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AIMS: To investigate the clinical performance of regenerative periodontal surgery in the treatment of furcation defects versus open flap debridement (OFD) and to compare different regenerative modalities. MATERIAL AND METHODS: A systematic search was conducted to identify RCTs evaluating regenerative surgical treatment of furcations with a minimum of 12-month follow-up. Three authors independently reviewed, selected and extracted data from the search conducted and assessed risk of bias. Primary outcomes were tooth loss, furcation improvement (closure/conversion) (FImp), gain of horizontal bone level (HBL) and attachment level (HCAL). Secondary outcomes were gain in vertical attachment level (VCAL), probing pocket depth (PPD) reduction, PROMs and adverse events. Data were summarized into Bayesian standard and network meta-analysis in order to estimate direct and indirect treatment effects and to establish a ranking of treatments. RESULTS: The search identified 19 articles, reporting on 20 RCTs (19 on class II, 1 on class III furcations) with a total of 575 patients/787 defects. Tooth loss was not reported. Furcation closure ranged between 0% and 60% (10 trials), and class I conversion from 29% to 100% (six trials). Regenerative techniques were superior to OFD for FImp (OR = 20.9; 90% CrI = 5.81, 69.41), HCAL gain (1.6 mm), VCAL gain (1.3 mm) and PPD reduction (1.3 mm). Bone replacement grafts (BRG) resulted in the highest probability (Pr = 61%) of being the best treatment for HBL gain. Non-resorbable membranes + BRG ranked as the best treatment for VCAL gain (Pr = 75%) and PPD reduction (Pr = 56%). CONCLUSIONS: Regenerative surgery of class II furcations is superior to OFD. FImp (furcation closure or class I conversion) can be expected for the majority of defects. Treatment modalities involving BRG are associated with higher performance.
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Defeitos da Furca , Teorema de Bayes , Defeitos da Furca/cirurgia , Regeneração Tecidual Guiada Periodontal , Humanos , Membranas Artificiais , Metanálise em Rede , Perda da Inserção Periodontal/cirurgia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
AIM: To evaluate the sequential and differential expression of a variety of antimicrobial peptides (AMPs) during the development of an experimentally induced gingivitis in humans. MATERIAL AND METHODS: In twenty healthy volunteers, gingival inflammation was induced by abstention from oral hygiene at 6 teeth. Bleeding on probing (BOP) and plaque index (PI) were assessed, and gingival biopsies and gingival crevicular fluid (GCF) were collected at 8 different time points (t0-t35). Gingival epithelial cells (GECs) were stimulated with various receptor agonists. In biopsies and GECs, mRNA expression of human beta-defensins (hBD-2, hBD-3), CC-chemokine ligand 20 (CCL20), S100A7/psoriasin (S100A7), and calgranulin A/B (S100A8, S100A9) was evaluated using real-time PCR, and protein profiles were measured by ELISA. Statistical analysis was performed using non-parametric tests. RESULTS: The clinical parameters BOP, PI and GCF increased over time (p < 0.0001). Tissue AMP mRNA expression was elevated, but at different and AMP-specific time points (p < 0.05). Protein analysis revealed a similar expression pattern for hBD-2 and CCL20 in GCF (p < 0.05). In GECs, multiple receptor stimulation was required to induce AMP gene expression (p < 0.0001). CONCLUSIONS: For the first time, this study showed the sequential and differential expression of AMPs during a developing inflammation in vivo providing further evidence for their role as guardians of a healthy periodontium.
