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

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

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).

Is Conventional Resin Cement Adhesive Performance to Dentin Better Than Self-adhesive? A Systematic Review and Meta-Analysis of Laboratory Studies.

CLINICAL RELEVANCE: Conventional multistep resin cements presented higher adhesive performance to dentin than simplified self-adhesive cements, which is an important criterion for indirect restoration prognosis. SUMMARY: This study aimed to conduct a systematic review of the literature on laboratory studies assessing bonding performance to dentin of conventional and self-adhesive resin cements, in cementing indirect restorations. This review was reported according to the PRISMA Statement. Of a total of 518 studies, 36 were screened full text and reviewed according to exclusion criteria. Nineteen papers were included in the systematic review and meta-analyses, according to the following inclusion criteria: studies that evaluated the bond strength to dentin of indirect restorations cemented with dual conventional or self-adhesive resin cements and those that presented bond strength data in MPa as an outcome. Statistical analyses were conducted using Rev-Man 5.1. Comparisons were performed with random effects models at 5% significance level. A global analysis comparing conventional and self-adhesive cements and three subgroup analyses comparing immediate and long-term results were performed. Global analysis showed a difference between groups, with conventional resin cements presenting higher bond strength results than self-adhesive resin cements, in immediate and long-term time periods (both p=0.03). Immediate and longterm bond strength results were different for self-adhesive cements, favoring immediate bond strength (p=0.03), but immediate and long-term bond strength results for conventional resin cements were not different (p=0.06). Medium or high risk of bias was found in all studies. Conventional multistep resin cements showed superior overall adhesive performance compared with simplified self-adhesive resin cements when used to cement indirect restorations to dentin.

Regulation of hepatokine gene expression in response to fasting and feeding: Influence of PPAR-α and insulin-dependent signalling in hepatocytes.

AIM: In hepatocytes, the peroxisome proliferator-activated receptor (PPAR)-α and insulin receptor (IR) are critical for transcriptional responses to fasting and feeding, respectively. The present report analyzes the effects of nutritional status (fasting vs feeding) on the expression of a large panel of hepatokines in hepatocyte-specific PPAR-α (Pparαhep-/-) and IR (IRhep-/-) null mice. METHODS: Pparαhep-/- and IRhep-/- mice, and their wild-type littermates, were subjected to fasting or feeding metabolic challenges, then analyzed for hepatokine gene expression. Experiments were conducted in mice of both genders. RESULTS: Our data confirmed that PPAR-α is essential for regulating fasting-induced Fgf21 and Angptl4 expression. In mice lacking PPAR-α, fasting led to increased Igfbp1 and Gdf15 gene expression. In the absence of hepatic IR, feeding induced overexpression of Igfbp1, follistatin (Fst) and adropin (Enho), and reduced activin E (Inhbe) expression. Gender had only a modest influence on hepatokine gene expression in the liver. CONCLUSION: The present results highlight the potential roles of hepatokines as a class of hormones that substantially influence nutritional regulation in both female and male mice.

Bovine tooth is a substitute for human tooth on bond strength studies: A systematic review and meta-analysis of in vitro studies.

OBJECTIVES: This study aimed to systematically review the literature to compare the bond strength values achieved from human and bovine teeth of in vitro studies. DATA AND SOURCE: The PubMed/MEDLINE, ISI Web of Science and Scopus electronic databases were searched to select laboratorial studies that evaluated adhesive systems bond strength to human and bovine teeth. No publication year or language restriction was considered. STUDY SELECTION: From 1,285 potentially eligible studies, 15 were selected for full-text analysis, 11 were included in the systematic review and 9 in the meta-analysis. Two authors independently selected the studies, extracted the data and assessed the risk of bias. Mean differences were obtained by comparing bond strength values between human and bovine teeth (overall analysis), and considering enamel and dentin separately (subgroups analysis). Statistical analysis was performed using RevMan5.1, with random effects model, at a significance level of p=0.05. RESULTS: No significant difference was found between human and bovine teeth (p=0.35), either for enamel (p=0.07) or for dentin (p=0.93) substrates. Low to moderate heterogeneity was found on the meta-analysis. All included studies in the systematic review scored between medium and high risk of bias. CONCLUSIONS: Bovine teeth can be a reliable substitute for human ones on bond strength studies of adhesive systems to both enamel and dentin substrates.

