Saliva, Plasma, and Multifluid Metabolomic Signatures of Periodontal Disease, Type 2 Diabetes Progression, and Markers of Glycemia and Dyslipidemia Among Puerto Rican Adults With Overweight and Obesity.

BACKGROUND: Evidence from cohort studies indicates a bidirectional relationship between periodontal disease and type 2 diabetes (T2D), but the underlying mechanisms remain unknown. In this study, we aimed to (1) identify saliva, plasma, and multifluid metabolomic signatures associated with periodontal disease and (2) determine if these signatures predict T2D progression and cardiometabolic biomarkers at year 3. METHODS AND RESULTS: We included participants from the SOALS (San Juan Overweight Adult Longitudinal Study) (n=911). Metabolites from saliva (k=635) and plasma (k=1051) were quantified using liquid chromatography-mass spectrometry. We applied elastic net regression with 10-fold cross-validation to identify baseline metabolomic signatures of periodontal disease. Multivariable Cox proportional hazards regression and linear regression were used to evaluate the association with T2D progression and biomarker concentrations. Metabolomic profiles included highly weighted metabolites related to lysine and pyrimidine metabolism. Periodontal disease or its 3 metabolomic signatures were not associated with T2D progression in 3 years. Prospectively, 1-SD increments in the multifluid and saliva metabolomic signatures were associated with higher low-density lipoprotein (multifluid: 12.9±5.70, P=0.02; saliva: 13.3±5.11, P=0.009). A 1-SD increment in the plasma metabolomic signature was also associated with Homeostatic Model Assessment for Insulin Resistance (2.67±1.14, P=0.02) and triglyceride (0.52±0.18, P=0.002). CONCLUSIONS: Although metabolomic signatures of periodontal disease could not predict T2D progression, they were associated with low-density lipoprotein, triglyceride, and Homeostatic Model Assessment for Insulin Resistance levels at year 3.

[Knowledge level of periodontal health in students of health sciences. a cross-sectional study]. / Nivel de conocimiento sobre salud periodontal de estudiantes de ciencias de la salud. un estudio transversal.

Introduction: Periodontal disease is a multifactorial chronic inflammatory disease, so knowledge about this disease is important for health professionals for an assertive and early diagnosis. Objective: Determine the level of knowledge about periodontal health in Health Sciences students at a private university in Lima-Perú. Materials and Methods: Through a descriptive and cross-sectional study, 200 students from the Faculty of Health Sciences were evaluated. The sample size was obtained using a proportion estimation formula. The level of knowledge about periodontal health was measured using a specific virtual and self-applicable questionnaire, which was fully validated. University students of legal age and who signed the informed consent were included. This consisted of 16 questions about the causes, signs, prevention habits and relationship with systemic diseases related to periodontal disease. The data were analyzed using descriptive statistics (absolute and relative frequencies) and means and averages for age. Results: The level of knowledge was medium in 38%, high in 32.5% and low in 29.5% of the students surveyed. 96.5% knew that periodontal disease is preventable; However, 91.5% do not know what its main clinical sign is. Conclusions: The use of a self-applicable and specific questionnaire is beneficial to evaluate and measure knowledge about periodontal health, and the Health Sciences students evaluated have a medium level of knowledge about periodontal health.

Evaluation of Antimicrobial Susceptibility and Resistance Patterns of Treponema denticola Isolated From Periodontal Disease: An In Vitro Study.

