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Motivation: Within the field of bio-implants one topic deals with the in-vitro production of 3D tissues from cell cultures. A major challenge in the cultivation of biopreparations is the imitation of the vascular system with its surrounding tissue. Additiv manufacturing of such vascularisation could be supported with an adequate template from high-resolution 3D radiographs. Goals: Evaluation of highresolution 3D-imaging methods and 3D-analysis approaches to extract the vascularisation from tissue samples. Methods: To provide such template, vascular structure of small tissues samples (partially treated with contrast medium) were recorded and compared using high-resolution CT and MRI imaging modalities. Optimal measurement parameters were selected for the acquisition of very small vessels. Interactive and semi-automated segmentation of the vessel system were investigated and compared. Results: MRI scans yield a higher contrast than CT scans, but are much slower. Duration of interactive segmentation ranges between 1 to 12 hours. Runtime of the (semi) automatic method was between 5 and 20 minutes, not counting manual adjustment of the parameters. Correlation between manual and automatic segmentation yield Hausdorff distances of 0.024 (CT) and 0.74 (MRI) and Dice coefficients of 0.7 (CT) and 0.39 (MRI). Conclusion: Both imaging methods are appropriate for high-resolution vessel detection and segmentation, nevertheless, MRI with no contrast agent seems preferable if the imaging time can be reduced.

Aim: To investigate the association of polymorphisms in the osteoprotegerin (OPG) and interleukin 1 (IL-1) genes with chronic periodontitis (CP). Material and Methods: One hundred and ninety-four individuals (97 CP patients, 97 controls) were genotyped for the OPG polymorphisms Lys3Asn and Met256Val and for the IL-1 polymorphisms IL-1A (-889C/T) and IL-1B (+3953C/T). Results: The homozygous variants coding for Lys3 were present at a higher frequency, whereas Asn3 and Met256 were present at a lower frequency in CP patients/controls (Lys3: 31%/25%, Asn3: 23%/32% and Met256: 66%/73%). Heterozygosity for Lys3Asn was observed at a higher frequency in CP patients/controls (46%/43%). Homozygosity for the Val256 genotype was observed in two CP patients (one in controls). Met256Val heterozygosity was more prevalent in CP patients/controls (32%/20%). All differences were statistically not significant between CP patients and controls. In contrast, both IL-1 polymorphisms were statistically significant. The heterozygous variant for IL-1A was present in 32% of the CP patients and in 20% of the controls (homozygosity (patients/controls) CC: 10%/21% and TT: 55%/33%). Heterozygosity for IL-1B was observed in 37% of the CP patients versus 34% in the controls (homozygosity (patients/controls) CC: 26%/57% and TT: 37%/9%). Conclusion: While the association between the IL-1 polymorphisms and CP was confirmed, no association between the OPG polymorphisms and CP could be found. [ABSTRACT FROM AUTHOR]

AIM: To determine the concentration of naturally available biologic mediators in autologous platelet concentrates and their correlation with periodontal regeneration outcomes. MATERIAL AND METHODS: In 25 patients with two intra-bony defects each, an autologous platelet concentrate (APC) was prepared by a laboratory thrombocyte apheresis technique pre-operatively. Both defects were treated using a bioresorbable guided tissue regeneration-membrane in combination with tricalciumphosphate (TCP). In the test defect, APC was additionally applied. In the APC, platelets were counted and the levels of growth factors and cytokines were determined by ELISA. Correlations between the platelet counts or the growth factor/cytokine levels and the potential clinical and radiographic regeneration outcomes due to APC were calculated after 3, 6, and 12 months. RESULTS: The APC contained 2.2 x 10(6) platelets/mul, which was 7.9 times more than in the venous blood. Transforming growth factor-beta1 (TGF-beta1), insulin-like growth factor-I (IGF-I), platelet-derived growth factor-AB (PDGF-AB), PDGF-BB, vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF) were found in the APC, whereas interleukin-1beta (IL-1beta), IL-6, tumor necrosis factor alpha (TNFalpha), IL-4, and IL-10 were not detectable. The regression analysis showed a weak correlation between the platelet counts or the growth factor levels and the clinical and radiographic regeneration outcomes (r2

The objective of teacher-training at university for political science is the development of professional competencies that enable teachers-in-training to act proficiently in all aspects of civic education. Although there are some studies that focus on civic education for teachers’ professional competencies, most of them relate to general capability and do not concern certain significant topics. Empirical results related to the definitive topics within civic education are scarce, particularly in the field of sustainable development. Questions arise regarding teacher-training where it relates to high self-efficacy and interest within the field of civic education compared to other subjects, based on the model of political competence by Detjen and colleagues. In this article, we present the results of a quasi-experimental trial with civic education teachers-in-training (N = 108). Results indicate that their self-efficacy in the field of sustainable development is low compared to other areas, although there is no significant difference in their level of interest in sustainable development compared to other topics.

Introduction: This questionnaire-based investigation aimed to assess Oral Health Behaviour (OHB) in 2-year-old children taking part in a birth cohort study and to identify relationships between general health, socioeconomic as well as psychosocial factors and OHB., Methods: Factors examined were single parent status, migration background, child's sex, parity, maternal age, education and social support, paternal employment, parental mental and physical health and child health, data for which were collected at birth, 4 weeks, or 1 year. Participants who answered all OHB questions at 2-years (n=730) were included. Nutritional score (NS), tooth brushing score (TS), and dental check-up score (CS) were used to calculate overall OHB score., Results: Overall OHB in this cohort was good. 62% ate fruit or vegetables daily, 75% brushed 2-3 times daily and 61% had already had a dental check-up. Children of single-mothers had significantly lower OHB scores. NS was significantly higher for children with migration background, children of mothers with better physical health or higher educational level, but lower for children of mothers reporting poor social support. TS was significantly lower in children of single-mothers and children of fathers reporting poorer mental health. CS was significantly higher in children of multiparous mothers. This study highlights the relevance of social support and parental health, in contributing to OHB patterns., Conclusion: Families with special healthcare needs or less robust social support may have difficulty maintaining good OHB., (The Author(s). Published by S. Karger AG, Basel.)

