The salivary proteome in relation to oral mucositis in autologous hematopoietic stem cell transplantation recipients: a labelled and label-free proteomics approach.

BACKGROUND: Oral mucositis is a frequently seen complication in the first weeks after hematopoietic stem cell transplantation recipients which can severely affects patients quality of life. In this study, a labelled and label-free proteomics approach were used to identify differences between the salivary proteomes of autologous hematopoietic stem cell transplantation (ASCT) recipients developing ulcerative oral mucositis (ULC-OM; WHO score ≥ 2) or not (NON-OM). METHODS: In the TMT-labelled analysis we pooled saliva samples from 5 ULC-OM patients at each of 5 timepoints: baseline, 1, 2, 3 weeks and 3 months after ASCT and compared these with pooled samples from 5 NON-OM patients. For the label-free analysis we analyzed saliva samples from 9 ULC-OM and 10 NON-OM patients at 6 different timepoints (including 12 months after ASCT) with Data-Independent Acquisition (DIA). As spectral library, all samples were grouped (ULC-OM vs NON-OM) and analyzed with Data Dependent Analysis (DDA). PCA plots and a volcano plot were generated in RStudio and differently regulated proteins were analyzed using GO analysis with g:Profiler. RESULTS: A different clustering of ULC-OM pools was found at baseline, weeks 2 and 3 after ASCT with TMT-labelled analysis. Using label-free analysis, week 1-3 samples clustered distinctly from the other timepoints. Unique and up-regulated proteins in the NON-OM group (DDA analysis) were involved in immune system-related processes, while those proteins in the ULC-OM group were intracellular proteins indicating cell lysis. CONCLUSIONS: The salivary proteome in ASCT recipients has a tissue protective or tissue-damage signature, that corresponded with the absence or presence of ulcerative oral mucositis, respectively. TRIAL REGISTRATION: The study is registered in the national trial register (NTR5760; automatically added to the International Clinical Trial Registry Platform).

[Measuring tooth wear with regular intra-oral 3D scanners: for still in the future, or is it already possible?] / Serie: Innovatieve technieken en ontwikkelingen in de mondzorg. Meten van gebitsslijtage met reguliere 3D-scanners: toekomstmuziek, of al mogelijk?

Quantitative tooth wear measurement is a method of increasing importance when measuring tooth wear progression. The Radboud university medical center has developed a protocol that measures height and volumetric differences on regular 3D-scans. Intra-oral scans were made on patients with tooth wear and superimposed. To assess reliability the precision , as well as intra- and inter-rater precision of the protocol was tested. T-tests were performed to determine the structural and random error. Our findings indicate that the method is precise enough to measure height differences in patients with severe tooth wear progression, or tooth wear with an interval longer than 1 year. The method is not precise enough to measure volumetric changes.

[Oral chronic graft versus host disease, what is it and how is it treated?] / Orale chronische graft-versus-hostziekte, wat is het en hoe wordt het behandeld?

Allogeneic stem cell transplantation can cause chronic graft versus host disease (cGVHD). A number of patients manifest cGVHD in and around the mouth. It can present itself as clinically as mucosal lesions and/or salivary gland dysfunction and/or sclerotic changes. Cheeks and tongue are most commonly affected, but the palate, gingiva and lips can also be impacted. Oral cGVHD is associated with mucosal sensitivity, pain, (severe) oral dryness, altered taste, restricted mouth opening and difficulty swallowing, all of which may contribute to a significant decrease of the patient's quality of life. Patients also run an increased risk of developing squamous cell carcinoma of the oral mucosa. The diagnosis of cGVHD is almost always based on the patient's medical history and clinical picture. Treatment of symptoms is based on the patient's problem(s). Dental professionals can provide patients with supportive preventive care aimed at reducing symptoms and preventing further deterioration of oral health.

[Self-reported oral health and oral health behaviour of asylum seekers]. / Zelfgerapporteerde mondgezondheid en mondgezondheidsgedrag van asielzoekers.

In order to assess the oral health and oral health behaviour of asylum seekers in the Netherlands, 542 asylum seekers completed questionnaires. There were questionnaires for the groups children (1-11 years), youths (12-17 years) and adults (18+ years). 4 Categories of questions were asked: 'demographic characteristics', 'complaints and symptoms', 'lifestyle and knowledge' and 'visiting the dentist'. Regression analyses were performed to see which demographic factors influenced oral health. Of the respondents, 42% of the children, 57% of the youths and 86% of the adults reported at least one oral complaint or symptom. Of them 42% of the children, 59% of the youths and 53% of the adults followed the basic recommendation to brush their teeth twice a day. Of those questioned, 45% of the children, 48% of the youths and 28% of the adults went to a dentist for check-ups. When these results are compared to the rest of the Dutch population, asylum seekers scored worse in all categories.

