RESUMO
Setting the condylar inclination of a dental articulator enables the delivery of prostheses without occlusal interferences. This technique article describes obtaining the sagittal condylar inclination (SCI) by using a facial and an intraoral scan of the protrusive interocclusal position. The SCI can be used on a virtual articulator in dental computer-aided design (CAD) software programs, which can facilitate the fabrication of functional prostheses without occlusal interferences.
Assuntos
Desenho Assistido por Computador , Articuladores Dentários , Registro da Relação MaxilomandibularRESUMO
For the retention and stability of removable complete dentures, the denture base should be fabricated with appropriate borders and polished surfaces. A technique for transferring the contour of a functional impression for digitally fabricated removable complete dentures is described.
Assuntos
Planejamento de Dentadura , Prótese Parcial Removível , Técnica de Moldagem Odontológica , Prótese Total , Prótese ParcialRESUMO
The articulator is a prerequisite device for the analysis of occlusion and prosthodontic treatment, and it is required to simulate patient jaw movements. This article describes the technique to obtain sagittal condylar inclination (SCI) using cone beam computed tomography (CBCT) data and intraoral scan of the protrusive interocclusal position. The SCI can be used on a virtual articulator in a computer-aided design software, and it can assist in the fabrication of prosthesis which is harmonious with the mandibular movement of individual patient.
Assuntos
Tomografia Computadorizada de Feixe Cônico , Articuladores Dentários , Desenho Assistido por Computador , Oclusão Dentária , Humanos , Imageamento Tridimensional , Registro da Relação Maxilomandibular , Mandíbula , Côndilo MandibularRESUMO
Reproducing soft tissue contours around a pontic area is important for the fabrication of an esthetic prosthesis, especially in the anterior area. A gingival model that precisely replicates the soft tissue structure around the pontic area can be easily obtained by taking a pick-up impression of an interim fixed dental prosthesis. After a working cast is fabricated using the customary technique, the pick-up model is superimposed onto the working model for the pontic area using computer-aided design and manufacturing (CAD/CAM). A definitive restoration using this technique would be well adapted to the pontic base, which is formed by the interim prosthesis.
Assuntos
Desenho Assistido por Computador , Coroas , Planejamento de Prótese Dentária , Prótese Dentária Fixada por Implante , Prótese Parcial Fixa , Gengiva/anatomia & histologia , Técnica de Moldagem Odontológica , Prótese Parcial Temporária , Estética Dentária , Modelos Dentários , Vaselina , Reprodutibilidade dos TestesRESUMO
The conventional method for impressions of flabby tissue uses modified trays and highly flowable materials, but mucostatic impressions are difficult to achieve due to the viscous and the elastic natures of impression materials. In this report, a technique is presented in which conventional impression and intraoral scanning for a fully edentulous patient with flabby tissue are combined. The definitive impression was obtained by applying appropriate pressure to each tissue area, and the denture can be maintained passively and stable at rest and during function.
Assuntos
Técnica de Moldagem Odontológica , Boca Edêntula , Materiais para Moldagem Odontológica , Prótese Total , HumanosRESUMO
Although we recently demonstrated that static magnetic fields (SMFs) of 3, 15, and 50 mT stimulate osteoblastic differentiation, the effects of SMFs on osteoclastogenesis are still poorly understood. This study focused on the suppressive effects of SMFs on receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclastogenesis and bone resorption. Direct SMFs inhibit RANKL-induced multinucleated osteoclast formation, tartrate-resistant acid phosphatase activity, and bone resorption in mouse bone marrow-derived macrophage cells. The conditioned medium from osteoblasts treated with SMFs also resulted in the inhibition of osteoclast differentiation as well as resorption. The RANKL-induced expression of osteoclast-specific transcription factors, such as c-Fos and NFATc1, was remarkably downregulated by SMF at 15 mT. In addition, SMF inhibited RANKL-activated Akt, glycogen synthase kinase 3ß (GSK3ß), extracellular signal-regulated kinase, c-jun N-terminal protein kinase, mitogen-activated protein kinase (MAPK), and nuclear factor-κB (NF-κB) formation. These findings indicate that SMF-mediated attenuation of RANKL-induced Akt, GSK3ß, MAPK, and NF-κB pathways could contribute to the direct and indirect inhibition of osteoclast formation and bone resorption. Therefore, SMFs could be developed as a therapeutic agent against periprosthetic or peri-implant osteolysis. Additionally, these could be used against osteolytic diseases such as osteoporosis and rheumatoid arthritis. Bioelectromagnetics. 39:394-404, 2018. © 2018 Wiley Periodicals, Inc.