Objective: To investigate the accumulation of cerium-nitrate and samarium-nitrate on dentin without or with smear-layer and to test their antibacterial activity., Design: 24 dentin-enamel slices were cut from 24 extracted molars. 12 slices underwent smear-layer creation (320 grit, 200 g, 5 s), the other 12 smear-layer removal (20 % EDTA, 300 s). Slices were halved to 48 semilunar-shaped specimens. One specimen per tooth was treated with either Ce(NO 3 ) 3 (50 wt% aqueous solution; pH = 1.29; n = 6) or Sm(NO 3 ) 3 (50 wt% aqueous solution; pH = 1.88; n = 6). The other specimen served as control (A. demin). After water rinsing, elemental composition (Ce, Sm, Ca, P, O, N, Na, Mg, C) was measured (EDX; EDAX Octane-Elect, APEX v2.5, low-vacuum) in dentin. Atomic percent (At%), Ca/P- and Ca/N-ratios were calculated and analyzed non-parametrically (α = 0.05, error rates method). Additionally, antibacterial activity (2 min exposure) of Ce(NO 3 ) 3 and Sm(NO 3 ) 3 against Streptococcus mutans, Actinomyces naeslundii, Schaalia odontolytica, and Enterococcus faecalis was determined (colony forming units) after anaerobic incubation at 37 °C for 24 h (control: 0.2 % CHX)., Results: At% (median) of Ce and Sm were as follows: Ce(NO 3 ) 3 3.4 and 0.9 At%Ce with and without smear-layer, respectively; Sm(NO 3 ) 3 2.4 and 1.3 At%Sm with and without smear-layer, respectively. Ce(NO 3 ) 3 and Sm(NO 3 ) 3 -application significantly decreased Ca/P-ratios (1.22 - 1.45; p ≤ 0.02) compared to controls (1.47 - 1.63). With smear-layer, significantly higher Ca/N-ratios (5.1 - 29.3) could be detected across all groups (p ≤ 0.004) compared to specimens without smear-layer (0.37 - 0.48). Ce(NO 3 ) 3 and Sm(NO 3 ) 3 showed reduction rates of up to ≥ 5 log10 steps for S. mutans, A. naeslundii, and S. odontolytica., Conclusions: Cerium and samarium nitrate showed accumulation on dentin and certain antibacterial activity and could therefore be identified as potential compounds to treat and prevent dentin and root caries and dentin hypersensitivity., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: The aim of this study was to analyze the precipitation of Cerium(III)nitrate hexahydrate [Ce(NO 3 ) 3 ] or Samarium(III)nitrate hexahydrate [Sm(NO 3 ) 3 ] solutions on human enamel with and without a salivary pellicle. Investigated parameters were At%Ce and At%Sm measured using energy dispersive x-ray spectroscopy (EDX) after test solution (two concentrations) application., Materials and Methods: Precipitation of Ce(NO 3 ) 3 and Sm(NO 3 ) 3 solutions was examined on human enamel with and without a salivary pellicle. 6 enamel specimens each were obtained from 12 freshly extracted human third molars. These specimens were ground flat and polished. A salivary pellicle was created on 3 of the 6 specimens per tooth by storing the samples in human saliva. Subsequently, an aqueous solution of Ce(NO 3 ) 3 was applied to 2 of the 6 specimens (one with, one without salivary pellicle) for 60 s. The same was carried out with an aqueous solution of Sm(NO 3 ) 3 on 2 further specimens. The remaining 2 specimens from each tooth were treated with demineralized water (negative control). Ce(NO 3 ) 3 and Sm(NO 3 ) 3 solutions were applied at 25 or 50 wt% (aqueous solutions). The test materials and concentrations were distributed using a randomization table. After 60 s exposure and rinsing with demineralized water, the elemental composition (Ce, Sm, Ca, P, O, N, Na, Mg) of the enamel surface was analyzed by EDX. Atomic percentages (At%), differences (ΔAt%) and calcium/phosphorous-ratios (Ca/P-ratios) were calculated and analyzed non-parametrically ( α  = 0.05)., Results: 2.0-2.3 At%Ce (median) was detected on Ce(NO 3 ) 3 -treated enamel and 0.4-0.7 At% Sm (median) was detected on Sm(NO 3 ) 3 -treated enamel. Ce was only detected on the surfaces after application of Ce(NO 3 ) 3 , Sm only after application of Sm(NO 3 ) 3 . The Ca/P-ratio was significantly lower (1.37-1.59; p  = 0.028) after the application of 25% and 50%Ce(NO 3 ) 3 as well as 50%Sm(NO 3 ) 3 compared to the control treatment (demineralized water; 1.61-1.63). After treatment with Ce(NO 3 ) 3 , At%Ca and At%Na were significantly lower ( p  ≤ 0.043) compared to treatment with Sm(NO 3 ) 3 . No significant differences were found between specimens treated with 25% or 50% lanthanide nitrate solution. Presence of a salivary pellicle had no significant influence on the measured At% with the exception of specimens treated with 50% Sm(NO 3 ) 3 with increased At%Sm ( p  ≤ 0.046)., Conclusions: Ce(NO 3 ) 3 and Sm(NO 3 ) 3 precipitate on human enamel independently of the presence of a salivary pellicle., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. KJS declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Kopp, Hiller, Cieplik, Pfitzner, Pielnhofer, Höfler, Dolle, Lennon, Bauer, Buchalla and Scholz.)

Since the molecular mechanisms behind adaptation and the bacterial stress response toward antimicrobial photodynamic therapy (aPDT) are not entirely clear yet, the aim of the present study was to investigate the transcriptomic stress response in Escherichia coli after sublethal treatment with aPDT using RNA sequencing (RNA-Seq). Planktonic cultures of stationary phase E. coli were treated with aPDT using a sublethal dose of the photosensitizer SAPYR. After treatment, RNA was extracted, and RNA-Seq was performed on the Illumina NextSeq 500. Differentially expressed genes were analyzed and validated by qRT-PCR. Furthermore, expression of specific stress response proteins was investigated using Western blot analysis.The analysis of the differential gene expression following pathway enrichment analysis revealed a considerable number of genes and pathways significantly up- or down-regulated in E. coli after sublethal treatment with aPDT. Expression of 1018 genes was up-regulated and of 648 genes was down-regulated after sublethal treatment with aPDT as compared to irradiated controls. Analysis of differentially expressed genes and significantly de-regulated pathways showed regulation of genes involved in oxidative stress response and bacterial membrane damage. In conclusion, the results show a transcriptomic stress response in E. coli upon exposure to aPDT using SAPYR and give an insight into potential molecular mechanisms that may result in development of adaptation., (© 2024. The Author(s).)

Introduction: Chlorhexidine (CHX) is a commonly used antiseptic in situations of limited oral hygiene ability such as after periodontal surgery. However, CHX is also considered as a possible factor in the emergence of cross-resistance to antibiotics. The aim of this study was to analyze the changes in the oral microbiota and the prevalence of antimicrobial resistance genes (ARGs) due to CHX treatment., Materials and Methods: We analyzed the oral metagenome of 20 patients who applied a 0.2% CHX mouthwash twice daily for 4 weeks following periodontal surgical procedures. Saliva and supragingival plaque samples were examined before, directly after 4 weeks, and another 4 weeks after discontinuing the CHX treatment., Results: Alpha-diversity decreased significantly with CHX use. The Bray-Curtis dissimilarity increased in both sample sites and mainly streptococci showed a higher relative abundance after CHX treatment. Although no significant changes of ARGs could be detected, an increase in prevalence was found for genes that encode for tetracycline efflux pumps., Conclusion: CHX treatment appears to promote a caries-associated bacterial community and the emergence of tetracycline resistance genes. Future research should focus on CHX-related changes in the microbial community and whether the discovered tetracycline resistance genes promote resistance to CHX., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Bartsch, Kohnert, Kreutz, Woelber, Anderson, Burkhardt, Hellwig, Buchalla, Hiller, Ratka-Krueger, Cieplik and Al-Ahmad.)

Objectives: Chewing gums containing antiseptics or other antimicrobial substances may be effective in reducing plaque and gingivitis. Therefore, the aim of this randomized placebo-controlled clinical trial was to investigate the efficacy of a novel antimicrobial chewing gum containing essential oils (cinnamon, lemon, peppermint) and extracts on reduction of dental plaque and gingivitis as well as on oral health-related quality of life (OHRQoL) in adolescent orthodontic patients., Materials: 52 patients (11-22 years of age) were randomly assigned to use a test chewing gum (COVIDGUM, Clevergum) or a commercially available control chewing gum over a period of 10 days. Approximal plaque index (API), papillary bleeding index (PBI) and an OHRQoL questionnaire for children (COHIP-G19) were assessed at baseline (BL), after 10 days (10d) and 30 days (30d). In addition, oral health and oral hygiene related questions of the COHIP-G19 questionnaire were evaluated separately in subscales at each timepoint. Data were analyzed using non-parametrical statistical procedures (α = 0.05)., Results: API and PBI decreased significantly over time from BL to 10d and from BL to 30d in both groups, without significant differences between the groups. In both groups, the COHIP-G19 score, oral health subscale and oral hygiene subscale decreased significantly over time. Regarding the oral hygiene subscale, the test group showed significantly better scores at 30d (p = 0.011)., Conclusion: Both chewing gums performed similarly effective in terms of reducing plaque accumulation and gingival inflammation and improving OHRQoL., Clinical Relevance: Chewing gums without antimicrobial ingredients may be sufficient to decrease plaque accumulation and gingival inflammation., (© 2024. The Author(s).)