[The anticaries effect of antibacterial bonding in vitro is lost with aging]. / Het cariësremmende effect van antibacteriële bonding in vitro gaat verloren door veroudering.

This in vitro study investigated whether aging of restorative materials influences secondary caries development. The research question was whether antibacterial bonding maintained its effectiveness after aging. 60 enamel-dentine blocks were restored using 3 different restorative materials (n = 20 per material): composite with conventional bonding, composite with antibacterial bonding and amalgam. Half of the samples in each group (n = 10) were artificially aged through exposure to a sucrose biofilm model. Lesion depth was subsequently measured using transversal microradiography. Aging led to deeper lesions in the composite with antibacterial bonding group (CAB), compared to fresh samples. These fresh samples showed lesions less deep than fresh samples of composite with conventional bonding. After aging, this effect was absent. Within the limitations of this short-term in vitro study, it can be concluded that aging of restorative materials can influence caries progression. Antibacterial bonding materials lose their effectiveness over time.

[Risk factors for class II dental restoration survival:a practice-based study]. / Risicofactoren voor klasse II-restauratieoverleving: een praktijkgebaseerd onderzoek.

The aim of this practice-based cohort study was to determine the performance and influence of possible variables in class II restorations related to practice, patient, tooth, and restoration. To do this, electronic patient files from 11 general practices in the Netherlands were collected, and 31,472 restorations placed between January 2015 and October 2017 were analysed. The observation time of restorations varied from 0 to 2.7 years, resulting in a mean annual failure rate (AFR) of 7.8% at 2 years. However, wide variation in AFRs existed among the operators, varying between 3.6% and 11.4%. An excess of patient-related variables, such as age, general health, periodontal status, caries risk and the presence of parafunctional habits and tooth or restoration-related factors, increases the risk of reintervention. Restorations placed due to fracture were more prone to fail than restorations placed due to caries. This study demonstrated that a wide variety of risk factors on the practice, patient, and tooth levels influences the survival of class II restorations.

[Cup-shaped tooth wear defects: more than erosive challenges?] / Komvormige defecten in occlusale vlakken van molaren: meer dan alleen erosieve belasting?

The underlying mechanism of the development of cups and grooves on occlusal tooth surfaces is still unclear. The aim of this study was to evaluate factors contributing to in-vitro cup formation, and to elucidate the clinical process. Extracted human molar teeth were exposed to acidic aqueous solutions at pH of 4.8 and 5.5 in combination with different loading conditions: no load (0N, control), 30N or 50N. Before and after 3 months exposure, the samples were scanned using a non-contact profilometer. A statistically significant difference between a loading of 0N and 50N was found at pH 4.8 (p < 0.002). Cup shaped lesions had formed only at pH of 4.8, in the 30N and 50N groups. The study showed that a cup can arise fully in enamel and that this requires simultaneous acidic and mechanical loading.

[Preventive dentistry 10. Erosive tooth wear]. / Preventieve tandheelkunde 10. Erosieve gebitsslijtage.

Erosive tooth wear has recently been at the centre of attention and its prevalence of erosive tooth wear among adolescents in the Netherlands appears to be rising. The multifactorial nature of the aetiology of the condition makes it difficult to identify the relevant causal factors, both in individual cases and within the general population. Preventive intervention is indicated in those cases where (active) erosive tooth wear is diagnosed. Early diagnosis is important, especially in younger patients. Preventive measures, such as dietary advice and the use of fluoride, are recommended but the scientific evidence for their effectiveness is still limited. In cases where acid reflux disease is the cause, treatment with medicines can have the effect of reducing the progression of tooth wear. Recognising a non-active condition, for example after successful preventive treatment, is difficult, but will be supported with digital methods in the near future.

[Results of the assessment procedure for dentists with a foreign degree in the Netherlands]. / Resultaten van de toetsingsprocedure van tandartsen met een buitenlands diploma.

