Periodontal disease: A systemic condition.

For decades, periodontitis has been considered to be a local inflammatory disease of the periodontal tissues in the oral cavity. Initially, associations of periodontitis with a multitude of noncommunicable diseases were each studied separately, and relationships were shown. The associations of periodontitis with morbidities, such as cardiovascular diseases, rheumatoid arthritis, diabetes mellitus, respiratory diseases, have been demonstrated. As most such studies were cross-sectional in nature, questions about causality cannot be univocally answered. And periodontitis as an independent risk factor for one systemic disease, becomes even more difficult to assess since recently periodontitis has also been associated with multimorbidity. Periodontitis and many systemic diseases share environmental, lifestyle and genetic risk factors, and share immunopathology. Moreover, suffering from one common noncommunicable disease may increase the susceptibility for another such chronic disease; the systemic effects of one condition may be one of various risk factors for another such disease. The overarching effect of any systemic disease is it causing a pro-inflammatory state in the individual; this has also been shown for periodontitis. Moreover, in periodontitis a prothrombotic state and elevated immunological activity have been shown. As such, when we consider periodontal disease as another systemic disease, it can affect the susceptibility and progression of other systemic diseases, and importantly, vice versa. And with this, it is not surprising that periodontitis is associated with a variety of other noncommunicable diseases. The medical definition of a systemic disease includes diseases that affect different organs and systems. Thus, the aim of this opinion paper is to propose that periodontitis should be considered a systemic disease in its own right and that it affects the individual's systemic condition and wellbeing. The dental and medical profession and researchers alike, should adapt this paradigm shift, advancing periodontal disease out of its isolated anatomical location into the total of chronic noncommunicable diseases, being for some conditions a comorbid disease and, vice versa, comorbidities can affect initiation and progression of periodontal disease.

Oral Pathobiont-Derived Outer Membrane Vesicles in the Oral-Gut Axis.

Oral pathobionts are essential in instigating local inflammation within the oral cavity and contribute to the pathogenesis of diseases in the gastrointestinal tract and other distant organs. Among the Gram-negative pathobionts, Porphyromonas gingivalis and Fusobacterium nucleatum emerge as critical drivers of periodontitis, exerting their influence not only locally but also as inducers of gut dysbiosis, intestinal disturbances, and systemic ailments. This dual impact is facilitated by their ectopic colonization of the intestinal mucosa and the subsequent mediation of distal systemic effects by releasing outer membrane vesicles (OMVs) into circulation. This review elucidates the principal components of oral pathobiont-derived OMVs implicated in disease pathogenesis within the oral-gut axis, detailing virulence factors that OMVs carry and their interactions with host epithelial and immune cells, both in vitro and in vivo. Additionally, we shed light on the less acknowledged interplay between oral pathobionts and the gut commensal Akkermansia muciniphila, which can directly impede oral pathobionts' growth and modulate bacterial gene expression. Notably, OMVs derived from A. muciniphila emerge as promoters of anti-inflammatory effects within the gastrointestinal and distant tissues. Consequently, we explore the potential of A. muciniphila-derived OMVs to interact with oral pathobionts and prevent disease in the oral-gut axis.

Mitochondrial Dysfunction in Periodontitis and Associated Systemic Diseases: Implications for Pathomechanisms and Therapeutic Strategies.

Periodontitis is a chronic infectious disorder damaging periodontal tissues, including the gingiva, periodontal ligament, cementum, and alveolar bone. It arises from the complex interplay between pathogenic oral bacteria and host immune response. Contrary to the previous view of "energy factories", mitochondria have recently been recognized as semi-autonomous organelles that fine-tune cell survival, death, metabolism, and other functions. Under physiological conditions, periodontal tissue cells participate in dynamic processes, including differentiation, mineralization, and regeneration. These fundamental activities depend on properly functioning mitochondria, which play a crucial role through bioenergetics, dynamics, mitophagy, and quality control. However, during the initiation and progression of periodontitis, mitochondrial quality control is compromised due to a range of challenges, such as bacterial-host interactions, inflammation, and oxidative stress. Currently, mounting evidence suggests that mitochondria dysfunction serves as a common pathological mechanism linking periodontitis with systemic conditions like type II diabetes, obesity, and cardiovascular diseases. Therefore, targeting mitochondria to intervene in periodontitis and multiple associated systemic diseases holds great therapeutic potential. This review provides advanced insights into the interplay between mitochondria, periodontitis, and associated systemic diseases. Moreover, we emphasize the significance of diverse therapeutic modulators and signaling pathways that regulate mitochondrial function in periodontal and systemic cells.