Red-fluorescing dentine indicates bacterial contamination [Caries Res 2002; 36: 315-319]. We investigated effect of removal of red fluorescent dentine caries on shear bond strength and fracture mode of 4 adhesive approaches. Sixty-five carious teeth and 50 noncarious controls were distributed into 4 groups: Clearfil™ self-etch (CSE), OptiBond™ FL total etch (OTE), Scotchbond™ Universal total etch (STE) and self-etch (SSE). Samples were excited at 405 nm and viewed through 530 nm filter. Carious samples were ground flat exposing strongly red-fluorescing (StrongRF) dentine, on which a composite cylinder was placed, using one of 4 adhesives. After 22 h in water, shear bond strength and fracture mode were analysed. StrongRF was removed; composite cylinders were placed on weakly red-fluorescing (WeakRF) dentine and tested as described above. Finally, red-fluorescing dentine was removed, and composite cylinders were placed on non-fluorescing (NonRF) dentine and tested. Composites were placed at 3 corresponding heights in controls. After 22 h in water, shear bond strength testing and fracture mode analysis were performed. Differences were tested using Mann-Whitney or Wilcoxon tests (p ≤0.05). Median (Q1, Q3) shear bond strength on StrongRF was SSE 14.4 (9.2, 18.2) MPa >CSE 10.2 (6.4, 17.3) MPa >STE 9.1 (6.9, 11.2) MPa >OTE 6.8 (4.0, 10.8) MPa. Shear bond strength increased statistically significantly for all adhesives on WeakRF: SSE 19.8 (13.6, 24.3) MPa >STE 19.5 (12.7, 23.1) MPa >CSE 17.5 (12.0, 22.5) MPa >OTE 15.8 (11.9, 20.9) MPa. Only STE 25.6 (22.4, 29.1) MPa and CSE 22.1 (17.6, 24.6) MPa were significantly different on NonRF compared to WeakRF. For controls tested at corresponding depths, superficial shear bond strength was OTE 18.7 (16.0, 22.1) MPa >STE 18.4 (12.0, 25.9) MPa >CSE 18.1 (12.7, 20.7) MPa >SSE 13.0 (9.6, 17.8) MPa. This was significantly higher compared to StrongRF except for SSE. Central shear bond strength was not significantly different to WeakRF, deep shear bond strength was significantly lower for SSE and CSE but higher for OTE compared to carious. Conclusion: StrongRF dentine should be removed for higher shear bond strength, but WeakRF dentine can often be preserved without compromising adhesive bond strength., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

The widespread occurrence of multi-resistant bacteria is a health problem of global dimension. Infections caused by multi-resistant pathogens are difficult to treat and often associated with high mortality. Therefore, new treatment strategies are of interest, such as the use of differently acting antibacterial concepts. One of these new concepts is the use of antiseptics in combination with the antibacterial photodynamic therapy (aPDT). Currently, no method has yet been established as a standard procedure for investigating combined effects and evaluating them in a generally valid and unambiguous manner. The focus of this study was on how cationic antiseptics benzalkonium chloride (BAC) and chlorhexidine digluconate (CHX) behave in a combined application with aPDT using the photosensitizer TMPyP. For this purpose, BAC and CHX were applied in combination with the aPDT using TMPyP in non-lethal concentrations to the three bacteria Escherichia coli, Staphylococcus aureus, and Enterococcus faecalis. The results of the combination experiments with sublethal concentrations of BAC or CHX with the aPDT showed that the binary application had a lethal effect. Irrespective of the bacteria, the reduction in concentrations in OPECC, compared to individual concentrations, was more than 50% for TMPyP, 23-40% for BAC, and 18-43% for CHX. Furthermore, the optimal effective concentration combinations (OPECCs) could be determined. The latter showed that the combined application allowed the reduction of both concentrations compared to the single application., (© 2023. The Author(s).)

Purpose: This follow-up of a randomized clinical split-mouth study aimed to investigate the influence of selective enamel etching on the long-term clinical performance of partial ceramic crowns (PCCs) luted with a self-adhesive resin cement., Materials and Methods: 43 patients received two PCCs (Vita Mark II; Cerec 3D) each for the restoration of extensive lesions with multiple cusp coverage, inserted with a self-adhesive resin cement (RelyX Unicem, RXU). Using a split-mouth design, one PCC received additional selective enamel etching (RXU+E) and one did not (RXU-E). Patients were clinically evaluated at baseline and after up to 15 years (median observation period 176 months) using modified USPHS and FDI criteria. The data were analyzed non-parametrically (chi-squared tests, α = 0.05). Clinical survival of all restorations after 15 years was evaluated using the Kaplan-Meier analysis., Results: After 15 years, 19 patients were available for clinical assessment (recall rate: 56%). Kaplan-Meier analysis showed a cumulative survival of 78.1% for RXU+E and of 42.9% for RXU-E, indicating a significantly higher survival rate for RXU+E (p = 0.004). Regarding the clinical performance of PCCs available for the 15-year evaluation, no statistically significant differences were found between RXU+E and RXU-E using modified USPHS and FDI criteria. Both groups revealed significant deterioration over time regarding surface luster, marginal adaptation, and marginal discoloration. RXU+E resulted in significantly inferior anatomic form over time and a significant improvement in post-operative hypersensitivity compared to baseline., Conclusion: For posterior PCCs, selective enamel etching can be recommended based on higher survival rates after 15 years. Clinically, deterioration due to aging is similar in both groups.

Objectives: Examination of patients claiming adverse effects from dental materials can be very challenging. Particularly, systemic aspects must be considered besides dental and orofacial diseases and allergies. Therefore, the aim of this study was to investigate a cohort of 687 patients reporting on adverse effects from dental materials focusing on findings related to known general diseases or conditions or medication-related findings with relevance to their subjective complaints., Methods: Six hundred eighty-seven patients visiting a specialized consultation on claimed adverse effects from dental materials were retrospectively investigated for their subjective complaints, findings related to known general diseases or conditions, medication-related findings, dental and orofacial findings, or allergies with relevance to their subjective complaints., Results: The most frequent subjective complaints were burning mouth (44.1%), taste disorders (28.5%), and dry mouth (23.7%). In 58.4% of the patients, dental and orofacial findings relevant to their complaints could be found. Findings related to known general diseases or conditions or medication-related findings were found in 28.7% or 21.0% of the patients, respectively. Regarding medications, findings related to antihypertensives (10.0%) and psychotropic drugs (5.7%) were found most frequently. Relevant diagnosed allergies toward dental materials were found in 11.9%, hyposalivation in 9.6% of the patients. In 15.1% of the patients, no objectifiable causes for the expressed complaints could be found., Conclusions: For patients complaining of adverse effects from dental materials, findings related to known general diseases or conditions and medications should be given particular consideration, while still in some patients, no objectifiable causes for their complaints can be found., Clinical Relevance: For patients complaining about adverse effects from dental materials, specialized consultations and close collaboration with experts from other medical fields are eligible., (© 2023. The Author(s).)

Soon after the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, preprocedural mouthwashes were recommended for temporarily reducing intraoral viral load and infectivity of individuals potentially infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in order to protect medical personnel. Particularly, the antiseptic cetylpyridinium chloride (CPC) has shown virucidal effects against SARS-CoV-2 in vitro. Therefore, the aim of this randomized controlled clinical trial was to investigate the efficacy of a commercially available mouthwash containing CPC and chlorhexidine digluconate (CHX) at 0.05% each in SARS-CoV-2-positive patients as compared to a placebo mouthwash. Sixty-one patients who tested positive for SARS-CoV-2 with onset of symptoms within the last 72 h were included in this study. Oropharyngeal specimens were taken at baseline, whereupon patients had to gargle mouth and throat with 20 mL test or placebo (0.9% NaCl) mouthwash for 60 s. After 30 min, further oropharyngeal specimens were collected. Viral load was analyzed by quantitative reverse transcriptase polymerase chain reaction, and infectivity of oropharyngeal specimens was analyzed by virus rescue in cell culture and quantified via determination of tissue culture infectious doses 50% (TCID 50 ). Data were analyzed nonparametrically (α = 0.05). Viral load slightly but significantly decreased upon gargling in the test group ( P = 0.0435) but not in the placebo group. Viral infectivity as measured by TCID 50 also significantly decreased in the test group ( P = 0.0313), whereas there was no significant effect but a trend in the placebo group. Furthermore, it was found that the specimens from patients with a vaccine booster exhibited significantly lower infectivity at baseline as compared to those without vaccine booster ( P = 0.0231). This study indicates that a preprocedural mouthwash containing CPC and CHX could slightly but significantly reduce the viral load and infectivity in SARS-CoV-2-positive patients. Further studies are needed to corroborate these results and investigate whether the observed reductions in viral load and infectivity could translate into clinically useful effects in reducing COVID-19 transmission (German Clinical Trials Register DRKS00027812).

