Challenges in conducting clinical research in primary care dentistry.

The integration of dentistry into primary health care is crucial for promoting patient well-being. However, clinical studies in dentistry face challenges, including issues with study design, transparency, and relevance to primary care. Clinical trials in dentistry often focus on specific issues with strict eligibility criteria, limiting the generalizability of findings. Randomized clinical trials (RCTs) face challenges in reflecting real-world conditions and using clinically relevant outcomes. The need for more pragmatic approaches and the inclusion of clinically relevant outcomes (CROs) is discussed, such as tooth loss or implant success. Solutions proposed include well-controlled observational studies, optimized data collection tools, and the integration of artificial intelligence (AI) for predictive modelling, computer-aided diagnostics and automated diagnosis. In this position paper advocates for more efficient trials with a focus on patient-centred outcomes, as well as the adoption of pragmatic study designs reflecting real-world conditions. Collaborative research networks, increased funding, enhanced data retrieval, and open science practices are also recommended. Technology, including intraoral scanners and AI, is highlighted for improving efficiency in dental research. AI is seen as a key tool for participant recruitment, predictive modelling, and outcome evaluation. However, ethical considerations and ongoing validation are emphasized to ensure the reliability and trustworthiness of AI-driven solutions in dental research. In conclusion, the efficient conduct of clinical research in primary care dentistry requires a comprehensive approach, including changes in study design, data collection, and analytical methods. The integration of AI is seen as pivotal in achieving these objectives in a meaningful and efficient way.

NaOCl Application after Acid Etching and Retention of Cervical Restorations: A 3-Year Randomized Clinical Trial.

This study evaluated the retention of composite resin restorations in noncarious cervical lesions (NCCLs) performed with or without pretreatment with 10% NaOCl solution (deproteinization). A randomized, controlled, split-mouth, double-blinded trial was carried out. Thirty patients with at least two NCCLs were included in the study. The NCCLs were randomly allocated into two treatment groups: control (acid etching with 37% phosphoric acid + placebo solution + Adper Single Bond 2/3M Oral Care + Filtek Z350/3M Oral Care) or experimental group (acid etching with 37% phosphoric acid + 10% NaOCl solution + Adper Single Bond 2 + Filtek Z350). A calibrated examiner evaluated the restorations at baseline (1 week) and recalls (6, 12, 24, and 36 months) using the FDI criteria. The primary outcome evaluated was retention of the restorations. Data were analyzed by the Kaplan-Meier method and the log-rank test (α=0.05). After 3 years, 64 restorations were evaluated in 23 patients. The annual failure rate was 9% for the control group and 17.8% for the experimental group (deproteinization technique). Considering the failures and their distribution among the characteristics of the patients and NCCLs, no statistically significant differences were observed for the control and experimental treatment groups (p=0.077) or the number of teeth in the mouth (p=0.320). Restorations in the mandible (p=0.039) and premolars (p=0.013) showed significantly lower clinical survival rates. The deproteinization pretreatment with a 10% NaOCl solution did not promote additional retention of restorations in NCCLs. (clinicaltrials. gov: NCT03086720).

Post-retained Restorations: A Cost-minimization Analysis Nested in a Randomized Clinical Trial.

OBJECTIVES: The aim of this study was to assess four post-retained restorative strategies for endodontically treated teeth using cost-minimization analysis. METHODS AND MATERIALS: The cost-minimization analysis was based on primary data from a randomized clinical trial and followed the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) guidelines. Two hundred twenty-five teeth (141 patients) restored using four strategies-teeth with ferrules+ restored with either glass fiber posts or direct composite or crowns, and teeth without ferrules- restored with either glass fiber or cast metal posts with crowns-were evaluated annually between 2009 and 2018. Initial costs and incremental costs per year were calculated. Survival curves were created using the Kaplan-Meier method and log-rank test. Kruskal-Wallis analysis was followed by Dunn's test, which was used to compare restorative treatments, with a significance level of 5%. RESULTS: Initial costs were greater for cast metal posts without crowns (US$153.14). Glass fiber posts with composite (US$27.11) were least costly; the most failures occurred in this group, but they were primarily repairable restoration fractures. The number of extractions, and thus cost, was greater for glass fiber posts with crowns. The mean annual cost was significantly lower for teeth restored with composite (p<0.001). Ferrule presence did not significantly impact annual costs. CONCLUSIONS: The use of glass fiber posts and direct composite incurred significantly lower annual costs than did other alternatives involving crowns or metal posts.