Diagnosis and initial management of children presenting with premature loss of primary teeth associated with a systemic condition: A scoping review and development of clinical aid.

BACKGROUND: Premature loss of primary teeth (PLPT) can be a rare presentation of systemic medical conditions. Premature loss of primary teeth may present a diagnostic dilemma to paediatric dentists. AIMS: To identify systemic conditions associated with PLPT and develop a clinical aid. DESIGN: OVID Medline, Embase and Web of Science were searched up to March 2023. Citation searching of review publications occurred. Exclusion occurred for conference abstracts, absence of PLPT and absence of English-language full text. RESULTS: Seven hundred and ninety-one publications were identified via databases and 476 by citation searching of review articles. Removal of 390 duplicates occurred. Following the exclusion of 466 records on abstract review, 411 publications were sought for retrieval, of which 142 met inclusion criteria. Thirty-one systemic conditions were identified. For 19 conditions, only one publication was identified. The majority of publications, 91% (n = 129), were case reports or series. Most publications, 44% (n = 62), were related to hypophosphatasia, and 25% (n = 35) were related to Papillon-Lefèvre. Diagnostic features were synthesised, and a clinical aid was produced by an iterative consensus approach. CONCLUSIONS: A diverse range of systemic diseases are associated with PLPT. Evidence quality, however, is low, with most diseases having a low number of supporting cases. This clinical aid supports paediatric dentists in differential diagnosis and onward referral.

Associations between Systemic and Dental Diseases in Elderly Korean Population.

Background and Objectives: Modernization and population aging have increased the prevalence of systemic diseases, such as diabetes and hypertension, which are often accompanied by various dental diseases. Our aim was to investigate associations between common dental conditions and major systemic diseases in an elderly Korean population. Materials and Methods: Utilizing electronic medical record data from 43,525 elderly patients, we examined the prevalence of systemic diseases (diabetes, hypertension, rheumatoid arthritis, osteoporosis, dementia) and dental conditions (caries, periodontal disease, pulp necrosis, tooth loss). The analysis focused on the correlations between these diseases. Results: Significant associations were found between systemic diseases and an increased prevalence of dental conditions. Patients with systemic diseases, especially those with multiple conditions, had higher incidences of periodontal disease and tooth loss. The correlation was particularly strong in patients with diabetes and rheumatoid arthritis. Interestingly, temporomandibular joint disorder was less frequent in this cohort. Conclusions: The findings highlight the importance of integrated dental care in managing systemic diseases in elderly populations. Enhanced dental monitoring and proactive treatment are essential due to the strong association between systemic diseases and dental conditions. Collaboration between dental and medical professionals is crucial for comprehensive care that improves health outcomes and quality of life for elderly patients.

Hereditary dentin defects with systemic diseases.

OBJECTIVE: This review aimed to summarize recent progress on syndromic dentin defects, promoting a better understanding of systemic diseases with dentin malformations, the molecules involved, and related mechanisms. SUBJECTS AND METHODS: References on genetic diseases with dentin malformations were obtained from various sources, including PubMed, OMIM, NCBI, and other websites. The clinical phenotypes and genetic backgrounds of these diseases were then summarized, analyzed, and compared. RESULTS: Over 10 systemic diseases, including osteogenesis imperfecta, hypophosphatemic rickets, vitamin D-dependent rickets, familial tumoral calcinosis, Ehlers-Danlos syndrome, Schimke immuno-osseous dysplasia, hypophosphatasia, Elsahy-Waters syndrome, Singleton-Merten syndrome, odontochondrodysplasia, and microcephalic osteodysplastic primordial dwarfism type II were examined. Most of these are bone disorders, and their pathogenic genes may regulate both dentin and bone development, involving extracellular matrix, cell differentiation, and metabolism of calcium, phosphorus, and vitamin D. The phenotypes of these syndromic dentin defects various with the involved genes, part of them are similar to dentinogenesis imperfecta or dentin dysplasia, while others only present one or two types of dentin abnormalities such as discoloration, irregular enlarged or obliterated pulp and canal, or root malformation. CONCLUSION: Some specific dentin defects associated with systemic diseases may serve as important phenotypes for dentists to diagnose. Furthermore, mechanistic studies on syndromic dentin defects may provide valuable insights into isolated dentin defects and general dentin development or mineralization.