Combination therapies appear to be beneficial for preventing bacterial resistance to antibacterial approaches. The aim of this study was to define and determine an optimal effective concentration combination (OPECC) for binary application of antibacterial compounds. The antiseptics chlorhexidine (CHX), benzalkonium chloride (BAC), and cetylpyridinium chloride (CPC), as well as the antibiotic ciprofloxacin (CIP), were tested against planktonic Escherichia coli in binary combinations by applying a checkerboard assay, and then evaluated according to the established synergism principles. Extending the checkerboard method, the optical density (OD) of the wells was measured photometrically. On the borderline between effective (OD = 0) and non-effective (OD > 0) eradication of the bacterial cultures, the OPECC was determined. Binary combinations of CPC or CHX with BAC were assessed as either synergistic or indifferent, respectively, while there was no OPECC to calculate. For all other binary combinations, an OPECC was derivable, and these were assessed as either synergistic or indifferent. In conclusion, the evaluation of the binary combination application of antibacterial compounds based on the checkerboard method was refined to such an extent that it was possible to determine at least one concentration pair that could be defined and considered as an OPECC, independently of the evaluation of the system according to the different synergy principles. In general, the method presented herein for determining an OPECC can be applied to any conceivable method or system aimed at the eradication of a pathogen.

Teeth with different chemical compositions can show vastly different physical properties, so knowledge of elemental composition is required to use animal teeth as substitutes for human teeth in research. In vitro, energy dispersive X-ray spectroscopy (EDX), improved by calibration standards and Si 3 N 4 -window material, enables determining local elemental compositions of inorganic and organic compounds without sample destruction. Six human molars, bovine incisors, murine incisors, and murine molars were analyzed. EDX-field scans and line scans were analyzed for elements Ca, P, O, C, N, F, Na, Mg, Fe, Cl, and S. Furthermore, Ca/P- and Ca/N-Ratios were calculated. The presence of iron in murine incisor enamel was investigated using additional wavelength dispersive X-ray spectroscopy measurements (WDX) near the enamel surface. Bovine and human enamel and dentin revealed close similarities regarding elemental composition. The median (25-75% percentiles) of At%Ca was 21.1 (20.8-21.3) in human enamel, 21.0 (20.7-21.2) in bovine enamel, and in murine enamel, 18.3 (17.85-18.88) for molars and 18.35 (18.00-18.75) for incisors. In dentin, murine teeth revealed a higher At%Ca compared to human and bovine teeth. Significant differences between human and bovine teeth were found for nitrogen in dentin, with a median of 4.5 (3.3-5) At%N for human dentin and 2.7 (2.3-3.2) At%N for bovine dentin. The Ca/P-Ratio was the highest in human and bovine enamel, which did not differ significantly. Enamel from murine molars had a higher Ca/P-Ratio than murine incisors and the highest Ca/P-Ratio in dentin was observed for human teeth and murine molars (1.49). WDX revealed iron in the outer 10 µm of pre- and post-eruptive enamel of murine incisors. Pre- and post-eruptive enamel on murine incisors only differed significantly in At%Ca ( p = 0.041) and At%P ( p = 0.026) with both At% higher in the pre-eruptive enamel. Murine teeth differ significantly from human and bovine teeth in terms of the elemental composition of enamel and dentin.

The objective of this study was to compare the ability of different endodontic irrigation activation methods to enable irrigant penetration, remove the smear layer from root canal walls after preparation, and investigate surface effects on dentine. Root canals of 90 single-rooted teeth were prepared and irrigated with EDTA (17%) and sodium hypochlorite (5%), where both irrigants or sodium hypochlorite only were activated as follows: conventional needle irrigation, ultrasonic activation, sonic activation (EDDY), or laser-based activation (photon-induced photoacoustic streaming/PIPS). For the evaluation of irrigant penetration into dentinal tubules, methylene blue was injected and activated as well. Subsequently, teeth were sectioned horizontally, and dye penetration depths were measured. Alternating sections were split in halves and randomly selected for scanning electron microscopic analysis. Root canal dentine was assessed for smear layer removal and surface disintegration according to a defined scoring system. The data were analyzed statistically with nonparametric and chi-squared tests for whole teeth and separately for coronal, middle, and apical thirds. All the tested activation methods removed a thicker smear layer than needle irrigation only. Additional activation of EDTA improved penetration depths of the irrigants, but not the smear layer removal. Surface disintegration of root canal dentine was observed with the additional activation of EDTA and particularly after laser-based techniques. Additional activation of EDTA does not seem to offer any convincing advantages in terms of irrigant penetration or smear layer removal but disrupts the dentine surface. Especially laser-based activation resulted in undesirable destruction of root canal wall dentine.

Objectives: Relapse after orthognathic surgery seems to depend on diverse factors. Proffit et al. postulated in 2007 a "hierarchy of stability" (Head Face Med 6:66, 2007), ranking posttreatment stability after various orthognathic procedures, but no systematically reviewed evidence was provided. Therefore, the aim of this review was to investigate the extent of class II relapse in orthognathic surgery of Angle class II patients depending on the surgical procedure used., Materials and Methods: Seven databases were searched for randomized and controlled clinical trials to compare relapse in surgical procedures for Angle class II patients. After duplicate study selection, data extraction and risk of bias assessment were performed with the ROBINS-I tool as well as data synthesis by frequency distribution, followed by assessment of the quality of evidence with GRADE., Results: Four non-randomized cohort-studies with a total of 132 patients were included. Bimaxillary procedures as well mandibular advancement procedures proved to be highly stable. Single jaw interventions at the maxilla achieved mostly stable results at sagittal dimension and problematic stability in the vertical dimension. However, there were only limited data available with low quality of evidence., Conclusions: Limited existing evidence of low quality partly support the postulated hierarchy of stability of Proffit et al. (Head Face Med 6:66, 2007) and indicates that a surgical correction of class II dysgnathia with bimaxillary procedures and mandibular advancement seems to be highly stable. However, additional studies are needed to address the relation between relapse and surgical orthognathic intervention. Trial registration PROSPERO 2019 CRD42019144873., (© 2022. The Author(s).)

The accumulation of caries-preventive compounds on sound enamel is crucial in order to improve the inhibition of carious lesion initiation. The aim of this research was to investigate the initial accumulation of cerium, oligopeptide p11-4, and fluoride from NaF or amine fluoride (AmF) on sound enamel in vitro by means of energy dispersive X-ray spectroscopy (EDX). Polished bovine enamel specimens (n = 120 from 60 teeth) were fabricated. Out of these, 12 specimens each were treated with CeCl3 (cerium(III) chloride heptahydrate 25%), oligopeptide p11-4 (Curodont Repair, Credentis), NaF (10,000 ppm F−), AmF (amine fluoride, Elmex Fluid, CP-GABA GmbH, 10,000 ppm F−), or Aqua demin (control). After rinsing with water, the surface elemental composition (Ce, N, F, Ca, P, O, Na, Mg) was measured (EDX; EDAX Octane Elect detector, APEX v2.0), expressed in atomic percent (At%) and analyzed (non-parametric statistics, α = 0.05, error rates method). Another 12 specimens per treatment group were fabricated and used for analyzing accumulation in cross-sections with EDX linescans and two-dimensional EDX-mappings. The surface median atomic percent of cerium (At%Ce) was 0.8 for CeCl3, but no Ce was found for any other group. N, specifically for oligopeptide p11-4, could not be detected. Fluorine could only be detected on fluoridated surfaces. The median atomic percent of fluorine (At%F) was 15.2 for NaF and 17.0 for AmF. The Ca/P ratio increased significantly compared to the control following the application of NaF and AmF (p < 0.001), but decreased significantly for CeCl3 (p < 0.001). In cross-sectioned specimens of the CeCl3-group, 12.5% of the linescans revealed cerium at the enamel surface, whereas 83.3% of the NaF linescans and 95.8% of the AmF linescans revealed fluorine at the enamel surface. Following the application of oligopeptide p11-4, no traces of N were detectable. In the depth of the samples, no signal was detected for any of the corresponding elements exceeding the background noise. Cerium and fluorine (from both NaF and AmF), but not the oligopeptide p11-4, precipitated on sound enamel.