Background Periodontal disease poses a significant oral health challenge, involving inflammatory conditions impacting tooth-supporting structures. Treponema denticola, a "red complex" organism, plays a crucial role in periodontal pathogenesis, forming biofilms in subgingival environments and contributing to dysbiosis. Antimicrobial therapy is pivotal in managing periodontal disease, requiring a nuanced understanding of susceptibility patterns exhibited by key pathogens like T. denticola. Aims and objectives This study aims to investigate the antimicrobial susceptibility and resistance profiles of Treponema denticola, a prominent bacterium in periodontal disease, by examining its responses to various antimicrobial agents commonly used in periodontal therapy. Methodology Plaque samples were meticulously collected from individuals diagnosed with periodontal disease to ensure a diverse representation of the oral microbiome. All the samples were cultured, and red complex bacteria were isolated under anaerobic culture. Treponema denticola isolates were cultured from these samples under anaerobic conditions, and molecular techniques were employed for species identification. A comprehensive panel of antimicrobial agents was selected to assess the response of Treponema denticola. In vitro antimicrobial susceptibility testing (AST) was conducted using the antimicrobial gradient method, employing a hybrid approach combining elements of disk-diffusion and dilution methods. Results Treponema denticola had exhibited resistance to metronidazole, a commonly used antibiotic effective against anaerobic bacteria, emphasizing limitations in its applicability. However, the bacterium displayed sensitivity to tetracycline, imipenem, cefoperazone, chloramphenicol, clindamycin, and moxifloxacin, offering diverse therapeutic options. The antimicrobial gradient strip test provided detailed minimum inhibitory concentration (MIC) values, contributing to a nuanced understanding of susceptibility and resistance patterns. Conclusion This study significantly advances our understanding of Treponema denticola's antimicrobial susceptibility and resistance profiles in the context of periodontal disease. The findings underscore the importance of tailored treatment strategies and contribute to broader efforts in antimicrobial stewardship, aligning with global initiatives to combat antibiotic resistance. This research lays the foundation for more effective and personalized approaches to periodontal care, emphasizing the intricate microbial dynamics associated with periodontal health and disease.

Dysbiosis linking periodontal disease and oral squamous cell carcinoma-A brief narrative review.

An association between periodontal disease and oral squamous cell carcinoma (OSCC) has been recognized. However, there is no causal relationship between the two. The polymicrobial etiology of periodontal disease is confirmed, and so are the proven etiological factors for OSCC. Inflammation lies at the core of periodontal pathogenesis induced by the putative microbes. OSCC has inflammatory overtures in its pathobiology. Bacterial species involved in periodontal disease have been extensively documented and validated. The microbial profile in OSCC has been explored with no specific conclusions. The scientific reasoning to link a common microbial signature that connects periodontal disease to OSCC has led to many studies but has not provided conclusive evidence. Therefore, it would be beneficial to know the status of any plausible microbiota having a similarity in periodontal disease and OSCC. This brief review attempted to clarify the existence of a dysbiotic "fingerprint" that may link these two diseases. The review examined the literature with a focused objective of identifying periodontal microbial profiles in OSCC that could provide insights into pathogen commonality. The review concluded that there is great diversity in microbial association, but important bacterial species that correlate with periodontal disease and OSCC are forthcoming.

Investigating the Interplay: Periodontal Disease and Type 1 Diabetes Mellitus-A Comprehensive Review of Clinical Studies.

Diabetes mellitus (DM) poses a significant challenge to global health, with its prevalence projected to rise dramatically by 2045. This narrative review explores the bidirectional relationship between periodontitis (PD) and type 1 diabetes mellitus (T1DM), focusing on cellular and molecular mechanisms derived from the interplay between oral microbiota and the host immune response. A comprehensive search of studies published between 2008 and 2023 was conducted to elucidate the association between these two diseases. Preclinical and clinical evidence suggests a bidirectional relationship, with individuals with T1DM exhibiting heightened susceptibility to periodontitis, and vice versa. The review includes recent findings from human clinical studies, revealing variations in oral microbiota composition in T1DM patients, including increases in certain pathogenic species such as Porphyromonas gingivalis, Prevotella intermedia, and Aggregatibacter actinomycetemcomitans, along with shifts in microbial diversity and abundance. Molecular mechanisms underlying this association involve oxidative stress and dysregulated host immune responses, mediated by inflammatory cytokines such as IL-6, IL-8, and MMPs. Furthermore, disruptions in bone turnover markers, such as RANKL and OPG, contribute to periodontal complications in T1DM patients. While preventive measures to manage periodontal complications in T1DM patients may improve overall health outcomes, further research is needed to understand the intricate interactions between oral microbiota, host response, periodontal disease, and systemic health in this population.