Occlusal and Esthetic Enhancement: A Noninvasive Approach to an Old Dilemma.

This article describes an indirect composite restoration technique for diastema closure and tooth lengthening with a noninvasive approach using regularly available materials such as silicone, composite resin, and an adhesive system. The procedure resulted in occlusal and functional improvement, with diastema closure, protrusive guide adjustment, and an increase in central incisor length. The procedure provided an adequate proportion of the central incisors with an esthetically natural appearance. It also resulted in simple, fast, and accurate manufacturing with a noninvasive esthetic indirect rehabilitation compared with more invasive preparation of ceramic veneers.

Morphology combined with ancillary techniques: An algorithm approach for thyroid nodules.

INTRODUCTION: Several authors have underlined the limits of morphological analysis mostly in the diagnosis of follicular neoplasms (FN). The application of ancillary techniques, including immunocytochemistry (ICC) and molecular testing, contributes to a better definition of the risk of malignancy (ROM) and management of FN. According to literature, the application of models, including the evaluation of ICC, somatic mutations (ie, BRAFV600E ), micro RNA analysis is proposed for FNs. This study discusses the validation of a diagnostic algorithm in FN with a special focus on the role of morphology then followed by ancillary techniques. METHODS: From June 2014 to January 2016, we enrolled 37 FNs with histological follow-up. In the same reference period, 20 benign nodules and 20 positive for malignancy were selected as control. ICC, BRAFV600E mutation and miR-375 were carried out on LBC. RESULTS: The 37 FNs included 14 atypia of undetermined significance/follicular lesion of undetermined significance and 23 FN. Specifically, atypia of undetermined significance/follicular lesion of undetermined significance resulted in three goitres, 10 follicular adenomas and one NIFTP whereas FN/suspicious for FN by seven follicular adenomas and 16 malignancies (nine non-invasive follicular thyroid neoplasms with papillary-like nuclear features, two invasive follicular variant of papillary thyroid carcinoma [PTC] and five PTC). The 20 positive for malignancy samples included two invasive follicular variant of PTC, 16 PTCs and two medullary carcinomas. The morphological features of BRAFV600E mutation (nuclear features of PTC and moderate/abundant eosinophilic cytoplasms) were associated with 100% ROM. In the wild type cases, ROM was 83.3% in presence of a concordant positive ICC panel whilst significantly lower (10.5%) in a negative concordant ICC. High expression values of MirR-375 provided 100% ROM. CONCLUSIONS: The adoption of an algorithm might represent the best choice for the correct diagnosis of FNs. The morphological detection of BRAFV600E represents the first step for the identification of malignant FNs. A significant reduction of unnecessary thyroidectomies is the goal of this application.

A Multicenter Randomized Double-blind Controlled Clinical Trial of Fiber Post Cementation Strategies.

OBJECTIVES: The aim of this prospective randomized multicenter clinical trial was to evaluate the survival rate of glass fiber-reinforced posts cemented with self-adhesive or regular resin cements. METHODS: The sample was comprised of 152 teeth randomized within two centers and in accordance with the adhesive strategies for RelyX U100/U200 (3M ESPE) or Single Bond and RelyX ARC (3M ESPE). The cementation procedures were standardized and performed by previously trained operators. The primary outcome evaluated was post debonding. A trained evaluator, one for each center, assessed all subjects at intervals of 12 months for up to 6 years. Statistical analysis was performed using the Kaplan-Meier method. RESULTS: There was no statistically significant difference in survival rates between the two strategies assessed ( p=0.991), with a 92.7% survival rate for the self-adhesive cement and 93.8% for the regular cement. CONCLUSION: Both the self-adhesive and the regular resin cements are good alternatives for glass fiber post cementation.

Antibiotic prescription for endodontic infections: a survey of Brazilian Endodontists.

