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Toddlerhood is a period of intensive and rapid socio-emotional development. The effects of different types of childcare settings on child development have been widely studied, but the results have often been contradictory. The aim of this study was to compare social competence and socio-emotional problems in two-year-old children (n = 1104; girls 47.2%) who were either participating in out-of-home, center-based childcare or were cared for at home by their parents in Finland. The results showed that mothers reported more internalizing symptoms in toddlers participating in out-of-home, center-based childcare when compared to children who were cared for at home. No differences regarding externalizing symptoms or social competence were found. Overall, the results suggest that out-of-home, center-based childcare is not associated with major differences in a toddler's socio-emotional development. More research is needed to investigate whether differences in the socio-emotional development of the children participating in different types of childcare develop later in childhood.

Abstract In children with poor oral hygiene, dental caries are the most common factor that causes periapical pathologies as a result of irreversible pulpal injuries and leads to the cessation of root development in immature permanent molar teeth. Objective The primary goal is to evaluate the effects of two different intracanal medicaments, calcium hydroxide [Ca(OH)2] and double antibiotic paste (DAP), on radiographic outcomes during regenerative endodontic procedures (REP) of immature permanent mandibular first molars with symptomatic irreversible pulpitis and symptomatic apical periodontitis (SIP/SAP). Additionally, the secondary goal was to evaluate MMP-8 levels during REP using two different intracanal medicaments. Methodology The study included 20 patients with immature mandibular first molars exhibiting SIP/SAP. Participants were randomly assigned into two groups based on the applied intracanal medicament. Ca(OH)2 (n=10) was prepared by mixing it with sterile distilled water, while the same amount of powdered metronidazole and ciprofloxacin were mixed and combined with sterile distilled water for DAP (n=10). MMP-8 in periapical samples were measured at baseline and on the 14th day using immunofluorometric assay. Image-J software with TurboReg plug-in was utilized to determine changes in root length, root width, radiographic root area (RRA) during the 12-month follow-up period. Data were analyzed by SPSS 25.0 (p0.05). Root length significantly increased in both groups (p=0.001), with Ca(OH)2 showing a greater increase (p=0.046). Root width and RRA increased similarly in both groups at 12th month. Conclusion Both Ca(OH)2 and DAP applications resulted in a significant increase in periapical MMP-8 levels. Increase in radiographic root width and root area was similar between two groups, but Ca(OH)2 led to a significantly greater increase in root length. Further studies with larger sample sizes are necessary to validate our findings during REP of vital immature permanent mandibular molars. Clinical Trials database: NCT05581706

BackgroundMatrix-degrading proteinases and their regulators, such as matrix metalloproteinase 8 (MMP-8) and tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), may contribute to various pathological events. Elevated MMP-8 concentrations have been associated with e.g., cardiovascular diseases and periodontitis. However, there is little knowledge on the physiological concentrations of these molecules in serum, or the effect of demographic or lifestyle factors on their levels.Design and methodsWe investigated the effect of various demographic characteristics and behavioral habits, such as aging, sex, smoking, and BMI, on serum concentrations of MMP-8 and TIMP-1. We used the FINRISK97 cohort (n = 8,446), which has comprehensive information on demographic and lifestyle factors, clinical data, laboratory measurements, and register data available. Further, we investigated the concentrations of MMP-8, TIMP-1, and the MMP-8/TIMP-1 ratio in different age groups of healthy and diseased participants. A t-test was used to compare log-transformed mean levels in different groups and linear regression was used to evaluate the association between MMP-8 and TIMP-1 and selected diseases and background variables.ResultsMMP-8 levels decreased with increasing age in the whole population and for women, while TIMP-1 concentration increased slightly with age for the whole population and both genders separately (p for linear trend

Abstract Objectives The aim of this study is to examine correlations between different oral rinse matrix metalloproteinase (MMP)‐8 protein species in western blot (WB) analysis, quantitative MMP‐8 measurements, and patient‐related factors. Elevated activated MMP‐8 (aMMP‐8) associate with periodontitis and a diagnostic point‐of‐care technology has been developed based on aMMP‐8. In WB, different MMP‐8 protein species can be analyzed. Relative abundancy of fragmented 20–25 kDa forms in WB has been associated with and reflects MMP‐8 activation and related fragmentation and elevated quantitative aMMP‐8 measurements. Material and Methods A random sample of 192 participants from a periodontal disease screening study was used for this study. Oral rinse samples for biomarker analyses were collected before clinical periodontal examinations. aMMP‐8 immunofluorometric (IFMA) and WB analysis (utilizing the same monoclonal antibody, 8708), polymorphonuclear leukocyte (PMN) elastase activity test and tissue inhibitor of metalloproteinases (TIMP)‐1 ELISA levels were performed from the oral rinse samples. Distinct MMP‐8 protein species were differentiated in the WB analysis. Principal component (PC) analysis was conducted to explore correlation patterns between the different species. Adjusted correlation analysis between the extracted PCs of WB and aMMP‐8 IFMA levels and multilevel regression analysis were conducted to explore if the other periodontal disease‐related biomarkers and clinical surrogate measures and patient‐related factors are co‐variating with the extracted components. Results Distinct correlation patterns between the MMP‐8 protein species were observed. The first four PCs explained 89% of the whole variance in PC analysis. Statistically significant correlation (p

This review is focused on the effects of lingonberry (Vaccinium vitis-idaea L.) fruit phenolic compounds in human in vitro cells and in vivo clinical studies. Studies with lingonberries, lingonberry juice/lingonberry nectar/fermented lingonberry juice, and phenolic fractions with active molecules are reviewed. Lingonberry’s bioactive substances have a diverse range of antimicrobial, anti-inflammatory, antiproteolytic, anticancer, and antioxidant properties. Fermentation of lingonberries and modulation of the dysbiotic microbiome to a more symbiotic composition by favoring the growth of lactobacilli and inhibiting the growth of human opportunistic pathogens are discussed. Research results suggest that more studies on humans are needed.