During the period from 1 January 2007 to 1 January 2017, 138 dentists with a foreign dental degree (obtained outside the European Economic Area or Switzerland) who wanted to practice dentistry in the Netherlands have undertaken the assessment procedure to obtain a certificate of professional competence. The procedure comprises a Dutch language proficiency and communications test, followed by tests of competence specific to the dental profession. For 68 dentists (49%), no deficiencies in knowledge or skills were identified. They could register in the BIG-register [for healthcare professionals] for the supervisory period. For 49 (36%), the deficiencies could be eliminated with specific training. In the case of 21 dentists (15%), training was not possible. The number of dentists from this group who were enrolled in the BIG-register in 2017 was determined. On the reference date, 100 dentists (73%) were enrolled. Of the 49 dentists who were permitted to participate in a specific educational programme, 48 had started such a programme: 38 had completed it by 2017, 9 are still actively involved, and 1 stopped the programme. If they complete the programme, the number of dentists who have been enrolled in the BIG-register after [successfully] finishing the assessment procedure could rise to 115 (83%).

In vitro biofilm models to study dental caries: a systematic review.

The aim of this systematic review is to characterize and discuss key methodological aspects of in vitro biofilm models for caries-related research and to verify the reproducibility and dose-response of models considering the response to anti-caries and/or antimicrobial substances. Inclusion criteria were divided into Part I (PI): an in vitro biofilm model that produces a cariogenic biofilm and/or caries-like lesions and allows pH fluctuations; and Part II (PII): models showing an effect of anti-caries and/or antimicrobial substances. Within PI, 72.9% consisted of dynamic biofilm models, while 27.1% consisted of batch models. Within PII, 75.5% corresponded to dynamic models, whereas 24.5% corresponded to batch models. Respectively, 20.4 and 14.3% of the studies reported dose-response validations and reproducibility, and 32.7% were classified as having a high risk of bias. Several in vitro biofilm models are available for caries-related research; however, most models lack validation by dose-response and reproducibility experiments for each proposed protocol.

[Preventive dentistry 5. Secondary caries]. / Preventieve tandheelkunde 5. Secundaire cariës.

Secondary caries is reported as one of the most important reasons for replacing restorations. The patient's general caries risk plays an important role in the development of secondary caries. The connection, at the patient level, between various factors, the risk of caries and restoration factors, such as the presence of a gap and the kind of restoration material, deserves additional investigation. The minimum gap width in which secondary caries can develop is most likely less than 100 µm and could depend on the patient's caries risk. Composite restorations seem more susceptible to secondary caries than amalgam restorations in patients with high caries risk. So far, there is no unambiguous explanation for this difference. The prevention of secondary caries is comparable to that of primary caries and stresses the importance of fluoride, diet and oral hygiene.

Consensus report of the European Federation of Conservative Dentistry: erosive tooth wear--diagnosis and management.

OBJECTIVE: Due to an increased focus on erosive tooth wear (ETW), the European Federation of Conservative Dentistry (EFCD) considered ETW as a relevant topic for generating this consensus report. MATERIALS AND METHODS: This report is based on a compilation of the scientific literature, an expert conference, and the approval by the General Assembly of EFCD. RESULTS: ETW is a chemical-mechanical process resulting in a cumulative loss of hard dental tissue not caused by bacteria, and it is characterized by loss of the natural surface morphology and contour of the teeth. A suitable index for classification of ETW is the basic erosive wear examination (BEWE). Regarding the etiology, patient-related factors include the pre-disposition to erosion, reflux, vomiting, drinking and eating habits, as well as medications and dietary supplements. Nutritional factors relate to the composition of foods and beverages, e.g., with low pH and high buffer capacity (major risk factors), and calcium concentration (major protective factor). Occupational factors are exposition of workers to acidic liquids or vapors. Preventive management of ETW aims at reducing or stopping the progression of the lesions. Restorative management aims at reducing symptoms of pain and dentine hypersensitivity, or to restore esthetic and function, but it should only be used in conjunction with preventive strategies. CONCLUSIONS: Effective management of ETW includes screening for early signs of ETW and evaluating all etiological factors. CLINICAL RELEVANCE: ETW is a clinical condition, which calls for the increased attention of the dental community and is a challenge for the cooperation with other medical specialities.

An in vitro evaluation of the fatigue behavior of resin composite materials as part of a translational research cycle.