Objectives: This randomized prospective split-mouth study evaluated the clinical performance of a novel, tooth-colored, self-adhesive bulk-fill restorative (SABF, 3M) for restoration of class II cavities as compared to a conventional bulk-fill composite (Filtek One, 3M; FOBF) over 36 months. The null-hypothesis was that both materials perform equally regarding clinical success and performance according to the FDI clinical criteria and scoring system., Methods: 30 patients received one SABF and one FOBF restoration each. For FOBF, Scotchbond Universal (3M) was used as adhesive (self-etch mode), whereas SABF was applied without adhesive. Two blinded examiners evaluated the restorations at baseline, 24 and 36 months using FDI criteria. Data were analyzed non-parametrically (χ 2 -tests; α=0.05)., Results: 29 patients were available for the 24- and 36-month examinations. Clinical success rate was 96.6% for both materials at 36-mo (one restoration failure due to secondary caries each). All other restorations revealed clinically acceptable FDI scores at all recalls. FOBF performed significantly better than SABF at all time points regarding surface lustre (p<0.001) and color match and translucency (p<0.001) and regarding marginal staining at 36-months (p=0.008). Marginal staining and marginal adaptation deteriorated significantly over time for both materials (both p<0.001)., Conclusions: The null-hypothesis could only partially be rejected. Both materials performed similarly regarding clinical success and performance within 36 months of clinical service, but SABF exhibited significantly inferior, but clinically fully acceptable esthetic properties as compared to FOBF. Both restorative materials showed clinically fully acceptable results over 36 months of clinical service and thus may be recommended for clinical use., Clinical Significance: The novel tooth-colored self-adhesive bulk-fill restorative exhibited clinically fully acceptable results over 36 months of clinical service, similarly to a conventional bulk-fill restorative used with a universal adhesive, but with slight shortcomings in esthetic properties. Therefore, both restorative materials may be recommended for clinical use., Competing Interests: Declaration of Competing Interest All authors declare that they have no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aim: The aim of the study was to investigate the influence of cavity cleaning and conditioning on marginal integrity of directly placed post-endodontic composite class-I-restorations in vitro., Methodology: A total of 168 fully intact teeth without caries or fillings received pre-endodontic composite restorations (class-II) after their extraction. Occlusal endodontic access-cavities were prepared, and root canals were instrumented and filled with gutta-percha and an epoxy resin-based sealer. Prior to post-endodontic class-I-restoration, access cavities were completely contaminated with sealer, cleaned with alcohol and pre-treated as follows: cleaner only (alcohol), glycine-polishing, Al 2 O 3 sandblasting, carbide bur (immediate as well as delayed restoration). A positive control (not contaminated with sealer and adhesive used) and negative control (cleaner used but no adhesive) were established. Half of the teeth from each group were subjected to thermocycling and mechanical loading (TCML). Marginal integrity of post-endodontic restoration was evaluated in oro-vestibular or mesio-distal sections after AgNO 3 dye penetration (DP) by standardized photomacroscopic imaging and expressed in per cent of margin length along all segments and separately for enamel, dentine and composite, respectively. Results were analysed non-parametrically (α = .05)., Results: No restorations or teeth fractured or debonded completely. Without TCML, the median DP of all segments was significantly higher for the negative control compared with all other groups in oro-vestibular cutting direction (53%; p = .002) and in mesio-distal cutting direction (51%; p ≤ .041). The other groups without TCML revealed 16%-24% DP (oro-vestibular) and 12%-24% DP (mesio-distal). With TCML, the median DP in oro-vestibular cutting direction for all segments ranged between 48% and 62% for all groups, a significant difference was only observed between glycine-polishing and carbide bur (p = .041). In mesio-distal cutting direction, the median DP in negative control was 69% with TCML and significantly higher compared with all other groups (p = .002). For all other groups, the median DP of all segments ranged between 28% and 40% with TCML without significant differences. Error rates method (k = 7) revealed a significant influence of TCML in general on penetration of all segments in both oro-vestibular and mesio-distal cutting directions., Conclusion: Additional access cavity pre-treatment after alcohol cleaning did not improve the marginal integrity of post-endodontic composite restorations. Thorough cleaning of the access cavity with alcohol seems to assure an acceptable marginal integrity to the tooth and restorative composite., (© 2022 The Authors. International Endodontic Journal published by John Wiley & Sons Ltd on behalf of British Endodontic Society.)

Antiseptics are widely used in dental practice and included in numerous over-the-counter oral care products. However, the effects of routine antiseptic use on microbial composition of oral biofilms and on the emergence of resistant phenotypes remain unclear. Microcosm biofilms were inoculated from saliva samples of four donors and cultured in the Amsterdam Active Attachment biofilm model for 3 days. Then, they were treated two times daily with chlorhexidine digluconate (CHX) or cetylpyridinium chloride (CPC) for a period of 7 days. Ecological changes upon these multiple antiseptic treatments were evaluated by semiconductor-based sequencing of bacterial 16S rRNA genes and identification of amplicon sequence variants (ASVs). Furthermore, culture-based approaches were used for colony-forming units (CFU) assay, identification of antiseptic-resistant phenotypes using an agar dilution method, and evaluation of their antibiotic susceptibilities. Both CHX and CPC showed only slight effects on CFU and could not inhibit biofilm growth despite the two times daily treatment for 7 days. Both antiseptics showed significant ecological effects on the microbial compositions of the surviving microbiota, whereby CHX led to enrichment of rather caries-associated saccharolytic taxa and CPC led to enrichment of rather gingivitis-associated proteolytic taxa. Antiseptic-resistant phenotypes were isolated on antiseptic-containing agar plates, which also exhibited phenotypic resistance to various antibiotics. Our results highlight the need for further research into potential detrimental effects of antiseptics on the microbial composition of oral biofilms and on the spread of antimicrobial resistance in the context of their frequent use in oral healthcare., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mao, Hiergeist, Auer, Scholz, Muehler, Hiller, Maisch, Buchalla, Hellwig, Gessner, Al-Ahmad and Cieplik.)

The need for dental rehabilitations under general anesthesia (DRGAs) is continuously increasing, particularly for dental treatment of children. The present retrospective cohort study aimed to investigate potential risk factors for repeated need of DRGA in a cohort of patients from a private pediatric dental practice. Demographic and anamnestic data, dental status, and treatments performed during DRGA were retrospectively analyzed from the electronic dental charts of 1155 children that received at least one DRGA between October 2016 and December 2021. The median age of all children was 5 years at time of their first DRGA. The rate of repeated DRGAs was 9%. Patients with repeated need of DRGA were significantly younger at time of their first DRGA and revealed significantly more often a history of preterm birth and current use of a baby bottle as compared to patients with only one DRGA. There were significantly fewer treatments (regardless of type) in the second DRGA than at the first. Within the limitations of this study, young age at first DRGA, a history of preterm birth, and current use of a baby bottle may be risk factors for repeated need of DRGA. The search for effective strategies to minimize the repeated need for DRGA in children remains critical.

Despite the wide-spread use of antiseptics in dental practice and oral care products, there is little public awareness of potential risks associated with antiseptic resistance and potentially concomitant cross-resistance. Therefore, the aim of this study was to investigate potential phenotypic adaptation in 177 clinical isolates of early colonizers of dental plaque ( Streptococcus , Actinomyces , Rothia and Veillonella spp.) upon repeated exposure to subinhibitory concentrations of chlorhexidine digluconate (CHX) or cetylpyridinium chloride (CPC) over 10 passages using a modified microdilution method. Stability of phenotypic adaptation was re-evaluated after culture in antiseptic-free nutrient broth for 24 or 72 h. Strains showing 8-fold minimal inhibitory concentration (MIC)-increase were further examined regarding their biofilm formation capacity, phenotypic antibiotic resistance and presence of antibiotic resistance genes (ARGs). Eight-fold MIC-increases to CHX were detected in four Streptococcus isolates. These strains mostly exhibited significantly increased biofilm formation capacity compared to their respective wild-type strains. Phenotypic antibiotic resistance was detected to tetracycline and erythromycin, consistent with the detected ARGs. In conclusion, this study shows that clinical isolates of early colonizers of dental plaque can phenotypically adapt toward antiseptics such as CHX upon repeated exposure. The underlying mechanisms at genomic and transcriptomic levels need to be investigated in future studies.