Candida glabrata is an opportunistic pathogen that may cause serious infections in an immunocompromised host. C. glabrata cell wall proteases directly interact with host cells and affect yeast virulence and host immune responses. This protocol describes methods to purify β-1,3-glucan-bonded cell wall proteases from C. glabrata. These cell wall proteases are detached from the cell wall glucan network by lyticase treatment, which hydrolyzes β-1,3-glucan bonds specifically without rupturing cells. The cell wall supernatant is further fractioned by centrifugal devices with cut-offs of 10 and 50 kDa, ion-exchange filtration(charge), and gel filtration (size exclusion). The enzymatic activity of C. glabrata proteases is verified with MDPF-gelatin zymography and the degradation of gelatin is visualized by loss of gelatin fluorescence. With this procedure, the enzymatic activities of the fractions are kept intact, differing from methods used in previous studies with trypsin digestion of the yeast cell wall. The protein bands may be eventually located from a parallel silver-stained gel and identified with LC–MS/MS spectrometry. The advantage of this methodology is that it allows further host protein degradation assays; the protocol is also suitable for studying other Candida yeast species.Key features• Uses basic materials and laboratory equipment, enabling low-cost studies.• Facilitates the selection and identification of proteases with certain molecular weights.• Enables further functional studies with host proteins, such as structural or immune response–related, or enzymes and candidate protease inhibitors(e.g., from natural substances).• This protocol has been optimized for C. glabrata but may be applied with modifications to other Candida species.Graphical overview

Abstract Objectives We aimed to study the effects of fermented lingonberry juice (FLJ) as a mouthwash on the levels of active matrix metalloproteinase‐8 (aMMP‐8) in peri‐implant sulcular fluid (PISF), bleeding on probing (BOP), and visible plaque index (VPI). We hypothesized that FLJ rinsing could reduce inflammation (aMMP‐8 and BOP) and microbial load (VPI) in the oral cavity, especially around dental implants. Materials and Methods A clinical pilot study was performed using FLJ as a mouthwash. The inclusion criteria were at least one dental implant in the anterior or posterior areas with a screw‐retained crown. Ten participants used 10 ml of mouthwash twice a day for 15 days, and 10 participants served as the control group. Point‐of‐care tests (POCTs) were used to measure aMMP‐8 levels in the PISF, and BOP and VPI were recorded at the beginning of the trial and after 15 and 30 days. Results The FLJ mouthwash had a reductive effect on aMMP‐8, VPI, and BOP in the mouthwash group; however, there was no significant difference compared to the control group. The difference in VPI and BOP levels between the groups diminished after the lingonberry regimen ended. The decrease in aMMP‐8 levels appeared to continue even after discontinuation of the mouthwash regimen. Conclusion The reduction in the amount of plaque, aMMP‐8, and BOP by FLJ was promising and continuous considering the relatively short study period and sample size. FLJ is a natural and safe supplement for oral and dental implant home care. Further studies are required to verify these promising results.

Abstract Objectives Periodontitis is a multifactorial biofilm‐induced inflammatory disease; however, clinical and radiographic information reflects events that have already occurred. aMMP‐8 lateral‐flow chairside or point‐of‐care‐test (POC‐test) results have also come to complement the overall status of the patient's current situation. The current study aimed to clarify the usefulness of aMMP‐8 chairside‐test (aMMP‐8 POCT) results to alert the initial or early periodontitis in adolescents, a potential periodontitis risk group with cut off 20 ng/ml in Stage I periodontitis, according to the current periodontitis classification system. Material and Methods A total of 117 adolescents were aMMP‐8 POC tested for aMMP‐8 levels and examined for the full mouth and were interviewed for questions concerning health behavior. Results Of all 117 participants, N = 38 (32.5%) was aMMP‐8 POCT positive, and N = 34 (29.1%) had at least one 4 mm periodontal deepened pocket; however, only N = 16 (13.7%) had both characteristics. The subclinical stage (N = 47) could not be classified either as gingivitis or Stage I. Of the participants, who did not have any deepened periodontal pockets, 18 tested negative. Conclusions Stage I is preceded by antecedent stages that should be tackled by oral healthcare prevention and personalized treatment modalities by professionals. Elevated (>20 ng/ml), positive aMMP‐8 POCT results can be regarded as initial alarmer such as emerging risk. This should be utilized in the preventive personalized interventions by oral health professionals.

The effect of head and neck cancer (HNC) radiotherapy (RT) on biomarkers is not known but there is a lot of potential for gaining more precise cancer treatments and less side effects. This cohort study investigated the levels and molecular forms of the matrix metalloproteinase (MMP) -8 and -9, tissue inhibitor of metalloproteinase (TIMP)-1, myeloperoxidase (MPO) and interleukin (IL)-6 in mouth-rinse samples as well as the clinical periodontal status in HNC patients (n = 21) receiving RT. Complete periodontal examinations were performed pre-RT and one month after RT. Mouth-rinse samples (pre-RT, after six weeks of RT and one month after RT) were assayed using a point-of-care-kit (PerioSafe®/ORALyzer® (Dentognostics GmbH, Jena, Germany)) for active MMP-8 and ELISA analysis for total MMP-8 and -9, MPO, TIMP-1, and IL-6 levels. Molecular forms of MMP-9 were assessed by gelatinolytic zymography and MMP-8 by western immunoblot. Significant changes were observed between the three time points in the mean levels of active and total MMP-8, active MMP-9, and IL-6. Their levels increased during the RT and decreased after the RT period. The aMMP-8 levels stayed elevated even one month after RT compared to the pre-RT. Clinical attachment loss, probing depths, and bleeding on probing were increased between pre- and post-calculations in periodontal status. Elevated inflammatory biomarker levels together with clinical recordings strongly suggest that RT eventually increases the risk to the periodontal tissue destruction by inducing the active proteolytical MMP-cascade, and especially by prolonged activity of collagenolytic aMMP-8. Eventually, the aMMP-8 point-of-care mouth-rinse test could be an easy, early detection tool for estimating the risk for periodontal damage by the destructive MMP-cascade in HNC patients with RT treatment.

Until now, in clinical dentistry, antibacterial photodynamic therapy (aPDT) has been restricted to in-office treatments, which hampers repeated applications. This pilot study tested the benefit of a commercially available Lumoral® device designed for regular periodontal dual-light aPDT treatment at home. Seven patients with peri-implant disease applied dual-light aPDT daily in addition to their normal dental hygiene for four weeks. A single Lumoral® treatment includes an indocyanine green mouth rinse followed by 40 J/cm2 radiant exposure to a combination of 810 nm and 405 nm light. A point-of-care analysis of active-matrix metalloproteinase (aMMP-8), visible plaque index (VPI), bleeding on probing (BOP), and peri-implant pocket depth (PPD) measurements was performed on day 0, day 15, and day 30. Reductions in aMMP-8 (p = 0.047), VPI (p = 0.03), and BOP (p = 0.03) were observed, and PPD was measured as being 1 mm lower in the implant (p = ns). These results suggest a benefit of regular application of dual-light aPDT in peri-implantitis. Frequently repeated application can be a promising approach to diminishing the microbial burden and to lowering the tissue destructive proteolytic and inflammatory load around dental implants. Further studies in larger populations are warranted to show the long-term benefits.