Therapeutic Strategies and Genetic Implications for Periodontal Disease Management: A Systematic Review.

The objective of this review is to identify the microbiological alterations caused by various therapy modalities by critically analyzing the current findings. We limited our search to English-language papers published between 1 January 2004 and 7 May 2024 in PubMed, Scopus, and Web of Science that were relevant to our topic. In the search approach, the Boolean keywords "microbio*" AND "periodontitis" were used. A total of 5152 papers were obtained from the databases Web of Science (2205), PubMed (1793), and Scopus (1154). This resulted in 3266 articles after eliminating duplicates (1886), and 1411 entries were eliminated after their titles and abstracts were examined. The qualitative analysis of the 22 final articles is included in this study. Research on periodontal disease shows that periodontitis alters the oral microbiome and increases antibiotic resistance. Treatments like scaling and root planing (SRP), especially when combined with minocycline, improve clinical outcomes by reducing harmful bacteria. Comprehensive mechanical debridement with antibiotics, probiotics, EMD with bone grafts, and other adjunctive therapies enhances periodontal health. Personalized treatment strategies and advanced microbial analyses are crucial for effective periodontal management and antibiotic resistance control.

Dipotassium glycyrrhizate prevents oral dysbiosis caused by Porphyromonas gingivalis in an in vitro saliva-derived polymicrobial biofilm model.

OBJECTIVES: Oral microbiome dysbiosis prevention is important to avoid the onset and progression of periodontal disease. Dipotassium glycyrrhizate (GK2) is a licorice root extract with anti-inflammatory effects, and its associated mechanisms have been well-reported. However, their effects on the oral microbiome have not been investigated. This study aimed to elucidate the effects of GK2 on the oral microbiome using an in vitro polymicrobial biofilm model. METHODS: An in vitro saliva-derived polymicrobial biofilm model was used to evaluate the effects of GK2 on the oral microbiome. One-week anaerobic culture was performed, in which GK2 was added to the medium. Subsequently, microbiome analysis was performed based on the V1-V2 region of the 16S rRNA gene, and pathogenicity indices were assessed. We investigated the effects of GK2 on various bacterial monocultures by evaluating its inhibitory effects on cell growth, based on culture turbidity. RESULTS: GK2 treatment altered the microbiome structure and decreased the relative abundance of periodontal pathogenic bacteria, including Porphyromonas. Moreover, GK2 treatment reduced the DPP4 activity -a pathogenicity index of periodontal disease. Specifically, GK2 exhibited selective antibacterial activity against periodontal pathogenic bacteria. CONCLUSIONS: These findings suggest that GK2 has a selective antibacterial effect against periodontal pathogenic bacteria; thus, preventing oral microbiome dysbiosis. Therefore, GK2 is expected to contribute to periodontal disease prevention by modulating the oral microbiome toward a state with low inflammatory potential, thereby utilizing its anti-inflammatory properties on the host.

Cytokine levels in gingival tissues as an indicator to understand periodontal disease severity.