The effect of grinding on the mechanical behavior of Y-TZP ceramics: A systematic review and meta-analyses.

The aim of this study was to systematically review the literature to assess the effect of grinding on the mechanical properties, structural stability and superficial characteristics of Y-TZP ceramics. The MEDLINE via PubMed and Web of Science (ISI - Web of Knowledge) electronic databases were searched with included peer-reviewed publications in English language and with no publication year limit. From 342 potentially eligible studies, 73 were selected for full-text analysis, 30 were included in the systematic review with 20 considered in the meta-analysis. Two reviewers independently selected the studies, extracted the data, and assessed the risk of bias. Statistical analyses were performed using RevMan 5.1, with random effects model, at a significance level of 0.05. A descriptive analysis considering phase transformation, Y-TZP grain size, Vickers hardness, residual stress and aging of all included studies were executed. Four outcomes were considered in the meta-analyses (factor: grinding x as-sintered) in global and subgroups analyses (grinding tool, grit-size and cooling) for flexural strength and roughness (Ra) data. A significant difference (p<0.05) was observed in the global analysis for strength, favoring as-sintered; subgroup analyses revealed that different parameters lead to different effects on strength. In the global analysis for roughness, a significant difference (p<0.05) was observed between conditions, favoring grinding; subgroup analyses revealed that different parameters also lead to different effects on roughness. High heterogeneity was found in some comparisons. Generally grinding promotes decrease in strength and increase in roughness of Y-TZP ceramics. However, the use of a grinding tool that allows greater accuracy of the movement (i.e. contra angle hand-pieces coupled to slowspeed turbines), small grit size (<50µm) and the use of plenty coolant seem to be the main factors to decrease the defect introduction and allow the occurrence of the toughening transformation mechanism, decreasing the risk of deleterious impact on Y-TZP mechanical properties.

White-to-brite conversion in human adipocytes promotes metabolic reprogramming towards fatty acid anabolic and catabolic pathways.

OBJECTIVE: Fat depots with thermogenic activity have been identified in humans. In mice, the appearance of thermogenic adipocytes within white adipose depots (so-called brown-in-white i.e., brite or beige adipocytes) protects from obesity and insulin resistance. Brite adipocytes may originate from direct conversion of white adipocytes. The purpose of this work was to characterize the metabolism of human brite adipocytes. METHODS: Human multipotent adipose-derived stem cells were differentiated into white adipocytes and then treated with peroxisome proliferator-activated receptor (PPAR)γ or PPARα agonists between day 14 and day 18. Gene expression profiling was determined using DNA microarrays and RT-qPCR. Variations of mRNA levels were confirmed in differentiated human preadipocytes from primary cultures. Fatty acid and glucose metabolism was investigated using radiolabelled tracers, Western blot analyses and assessment of oxygen consumption. Pyruvate dehydrogenase kinase 4 (PDK4) knockdown was achieved using siRNA. In vivo, wild type and PPARα-null mice were treated with a ß3-adrenergic receptor agonist (CL316,243) to induce appearance of brite adipocytes in white fat depot. Determination of mRNA and protein levels was performed on inguinal white adipose tissue. RESULTS: PPAR agonists promote a conversion of white adipocytes into cells displaying a brite molecular pattern. This conversion is associated with transcriptional changes leading to major metabolic adaptations. Fatty acid anabolism i.e., fatty acid esterification into triglycerides, and catabolism i.e., lipolysis and fatty acid oxidation, are increased. Glucose utilization is redirected from oxidation towards glycerol-3-phophate production for triglyceride synthesis. This metabolic shift is dependent on the activation of PDK4 through inactivation of the pyruvate dehydrogenase complex. In vivo, PDK4 expression is markedly induced in wild-type mice in response to CL316,243, while this increase is blunted in PPARα-null mice displaying an impaired britening response. CONCLUSIONS: Conversion of human white fat cells into brite adipocytes results in a major metabolic reprogramming inducing fatty acid anabolic and catabolic pathways. PDK4 redirects glucose from oxidation towards triglyceride synthesis and favors the use of fatty acids as energy source for uncoupling mitochondria.

