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The aim of the present in vitro study was to evaluate specific mechanical and physicochemical properties of three calcium silicate-based sealers, BioRoot™ Flow (BRF), CeraSeal (CRS) and TotalFill® (TF). Samples were prepared to evaluate different physicochemical and mechanical properties of the tested sealers. These evaluations were accomplished by investigating the pH changes over time, porosity, roughness, flow properties, compressive strength and wettability. The results were statistically evaluated using one-way analysis of variance. All three sealers demonstrated an alkaline pH from 1 h of immersion in water to 168 h. A higher porosity and hydrophily were detected in BRF samples compared to CRS and TF. No significant difference was found between the tested materials in the flow properties. Lower compressive strength values were observed for BRF compared to TF and CRS. Differently shaped structures were detected on the three materials after 7 days of immersion in PBS. The three materials demonstrated a higher solubility than 3% after 24 h of immersion in water (CRS < BRF < TF). The novel premixed calcium silicate sealer (BRF) had comparable physicochemical properties to the existing sealers. The lower compressive strength values could facilitate the removal of these materials during retreatment procedures. Further studies should investigate the biological effects of the novel sealer.
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OBJECTIVES: The purpose of the present study was to investigate the created roughness and cell attachment of intact teeth (C), obturated teeth with bioceramic (BR), or epoxy resin (AH) after root resection using piezoelectric ultrasonic and carbide bur. MATERIALS AND METHODS: Three groups of first mandibular premolars were used in the present study: control group (without any preparation or obturation) (C); second group was obturated with an epoxy resin sealer (AH, AH Plus Jet); and finally, the third one was obturated with a bioceramic sealer (BR, BioRoot RCS). All teeth were incubated for 4 months at 37°C. After that, the samples were sectioned using tungsten carbide bur or piezoelectric ultrasonic. Roughness and then cell attachment of periodontal ligament cells on the sectioned surfaces were investigated by profilometer and confocal microscope, respectively. STATISTICAL ANALYSIS: Data were statistically analyzed using one-way analysis of variance. RESULTS: After root resection, no significant difference was found between the roughness among the three groups sectioned using the piezoelectric technique (p > 0.05). In contrast, concerning the sectioned samples by burs, C demonstrated a rougher surface compared with BR (p < 0.05). There was a significant higher cell attachment in BR compared with AH in the piezoelectric groups (p = 0.047), while no statistically significant difference was found between the groups sectioned with bur (p > 0.05). CONCLUSION: Dentists are now focused on the use of calcium silicate-based sealers due to their bioactivity. The present study advises dentists to use bioceramic sealer which could improve the dentin characteristics which ameliorate the cell attachment.
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Solvent evaporation within an adhesive layer is a crucial step during a bonding process. The aim of this current research was to test whether the use of different air temperatures (20 °C, 40 °C, and 60 °C) for solvent evaporation improves the performance of four adhesive systems to dentin. Sixty non-carious human molar teeth were randomly prepared for micro-tensile bond strength (µTBS) tests. Four different adhesive systems, Prime&Bond Universal (PBU), OptiBond Universal (OBU), OptiBond FL (OBFL), and Clearfil SE (CSE), were applied following the manufacturer's instructions. Three groups based on the air-drying temperature were used: solvent evaporation was performed with either of warm (40 °C), (60 °C), and cold air as control group (20 °C) for 10 s at a distance of 5 cm. In all bonded surfaces, three resin composite (Reflectys, Itena Clinical, Paris, France) layers of 2 mm thickness were built up. The resin-dentin samples were kept in distilled water at 37 °C for 24 h and 6 months, respectively, before µTBS testing. Failure analysis, scanning electron microscopy of resin-dentin bonded interface, and solvent evaporation rate were tested as secondary variables. All analyses were conducted using a significance level of α = 0.05. Bond strength (BS) values were similar among all the adhesive systems used (p > 0.05). Also, the aging factor did not affect the BS (p > 0.05). Only the factor of temperature used for solvent evaporation resulted in a statistically significant effect (p < 0.05), with the temperature of 60 °C being the highest value (p < 0.05). A failure mode evaluation revealed mostly adhesive or mixed modes of failures in all the different temperatures of air used for the solvent evaporation of each adhesive system. The thickness of the adhesive layer and the creation of resin tags varied amongst the temperatures evaluated. For all adhesive systems tested, the use of 40 °C or 60 °C air for solvent evaporation led to an increased mass loss. Warmer temperatures for solvent evaporation contributed positively to bonding performance, enhancing both the quality of the adhesive layer and its interaction with the dentin tissue. Optimizing solvent evaporation with warmer air temperatures (40 °C and 60 °C) significantly improved µTBS, offering a practical means to enhance the quality and longevity of adhesive restorations in esthetic dentistry.