Objective: Dental pulp cells interact with immunogenic components such as LPS (lipopolysaccharide) or LTA (lipoteichoic acid) released from microorganisms in carious lesions. In the present investigation, the formation of the pro-inflammatory cytokines TNFα and IL-6 in LPS- or LTA-stimulated cells from the dental pulp interface and pulp fibroblasts was analyzed in the presence of the resin monomer 2-hydroxyethyl methacrylate (HEMA) under varying cellular redox conditions., Method: Human pulp fibroblasts (HPC) or cells from the dental pulp interface expressing an odontoblast phenotype (hOD-1) were exposed to LTA, LPS or HEMA for 1 h or 24 h. Redox homeostasis was modified by the prooxidant BSO (L-buthionine sulfoximine) or the antioxidant NAC (N-acetyl cysteine). Formation of TNFα or IL-6 was analyzed by ELISA, and cell survival was determined by a crystal violet assay. Statistical analyses were performed using the Mann-Whitney-U-test., Results: Secretion of TNFα was not detected in LPS- or LTA-stimulated HPC or hOD-1, and IL-6 was not found after a short exposure (1 h). After a 24 h exposure, LPS induced a 3-fold increase in IL-6 formation in HPC, while LTA stimulated IL-6 release about 20-fold. Likewise, LTA was more effective than LPS in hOD-1 stimulating IL-6 levels about 50-fold. HEMA inhibited the LPS- and LTA-induced IL-6 release, and this effect was enhanced by BSO but counteracted by NAC in both cell types. IL-6 release was independent of cell survival rates., Conclusions: The protective immune response in odontoblasts and pulp fibroblasts is impaired by monomers such as HEMA through the disturbance of the redox homeostasis., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Statement of Problem: Zirconia frameworks luted on titanium bases have been increasingly used for implant-supported prostheses. A reliable bond strength between the framework and the base is a key factor for clinical success. Autoclaving of the abutments before clinical use has been strongly suggested since abutments have been classified as class II medical devices. However, comprehensive knowledge on the susceptibility of the composite resin luting agents' adhesion to autoclave sterilization is lacking., Purpose: The purpose of this in vitro study was to assess the bond strength between zirconia frameworks and titanium bases using different composite resin luting agents with and without thermocycling and autoclaving., Material and Methods: A total of 200 titanium implants were copy milled and 200 zirconia frameworks (Cercon) were generated by computer-aided design and computer-aided manufacturing (CAD-CAM). They were adhesively luted using Multilink Hybrid Abutment (MHA), Panavia F2.0 (PF2), Panavia V5 (PV5), RelyX Ultimate (RXU), or Panavia SA Cement Plus (PSA). Autoclaving (134 °C, 0.21 MPa, 5.5 minutes) and thermocycling (3000 cycles, 5 °C and 55 °C) were performed. The push out bond strength was tested at a crosshead speed of 1 mm/min. Statistical analysis was performed by using the Mann-Whitney U test (α=.05) and the family-wise error rate method., Results: Median bond strength values (interquartile range) after autoclaving and thermocycling ranged between 33.7 (26.7-41.8) MPa for MHA and 7.6 (7.3-8.5) MPa for PF2. MHA showed significantly higher values than all other composite resin luting agents regardless of thermocycling or autoclaving. PV5 showed equal or higher bond strength values than PSA, RXU, and PF2. Autoclaving had no significant influence on MHA or PV5, but had a negative effect on PSA and RXU. The family-wise error rate method showed that both the composite resin luting agent and autoclave sterilization had an overall influence on bond strength., Conclusions: MHA and PV5 were not significantly influenced by autoclaving and showed acceptable bond strength values. Because MHA showed significantly higher bond strength than all other materials and is released for autoclaving by the manufacturer, it is the first choice for extraoral bonding of zirconia frameworks to titanium bases. Manufacturers who state the indication of extraoral cementation of frameworks on titanium bases should also indicate whether their composite luting material is affected by autoclaving., (Copyright © 2022 Editorial Council for The Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Despite the widespread use of antiseptics such as chlorhexidine digluconate (CHX) in dental practice and oral care, the risks of potential resistance toward these antimicrobial compounds in oral bacteria have only been highlighted very recently. Since the molecular mechanisms behind antiseptic resistance or adaptation are not entirely clear and the bacterial stress response has not been investigated systematically so far, the aim of the present study was to investigate the transcriptomic stress response in Streptococcus mutans after treatment with CHX using RNA sequencing (RNA-seq). Planktonic cultures of stationary-phase S. mutans were treated with a sublethal dose of CHX (125 µg/mL) for 5 min. After treatment, RNA was extracted, and RNA-seq was performed on an Illumina NextSeq 500. Differentially expressed genes were analyzed and validated by qRT-PCR. Analysis of differential gene expression following pathway analysis revealed a considerable number of genes and pathways significantly up- or downregulated in S. mutans after sublethal treatment with CHX. In summary, the expression of 404 genes was upregulated, and that of 271 genes was downregulated after sublethal CHX treatment. Analysis of differentially expressed genes and significantly regulated pathways showed regulation of genes involved in purine nucleotide synthesis, biofilm formation, transport systems and stress responses. In conclusion, the results show a transcriptomic stress response in S. mutans upon exposure to CHX and offer insight into potential mechanisms that may result in development of resistances.

The influence of patient-specific factors such as medical conditions, low-density lipoprotein cholesterol (LDL-C) or levels of 25-hydroxyvitamin D (25OHD) on periodontal diseases is frequently discussed in the literature. Therefore, the aim of this retrospective cross-sectional study was to evaluate potential associations between radiographic bone loss (RBL) and patient-specific risk factors, particularly LDL-C and 25OHD levels. Patients from a dental practice, who received full-mouth cone beam CTs (CBCTs) and blood-sampling in the course of implant treatment planning, were included in this study. RBL was determined at six sites per tooth from CBCT data. LDL-C and 25OHD levels were measured from venous blood samples. Other patient-specific risk factors were assessed based on anamnesis and dental charts. Statistical analysis was performed applying non-parametric procedures (Mann-Whitney U tests, error rates method). Data from 163 patients could be included in the analysis. RBL was significantly higher in male patients, older age groups, smokers, patients with high DMFT (decayed/missing/filled teeth) score, lower number of teeth, and high LDL-C levels (≥160 mg/dL). Furthermore, patients with high 25OHD levels (≥40 ng/mL) exhibited significantly less RBL. In summary, RBL was found to be associated with known patient-specific markers, particularly with age and high LDL-C levels.

The worldwide threat of antibiotic resistance requires alternative strategies to fight bacterial infections. A promising approach to support conventional antibiotic therapy is the antimicrobial photodynamic inactivation (aPDI). The aim of this work was to show further insights into the antimicrobial photodynamic principle using two photosensitizers (PS) of different chemical classes, Methylene Blue (MB) and TMPyP, and the organisms Escherichia coli and Staphylococcus aureus as Gram-negative and Gram-positive representatives. Planktonic cultures of both species were cultured under aerobic conditions for 24 h followed by treatment with MB or TMPyP at various concentrations for an incubation period of 10 min and subsequent irradiation for 10 min. Ability to replicate was evaluated by CFU assay. Accumulation of PS was measured using a spectrophotometer. The cytoplasmic membrane integrity was investigated by flow cytometry using SYBR Green and propidium iodide. In experiments on the replication ability of bacteria after photodynamic treatment with TMPyP or MB, a killing rate of 5 log 10 steps of the bacteria was achieved. Concentration-dependent accumulation of both PS was shown by spectrophotometric measurements whereby a higher accumulation of TMPyP and less accumulation of MB was found for S. aureus as compared to E. coli. For the first time, a membrane-damaging effect of TMPyP and MB in both bacterial strains could be shown using flow cytometry analyses. Furthermore, we found that reduction of the replication ability occurs with lower concentrations than needed for membrane damage upon MB suggesting that membrane damage is not the only mechanism of aPDI using MB., (© 2022. The Author(s).)

