Effect of light-, chemical-, and dual-cured universal adhesives on the internal adaptation of resin composites to pulpal and gingival internal walls.

PURPOSE: To compare the internal adaptation of restorative systems bonded to mid-coronal and gingival dentin using light-cured, chemical-cured, and dual-cured adhesives, both immediately and after aging. METHODS: 60 molars were selected and received occluso-mesial preparations with dentin gingival margins. Restorations were performed using different restorative systems with light-cured, chemical-cured, and dual-cured adhesives. Internal adaptation was assessed by examining the percentage of continuous margin (%CM) at the pulpal and gingival dentin under a scanning electron microscope at x200 magnification. Half of the teeth were stored in sterile water for 24 hours, while the other half underwent 10,000 thermal cycles. Micro-morphological analysis was conducted on representative samples at x1,000 magnification. RESULTS: The restorative system with light-cured adhesive exhibited significantly lower %CM values at the gingival dentin, particularly after aging. Aging had a negative impact on the %CM values of the pulpal and gingival dentin in restorative systems with light-cured and dual-cured adhesives. Regional dentin variations influenced the %CM values, especially after aging, regardless of the restorative system used. The tested restorative system with chemical-cured adhesive is preferable for achieving improved internal adaptation when bonding to both mid-coronal and gingival dentin, compared to the other tested systems. CLINICAL SIGNIFICANCE: The study highlights the variations in adhesive performance between different regional dentin areas using the tested restorative systems.

Effect of different storage media on elemental analysis and microhardness of cervical cavity margins restored with a bioactive material.

Objectives: This study aimed to investigate the elemental analysis and microhardness of a bioactive material (Activa) and marginal tooth structure after storage in different media. Materials and Methods: Fifteen teeth received cervical restorations with occlusal enamel and gingival dentin margins using the tested material bonded with a universal adhesive, 5 of them on the 4 axial surfaces and the other 10 on only the 2 proximal surfaces. The first 5 teeth were sectioned into 4 restorations each, then stored in 4 different media; deionized water, Dulbecco's phosphate buffered saline (DPBS), Tris buffer, and saliva. The storage period for deionized water was 24 hours while it was 3 months for the other media. Each part was analyzed by scanning electron microscopy-energy dispersive spectroscopy (SEM-EDS) analysis for different substrates/distances and the wt% of calcium, phosphorus, silica, and fluoride were calculated. The other 10 teeth were sectioned across the restoration, stored in either Tris buffer or saliva for 24 hours or 3 months, and were evaluated for microhardness of different substrates/areas. Data were analyzed using analysis of variance and Tukey's post hoc test. Results: Enamel and dentin interfaces in the DPBS group exhibited a significant increase in calcium and phosphorus wt%. Both silica and fluoride significantly increased in tooth structure up to a distance of 75 µm in the 3-month-media groups than the immediate group. Storage media did not affect the microhardness values. Conclusions: SEM-EDS analysis suggests an ion movement between Activa and tooth structure through a universal adhesive while stored in DPBS.

Effect of different restorative systems and aging on marginal adaptation of resin composites to deep proximal margins.

OBJECTIVES: To evaluate and compare the marginal integrity of different restorative systems bonded to proximal gingival dentin, and determine the consistency level of the results obtained by two in vitro methods. MATERIALS AND METHODS: Thirty molars received occluso-mesial preparations with dentin/cementum gingival margins. They were divided into three groups and restored using different restorative systems with light-cured (Adhese Universal), self-cured (Palfique universal bond), and dual-cured (Futurabond U) adhesives. The restoration/gingival dentin interfaces were observed using scanning electron microscopy (SEM) and evaluated based on the World Dental Federation (FDI) criteria. After 10,000 thermal cycles, the marginal integrity was re-evaluated. Marginal integrity was evaluated by the percentage of continuous margin (% CM) at ×200 for SEM and as the frequency of each score within the FDI ranking. RESULTS: No significant differences were found between the restorative systems immediately, however, the system with the light-cured adhesive had the lowest marginal integrity after aging. All tested restorative systems were adversely affected by aging. A moderate inverse correlation was identified between evaluation techniques. CONCLUSION: The tested restorative systems utilizing self-cured and dual-cured adhesives may be preferable for achieving optimal marginal integrity when bonding to deep proximal margins, compared to the tested system with light-cured adhesive. CLINICAL SIGNIFICANCE: When performing deep margin elevation, it is important to consider the adhesive system being used.

