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Endometriosis is a frequent and chronic inflammatory disease with impacts on reproduction, health and quality of life. This disorder is highly estrogen-dependent and the purpose of hormonal treatments is to decrease the endogenous ovarian production of estrogens. High estrogen production is a consistently observed endocrine feature of endometriosis. mRNA and protein levels of estrogen receptors (ER) are different between a normal healthy endometrium and ectopic/eutopic endometrial lesions: endometriotic stromal cells express extraordinarily higher ERß and significantly lower ERα levels compared with endometrial stromal cells. Aberrant epigenetic regulation such as DNA methylation in endometriotic cells is associated with the pathogenesis and development of endometriosis. Although there is a large body of data regarding ERs in endometriosis, our understanding of the roles of ERα and ERß in the pathogenesis of endometriosis remains incomplete. The goal of this review is to provide an overview of the links between endometriosis, ERs and the recent advances of treatment strategies based on ERs modulation. We will also attempt to summarize the current understanding of the molecular and cellular mechanisms of action of ERs and how this could pave the way to new therapeutic strategies.
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Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/genética , Receptor beta de Estrogênio/metabolismo , Receptores de Estrogênio/metabolismo , Metilação de DNA , Endométrio/citologia , Endométrio/metabolismo , Epigênese Genética , Feminino , Regulação da Expressão Gênica , Humanos , Receptores de Estrogênio/genética , Células Estromais/metabolismoRESUMO
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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OBJECTIVE: The study aimed to describe and to analyze the first morbidity and mortality review (MMRs) set up within a Dental University Hospital using detailed case reports to highlight the benefits of MMRs for patients, practitioners, teachers and to implement appropriate protocols to prevent recurrence. MATERIALS AND METHODS: The MMRs were performed within the dentistry departments of the hospital over the 1-year study period. Each case was reviewed according to a protocol based on a tool defined by the Clinical Risk Unit and the Association of Litigation and Risk Management (ALARM). RESULTS: Four cases were selected based on an oral report by a doctor from the dental service, a downstream service, or by the attending physician. The first case report related to a patient who suffered a breathing shock. The second concerned a tooth inhalation by a young disabled boy. The third was a therapeutic failure instigated by a student during a tooth preparation, and the fourth case involved an unexpected face-to-face meeting between a prisoner accompanied by police guards and an ancient victim at the dental hospital. DISCUSSION: Clinical incidents were investigated with the ALARM protocol. This process is also less focused on the individual who makes the error and more on contributing systemic factors. The systematic analysis of cases associated with bibliographic reviews improves learning and performance outcomes. Clear answers were given in response to the problems raised during these MMRs. CONCLUSION: In dental hospitals, the culture of MMRs needs to be integrated into resident training like in medical hospitals.
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OBJECTIVES: The location of the mandibular foramen is essential for the quality of the inferior alveolar nerve block anaesthesia and has often been studied with contradictory results over the years. The aim of this study was to locate the mandibular foramen, according to the dental age of the subject, through 3D analysis. METHODS: Three-dimensional images were reconstructed from mandibular computed tomography of 260 children, adolescents and adults. The occlusal plane was determined as the average plane passing through the buccal cusps of mandibular molars, premolars, and canines, and through the incisor edge. The mandibular foramen was located three dimensionally in relation to the anterior edge of the ramus (or coronoid notch), the sagittal plane and the occlusal plane. RESULTS: All along mandibular growth, the three distances defining the relative position of the mandibular foramen showed negligible changes. The mandibular foramen is located from - 0.4 to 2.9 mm above the occlusal plane. The distance between the mandibular foramen and the leading edge of the mandibular ramus ranged from 17 to 19.5 mm. The angle between the ramus and the sagittal plane ranged from 3° to 5.4°. CONCLUSION: In our sample, and using the occlusal plane and the anterior edge of the ramus as anatomical references, the location of the mandibular foramen was considered to be similar in all patients regardless of age.
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Mandíbula , Dente Molar , Adolescente , Adulto , Dente Pré-Molar , Criança , Humanos , Imageamento Tridimensional , Mandíbula/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
Estrogen-progestin therapy was previously considered as the standard of care for managing bothersome symptoms associated with menopause, but it increases risks of breast cancer and of thromboembolism. The combination of conjugated estrogen (CE) with bazedoxifene (BZA) named tissue-selective estrogen complex (TSEC) was designed to minimize or even abrogate the undesirable effects on breast, while maintaining the beneficial effects such as prevention of osteoporosis and suppression of climacteric symptoms. The risk on thromboembolism associated with TSEC is unknown, although the clinical available data are reassuring. The aim of this study was to define the impact of a chronic administration of CE, BZA or CE + BZA on hemostasis and thrombosis in ovariectomized mice. As expected, CE, but not BZA neither CE + BZA, induced uterine and vagina hypertrophy. As previously demonstrated for 17ß-estradiol (E2), we found that CE (i) increased tail-bleeding time, (ii) prevented occlusive thrombus formation in injured carotid artery and (iii) protected against collagen/epinephrine-induced thromboembolism. Thus, whereas BZA antagonized CE action on reproductive tissues, it had no impact on the effect of CE on hemostasis, thromboembolism and arterial thrombosis in mice. CE + BZA shared the anti-thrombotic actions of CE in these mouse models. If a similar process is at work in women, CE combined with BZA could contribute to minimize the risk of thrombosis associated with hormone replacement therapy.