Low-temperature degradation of Y-TZP ceramics: A systematic review and meta-analysis.

The aim of this study was to systematically review the literature to assess if low-temperature degradation (LTD) simulation in autoclave promotes deleterious impact on the mechanical properties and superficial characteristics of Y-TZP ceramics compared to the non-aged protocol. The MEDLINE via PubMed electronic database was searched with included peer-reviewed publications in English language and with no publication year limit. From 413 potentially eligible studies, 49 were selected for full-text analysis, 19 were included in the systematic review with 12 considered in the meta-analysis. Two reviewers independently selected the studies, extracted the data, and assessed the risk of bias. Statistical analysis was performed using RevMan 5.1, with random effects model, at a significance level of p<0.05. Descriptive analysis of monoclinic phase content data showed that aging in autoclave promotes an increase in m-phase content (ranging from 0% up to 13.4% before and 2.13% up to 81.4% after aging) with intensity associated to the material susceptibility and to the aging parameters (time, pressure and temperature). Risk of bias analysis showed that only 1 study presented high risk, while the majority showed medium risk. Five meta-analyzes (factor: aging×control) were performed considering global and subgroups analyzes (pressure, time, temperature and m-phase % content) for flexural strength data. In the global analysis a significant difference (p<0.05) was observed between conditions, favoring non-aging group. Subgroup analysis revealed statistical difference (p<0.05) favoring non-aging, for aging time >20h. However, for shorter aging times (≤20h), there was no difference between groups. Pressure subgroup analysis presented a statistical difference (p<0.05) only when a pressure ≥2bar was employed, favoring non-aging group. Temperature subgroup analysis showed a statistical difference (p<0.05) only when temperature=134°C was used, favoring the non-aging group. M-phase % content analysis presented statistical difference (p<0.05) when more than 50% of m-phase content was observed, favoring non-aging group. High heterogeneity was found in some comparisons. Aging in autoclave promoted low-temperature degradation, impacting deleteriously on mechanical properties of Y-TZP ceramics. However, the effect of LTD depends on some methodological parameters indicating that aging time higher than 20h; pressure ≥2bar and temperature of 134°C are ideal parameters to promote LTD effects, and that those effect are only observed when more than 50% m-phase content is observed.

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.

A multifunctional device to simulate oral ageing: the "Rub&Roll".

UNLABELLED: This article describes an in vitro fatigue and/or wear simulator enabling controlled application of force, speed, type of liquids and duration, to mimic challenges representative for the human oral environment. The device consists of a container in which a cylinder with specimen holder is placed which drives another cylinder (rod). The rod rotates in an opposite direction to the rotation of the stirring motor, rolling over the specimens mounted in the cylinder. When the rod contacts the specimen a force is applied to mimic processes in the oral environment. The design, working and construction principles of a new device, the Rub&Roll, and some of the possible applications are described Four different application examples are presented: occlusal wear in an low acidic abrasive slurry; combined erosive and abrasive wear of enamel exposed to apple juice or apple pulp; the wear of sealant material in natural teeth in an abrasive slurry; and the influence of mechanical loading cycles on micro tensile bond strength of an adhesive system to dentin Application of the "Rub & Roll" device showed results which are clinically relevant, reproducible and in accordance with existing literature. CONCLUSIONS: The Rub&Roll enables controlled application of chemical and mechanical loading, allowing variation of force, sliding distance, velocity, number of cycles, and frequency, and a combination with erosive and abrasive challenges representative of those in the oral environment.

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.

Proton pump inhibitor administration via nasogastric tube in pediatric practice: comparative analysis with protocol optimization.