Clinical evaluation of subgingival open sandwich restorations: 3-year results of a randomized double-blind trial.

OBJECTIVES: To provide a 3-year follow-up of previously treated patients to assess and compare the periodontal responses and clinical performance of proximal subgingival open sandwich restorations. MATERIALS AND METHODS: Ninety-five adults participated in the study, with a combined total of 120 compound Class II cavities. These cavities had gingival margins located below the CEJ. Four different restorative materials were used to elevate the dentin/cementum gingival margins of the cavities: resin-modified glass ionomer, glass hybrid, flowable bulk-fill composite, or ion-releasing material, which were then completed with the same overlaying composite. Different periodontal and clinical evaluations, based on the criteria set by the World Dental Federation (FDI) criteria, were performed at different time intervals, including baseline, 6 months, 1, 2, and 3 years. RESULTS: The type of base material did not affect the periodontal evaluations. There were no statistically significant differences between different time intervals or base material groups in any of the evaluated FDI parameters. However, the ion-releasing material scored significantly worse in the radiographic evaluation than any of the other groups. CONCLUSIONS: All tested materials are suitable for proximal subgingival open sandwich restorations, as long as the restoration/tooth margin is at least 2-mm away from the bone crest. CLINICAL SIGNIFICANCE: Clinicians can confidently choose any of the tested materials for proximal subgingival open sandwich restorations, as they have shown good outcomes from both periodontal and clinical perspectives.

Periodontal Evaluation of Subgingival Open Sandwich Restorations: 2-Year Results of a Randomized Double-Blind Trial.

This study aimed to evaluate the periodontal responses of subgingival proximal margins elevated using different restorative materials. A total of 120 proximal cavities with dentin/cementum gingival margins were elevated using one of four materials (resin-modified glass ionomer, glass hybrid, flowable bulk-fill resin composite, or bioactive ionic resin) and completed with the same overlaying resin composite. At 2 weeks (baseline), 6 months, 1 year, and 2 years postrestoration, periodontal parameters and the radiographic distance between the restoration margin and bone crest were evaluated. Appropriate statistical analyses were performed. The values of all periodontal parameters increased with time, although only the increases in Plaque Index and probing depth within each material group were statistically significant. There were no statistically significant differences in any of the periodontal parameters between the different materials within the same evaluation period, nor between different time points or material groups in the radiographic distances. Both glass ionomer-based and resin-based materials were periodontally safe as subgingival open sandwich restorations.

Microhardness of different thicknesses of bulk fill composites.

PURPOSE: To compare the microhardness values and bottom/top hardness ratios of different composites after being cured in 2 or 4 mm increments. METHODS: Two bulk fill composites, methacrylate-based and ormocer-based, and one conventional composite were tested. 36 cylindrical discs were prepared (n=12/composite, with six for 2 mm, and six for 4 mm thickness) by pressing each composite into a mold between two glass slides covered by Mylar strips. The top and bottom surfaces of each sample were evaluated using a Buehler hardness tester for Knoop microhardness, with a 50 g static load applied for 10 seconds at three different locations of the central part of each sample. The bottom/top hardness ratio was calculated for each sample. The Knoop microhardness data and bottom/top ratio percentages were analyzed using two-way repeated measures ANOVA and Holm-Sidak post hoc test, with significance at P< 0.05. RESULTS: The tested methacrylate-based bulk fill had the highest overall microhardness among the three tested composites. All three composite types showed a significant difference in microhardness between the top and bottom of the 4 mm discs. The bottom/top ratio percentages differed significantly for both tested bulk fill composites across different thicknesses. Both tested bulk fill materials had a bottom/top ratio of ≥ 80% at the deepest level of a 4 mm increment. CLINICAL SIGNIFICANCE: The type of material significantly affected both the bottom and top microhardness values under the experimental conditions used. While both tested bulk fill composites showed a decline in microhardness at the bottom of the 4 mm depth, they had clinically acceptable microhardness ratios at greater depths.

The Effect of Finishing and Polishing Systems on Surface Roughness and Microbial Adhesion of Bulk Fill Composites: A Systematic Review and Meta-Analysis.