A meta-analysis on the association between obstructive sleep apnea and periodontitis.

PURPOSE: The present meta-analysis aimed to evaluate quantitively the recent scientific evidence regarding the association between obstructive sleep apnea (OSA) and periodontitis. METHODS: Databases searched were PubMed, EMBASE, Scopus, and Web of Science. Publications were included according to the inclusion criteria. The following outcomes were evaluated: the prevalence of periodontitis, probing depth (PD), clinical attachment loss (CAL), the percentage of sites with bleeding on probing (BOP), plaque index (PI), and gingival index (GI). The statistical analysis was processed using the software STATA. RESULTS: Thirteen eligible studies comprising a total of 31,800 patients were included. The meta-analysis showed an increased prevalence of periodontitis in OSA populations compared to controls. Both PD and CAL were increased in OSA populations compared with controls. (Prevalence of periodontitis: OR 2.348; 95%CI 2.221-2.482; PD: SMD = 0.681, 95% CI: 0.062-1.301, Z = 2.61, P = 0.031; CAL: SMD = 0.694, 95% CI: 0.167-1.22, Z = 2.58, P = 0.01). The study also found significantly increased BOP in patients with OSA after heterogeneity was clarified. (SMD = 0.357, 95% CI: 0.079-0.635, Z = 2.52, P = 0.012). CONCLUSIONS: The findings suggest that OSA was associated with an increased prevalence of periodontitis.

Gut microbiota may mediate the impact of chronic apical periodontitis on atherosclerosis in apolipoprotein E-deficient mice.

AIM: There are growing evidences linking chronic apical periodontitis (CAP) to atherosclerosis. Gut microbiota is found to be involved in the development of atherosclerosis. Recent studies have shown that CAP could change the diversity and composition of the gut microbiota. It was therefore, we hypothesized that gut microbiota and its metabolites could mediate the impact of CAP on atherosclerosis. METHODOLOGY: Twenty-four 5-week-old lipoprotein E knockout (apoE-/- ) mice were randomly divided into four groups: the CAP group, Con group, Co-CAP (cohoused with CAP) and Co-Con (cohoused with Con) group. In the CAP group, sterile cotton wool containing P. gingivalis was placed into the exposed pulp chamber, followed by coronal resin-based composite restoration of the bilateral maxillary first and second molars. In the Con group, a sham operation was performed. Biweekly, mice in the CAP group were anaesthetised to check the sealing of coronal access. Meanwhile, the animals in the Con group were anaesthetised. The cohousing approach was used to introduce gut microbiota from the CAP and Con groups into the Co-CAP and Co-Con groups, respectively. Alterations in the abundance and diversity of the gut microbiota were detected using 16S rRNA sequencing, Oil-red O staining was used to demonstrate the extent of lesions, and serum levels of trimethylamine N-oxide (TMAO), and immunohistochemistry of flavin-containing monooxygenase 3 (FMO3) in liver were used to assess TMAO-related metabolic alterations. RESULTS: Alterations of alpha and beta diversity were shown both in the CAP and the Co-CAP groups. Moreover, the percentage of atherosclerotic lesion area increased in the CAP and Co-CAP groups (p < .05). Linear discriminant analysis effect size (LEfSe) at the family level found the increases of Lachnospiraceae and Ruminococcaceae (p < .05), which were positively correlated with serum TMAO levels (p < .05). In the redundancy analysis technique (RDA), serum levels of TMAO were positively associated with the atherosclerotic lesions. Co-occurrence analysis revealed that the relative abundances of Lachnospiraceae and Porphyromonadacae were positively correlated with both the percentage of lesion area and TMAO level (p < .05). CONCLUSION: Thus, within the limitations of this study, the data suggest that the gut microbiota can mediate the effects of CAP on atherosclerosis.