Proton pump inhibitors (PPIs) are largely prescribed to children because their efficacy and tolerance are now well-established. One disadvantage resides in the absence of liquid form which causes problems for their administration in nasogastric tubes. Indeed, the absence of use recommendations involves many misuses responsible for inefficiency and/or tube obstruction. We tried to evaluate if PPIs can be administered through pediatric nasogastric tubes. We administered four PPIs (Omeprazole, esomeprazole, lansoprazole and lansoprazole orally disintegrating tablet) through nasogastric tubes. For each PPI a study plan was drawn up to assess the influence of different variables: the volume of water to dissolve or put in suspension the PPIs (2ml or 5ml), the volume of tube flush-through water post-PPI administration (2ml, 5ml or 10ml), the length (50cm or 125cm) and the diameter (6 or 8 French) of the polyurethane tubes. For each assay an analysis of each active ingredient at the tube outlet by UV spectrometry was carried out. All 6 F tubes were obstructed by PPIs. Through 8 F tubes, we observed a mean recovery of active ingredient of 86.2% for lansoprazole orally disintegrating tablet, 36.9% for esomeprazole but only 7.1% for lansoprazole and 3.9% for omeprazole. It is disadvised using omeprazole and lansoprazole through 8 F nasogastric tubes because no condition ensures the transit of an efficient concentration of active ingredient. For esomeprazole, the best conditions of administration were a water volume of 5ml and a rinse volume of 5ml but only a half of the microgranules administered were recovered. The most satisfactory results were obtained with lansoprazole orally disintegrating tablet. A 5ml volume of water diluent for suspension and a 10ml volume of flush-through water made it possible to deliver the full lansoprazole dose administered.

How do Shp2 mutations that oppositely influence its biochemical activity result in syndromes with overlapping symptoms?

Activating and inactivating mutations of SHP-2 are responsible, respectively, for the Noonan (NS) and the LEOPARD (LS) syndromes. Clinically, these developmental disorders overlap greatly, resulting in the apparent paradox of similar diseases caused by mutations that oppositely influence SHP-2 phosphatase activity. While the mechanisms remain unclear, recent functional analysis of SHP-2, along with the identification of other genes involved in NS and in other related syndromes (neurofibromatosis-1, Costello and cardio-facio-cutaneous syndromes), strongly suggest that Ras/MAPK represents the major signaling pathway deregulated by SHP-2 mutants. We discuss the idea that, with the exception of LS mutations that have been shown to exert a dominant negative effect, all disease-causing mutations involved in Ras/MAPK-mediated signaling, including SHP-2, might lead to enhanced MAPK activation. This suggests that a narrow range of MAPK signaling is required for appropriate development. We also discuss the possibility that LS mutations may not simply exhibit dominant negative activity.

[Lysophospholipids and cancer: current status and perspectives]. / Lysophospholipides et cancer: état des lieux et perspectives.

Circulating phospholipids carrying a single esterified fatty acid, the so-called lysophospholipids, are now considered as mediators of the intercellular communication. Their major members are the lysophosphatidic acid and the sphingosine 1-phosphate, two molecules displaying biological activities similar to those of growth factors or cytokines, through a recently identified subfamily of G protein-coupled receptors. They are involved in various biological processes, e.g., brain development and angiogenesis, but the following evidences suggest that these lipids are also significant actors of tumour development: (i) they stimulate the growth, survival and migration of tumour cells from various origins (ovary, prostate, glioblastoma...); (ii) they are abundant in malignant effusions; (iii) the lysophospholipid-producing enzymes are tumourigenic. Even if it remains necessary to define the role of these "oncolipids" in relationship with oncogenes and tumor suppressors, they may well be the mediators of an efficient autostimulatory system of the proliferating and migratory capacities of cancer cells, suggesting that lysophospholipids could represent novel valuable targets for anticancer pharmacology.

ConSSeq: a web-based application for analysis of amino acid conservation based on HSSP database and within context of structure.

SUMMARY: A web-based application to analyze protein amino acids conservation-Consensus Sequence (ConSSeq) is presented. ConSSeq graphically represents information about amino acid conservation based on sequence alignments reported in homology-derived structures of proteins. Beyond the relative entropy for each position in the alignment, ConSSeq also presents the consensus sequence and information about the amino acids, which are predominant at each position of the alignment. ConSSeq is part of the STING Millennium Suite and is implemented as a Java Applet. AVAILABILITY: http://sms.cbi.cnptia.embrapa.br/SMS/STINGm/consseq/, http://trantor.bioc.columbia.edu/SMS/STINGm/consseq/, http://mirrors.rcsb.org//SMS/STINGm/consseq/, http://www.es.embnet.org/SMS/STINGm/consseq/ and http://www.ar.embnet.org/SMS/STINGm/consseq/