Cytokines regulate periodontal pathogenesis and are relevant estimates of current disease activity. There is sparse information on status of cytokine protein levels in periodontal pocket (gingival) tissues. The current study analysed proteins and transcripts of selected cytokines in varying severity of periodontal disease and elucidated cytokine/cytokine ratios that best indicated periodontal disease severity, in gingival tissues. A total of 92 participants comprising of generalised moderate periodontitis (GMP, n = 18), generalised severe periodontitis (GSP, n = 46) and periodontally healthy controls (PHC, n = 25) were recruited for the study. Interproximal gingival tissue samples were utilised for cytokine protein estimation and mRNA quantification by qRT-PCR and ELISA respectively. Selected key pro and anti-inflammatory cytokines, also representative of various Th subsets were analysed. ROC curve analysis was performed and Youden index was calculated for individual cytokines and pro/anti-inflammatory cytokine ratio to estimate the best indicator of periodontal severity/progression in tissues. IL-1ß, TGF-ß and IFN-γ cytokine protein levels varied significantly (p ≤ 0.05) with severity of periodontal disease between groups. On comparison between deep and shallow sites within same participant, deep sites showed significant elevation of TGF-ß (p ≤ 0.01) and IFN-γ (p ≤ 0.05) and IL-17 cytokines and shallow sites showed elevation of IL-4(p ≤ 0.01) and IL-1ß (p ≤ 0.05) cytokines. Analysis of transcripts showed IFN-γ and IL-1ß transcript predominance in GSP (p = 0.01) compared to PHC. ROC analysis illustrated 97% sensitivity, 93% specificity with Youden index of 90% for IL-1ß cytokine and 81%sensitivity, 79% specificity with a Youden index of 60% for IL-1ß/TGF-ß ratio In periodontal pocket tissue, a lack of distinct predominance of specific cytokines between study groups or between shallow and deep sites affected by periodontal disease was observed. However, ROC analysis of cytokines revealed IL-1ß cytokine and IL-1ß/TGF-ß ratio as promising indicators of periodontal disease severity in gingival tissues.

Unravelling the intricacies of Porphyromonas gingivalis: virulence factors, lifecycle dynamics and phytochemical interventions for periodontal disease management.

Porphyromonas gingivalis is a gram-negative anaerobic bacterium recognized for its pivotal role in the pathogenesis of periodontal diseases. This review covers an overview of the virulence factors and lifecycle stages of P. gingivalis, with a specific focus on attachment and colonization, biofilm formation, growth and multiplication, dormancy survival and dissemination. Additionally, we explore the significance of inter-bacterial cross-feeding within biofilms. Furthermore, we discuss potential phytochemical-based strategies to target P. gingivalis, including the use of curcumin, apigenin, quercetin and resveratrol. Understanding the virulence factors and lifecycle stages of P. gingivalis, along with the promising phytochemical-based interventions, holds promise for advancing strategies in periodontal disease management and oral health promotion.

An interdisciplinary treatment to reshape upper anterior displaced teeth by using dynamic occlusal recording with an intraoral scanner.

OBJECTIVE: This article describes an interdisciplinary treatment that helped a patient with displaced upper anterior teeth. A gingivectomy, root canal therapies, digital smile design, digital wax-up, and guided tooth preparations were applied. CLINICAL CONSIDERATIONS: A patient with pathologically migrated teeth asked for treatment without orthodontic involvement due to a primary failed orthodontic treatment history. A smile photo was taken and superimposed with the dentition in a CAD software to accomplish a digital smile design. The jaw movements were recorded with two different methods, a mechanical articulator and an intraoral scanner with Patient-Specific-Motion function. The occlusal contacts during protrusive and lateral movements were compared and the digital wax-up was designed according to the later occlusal data. An aesthetic crown lengthening and pre-op root canal treatment were carried out in advance accordingly. After guided tooth preparation with a silicone index, the final fixed restorations were manufactured and cemented. A 2-year follow-up showed that our prosthesis functions well. CONCLUSIONS: This clinical report revealed that an intraoral scanner with Patient-Specific-Motion function can effectively record individual dynamic occlusal patterns and these data can be integrated into the CAD/CAM process to enhance the fulfillment of clinical requirements. CLINICAL SIGNIFICANCE: This clinical procedure with a 2-year follow-up demonstrated that a prosthodontic-based interdisciplinary treatment of pathologically migrated teeth using dynamic occlusal recording with an intraoral scanner could achieve satisfactory esthetics in a relatively short treatment period. The Patient Specific Motion module may be used to record a personalized functional movement and the data can be integrated into the design process of the final restorations.

Oral health indicators and bone mineral density disorders in older age: A systematic review.