Cell homing for dental pulp tissue engineering has been advocated as a feasible approach to regenerate dental pulp in a clinical setting. In order to develop a translational protocol for clinical application, we wanted to determine the effects of disinfectants on the availability of growth factors from the root canal, the amount that can be obtained in this context, and whether they can be processed for use in tissue engineering procedures. The extraction of growth factors should also be confirmed in a clinical setting. Root canals were prepared in 36 extracted mature teeth, and the amount of TGF-β1 in solution was quantified after different irrigation protocols (sodium hypochlorite, chlorhexidine) and after intracanal medication (calcium hydroxide). Centrifugal filters with a cut-off of 10,000 Da and 3000 Da were used for efficient concentration, and volumes and amounts of retained TGF-β1 were measured at different time points. During conventional endodontic treatment, ethylenediaminotetraacetic acid (EDTA) solution was collected after ultrasonic activation from the root canals of mature teeth of 38 patients, and growth factor content was quantified via enzyme-linked immunosorbent assay (ELISA). Irrigation with sodium hypochlorite reduced TGF-β1 release into EDTA. This effect was partially reversed by canal enlargement after the use of sodium hypochlorite and by subsequent use of calcium hydroxide. A few minutes of centrifugation with a cut-off of 10,000 Da reduced the initial volume of the irrigant by 90% and led to a continuous increase in concentration to the same extent. Furthermore, TGF-β1 was obtained from root canals of mature teeth during endodontic treatment in quantities that have been shown to elicit desirable cellular responses in a subsequent clinical application. A mixture with a suitable scaffold material and injection into the root canal has the potential to promote dental pulp regeneration.

Objectives: In the context of the phase-down of amalgam, development of easily applicable, permanent restorative materials is of high clinical interest. Aim of this study was to evaluate the clinical performance of a novel, tooth-colored, self-adhesive bulk-fill restorative (SABF, 3M Oral Care) and a conventional bulk-fill composite (Filtek One, 3M Oral Care; FOBF) for restoring class II cavities. The null-hypothesis tested was that both materials perform similar regarding clinical performance., Materials and Methods: In this randomized split-mouth study, 30 patients received one SABF and one FOBF restoration each. Scotchbond Universal (3M Oral Care) was used as adhesive for FOBF (self-etch mode), while SABF was applied directly without adhesive. Restorations were evaluated by two blinded examiners at baseline, 6 months and 12 months employing FDI criteria. Non-parametric statistical analyses and χ 2 -tests (α = 0.05) were applied., Results: Thirty patients (60 restorations) were available for the 6- and 12-month recalls exhibiting 100% restoration survival. All restorations revealed clinically acceptable FDI scores at all time points and for all criteria. Only regarding esthetic properties, FOBF performed significantly better than SABF regarding surface lustre (A1) and color match and translucency (A3) at all time points and marginal staining (A2b) at 12 months., Conclusions: The null-hypothesis could not be rejected. Both materials performed similarly regarding clinical performance within the first year of clinical service. SABF exhibited slightly inferior, but clinically fully acceptable esthetic properties as compared to FOBF., Clinical Relevance: Within the limitations of this study, the self-adhesive bulk-fill restorative showed promising results and may be recommended for clinical use., (© 2021. The Author(s).)

Objectives To determine the clinical performance of partial ceramic crowns (PCCs) luted with a conventional resin cement combined with a universal adhesive without or with selective enamel etching or luted with a self-adhesive resin cement. Methods In a split-mouth design, each three CAD/CAM-PCCs (Vita Mark II, Cerec) were placed in 50 patients. Two PCCs were luted with a conventional resin cement (RelyX Ultimate) combined with a universal adhesive (Scotchbond Universal) without (SB-E) or with (SB+E) selective enamel etching. The third PCC was luted with a self-adhesive resin cement (RelyX Unicem 2; RXU). Chi-square tests (α≤0.05) were applied. Based on clinical failures (complete debonding or need for replacement of the restorations), Kaplan-Meier survival analysis was performed. Results 31 patients were evaluated clinically using FDI criteria at 39 months. Clinically acceptable results were detected over time, except for "fracture of material and retention" (inacceptable fractures and debondings). Within materials, statistically significant differences (p ≤ 0.003) between baseline and 39 months were found for "marginal adaptation" and "marginal staining". At 39-month, SB+E and SB-E showed significantly better results compared to RXU in "marginal adaptation"(p ≤ 0.021) and "marginal staining"(p ≤ 0.013). Kaplan-Meier analysis showed higher survival rates after 39 months for SB+E (96%) and SB-E (88%) compared to RXU (69%) with statistically significant differences between RXU vs. SB-E (p = 0.022) and RXU vs. SB+E (p ≤ 0.001). Conclusions After 39-months, PCCs luted with the self-adhesive resin cement exhibited a statistically significant inferior survival rate compared to restorations luted with the conventional resin cement combined with a universal adhesive without or with selective enamel etching. Clinical significance Currently, self-adhesive resin cements cannot be recommended for luting partial ceramic crowns. However, the standard adhesive luting procedure comprising a universal adhesive and luting composite yielded good clinical results for more than 3 years irrespectively of application of a selective enamel etching step., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Extracorporeal cardiopulmonary resuscitation (ECPR) performed at the emergency scene in out-of-hospital cardiac arrest (OHCA) can minimize low-flow time. Target temperature management (TTM) after cardiac arrest can improve neurological outcome. A combination of ECPR and TTM, both implemented as soon as possible on scene, appears to have promising results in OHCA. To date, it is still unknown whether the implementation of TTM and ECPR on scene affects the time course and value of neurological biomarkers., Methods: 69 ECPR patients were examined in this study. Blood samples were collected between 1 and 72 h after ECPR and analyzed for S100, neuron-specific enolase (NSE), lactate, D-dimers and interleukin 6 (IL6). Cerebral performance category (CPC) scores were used to assess neurological outcome after ECPR upon hospital discharge. Resuscitation data were extracted from the Regensburg extracorporeal membrane oxygenation database and all data were analyzed by a statistician. The data were analyzed using non-parametric methods. Diagnostic accuracy of biomarkers was determined by area under the curve (AUC) analysis. Results were compared to the relevant literature., Results: Non-hypoxic origin of cardiac arrest, manual chest compression until ECPR, a short low-flow time until ECPR initiation, low body mass index (BMI) and only a minimal need of extra-corporeal membrane oxygenation support were associated with a good neurological outcome after ECPR. Survivors with good neurological outcome had significantly lower lactate, IL6, D-dimer, and NSE values and demonstrated a rapid decrease in the initial S100 value compared to non-survivors., Conclusions: A short low-flow time until ECPR initiation is important for a good neurological outcome. Hypoxia-induced cardiac arrest has a high mortality rate even when ECPR and TTM are performed at the emergency scene. ECPR patients with a higher BMI had a worse neurological outcome than patients with a normal BMI. The prognostic biomarkers S100, NSE, lactate, D-dimers and IL6 were reliable indicators of neurological outcome when ECPR and TTM were performed at the emergency scene., (© 2021. The Author(s).)

Objective: In a cohort of 500 patients complaining about adverse effects from dental materials, allergies were found to be contributing to the patients' subjective complaints in only about 14% of the cases. Therefore, the aim of this retrospective study was to investigate an enlarged cohort of 625 patients reporting on adverse effects from dental materials on non-allergy-related dental or orofacial findings with relevance for their subjective complaints., Methods: 625 patients visiting a specialized consultation on suspected adverse effects from dental materials were characterized regarding age and sex distribution, subjective complaints, allergies, and dental and orofacial findings with relevance for their subjective complaints., Results: This cohort comprised about 81% females and the median age was 58 years. The most often reported subjective complaints were burning mouth (43.8%), taste disorders (28.8%) and dry mouth (22.7%). Allergies toward dental materials were found in 12.3%. In 28.0% of the patients, no dental or orofacial findings with relevance for the subjective complaints expressed by the patients could be found. 19.8% of the patients exhibited relevant functional symptoms, 16.2% relevant orofacial diseases, 15.2% relevant mechanical irritations, 10.1% or 9.4% relevant tooth-related or plaque-related symptoms, respectively, 9.4% hyposalivation, and in 7.2% relevant manufacturing faults were found., Significance: In patients complaining about adverse effects from dental materials, a wide variety of dental or orofacial findings need to be considered despite allergies, although a quarter of the patients did not present any relevant dental or orofacial finding. Therefore, specialized consultations and close collaboration with experts from other fields are eligible., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Helicobacter pylori is associated with chronic gastritis, gastric or duodenal ulcers, and gastric cancer. Since the oral cavity is the entry port and the first component of the gastrointestinal system, the oral cavity has been discussed as a potential reservoir of H. pylori . Accordingly, a potential oral-oral transmission route of H. pylori raises the question concerning whether close contact such as kissing or sharing a meal can cause the transmission of H. pylori . Therefore, this topic has been investigated in many studies, applying different techniques for detection of H. pylori from oral samples, i.e. molecular techniques, immunological or biochemical methods and traditional culture techniques. While molecular, immunological or biochemical methods usually yield high detection rates, there is no definitive evidence that H. pylori has ever been isolated from the oral cavity. The specificity of those methods may be limited due to potential cross-reactivity, especially with H. pylori -like microorganisms such as Campylobacter spp. Furthermore, the influence of gastroesophageal reflux has not been investigated so far. This review aims to summarize and critically discuss previous studies investigating the potential colonization of H. pylori in the oral cavity and suggest novel research directions for targeting this critical research question.