Evaluating the relationship between ankylosing spondylitis and periodontal disease: a case-control study.

OBJECTIVES: This study aimed to determine the possible relationship between periodontal disease and ankylosing spondylitis (AS) by evaluating clinical periodontal measurements and gingival crevicular fluid (GCF) levels of sclerostin, interleukin-1ß (IL-1ß), and matrix metalloproteinase-8 (MMP-8) levels. MATERIALS AND METHODS: Twenty-eight patients with AS (AS group) and 28 systemically healthy controls (C group) were enrolled in this study. Full-mouth periodontal measurements: plaque index, bleeding on probing (BOP), probing pocket depth (PPD), and clinical attachment level (CAL) measurements were obtained from all patients. AS-related parameters were included in the data analyses. An enzyme-linked immunosorbent assay determined GCF IL-1ß, MMP-8, and sclerostin levels. RESULTS: There were no significant differences in the clinical periodontal measurements between the two groups (p > 0.05). Interestingly, patients with AS had significantly lower GCF sclerostin levels than the C group (p < 0.05). But there were no statistical differences in the GCF levels of IL-1ß and MMP-8 between the two groups (p > 0.05). Serum C-reactive protein (CRP) levels strongly correlated with both BOP (r = 0.497, p < 0.05) and PPD (r = 0.570, p < 0.05) in the AS group. Bath AS Metrology Index (BASMI) also positively correlated with both BOP (r = 0.530, p < 0.05) and CAL (r = 0.568, p < 0.05). Similarly, Maastricht Ankylosing Spondylitis Enthesis Score (MASES) strongly correlated with both BOP (r = 0.487, p < 0.05) and CAL (r = 0.522, p < 0.05). CONCLUSION: These results suggest that the patient's systemic condition may influence local sclerostin levels in GCF, and the strong correlations between periodontal measurements and AS-related parameters may indicate an interrelationship between inflammatory periodontal disease and AS. CLINICAL RELEVANCE: The present study provides important information concerning the relationship between periodontal disease and ankylosing spondylitis. TRIAL REGISTRATION: Thai Clinical Trials.gov (TCTR20200908001) (08. September 2020).

Genetic Control of GCF Exudation: Innate Immunity Genes and Periodontitis Susceptibility.

Chronic periodontitis is a bacterial infection associated with dentally adherent biofilm (plaque) accumulation and age-related comorbidities. The disease begins as an inflammatory exudate from gingival margins, gingival crevicular fluid (GCF) in response to biofilm lysine. After a week of experimental gingivitis (no oral hygiene), biofilm lysine concentration was linearly related to biofilm accumulation (plaque index) but to GCF as an arch-shaped double curve which separated 9 strong from 6 weak GCF responders (hosts). Host DNA was examined for single nucleotide polymorphisms (SNPs) of alleles reported in 7 periodontitis-associated genes. Across all 15 hosts, an adenine SNP (A) at IL1B-511 (rs16944), was significant for strong GCF (Fisher's exact test, p < 0.05), and a thymidine SNP (T) at IL1B+3954 (rs1143634) for weak GCF provided 2 hosts possessing IL6-1363(T), rs2069827, were included. The phenotype of IL1B+3954(T) was converted from weak to strong in one host, and of the non-T allele from strong to weak in the other (specific epistasis, Fisher's exact test, p < 0.01). Together with homozygous alternate or reference SNPs at IL10-1082 or CD14-260 in 4 hosts, all hosts were identified as strong or weak GCF responders. The GCF response is therefore a strong or weak genetic trait that indicates strong or weak innate immunity in EG and controllable or uncontrollable periodontal disease, dental implant survival and late-life comorbidities.

Salivary Alterations of Myeloperoxidase in Patients with Systemic Diseases: A Systematic Review.