PURPOSE: This study aimed to reproduce and translate clinical presentations in an in vitro set-up and evaluate laboratory outcomes of mechanical properties (flexural strength, fatigue resistance, wear resistance) and link them to the clinical outcomes of the employed materials in the Radboud Tooth Wear Project (RTWP). MATERIALS AND METHODS: Four dental resin composites were selected. 30 discs (Ø12.0 mm, 1.2 mm thick) were fabricated for each of Clearfil TM AP-X (AP), Filtek TM Supreme XTE (FS), Estenia TM C&B (ES), and Lava Ultimate (LU). Cyclic loading (200 N, 2 Hz frequency) was applied concentrically to 15 specimens per group with a spherical steatite indenter (r = 3.18 mm) in water in a contact-load-slide-liftoff motion (105 cycles). The wear scar was analysed using profilometry and the volume loss was digitally computed. Finally, all specimens were loaded (fatigued specimens with their worn surface loaded in tension) until fracture in a biaxial flexure apparatus. The differences in volume loss and flexural strength were determined using regression analysis. RESULTS: Compared to AP and FS, ES and LU showed a significantly lower volume loss (p < 0.05). Non-fatigued ES specimens had a similar flexural strength compared to nonfatigued AP, while non-fatigued FS and LU specimens had a lower flexural strength (p < 0.001; 95 %CI: -80.0 - 51.8). The fatigue test resulted in a significant decrease of the flexural strength of ES specimens, only (p < 0.001; 95 %CI: -96.1 - -54.6). CLINICAL RELEVANCE: These outcomes concur with the outcomes of clinical studies on the longevity of these composites in patients with tooth wear. Therefore, the employed laboratory test seems to have the potential to test materials in a clinically relevant way.

Diagnostic Strategies for Restorations Management: A 70-Month RCT.

We aimed to evaluate the impact of 2 visual diagnostic strategies for assessing secondary caries and managing permanent posterior restorations on long-term survival. We conducted a diagnostic cluster-randomized clinical trial with 2 parallel groups using different diagnostic strategies: (C+AS) based on caries assessment, marginal adaptation, and marginal staining aspects of the FDI (World Dental Federation) criteria and (C) based on caries assessment using the Caries Associated with Restorations or Sealants (CARS) criteria described by the International Caries Detection and Assessment System (ICDAS). The treatment for the restoration was conducted based on the decision made following the allocated diagnostic strategy. The restorations were then clinically reevaluated for up to 71 mo. The primary outcome was restoration failure (including tooth-level failure: pain, endodontic treatment, and extraction). Cox regression analyses with shared frailty were conducted in the intention-to-treat population, and hazard ratios (HRs) and 95% confidence intervals (95% CIs) were derived. We included 727 restorations from 185 participants and reassessed 502 (69.1%) restorations during follow-up. The evaluations occurred between 6 and 71 mo. At baseline, C led to almost 4 times fewer interventions compared with the C+AS strategy. A total of 371 restorations were assessed in the C group, from which 31 (8.4%) were repaired or replaced. In contrast, the C+AS group had 356 restorations assessed, from which 113 (31.7%) were repaired or replaced. During follow-up, 34 (9.2%) failures were detected in the restorations allocated to the C group and 30 (8.4%) allocated to the C+AS group in the intention-to-treat population, with no significant difference between the groups (HR = 0.83; 95% CI = 0.51 to 1.38; P = 0.435, C+AS as reference). In conclusion, a diagnostic strategy focusing on marginal defects results in more initial interventions but does not improve longevity over the caries-focused strategy, suggesting the need for more conservative approaches.

Reduction of erosion by protein-containing toothpastes.

AIM: To assess the effect of protein-containing toothpastes on the progression of dental erosion in situ (with pellicle) and in vitro (without pellicle). METHODS: A combined split-mouth (extraoral water or toothpaste brushing) and crossover (type of toothpaste) setup was used. Two protein-containing (high/low concentrations of colostrum) and one nonprotein (placebo) toothpaste were investigated. Sixteen volunteers wore intraoral appliances containing 2 human enamel samples on 3 afternoons for pellicle growth during 90 min. One enamel sample was brushed for 5 s with one of the three toothpastes and subsequently exposed to a slurry of the corresponding toothpaste for 2 min. The other sample was exposed to water. Both samples were subsequently exposed to citric acid (extraorally). Loss of calcium and inorganic phosphate were determined. The same sequence of exposures was applied to 16 enamel samples in an in vitro setup without pellicle. RESULTS: With the in situ-formed pellicle, all toothpastes significantly reduced calcium loss compared to water brushing, although no significant differences were found among toothpastes (p = 0.073). For the loss of phosphate, a significant reduction could be found with the use of the high-protein toothpaste compared to the nonprotein toothpaste. Overall there were only slight differences between the toothpastes. Toothpaste effects were less clear in the in vitro experiment. CONCLUSION: The addition of proteins to toothpaste shows some promise for the prevention of erosion. Further research is needed to investigate the performance of the protein-containing toothpastes in longer in situ studies with regard to erosive wear.

Saliva parameters and erosive wear in adolescents.

