabetes duration or smoking-also may be useful in predicting clinical changes in this population.

Dentists' practice behaviors and perceived barriers regarding oral-systemic evidence: implications for education.

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<0.05) more likely to inquire about patient blood glucose levels and utilize blood pressure guidelines. Perceived patient objections to additional fees and lack of patient acceptance were reported as significant barriers, especially among younger dentists. Significantly more rural dentists reported lack of appropriate referral options as a barrier (p<0.05). In the multivariate analysis, gender and type of practice but not age were statistically significant predictors of respondents' perceptions of patients' objection to additional fees. Dental schools need to prepare dental students for future roles in the assessment, management, and interprofessional collaboration that will be needed in the future.

The effect of nonsurgical periodontal therapy on hemoglobin A1c levels in persons with type 2 diabetes and chronic periodontitis: a randomized clinical trial.

IMPORTANCE: Chronic periodontitis, a destructive inflammatory disorder of the supporting structures of the teeth, is prevalent in patients with diabetes. Limited evidence suggests that periodontal therapy may improve glycemic control. OBJECTIVE: To determine if nonsurgical periodontal treatment reduces levels of glycated hemoglobin (HbA1c) in persons with type 2 diabetes and moderate to advanced chronic periodontitis. DESIGN, SETTING, AND PARTICIPANTS: The Diabetes and Periodontal Therapy Trial (DPTT), a 6-month, single-masked, multicenter, randomized clinical trial. Participants had type 2 diabetes, were taking stable doses of medications, had HbA1c levels between 7% and less than 9%, and untreated chronic periodontitis. Five hundred fourteen participants were enrolled between November 2009 and March 2012 from diabetes and dental clinics and communities affiliated with 5 academic medical centers. INTERVENTIONS: The treatment group (n = 257) received scaling and root planing plus chlorhexidine oral rinse at baseline and supportive periodontal therapy at 3 and 6 months. The control group (n = 257) received no treatment for 6 months. MAIN OUTCOMES AND MEASURES: Difference in change in HbA1c level from baseline between groups at 6 months. Secondary outcomes included changes in probing pocket depths, clinical attachment loss, bleeding on probing, gingival index, fasting glucose level, and Homeostasis Model Assessment (HOMA2) score. RESULTS: Enrollment was stopped early because of futility. At 6 months, mean HbA1c levels in the periodontal therapy group increased 0.17% (SD, 1.0), compared with 0.11% (SD, 1.0) in the control group, with no significant difference between groups based on a linear regression model adjusting for clinical site (mean difference, -0.05% [95% CI, -0.23% to 0.12%]; P = .55). Periodontal measures improved in the treatment group compared with the control group at 6 months, with adjusted between-group differences of 0.28 mm (95% CI, 0.18 to 0.37) for probing depth, 0.25 mm (95% CI, 0.14 to 0.36) for clinical attachment loss, 13.1% (95% CI, 8.1% to 18.1%) for bleeding on probing, and 0.27 (95% CI, 0.17 to 0.37) for gingival index (P < .001 for all). CONCLUSIONS AND RELEVANCE: Nonsurgical periodontal therapy did not improve glycemic control in patients with type 2 diabetes and moderate to advanced chronic periodontitis. These findings do not support the use of nonsurgical periodontal treatment in patients with diabetes for the purpose of lowering levels of HbA1c. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00997178.

In vivo assessment of osseous wound healing using a novel bone putty containing lidocaine in the surgical management of tooth extractions.

Objective. This preclinical pilot study evaluated the systemic, radiographic, and histological responses to bone putty containing lidocaine in a canine tooth extraction model. Methods. In five beagle dogs the right mandibular premolars were extracted and sockets grafted with (1) xenograft particulate bone and a collagen sponge plug (control), (2) bone putty alone, (3) bone putty mixed with xenograft (3 : 1), or (4) xenograft sandwiched between bone putty. At 6 weeks post-op, the systemic and local responses were evaluated using a blood chemistry panel, micro-CT, and histological analyses. Results. No significant differences in blood chemistries were noted at 6 weeks postgrafting compared to baseline. Sockets grafted with either bone putty formulation demonstrated comparable radiographic and histologic evidence of bone healing compared to control sockets. Conclusions. Our preclinical results indicate that this bone putty appears to be a safe biocompatible device that may be useful in the postoperative management of tooth extractions.

Dental hygienists' knowledge and opinions of oral-systemic connections: implications for education.

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.

Incorporating oral-systemic evidence into patient care: practice behaviors and barriers of North Carolina dental hygienists.

PURPOSE: Current research has reported associations between periodontal and systemic health, however, there is little data regarding how dental hygienists are incorporating this evidence into the dental hygiene practice. The purpose of this survey research was to determine what practice behaviors are prevalent among North Carolina dental hygienists regarding the incorporation of oral-systemic evidence into practice as well as perceived barriers to implementation. METHODS: A questionnaire was developed, pilot tested, revised and mailed to 1,665 licensed dental hygienists in North Carolina. After 3 mailings the response rate was 62%, with 52% (n=859) of respondents meeting inclusion criteria. Survey data was analyzed using descriptive statistics and Chi-square analysis. RESULTS: Respondents were predominately female (99%) with a 2 year degree (84%). While a minority of dental hygienists (20%) reported measuring blood pressure routinely on all patients, a majority (62%) measure blood pressure in select patients. Oral cancer screenings were performed by 89% of respondents. Eight percent record blood sugar levels, but only 3% record HbA1c values. Fifty percent of dental hygienists are extremely likely to refer patients to a medical provider for follow up assessments. Conditions dental hygienists are likely to discuss with patients include tobacco use (89%), pregnancy (84%) and genetics (79%). Significant barriers to implementing oral-systemic evidence include lack of time (52%), concern over legal risks (44%) and lack of education (27%). CONCLUSION: North Carolina dental hygienists are implementing some aspects of oral-systemic evidence into practice, but could take a more active role if they had more allotted time, education and training.