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The aim of this investigation was to conduct a systematic review and meta-analysis to determine the necessity of a white diet during or following a bleaching procedure. This systematic review and meta-analysis followed the PRISMA guidelines meticulously. The research question was: Is a white diet necessary during and/or after a bleaching treatment? In vitro studies or clinical trials reporting the color change in bleached enamel after the use of a free-staining diet were considered for full-text review. For the analyses, a random-effects model was employed. Statistical significance was defined as a p-value < 0.05. A total of 17 documents were eligible for qualitative analysis: 5 clinical trials and 12 in vitro studies. Only data from the clinical trials were included in the meta-analysis. For at-home bleaching, differences in the color among the subjects were not statistically significant during the first (p = 0.64), second (p = 0.26) or third (p = 0.43) weeks of treatment. Also, the color difference one month after finishing the bleaching treatment were not statistically significant (p = 0.27). The color difference one month after finishing an in-office treatment showed that the restrictions on diet did not significantly improve the bleaching outcomes (p = 0.90). According to the findings of this review, dietary restrictions are not necessary during or after bleaching procedures.
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The present in vitro study focuses on the filling ability of three different bioceramic cements with or without the addition of a bioceramic sealer in an open apex model on the marginal apical adaptation, tubule infiltrations, and void distributions as well as the interface between the cement and the sealer materials. To this end, sixty mandibular premolars were used. MTA-Biorep (BR), Biodentine (BD), and Well-Root Putty (WR) were used to obturate the open apex model with or without the addition of a bioceramic sealer, namely TotalFill® BC sealer™ (TF). A digital optical microscope and scanning electron microscope (SEM) were used to investigate the cement-dentin interface, marginal apical adaptation, and the material infiltration into the dentinal tubules. Micro-computed X-ray tomography and digital optical microscopy were used to investigate the cement-sealer interface. The results were analyzed by using the Kruskal-Wallis test. No significant difference was found between the groups for the marginal apical adaptation quality (p > 0.05). Good adaptation of the dentin-cement interface was found for all tested groups and the sealer was placed between the cement material and dentinal walls. All the groups demonstrated some infiltrations into the dentinal tubules at the coronal part except for the BR group. A good internal interface was found between the cement and the sealer with the presence of voids at the external interface. A larger number of voids were found in the case of the BD-TF group compared to each of the other two groups (p < 0.05). Within the limitations of the present in vitro study, all the groups demonstrated good marginal apical adaptation. The use of a sealer in an open apex does not guarantee good filling and, in addition, creates voids at the external interfaces with the dental walls when the premixed sealer is used with powder-liquid cement systems. The use of a premixed bioceramic cement could offer fewer complications than when a powder-liquid cement system is used.
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Melanoma frequently harbors genetic alterations in key molecules leading to the aberrant activation of PI3K and its downstream pathways. Although the role of PI3K/AKT/mTOR in melanoma progression and drug resistance is well documented, targeting the PI3K/AKT/mTOR pathway showed less efficiency in clinical trials than might have been expected, since the suppression of the PI3K/mTOR signaling pathway-induced feedback loops is mostly associated with the activation of compensatory pathways such as MAPK/MEK/ERK. Consequently, the development of intrinsic and acquired resistance can occur. As a solid tumor, melanoma is notorious for its heterogeneity. This can be expressed in the form of genetically divergent subpopulations including a small fraction of cancer stem-like cells (CSCs) and non-cancer stem cells (non-CSCs) that make the most of the tumor mass. Like other CSCs, melanoma stem-like cells (MSCs) are characterized by their unique cell surface proteins/stemness markers and aberrant signaling pathways. In addition to its function as a robust marker for stemness properties, CD133 is crucial for the maintenance of stemness properties and drug resistance. Herein, the role of CD133-dependent activation of PI3K/mTOR in the regulation of melanoma progression, drug resistance, and recurrence is reviewed.