As we age, maintaining good oral health becomes increasingly crucial for performing daily tasks. Age-related physiological decline can disrupt various biological systems, causing a significant challenge for geriatric dentistry. A systematic review of the literature using six different electronic databases was conducted to investigate the relationship between oral health indicators and bone mineral density disorders in older adults. The study is registered as a priori protocol on PROSPERO (CRD42023403340). A minimum age of 60 years was the main inclusion criterion for all original research articles. Two independent researchers assessed the eligibility of 19,362 records against the inclusion criteria and found 12 articles fitting the eligibility requirements. Five different indicators of poor oral health [number of teeth, periodontal disease, general oral health (dental caries prevalence and dental treatment needs), masticatory function, and occlusal force)] were found related to three outcomes linked to bone mineral density disorders (osteoporosis, fractures, and decreased bone mineral density), regardless of the adopted assessment tools. The number of teeth was negatively associated with fractures and a decreased bone mineral density, while periodontal disease was positively associated with osteoporosis and a decreased bone mineral density. Masticatory function was associated only with osteoporosis, while general oral health was associated only with fractures and occlusal force only with bone mineral density. The oral health indicator most frequently associated with outcomes linked to bone mineral density disorders was the number of teeth. The present findings could help to assess the contribution of each oral health indicator to the development of bone mineral density disorders in older age.

The relationship between periodontal disease and cancer: Insights from a Systematic Literature Network Analysis.

This paper investigates the relationship between periodontal disease and various cancer types. It provides a comprehensive overview of the existing knowledge about the interaction between periodontal disease and carcinogenesis, explores the underlying biological mechanisms of this connection, and consider the impact of these findings on healthcare practices and future research directions. Utilizing Systematic Literature Network Analysis, which combines bibliometric analysis with Systematic Literature Review, this study analyzes 164 documents from 2000 to 2023. Focus is placed on the 38 most globally cited papers, enabling a targeted and comprehensive analysis of the predominant research within this scope. This review highlights that colorectal, oral, pancreatic, lung, and gastrointestinal cancers have consistent associations with periodontal disease. On the other hand, hematological, breast and prostate cancers show associations with periodontal disease, but these links are less pronounced and more variable, indicating the need for targeted research in these domains. These insights emphasize the necessity for a multidisciplinary healthcare approach, recognizing the systemic implications of periodontal disease.

Far-ultraviolet irradiation at 222 nm destroys and sterilizes the biofilms formed by periodontitis pathogens.

BACKGROUND: Periodontal disease is the leading cause of tooth loss, and an association between periodontal disease and non-oral systemic diseases has been shown. Formation of biofilm by periodontal pathogens such as Fusobacterium nucleatum, Porphyromonas gingivalis, and Streptococcus mutans and their resistance to antimicrobial agents are at the root of persistent and chronic bacterial infections. METHODS: The bactericidal effect of far-ultraviolet (F-UV) light irradiation at 222 nm on periodontal bacteria was assessed qualitatively and quantitatively. The effect of biofilm disruption by F-UV light on periodontal bacteria was examined by crystal violet staining, and the morphologic changes of the biofilm after F-UV irradiation were explored by confocal laser microscopy and scanning electron microscopy. We developed a thin fiber-type 222 nm F-UV irradiator and studied its safety and effect of reducing bacteria in rodent models. RESULTS: F-UV light at 222 nm had a bactericidal effect on F. nucleatum, P. gingivalis, and S. mutans. Irradiation with F-UV light reduced the biofilm formed by the bacteria and sterilized them from within. Confocal laser microscopy showed a clear reduction in biofilm thickness, and scanning electron microscopy confirmed disintegration of the biofilm architecture. F-UV irradiation was less damaging to DNA and less cytotoxic than deep-ultraviolet light, and it reduced bacterial counts on the tooth surface. CONCLUSION: F-UV irradiation has the potential to destroy biofilm and act as a bactericide against pathogenic bacteria in the biofilm.

