m6Am Methyltransferase PCIF1 Regulates Periodontal Inflammation.

N6,2'-O-dimethyladenosine (m6Am), a common mRNA modification in eukaryotic capped mRNAs, plays a pivotal role in cellular functions and disease progression. However, its involvement in host inflammation remains elusive. Here, we demonstrate that loss of m6Am methyltransferase phosphorylated CTD interacting factor 1 (PCIF1) attenuates periodontal inflammation in whole-body and myeloid lineage-specific knockout mouse models. Pcif1 deletion inhibits macrophage phagocytosis and migration through m6Am-Csf1r signaling. In addition, colony-stimulating factor-1 receptor (CSF1R) is identified as a potential target for the treatment of periodontitis. We thus reveal a previously unrecognized role for PCIF1-mediated m6Am modification in governing macrophage responses and periodontal inflammation.

Inclusion of Dental Services in Medicare to Improve Oral and General Health for Older Americans.

Poor oral health negatively impacts overall health, quality of life, and well-being. Increasing evidence suggests that provision of basic dental care for elderly Americans would improve outcomes for a variety of systemic diseases and reduce the overall cost of healthcare. As a result, recent changes have been implemented to include some dental benefits in the Medicare program. This article outlines evidence, rationale, and approaches required for inclusion of dental benefits for more Americans through the Medicare program. Improving access to dental services through Medicare to help prevent and manage common chronic diseases is an important step toward integration of dental care with general healthcare to improve the overall health, quality of life, and well-being for many older Americans.

The effect of antireaction medications on the association between periodontitis and leprosy reactions: An important methodological issue in periodontal medicine.

BACKGROUND: The treatment of leprosy reactions (LRs) involves thalidomide, corticosteroids, and other immunomodulatory medications. This study evaluated the effect of these treatments on the association between periodontitis and LRs, as well as factors associated with LRs. METHODS: This case-control study was conducted on 283 individuals followed at a leprosy outpatient clinic in Brazil. The case group was comprised of 158 individuals presenting type 1 or type 2 LRs, and the control group of 125 leprosy individuals without reactions. A complete oral examination was performed to diagnose periodontitis, the independent variable. Antireaction medication used was collected from medical records, and participants were classified according to the use of prednisone and/or thalidomide, time of use, or non-use of medication. Socioeconomic-demographic, clinical, and lifestyle covariables were collected by interview. Unconditional logistic regression analysis by subgroups evaluated the effect of antireaction medication on the association between periodontitis and LRs, estimating the odds ratio with a 95% confidence interval (OR; 95% CI). RESULTS: A relationship between periodontitis and LRs was observed only in the subgroup using the association prednisone and thalidomide: ORadjusted = 0.32; 95% CI = 0.11-0.95. Conversely, more severe periodontal clinical parameters were observed in cases versus controls. Several socioeconomic, health conditions, and lifestyle factors were associated with the presence of LRs. CONCLUSIONS: Although periodontal disease indicators were worse among the cases, the findings showed a negative relationship between periodontitis and LRs in individuals receiving associated prednisone and thalidomide. These medications appear to influence the inflammatory cascade between diseases, modifying and masking the manifestations of periodontitis.

Prevalence of Non-diabetic Hyperglycemia in Young Adults and Its Impact on Periodontal Health.