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Melanoma , Sirolimo , Humanos , Sirolimo/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Melanoma/patologia , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Resistencia a Medicamentos AntineoplásicosRESUMO
Kohlschütter-Tönz syndrome (KTS) is a rare autosomal recessive disorder characterized by severe intellectual disability, early-onset epileptic seizures, and amelogenesis imperfecta. Here, we present a novel Rogdi mutant mouse deleting exons 6-11- a mutation found in KTS patients disabling ROGDI function. This Rogdi-/- mutant model recapitulates most KTS symptoms. Mutants displayed pentylenetetrazol-induced seizures, confirming epilepsy susceptibility. Spontaneous locomotion and circadian activity tests demonstrate Rogdi mutant hyperactivity mirroring patient spasticity. Object recognition impairment indicates memory deficits. Rogdi-/- mutant enamel was markedly less mature. Scanning electron microscopy confirmed its hypomineralized/hypomature crystallization, as well as its low mineral content. Transcriptomic RNA sequencing of postnatal day 5 lower incisors showed downregulated enamel matrix proteins Enam, Amelx, and Ambn. Enamel crystallization appears highly pH-dependent, cycling between an acidic and neutral pH during enamel maturation. Rogdi-/- teeth exhibit no signs of cyclic dental acidification. Additionally, expression changes in Wdr72, Slc9a3r2, and Atp6v0c were identified as potential contributors to these tooth acidification abnormalities. These proteins interact through the acidifying V-ATPase complex. Here, we present the Rogdi-/- mutant as a novel model to partially decipher KTS pathophysiology. Rogdi-/- mutant defects in acidification might explain the unusual combination of enamel and rare neurological disease symptoms.
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Amelogênese Imperfeita , Demência , Epilepsia , Anormalidades Dentárias , Humanos , Animais , Camundongos , Amelogênese Imperfeita/genética , Convulsões , Mutação , Proteínas de Membrana/genética , Proteínas Nucleares/genéticaRESUMO
Melanoma is the third most common type of skin cancer, characterized by its heterogeneity and propensity to metastasize to distant organs. Melanoma is a heterogeneous tumor, composed of genetically divergent subpopulations, including a small fraction of melanoma-initiating cancer stem-like cells (CSCs) and many non-cancer stem cells (non-CSCs). CSCs are characterized by their unique surface proteins associated with aberrant signaling pathways with a causal or consequential relationship with tumor progression, drug resistance, and recurrence. Melanomas also harbor significant alterations in functional genes (BRAF, CDKN2A, NRAS, TP53, and NF1). Of these, the most common are the BRAF and NRAS oncogenes, with 50% of melanomas demonstrating the BRAF mutation (BRAFV600E). While the successful targeting of BRAFV600E does improve overall survival, the long-term efficacy of available therapeutic options is limited due to adverse side effects and reduced clinical efficacy. Additionally, drug resistance develops rapidly via mechanisms involving fast feedback re-activation of MAPK signaling pathways. This article updates information relevant to the mechanisms of melanoma progression and resistance and particularly the mechanistic role of CSCs in melanoma progression, drug resistance, and recurrence.
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BACKGROUND: Calcium silicate-based sealers have gained in popularity over time due to their physicochemical/biological properties and their possible use with single-cone obturation. The single cone technique is a sealer-based obturation and there is still a knowledge gap regarding the potential impact of the sealer insertion method on the root canal-filling quality. Therefore, the aim of this micro-CT study was to assess the impact of the calcium silicate-based sealer insertion technique on void occurrence and on the sealer extrusion following single-cone obturation. METHODS: Thirty-six single-rooted mandibular premolars with one canal were shaped with Reciproc® R25 (VDW, Munich, Germany) then divided randomly into four groups of nine canals, each depending on the TotalFill® BC Sealer insertion technique used with single cone obturation: injection in the coronal two-thirds (group A); injection in the coronal two-thirds followed by direct sonic activation (group B); injection in the coronal two-thirds followed by indirect ultrasonic activation on tweezers (group C); sealer applied only on the master-cone (control group D). Samples were then scanned using micro-CT for voids and sealer extrusion calculation. Data were statistically analyzed using v.26 IBM; Results: No statistically significant differences were noted between the four groups in terms of voids; nevertheless, sonic activation (group B) followed by ultrasonic activation on the tweezers (group C) showed the best results (p = 0.066). Group D showed significantly less sealer extrusion when compared with group C (p = 0.044), with no statistically significant differences between groups D, A and B (p > 0.05). CONCLUSIONS: Despite no significant differences observed between the different sealer placement techniques, the use of sonic and ultrasonic activation might be promising to reduce void occurrence. Further investigations are needed to demonstrate the potential benefit of calcium silicate-based sealer activation especially in wide and oval root canals in order to improve the quality of the single-cone obturation.