Radiotherapy for head and neck carcinoma (HNC) has both curative and palliative purposes. This study investigated mouthrinse aMMP-8 levels, molecular forms of MMP-8, blood neutrophil counts and neurophil/lymphocyte ratios before and 3 weeks after HNC radiotherapy started. Thirteen HNC patients undergoing radiotherapy were included. Mouthrinse samples (before and 3 weeks after HNC radiotherapy had started) were assayed quantitatively by aMMP-8 point-of-care-kit (PerioSafe®/ORALyzer®) and by western immunoblot. Total neutrophil counts and neutrophil/lymphocyte ratios were evaluated in the hemogram results. Three weeks after HNC radiotherapy started, significant increases in aMMP-8 levels and neutrophil/lymphocyte ratios were observed. No significant difference was found in total neutrophil counts. Elevations of the activated and fragmented MMP-8 levels after HNC radiotherapy application were observed on western immunoblot analysis. The increase in the aMMP-8 levels and neutrophil/lymphocyte ratios indicate inflammation both locally and systemically suggesting increased risk for periodontitis due to the HNC radiotherapy.

Abstract Objectives This case control study examined the associations of HLA antigens and periodontitis with the salivary level of active MMP‐8 (aMMP‐8). Materials and Methods A total of 202 subjects, registered as Swiss bone marrow donors, participated in the study. HLA‐A, ‐B, and ‐C types were determined by serology or PCR. Saliva samples were collected from subjects, followed by a periodontal examination. The salivary level of aMMP‐8 was determined with immunofluorometric assay. Results The mean salivary level of aMMP‐8 was directly comparable to the grade of periodontitis and increased from healthy to mild/moderate to severe (125.0 ± 132.1, 200.6 ± 170.2, 290.1 ± 202.3 ng/ml; p

Parental mentalization refers to a parents’ capacity and interest to consider the individual experience and mental state underlying the behaviors of the child. Higher mentalization is considered a key aspect for parental sensitivity in interaction, fostering child’s socioemotional and self-regulatory development. Yet, previous studies have not examined the dynamic pathways through which the maternal mentalization may develop, nor their effects on child development. Thus, in the current person-oriented study, first, we identify distinct profiles and longitudinal trajectories of maternal mentalization from pregnancy to child’s 2 years of age. Second, we test how the profiles and trajectories associate with children’s internalizing and externalizing problems, social–emotional competence and effortful control at the age of 2 years. Third, we examine how the profiles and trajectories associate with contextual demographic and child related. The substudy was part of the FinnBrain Birth Cohort and included families from general population (n = 2,687). Mothers reported their parental reflective functioning (PRF) at late pregnancy, 6 months and 2 years of child’s age. Both mothers (n = 1,437) and fathers (n = 715) reported the developmental child outcomes at the child’s age of 2 years. Latent Profile Analysis and Latent Transition Analysis were used to identify PRF profiles and trajectories. The results showed decreasing heterogeneity in PRF from pregnancy to child’s age of 6 months and 2 years (i.e., four, three and two latent classes, respectively). Most mothers progressed towards high PRF over time. Second, the profiles and trajectories depicting high PRF associated with child high social–emotional competence at the age of 2 years, yet no clear positive effects were found on child’s problems and effortful control. The group of mixed PRF trajectories showed strongest association with child’s internalizing and externalizing problems. Finally, there were theoretically meaningful associations between the PRF trajectories and both the contextual (e.g., parity) and child related (e.g., infant temperament) factors. This was the first study to explore the early unfolding of maternal mentalization. The results are discussed in relation with the potential mechanisms accounting for child development and with the nature and limitations of self-reported parental mentalization.

This retrospective study addressed the role of oral potentially malignant disorders and the presence of intraepithelial Candida hyphae in the carcinogenesis of the oral tongue squamous cell carcinoma and its association with smoking, alcohol consumption, and oral inflammatory burden. The medical records of 183 subjects diagnosed with oral tongue squamous cell carcinoma at the Helsinki University Hospital were investigated. Preceding oral lichen planus, lichenoid reaction, and leukoplakia diagnosis were recorded. Further, the data on Candida hyphae in histological samples as an indicator of oral candidiasis, oral inflammatory burden, smoking, and alcohol consumption were recorded and analyzed. The histopathological diagnosis of oral lichen planus/lichenoid reaction (p < 0.001) and the presence of Candida hyphae (p = 0.005) were associated significantly with female gender. Oral lichen planus/lichenoid reaction patients were less often smokers than patients without these lesions. Candida hyphae were more often recorded in patients without alcohol use (p = 0.012). Oral lichen planus/lichenoid reaction and Candida hyphae in histological samples were associated with female gender and lower levels of typical risk factors, such as alcohol use and smoking, in oral tongue squamous cell carcinoma patients. Therefore, these patients should be well monitored despite a potential lack of the classical risk factors of oral carcinoma.

Background: The link between diabetes and periodontitis is bi-directional: high glucose levels increase the risk of periodontitis and elevated oral fluid aMMP-8 as well as diabetic development while untreated periodontitis worsens glycaemic control. Methods: Type-2 patients (N = 161) underwent an aMMP-8 Point-of-Care Test (POCT) at diabetes clinics. If the test was positive, the patient was sent to an oral health care clinic and oral health examination, health-promoting as well as necessary treatment procedures were carried out. Only 41 patients underwent full clinical evaluations. At the end of the treatment, an aMMP-8 POCT (B) was performed and if the test was positive, the treatment was continued and a new test (C) was performed, aiming for test negativity. The glycated haemoglobin (GHbA1c) test was performed approximately 6 months from the original appointment. Results: GHbA1c concentrations did not decrease during the follow-up. The concentrations of aMMP-8 assessed by POCT, and clinical parameters decreased. Changes in GHbA1c and aMMP-8 levels assessed by POCT during the treatment correlated positively with each other (p < 0.01). Conclusion: aMMP-8 POCT proved its reliability, and that its use is beneficial in the diabetes clinic, it enables identifying patients with periodontal findings reliably and guides them directly to an oral health clinic.