AIM: To investigate antibiotic prescribing habits reported by Brazilian endodontists in specific clinical situations. METHODOLOGY: Brazilian endodontists (n = 13 853) were invited to answer an online questionnaire. The questionnaire consisted of two parts: the first part contained personal data such as age, gender, years of experience and location of endodontic practice; the second part included questions regarding their behaviour when prescribing antibiotics in dental practice. The subjects provided their registration number in the Regional Council of Dentistry (RCD) to prevent duplication of data. Data were collected and analysed by SPSS 17.0 (SPSS, Inc., Chicago, IL, USA). Chi-square and Fisher's exact tests were used to test the significance of possible associations (P < 0.05). RESULTS: From the 13 853 questionnaires, a total of 615 were answered (4.44%). The first-choice antibiotic was amoxicillin (81.5%), followed by amoxicillin + clavulanic acid (30.7%). For acute apical abscesses with intra- and extraoral diffuse swelling, fever and trismus, 90.1% reported they would prescribe antibiotics, whilst 88.1% reported they would prescribe antibiotics even without extraoral swelling, fever and trismus, and 20.5% would prescribe antibiotics in cases of chronic apical periodontitis, and sinus tract. The first-choice antibiotics varied by age of dentist (P < 0.001) and time elapsed since their endodontic graduation (P = 0.001). CONCLUSIONS: Many endodontists reported prescribing antibiotics in situations where they would not be indicated. Likewise, the general administration of antibiotics was longer in duration than necessary, reinforcing the need of continuous education regarding the use of antibiotics.

A phase 2 study of temozolomide in pretreated metastatic colorectal cancer with MGMT promoter methylation.

BACKGROUND: Presently, few options are available for refractory colorectal cancer (CRC). O6-methyl-guanine-DNA-methyltransferase (MGMT) promoter methylation is a frequent and early event in CRC tumourigenesis. This epigenetic silencing is a predictor of response to the alkylating drug temozolomide in glioblastoma. Preclinical evidences and some case reports showed temozolomide activity in CRC with MGMT silencing, but the available data from clinical trials are inconsistent. METHODS: This was a multicentre, phase 2 trial, planned according to a two-stage Simon's optimal design to investigate activity and safety of temozolomide in refractory CRC harbouring MGMT promoter methylation. The primary end point was overall response rate (ORR). Patients who failed two or more prior treatments received temozolomide at a dose of 150-200 mg m-2 per day on days 1-5 every 28 days. RESULTS: From July 2012 to June 2016, 225 patients were screened, 80 showed MGMT promoter methylation and 41 were enrolled. Overall response rate was 10% and disease control rate was 32%. Median progression-free survival and overall survival were 1.9 and 5.1 months, respectively. CONCLUSIONS: Temozolomide showed a modest activity in this heavily pretreated population and the study did not meet its primary end point. The role of temozolomide in CRC remains still controversial and further research is warranted.

Effect of different surface treatment techniques on the repair strength of indirect composites.

OBJECTIVES: Composite resin restorations present high survival rates and when a failure occurs repair is often possible. The aim of this study was to assess the effect of various repair techniques on indirect restorations. METHODS: LAVA Ultimate (3M), and Clearfil Estenia blocks (Kuraray) were repaired with our without surface roughness treatments, silane application and artificial ageing. Micro-shear bond stress tests were performed, while cohesive strength served as positive control. ANOVA was used for cohesive strength and effect of ageing, and linear mixed models to evaluate the effect of treatment variables on repair strength. RESULTS: Both materials reacted differently on surface treatments. Untreated (no treatment, no silane) repair strength was 16.3±6.3MPa for LAVA Ultimate and 19.0±4.3MPa for Estenia. Thermal cycling resulted in a 14-58% reduction of cohesive strength. Without cycling, all treatments resulted in a significant increase of bond strength in LAVA Ultimate (p<0.003). After cycling use of air-abrasion showed a positive trend for both substrates, significantly effective for LAVA Ultimate (p<0.04), and silane and CoJet for Estenia (p<0.024). The positive effect of HF treatment disappeared after cycling. CONCLUSION: It may be concluded that (1) the effect of surface treatment procedures on the repair bond strength of indirect composites is depended on the substrate and ageing. (2) Silane did not have a clear overall positive effect on bond strength and (3) artificial ageing had a strong negative influence on the stability of the adhesive interface and on the cohesive strength of one indirect composite resin material, but not the other.