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The goal of this article was to assess the effect of modified triple-layer application (MTLA) in conjunction with the active bonding technique on the bond strength of four adhesive systems to dentinal substrate. The adhesives tested were Prime&Bond Universal (PBU), OptiBond Universal (OBU), OptiBond FL (OBFL), and Clearfil SE (CSE). The adhesives were applied according to the following strategies: single active application (A) and triple adhesive layer application including Active-Passive-Passive (APP); AAP; and AAA. The micro-tensile bond strength test was evaluated following 24 h or 6 months of storage. The composite-dentin interface morphology was investigated using scanning electron microscopy. The data were statistically analyzed with a significance level of α = 0.05. At 24 h of aging, all of the factors tested were not significant (p > 0.05) for CSE. For OBFL, OBU, and PBU, statistically higher values were observed for the A technique (p < 0.05). Plus, there were no significant variances between the APP, AAP, and AAA techniques (p > 0.05) for OBFL and PBU. However, for OBU, there were no significant differences between the A and AAA techniques (p > 0.05). After 6 months of aging, the A technique showed statistically higher values when compared to the other techniques (p < 0.01), except for OBFL, where the A and AAA techniques showed promising outcomes. When comparing the bond strength values of 24 h and 6 months, only for PBU, all of the techniques used resulted in bond strength stability over time (p > 0.05). Thicker adhesive layers were observed when MTLA was applied. Only the OBFL adhesive showed the formation of resin tags in all of the modalities tested. The bonding performances of the different application techniques used were material-dependent.
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One of the major goals of adhesive dentistry is to improve the interaction of the already-existing adhesives with different substrates by using different application techniques. Thus, the objective of the present in vitro study was to assess the bond performance of four adhesive systems, Prime&Bond Universal (PBU), Clearfil SE Bond (CSE), OptiBond Universal (OBU), and OptiBond FL (OBFL), to dentin using various application modes: passive application (PA), active application (AA), Compo-Vibes modified application (CVM), and Compo-Vibes application (CV). Eighty extracted human molars were allocated into four groups based on the application modalities tested. The micro-tensile bond strength as well as fracture mode were tested in accordance with ISO/TS 11.405 after 24 h and 6 months of aging. Adhesive contact angle (CA) and scanning electron microscope analysis were also performed (n = 3). Statistical tests were performed with α = 0.05. After 24 h, a significant difference with a higher bond strength value was found for PBU in the AA modality and for CSE in the CVM modality (p < 0.05). However, no significant difference was shown between the techniques used among the other adhesives (OBFL and OBU). Moreover, at 24 h, only the PA demonstrated significant differences between the tested materials (p < 0.05). After 6 months, CSE, PBU, and OBU demonstrated significant differences between the techniques (p < 0.05), with a higher bond strength for CSE in AA and CVM modalities, for PBU in AA modality, and for OBU in AA and PA modalities. No significant differences were found between the techniques used among the OBFL (p > 0.05). In addition, only the CVM technique demonstrated significant differences between the tested materials after 6 months. CV and CVM showed a decreased value after aging for CSE and PBU, respectively. However, all the modalities decreased for OBU and OBFL after aging. All the adhesives showed marked resin infiltration into dentinal tubules in AA among all the modalities tested. Both universal adhesive systems (OBU and PBU) demonstrated statistically lower CA when compared to the other systems (CSE and OBFL) (p < 0.05) when applied in the PA mode. Concerning the AA mode, only CSE and OBFL were tested. The AA demonstrated lower CA values compared to the same adhesives in PA (p < 0.05). It could be concluded that the bond strength could be influenced by both materials and application techniques. It seems that the AA technique could be recommended as a gold standard for the application of an adhesive system to dentin. Plus, the CV and CVM modalities after 6 months of aging were considered stable for PBU and CSE, respectively. Consequently, the performance of these adhesive systems might vary when applied to other modalities. Future studies are needed to test this hypothesis.