Salivary myeloperoxidase (MPO) is a key mediator of the oral immune system, acting as an enzyme that utilises H2O2 to generate molecules with high bactericidal activity. While MPO determination in plasma is quite common, the use of saliva is still rare. Our systematic review was designed to answer the question "Are salivary levels of myeloperoxidase altered in patients with systemic diseases?". Following the inclusion and exclusion criteria, we included twenty-six studies. Altered MPO levels in saliva were most commonly found in patients with cardiovascular and gastrointestinal diseases. Most studies concerned unstimulated whole saliva, and only a few of them stimulated, mainly by chewing paraffin. Enzyme-linked immunosorbent assay (ELISA) was the most common method for determination of MPO concentrations in saliva. Increased salivary MPO levels were more often observed for inflammatory diseases, except patients with inflammatory bowel diseases who were eligible for biologic therapy. In conclusion, MPO could be altered in the saliva of patients with systematic diseases, especially cardiovascular or gastrointestinal diseases. However, further investigations are recommended to validate these outcomes.

Digital Form for Assessing Dentistry Undergraduates Regarding Periodontal Disease Associated with Cardiovascular Diseases.

Background: Throughout recent years, periodontal disease (PD) has been linked to innumerable medical systemic conditions, such as cardiovascular disease (CVD). This association could negatively impact oral health, so the knowledge of dentists who have graduated must follow modern dentistry in order to promote oral health, mainly in systemically compromised patients. Therefore, the present study aimed to determine and evaluate the knowledge level of dentistry undergraduate students (DUS) regarding the correct periodontal treatment and management of cardiac patients with PD. Methods: This cross-sectional and populational-based study was conducted between March and June 2022 in northern Brazil. A total of 153 DUS received an anonymous digital form (Google Forms Platform) using a non-probabilistic "snowball" sampling technique. The digital form was composed of four blocks of dichotomous and multiple-choice questions. After signing the informed consent term, DUS were divided into three groups according to their period/semester in dentistry graduation during the study time (G1: 1st period/semester; G2: 5th period/semester and G3: 10th period/semester). A total of 25 questions referring to demographic, educational and knowledge data about the dental and periodontal care of cardiac patients with PD were asked, and all data were presented as descriptive percentages and then analyzed using the Kappa test. Results: From a total of 153 (100%) DUS, the sample was mostly composed of 104 (68%) female participants, with an average age of 21.1 years. Regarding basic knowledge, the majority of answers were no, with G1 being higher than G2 and G3. Regarding clinical questions, 1247 (58.3%) answers were no. Additionally, regarding fundamental clinical questions 1, 2, 3, 7, 9, 11, 13 and 14, the majority of G1, G2 and G3 answered no, demonstrating a major lack of knowledge. Conclusions: In our study, DUS demonstrated a low knowledge level of the dental and periodontal care of cardiac patients with PD and its bi-directional link. Thus, according to our results, an improvement in dentistry educational programs regarding periodontal medicine must be implemented.

[Developments in Research on Salivary Biomarkers in the Diagnosis of Systemic Diseases].

Saliva, an important biological fluid secreted by oral glands, serves multiple functions. It performs cleaning and protective functions for oral tissues, safeguarding against biological, mechanical and chemical stimuli, while allowing for the sensory perception of taste and temperature. It is also responsible for the preliminary digestion of food. These functions and properties of saliva are attributed to the presence of electrolytes, buffers, proteins, glycoproteins, and lipids in saliva. Recent studies have found that saliva contains biomarkers that are closely connected with the pathophysiological status of the human body, suggesting that saliva makes an ideal biological fluid for drug monitoring and biomarker screening. Therefore, salivary biomarkers can be used as an instrument for physical monitoring and localization of the occurrence of diseases, thereby accomplishing early diagnosis of diseases and assessment of the overall health status of patients. However, the actual application of salivary biomarkers in the diagnosis and treatment of systemic diseases is still not widely available, and the establishment of evaluation criteria and the exploration of its mechanism are not sufficiently investigated. Herein, we reviewed the latest research findings on applying the salivary biomarkers in the diagnosis of systemic diseases.

Photobiomodulation stimulates surrounding bone formation and increases stability of titanium alloy miniscrews in ovariectomized rats.