Abstract Objective The aim of the study was to propose an efficient chairside clinical strategy for the identification of undiagnosed hyperglycaemia in periodontal clinics. Material and methods Α chairside system was used for assessment of glycated hemoglobin 1c (HbA1c) and active Matrix Metalloproteinase‐8 levels (aMMP‐8) were analyzed by immunotest in patients (n = 150) who fulfilled the criteria for screening of the Centers for Disease Control and Prevention. Full‐mouth periodontal parameters were assessed and various data such as Body Mass Index (BMI), smoking and education were recorded. Results Thirty‐one patients out of 150 tested were found with unknown hyperglycaemia (20.7%). Regarding sex, education, parent with diabetes, normal BMI, smoking, age ≥45 years and prior testing for diabetes, no differences were observed between subjects displaying HbA1c .05). Subgroups differed regarding BMI (kg/m2), tooth count, percentages of 4 and 5 mm pockets (Mann–Whitney and z‐test, p

The manuscript uses the previously published literature and highlights the benefits of active-matrix metalloproteinase (aMMP)-8 chairside/point-of-care (PoC) diagnostic tools as adjunctive measures in oral and systemic diseases. Previous studies suggest that as a biomarker, aMMP-8 is more precise than total MMP-8, MMP-9, MMP-2, MMP-3, MMP-13, MMP-7, MMP-1, calprotectin, myeloperoxidase (MPO), human neutrophil elastase (HNE), tissue inhibitor of matrix metalloproteinase (TIMP)-1, and bleeding of probing (BOP). Therefore, aMMP-8 could be implemented as the needed key biomarker for the new disease classification for both periodontitis and peri-implantitis. With a sensitivity to the tune of 75–85% and specificity in the range of 80–90%, lateral flow aMMP-8 PoC testing is comparable to catalytic protease activity assays for aMMP-8. The test can be further applied to estimate the glycemic status of an individual, to ascertain whether a person is at risk for COVID-19, in managing the oral side effects of radiotherapy carried in head and neck cancers, and in selected cases pertaining to reproductive health. In the future, aMMP-8 could find application as a potential systemic biomarker in diseases affecting the cardiovascular system, cancers, bacteremia, sepsis, diabetes, obesity, meningitis, as well as pancreatitis. The aMMP-8 PoCT is the first practical test in the emerging new dental clinical field, that is, oral clinical chemistry representing oral medicine, clinical chemistry, peri-implantology, and periodontology.

Background: Previous studies have revealed the potential diagnostic utility of aMMP-8, an active form of MMP-8, in periodontal and peri-implant diseases. While non-invasive point-of-care (PoC) chairside aMMP-8 tests have shown promise in this regard, there is a dearth of literature on the evaluation of treatment response using these tests. The present study aimed to investigate treatment-related changes in aMMP-8 levels in individuals with Stage III/IV—Grade C periodontitis compared to a healthy control group, using a quantitative chairside PoC aMMP-8 test, and to determine its correlation with clinical parameters. Methods: The study included 27 adult patients (13 smoker, 14 non-smoker) with stage III/IV-grade C periodontitis and 25 healthy adult subjects. Clinical periodontal measurements, real-time PoC aMMP-8, IFMA aMMP-8, and Western immunoblot analyses were performed before and 1 month after anti-infective scaling and root planing periodontal treatment. Time 0 measurements were taken from the healthy control group to test the consistency of the diagnostic test. Results: Both PoC aMMP-8 and IFMA aMMP-8 tests showed a statistically significant decrease in aMMP-8 levels and improvement in periodontal clinical parameters following treatment (p < 0.05). The PoC aMMP-8 test had high diagnostic sensitivity (85.2%) and specificity (100.0%) for periodontitis and was not affected by smoking (p > 0.05). Treatment also reduced MMP-8 immunoreactivity and activation as demonstrated by Western immunoblot analysis. Conclusion: The PoC aMMP-8 test shows promise as a useful tool for the real-time diagnosis and monitoring of periodontal therapy.

A single-site, randomized clinical trial was designed to determine the efficacy of regular home use of Lumoral® dual-light antibacterial aPDT in periodontitis patients. For the study, 200 patients were randomized to receive non-surgical periodontal treatment (NSPT), including standardized hygiene instructions and electric toothbrush, scaling and root planing, or NSPT with adjunctive Lumoral® treatment. A complete clinical intraoral examination was conducted in the beginning, at three months, and at six months. This report presents the three-month results of the first 59 consecutive randomized subjects. At three months, bleeding on probing (BOP) was lower in the NSPT + Lumoral®-group than in the NSPT group (p = 0.045), and more patients in the NSPT + Lumoral®-group had their BOP below 10% (54% vs. 22%, respectively, p = 0.008). In addition, patients in the NSPT + Lumoral®-group improved their oral hygiene by visible-plaque-index (p = 0.0003), while the NSPT group showed no statistical improvement compared to the baseline. Both groups significantly reduced the number of deep periodontal pockets, but more patients with a reduction in their deep pocket number were found in the NSPT + Lumoral® group (92% vs. 63%, p = 0.02). Patients whose number of deep pockets was reduced by 50% or more were also more frequent in the NSPT + Lumoral®-group (71% vs. 33%, p = 0.01). Patients with initially less than ten deep pockets had fewer deep pockets at the three-month follow-up in the Lumoral® group (p = 0.01). In conclusion, adjunctive use of Lumoral® in NSPT results in improved treatment outcomes at three months post-therapy.

BackgroundMatrix metalloproteinase-8 (MMP-8) and tissue inhibitor of metalloproteinases-1 (TIMP-1) have been shown to predict prognosis in sepsis. However, MMP-8 and TIMP-1 in Staphylococcus aureus bacteremia (SAB) lacks evaluation and their role in the pathogenesis of SAB is unclear.MethodsMMP-8 and TIMP-1 and MMP-8/TIMP-1 molar ratio were determined at days 3, 5 and 28 from positive blood cultures in patients with methicillin-sensitive SAB and the connection to disease severity and early mortality was determined.ResultsAltogether 395 SAB patients were included. Patients with severe sepsis or infection focus presented higher MMP-8 levels at day 3 and 5 (pConclusionMMP-8 and MMP-8/TIMP-1 ratio were high 3-5 days after MS-SAB diagnosis in patients with an infection focus, severe sepsis or mortality within 14 days suggesting that matrix metalloproteinase activation might play a role in severe SAB.