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A void-free obturation during root canal treatment on primary teeth is currently very difficult to attain. In this study, the pulpectomy filling abilities of Bio-C Pulpecto (Angelus, Basil, Londrina, Paraná, Brazil) and of zinc oxide eugenol, or "ZOE" (DenPro, Prevest, New York, NY, USA), were compared using several in vitro techniques. Therefore, 30 primary anterior teeth were used in the present in vitro study. Analysis of variance (ANOVA), including a multiple comparison procedure (Holm-Sidak method, Dunn's Method, or Tukey test), was used. On micro-CT, Bio-C Pulpecto exhibited higher void percentages than did ZOE (10.3 ± 3.8%, and 3.5 ± 1.3%), respectively (p < 0.05). With digital microscopy, higher total void percentages were found in the BC (13.2 ± 26.7%) group compared to the ZOE (2.7 ± 2.8%) group (p < 0.05). With the CLSM, mean tubular penetration depths were higher for Bio-C Pulpecto than for ZOE in all canal thirds (p < 0.05). SEM images demonstrated no tags into dentinal tubules in either group throughout the three thirds. Moreover, higher statistically significant flowability was found for Bio-C (2.657 ± 0.06 mm) compared to ZOE (1.8 ± 0.13 mm) (p < 0.05). The findings of this study indicate that neither ZOE nor Bio-C Pulpecto appears to meet the criteria for an ideal root canal filling paste for primary teeth. This study laid the groundwork for future research by determining how micro-CT, digital microscopy, SEM, and CLSM contribute to our understanding of the filling process of primary teeth. More thorough research on the mechanism of root canal obturation on primary teeth is required to achieve a long-term successful root canal therapy in young children.
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This prospective study aimed to evaluate the success rate of partial pulpotomy using mineral trioxide aggregate (MTA), in permanent molars with symptomatic irreversible pulpitis. Moreover, this study aimed to investigate the effect of carious lesion depth and activity and bleeding time on the outcome of partial pulpotomy. Forty permanent molars with deep and extremely deep carious lesions clinically diagnosed with symptomatic irreversible pulpitis were included. The status of the carious lesion was evaluated clinically and radiographically to determine its activity (rapidly or slowly progressing) and depth (deep or extremely deep). A partial pulpotomy was performed and MTA was used. Clinical and radiographic analysis were performed at 3, 6 and 12 months. Chi-square analysis and Fisher's exact test were used. Scanning electron microscope and energy dispersive X-rays were used to investigate the crystalline structures and their chemical composition onto MTA surfaces after immersion in several conditions. The partial pulpotomy was 88.9% successful, with no significant difference in outcome between deep and extremely deep carious lesions (p = 0.22) or between rapidly and slowly progressing lesions (p = 0.18). Nevertheless, all failed cases were associated with rapidly progressing lesions and extremely deep lesions. All failures occurred when the bleeding time was more than 3 min (p = 0.10). Different crystalline structures were detected on MTA surfaces, with higher calcium percentages in PBS conditions. Within the limitations of the present study, favorable results demonstrated that MTA might be recommended as a suitable agent for partial pulpotomy in permanent molars with irreversible pulpitis. The depth and activity of the carious lesion as well as the bleeding time are important factors in the success of partial pulpotomy treatment. The prolonged bleeding time and the extremely deep rapidly progressing caries could be related with the failure cases in partial pulpotomy treatment of irreversible pulpitis.
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The role of the tumor microenvironment in tumor growth and therapy has recently attracted more attention in research and drug development. The ability of the microenvironment to trigger tumor maintenance, progression, and resistance is the main cause for treatment failure and tumor relapse. Accumulated evidence indicates that the maintenance and progression of tumor cells is determined by components of the microenvironment, which include stromal cells (endothelial cells, fibroblasts, mesenchymal stem cells, and immune cells), extracellular matrix (ECM), and soluble molecules (chemokines, cytokines, growth factors, and extracellular vesicles). As a solid tumor, melanoma is not only a tumor mass of monolithic tumor cells, but it also contains supporting stroma, ECM, and soluble molecules. Melanoma cells are continuously in interaction with the components of the microenvironment. In the present review, we focus on the role of the tumor microenvironment components in the modulation of tumor progression and treatment resistance as well as the impact of the tumor microenvironment as a therapeutic target in melanoma.