Objectives: This paper presents a systematic review and meta-analysis of the effect of different finishing and polishing (F/P) systems on surface roughness (SR) and microbial adhesion to bulk fill (BF) composites. Materials and Methods: An electronic search of 3 databases (the National Library of Medicine [MEDLINE/PubMed], Scopus, and ScienceDirect) was conducted. Only in vitro studies that evaluated SR and microbial adhesion to BF composites were included. The included studies were individually evaluated for the risk of bias following predetermined criteria. A meta-analysis of the reviewed studies was conducted to compare the SR values of both Filtek Bulk Fill and Tetric EvoCeram Bulk Fill with and without F/P using the Comprehensive Meta-Analysis software. Results: A total of 12 studies fulfilled the inclusion criteria. The meta-analysis showed no significant difference between Filtek Bulk Fill and Tetric EvoCeram Bulk Fill without F/P or after F/P using multi-step systems. Different F/P systems affected the SR values, on the other hand, did not affect microbial adhesion values. Conclusion: Both Filtek Bulk Fill and Tetric EvoCeram Bulk Fill had comparable roughness results. Multi-step systems may be preferable for F/P of BF composites.

Design, molecular modelling and synthesis of novel benzothiazole derivatives as BCL-2 inhibitors.

Apoptosis plays a crucial role in cancer pathogenesis and drug resistance. BCL-2 family of enzymes is considered as one of the key enzymes which is involved in apoptosis. When there is disruption in the balance between anti-apoptotic and pro-apoptotic members of the BCL-2 family apoptosis is dysregulated in the affected cells. Herein, 33 novel benzothiazole-based molecules 7a-i, 8a-f, 9a-b, 12a-e, 13a-d, 14a,b, and 17a-j were designed, synthesized and tested for their BCL-2 inhibitory activity. Scaffold hopping strategy was applied in designing of the target compounds. Compounds 13c and 13d showed the highest activity with IC50 values equal to 0.471 and 0.363 µM, respectively. Molecular docking studies of the synthesized compounds showed comparable binding interactions with the lead compound. Structure activity relationship study was performed to show the effects of structural modifications on the inhibitory activities on BCL-2.

Comparative evaluation of subgingival scaling and polishing techniques on dental material surface roughness.

PURPOSE: To evaluate and compare the effects of different scaling and polishing techniques on the surface roughness of four different restorative materials. METHODS: 72 specimens were prepared, molded to a size of 8.0 by 2.0 mm, and cured according to the manufacturers' instructions. The specimens were stored at 37°C for 24 hours and then thermocycled for 5,000 cycles (from 55°C to 5°C) to simulate 6 months of clinical use. Surface roughness (Ra/average and Rz/max-overall heights) was calculated using a stylus profilometer by subtracting the simulated treatments of hand scaling, ultrasonic scaling, and air polishing from the baseline measurements. The difference in Ra and Rz data were compared independently for each measurement using a two-way ANOVA on Ranks and the Holm-Sidak test, with α< 0.05 used to determine significance. RESULTS: Irrespective of the scaling or polishing technique employed, flowable bulk fill demonstrated the lowest Ra and Rz values. Hand scaling exhibited the highest roughness and variability among the other techniques, regardless of the materials tested (P< 0.001). Air polishing with glycine resulted in the lowest roughness values across all tested materials, with the exception of the tested bioactive restorative material group. CLINICAL SIGNIFICANCE: Regarding surface roughness, air polishing with glycine may be an effective and safe intervention for periodontal maintenance of subgingival restorations compared to the other tested scaling methods.

Secondary caries adjacent to bulk fill resin composite restorations lined with fluoride agents.