The number of older individuals (> 60 years) treated in orthodontic dental practice is constantly growing, and osteoporosis is a common disease within this age range. Orthodontic treatment for this group tends to be challenging, often requiring the use of mini-implants. Mini-implants are important accessories in orthodontic treatment that provide solutions to complex cases. Despite the high level of success, these devices are prone to failure if insufficient bone stability is achieved. This study aimed to evaluate the effects of photobiomodulation on bone neoformation around mini-implants using fluorescence analysis in ovariectomized rats. A total of 12 female rats (Wistar) were ovariectomized and divided into three groups: two groups of low-level laser therapy irradiation in two different protocols, as follows: in the PBM1 group, applications were performed using 2 J, for 20 s each for 48 h, 6 irradiations in total, and in the PBM2 group, a single application of 4 J was performed for 40 s, and the third group represented the control group, and no laser therapy was applied. Each rat received two mini-implants placed immediately behind the upper incisors, and 0 g of force was applied using a NiTi spring. All rats received two bone markers, tetracycline (days 0-4) and alizarin (days 7-10), for 5 days each. Both markers were bound to calcium, allowing visualization of bone neoformation through fluorescence microscopy. After 12 days, euthanasia was performed; the results revealed that both irradiated groups showed significantly greater bone neoformation compared to the control group (p < 0.05). Mini-implant stability was measured in all animals using the Periotest device on day 0 and on the day of euthanasia. A significant increase in stability was observed in the group that received more laser application (p < 0.05). Photobiomodulation had a positive effect on bone neoformation around mini-implants in ovariectomized rats, with an increase in stability when more irradiation was performed.

Porphyromonas gingivalis outside the oral cavity.

Porphyromonas gingivalis, a Gram-negative anaerobic bacillus present in periodontal disease, is considered one of the major pathogens in periodontitis. A literature search for English original studies, case series and review articles published up to December 2019 was performed using the MEDLINE, PubMed and GoogleScholar databases, with the search terms "Porphyromonas gingivalis" AND the potentially associated condition or systemic disease Abstracts and full text articles were used to make a review of published research literature on P. gingivalis outside the oral cavity. The main points of interest of this narrative review were: (i) a potential direct action of the bacterium and not the systemic effects of the inflammatory acute-phase response induced by the periodontitis, (ii) the presence of the bacterium (viable or not) in the organ, or (iii) the presence of its virulence factors. Virulence factors (gingipains, capsule, fimbriae, hemagglutinins, lipopolysaccharide, hemolysin, iron uptake transporters, toxic outer membrane blebs/vesicles, and DNA) associated with P. gingivalis can deregulate certain functions in humans, particularly host immune systems, and cause various local and systemic pathologies. The most recent studies linking P. gingivalis to systemic diseases were discussed, remembering particularly the molecular mechanisms involved in different infections, including cerebral, cardiovascular, pulmonary, bone, digestive and peri-natal infections. Recent involvement of P. gingivalis in neurological diseases has been demonstrated. P. gingivalis modulates cellular homeostasis and increases markers of inflammation. It is also a factor in the oxidative stress involved in beta-amyloid production.

Potential Roles of Selectins in Periodontal Diseases and Associated Systemic Diseases: Could They Be Targets for Immunotherapy?

Periodontal diseases are predisposing factors to the development of many systemic disorders, which is often initiated via leukocyte infiltration and vascular inflammation. These diseases could significantly affect human health and quality of life. Hence, it is vital to explore effective therapies to prevent disease progression. Periodontitis, which is characterized by gingival bleeding, disruption of the gingival capillary's integrity, and irreversible destruction of the periodontal supporting bone, appears to be caused by overexpression of selectins in periodontal tissues. Selectins (P-, L-, and E-selectins) are vital members of adhesion molecules regulating inflammatory and immune responses. They are mainly located in platelets, leukocytes, and endothelial cells. Furthermore, selectins are involved in the immunopathogenesis of vascular inflammatory diseases, such as cardiovascular disease, diabetes, cancers, and so on, by mediating leukocyte recruitment, platelet activation, and alteration of endothelial barrier permeability. Therefore, selectins could be new immunotherapeutic targets for periodontal disorders and their associated systemic diseases since they play a crucial role in immune regulation and endothelium dysfunction. However, the research on selectins and their association with periodontal and systemic diseases remains limited. This review aims to discuss the critical roles of selectins in periodontitis and associated systemic disorders and highlights the potential of selectins as therapeutic targets.