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The use of materials for computer-aided design/computer-aided manufacturing (CAD/CAM) has been rapidly increasing in daily practice. However, one of the main issues regarding modern CAD/CAM materials is their aging in the oral environment, which may lead to significant changes in their overall properties. The aim of this study was to compare the flexural strength, water sorption, cross-link density (softening ratio%), surface roughness, and SEM analysis of three modern CAD/CAM "multicolor" composites. Grandio (Grandio disc multicolor-VOCO GmbH, Cuxhaven, Germany), Shofu (Shofu Block HC-Shofu Inc., Kyoto, Japan), and Vita (Vita Enamic multiColor-Vita Zahnfabrik, Bad Sackingen, Germany) were tested in this study. They were prepared in stick-shaped specimens and submitted to different tests after several aging protocols, such as thermocycling and mechanical cycle loading challenge. Further disc-shaped specimens were also created and tested for water sorption, cross-link density, surface roughness, and SEM ultramorphology, before and after storage in an ethanol-based solution. For flexural strength and ultimate tensile strength, Grandio showed the greatest values both at baseline and after aging (p < 0.05). Grandio and Vita Enamic presented the highest modulus of elasticity and the lowest water sorption (p < 0.05). A significant reduction (p < 0.05) in microhardness after ethanol storage (softening ratio%) was observed especially in Shofu. Grandio had the lowest roughness parameters compared to the other tested CAD/CAM materials, while ethanol storage significantly increased the Ra and RSm values in Shofu (p < 0.05). Despite the comparable modulus of elasticity of Vita and Grandio, this latter showed greater flexural strength and ultimate tensile strength both at baseline and after aging. Hence, Grandio and Vita Enamic may be employed for the anterior teeth and for those restorations requiring load-bearing capacity. Conversely, aging seems to affect several properties of Shofu, so its use for permanent restorations should be well-pondered based on the clinical situation.
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Any excess solvent from dental adhesive systems must be eliminated prior to material photopolymerization. For this purpose, numerous approaches have been proposed, including the use of a warm air stream. This study aimed to investigate the effect of different temperatures of warm air blowing used for solvent evaporation on the bond strength of resin-based materials to dental and nondental substrates. Two different reviewers screened the literature in diverse electronic databases. In vitro studies recording the effect of warm air blowing to evaporate solvents of adhesive systems on the bond strength of resin-based materials to direct and indirect substrates were included. A total of 6626 articles were retrieved from all databases. From this, 28 articles were included in the qualitative analysis, and 27 remained for the quantitative analysis. The results of the meta-analysis for etch-and-rinse adhesives revealed that the use of warm air for solvent evaporation was statistically significantly higher (p = 0.005). For self-etch adhesives and silane-based materials, this effect was observed too (p < 0.001). The use of a warm air stream for solvent evaporation enhanced the bonding performance of alcohol-/water-based adhesive systems for dentin. This effect seems to be similar when a silane coupling agent is submitted to a heat treatment before the cementation of a glass-based ceramic.
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Amelogenesis imperfecta (AI) is a heterogeneous group of genetic rare diseases disrupting enamel development (Smith et al., Front Physiol, 2017a, 8, 333). The clinical enamel phenotypes can be described as hypoplastic, hypomineralized or hypomature and serve as a basis, together with the mode of inheritance, to Witkop's classification (Witkop, J Oral Pathol, 1988, 17, 547-553). AI can be described in isolation or associated with others symptoms in syndromes. Its occurrence was estimated to range from 1/700 to 1/14,000. More than 70 genes have currently been identified as causative. Objectives: We analyzed using next-generation sequencing (NGS) a heterogeneous cohort of AI patients in order to determine the molecular etiology of AI and to improve diagnosis and disease management. Methods: Individuals presenting with so called "isolated" or syndromic AI were enrolled and examined at the Reference Centre for Rare Oral and Dental Diseases (O-Rares) using D4/phenodent protocol (www.phenodent.org). Families gave written informed consents for both phenotyping and molecular analysis and diagnosis using a dedicated NGS panel named GenoDENT. This panel explores currently simultaneously 567 genes. The study is registered under NCT01746121 and NCT02397824 (https://clinicaltrials.gov/). Results: GenoDENT obtained a 60% diagnostic rate. We reported genetics results for 221 persons divided between 115 AI index cases and their 106 associated relatives from a total of 111 families. From this index cohort, 73% were diagnosed with non-syndromic amelogenesis imperfecta and 27% with syndromic amelogenesis imperfecta. Each individual was classified according to the AI phenotype. Type I hypoplastic AI represented 61 individuals (53%), Type II hypomature AI affected 31 individuals (27%), Type III hypomineralized AI was diagnosed in 18 individuals (16%) and Type IV hypoplastic-hypomature AI with taurodontism concerned 5 individuals (4%). We validated the genetic diagnosis, with class 4 (likely pathogenic) or class 5 (pathogenic) variants, for 81% of the cohort, and identified candidate variants (variant of uncertain significance or VUS) for 19% of index cases. Among the 151 sequenced variants, 47 are newly reported and classified as class 4 or 5. The most frequently discovered genotypes were associated with MMP20 and FAM83H for isolated AI. FAM20A and LTBP3 genes were the most frequent genes identified for syndromic AI. Patients negative to the panel were resolved with exome sequencing elucidating for example the gene involved ie ACP4 or digenic inheritance. Conclusion: NGS GenoDENT panel is a validated and cost-efficient technique offering new perspectives to understand underlying molecular mechanisms of AI. Discovering variants in genes involved in syndromic AI (CNNM4, WDR72, FAM20A ) transformed patient overall care. Unravelling the genetic basis of AI sheds light on Witkop's AI classification.