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Anti-Infecciosos , Gengivite , Gengiva , Líquido do Sulco Gengival , Humanos , InflamaçãoRESUMO
Host immune responses play a key role in promoting bone resorption in periodontitis via receptor activator of NF-κB ligand (RANKL)-dependent osteoclastogenesis. Both membrane-bound RANKL (mRANKL) expressed on lymphocytes and soluble RANKL (sRANKL) are found in periodontal lesions. However, the underlying mechanism and cellular source of sRANKL release and its biological role in periodontitis are unclear. TNF-α-converting enzyme (TACE) is reported to cleave the following: 1) precursor TNF-α with release of mature, soluble TNF-α and 2) mRANKL with release of sRANKL. Both soluble TNF-α and sRANKL are found in the periodontitis lesion, leading to the hypothesis that TACE expressed on lymphocytes is engaged in RANKL shedding and that the resulting sRANKL induces osteoclastogenesis. In the current study, upon stimulating PBLs with mitogens in vitro, RANKL expression, sRANKL secretion, and TACE expression were all upregulated. Among the four putative mRANKL sheddases examined in neutralization assays, TACE was the only functional sheddase able to cleave mRANKL expressed on PBL. Moreover, PBL culture supernatant stimulated with mitogens in the presence of anti-TACE Ab or anti-RANKL Ab showed a marked reduction of osteoclastogenesis from osteoclast precursors, indicating that TACE-mediated sRANKL may possess sufficient osteoclastogenic activity. According to double-color confocal microscopy, B cells expressed a more pronounced level of RANKL and TACE expression than T cells or monocytes in periodontally diseased gingiva. Conditioned medium of patients' gingival lymphocyte culture increased in vitro osteoclastogenic activity, which was suppressed by the addition of anti-TACE Ab and anti-RANKL Ab. Therefore, TACE-mediated cleavage of sRANKL from activated lymphocytes, especially B cells, can promote osteoclastogenesis in periodontitis.
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Proteína ADAM17/metabolismo , Ativação Linfocitária , Osteogênese , Periodontite/imunologia , Ligante RANK/metabolismo , Linfócitos T/imunologia , Proteína ADAM17/genética , Linfócitos B/efeitos dos fármacos , Linfócitos B/imunologia , Linfócitos B/metabolismo , Reabsorção Óssea , Células Cultivadas , Gengiva/citologia , Gengiva/imunologia , Humanos , Lipopolissacarídeos/imunologia , Masculino , Monócitos/imunologia , Osteoclastos/imunologia , Periodontite/fisiopatologia , Ligante RANK/genética , Solubilidade , Linfócitos T/metabolismoRESUMO
Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine and counter-regulator of endogenous glucocorticoids (GCs). It is implicated in acute and chronic inflammatory diseases. This study investigated the role of the MIF-GC regulatory dyad in the expression and release of matrix metalloproteinase-2 (MMP-2) during periodontitis, in vivo and in vitro. In a Mif-knockout (KO) mouse model of ligature-induced periodontitis, gingival tissues and blood were collected and analysed for levels of interleukin-6 (IL-6), MIF, MMP-2, and corticosterone. In addition, human gingival fibroblasts (HGFs) were tested for production of IL-6 and MMP-2 after stimulation with hydrocortisone (HC), MIF, tumour necrosis factor-alpha (TNF-α), or Fusobacterium nucleatum, a pathogen known to elicit immune responses during periodontitis. Wild-type (WT) mice showed a local and systemic increase of MIF levels during inflammation, which was confirmed by increased local IL-6 concentrations. Systemic GC levels were reduced in WT and Mif-KO mice during inflammation, with overall lower concentrations in Mif-KO mice. In vivo and in vitro, MMP-2 production was not dependent on MIF or inflammatory stimuli, but was inhibited by HC. Therefore, MIF does not appear to stimulate expression of MMP-2 in the gingival tissues, whereas GC upregulates MIF and downregulates MMP-2. Our findings further suggest that MIF may regulate systemic GC levels.
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Corticosterona/farmacologia , Fatores Inibidores da Migração de Macrófagos/farmacologia , Metaloproteinase 2 da Matriz/metabolismo , Periodontite/metabolismo , Animais , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Fibroblastos/metabolismo , Fusobacterium nucleatum/patogenicidade , Humanos , Hidrocortisona/farmacologia , Interleucina-6/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Reação em Cadeia da Polimerase , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
Bacterial biofilms cause a considerable amount of prosthetic joint infections every year, resulting in morbidity and expensive revision surgery. To address this problem, surface modifications of implant materials such as carbon nanotube (CNT) coatings have been investigated in the past years. CNTs are biologically compatible and can be utilized as drug delivery systems. In this study, multi-walled carbon nanotube (MWCNT) coated TiAl6V4 titanium alloy discs were fabricated and impregnated with Rifampicin, and tested for their ability to prevent biofilm formation over a period of ten days. Agar plate-based assays were employed to assess the antimicrobial activity of these surfaces against Staphylococcus epidermidis. It was shown that vertically aligned MWCNTs were more stable against attrition on rough surfaces than on polished TiAl6V4 surfaces. Discs with coated surfaces caused a significant inhibition of biofilm formation for up to five days. Therefore, MWCNT-modified surfaces may be effective against pathogenic biofilm formation on endoprostheses.