Effect of Oral Care on Endothelial Dysfunction in Patients with Acute Coronary Syndrome.

Periodontitis is a common chronic infection and is associated with cardiovascular disease. This study evaluated whether basic oral care for periodontal disease could improve endothelial function in patients with acute coronary syndrome (ACS).This study enrolled 54 patients with acute coronary syndrome admitted to Kagoshima City Hospital and who had undergone percutaneous coronary intervention. Flow-mediated endothelium-dependent dilatation (FMD) was measured before discharge (initial FMD) and at 8 months after percutaneous coronary intervention (follow-up FMD). The following periodontal characteristics were measured: periodontal pocket depth (PPD, mm), plaque control record (%), and bleeding on probing (%). All patients received basic oral care instructions from dentists. The oral health condition was generally poor in the participants and there were 24 patients (44.4%) who had severe PPD. Despite the intervention of basic oral care, the periodontal characteristics did not improve during the study period; initial FMD and follow-up FMD did not significantly differ (4.38 ± 2.74% versus 4.56 ± 2.51%, P = 0.562). However, the follow-up FMD was significantly lower in patients with severe PPD (≥ 6.0 mm, n = 24) than in patients without severe PPD (≤ 5.0 mm, n = 30) (FMD: 3.58 ± 1.91% versus 5.37 ± 2.67%, P = 0.007). FMD tended to be worse in patients with severe PPD than in patients without severe PPD (ΔFMD: -0.55 ± 2.12 versus 0.81 ± 2.77 %, P = 0.055). In conclusion, during the use of basic oral care, endothelial function improved in patients without severe PPD, while it worsened in patients with severe PPD.

Periodontal considerations during orthodontic intrusion and extrusion in healthy and reduced periodontium.

In patients with advanced periodontal disease, pathological tooth migration may occur, which may require subsequent orthodontic treatment for both aesthetic and functional purposes. When planning orthodontic treatment mechanics, intrusive or extrusive forces are frequently indicated. Understanding tissue reactions during these movements is essential for clinicians when devising a comprehensive orthodontic-periodontal treatment plan. This knowledge enables clinicians to be fully aware of and account for the potential effects on the surrounding tissues. The majority of our understanding regarding the behavior of periodontal tissues in both healthy and compromised periodontal conditions is derived from animal studies. These studies offer the advantage of conducting histological and other assessments that would not be feasible in human research. Human studies are nevertheless invaluable in being able to understand the clinically relevant response elicited by the periodontal tissues following orthodontic tooth movement. Animal and human data show that in dentitions with reduced periodontal support, orthodontic intrusion of the teeth does not induce periodontal damage, provided the periodontal tissues do not have inflammation and plaque control with excellent oral hygiene is maintained. On the contrary, when inflammation is not fully controlled, orthodontic intrusion may accelerate the progression of periodontal destruction, with bacterial plaque remnants being displaced subgingivally, leading to further loss of attachment. Orthodontic extrusion, on the other hand, does not seem to cause further periodontal breakdown in dentitions with reduced periodontal support, even in cases with deficient plaque control. This is attributed to the nature of the tooth movement, which directs any plaque remnants coronally (supragingivally), reducing the risk of adverse effects on the periodontal tissues. This specific type of tooth movement can be leveraged to benefit periodontal conditions by facilitating the regeneration of lost hard and soft periodontal tissues in a coronal direction. As a result, orthodontic extrusion can be employed in implant site development, offering an advantageous alternative to more invasive surgical procedures like bone grafting. Regardless of the tooth movement prescribed, when periodontal involvement is present, it is essential to prioritize periodontal therapy before commencing orthodontic treatment. Adequate plaque control is also imperative for successful outcomes. Additionally, utilizing light orthodontic forces is advisable to achieve efficient tooth movement while minimizing the risk of adverse effects, notably root resorption. By adhering to these principles, a more favorable and effective combined orthodontic-periodontal approach can be ensured. The present article describes indications, mechanisms, side effects, and histological and clinical evidence supporting orthodontic extrusion and intrusion in intact and reduced periodontal conditions.