Morphological features that can predict BRAFV600E -mutated carcinoma in paediatric thyroid cytology.

OBJECTIVE: BRAFV600E represents the most common diagnostic marker in papillary thyroid carcinoma (PTC). A few papers have demonstrated the correlation between BRAFV600E and specific morphological findings on PTCs in the adult population. This is the first reported series investigating cytological morphological parameters in paediatric thyroid carcinoma. METHODS: One hundred and nineteen paediatric samples (56 male and 63 female patients), diagnosed in the period between April 2013 and July 2015, were enrolled in the study. Fifteen patients with inadequate results were excluded. Cytological cases were processed with liquid-based cytology (LBC). BRAFV600E and immunocytochemistry for the VE1 antibody were performed on LBC. RESULTS: The diagnostic series included 10 mutated and 94 wild-type (WT) cases. Twenty two percent surgical samples showed 96% cytohistological concordance. The morphological analysis revealed plump cells (abundant eosinophilic cytoplasm and PTC nuclei) in all 10 mutated cases with only four cases showing a focal (less than 20% of the cells) plump component. None of the WT showed plump cells. A sickle nuclear shape was seen only in the mutated cases. VE1 yielded 100% positivity on mutated cases with three cytohistological discrepancies. CONCLUSIONS: The BRAFV600E mutation is also seen in paediatric cytology and the morphological features showed a high accuracy as both predictive mutational parameters and a helpful aid in management mainly of the aggressive BRAFV600E mutated carcinomas.

Fractographical Analysis and Biomechanical Considerations of a Tooth Restored With Intracanal Fiber Post: Report of the Fracture and Importance of the Fiber Arrangements.

OBJECTIVE: This article aims to present a fractographic analysis of an anterior tooth restored with a glass fiber post with parallel fiber arrangement, taking into account force vectors, finite element analysis, and scanning electron microscopy (SEM). METHODS: A patient presented at the Faculty of Dentistry (Federal University of Santa Maria, Brazil) with an endodontically treated tooth (ETT), a lateral incisor that had a restorable fracture. The treatment was performed, and the fractured piece was analyzed using stereomicroscopy, SEM, and finite element analysis. RESULTS: The absence of remaining coronal tooth structure might have been the main factor for the clinical failure. We observed different stresses actuating in an ETT restored with a fiber post as well as their relationship with the ultimate fracture. Tensile, compression, and shear stresses presented at different levels inside the restored tooth. Tensile and compressive stresses acted together and were at a maximum in the outer portions and a minimum in the inner portions. In contrast, shear stresses acted concomitantly with tensile and compressive stresses. Shear was higher in the inner portions (center of the post), and lower in the outer portions. This was confirmed by finite element analysis. The SEM analysis showed tensile and compression areas in the fiber post (exposed fibers=tensile areas=lingual surface; nonexposed fibers=compression areas=buccal surface) and shear areas inside the post (scallops and hackle lines). Stereomicroscopic analysis showed brown stains in the crown/root interface, indicating the presence of microleakage (tensile area=lingual surface). CONCLUSION: We concluded that glass fiber posts with parallel fibers (0°), when restoring anterior teeth, present a greater fracture potential by shear stress because parallel fibers are not mechanically resistant to support oblique occlusal loads. Factors such as the presence of remaining coronal tooth structure and occlusal stability assist in the biomechanical equilibrium of stresses that act upon anterior teeth.

Ferrule Effect: A Meta-analysis.