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This paper investigates the influence of cavity configuration and post-endodontic restoration on the fracture resistance, failure mode and stress distribution of premolars by using a method of fracture failure test and finite elements analysis (FEA) coupled to Weibull analysis (WA). One hundred premolars were divided into one control group (Gcontr) (n = 10) and three experimental groups, according to the post-endodontic restoration (n = 30), G1, restored using composite, G2, restored using single fiber post and G3, restored using multifilament fiberglass posts (m-FGP) without post-space preparation. Each experimental group was divided into three subgroups according to the type of coronal cavity configuration (n = 10): G1O, G2O, and G3O with occlusal (O) cavity configuration; G1MO, G2MO, and G3MO with mesio-occlusal (MO); and G1MOD, G2MOD, and G3MOD with mesio-occluso-distal (MOD). After thermomechanical aging, all the specimens were tested under compression load, and failure mode was determined. FEA and WA supplemented destructive tests. Data were statistically analyzed. Irrespective of residual tooth substance, G1 and G2 exhibited lower fracture resistance than Gcontr (p < 0.05), whereas G3 showed no difference compared to Gcontr (p > 0.05). Regarding the type of restoration, no difference was highlighted between G1O and G2O, G1MO and G2MO, or G1MOD and G2MOD (p > 0.05), whereas G3O, G3MO, and G3MOD exhibit higher fracture resistance (p < 0.05) than G1O and G2O, G1MO and G2MO, and G1MOD and G2MOD, respectively. Regarding cavity configuration: in G1 and G2, G1O and G2O exhibited higher fracture resistance than G1MOD and G2MOD, respectively (p < 0.05). In G3, there was no difference among G3O, G3MO and G3MOD (p > 0.05). No difference was found among the different groups and subgroups regarding the failure mode. After aging, premolars restored with multifilament fiberglass posts demonstrated fracture resistance values comparable to those of an intact tooth, irrespective of the different type of cavity configuration.
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The aim of the present study was to investigate the influence of the mechanical properties of three different calcium-silicate-based cements on the stress distribution of three different retrograde cavity preparations. Biodentine™ "BD", MTA Biorep "BR", and Well-Root™ PT "WR" were used. The compression strengths of ten cylindrical samples of each material were tested. The porosity of each cement was investigated by using micro-computed X-ray tomography. Finite element analysis (FEA) was used to simulate three retrograde conical cavity preparations with an apical diameter of 1 mm (Tip I), 1.4 mm (Tip II), and 1.8 mm (Tip III) after an apical 3 mm resection. BR demonstrated the lowest compression strength values (17.6 ± 5.5 MPa) and porosity percentages (0.57 ± 0.14%) compared to BD (80 ± 17 MPa-1.22 ± 0.31%) and WR (90 ± 22 MPa-1.93 ± 0.12%) (p < 0.05). FEA demonstrated that the larger cavity preparation demonstrated higher stress distribution in the root whereas stiffer cement demonstrated lower stress in the root but higher stress in the material. We can conclude that a respected root end preparation associated with cement with good stiffness could offer optimal endodontic microsurgery. Further studies are needed to define the adapted cavity diameter and cement stiffness in order to have optimal mechanical resistance with less stress distribution in the root.