PURPOSE: To evaluate the potential secondary caries reduction of bulk-fill resin composite restorations treated with different fluoride (F)-based agents prior to restoration placement. METHODS: 25 upper extracted molars received Class V cavities on both buccal and lingual surfaces with an enamel margin and root surface margin. The teeth were randomly assigned into five groups with five teeth per group (n=10). The treatment groups were: control group, with no treatment; the other groups received treatment using different F-based agents prior to bonding. All teeth were restored using a selective etch bonding technique and bulk fill resin composite. All teeth received 10,000 thermal cycles followed by immersion in demineralizing solution to produce artificial caries-like lesions. Polarized light microscope evaluation was performed on longitudinal sections (30 enamel lesions and 30 root surface lesions per group). Lesion depth and wall lesions for both enamel and root surface adjacent to the restorations were evaluated. RESULTS: Both lesion depths and frequency of wall lesions in the enamel and root surfaces in all treatment groups were significantly reduced compared with the control group. Among the different F-based agents, no significant difference was seen on the enamel or root surface lesion depth, showing a similar presence of enamel and root cavosurface wall lesions. CLINICAL SIGNIFICANCE: F-based agent treatment of adjacent enamel and root surfaces prior to placement of restorative materials provided resistance to the development of secondary caries during an in vitro caries model.

Artificial Intelligence Role in Subclassifying Cytology of Thyroid Follicular Neoplasm.

OBJECTIVE: Fine needle aspiration cytology has higher sensitivity and predictive value for diagnosis of thyroid nodules than any other single diagnostic methods.  In the Bethesda system for reporting thyroid, the category IV, encompasses both adenoma and carcinoma, but it is not possible to differentiate both lesions in the cytology practice and can be only differentiated after resection. In this work, we aim at exploring the ability of a convolutional neural network (CNN) model to sub-classifying cytological images of Bethesda category IV diagnosis into follicular adenoma and follicular carcinoma. METHODS: We used a cohort of cytology cases n= 43 with extracted images n= 886 to train CNN model aiming to sub-classify follicular neoplasm (Bethesda category IV) into either follicular adenoma or follicular carcinoma. RESULT: In our study, the model subclassification of follicular neoplasm into follicular adenoma (n = 28/43, images n = 527/886) from follicular carcinoma (n = 15/43, images n= 359/886), has achieved an accuracy of 78%, with a sensitivity of 88.4%, and a specificity of 64% and an area under the curve (AUC) score of 0.87 for each of follicular adenoma and follicular carcinoma. CONCLUSION: Our CNN model has achieved high sensitivity in recognizing follicular adenoma amongest cytology smears of follciualr neoplasms, thus it can be used as an ancillary technique in the subcalssification of Bethesda Iv category cytology smears.

Periodontopathic bacterial adhesion to different restorative materials used to elevate proximal subgingival margins.

This study compared the periodontopathic bacterial adhesion to four restorative materials used for deep margin elevation at 2, 24, and 48-h after incubation. Discs were produced from four restorative materials: resin modified glass ionomer, glass hybrid, flowable bulk fill resin composite, and bioactive ionic resin. Root dentin was used as control. Specimens were coated with saliva and used to culture a biofilm comprised of three strains of periodontopathic bacteria; Porphyromonas gingivalis, Prevotella intermedia, and Aggregatibacter actinomycetemcomitans. Bacterial adherence was assessed by colony count assay, crystal violet staining, and visualized using confocal laser scanning microscopy. Data were analyzed by two-way ANOVA followed by Tukey's post hoc tests. The adhesion values for the control specimens were significantly higher than for other materials, while those for the flowable bulk fill were significantly lower than for any other material within all evaluation assays. The 2-h incubation period showed the lowest adhesion values regardless of the group. The 48-h adhesion values were higher than the 24-h results in all groups except the flowable bulk fill. Microscopic imaging partially supported the findings of the measurements. In terms of periodontopathic bacterial adhesion, the tested flowable bulk fill may be preferable for subgingival use over other tested materials.

Comparative analysis of the effect of Bioactive Glass 45S5 on enamel erosion progression in human dentitions (in vitro study).