A one-year prospective human intervention study was performed to examine the effects of fermented lingonberry juice (FLJ), used as a mouthwash for six months, on salivary parameters. A total of 25 adult participants used 10 mL of FLJ as mouthwash 30 s daily for 6 months in addition to their normal oral homecare routines. Standard oral examinations and gathering of samples were performed at the beginning of the study and after six months and one year. Resting and stimulated saliva secretion rates, resting saliva pH, and stimulated saliva buffering capacity were determined. A questionnaire of participants’ subjective sensations of mouth dryness was also recorded at each timepoint. Fermented lingonberry juice mouthwash had positive effect to all five salivary parameters and were, according to the omnibus test, statistically significant during the study period. Analysis of the subjective dry mouth sensation questionnaires revealed that symptoms of xerostomia decreased due to the use of FLJ. This study revealed that the once-a-day use of FLJ mouthwash had a beneficial, increasing effect on salivary flow rates, buffering capacity, and salivary pH. FLJ thus can be safely used as an adjunctive and beneficial therapy in oral homecare, protecting teeth and oral mucosa, including periodontium, and also relieving dry mouth symptoms.

Introduction: Even adolescents have early signs of periodontitis, an infectious inflammatory disease. Young patients at risk must be identified for the preventive interventions and treatment at enough early. Aim: To find out whether participants at risk for subclinical periodontitis could be identified using an active Matrix Metalloproteinase-8 (aMMP-8) chairside mouth rinse test, and to study if health behaviour and oral health are linked to the test result in Finnish adolescents. Materials and Methods: This study was carried out at the Hämeenlinna Health Center in South Finland in 2017-2018. Altogether 125 participants gave their consent to the study. Adolescents (14-15-year-old) were randomly divided into the control group (n=55) and the test group (n=70). All participants of oral health was examined, and they filled a questionnaire. The aMMP-8 chairside mouth rinse test was performed for the test group. Test positives were followed four monthly for a year. Data analysis was performed by IBM SPSS Statistics Version 25 by different statistical tests, including the Mann Whitney U test, the Friedman’s test, the Dunn-Bonferroni test and the Wilcoxon test. Results: Visible Plaque Index Percentage (VPI%) was significantly higher in test positives (p=0.005). Bleeding On Probing Percentage (BOP%) reached almost statistically significant difference (p=0.052). Periodontal treatment intervention decreased aMMP-8 levels assessed by a change in the test stick result from positive (+) to negative (-) during follow-up time. Conclusion: The aMMP-8 chairside mouth rinse test identified and alarmed adolescents with poor oral hygiene at risk for subclinical periodontitis without detectable and visible manifestations of the illness, such as deepened periodontal pockets. The aMMP-8 test is fast, inexpensive, predictive, easy to use and follow the effectiveness of intervention of subclinical periodontitis.

Abstract Background Almost all of the extracellular matrix (ECM) components can be degraded by the endoproteinases matrix metalloproteinases (MMPs). Important regulators of MMPs, and thereby of the extracellular environment, are tissue inhibitors of metalloproteinases (TIMPs), and especially TIMP-1. Early tumor development, as well as distant metastasis, may be results of an MMP/TIMP ratio imbalance altering the ECM. MMPs are elevated in several inflammatory conditions. Our aim is to investigate the prognostic role of MMP-8, − 9, and TIMP-1 in colorectal cancer (CRC) and their relationship to inflammation. Methods We included 337 colorectal cancer patients and 47 controls undergoing surgery at Helsinki University Hospital in Finland, 1998–2011. Serum levels of MMP-8 and plasma levels of C-reactive protein (CRP) were determined with a time-resolved immunofluorometric assay (IFMA), and MMP-9 and TIMP-1 with commercial enzyme-linked immunosorbent assay (ELISA) kits. Association and correlation analyses were performed with the Mann-Whitney U, Kruskal-Wallis, and Spearman rank correlation tests. Survival curves were constructed according to the Kaplan-Meier method and compared with the log-rank test. Results Among patients with advanced disease, serum levels of MMP-8 and TIMP-1 were elevated. CRC patients with high MMP-8 (HR (hazard ratio) 1.72, 95% confidence interval (CI) 1.17–2.52, P = 0.005) and those with high TIMP-1 (HR 1.80, 95% CI 1.23–2.64, P = 0.002) had worse prognoses. MMP-9 level failed to serve as a prognostic factor. In multivariable survival analysis, Dukes stage, and low MMP-9/TIMP-1 molar ratio (HR 0.46, 95% CI 0.33–0.98, P = 0.042) were independently predicted prognosis. A weak correlation between CRP and MMP-8 (rS = 0.229, P

Periodontitis is a host-mediated bacterial disease that affects the tooth attachment apparatus. Metalloproteinase-8 (MMP-8), a validated biomarker, could aid in clinical diagnosis. This study aimed to evaluate the diagnostic performance of active (a) MMP-8 immunotest versus total (t) MMP-8 ELISA for quantitative real-time diagnosis and assessment of periodontitis severity at the site level. Gingival crevicular fluid (GCF) was sampled from 30 healthy, 42 mild, and 59 severe periodontitis sites from thirty-one volunteers. MMP-8 concentrations were determined by time-resolved immunofluorometric assay (IFMA) and enzyme-linked immunosorbent assay (ELISA). Statistical analysis was performed using the STATA package. Both active and total MMP-8-based methods discriminated among sites according to periodontal diagnosis and severity, with a positive correlation between the two tests (p < 0.001). (a) MMP-8 models showed the best performance in receiver operating characteristic (ROC) curves to discriminate between healthy and periodontitis sites (area under the curve [AUC] = 0.89), while (t) MMP-8 demonstrated a high diagnostic precision in the detection of mild from severe periodontitis sites (AUC ≥ 0.80). The use of (a) MMP-8 and (t) MMP-8 could represent a useful adjunctive tool for periodontitis diagnosis and severity. These results support the applicability of new point-of-care methods in the monitoring of high-risk periodontal patients.

Abstract Bladder cancer (BC) is the ninth most common cancer worldwide. Radical cystectomy (RC) with neoadjuvant chemotherapy (NAC) is recommended for muscle-invasive BC. The challenge of the neoadjuvant approach relates to challenges in selection of patients to chemotherapy that are likely to respond to the treatment. To date, there are no validated molecular markers or baseline clinical characteristics to identify these patients. Different inflammatory markers, including tumor associated macrophages with their plastic pro-tumorigenic and anti-tumorigenic functions, have extensively been under interests as potential prognostic and predictive biomarkers in different cancer types. In this immunohistochemical study we evaluated the predictive roles of three immunological markers, CD68, MAC387, and CLEVER-1, in response to NAC and outcome of BC. 41% of the patients had a complete response (pT0N0) to NAC. Basic clinicopathological variables did not predict response to NAC. In contrast, MAC387+ cells and CLEVER-1+ macrophages associated with poor NAC response, while CLEVER-1+ vessels associated with more favourable response to NAC. Higher counts of CLEVER-1+ macrophages associated with poorer overall survival and CD68+ macrophages seem to have an independent prognostic value in BC patients treated with NAC. Our findings point out that CD68, MAC387, and CLEVER-1 may be useful prognostic and predictive markers in BC.