The aim of this study was to systematically review the literature for laboratory and clinical studies to evaluate the effect of ferrule in restored endodontically treated teeth. The search was conducted in 2 databases (PubMed, Scopus) with no publication year/language limits. From 1,872 potentially eligible studies, 124 studies were selected for full-text analysis, and 37 were included for review, with 32 of those considered in the meta-analysis and 5 considered in the survival analysis. Two reviewers independently selected the studies, extracted the data, and assessed the risk of bias. For laboratory studies, a meta-analysis was performed for the comparison of the fracture resistance of teeth with and without ferrule, and 3 subgroup analyses were conducted for ferrule height, post type, and type of tooth. For clinical studies, the Kaplan-Meier method was used to determine the survival of restorations, with log-rank test used to identify differences between groups ( α = 5%). Teeth without ferrule had a lower fracture resistance ( P < 0.00001), and the higher the height of ferrule, the greater the fracture resistance was, irrespective of the type of post ( P < .000001). Teeth with ferrule had higher clinical longevity ( P = 0.002); however, the presence of a ferrule was related to higher survival only for premolars ( P = 0.05). In conclusion, the presence of a ferrule is responsible for an improvement in the fracture resistance of the restoration in laboratory studies. Yet, other clinical factors besides the ferrule may be associated with survival in molars and anterior teeth and need to be further investigated. Knowledge Transfer Statement: The results of this study can be used by clinicians when deciding which approach to use when planning the restoration of endodontically treated teeth with and without ferrule. Ferrule may lead to higher tooth/restoration survival, while tooth location may influence therapeutic decisions.

Can Silanization Increase the Retention of Glass-fiber posts? A Systematic Review and Meta-analysis of In Vitro Studies.

The role of silanes in the bonding of resin luting agents to glass-fiber posts (GFPs) is a controversial topic, and the question still remains whether post silanization is able to improve the retention of GFPs luted into root canals. Thus, this study was designed to determine whether evidence exists to justify silanization of GFPs before cementation to increase their retention into root canals. In vitro studies that evaluated the retention of GFPs cemented into root canals or artificial substrates and that used silane coupling agents for pretreatment of the post were selected. Searches were carried out in PubMed and Scopus databases with no publication year or language limits. The last search was carried out in August 2014. Two distinct data analyses were carried out: 1) control group (no post pretreatment) vs silane only and 2) post pretreatment + silane vs silane only. Pooled-effect estimates were obtained by comparing the difference between each bond strength mean value and were expressed as the weighted mean difference between groups (p≤0.05). A total of 178 articles were found, and 23 were included in the review. The results were affected by the substrate into which the GFPs were luted (teeth or artificial devices). The analysis between control group and silane only for studies that used artificial devices favored the use of silane (p<0.0001), but considering studies that used teeth as substrate, no significant difference was observed (p=0.35). The analysis between silane only and pretreatment + silane did not show a significant difference between groups when artificial devices were used (p=0.71), whereas the analysis favored the use of post pretreatment + silane over silane (p<0.00001) only when the GFPs were luted into teeth. In conclusion, this review indicates that silanization improves the retention of GFPs luted into root canals provided that selective surface pretreatments are applied to the post before silanization.

Pituitary-tumour-transforming-gene 1 expression in testicular cancer.

Genomic instability is a feature of germ cell tumours. The pituitary-tumour-transforming-gene 1 (PTTG1) is the major effector of chromosome segregation during mitosis, protecting the cell from aneuploidy. The protein expression of this gene has been evaluated in testicular tumours by immunohistochemistry. Formalin-fixed and paraffin-embedded specimens of testicular tissues from 83 patients undergoing therapeutic orchidectomy for seminomas (n = 53), embryonal carcinoma (n = 10), yolk sac tumour (n = 10) and teratoma (n = 10) were examined. Seminoma was associated with in situ carcinoma (CIS) in 23 samples. PTTG1 immunostaining was performed using rabbit anti-PTTG1 as a primary antibody. In CIS, only isolated cells showed nuclear staining for PTTG1. In the peripheral area of seminoma, PTTG1 was mostly detected as localised in the nucleus; in the central area of seminoma, PTTG1 staining was more intense in cytoplasm. PTTG1-positive cells were also present in the areas of seminoma infiltration. On the other hand, in embryonal carcinoma, cells had a diffuse positive immunostaining, mainly cytoplasmatic, while we did not observe an expression of PTTG1 in yolk sac tumour and mature teratoma. We firstly identified the PTTG1 expression pattern in normal testis, CIS and testicular cancer. Further investigation is needed to clarify the functional activity of PTTG1 in testicular oncogenesis.