Background Non-diabetic hyperglycemia is a transitional phase of hyperglycemia that poses a hidden risk for the development of diabetes mellitus and related complications, including periodontal destruction. The current study sought to determine the prevalence of non-diabetic hyperglycemia in young adults and any possible links to periodontal health. Methods A total of 400 participants in this cross-sectional study were evaluated for non-diabetic hyperglycemia between the ages of 18 and 35 years. Group I consisted of non-diabetic hyperglycemic participants. Group II comprised an equal number of matched, healthy subjects. The groups' hyperglycemic and clinical periodontal characteristics were contrasted. Using a one-sample t-test and logistic regression analysis, the acquired data were subjected to statistical analysis. Results The prevalence of non-diabetic hyperglycemia was 19%, with men (13%) having a higher prevalence than women (6%). The mean fasting plasma glucose and hemoglobin A1c (HbA1c) levels were 114.47 ± 6.40 mg/dL and 6.10 ± 0.21%, respectively, for group I, and 85.72 ± 7.24 mg/dL and 4.38 ± 0.70% for group II. When compared to healthy controls, all periodontal parameters, including plaque index, gingival index, bleeding on probing, probing depth, and clinical attachment loss, were significantly higher in group I non-diabetic hyperglycemic patients. The regression analysis revealed statistically significant links between hyperglycemic and periodontal parameters. Conclusion The prevalence of non-diabetic hyperglycemia among young adults is a serious concern similar to that of older adults with the risk for periodontal diseases. Non-diabetic hyperglycemic considerations in young adults should be emphasized in dental and medical clinics to reduce the risk of developing diabetes mellitus and to avoid irreversible periodontal tissue damage.

The bidirectional association between diabetes and periodontitis, from basic to clinical.

The prevalence and severity of periodontitis are increased and advanced in diabetes. Severe periodontitis elicits adverse effects on diabetes by impairing insulin actions due to systemic microinflammation. Recent studies unveil the emerging findings and molecular basis of the bidirectional relationship between periodontitis and diabetes. In addition to conventional mechanisms such as hyperglycemia, hyperlipidemia, and chronic inflammation, deficient insulin action may play a pathogenic role in the progression of periodontitis under diabetes. Epidemiologically, from the viewpoint of the adverse effect of periodontitis on diabetes, recent studies have suggested that Asians including Japanese and Asian Americans with diabetes and mild obesity (BMI <25 kg/m2) should pay more attention to their increased risk for cardiovascular diseases. In this review, we summarize recent findings on the effect of diabetes on periodontitis from the viewpoint of abnormalities in metabolism and insulin resistance with novel mechanisms, and the influence of periodontitis on diabetes mainly focused on micro-inflammation related to mature adipose tissue and discuss future perspectives about novel approaches to interrupt the adverse interrelationship.

Periodontitis and risk of cancer: Mechanistic evidence.

This review aims to critically analyze the pathways of interaction and the pathogenic mechanisms linking periodontitis and oral bacteria with the initiation/progression of cancer at different body compartments. A higher risk of head and neck cancer has been consistently associated with periodontitis. This relationship has been explained by the local promotion of dysbiosis, chronic inflammation, immune evasion, and direct (epi)genetic damage to epithelial cells by periodontal pathobionts and their toxins. Epidemiological reports have also studied a possible link between periodontitis and the incidence of other malignancies at distant sites, such as lung, breast, prostate, and digestive tract cancers. Mechanistically, different pathways have been involved, including the induction of a chronic systemic inflammatory state and the spreading of oral pathobionts with carcinogenic potential. Indeed, periodontitis may promote low-grade systemic inflammation and phenotypic changes in the mononuclear cells, leading to the release of free radicals and cytokines, as well as extracellular matrix degradation, which are all mechanisms involved in carcinogenic and metastatic processes. Moreover, the transient hematogenous spill out or micro-aspiration/swallowing of periodontal bacteria and their virulence factors (i.e., lipopolysaccharides, fimbriae), may lead to non-indigenous bacterial colonization of multiple microenvironments. These events may in turn replenish the tumor-associated microbiome and thus influence the molecular hallmarks of cancer. Particularly, specific strains of oral pathobionts (e.g., Porphyromonas gingivalis and Fusobacterium nucleatum) may translocate through the hematogenous and enteral routes, being implicated in esophageal, gastric, pancreatic, and colorectal tumorigenesis through the modulation of the gastrointestinal antitumor immune system (i.e., tumor-infiltrating T cells) and the increased expression of pro-inflammatory/oncogenic genes. Ultimately, the potential influence of common risk factors, relevant comorbidities, and upstream drivers, such as gerovulnerability to multiple diseases, in explaining the relationship cannot be disregarded. The evidence analyzed here emphasizes the possible relevance of periodontitis in cancer initiation/progression and stimulates future research endeavors.

