Needs for re-intervention on restored teeth in adults: a practice-based study.

OBJECTIVES: Evaluate the need for re-intervention on dental coronal restorations in adults seen in a network of general dental practitioners (ReCOL).  MATERIALS AND METHODS: This observational, cross-sectional, multicenter study involved 40 practitioners and 400 patients. Coronal restoration failures (needing re-intervention for unsatisfactory outcomes) were assessed with a simplified rating scale of seven criteria from the FDI World Dental Federation. The oral health status, the risk factors, and Oral Health Impact Profile-14 were also examined. Previous restoration characteristics (extent, technique, material) were analyzed according to the need for re-intervention (yes/no), the age group, and the risk profile. Qualitative variables were compared between "re-intervention" and "no re-intervention" group using Fisher exact test. RESULTS: The need for re-intervention was estimated at 74% (95% CI: 70; 79); it increased with age (49 to 90%), unfavorable risk profile (82 vs. 62%), and extent of the filling (32, 39, 44, and 44% on 1, 2, 3 surfaces, and crowns, respectively). More posterior than anterior teeth were restored (median per patient: 6 vs. 1) or needed re-intervention (median per patient: 1 vs. 0). CONCLUSIONS: The needs for re-intervention in adults are still high within a context of ever-changing materials and techniques, simplified and rationalized decision-makings, and demands for patient involvement. CLINICAL RELEVANCE: Meeting these needs requires the following: (i) consensus definitions and assessment methods for "failure" and (ii) reliable feedbacks on materials, procedures, and satisfaction. Building large and detailed databases fed by networks of motivated practitioners will help analyzing complex success/failure data by artificial intelligence and guiding treatment and research.

Dental practice-based research networks (D-PBRN) worldwide: A scoping review.

OBJECTIVES: For more than twenty years, dental practice-based research networks (D-PBRN) have helped to structure clinical research in private practice. They bring together practitioners working in several structures and may include a greater number of subjects. The aims of this study were thus to systematically explore the scientific production from dental private practices in general and to map and describe the D-PBRN activity worldwide. DATA SOURCES: Two research procedures were carried out in parallel. The first was conducted as a scoping review to examine peer-reviewed literature indexed in the PubMed database and the second was performed on the World Wide Web to identify the main characteristics of the networks (location, scientific production…). STUDY SELECTION: 368 publications were identified among which 202 were published by PBRN members and the others by private practitioners not affiliated to any network. 210 (57 % of the included articles) were produced in the USA. A higher number of diverse centers are involved in each study when it is conducted by a PBRN (59.06 ± 66.59 vs. 13.51 ± 31.58 for networks and independent teams, respectively; p < 0.01). 24 D-PBRN were identified, a majority being based in the USA and 8 in Europe. CONCLUSIONS: Although dental practice-based research has grown over the years, the number of D-PBRN worldwide remains low. Even if it requires some investment to produce research in dental offices, this type of networks helps to fill the gap between private practice and research and to improve knowledge on oral health. RELEVANCE: The mapping of all the dental PBRN together with the research topics studied throughout the world make the relevance of this article. The ways to improve practice-based research in dentistry are also discussed in the paper.

Thyroglobulin Represents a Novel Molecular Architecture of Vertebrates.

Thyroid hormones modulate not only multiple functions in vertebrates (energy metabolism, central nervous system function, seasonal changes in physiology, and behavior) but also in some non-vertebrates where they control critical post-embryonic developmental transitions such as metamorphosis. Despite their obvious biological importance, the thyroid hormone precursor protein, thyroglobulin (Tg), has been experimentally investigated only in mammals. This may bias our view of how thyroid hormones are produced in other organisms. In this study we searched genomic databases and found Tg orthologs in all vertebrates including the sea lamprey (Petromyzon marinus). We cloned a full-size Tg coding sequence from western clawed frog (Xenopus tropicalis) and zebrafish (Danio rerio). Comparisons between the representative mammal, amphibian, teleost fish, and basal vertebrate indicate that all of the different domains of Tg, as well as Tg regional structure, are conserved throughout the vertebrates. Indeed, in Xenopus, zebrafish, and lamprey Tgs, key residues, including the hormonogenic tyrosines and the disulfide bond-forming cysteines critical for Tg function, are well conserved despite overall divergence of amino acid sequences. We uncovered upstream sequences that include start codons of zebrafish and Xenopus Tgs and experimentally proved that these are full-length secreted proteins, which are specifically recognized by antibodies against rat Tg. By contrast, we have not been able to find any orthologs of Tg among non-vertebrate species. Thus, Tg appears to be a novel protein elaborated as a single event at the base of vertebrates and virtually unchanged thereafter.

In Vivo Screening Using Transgenic Zebrafish Embryos Reveals New Effects of HDAC Inhibitors Trichostatin A and Valproic Acid on Organogenesis.