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Antibacterianos/química , Biofilmes/efeitos dos fármacos , Nanotubos de Carbono/química , Staphylococcus epidermidis/efeitos dos fármacos , Titânio/química , Ligas/química , Materiais Revestidos Biocompatíveis/química , Liberação Controlada de Fármacos , Próteses e Implantes/microbiologia , Infecções Relacionadas à Prótese/tratamento farmacológico , Rifampina/químicaRESUMO
Porphyromonas gingivalis is an important member of the anaerobic oral flora. Its presence fosters growth of periodontal biofilm and development of periodontitis. In this study, we demonstrated that lipophilic outer membrane vesicles (OMV) shed from P. gingivalis promote monocyte unresponsiveness to live P. gingivalis but retain reactivity to stimulation with bacterial DNA isolated from P. gingivalis or AIM2 ligand poly(dA·dT). OMV-mediated tolerance of P. gingivalis is characterized by selective abrogation of tumor necrosis factor (TNF). Neutralization of interleukin-10 (IL-10) during OMV challenge partially restores monocyte responsiveness toP. gingivalis; full reactivity toP. gingivalis can be restored by inhibition of mTOR signaling, which we previously identified as the major signaling pathway promoting Toll-like receptor 2 and Toll-like receptor 4 (TLR2/4)-mediated tolerance in monocytes. However, despite previous reports emphasizing a central role of TLR2 in innate immune recognition of P. gingivalis, our current findings highlight a selective role of TLR4 in the promotion of OMV-mediated TNF tolerance: only blockade of TLR4-and not of TLR2-restores responsiveness toP. gingivalis Of further note, OMV-mediated tolerance is preserved in the presence of cytochalasin B and chloroquine, indicating that triggering of surface TLR4 is sufficient for this effect. Taking the results together, we propose that P. gingivalis OMV contribute to local immune evasion of P. gingivalis by hampering the host response.
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Membrana Celular , Lipopolissacarídeos/metabolismo , Porphyromonas gingivalis/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/fisiologia , Células HEK293 , Humanos , Lipopolissacarídeos/farmacologia , Monócitos/metabolismo , Serina-Treonina Quinases TOR/genética , Receptor 4 Toll-Like/genética , Fator de Necrose Tumoral alfa/genéticaRESUMO
BACKGROUND: Oral biofilms are the causative agents of the highly prevalent oral diseases periodontitis and caries. Additionally, the host immune response is thought to play a critical role in disease onset. Neutrophils are known to be a key host response factor to bacterial challenge on host surfaces. Release of neutrophil extracellular traps (NETs) as a novel antimicrobial defense strategy has gained increasing attention in the past years. Here, we investigated the influx of neutrophils into the dental plaque and the ability of oral bacteria to trigger intra-biofilm release of NETs and intracellular proteins. METHODS: Supragingival biofilms and whole saliva were sampled from systemically healthy subjects participating in an experimental gingivitis study. Biofilms were analysed by immunofluorescence followed by confocal and fluorescence microscopy. Moreover, concentrations of cytokines and immune-associated proteins in biofilm suspensions and saliva were assessed by ELISA. Neutrophils obtained from blood were stimulated with twelve bacterial species isolated from cultured biofilms or with lipopolysaccharide to monitor NET formation. RESULTS: Neutrophils, NETs, neutrophil-associated proteins (myeloperoxidase, elastase-2, cathepsin G, cathelicidin LL-37), interleukin-8, interleukin-1ß and tumor necrosis factor were detected within plaque samples and saliva. All tested bacterial species as well as the polymicrobial samples isolated from the plaque of each donor induced release of NETs and interleukin-8. The degree of NET formation varied among different subjects and did not correlate with plaque scores or clinical signs of local inflammation. CONCLUSIONS: Our findings indicate that neutrophils are attracted towards dental biofilms, in which they become incorporated and where they are stimulated by microbes to release NETs and immunostimulatory proteins. Thus, neutrophils and NETs may be involved in host biofilm control, although their specific role needs to be further elucidated. Moreover, inter-patient variability suggests NET formation as a potential factor influencing the individual course of disease.