Periodontitis and Metabolic Syndrome: Statistical and Machine Learning Analytics of a Nationwide Study.

This study aimed to analyze the associations between periodontitis and metabolic syndrome (MetS) components and related conditions while controlling for sociodemographics, health behaviors, and caries levels among young and middle-aged adults. We analyzed data from the Dental, Oral, and Medical Epidemiological (DOME) record-based cross-sectional study that combines comprehensive sociodemographic, medical, and dental databases of a nationally representative sample of military personnel. The research consisted of 57,496 records of patients, and the prevalence of periodontitis was 9.79% (5630/57,496). The following parameters retained a significant positive association with subsequent periodontitis multivariate analysis (from the highest to the lowest OR (odds ratio)): brushing teeth (OR = 2.985 (2.739-3.257)), obstructive sleep apnea (OSA) (OR = 2.188 (1.545-3.105)), cariogenic diet consumption (OR = 1.652 (1.536-1.776)), non-alcoholic fatty liver disease (NAFLD) (OR = 1.483 (1.171-1.879)), smoking (OR = 1.176 (1.047-1.322)), and age (OR = 1.040 (1.035-1.046)). The following parameters retained a significant negative association (protective effect) with periodontitis in the multivariate analysis (from the highest to the lowest OR): the mean number of decayed teeth (OR = 0.980 (0.970-0.991)); North America as the birth country compared to native Israelis (OR = 0.775 (0.608-0.988)); urban non-Jewish (OR = 0.442 (0.280-0.698)); and urban Jewish (OR = 0.395 (0.251-0.620)) compared to the rural locality of residence. Feature importance analysis using the eXtreme Gradient Boosting (XGBoost) machine learning algorithm with periodontitis as the target variable ranked obesity, OSA, and NAFLD as the most important systemic conditions in the model. We identified a profile of the "patient vulnerable to periodontitis" characterized by older age, rural residency, smoking, brushing teeth, cariogenic diet, comorbidities of obesity, OSA and NAFLD, and fewer untreated decayed teeth. North American-born individuals had a lower prevalence of periodontitis than native Israelis. This study emphasizes the holistic view of the MetS cluster and explores less-investigated MetS-related conditions in the context of periodontitis. A comprehensive assessment of disease risk factors is crucial to target high-risk populations for periodontitis and MetS.

Systematic review and meta-analysis of randomized controlled trials evaluating the efficacy of non-surgical periodontal treatment in patients with concurrent systemic conditions.

OBJECTIVE: To conduct a systematic review of the published scientific evidence to evaluate the efficacy of nonsurgical periodontal therapy (NSPT) in treating periodontitis in patients with concurrent systemic conditions (diabetes, CVD, erectile dysfunction, chronic kidney disease, rheumatoid arthritis, polycystic ovarian syndrome, obesity, pregnancy). We hypothesised that NSPT results in better periodontal outcomes when compared to untreated controls after follow-up. MATERIALS AND METHODS: A systematic search (PUBMED/EMBASE) was conducted from 1995 to 2023 to identify randomised controlled trials (RCTs) with a minimum follow-up of 3 months. The primary outcome was the difference in mean probing depth (PD), and the secondary outcomes were mean clinical attachment loss (CAL), percentage of sites with PD ≤ 3 mm (%PD ≤ 3 mm) and percentage of sites with bleeding on probing (%BOP) between the treated and untreated control group in patients with comorbidities. RESULTS: The electronic search resulted in 2,403 hits. After removing duplicates, 1,565 titles and abstracts were screened according to the eligibility criteria, resulting in 126 articles for full-text screening. Following this, 44 studies were analysed. Restricting to studies with low bias or some concerns, NSPT group demonstrated a 0.55 mm lower mean PD (95%CI: -0.69; -0.41) after 3 months compared to the control group. CONCLUSION: Compared to the untreated controls, NSPT notably reduced mean PD, mean CAL, and %BOP while increasing %PD ≤ 3 mm in patients with concurrent systemic conditions. These findings suggest that NSPT is also an effective procedure in managing periodontitis in patients with concurrent systemic conditions. TRIAL REGISTRATION: This systematic review was registered under the protocol registration number CRD42021241517/PROSPERO.

