The analysis of the disease-specific oral and systemic biomarkers in saliva and oral fluids (i.e., mouth rinse, gingival crevicular fluid (GCF), and peri-implantitis fluid (PISF)) is demanding. ...Several hosts and microbial factors may influence their expression, release, and levels. The type of saliva/oral fluids utilized for the diagnostics affects the analysis. High sensitivity and specificities together with sophisticated methods and techniques are essential for valuable outcome. We describe here recently developed practical, convenient, inexpensive, noninvasive, and quantitative mouth rinse and PISF/GCF/chair-side/point-of-care (PoC) lateral-flow aMMP-8 immunoassays (PerioSafe and ImplantSafe/ORALyser) to detect, predict, and monitor successfully the course, treatment, and prevention of periodontitis and peri-implantitis, respectively. The tests have been independently and successfully validated to differentiate periodontal and peri-implant health and disease in Finland, Germany, Netherland, Sweden, Turkey, Nigeria, Malawi, and USA. The clinical use of salivary/oral fluid biomarkers to identify oral and systemic conditions requires additional studies utilizing these noninvasive screening, diagnostic, and preventive aMMP-8 PoC/chair-side technologies.
Purpose
This study aims to validate label‐free quantitative proteomics (LFQ) against antibody‐based methods for quantifying established periodontal disease biomarkers in saliva.
Experimental Design
...In an experimental gingivitis model, healthy volunteers (n = 10) provide saliva at baseline (d0), during the induction (d7, d14, d21) and resolution (d35) of gingival inflammation (total n = 50). Biomarker levels are analyzed by LFQ and time‐resolved immunofluorometric assay (IFMA) or enzyme‐linked immunosorbent assay (ELISA). Molecular matrix metalloproteinase (MMP)‐8 forms are assessed by Western blot (WB) analysis.
Results
LFQ detects significantly (p < 0.05) elevated MMP‐8 (d21vsd7, d35vsd7) and tissue inhibitor of matrix metalloproteinases (TIMP)‐1 (d35vsd7). Latent MMP‐8 (70–80 kDa) is present (d0–d35), but not active MMP‐8 (50–60 kDa). LFQ and immunoassay data significantly correlate for MMP‐8 (r = 0.36), myeloperoxidase (r = 0.39), polymorphonuclear leukocyte elastase (r = 0.33), and TIMP‐1 (r = −0.24).
Conclusion and Clinical Relevance
LFQ can quantify enzyme levels in saliva, however lacks the ability to measure enzymatic activity. WB analysis reveals that MMP‐8 may not be activated during induction of gingival inflammation. Significant but weak correlations between IFMA or ELISA and LFQ suggest a limited capacity of available antibodies to reliably quantify salivary biomarkers for periodontal diseases. Novel “anti‐peptide” antibodies designed by newer targeted mass spectrometry‐based approaches can help to overcome these drawbacks.
Objective
The aim of this study was to investigate the utility of the active matrix metalloproteinase (aMMP‐8)‐point‐of‐care (PoC) test as a quantitative real‐time chair‐side diagnostic tool for ...peri‐implant diagnosis, as well as assess the potentially developing and ongoing risk relative to the traditional clinical methods.
Background
Current peri‐implant and periodontal disease diagnoses rely on clinical and radiological examinations. This case‐control study investigated the applicability of aMMP‐8‐PoC immunotest for quantitative real‐time diagnosis and monitoring of dental implants in health and disease.
Methods
Sixty‐eight patients visiting a specialist clinic for maintenance following dental implant placement underwent assessment of their peri‐implant health. aMMP‐8‐PoC peri‐implant sulcular fluid (PISF) lateral‐flow immunotests were performed using ImplantSafe® technology quantitated by ORALyzer®. In addition, the PISF samples were analyzed for total MMP‐8, calprotectin, and interleukin (IL)‐6 by enzyme‐linked immunosorbent assays (ELISA), aMMP‐8 by western immunoblot, and MMP‐2 and MMP‐9 by gelatin zymography.
Results
The aMMP‐8‐PoC test promptly recorded and reflected peri‐implant disease, differentiating it clearly from health. X‐ray findings (bone loss > 2 mm), peri‐implant pocket depth ≥ 3 mm, and bleeding on probing were significantly more prevalent among implants positive for the aMMP‐8‐PoC test. aMMP‐8/ORALyzer analysis was more precise in recording disease than total MMP‐8, calprotectin, IL‐6, MMP‐2, and MMP‐9.