The antimicrobial photodynamic therapy (aPDT) is a promising approach for the control of microbial and especially fungal infections such as mucosal mycosis. TMPyP [5,10,15, 20-tetrakis(1-methylpyridinium-4-yl)-porphyrin tetra p-toluenesulfonate] is an effective photosensitizer (PS) that is commonly used in aPDT. The aim of this study was to examine the localization of TMPyP in Candida albicans before and after irradiation with visible light to get information about the cellular mechanism of antifungal action of the photodynamic process using this PS. Immediately after incubation of C. albicans with TMPyP, fluorescence microscopy revealed an accumulation of the PS in the cell envelope. After irradiation with blue light the complete cell showed red fluorescence, which indicates, that aPDT is leading to a damage in the cell wall with following influx of PS into the cytosol. Incubation of C. albicans with Wheat Germ Agglutinin (WGA) could confirm the cell wall as primary binding site of TMPyP. The finding that the porphyrin accumulates in the fungal cell wall and does not enter the interior of the cell before irradiation makes it unlikely that resistances can emerge upon aPDT. The results of this study may help in further development and modification of PS in order to increase efficacy against fungal infections such as those caused by C. albicans ., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Voit, Cieplik, Regensburger, Hiller, Gollmer, Buchalla and Maisch.)

Objectives: The aims of this study were to investigate the antimicrobial efficacy of antiseptics in saliva-derived microcosm biofilms, and to examine phenotypic adaption of bacteria upon repeated exposure to sub-inhibitory antiseptic concentrations., Methods: Saliva-derived biofilms were formed mimicking caries- or gingivitis-associated conditions, respectively. Microbial compositions were analyzed by semiconductor-based 16S rRNA sequencing. Biofilms were treated with CHX, CPC, BAC, ALX, and DQC for 1 or 10 min, and colony forming units (CFU) were evaluated. Phenotypic adaptation of six selected bacterial reference strains toward CHX, CPC, and BAC was assessed by measuring minimum inhibitory concentrations (MICs) over 10 passages of sub-inhibitory exposure. Protein expression profiles were investigated by SDS-PAGE., Results: Both biofilms showed outgrowth of streptococci and Veillonella spp., while gingivitis biofilms also showed increased relative abundances of Actinomyces, Granulicatella, and Gemella spp. Antiseptic treatment for 1 min led to no relevant CFU-reductions despite for CPC. When treated for 10 min, CPC was most effective followed by BAC, ALX, CHX, and DQC. Stable adaptations with up to fourfold MIC increases were found in E. coli toward all tested antiseptics, in E. faecalis toward CHX and BAC, and in S. aureus toward CPC. Adapted E. coli strains showed different protein expression as compared with the wildtype strain., Conclusion: Antiseptics showed limited antimicrobial efficacy toward mature biofilms when applied for clinically relevant treatment periods. Bacteria showed phenotypic adaptation upon repeated sub-inhibitory exposure., Clinical Relevance: Clinicians should be aware that wide-spread use of antiseptics may pose the risk of inducing resistances in oral bacteria.

Objective: Failure of membrane oxygenator (MO) function of venovenous extracorporeal membrane oxygenators (VV ECMO) remains problematic. The development of device-induced coagulation disorder (COD) or worsened gas transfer (WGT) necessitates a system exchange. The aim was to correlate von Willebrand factor antigen (vWF:Ag) with the predisposition to MO failure and mortality., Methods: Laboratory parameters (inflammation, coagulation) and ECMO-related data from 31 VV ECMO patients were analyzed before and after the first MO exchange. Study groups were identified according to the exchange reasons (COD, WGT) and the extent of vWF:Ag (low, ≤425%; high, >425%)., Results: vWF:Ag remained unchanged after system exchange. High vWF:Ag was associated with systemic endothelial activation of older and obese patients with elevated SOFA score, increased norepinephrine and higher requirement of continuous renal replacement therapy without an effect on MO runtime and mortality. Including the mechanism of MO failure (COD, WGT), various patient group emerged. COD/low vWF:Ag summarized younger and less critically ill patients that benefit mainly from ECMO by a significant improvement of their inflammatory and coagulation status (CRP, D-dimers, fibrinogen) and highest survival rate (91%). Instead, WGT/high vWF:Ag presented older and more obese patients with a two-digit SOFA score, highest norepinephrine, and aggravated gas transfer. They benefited temporarily from system exchange but with worst survival (33%)., Conclusions: vWF:Ag levels alone cannot predict early MO failure and outcome in VV ECMO patients. Probably, the mechanism of clotting disorder in combination with the vWF:Ag level seems to be essential for clot formation within the MO. In addition, vWF:Ag levels allows the identification different patient populations In particular, WGT/high vWF:Ag represented a critically ill population with higher ECMO-associated mortality., Competing Interests: The authors have declared that no competing interests exist.

Background: Dental odontoblasts produce dentin mineralized matrix, trigger immune responses and act as sensory cells. The understanding of the mechanisms of these functions has been particularly restricted due to the lack of odontoblasts being cultivable in vitro. Because of the lack of specific markers to identify cells of the odontoblastic lineage, properties of the cells isolated from the dentin-pulp interface were compared to dental pulp cells, periodontal ligament cells, osteoblasts, skin fibroblasts, epithelial cells (A549) and HeLa in the present study., Methods: After surgical procedures, the pulp tissue was removed from the tooth crown, and cells were scrapped off the dentin-pulp interface. Explants from teeth of three patients were routinely cultivated, and cells were harvested after several weeks. Cell morphology and ultrastructure was studied by light microscopy (LM), scanning (SEM) or transmission electron microscopy (TEM). Expression of dentin sialophosphoprotein (DSPP), dentin matrix protein 1 (DMP1), TRPV4, and S100 calcium binding protein A4 (S100A4) were analyzed at the protein level by sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) and Western blotting using specific antibodies. The differential expression of S100A4 in the various cell lines was further investigated at the gene level by semiquantitative real-time PCR. Mineralization in the various cell types was observed after alizarin red staining after a 28 days incubation period. The immunophenotype of the cells was examined by flow cytometry using monoclonal anti-human antibodies CD90-FITC, CD73-PE, CD105-PE, CD29-PE, CD140a-FITC, CD144-PE, CD45-FITC or CD34-FITC. Differences between median values were statistically analyzed (Mann-Whitney U-test)., Results: Cells from the dentin-pulp interface retain the polarity of odontoblast morphology in culture with an elongated, rounded cell body, and an extended cellular process. Ultrastructural analysis of the cells indicates high secretory activity including the extracellular deposition of fibrillar collagen. An extended rough endoplasmic reticulum is lined by a large number of ribosomes, and a vast number of secretory granules merges with the cell membrane. Protein expression of DSPP, DMP1, and TRPV4 as a transient receptor potential cation was detected in all cell lines. S100A4 was found differentially expressed in cultures of cells from tooth tissues. High expression of S100A4 was observed at the protein and gene level in two fractions of cells isolated from the dentin-pulp interface, but was absent or only weakly expressed in pulp cells. S100A4 expression in cells from the dentin-pulp interface and pulp cells is consistent with the intensity of the formation of mineralized nodules detected by alizarin red staining. Immunophenotyping revealed that a high percentage of CD73 (ecto-5-nucleotidase), an enzyme active on the surface of immune-competent cells, was expressed in cells of the dentin-pulp interface. While 72%-78% of positive cells were detected in dentin-pulp interface fractions, only 28-64% of the cells in pulp cell cultures were stained., Conclusions: The present findings obtained with a variety of cells of different origin provide experimental evidence that cells isolated from the dentin-pulp interface express unique properties different from dental pulp cells in particular. The differential expression of S100A4 is a relevant marker candidate for differentiating between dental pulp cells and cells of the odontoblast lineage., (Copyright © 2020 Elsevier GmbH. All rights reserved.)