Abstract Background Gestational diabetes mellitus (GDM) has significant implications for the future health of the mother. Some clinical studies have suggested subclinical inflammation and vascular dysfunction after GDM. We aimed to study whether concentrations of high-sensitivity C-reactive protein (hsCRP), tissue inhibitor of metalloproteinase-1 (TIMP-1), matrix metalloproteinase-8 (MMP-8) and -9, as well as values of arterial stiffness differ between women with and without a history of GDM a few years after delivery. We also investigated possible effects of obesity on the results. Methods We studied two cohorts—120 women with a history of GDM and 120 controls—on average 3.7 years after delivery. Serum concentrations of hsCRP were determined by immunonephelometric and immunoturbidimetric methods, MMP-8 by immunofluorometric assay, and MMP-9 and TIMP-1 by enzyme-linked immunosorbent assays. Pulse wave velocity (PWV) was determined using the foot-to-foot velocity method from carotid and femoral waveforms by using a SphygmoCor device. Arterial compliance was measured non-invasively by an HDI/PulseWave™CR-2000 arterial tonometer. All 240 women were also included in subgroup analyses to study the effect of obesity on the results. Multiple linear regression analyses were performed with adjustment for confounding factors. Results PWV after pregnancy complicated by GDM was significantly higher than after normal pregnancy, 6.44 ± 0.83 (SD) vs. 6.17 ± 0.74 m/s (p = 0.009). Previous GDM was also one of the significant determinants of PWV in multiple linear regression analyses. On the other hand, compliance indices of both large (p = 0.092) and small (p = 0.681) arteries did not differ between the study cohorts. Serum TIMP-1 levels were significantly increased after previous GDM (p = 0.020). However, no differences were found in the serum levels of MMP-8, MMP-9 or hsCRP. In subgroup analyses, there were significantly higher concentrations of hsCRP (p = 0.015) and higher PWV (p

Background. Matrix metalloproteinases (MMPs) and myeloperoxidase (MPO) contribute to the inflammatory cascade in the cerebrospinal fluid (CSF) during bacterial meningitis. We determined levels of MPO, MMP-8, MMP-9, and tissue inhibitor of metalloproteinase- (TIMP-) 1 in the CSF of children with bacterial meningitis and investigated how these inflammatory mediators relate to each other and to the disease outcomes. Methods. Clinical data and the diagnostic CSF samples from 245 children (median age eight months) with bacterial meningitis were obtained from a clinical trial in Latin America in 1996–2003. MMP-9 levels in the CSF were assessed by zymography, while MMP-8, MPO, and TIMP-1 concentrations were determined with immunofluorometric and enzyme-linked immunosorbent assays. Results. MPO correlated positively with MMP-8 (rho 0.496, P

The aim of this cross-sectional study is to propose an efficient strategy based on biomarkers adjunct with an interview/questionnaire covering risk factors for periodontitis for the identification of undiagnosed periodontitis by medical professionals. Active matrix metalloproteinase (aMMP)-8 levels in mouthrinse were analyzed by a point-of-care (PoC)/chairside lateral-flow immunotest, and salivary total MMP-8, total MMP-9 and calprotectin levels were analyzed by enzyme-linked immunosorbent assays (ELISAs) and active MMP-9 by gelatin zymography for 149 Greek patients. Patients underwent a full-mouth oral health examination for diagnosis according to the 2018 classification system of periodontal diseases. In addition, patient characteristics (risk factors: age, gender, education level, smoking and body mass index) were recorded. Receiver operating curve (ROC) analysis indicated better diagnostic precision to identify undiagnosed periodontitis for oral fluid biomarkers in adjunct with an interview/questionnaire compared with a plain questionnaire (i.e., risk factors): aMMP-8 AUC (95% confidence interval) = 0.834 (0.761−0.906), total MMP-8 = 0.800 (0.722–0.878), active MMP-9 = 0.787 (0.704–0.870), total MMP-9 = 0.773 (0.687−0.858) and calprotectin = 0.773 (0.687–0.858) vs. questionnaire = 0.764 (0.676–0.851). The findings of this study suggest that oral fluid biomarker analysis, such as a rapid aMMP-8 PoC immunotest, could be used as an adjunct to an interview/questionnaire to improve the precision of timely identification of asymptomatic, undiagnosed periodontitis patients by medical professionals. This strategy appears to be viable for referring patients to a dentist for diagnosis and treatment need assessment.

Salivary biomarkers have been linked to various systemic diseases. We examined the association between salivary biomarkers, periodontal health, and microbial burden in liver transplant (LT) recipients with and without diabetes, after transplantation. We hypothesized that diabetic recipients would exhibit impaired parameters. This study included 84 adults who received an LT between 2000 and 2006 in Finland. Dental treatment preceded transplantation. The recipients were re-examined, on average, six years later. We evaluated a battery of salivary biomarkers, microbiota, and subjective oral symptoms. Periodontal health was assessed, and immunosuppressive treatments were recorded. Recipients with impaired periodontal health showed higher matrix metalloproteinase-8 (MMP-8) levels (p < 0.05) and MMP-8/tissue inhibitor of matrix metalloproteinase 1 (TIMP1) ratios (p < 0.001) than recipients with good periodontal health. Diabetes post-LT was associated with impaired periodontal health (p < 0.05). No difference between groups was found in the microbial counts. Salivary biomarker levels did not seem to be affected by diabetes. However, the advanced pro-inflammatory state induced by and associated with periodontal inflammation was reflected in the salivary biomarker levels, especially MMP-8 and the MMP-8/TIMP-1 molar ratio. Thus, these salivary biomarkers may be useful for monitoring the oral inflammatory state and the course of LT recipients.