Conclusions
The aMMP‐8‐PoC test can be conveniently implemented to alert for and detect active collagenolysis affecting peri‐implant tissues, both in the early and advanced stages of the disease. Active and fragmented MMP‐8 exhibits a strong and significant association with peri‐implantitis as compared to total MMP‐8 and other biomarkers and can be utilized as the POC/chairside biomarker of choice in the new classification of peri‐implantitis.
AbstractStudies on the reception and impact of ancient models in the emergence of Republican civic structures during the Renaissance have adopted, either of two competing models: continuity or ...reform. The purpose of this article is to engage in this debate by exploring how the ideals of ancient Roman Republicanism were adopted and utilized in the making of new civic spaces and in the formation of institutions in Renaissance Florence. The article examines four key aspects of this transformation: 1) the self-identification of the leaders of Florence with the ancient Romans in Florentine public monuments 2) the reconstruction of administrative spaces and the attempts at realizing the ideals of citizen participation in government; 3) the reformulation of the ideas of Republicanism and popular sovereignty in Florence during the corporatist-republican system exemplified by the guilds; and 4) the emerging ideas of an ideal city, such as those presented by the architect Leon Battista Alberti, and his reinterpretation of ancient Roman ideals. What the article illustrates is the complexity and strategic dynamism of relations that Florence had to not only its own past as a Roman city but to the ideal of ancient Rome and its Republics.
ObjectivesTo investigate the association between rheumatoid arthritis (RA) and periodontitis with special emphasis on the role of antirheumatic drugs in periodontal health.DesignProspective follow-up ...study. Patients with early untreated RA and chronic active RA were examined at baseline and 16 months later. Controls were examined once.Settings and participantsThe study was conducted in Finland from September 2005 to May 2014 at the Helsinki University Hospital. Overall, 124 participants were recruited for dental and medical examinations: 53 were patients with early disease-modifying antirheumatic drug (DMARD) naїve RA (ERA), 28 were patients with chronic RA (CRA) with insufficient response to conventional DMARDs. After baseline examination, patients with ERA started treatment with synthetic DMARDs and patients with CRA with biological DMARDs. Controls were 43 age-matched, gender-matched and community-matched participants.Outcome measuresDegree of periodontitis (defined according to the Center for Disease Control and Prevention and the American Academy of Periodontology). Prevalence of periodontal bacteria (analysed from plaque samples), clinical rheumatological status by Disease Activity Score, 28-joint count (DAS28), function by Health Assessment Questionnaire (HAQ) and treatment response by European League Against Rheumatism (EULAR) criteria.ResultsModerate periodontitis was present in 67.3% of patients with ERA, 64.3% of patients with CRA and 39.5% of control participants (p=0.001). Further, patients with RA had significantly more periodontal findings compared with controls, recorded with common periodontal indexes. In the re-examination, patients with RA still showed poor periodontal health in spite of treatment with DMARDs after baseline examination. The prevalence of Porphyromonas gingivalis was higher in patients with ERA with periodontal probing depth ≥4 mm compared with patients with CRA and controls. Antirheumatic medication did not seem to affect the results.ConclusionsModerate periodontitis was more frequent in patients with RA than in controls. Patients with ERA and CRA exhibited poorer periodontal health parameters when compared with controls. There was no association between antirheumatic treatment and periodontal parameters.
Human saliva is an easily accessible biological fluid and contains a variety of disease-related biomarkers, which makes it a potential diagnostic medium. The clinical use of salivary/oral fluid ...biomarkers to identify oral and systemic conditions requires the development of non-invasive screening and diagnostic technologies, and is among the main goals of oral fluid researchers. The analysis of the disease-specific oral and systemic biomarkers in saliva and oral fluids (i.e., mouth-rinse, gingival crevicular fluid (GCF) and peri-implantitis sulcular fluid (PISF)) is demanding. Several factors influence their expression and release; these factors include the intracellular location, the molecular size and the flow characteristics of the biological fluid. The type of saliva/oral fluid utilized for the diagnostics affects the analysis. High sensitivity together with sophisticated methods and techniques are essential to get a useful outcome. We describe here a recently developed mouth-rinse that is practical, convenient and inexpensive, as well as PISF chair-side/point of care (PoC) lateral-flow active matrix metalloproteinase (aMMP-8) immunoassays to detect, predict and monitor the course and treatment of periodontitis and peri-implantitis.