The effects of endocrine disrupting chemicals (EDCs) on reproduction are well known, whereas their developmental effects are much less characterized. However, exposure to endocrine disruptors during organogenesis may lead to deleterious and permanent problems later in life. Zebrafish (Danio rerio) transgenic lines expressing the green fluorescent protein (GFP) in specific organs and tissues are powerful tools to uncover developmental defects elicited by EDCs. Here, we used seven transgenic lines to visualize in vivo whether a series of EDCs and other pharmaceutical compounds can alter organogenesis in zebrafish. We used transgenic lines expressing GFP in pancreas, liver, blood vessels, inner ear, nervous system, pharyngeal tooth and pectoral fins. This screen revealed that four of the tested chemicals have detectable effects on different organs, which shows that the range of effects elicited by EDCs is wider than anticipated. The endocrine disruptor tetrabromobisphenol-A (TBBPA), as well as the three drugs diclofenac, trichostatin A (TSA) and valproic acid (VPA) induced abnormalities in the embryonic vascular system of zebrafish. Moreover, TSA and VPA induced specific alterations during the development of pancreas, an observation that was confirmed by in situ hybridization with specific markers. Developmental delays were also induced by TSA and VPA in the liver and in pharyngeal teeth, resulting in smaller organ size. Our results show that EDCs can induce a large range of developmental alterations during embryogenesis of zebrafish and establish GFP transgenic lines as powerful tools to screen for EDCs effects in vivo.

Tinkering signaling pathways by gain and loss of protein isoforms: the case of the EDA pathway regulator EDARADD.

BACKGROUND: Only a handful of signaling pathways are major actors of development and responsible for both the conservation and the diversification of animal morphologies. To explain this twofold nature, gene duplication and enhancer evolution were predominantly put forth as tinkering mechanisms whereas the evolution of alternative isoforms has been, so far, overlooked. We investigate here the role of gain and loss of isoforms using Edaradd, a gene of the Ecodysplasin pathway, implicated in morphological evolution. A previous study had suggested a scenario of isoform gain and loss with an alternative isoform (A) newly gained in mammals but secondarily lost in mouse lineage. RESULTS: For a comprehensive view of A and B Edaradd isoforms history during mammal evolution, we obtained sequences for both isoforms in representative mammals and performed in vitro translations to support functional predictions. We showed that the ancestral B isoform is well conserved, whereas the mammal-specific A isoform was lost at least 7 times independently in terminal lineages throughout mammal phylogeny. Then, to gain insights into the functional relevance of this evolutionary pattern, we compared the biological function of these isoforms: i) In cellulo promoter assays showed that they are transcribed from two alternative promoters, only B exhibiting feedback regulation. ii) RT-PCR in various tissues and ENCODE data suggested that B isoform is systematically expressed whereas A isoform showed a more tissue-specific expression. iii) Both isoforms activated the NF-κB pathway in an in cellulo reporter assay, albeit at different levels and with different dynamics since A isoform exhibited feedback regulation at the protein level. Finally, only B isoform could rescue a zebrafish edaradd knockdown. CONCLUSIONS: These results suggest that the newly evolved A isoform enables modulating EDA signaling in specific conditions and with different dynamics. We speculate that during mammal diversification, A isoform regulation may have evolved rapidly, accompanying and possibly supporting the diversity of ectodermal appendages, while B isoform may have ensured essential roles. This study makes the case to pay greater attention to mosaic loss of evolutionarily speaking "young" isoforms as an important mechanism underlying phenotypic diversity and not simply as a manifestation of neutral evolution.

Estrogen-related receptor γ is an in vivo receptor of bisphenol A.

Bisphenol A (BPA) is an endocrine disruptor that displays estrogenic activity. Several reports suggest that BPA may have estrogen receptor-independent effects. In zebrafish, 50 µM BPA exposure induces otic vesicle abnormalities, including otolith aggregation. The purpose of this study was to test if BPA action was mediated in vivo during zebrafish development by the orphan nuclear estrogen related receptor (ERR) γ. Combining pharmacological and functional approaches, we demonstrate that the zebrafish ERRγ mediates BPA-induced malformations in otoliths. Using different bisphenol derivatives, we show that different compounds can induce a similar otolith phenotype than BPA and that the binding affinity of these derivatives to the zebrafish ERRγ correlates with their ability to induce otolith malformations. Morpholino knockdown of ERRγ function suppresses the BPA effect on otoliths whereas overexpression of ERRγ led to a BPA-like otolith phenotype. Moreover, a subphenotypical dose of BPA (1 µM) combined with ERRγ overexpression led to a full-dose (50 µM) BPA otolith phenotype. We therefore conclude that ERRγ mediates the otic vesicle phenotype generated by BPA. Our results suggest that the range of pathways perturbed by this compound and its potential harmful effect are larger than expected.-Tohmé, M., Prud'homme, S. M., Boulahtouf, A., Samarut, E., Brunet, F., Bernard, L., Bourguet, W., Gibert, Y., Balaguer, P., Laudet, V. Estrogen-related receptor γ is an in vivo receptor of bisphenol A.