MMP Inhibitors on Dentin Stability: A Systematic Review and Meta-analysis.

The aim of this study was to systematically review the literature for in vitro and ex vivo studies that evaluated the effect of matrix metalloproteinase (MMP) inhibitors during the adhesive procedure on the immediate and long-term resin-dentin bond strength. The search was conducted in 6 databases with no publication year or language limits, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. From 1,336 potentially eligible studies, 48 were selected for full-text analysis, and 30 were included for review, with 17 considered in the meta-analysis. Two reviewers independently selected the studies, extracted the data, and assessed the risk of bias. Pooled effect estimates were expressed as the weighted mean difference between groups. The most used MMP inhibitor was chlorhexidine (CHX). Immediate bond strength results showed no difference between 2% CHX and control; however, a difference was found between 0.2% CHX and control at baseline. After aging, CHX presented higher bond strength values compared to control groups (p < .05). However, this was not observed for longer periods of aging. High heterogeneity was found in some comparisons, especially for the water storage aging subgroup. Subgroup analyses showed that self-etching and etch-and-rinse adhesives are benefited by the CHX use. From the studies included, only 1 presented low risk of bias, while the others showed medium or high risk of bias. The use of MMP inhibitors did not affect the immediate bond strength overall, while it influenced the aged bond strength. Aging procedures influenced bond strength values of the dentin adhesion stability.

The role of resin cement on bond strength of glass-fiber posts luted into root canals: a systematic review and meta-analysis of in vitro studies.

Because there are several ways to cement glass-fiber posts (GFPs) into root canals, there is no consensus on the best strategy to achieve high bond strengths. A systematic review was conducted to determine if there is difference in bond strength to dentin between regular and self-adhesive resin cements and to verify the influence of several variables on the retention of GFPs. This report followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. In vitro studies that investigated the bond strength of GFPs luted with self-adhesive and regular resin cements were selected. Searches were carried out in the PubMed and Scopus databases. No publication year or language limit was used, and the last search was done in October 2012. A global comparison was performed between self-adhesive and regular resin cements. Two subgroup analyses were performed: 1) Self-adhesive × Regular resin cement + Etch-and-rinse adhesive and 2) Self-adhesive × Regular resin cement + Self-etch adhesive. The analyses were carried out using fixed-effect and random-effects models. The results showed heterogeneity in all comparisons, and higher bond strength to dentin was identified for self-adhesive cements. Although the articles included in this meta-analysis showed high heterogeneity and high risk of bias, the in vitro literature seems to suggest that use of self-adhesive resin cement could improve the retention of GFPs into root canals.

Do educational methods affect students' ability to remove artificial carious dentine? A randomised controlled trial.

This trial aimed to evaluate the influence of two educational methods on students' ability to remove artificial carious dentine. Traditional lecture and lecture plus a live demonstration of artificial carious tissue removal were compared in a blind two-parallel-group design. Twenty-six students were randomly divided into two groups, and their skills were evaluated according to the following criteria: time spent on the dentine excavation procedure (in min), students' perceived confidence in conducting the procedure (graded assessed on a scale from 0 to 10), and the outcome of artificial carious tissue removal, evaluated by measuring the residual dyed artificial carious dentine layer (in µm). Statistical analyses were carried out using a t-test to compare the students' confidence and time spent on the procedure, and a two-way ANOVA was used to compare residual artificial decayed dentine with educational methods and tooth region (incisal, medium, and cervical thirds) as factors. There were no differences between the methods regarding excavation time (P = 0.898) and students' confidence (P = 0.382). The residual artificial carious dentine results showed that the educational method (P < 0.001) and cavity region (P < 0.001) were statistically significant, as was their interaction (P = 0.040). The lecture plus live demonstration group presented the best results for artificial caries removal. Although there were no differences between the two groups for the cervical region, the best results for the lecture plus live demonstration group was in the other two-thirds of the tooth.

KRAS mutational status affects oxaliplatin-based chemotherapy independently from basal mRNA ERCC-1 expression in metastatic colorectal cancer patients.