Radiographic diagnosis of periodontal diseases - Current evidence versus innovations.

Accurate diagnosis of periodontal and peri-implant diseases relies significantly on radiographic examination, especially for assessing alveolar bone levels, bone defect morphology, and bone quality. This narrative review aimed to comprehensively outline the current state-of-the-art in radiographic diagnosis of alveolar bone diseases, covering both two-dimensional (2D) and three-dimensional (3D) modalities. Additionally, this review explores recent technological advances in periodontal imaging diagnosis, focusing on their potential integration into clinical practice. Clinical probing and intraoral radiography, while crucial, encounter limitations in effectively assessing complex periodontal bone defects. Recognizing these challenges, 3D imaging modalities, such as cone beam computed tomography (CBCT), have been explored for a more comprehensive understanding of periodontal structures. The significance of the radiographic assessment approach is evidenced by its ability to offer an objective and standardized means of evaluating hard tissues, reducing variability associated with manual clinical measurements and contributing to a more precise diagnosis of periodontal health. However, clinicians should be aware of challenges related to CBCT imaging assessment, including beam-hardening artifacts generated by the high-density materials present in the field of view, which might affect image quality. Integration of digital technologies, such as artificial intelligence-based tools in intraoral radiography software, the enhances the diagnostic process. The overarching recommendation is a judicious combination of CBCT and digital intraoral radiography for enhanced periodontal bone assessment. Therefore, it is crucial for clinicians to weigh the benefits against the risks associated with higher radiation exposure on a case-by-case basis, prioritizing patient safety and treatment outcomes.

Molecularly imprinted nanogels as synthetic recognition materials for the ultrasensitive detection of periodontal disease biomarkers.

Periodontal disease affects supporting dental structures and ranks among one of the top most expensive conditions to treat in the world. Moreover, in recent years, the disease has also been linked to cardiovascular and Alzheimer's diseases. At present, there is a serious lack of accurate diagnostic tools to identify people at severe risk of periodontal disease progression. Porphyromonas gingivalis is often considered one of the most contributing factors towards disease progression. It produces the Arg- and Lys-specific proteases Rgp and Kgp, respectively. Within this work, a short epitope sequence of these proteases is immobilised onto a magnetic nanoparticle platform. These are then used as a template to produce high-affinity, selective molecularly imprinted nanogels, using the common monomers N-tert-butylacrylamide (TBAM), N-isopropyl acrylamide (NIPAM), and N-(3-aminopropyl) methacrylamide hydrochloride (APMA). N,N-Methylene bis(acrylamide) (BIS) was used as a crosslinking monomer to form the interconnected polymeric network. The produced nanogels were immobilised onto a planar gold surface and characterised using the optical technique of surface plasmon resonance. They showed high selectivity and affinity towards their template, with affinity constants of 79.4 and 89.7 nM for the Rgp and Kgp epitope nanogels, respectively. From their calibration curves, the theoretical limit of detection was determined to be 1.27 nM for the Rgp nanogels and 2.00 nM for the Kgp nanogels. Furthermore, they also showed excellent selectivity against bacterial culture supernatants E8 (Rgp knockout), K1A (Kgp knockout), and W50-d (wild-type) strains in complex medium of brain heart infusion (BHI).

Data-driven prediction model for periodontal disease based on correlational feature analysis and clinical validation.