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Bactérias/imunologia , Fenômenos Fisiológicos Bacterianos , Biofilmes/crescimento & desenvolvimento , Armadilhas Extracelulares/metabolismo , Gengiva/imunologia , Gengiva/microbiologia , Adulto , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Adulto JovemRESUMO
Carriers of highly leukotoxic genotypes of Aggregatibacter actinomycetemcomitans are at high risk for rapid degradation of tooth-supporting tissues. The leukotoxin (LtxA) expressed by this bacterium induces a rapid pro-inflammatory response in leukocytes that results in cell death. The aim of the present study was to increase the understanding of LtxA-induced leukocyte activation mechanisms and of possible associated osteoclast differentiation. The effect of LtxA on activation of the inflammasome complex was studied in THP-1 wild type and in NLRP3- and ASC knockout cells. Cell-to-cell communication was assessed by fluorescent parachute assays, and THP-1 differentiation into osteoclast-like cells was investigated microscopically. The results showed that LtxA induced inflammatory cell death, which involved activation of the NLRP3 inflammasome and gap junction cell-to-cell communication. THP-1 cells treated with lipopolysaccharide (LPS) and LtxA together differentiated into an osteoclast-like phenotype. Here, LPS prevented LtxA-mediated cell death but failed to induce osteoclast differentiation on its own. However, pit formation was not significantly enhanced by LtxA. We conclude that A. actinomycetemcomitans leukotoxicity mediates activation of the NLRP3 inflammasome and cell-to-cell communication in the induced pro-inflammatory cell death. In addition, LtxA stimulated differentiation towards osteoclasts-like cells in LPS-treated THP-1 cells.
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BACKGROUND: Pathological root resorption affects permanent teeth and is usually triggered by infectious-inflammatory stimuli and/or dental trauma. Periodontitis and traumatic occlusion have been reported as possible causative factors of root resorptions, whilst the impact of systemic diseases is less well understood. This case highlights the need for consideration of multiple risk factors, especially when presenting in combination. METHODS AND RESULTS: A 62-year-old South Asian female presented with unstable Stage IV Grade C periodontitis, poor oral hygiene and multiple autoimmune conditions including oral lichen planus. Clinical and radiographic examination revealed multiple advanced apical and external root resorptions of the patient's molars associated with periapical bone loss, despite of a minimally restored dental status. CONCLUSION: A likely etiology of this patient's multiple root resorptions is the presence of unstable periodontitis with periodontal-endodontic lesions, exacerbated by a dysbalanced immune response to infectious agents. Appropriate monitoring and managing of such patients can prevent or limit the pathological process of inflammatory root resorption. KEY POINTS: Why is this case new information? This is the first report documenting advanced multiple external inflammatory root resorptions in a periodontitis patient with oral and systemic co-morbidities. What are the keys to successful management of this case? Early diagnosis, prevention and intervention to limit periodontal inflammation, endodontic infection and occlusal trauma. What are the primary limitations to success in this case? Late diagnosis of multiple root resorptions, palliative periodontal treatment due to poor oral hygiene compliance, and poorly controlled systemic inflammation favoring the persistence of a dysregulated immune response to the oral microbiota.