BACKGROUND: In this study, we evaluated the possibility that KRAS mutational status might be predictive of oxaliplatin (OXA) efficacy. We also explored the role of excision repair cross complementing group-1 (ERCC-1). METHODS: Ninety anti-epidermal growth factor receptor-naive advanced colorectal cancer patients were retrospectively analysed. In all patients KRAS mutational status was assessed. In 60 patients mRNA ERCC-1 expression was also investigated. Response rate (RR) and progression-free survival (PFS) after FOLFOX-6±bevacizumab were evaluated according to KRAS status and mRNA ERCC-1 expression. RESULTS: Among 90 patients 47% wild-type (wt) and 53% mutated (mt) KRAS tumours were found. Response rate was 26% in the wt KRAS group, whereas it was 56% in the mt KRAS group; the difference is statistically significant in the total sample (P=0.008) and when only patients receiving FOLFOX-6±bevacizumab as first-line are considered (P=0.01). Progression-free survival was longer in mt than in wt KRAS patients over all patients (10 vs 8 months, respectively, P=0.001) and in those treated as first-line (10 vs 8 months, respectively, P=0.0069). Mt KRAS patients experienced a longer survival (24 vs 18 months; P=0.01). ERCC-1 mRNA expression was not found to correlate with FOLFOX activity in our analysis. CONCLUSION: Our results suggest that activating mutation of KRAS oncogene may predict response to OXA. Basal expression of ERCC-1 mRNA does not explain the high efficacy of FOLFOX-6 in mt KRAS patients.

Can viscosity of acid etchant influence the adhesion of fibre posts to root canal dentine?

AIM: To evaluate the influence of acid viscosity, endodontic sealer and root canal region on the push-out bond strength of a glass fibre post. METHODOLOGY: Seventy-eight single-rooted human teeth were selected (60 for push-out and 18 for scanning electron microscopy characterization, SEM, n = 13 per group). The root canals were prepared with a step-back technique and then filled with Endofill or AH Plus sealer. Teeth without root fillings were used as controls. The preparation of the post-space was to a length of 11 mm using standardized rotary instruments. The root dentine was treated with 37% phosphoric acid (gel or liquid). The fibre posts (Reforpost) were silanized, and resin cement (Enforce) was used for luting procedures. Each root was cross-sectioned, and samples from the cervical and apical regions were subjected to a push-out bond strength test. Specimens from each group were sectioned longitudinally and subjected to SEM characterization for the dentine/cement/post interface. Statistical analysis for push-out tests was carried out using factorial anova followed by Tukey's test (P < 0.05). RESULTS: The three factors under evaluation (acid, endodontic sealer and region) and their interaction significantly influenced bond strength values (P < 0.05). In general, liquid phosphoric acid had significantly higher bond strength values in the apical region (P < 0.05), with hybrid layer formation, while endodontic sealers reduced bond strength values compared to the control (P < 0.05). CONCLUSION: The use of a liquid acid etchant created higher bond strength values in the apical region.

Molecular and cellular mechanisms that lead to Candida biofilm formation.

Fungal infections in the oral cavity are mainly caused by C. albicans, but other Candida species are also frequently identified. They are increasing in prevalence, especially in denture-wearers and aging people, and may lead to invasive infections, which have a high mortality rate. Attachment to mucosal tissues and to abiotic surfaces and the formation of biofilms are crucial steps for Candida survival and proliferation in the oral cavity. Candida species possess a wide arsenal of glycoproteins located at the exterior side of the cell wall, many of which play a determining role in these steps. In addition, C. albicans secretes signaling molecules that inhibit the yeast-to-hypha transition and biofilm formation. In vivo, Candida species are members of mixed biofilms, and subject to various antagonistic and synergistic interactions, which are beginning to be explored. We believe that these new insights will allow for more efficacious treatments of fungal oral infections. For example, the use of signaling molecules that inhibit biofilm formation should be considered. In addition, cell-wall biosynthetic enzymes, wall cross-linking enzymes, and wall proteins, which include adhesins, proteins involved in biofilm formation, fungal-bacterial interactions, and competition for surface colonization sites, offer a wide range of potential targets for therapeutic intervention.