OBJECTIVES: The aim of the present study was to compare the surface morphology alterations, mineral content, and surface roughness of eroded enamel surface versus eroded enamel surface which was preceded by Bioactive Glass 45S5 (BAG45S5) application in both primary and permanent human dentitions. MATERIALS AND METHODS: Fifty-two primary teeth and fifty-two permanent teeth were selected. Teeth were randomly divided into 4 groups of twenty-six teeth each. Groups A1 and B1 underwent erosion with 1% citric acid, while groups A2 and B2 were subjected to application of BAG45S5 powder followed by the same erosive conditions as A1 and B1. Measurements were performed by scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), and surface profilometry. They were used to examine the surface morphology alterations, mineral content, and surface roughness, respectively. RESULTS: SEM of enamel which received BAG45S5 showed smoother surface in primary teeth post erosion. EDX analysis showed that enamel exhibited crucial resistance to mineral loss in the group which received BAG45S5 prior to inducing erosion as compared to the induced erosion-only group. This was significant (p < 0.005) in both human dentitions. Erosion-only groups showed significantly less surface roughness in permanent teeth (p < 0.045). A marked decrease in surface roughness was observed in surfaces receiving BAG45S5, primary teeth (p < 0.001), and permanent teeth (p < 0.001). CONCLUSIONS: Bioactive Glass 45S5 proved successful against erosive conditions in both primary and permanent teeth with better performance in the permanent teeth so it can be regarded as a means of prevention. CLINICAL RELEVANCE: Bioactive Glass 45S5 powder could be used not only to remove stains but also as a prophylactic preventive measure against the multiple episodes of acidic food and beverage consumption in children.

Correlation between different methodologies used to evaluate the marginal adaptation of proximal dentin gingival margins elevated using a glass hybrid.

Objectives: This study aimed to evaluate the effect of aging on the marginal quality of glass hybrid (GH) material used to elevate dentin gingival margins, and to analyze the consistency of the results obtained by 3 in vitro methods. Materials and Methods: Ten teeth received compound class II cavities with subgingival margins. The dentin gingival margins were elevated with GH, followed by resin composite. The GH/gingival dentin interfaces were examined through digital microscopy, scanning electron microscopy (SEM) using resin replicas, and according to the World Dental Federation (FDI) criteria. After initial evaluations, all teeth were subjected to 10,000 thermal cycles, followed by repeating the same marginal evaluations and energy dispersive spectroscopy (EDS) analysis for the interfacial zone of 2 specimens. Marginal quality was expressed as the percentage of continuous margin at ×200 for microscopic techniques and as the frequency of each score for FDI ranking. Data were analyzed using the paired sample t-test, Wilcoxon signed-rank test, and Pearson and Spearmen correlation coefficients. Results: None of the testing techniques proved the significance of the aging factor. Moderate and strong significant correlations were found between the testing techniques. The EDS results suggested the presence of an ion-exchange layer along the GH/gingival dentin interface of aged specimens. Conclusions: The marginal quality of the GH/dentin gingival interface defied aging by thermocycling. The replica SEM and FDI ranking results had stronger correlations with each other than either showed with the digital microscopy results.

Effect of pressure during curing placement technique on bond strength of resin composite to human dentin.

PURPOSE: To evaluate and compare the effect of pressure during curing on resin composite bond strength to dentin using a self-etch bonding protocol. METHODS: 20 human teeth were cut to the mid-coronal dentin and received a standardized smear layer. The prepared teeth were randomly assigned to the following two groups (n= 10/group): (1) without pressure during curing (control) or (2) with pressure during curing. Teeth in the control group received a 4 mm-thick buildup of a nanohybrid resin composite in two separately cured increments, adapted using a composite placement instrument, and bonded with a universal adhesive, while teeth in the treatment group were restored with the same adhesive and resin composite but a plexiglass pressure cylinder was used to apply pressure while each increment was cured. Each group was further divided into two subgroups, one of which was sectioned and subjected to microtensile bond strength (µTBS) testing after 24 hours (immediate samples; n= 5), while the other was subjected to 10,000 thermal cycles (TC; n= 5) prior to sectioning and µTBS testing. The resulting failure patterns were assessed under a stereomicroscope. In addition, one representative specimen from each subgroup was subjected to qualitative microscopic morphological analysis of the internal restoration/dentin interface. Data were analyzed by two-way ANOVA followed by Tukey' post hoc test and values with P< 0.05 were considered to be statistically significant. RESULTS: After TC, the group cured with pressure exhibited significantly higher µTBS values than did the control (P< 0.05), although TC had a detrimental effect on all µTBS values. Microscopic examination revealed that the control specimens had more voids in the resin composite part, relative to specimens that were under pressure during the curing process. CLINICAL SIGNIFICANCE: Pressure application during curing of resin composite may have a positive effect on bond strength to dentin.