To evaluate the effect of adjunctive antiseptic irrigation of periodontal pockets on microbial and cytokine profiles. Fifty-nine patients with severe periodontitis were allocated to one of three groups for scaling and root planing facilitated with different adjunctive antiseptics: 1% polyhexamethyleneguanidine phosphate (PHMG-P) (n = 19), 0.2% chlorhexidine (CHX) (n = 21) or distilled water (n = 19). Gingival crevicular fluid and subgingival bacterial samples were collected at baseline, and at 2 weeks, and 1 and 4 months. The levels of interleukin (IL)-1β, IL-8, IL-10, and IL-17A, matrix metalloproteinase (MMP)-8, Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, Fusobacterium nucleatum,Aggregatibacter actinomycetemcomitans, and Prevotella intermedia were determined. There were no intergroup differences in cytokine concentrations and bacterial counts at any follow-up, however, varying patterns were observed. In the PHMG-P and water groups IL-1β expression peaked at 2 weeks and then gradually declined. In all three groups, the dynamics of MMP-8 concentration were non-linear, increasing by 2 weeks and then declining to below baseline (p > 0.05). P. gingivalis and T. forsythia declined within the first month and increased thereafter, not regaining the baseline level. Adjunctive antiseptic treatment was associated with changes in biomarkers and bacterial counts in the course of the study. The effects of adjunctive antiseptic irrigation were limited in the applied protocol.

Biomarkers represent promising aids in periodontitis, host-mediate diseases of the tooth-supporting tissues. We assessed the diagnostic potential of matrix metalloproteinase-8 (MMP-8), tartrate-resistant acid phosphatase-5 (TRAP-5), and osteoprotegerin (OPG) to discriminate between healthy patients’, mild and severe periodontitis sites. Thirty-one otherwise healthy volunteers with and without periodontal disease were enrolled at the Faculty of Dentistry, University of Chile. Periodontal parameters were examined and gingival crevicular fluid was sampled from mild periodontitis sites (M; n = 42), severe periodontitis sites (S; n = 59), and healthy volunteer sites (H; n = 30). TRAP-5 and OPG were determined by commercial multiplex assay and MMP-8 by the immunofluorometric (IFMA) method. STATA software was used. All biomarkers showed a good discrimination performance. MMP-8 had the overall best performance in regression models and Receiver Operating Characteristic (ROC) curves, with high discrimination of healthy from periodontitis sites (area under the curve (AUC) = 0.901). OPG showed a very high diagnostic precision (AUC ≥ 0.95) to identify severe periodontitis sites (S versus H + M), while TRAP-5 identified both healthy and severe sites. As conclusions, MMP-8, TRAP-5, and OPG present a high precision potential in the identification of periodontal disease destruction, with MMP-8 as the most accurate diagnostic biomarker.

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.

The diagnostic accuracy of point-of-care (PoC) applications may be compromised in individuals with additional inflammatory conditions. This cross-sectional study examined the performance of a commercial oral rinse active matrix metalloproteinase-8 (aMMP-8) PoC immunotest in individuals with (n = 47) and without Crohn’s disease (CD) (n = 41). Oral rinse collected from the participants was analyzed by the PoC immunotest. Molecular forms and fragments of salivary MMP-8 were detected by western immunoblotting. The sensitivity of the immunotest for periodontitis was 60.0% in the CD group and 90.0% in the control group. The respective specificity was 75.0% and 80.0%. In both groups, clinical diagnosis of periodontitis exhibited a significant association with the immunotest results, however, the odds ratio (OR) was more than ten-fold in controls (OR 54.3, 95% CI: 3.1−953, p = 0.006) in comparison to CD patients (OR 5.2, 95% CI: 1.3−21.6, p = 0.022). According to Western immunoblot results, the immunotest MMP-8 positivity was not related to elevated levels of molecular forms and fragments of MMP-8 in the CD group, as in the control group. The diagnostic accuracy of the aMMP-8 PoC oral rinse immunotest is reduced in CD patients, which may be related to lower levels or undetectable complexes.

Despite gastric cancer being rare nowadays in Western countries, it remains one of the leading causes of cancer death worldwide. The course of the disease varies, so the individual gastric cancer patient’s prognosis is difficult to determine. The need for new biomarkers is crucial. The aim of this study was to evaluate the prognostic value of serum matrix metalloproteinase-8, serum tissue inhibitor of metalloproteinase-1, and tissue matrix metalloproteinase-8 in patients with gastric cancer. Preoperative serum samples from 233 patients with gastric cancer were retrospectively analyzed. Serum levels of matrix metalloproteinase-8 were analyzed with immunofluorometric assay, and tissue inhibitor of metalloproteinase-1 levels were determined by enzyme-linked immunosorbent assay. We also determined the tissue expression of matrix metalloproteinase-8 in 276 gastric cancer samples by immunohistochemistry. Survival data and death causes came from patient records, the Population Register Center of Finland, and Statistics Finland. Patients with a low (131 ng/mL) serum matrix metalloproteinase-8 level had a considerably unfavorable prognosis (p = 0.002). Those patients with a high (≥170 ng/mL) serum tissue inhibitor of metalloproteinase-1 level also had a poor prognosis (p 0.30) molar ratios predicted a worse prognosis (p = 0.020). Tissue matrix metalloproteinase-8 did not influence prognosis. These results suggest that serum matrix metalloproteinase-8, tissue inhibitor of metalloproteinase-1, and the ratio of matrix metalloproteinase-8/ tissue inhibitor of metalloproteinase-1 may prove useful biomarkers for prediction of prognosis in patients with gastric cancer.

Matrix metalloproteinases (MMPs), endopeptidases with diverse biochemical functions, can promote cancer cell invasion and metastasis by degrading the extracellular matrix. A high matrix metalloproteinase-14 (MMP-14) expression in gastric cancer tissue has been associated with metastasis and poor prognosis. To further understand this association, we investigated serum MMP-14 as a biomarker in gastric cancer patients. The patient cohort consisted of 240 gastric adenocarcinoma patients who underwent surgery at Helsinki University Hospital, Finland, between 2000 and 2009. We determined the soluble MMP-14 serum levels using an enzyme-linked immunosorbent assay. We then calculated the associations between serum levels and clinicopathologic variables using the Mann-Whitney U-test or the Kruskal-Wallis test. We constructed survival curves using the Kaplan-Meier method and calculating the hazard ratios using the Cox proportional hazard model. We revealed a positive association between a high serum MMP-14 level and stages III-IV (p = 0.029), and between a high serum MMP-14 and distant metastasis (p = 0.022). Patients with a low serum MMP-14 had a 5-year disease-specific survival of 49.2% (95% confidence interval [CI] 45.5-52.9), whereas patients with a high serum MMP-14 had a 5-year survival of 22.1% (95% CI 15.2-29.0; p = 0.001). High serum MMP-14 was a statistically significant prognostic factor among patients with an intestinal type of cancer (hazard ratio [HR] 3.54; 95% CI 1.51-8.33; p = 0.004), but not among patients with a diffuse type. The serum MMP-14 level remained an independent prognostic factor in our multivariate survival analysis (HR 1.55; 95% CI 1.02-2.35; p = 0.040). This study indicates for the first time that high serum soluble MMP-14 levels in gastric cancer serves as a marker for a poor prognosis, possibly indicating the presence of distant metastases.