Objectives: This study aimed to investigate the performance and reliability of data-driven models employing correlational feature analysis and clinical validation for predicting periodontal disease. Methods: The 7th Korea National Health and Nutrition Examination Survey (n = 10,654) was used for correlation analysis to identify significant risk factors for periodontitis. Periodontal prediction models were developed with the selected factors and database, followed by internal validation with 5-fold cross-validation and 1000 bootstrap resampling. External validation was conducted with clinical data (n = 120) collected through self-reported questionnaires, clinical periodontal parameters, and radiographic image analysis. Predictive performance was assessed for logistics regression, support vector machine, random forest, XGBoost, and neural network algorithms using the area under the receiver operating characteristic curves (AUC) and other performance metrics. Results: Correlation analysis identified 16 features from over 1000 potential risk factors for periodontitis. The best data-driven model (XGBoost) showed AUC values of 0.823 and 0.796 for internal and external validations, respectively. Modeling with clinical data revealed those same measures to be 0.836 and 0.649, respectively. In addition, the data-driven model could predict other clinical periodontal parameters including severe bone loss (AUC = 0.813), gingival bleeding (AUC = 0.694), and tooth loss (AUC = 0.734). A patient case study about prognostic predictions revealed that the probability of periodontitis can be reduced by 6.0 % (stop smoking) and 0.6 % (stop drinking) on average. Conclusions: Data-driven models for predicting periodontitis and other periodontal parameters were developed from 16 risk factors, demonstrating enhanced prediction performance and reproducibility in internal-external validations.

Impact of periodontal disease on cognitive disorders, dementia, and depression: a systematic review and meta-analysis.

A growing body of research suggested that there was a link between poor periodontal health and systemic diseases, particularly with the early development of cognitive disorders, dementia, and depression. This is especially true in cases of changes in diet, malnutrition, loss of muscular endurance, and abnormal systemic inflammatory response. Our study aimed to determine the extent of these associations to better target the multi-level healthy aging challenge investigating the impact of periodontal disease on cognitive disorders (cognitive impairment and cognitive decline), dementia, and depression. We conducted a comprehensive literature search up to November 2023 using six different electronic databases. Two independent researchers assessed the eligibility of 7363 records against the inclusion criteria and found only 46 records that met the requirements. The study is registered on PROSPERO (CRD42023485688). We generated random effects pooled estimates and 95% confidence intervals (CI) to evaluate whether periodontal disease increased the risk of the investigated outcomes. The quality assessment revealed moderate quality of evidence and risk of bias. Periodontal disease was found to be associated with both cognitive disorders (relative risk (RR) 1.25, 95% CI 1.11-1.40, in the analysis of cross-sectional studies); cognitive impairment (RR 3.01, 95% CI 1.52-5.95 for longitudinal studies, cognitive decline); and dementia (RR 1.22, 95% CI 1.10-1.36). However, no significant increased risk of depression among subjects with periodontal disease was found (RR 1.07, 95% CI 0.95-1.21). Despite the association with two of the three explored outcomes, the available evidence on periodontal diseases and dementia, cognitive disorders, and depression is controversial due to several limitations. Therefore, further investigations involving validated and standardized tools are required.

An update on periodontal inflammation and bone loss.

Periodontal disease is a chronic inflammatory condition that affects the supporting structures of the teeth, including the periodontal ligament and alveolar bone. Periodontal disease is due to an immune response that stimulates gingivitis and periodontitis, and its systemic consequences. This immune response is triggered by bacteria and may be modulated by environmental conditions such as smoking or systemic disease. Recent advances in single cell RNA-seq (scRNA-seq) and in vivo animal studies have provided new insight into the immune response triggered by bacteria that causes periodontitis and gingivitis. Dysbiosis, which constitutes a change in the bacterial composition of the microbiome, is a key factor in the initiation and progression of periodontitis. The host immune response to dysbiosis involves the activation of various cell types, including keratinocytes, stromal cells, neutrophils, monocytes/macrophages, dendritic cells and several lymphocyte subsets, which release pro-inflammatory cytokines and chemokines. Periodontal disease has been implicated in contributing to the pathogenesis of several systemic conditions, including diabetes, rheumatoid arthritis, cardiovascular disease and Alzheimer's disease. Understanding the complex interplay between the oral microbiome and the host immune response is critical for the development of new therapeutic strategies for the prevention and treatment of periodontitis and its systemic consequences.