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Development of dysbiosis in complex multispecies bacterial biofilms forming on teeth, known as dental plaque, is one of the factors causing periodontitis. Fusobacterium nucleatum (F. nucleatum) is recognised as a key microorganism in subgingival dental plaque, and is linked to periodontitis as well as colorectal cancer and systemic diseases. Five subspecies of F. nucleatum have been identified: animalis, fusiforme, nucleatum, polymorphum, and vincentii. Differential integration of subspecies into multispecies biofilm models has been reported, however, biofilm forming ability of individual F. nucleatum subspecies is largely unknown. The aim of this study was to determine the single-subspecies biofilm forming abilities of F. nucleatum ATCC type strains. Static single subspecies F. nucleatum biofilms were grown anaerobically for 3 days on untreated or surface-modified (sandblasting, artificial saliva, fibronectin, gelatin, or poly-L-lysine coating) plastic and glass coverslips. Biofilm mass was quantified using crystal violet (CV) staining. Biofilm architecture and thickness were analysed by scanning electron microscopy and confocal laser scanning microscopy. Bioinformatic analysis was performed to identify orthologues of known adhesion proteins in F. nucleatum subspecies. Surface type and treatment significantly influenced single-subspecies biofilm formation. Biofilm formation was overall highest on poly-L-lysine coated surfaces and sandblasted glass surfaces. Biofilm thickness and stability, as well as architecture, varied amongst the subspecies. Interestingly, F. nucleatum ssp. polymorphum did not form a detectable, continuous layer of biofilm on any of the tested substrates. Consistent with limited biofilm forming ability in vitro, F. nucleatum ssp. polymorphum showed the least conservation of the adhesion proteins CmpA and Fap2 in silico. Here, we show that biofilm formation by F. nucleatum in vitro is subspecies- and substrate-specific. Additionally, F. nucleatum ssp. polymorphum does not appear to form stable single-subspecies continuous layers of biofilm in vitro. Understanding the differences in F. nucleatum single-subspecies biofilm formation may shed light on multi-species biofilm formation mechanisms and may reveal new virulence factors as novel therapeutic targets for prevention and treatment of F. nucleatum-mediated infections and diseases.
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OBJECTIVE: To investigate the association of dental and cardiac disease in a cohort of captive chimpanzees DESIGN: 12 captive chimpanzees underwent periodontal and cardiac examinations under anaesthesia during a relocation to a new enclosure. Blood samples were taken for analysis of circulating markers of cardiac health, nutritional status and isolation of neutrophils for functional assays. They were then observed for three years for signs of heart disease. RESULTS: Although the chimpanzees displayed large quantities of supragingival plaque, they had low bleeding scores. Peripheral blood neutrophils responded to innate and adaptive immune stimuli. In the follow up period two animals died and post mortem confirmed heart disease. Levels of NT-proBNP were found to be high in chimpanzees that died from heart disease. CONCLUSIONS: Whilst there appeared to be a correlation between probing depth and age, there appeared to be no correlation between dental data and heart data in this cohort.
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Neutrófilos , Pan troglodytes , Animais , Estudos de Coortes , HumanosRESUMO
Neutrophils are amongst the most abundant immune cells within the periodontal tissues and oral cavity. As innate immune cells, they are first line defenders at the tooth-mucosa interface, and can perform an array of different functions. With regard to these, it has been observed over many years that neutrophils are highly heterogeneous in their behavior. Therefore, it has been speculated that neutrophils, similarly to other leukocytes, exist in distinct subsets. Several studies have investigated different markers of neutrophils in oral health and disease in recent years in order to define potential cell subsets and their specific tasks. This research was inspired by recent advancements in other fields of medicine in this field. The aim of this review is to give an overview of the current evidence regarding the existence and presence of neutrophil subsets and their possible functions, specifically in the context of periodontitis, gingivitis, and periodontal health.
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Suscetibilidade a Doenças , Homeostase , Neutrófilos/imunologia , Neutrófilos/metabolismo , Periodontite/etiologia , Periodontite/metabolismo , Periodonto/imunologia , Periodonto/metabolismo , Animais , Plasticidade Celular , Humanos , Leucócitos/imunologia , Leucócitos/metabolismo , Leucócitos/patologia , Neutrófilos/patologia , Periodontite/patologiaRESUMO
Periodontitis and gingivitis remain two of the most common diseases that affect the oral cavity. As they are caused by plaque, effective oral hygiene, elimination of plaque-retentive factors and successful periodontal treatment will result in resolution of gingival and periodontal inflammation. Certain systemic diseases can have a clinical appearance similar to periodontal diseases or exacerbate existing periodontitis/gingivitis and vice versa. This paper aims to provide the dental practitioner with an understanding of the manifestations of systemic diseases to the periodontium and highlights elements in the clinical assessment, which will aid in establishing a correct diagnosis. Additional anamnestic and clinical clues are important for distinguishing between plaque-induced and non-plaque-induced lesions. The first part of this compendium covers immune-mediated and hereditary conditions as causes of gingival lesions, which can resemble those caused by dental plaque. The different conditions are presented concisely and exemplified by clinical photographs. Dental practitioners should be aware of the various manifestations of systemic diseases to the periodontium in order to offer appropriate diagnosis and treatment, which can reduce both patient morbidity and mortality.