The purpose of this study was to investigate whether competition is an effective method to remind primary oral health care dentists to record diagnoses (RRD). The effectiveness of competition was ...examined in comparison with financial group bonuses (FGBs) and electronic reminders (ERs) of the electronic health record, together with superior-subordinate or development discussions. Putative differences in the diagnosis recording cultures of Finnish public health care physicians and dentists were studied. This was a retrospective quasi-experimental observational study in which the effects of the interventions on the rate of recording diagnoses were identified using a general linear regression model and proportions of visits with recorded diagnoses. The rate of increase in the recording of diagnoses in dentists was 0.995 ± 0.273%/month (mean ± SEM) after the implementation of RRDs and this did not differ from that obtained after starting FGBs (0.919 ± 0.130%/month) or ERs with superior-subordinate or development discussions (1.562 ± 0.277%/month) in physicians. As the rates of increase did not differ none of the applied methods seemed to be more effective than the others when trying to influence the behaviour of primary health care clinicians. Altogether, public primary health care physicians were more active than respective primary oral health care dentists to record diagnoses.
This study, conducted in a Finnish city, examined whether decreasing emergency department (ED) services in an overcrowded primary care ED and corresponding direction to office-hour primary care would ...guide patients to office-hour visits to general practitioners (GP). This was an observational retrospective study based on a before-and-after design carried out by gradually decreasing ED services in primary care. The interventions were (a) application of ABCDE-triage combined with public guidance on the proper use of EDs, (b) cessation of a minor supplementary ED, and finally (c) application of “reverse triage” with enhanced direction of the public to office-hour services from the remaining ED. The numbers of visits to office-hour primary care GPs in a month were recorded before applying the interventions fully (preintervention period) and in the postintervention period. The putative effect of the interventions on the development rate of mortality in different age groups was also studied as a measure of safety. The total number of monthly visits to office-hour GPs decreased slowly over the whole study period without difference in this rate between pre- and postintervention periods. The numbers of office-hour GP visits per 1000 inhabitants decreased similarly. The rate of monthly visits to office-hour GP/per GP did not change in the preintervention period but decreased in the postintervention period. There was no increase in the mortality in any of the studied age groups (0-19, 20-64, 65+ years) after application of the ED interventions. There is no guarantee that decreasing activity in a primary care ED and consecutive enhanced redirecting of patients to the office-hour primary care systems would shift patients to office-hour GPs. On the other hand, this decrease in the ED activity does not seem to increase mortality either.
This cross-sectional study compares the effectiveness of an active MMP-8 (aMMP-8) point-of-care (PoC)/chairside mouthrinse test to the conventional bleeding on probing (BOP) (cutoff 20%) test in ...detecting subclinical periodontitis/pre-periodontitis in Finnish adolescents. The study was carried out at the Kotka Health Center, Finland. A total of 47 adolescents (30 boys/17 girls) aged 15⁻17 were first tested with the aMMP-8 PoC test, followed by a full-mouth evaluation of clinical parameters of oral health including periodontal, oral mucosal, and caries assessment. A periodontist performed these clinical examinations. The aMMP-8 PoC test result had much stronger association with subclinical periodontitis than the BOP 20% test (2.8⁻5.3 times stronger in terms of odds ratio). The aMMP-8 PoC test had ≥2 times higher sensitivity than the BOP 20% test with, generally, the same specificity. Further, the aMMP-8 PoC test had generally better accuracy and lower false negative percentages. The aMMP-8 PoC test seemed to be more effective than the conventional BOP test in detecting subclinical periodontitis/pre-periodontitis in adolescents reducing the risk of their undertreatment. However, the sample size may be a limiting factor, and more studies are needed to confirm our results for both adolescents and adults.
This communication article addresses currently available rapid non-invasive methods to screen and detect periodontitis and dental peri-implantitis. In this regard, oral fluid biomarkers have been ...researched extensively but self-reported oral health (SROH)-questionnaires have also been developed. Both alternatives may offer a quick and easy way to screen and detect diseased patients. Active matrix metalloproteinase (aMMP-8) is one of the most validated biomarkers for screening and detecting periodontal breakdown related to periodontitis and peri-implantitis and monitoring their treatment effects revealing successful, less- and non-successful treatment results. Currently available aMMP-8 lateral-flow technologies allow this kind of analysis, as demonstrated here, to be conducted quantitatively online and real-time as point-of-care/chairside testing in dental and even medical care settings. In this study, an aMMP-8 peri-implant sulcular fluid point-of-care-test diagnosed peri-implantitis and healthy implants far more accurately than bleeding-on-probing or the other biomarkers, such as polymorphonuclear (PMN)/neutrophil elastase, myeloperoxidase and MMP-9. Although, SROH-questionnaires allow screening in similar settings but they lack the information about the current disease activity of periodontitis and peri-implantitis, which is of essential value in periodontal diagnostics and treatment monitoring. Thus, both methods can be considered as adjunct methods for periodontitis and peri-implant diagnostics, but the value of oral fluid biomarkers analysis does not seem to be substitutable.
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