Secondary analysis of potential associations between oral health and infection-related parameters in patients with severe heart failure-results of a German cohort.

OBJECTIVES: Aim of this retrospective cohort study was to evaluate whether oral health parameters would be associated with infection-related parameters and overall survival of patients with severe heart failure (HF). METHODS: Patients with severe HF, heart transplantation (HTx) and left-ventricular assist device (LVAD), which underwent a full oral examination between 2017 and 2018 were included. Infection-related and survival data were assessed from the patient´s medical records. The oral examination included: remaining teeth, caries and periodontal condition, including periodontal probing depth (PPD), clinical attachment loss (CAL), bleeding on probing (BOP), and diagnosis (staging/grading). In addition, the periodontal inflamed surface area (PISA) was determined. Statistical analysis included Chi-square, Fisher´s exact and Mann-Whitney-U test, as well as a logistic regression, considering age, gender, body-mass-index (BMI), diabetes and several oral health parameters with regard to overall survival and infections at heart/driveline. RESULTS: 329 patients (HTx: 34%, LVAD: 38.9%, HF: 27.1%), were included. Patients had on average 18.96 ± 8.90 remaining teeth, whereby the majority had a periodontitis stage III or IV (88.7%) and a grade B (80.5%). Higher BOP was associated with infections at heart/driveline (p = 0.04) and outside the heart (p < 0.01) during follow-up. Increased PISA was significantly associated with bacterial infections outside the heart (p < 0.01) and sepsis (p = 0.02). Only BMI of 25 or higher correlated with an increased risk of infections at heart/driveline in regression analysis (OR 3.063, CI95 1.158-8.101, p = 0.02), while no associations between oral health parameters and infections at heart/driveline or overall survival were confirmed. CONCLUSIONS: In patients with severe HF, periodontal inflammation might be associated with infection-related parameters. Improved dental care, especially including periodontal therapy and maintenance might be favourable to support prevention of infections in patients with severe HF.

The Gum-Gut Axis: Periodontitis and the Risk of Gastrointestinal Cancers.

Periodontitis has been linked to an increased risk of various chronic non-communicable diseases, including gastrointestinal cancers. Indeed, dysbiosis of the oral microbiome and immune-inflammatory pathways related to periodontitis may impact the pathophysiology of the gastrointestinal tract and its accessory organs through the so-called "gum-gut axis". In addition to the hematogenous spread of periodontal pathogens and inflammatory cytokines, recent research suggests that oral pathobionts may translocate to the gastrointestinal tract through saliva, possibly impacting neoplastic processes in the gastrointestinal, liver, and pancreatic systems. The exact mechanisms by which oral pathogens contribute to the development of digestive tract cancers are not fully understood but may involve dysbiosis of the gut microbiome, chronic inflammation, and immune modulation/evasion, mainly through the interaction with T-helper and monocytic cells. Specifically, keystone periodontal pathogens, including Porphyromonas gingivalis and Fusobacterium nucleatum, are known to interact with the molecular hallmarks of gastrointestinal cancers, inducing genomic mutations, and promote a permissive immune microenvironment by impairing anti-tumor checkpoints. The evidence gathered here suggests a possible role of periodontitis and oral dysbiosis in the carcinogenesis of the enteral tract. The "gum-gut axis" may therefore represent a promising target for the development of strategies for the prevention and treatment of gastrointestinal cancers.