In vitro marginal and internal adaptation of four different base materials used to elevate proximal dentin gingival margins.

Background: There is still debate about the most appropriate restorative material category to relocate the proximal deep cervical margins, thus, this study aimed to compare the marginal and internal adaptation of four base materials used for deep margin elevation, and to evaluate each base material/overlying composite interface. Material and Methods: Fifty six molars received class II cavities with dentin/cementum gingival margins. They were divided into four groups and their gingival margins were elevated using either; resin modified glass ionomer (RMGI), highly viscous conventional glass ionomer (HV-GIC), flowable bulk fill resin composite (Bulk Flow) and bioactive ionic resin (Activa). The rest of the cavities were completed with the same overlying composite. Half of each group was either; kept in sterile water for 1 week, or subjected to 18 months water storage and 15,000 thermal cycles. Base materials/gingival dentin interfaces were examined under a scanning electron microscope at different magnifications, and percentage of continuous margin (% CM) and maximum gap width (MGW) were analyzed, in addition to base materials/overlying composite interfaces evaluations. % CM values were statistically analyzed using Two-way analysis of variance, Tukey post hoc tests (at p<0.05) and Pearson's correlation while MGW values were analyzed using Kruskal-Wallis, Mann-Whitney U tests and Spearmen correlation. Results: Both Bulk Flow and Activa had better marginal integrity than RMGI and HV-GIC. All base materials were adversely affected by aging. All base materials/overlying composite interfaces were continuous and age defying. Conclusions: In terms of marginal integrity, Bulk Flow and Activa might be preferable for proximal dentin margin elevation under direct restoration compared to the other tested base materials. Key words:Deep proximal margin, interface analysis, marginal quality, open sandwich technique.

The prognostic role of PD-1, PD-L1, ALK, and ROS1 proteins expression in non-small cell lung carcinoma patients from Egypt.

BACKGROUND: Programmed death ligand-1 (PD-L1), anaplastic lymphoma kinase (ALK), and c-ros oncogene1 (ROS1) expression may influence the prognosis of non-small cell lung carcinoma (NSCLC). We aimed to investigate the prognostic and predictive significance of PD-1/PD-L1 along with c-ros ROS1 and ALK in NSCLC patients. METHODS: Immunohistochemistry used to identify ALK, ROS1, PD-1, and PD-L1 proteins expression as well as ROS1 rearrangement via fluorescence in situ hybridization, in 70 NSCLC patients. Results were related to clinicopathological feature, survival, and treatment response. RESULTS: Expression of ROS1, ALK, PD-1, and PD-L1 and ROS1-rearrangement were detected in 18.57%, 54.29%, 84.29%, 87.14%, and 15.71% of the cases, respectively. No association was found between ROS1, PD-1, and PD-L1 and any clinicopathological features, survival, or treatment outcome. ALK expression significantly associated with stage-IV and left-sided tumors. Epidermal growth factor receptor (EGFR) mutation and ALK-positive patients had significantly reduced progression-free survival than patients with wild type EGFR [HR: 1.99, 95% CI: 1.37-2.93, p < 0.001] and negative-ALK expression [HR: 1.46, 95% CI: 1.03-2.07, p = 0.03]. In multivariate analysis, lymph node metastasis, EGFR-mutations, and ALK were independent predictors of NSCLC. PD-L1 expression was significantly correlated with PD-1 but not with ROS1, ALK, or EGFR-mutation. CONCLUSION: Positive ALK expression and EGFR-mutations are independent adverse predictors of NSCLC. Overexpression of PD-1/PD-L1 is not a significant prognostic marker in NSCLC patients receiving chemotherapy, making them susceptible to immunotherapy. Since PD-1/PD-L1 expression is independent to oncogenic driver mutations, future studies into specific immune checkpoint inhibitors combined with targeted therapies for individualized treatment of NSCLC is warranted. Positive ALK expression and EGFR mutations are independent risk factors for NSCLC. Overexpression of PD-1/PD-L1 is not a significant prognostic factor in patients with NSCLC who are receiving chemotherapy, making them immunotherapy susceptible. Given that PD-1/PD-L1 expression is not dependent on oncogenic driver mutations, additional research into specific immune checkpoint inhibitors in combination with targeted therapies for the treatment of NSCLC on an individual basis is warranted.

