Born too young and likely to die : Should this continue?

Peer reviewe

Implementing of aMMP-8 point-of-care test with a modified new disease classification in Finnish adolescent cohorts

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 nglml), 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.Peer reviewe

Prediction of neo-adjuvant chemotherapy response in bladder cancer : the impact of clinical parameters and routine biomarkers

Purpose To investigate the role of clinical parameters and immunohistochemical (IHC) biomarkers in their feasibility to predict the effect of neo-adjuvant chemotherapy (NAC) in patients with muscle-invasive urothelial bladder cancer (MIBC). Materials and methods The first 76 consecutive patients with MIBC treated with NAC and radical cystectomy in two University hospitals in Finland between 2008 and 2013 were chosen for this study. After excluding patients with non-urothelial cancer, less than two cycles of chemotherapy, no tissue material for IHC analysis or non-muscle-invasive bladder cancer in re-review, 59 patients were included in the final analysis. A tissue microarray block was constructed from the transurethral resection samples and IHC stainings of Ki-67, p53, Her-2 and EGFR were made. The correlations between histological features in transurethral resection samples and immune-histochemical stainings were calculated. The associations of clinicopathological parameters and IHC stainings with NAC response were evaluated. Factors affecting survival were estimated. Results The complete response rate after NAC was 44%. A higher number of chemotherapy cycles was associated with better response to neo-adjuvant chemotherapy. No response to neo-adjuvant chemotherapy and female gender was associated with decreased cancer-specific survival. The IHC stainings used failed to show an association with neo-adjuvant chemotherapy response and overall or cancer specific survival. Conclusions Patients who do not respond to neo-adjuvant chemotherapy do significantly worse than responders. This study could not find clinical tools to distinguish responders from non-responders. Further studies preferably with larger cohorts addressing this issue are warranted to improve the selection of patients for neo-adjuvant chemotherapy.Peer reviewe

Ability of matrix metalloproteinase-8 biosensor, IFMA, and ELISA immunoassays to differentiate between periodontal health, gingivitis, and periodontitis

Publisher Copyright: © 2022 The Authors. Journal of Periodontal Research published by John Wiley & Sons Ltd.Objective: The aim of this study was to determine the diagnostic utility of an MMP-8 biosensor assay in differentiating periodontal health from gingivitis and periodontitis and compare it with an established time-resolved immunofluorescence assay (IFMA) and enzyme-linked immunosorbent assay (ELISA). Background: Currently available antibody-based assays display a wide variability in their ability to accurately measure matrix metalloproteinase-8 (MMP-8) levels in saliva. Methods: Salivary MMP-8 levels were analyzed in 189 systemically healthy participants using an antibody-based biosensor prototype that operates using a surface acoustic wave technology and compared with IFMA and ELISA antibody assays. Participants were categorized into 3 groups: periodontal health (59), gingivitis (63), and periodontitis (67). A sub-population of participants (n = 20) with periodontitis received periodontal treatment and were monitored for 6 months. Results: All the assays demonstrated significantly higher salivary MMP-8 concentrations in participants with periodontitis versus gingivitis, periodontitis versus health, and gingivitis versus health (all p <.05). The biosensor data demonstrated significant correlations with IFMA (r =.354, p <.001) and ELISA (r =.681, p <.001). Significant reductions in salivary MMP-8 concentrations were detected by the biosensor (p =.030) and IFMA (p =.002) in participants with periodontitis 6 months after non-surgical periodontal treatment. IFMA had the best sensitivity (89.2%) for detecting periodontitis and gingivitis versus health and 96.6% for detecting periodontitis versus health and gingivitis. The biosensor had an AUC value of 0.81 and diagnostic accuracy of 74.2% for differentiating periodontitis and gingivitis from health; an AUC value of 0.86 and diagnostic accuracy of 82.8% for periodontitis versus health and gingivitis. Conclusions: The biosensor, IFMA, and ELISA assays differentiated between periodontal health, gingivitis, and periodontitis based on salivary MMP-8 levels. Only the biosensor and, particularly, IFMA identified an effect of periodontal treatment in the participants with periodontitis. Our findings support the potential utility of salivary oral fluid aMMP-8-based point-of-care technology in the future of periodontal diagnostics.Peer reviewe

Diagnosis of Newly Delivered Mothers for Periodontitis with a Novel Oral-Rinse aMMP-8 Point-of-Care Test in a Rural Malawian Population