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UNLABELLED: Morphological study of fiber post/bonding system/root dentin interface by evaluation of two bonding systems. OBJECTIVES: The aim of the study was to analyze the interfaces, and thus the seal, between root dentin and bonded fiber-reinforced posts. The interfaces were obtained by applying two enamel-dentin adhesive systems, a one-bottle system used after application of phosphoric acid and a self-etch system, both used with an adhesive cement. The interface was evaluated by SEM observation of the continuity of the hybrid layer and the morphology of the resin tags, in terms of length, density and presence of side branches, at the interface between the fiber-reinforced post, the bonding system and the root dentin. METHODS: Twenty-six anterior single-rooted teeth extracted for periodontal reasons were treated endodontically and then randomly separated into two groups of 13 teeth each: group 1: Excite DSC (Ivoclar Vivadent, Liechtenstein); group 2: AdheSE DC (Ivoclar Vivadent, Schaan, Liechtenstein). After preparation of the root canal and application of the adhesive, each specimen received a Postec translucent FRC post (Ivoclar Vivadent, Schaan, Liechtenstein) that was cemented in with Variolink II dual-curing luting composite (Ivoclar Vivadent, Schaan, Liechtenstein). The specimens were then prepared for SEM observation of the continuity of the hybrid layer and scoring of the morphology of the resin tags in each third of the root (at 1, 4.5 and 8mm from the coronal surface). RESULTS: There was no significant difference (at p<0.05) between the two groups in terms of continuity of the hybrid layer or morphology of the resin tags. The hybrid layer was present, unbroken and uniform in both the group where adhesive was used with a phosphoric acid total etch and the self-etch system group. Whatever the bonding system, the resin tags had side branches, and greater length and density in the cervical third than in the middle or apical thirds. Bubbles were found in the cement layer in most of the specimens. CONCLUSIONS: The one-bottle and self-etch bonding systems gave similar results in terms of interface morphology when a translucent fiber-reinforced post was cemented into the endodontically prepared roots.
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Colagem Dentária , Adesivos Dentinários , Técnica para Retentor Intrarradicular , Cimentos de Resina , Condicionamento Ácido do Dente/métodos , Resinas Acrílicas , Análise de Variância , Resinas Compostas , Dentina , Permeabilidade da Dentina , Humanos , Metacrilatos , Microscopia Eletrônica de VarreduraRESUMO
After a dental trauma, difficulties of communication and the consequences of the complex clinical situation often make regular chairside oral care long and complicated for special needs patients. The aim of this case report is to show how CAD/CAM technology may help in the prosthetic treatment of a clinical situation by keeping the number and duration of clinical sessions to a minimum while enabling a good aesthetic and functional result to be achieved in the long term.
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Desenho Assistido por Computador , Assistência Odontológica para a Pessoa com Deficiência , Planejamento de Prótese Dentária , Restauração Dentária Permanente/métodos , Incisivo/lesões , Fraturas dos Dentes/terapia , Acidentes por Quedas , Adolescente , Estética Dentária , Feminino , HumanosRESUMO
A promising alternative to conventional hormone therapy for postmenopausal symptoms is treatment combining Bazedoxifene (BZA), a third-generation selective estrogen receptor modulator (SERM), and conjugated equine estrogen (CE). This combination is also known as a tissue-selective estrogen complex (TSEC). Understanding the tissue-specific actions of SERMs and the TSEC remains a major challenge to try to predict their clinical effects. The aim of this study was to compare acute versus chronic treatment with BZA, CE or CE + BZA in two major targets of estrogens, the uterus and the liver. In these two tissues, acute treatment with CE, but not with BZA, induced similar gene expression change than the most important endogenous estrogen, 17-ß estradiol (E2). Acute induction of gene expression by E2 or by CE was antagonized by the addition of BZA. Concomitantly, BZA alone or in combination with E2 or CE induced a partial degradation of ERα protein after acute exposure. In uterus, chronic treatment of BZA alone had no impact on tissue weight gain or on epithelial cell proliferation, and also antagonized CE-effect in uterus, thereby mimicking the acute effect. By contrast, in the liver, chronic BZA and CE + BZA elicited agonistic transcriptional effects similar to those of CE alone. In addition, at variance to BZA acute effect, no change in ERα protein abundance was observed after chronic treatment in this tissue. These experimental in vivo data highlight a new aspect of the time-dependent tissue-specific action of BZA or TSEC, i.e. they can act acutely as antagonists but become agonists after chronic treatment. This shift was observed in liver tissue, but not in proliferative sex target such as the uterus.