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Placa Dentária , Gengivite , Doenças Periodontais , Periodontite , Humanos , InflamaçãoRESUMO
Periodontitis and gingivitis are highly prevalent inflammatory diseases of the oral cavity, and typically are characterised by the presence of dental plaque. However, other causes of oral inflammation exist, which can resemble plaque-induced gingivitis and periodontitis, and may thus first be seen by a dental practitioner. This paper aims to provide dentists with an understanding of the manifestations of systemic diseases to the periodontium and highlights anamnestic and clinical clues important for distinguishing between plaque-induced and non plaque-induced lesions. In the first part of this series immune-mediated and hereditary conditions as causes of gingival lesions were discussed; this second part highlights cancer-related gingival lesions as well as those caused by specific pathogens, medication or malnutrition. A clear clinical, epidemiological and visual overview of the different conditions is provided. Early diagnosis of non plaque-related causes of gingival lesions can be vital for affected patients. Therefore, dental practitioners should be aware of the various manifestations of systemic diseases to the periodontium.
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Gengivite , Neoplasias , Doenças Periodontais , Odontólogos , Humanos , InflamaçãoRESUMO
BACKGROUND: Orthodontic treatment can successfully align pathologically migrated teeth and lead to improvement of periodontal stability in patients with periodontitis. Periodontic-orthodontic approaches have gained increasing attention in the past years. Here, we investigated the interest of adults affected by chronic periodontitis in undergoing orthodontic treatment as well as patient-related and tooth-related influence factors. METHODS: Periodontal and orthodontic measurements/indices were taken from 115 adult patients with moderate-to-severe periodontitis. The study participants answered a questionnaire investigating patient demographics, quality of life aspects, and their interest in undergoing orthodontic treatment. Correlations between clinical data, questionnaire responses, and this interest were analyzed by means of an age- and sex-adjusted multiple regression model. RESULTS: Two-thirds of the participants were interested in orthodontic therapy and indicated long-term healthy and esthetically appealing teeth as their main motives. A significant correlation was found between subjectively felt impaired dental esthetics and an interest in orthodontic treatment. However, there were no correlations with the severity of periodontitis, tooth alignment, or patient demographics, including sex. Older patients were significantly more often interested in orthodontic treatment. Most participants had never been provided with information about orthodontic treatment options for adults. CONCLUSIONS: A considerable number of adult patients with periodontitis were interested in orthodontics to improve tooth alignment. However, severity of periodontitis and tooth misalignment or demographic factors may not be indicative thereof. Therefore, dental practitioners need to be aware of patients wishing to align their teeth and to provide them with the relevant information and, if appropriate, enable interdisciplinary treatment planning.
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Periodontite , Qualidade de Vida , Adulto , Estudos Transversais , Humanos , Projetos Piloto , Inquéritos e QuestionáriosRESUMO
Gingivitis and periodontitis are both highly prevalent gum diseases characterized by an accumulation of a polymicrobial biofilm (dental plaque) around teeth and inflammation in adjacent soft tissues. During dental procedures, even tooth brushing, these bacteria and their components, such as endotoxin, can easily disseminate into the systemic circulation through minor or major gingival injuries. Particularly in immuno-compromised subjects or patients with preexisting pathologic conditions, bacteremia may lead to bacterial infection of distant organs, which may cause immunological reactions. Oral bacteria and endotoxins have been found in sepsis, infective endocarditis, lung infection, liver disease and many other potentially lethal disorders. This article presents a review of the possible pathologic consequences of bacteremia originating in the oral cavity and points out the most commonly affected organs as well as preventive and treatment measures. At the present time, plaque control by subjects and/or dental professionals is one of the most effective means to prevent the onset and progression of oral bacteremia-induced systemic diseases.