The aim of this study was to investigate the relationship between several parameters of saliva and erosive wear in adolescents. (Un-)stimulated saliva was collected from 88 adolescents with erosion and 49 controls (age 16 ± 1 years). Flow rate, pH and buffer capacity were determined immediately. Total protein content, carbonic anhydrase VI, amylase, albumin, calcium, phosphate, urea, sodium, chloride and potassium were measured at a later time. Unstimulated flow rate was found to be significantly lower in subjects with erosive wear (p = 0.016). The chloride concentration in unstimulated saliva was found to be significantly higher in the erosion group (p = 0.019).

Effectiveness of adhesive containing MDPB: A practice-based clinical trial.

OBJECTIVES: This prospective practice-based trial assessed the longevity of composite restorations made with an adhesive containing an antibacterial monomer compared to a conventional adhesive. METHODS: 9 general practices in the Netherlands were provided with two composite resin adhesives, each for a period of 9 months. Adhesive P contained the quaternary ammonium salt MDPB, and Adhesive S was a control. Patient's age and caries risk, as well as tooth type/number, reason for restoration placement, used restorative material and adhesive, and restored surfaces were recorded. All interventions carried out on these teeth in the 6 years after restoration were extracted from the electronic patient records, along with their date, type, reason, and surfaces. Two dependent variables were defined: general failure, and failure due to secondary caries. All data handling and multiple Cox regression analysis were carried out in R 4.0.5. RESULTS: 11 dentists from 7 practices made 10,151 restorations over a period of two years in 5102 patients. 4591 restorations were made with adhesive P, whereas 5560 were made with adhesive S. The observation period was up to 6.29 years, median observation time was 3.74 years. Cox regression showed no significant difference between the two adhesive materials when corrected for age, tooth type and caries risk, for general failure nor failure due to caries. SIGNIFICANCE: No difference in restoration survival could be shown between composite restorations made using an adhesive containing MDPB and control. Restorations made with the adhesive containing MDPB also did not fail more or less frequently due to secondary caries. This trial is registered on clinicaltrials.gov with identifier NCT05118100.

Shifts in the microbial population in relation to in situ caries progression.

The shift in microbial diversity from young to mature plaque, related to caries activity on sound and restored surfaces, was studied using denaturing gradient gel electrophoresis. During a 20-week in situ study on caries progression 8 subjects wearing restored and unrestored dentin and enamel sections, biofilm was sampled after 1 and 20 weeks (young or mature plaque). A higher microbial diversity (mature plaque) was seen in caries-active compared to caries-free subjects. Rothia dentocariosa and Scardovia inopinata were absent from all caries-free sites, but appeared in 50% of the caries-active sites.

Detection of dental decay and its extent using a.c. impedance spectroscopy.

Dental caries (decay), the most prevalent of diseases, represents a health problem of immense proportions. It principally affects posterior (back) teeth on occlusal (biting) and approximal (adjacent contacting) surfaces. Caries starts as a subsurface demineralization of enamel, may progress to the underlying dentine and, eventually, to cavitation of the surface. Accurate diagnosis before cavitation would permit targeted preventive treatment, thereby significantly improving dental health and reducing the need for expensive drilling and filling. Inaccessibility of caries initiation sites and recent changes in lesion morphology contribute to the relatively poor accuracy of conventional diagnostic methods. Among alternative techniques, measurements of electrical resistance have shown the most promise. Here we describe a new experimental technique that demonstrates an outstanding 100% correlation between a.c. impedance measurements of whole teeth and the actual extent of approximal caries in vitro. Only relatively minor modifications should be required to transfer the technique to in vivo applications.

An in vitro biofilm model for enamel demineralization and antimicrobial dose-response studies.

Microcosm biofilms formed in microplates have demonstrated complex community dynamics similar to natural dental biofilm. No simplified microcosm models to evaluate enamel demineralization and dose-response effect to anticariogenic therapies have yet been established, thus this study was designed to develop a pre-clinical model fulfilling this purpose. Experiments were carried out to establish the time of biofilm formation and the sucrose concentration and exposure regimen. Biofilms were initiated from saliva and grown for up to 10 days on bovine enamel discs in 24-well plates, with a saliva analogue medium. Data were collected as pH readings and the percentage enamel surface hardness change. A dose-response evaluation was performed with chlorhexidine, which significantly affected the pH and mineral loss. Overall, the established model parameters, 5 days of biofilm growth with intermittent 1% sucrose exposure of 6 h per day, was suitable as a pre-clinical model for enamel demineralization and dose-response studies.