Oral health's inextricable connection to systemic health: Special populations bring to bear multimodal relationships and factors connecting periodontal disease to systemic diseases and conditions.

The landscape in dentistry is changing as emerging studies continue to reveal that periodontal health impacts systemic health, and vice versa. Population studies, clinical studies, and in vitro animal studies underscore the critical importance of oral health to systemic health. These inextricable relationships come to the forefront as oral diseases, such as periodontal disease, take root. Special populations bring to bear the multimodal relationships between oral and systemic health. Specifically, periodontal disease has been associated with diabetes, metabolic syndrome, obesity, eating disorders, liver disease, cardiovascular disease, Alzheimer disease, rheumatoid arthritis, adverse pregnancy outcomes, and cancer. Although bidirectional relationships are recognized, the potential for multiple comorbidities, relationships, and connections (multimodal relationships) also exists. Proposed mechanisms that mediate this connection between oral and systemic health include predisposing and precipitating factors, such as genetic factors (gene polymorphisms), environmental factors (stress, habits-such as smoking and high-fat diets/consumption of highly processed foods), medications, microbial dysbiosis and bacteremias/viremias/microbemias, and an altered host immune response. Thus, in a susceptible host, these predisposing and precipitating factors trigger the onset of periodontal disease and systemic disease/conditions. Further, high-throughput sequencing technologies are shedding light on the dark matter that comprises the oral microbiome. This has resulted in better characterization of the oral microbial dysbiosis, including putative bacterial periodontopathogens and shifts in oral virome composition during disease. Multiple laboratory and clinical studies have illustrated that both eukaryotic and prokaryotic viruses within subgingival plaque and periodontal tissues affect periodontal inflammation, putative periodontopathogens, and the host immune response. Although the association between herpesviruses and periodontitis and the degree to which these viruses directly aggravate periodontal tissue damage remain unclear, the benefits to periodontal health found from prolonged administration of antivirals in immunocompromised or immunodeficient individuals demonstrates that specific populations are possibly more susceptible to viral periodontopathogens. Thus, it may be important to further examine the implications of viral pathogen involvement in periodontitis and perhaps it is time to embrace the viral dark matter within the periodontal environment to fully comprehend the pathogenesis and systemic implications of periodontitis. Emerging data from the coronavirus disease 2019 pandemic further underscores the inextricable connection between oral and systemic health, with high levels of the severe acute respiratory syndrome coronavirus 2 angiotensin-converting enzyme 2 receptor noted on oral tissues (tongue) and an allostatic load or overload paradigm of chronic stress likely contributing to rapid breakdown of oral/dental, periodontal, and peri-implant tissues. These associations exist within a framework of viremias/bacteremias/microbemias, systemic inflammation, and/or disturbances of the immune system in a susceptible host. A thorough review of systemic and oral diseases and conditions and their mechanistic, predisposing, and precipitating factors are paramount to better addressing the oral and systemic health and needs of our patients.

Dermatologic findings in individuals with genetically confirmed Proteus syndrome.

BACKGROUND/OBJECTIVE: Proteus syndrome, caused by a mosaic activating AKT1 variant, typically presents in toddlers with progressive, asymmetric overgrowth of the skin and bones. We aimed to define the spectrum of dermatologic disease in individuals with genetically confirmed Proteus syndrome. METHODS: We conducted a retrospective review of records from dermatologic examinations of individuals evaluated at the NIH with a molecular diagnosis of Proteus syndrome. The types, prevalence, and localization of dermatologic findings were assessed. RESULTS: Fifty-one individuals (29 males, 22 females, mean age: 9 years) with clinical features of Proteus syndrome had the mosaic c.49G>A, p.Glu17Lys AKT1 variant. Fifty (98%) had at least one cutaneous feature constituting current clinical diagnostic criteria, including vascular malformations in 42 (82%), epidermal nevus in 41 (80%), volar cerebriform connective tissue nevi in 34 (67%), and adipose dysregulation in 30 (59%). Forty-nine (96%) had at least one dermatologic finding not included within the diagnostic criteria, including confluent volar skin-colored to hypopigmented papules or nodules (n = 33, 65%), papules or nodules on the digits or face (n = 27, 53%), and nonlinear epidermal nevi (n = 15, 29%). Other frequently observed features include nail changes (n = 28, 55%), hyperpigmented macules (n = 27, 53%), patchy dermal hypoplasia (n = 18, 35%), gingival/oral mucosal overgrowth (n = 17, 33%), hypopigmented macules (n = 16, 31%), dental enamel changes (n = 9, 18%), acrochordons (n = 6, 12%), and lingual overgrowth (n = 4, 8%). CONCLUSIONS: The range of mucocutaneous features occurring in Proteus syndrome is broader than previously considered. These observations may assist in earlier diagnosis and management and provide novel insights regarding the pathogenesis of the condition.