Background. Dental caries is the most common infection in the world and is influenced by genetic and environmental factors. Environmental factors are largely known, but the role of genetic factors is quite unknown. The aim was to investigate the genetic background of caries in Finnish adolescents. Materials and Methods. This study was carried out at the Kotka Health Center in Eastern Finland. 94 participants aged 15–17 years gave approval for the saliva and DNA analyses. However, one was excluded in DNA analysis; thus, the overall number of participants in analysis was 93. Caries status was recorded clinically and from bite-wing X-rays to all 94 participants. Genomic DNA was extracted by genomic QIAamp® DNA Blood Mini Kit and genotyped for polymorphisms. The results were analyzed using additive and logistic regression models. Results. No significant associations between caries and the genes studied were found. However, SNPs in DDX39B and MPO showed association tendencies but were not statistically significant after false discovery rate (FDR) analysis. SNPs in VDR, LTA, and MMP3 were not statistically significant with initial caries lesions after FDR analysis. Conclusion. The present study could not demonstrate statistically significant associations between caries and the genes studied. Further studies with larger populations are needed.

Levels of and especially the degree of activation of matrix metalloproteinase (MMP-8) in oral fluids (i.e., saliva, mouth rinse, gingival crevicular fluid (GCF) and peri-implantitis sulcular fluid (PISF)) increase to pathologically elevated levels in the periodontal and peri-implant diseases. This study aimed at collecting and collating data from previously published studies and determining whether active MMP-8 (aMMP-8) could serve as a biomarker for the diagnosis and prevention of periodontal and peri-implant diseases. The literature search identified a total of 284 articles. Out of 284 articles, 61 articles were found to be relevant. Data obtained from the selected studies were combined, and it indicated that aMMP-8 in oral fluids exerts the strong potential to serve as a useful adjunctive diagnostic and preventive biotechnological tool in periodontal and peri-implant diseases. aMMP-8 can be used alone or in combination with other proinflammatory and/or microbiological biomarkers.

Introduction: Periodontitis is a multifactorial infectious disease of the supporting tissues of teeth in which bacterial, genetic and lifestyle factors such as smoking have an important role. Aim: The aim was to examine if Bleeding On Probing (BOP ≥ 20%) and ≥ 4 mm deep pockets correlated with any suspicion of initial radiological findings of periodontitis and bone loss. We also investigated whether any pro-inflammatory-related candidate Single Nucleotide Polymorphisms (SNPs) were associated with any suspicion of radiological findings. Materials and Methods: Altogether 47 generally healthy adolescent patients of one birth cohort had given their approval for their saliva samples to be used for DNA analysis. One participant was excluded after discrepant gender check. An oral radiologist analysed right and left bitewing radiographs of 47 patients. Clinical parameters such as BOP ≥ 20%, ≥ 4 mm pockets, Visible Plaque Index of all teeth (VPI%), as well as smoking habits were recorded. DNA was extracted and 71 SNPs from candidate genes for initial periodontitis were genotyped. The association between ≥ 4 mm pockets and BOP ≥ 20% with radiological findings and selected SNPs was modelled using logistic regression. Results: Variants in Toll-Like Receptors 4 (TLR4) gene (rs498670) (OR=5.8, {CI95% 1.6–20.7}, p=0.02, FDR q-value=0.13) and TNFSF11 gene (rs2277438, OR=0.3 {CI95% 0.1–0.9}, p=0.002, FDR q-value=0.56) were associated with any suspicious radiological findings; however the significance vanished after False Discovery Rate analysis (FDR). The association between BOP ≥ 20% and any radiographic signs of periodontitis was found to be statistically significant, OR=1.6, CI 95% 1.0-2.4, p=0.04. Conclusion: Only TLR4 (rs498670) and TNFSF11 (rs2277438) genes were found to have a positive correlation with radiological findings suggestive of initial periodontitis after adjustment for smoking and visible plaque.

BACKGROUND:Matrix metalloproteinase 8 (MMP-8) is the most potent type-I collagen protease. Such collagen mainly constitutes the transient fibrosis in takotsubo cardiomyopathy (TTC) endomyocardial biopsies. High MMP-8 and tissue-inhibitor of matrix metalloproteinase-1 (TIMP-1) levels are implicated in acute coronary syndrome (ACS). We compared MMP-8 and TIMP-1 levels in consecutive TTC and ACS patients, and their association to TTC severity. METHODS AND RESULTS:In 45 acute serum samples of TTC, 2072 ACS and 1000 controls, TIMP-1 differed between ACS 146.7ng/mL (115.0-186.3) (median (interquartile range)), TTC 115.7 (94.3-137.7) and controls 80.9 (73.2-90.4), (p

High leptin concentration, low-grade inflammation, and insulin resistance often coexist in obese subjects; this adverse metabolic milieu may be the main culprit for increased fracture risk and impaired bone quality seen in patients with type 2 diabetes. We examined the associations of leptin, hs (high sensitivity)- CRP and insulin resistance with bone turnover markers (BTMs) and bone characteristics in 55 young obese adults (median BMI 40 kg/m2) and 65 non-obese controls. Mean age of the subjects was 19.5 ± 2.5 years (mean ± SD). Concentrations of leptin, adiponectin, hs-CRP, MMP-8 and TIMP-1, fasting plasma glucose and insulin (to calculate HOMA), BTMs (BAP, P1NP, CTX-1, and TRAC5b) were measured. Bone characteristics were determined with pQCT at radius and tibia, and with DXA for central sites. Leptin, hs-CRP and HOMA correlated inversely with BTMs: the partial coefficients were 1.5-1.9 fold higher in males than in females. After adjusting for age, BMI, and other endocrine factors, leptin displayed an independent effect in males on radial bone mass (p = 0.019), tibial trabecular density (p = 0.025) and total hip BMD (p = 0.043), with lower densities in males with high leptin. In females, the model adjusting for age, BMI, and other endocrine factors, revealed that hs-CRP had independent effects on radial bone mass (p = 0.034) and lumbar spine BMD (p = 0.016), women with high hs-CRP having lower values. Partial correlations of adiponectin and TIMP-1 with bone characteristics were discrepant; MMP-8 showed no associations. In conclusion, in young obese adults and their controls, leptin, hs-CRP and HOMA associate inversely with BTMs and bone characteristics. Leptin appears to be the key independent effector in males, whereas hs-CRP displayed a predominant role in females.