A novel qualitative point-of-care test of activated matrix metalloproteinase-8 (aMMP-8) using noninvasive oral rinse sampling procedures has been developed for the early detection of collagen breakdown indicating periodontal tissue destruction. The main object of this study was to assess the reliability of the test in a low-income setting to identify participants with history of periodontal destruction detected as alveolar bone loss (ABL) in radiographs. This cross-sectional study included 486 women who had recently delivered in rural Malawi. The aMMP-8 test and dental panoramic radiographs were taken within 48 h of delivery. The performance of the test in comparison to radiological examinations was tested by following the standards for reporting of diagnostic accuracy studies protocol (STARD) with respective statistical measures and 95% confidence intervals. From the 486 eligible participants, 461 mothers with complete data, aged from 15 to 46 years (mean 24.8, SD 6.0) were included in the analysis. ABL was identified in 116 of 461 participants. There was 56% agreement between the aMMP-8 test results and detected ABL (yes or no) in radiographs. Calculated sensitivity of the test was 80% (72–87%), specificity 48% (43–54%), positive predictive value 34% (31–37%), negative predictive value 88% (83–91%), positive likelihood ratio 1.55 (1.35–1.77), and negative likelihood ratio 0.41(0.28–0.60). The aMMP-8 test sensitivity and negative predictive value to identify the ABL cases were relatively high, but there was additionally a high rate of test-positive results in participants without ABL, especially in young mothers, leading to low overall agreement between the test results and radiological bone loss. Further longitudinal studies are needed to examine if the test positive subjects are in risk of future bone loss before the detectable signs of periodontitis in radiographs.Peer reviewe

Immunological tumor status may predict response to neoadjuvant chemotherapy and outcome after radical cystectomy in bladder cancer

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

Early pathways of maternal mentalization: Associations with child development in the FinnBrain birth cohort study

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 studies, 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

Early pathways of maternal mentalization : Associations with child development in the FinnBrain birth cohort study

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.publishedVersionPeer reviewe

Matrix-metalloproteinase-2,-8 and-9 in serum and skin blister fluid in patients with severe sepsis

Peer reviewe

Prognostic Role of Survivin and Macrophage Infiltration Quantified on Protein and mRNA Level in Molecular Subtypes Determined by RT-qPCR of KRT5, KRT20, and ERBB2 in Muscle-Invasive Bladder Cancer Treated by Adjuvant Chemotherapy

Objectives: Bladder cancer is a heterogeneous malignancy. Therefore, it is difficult to find single predictive markers. Moreover, most studies focus on either the immunohistochemical or molecular assessment of tumor tissues by next-generation sequencing (NGS) or PCR, while a combination of immunohistochemistry (IHC) and PCR for tumor marker assessment might have the strongest impact to predict outcome and select optimal therapies in real-world application. We investigated the role of proliferation survivin/BIRC5 and macrophage infiltration (CD68, MAC387, CLEVER-1) on the basis of molecular subtypes of bladder cancer (KRT5, KRT20, ERBB2) to predict outcomes of adjuvant treated muscle-invasive bladder cancer patients with regard to progression-free survival (PFS) and disease-specific survival (DSS). Materials and Methods: We used tissue microarrays (TMA) from n = 50 patients (38 males, 12 female) with muscle-invasive bladder cancer. All patients had been treated with radical cystectomy followed by adjuvant triple chemotherapy. Median follow-up time was 60.5 months. CD68, CLEVER-1, MAC387, and survivin protein were detected by immunostaining and subsequent visual inspection. BIRC5, KRT5, KRT20, ERBB2, and CD68 mRNAs were detected by standardized RT-qPCR after tissue dot RNA extraction using a novel stamp technology. All these markers were evaluated in three different centers of excellence. Results: Nuclear staining rather than cytoplasmic staining of survivin predicted DSS as a single marker with high levels of survivin being associated with better PFS and DSS upon adjuvant chemotherapy (p = 0.0138 and p = 0.001, respectively). These results were validated by the quantitation of BIRC5 mRNA by PCR (p = 0.0004 and p = 0.0508, respectively). Interestingly, nuclear staining of survivin protein was positively associated with BIRC5 mRNA, while cytoplasmic staining was inversely related, indicating that the translocation of survivin protein into the nucleus occurred at a discrete, higher level of its mRNA. Combining survivin/BIRC5 levels based on molecular subtype being assessed by KRT20 expression improved the predictive value, with tumors having low survivin/BIRC5 and KRT20 mRNA levels having the best survival (75% vs. 20% vs. 10% 5-year DSS, p = 0.0005), and these values were independent of grading, node status, and tumor stage in multivariate analysis (p = 0.0167). Macrophage infiltration dominated in basal tumors and was inversely related with the luminal subtype marker gene expression. The presence of macrophages in survivin-positive or ERBB2-positive tumors was associated with worse DSS. Conclusions: For muscle-invasive bladder cancer patients, the proliferative activity as determined by the nuclear staining of survivin or RT-qPCR on the basis of molecular subtype characteristics outperforms single marker detections and single technology approaches. Infiltration by macrophages detected by IHC or PCR is associated with worse outcome in defined subsets of tumors. The limitations of this study are the retrospective nature and the limited number of patients. However, the number of molecular markers has been restricted and based on predefined assumptions, which resulted in the dissection of muscle-invasive disease into tumor–biological axes of high prognostic relevance, which warrant further investigation and validation.</p