Application of Ligature-Induced Periodontitis in Mice to Explore the Molecular Mechanism of Periodontal Disease.

Periodontitis is an inflammatory disease characterized by the destruction of the periodontium. In the last decade, a new murine model of periodontitis has been widely used to simulate alveolar bone resorption and periodontal soft tissue destruction by ligation. Typically, 3-0 to 9-0 silks are selected for ligation around the molars in mice, and significant bone loss and inflammatory infiltration are observed within a week. The ligature-maintained period can vary according to specific aims. We reviewed the findings on the interaction of systemic diseases with periodontitis, periodontal tissue destruction, the immunological and bacteriological responses, and new treatments. In these studies, the activation of osteoclasts, upregulation of pro-inflammatory factors, and excessive immune response have been considered as major factors in periodontal disruption. Multiple genes identified in periodontal tissues partly reflect the complexity of the pathogenesis of periodontitis. The effects of novel treatment methods on periodontitis have also been evaluated in a ligature-induced periodontitis model in mice. This model cannot completely represent all aspects of periodontitis in humans but is considered an effective method for the exploration of its mechanisms. Through this review, we aimed to provide evidence and enlightenment for future studies planning to use this model.

Oral manifestations of patients with systemic sclerosis: a meta-analysis for case-controlled studies.

BACKGROUND: Systemic sclerosis (SSc) is a multisystem rheumatic disease. Orofacial manifestations are commonly in SSc but maybe usually ignored and overshadowed by other systemic complications. Multiple comparative studies have been conducted to investigate the possible links between SSc and oral manifestations. The present study aimed to investigate the oral health status in patients with SSc. METHODS: Pubmed, Embase, Web of Science, and Scopus were searched up to July 2020. Following outcomes were evaluated: Probing depth (PD), Attachment loss (AL), Bleeding on probing (BOP), Number or percentage of Sites with PD ≥ 4 mm, Prevalence of periodontitis, Number of teeth, Decayed Teeth, Missing teeth, Filled teeth, DMFT index, and the interincisal distance. Newcastle-Ottawa Scale (NOS) were applied for quality assessment. The statistical analysis was processed using the software STATA. RESULTS: 11 eligible studies were included. The maximum interincisor distance was significantly restricted in SSc patients (SMD - 1.061; 95 %CI [- 1.546, - 0.576]; Z = 4.29, P = 0.000).The prevalence of Periodontitis (OR 7.007; 95 %CI [3.529, 13.915]; Z = 5.56, P = 0.000), PD (SMD 3.101; 95 %CI [1.374, 4.829]; Z = 3.52, P = 0.000), AL(SMD 2.584; 95 %CI [0.321, 4.846]; Z = 2.24, P = 0.025), sites with PD ≥ 4mm (SMD 2.071 ; 95 %CI [0.267, 3.875]; Z = 2.25, P = 0.024) and the number of decayed teeth (SMD, 0.186; 95 %CI [0.007, 0.365]; Z = 2.04, P = 0.041) were increased significantly in SSc population in comparison with the controls. CONCLUSIONS: SSc patients have limited mouth opening, higher periodontitis prevalence, and worse periodontal status, as well as an increased number of decayed teeth. Routinely oral hygiene instruction and initial periodontal treatment is recommended for SSc patients.