Expression of PD-L1 in Locally Advanced Breast Cancer and Its Impact on Neoadjuvant Chemotherapy Response.

OBJECTIVES: Programmed cell death-ligand 1 (PD-L1) is a new target in breast cancer (BC) and its impact on neoadjuvant chemotherapy (NACTH) response is still unclear. The aim of this study was to investigate the prevalence of PD-L1 in locally advanced invasive BC of different molecular subtypes and to elucidate its relation to tumor-infiltrating lymphocytes (TILs) density, established clinicopathological factors, pathological therapy response after neoadjuvant chemotherapy and patients' outcome. MATERIALS AND METHODS: One hundred and five cases of locally advanced invasive BC were enrolled in our study. Cases were classified into five molecular subtypes according to the Immuno-histochemical data. PD-L1 immunostaining was analyzed for all studied cases and its expression was correlated with TILs density, histopathologic parameters, BC molecular subtypes, Pathological therapy response, 7-years disease-free survival (DFS) and overall survival (OS). RESULTS: PD-L1 was expressed in 32.4% of the studied locally advanced BC cases. It showed a significant correlation with old age group (p= 0.010), high tumor grade (p= 0.046) and high pretherapy TILs density (p= <0.001). PD-L1 expression was higher in HER2/neu-enriched group (45.5%) followed by TNBC (44.4%). There were no significant relations between PD-L1 expression and DFS, OS as well as pathological therapy response, although, it revealed more expression in cases with complete and marked therapy response. CONCLUSION: In spite our results fail to prove that PD-L1 is a bad prognostic biomarker in locally advanced BC, but they indicate PD-L1 could be a new target for the treatment of patients with high grade breast carcinoma and TNBC group.

Deep proximal margin rebuilding with direct esthetic restorations: a systematic review of marginal adaptation and bond strength.

This review aimed to characterize the effect of direct restorative material types and adhesive protocols on marginal adaptation and the bond strength of the interface between the material and the proximal dentin/cementum. An electronic search of 3 databases (the National Library of Medicine [MEDLINE/PubMed], Scopus, and ScienceDirect) was conducted. Studies were included if they evaluated marginal adaptation or bond strength tests for proximal restorations under the cementoenamel junction. Only 16 studies met the inclusion criteria and were included in this review. These studies presented a high degree of heterogeneity in terms of the materials used and the methodologies and evaluation criteria of each test; therefore, only a descriptive analysis could be conducted. The included studies were individually evaluated for the risk of bias following predetermined criteria. To summarize the results of the included studies, the type of restorative material affected the test results, whereas the use of different adhesive protocols had an insignificant effect on the results. It could be concluded that various categories of resin-based composites could be a suitable choice for clinicians to elevate proximal dentin/cementum margins, rather than the open sandwich technique with resin-modified glass ionomers. Despite challenges in bonding to proximal dentin/cementum margins, different adhesive protocols provided comparable outcomes.

In vitro biocompatibility testing of different base materials used for elevation of proximal subgingival margins using human gingival epithelial cells.

PURPOSE: To analyze the biological effects of four base materials used for elevation of proximal subgingival margins on gingival epithelial cells. METHODS: Twenty-eight specimens for each of the four base materials (total 112 specimens) were used: resin-modified glass ionomer (RMGI), glass hybrid (HV-GIC), flowable bulk fill resin composite (Bulk Flow) and bioactive ionic resin (Activa). Proximal enamel and root dentin were used as controls. Gingival epithelial cell viability was calculated after direct incubation on all four types of material for either 24 h or 72 h using both the methyl tetrazolium and trypan blue dye exclusion assays. Data were analyzed statistically using one-way analysis of variance, Tukey post hoc test and independent sample t-test (P < 0.05). RESULTS: Cell viability values in both assays showed significant differences among the study groups. Bulk Flow showed the highest values, followed in order by Activa and the control groups. Both HV-GIC and RMGI had the lowest values. Cell viability in all of the study groups was higher after incubation for 72 h than after 24 h. CONCLUSION: In terms of biocompatibility with epithelial tissues, bulk fill resin composite appears to be most suitable, followed by bioactive composite, for subgingival placement than glass ionomer-based materials, especially that containing 2-hydroxy-ethyl methacrylate.