Assuntos
Células da Medula Óssea/fisiologia , Diferenciação Celular/fisiologia , Campos Magnéticos , Osteoclastos/fisiologia , Animais , Células da Medula Óssea/citologia , Reabsorção Óssea/patologia , Reabsorção Óssea/fisiopatologia , Células Cultivadas , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Glicogênio Sintase Quinase 3 beta/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Camundongos Endogâmicos ICR , NF-kappa B/metabolismo , Fatores de Transcrição NFATC/metabolismo , Osteoclastos/citologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ligante RANK/metabolismo , Transdução de SinaisRESUMO
Since the introduction of immediate implant placements, the buccal bony wall has been a major consideration for success due to its correlation with soft tissue contour and color. This report presents the stability of the buccal wall thickness of an immediately placed implant at the anterior maxilla over 10 years. Although the width of the buccal wall decreased at the 2-year post-op follow-up, it remained stable afterward according to cone beam computerized tomography (CBCT) scans. Hence, this report suggests that ensuring adequate bony wall thickness with bone augmentation and fixture position may promise the longevity of the buccal bony wall and surrounding soft tissue in an immediate implant placement.
Assuntos
Processo Alveolar , Tomografia Computadorizada de Feixe Cônico , Maxila , Processo Alveolar/diagnóstico por imagem , Humanos , Maxila/diagnóstico por imagem , Próteses e Implantes , ZigomaRESUMO
In the present study, we evaluated the potential of poly-l-lysine/hyaluronic acid (HA/PLL) hydrogels containing curcumin (CUR) and bone morphogenetic protein-2 (BMP-2) as bone tissue regeneration scaffolds. Hydrogels HP-1Ë2 were formed by amide bonds via the condensation reactions between 0.02 µmol HA and 0.060.12 µmol poly-l-lysine · hydrobromide (PLL · HBr). Physical, chemical, and thermal analyses revealed that the amount of PLL · HBr significantly influenced hydrogel properties. Based on an In Vitro MG-63 cell proliferation test, HP-1Ë2 were cytocompatible, and all hydrogels containing different amounts of CUR and BMP-2, except for HA0.02/PLL0.06/CUR20/BMP-2100 (HPCB-4), resulted in cell proliferation above 80%. An In Vitro release test showed that CUR and BMP-2 were consistently released from HA0.02/PLL0.06/CUR15 (HPC), HA0.02/PLL0.06/BMP-2100 (HPB), HA0.02/PLL0.06/CUR15/BMP-210 , 50 , or 100 (HPCB-1Ë3), and HA0.02/PLL0.06/CUR10 or 20/BMP-2100 (HPCB-4Ë5) for 7 and 28 days, respectively. In Vitro ALP activity and calcium deposition and In Vivo micro-computed tomography (micro-CT) tests demonstrated the potential application of HPCB-3 as bone tissue regeneration scaffolds, suggesting that bone tissue regeneration can be optimized by controlling the amounts of CUR and BMP-2.
Assuntos
Proteína Morfogenética Óssea 2/farmacologia , Curcumina/farmacologia , Osteogênese/efeitos dos fármacos , Engenharia Tecidual/métodos , Animais , Regeneração Óssea/efeitos dos fármacos , Ácido Hialurônico/química , Hidrogéis/química , Camundongos , Polilisina/química , Alicerces Teciduais/química , Microtomografia por Raio-XRESUMO
Simvastatin (SIM) accelerates new bone formation both in vitro and In Vivo by enhancing the expression of recombinant human bone morphogenetic protein-2 (rhBMP-2). In this study, we evaluated the effect of water-solubility of SIM on new bone formation by preparing two types of supramolecular hydrogels: pseudopolyrotaxanes (PPRXs) based on metoxy polyethyleneglycol-grafted hyaluronic acid (MPEG-g-HA) and α-cyclodextrin (α-CD) containing water-soluble hydroxypropyl ß-cyclodextrin/simvastatin inclusion complex (HP-ß-CD-ic-SIM; MPEG-g-HA/α-CD/HP-ß-CD-ic-SIM) or only SIM (MPEG-g-HA/α-CD/SIM). As compared to MPEG-g- HA/α-CD/SIM, SIM was more rapidly released from MPEG-g-HA/α-CD/HP-ß-CD-ic-SIM in a sustained manner owing to increased water-solubility. New bone actively formed at the calvarial defect site in a rabbit model 4 weeks after implantation, as examined by micro computed tomography (micro CT), hematoxylin and eosin (H&E) staining, and Goldner's trichrome staining. The results showed that the water-solubility of SIM plays a significant role in enhancing new bone formation in vivo.
Assuntos
Ciclodextrinas/química , Ácido Hialurônico/química , Hidrogéis/química , Osteogênese/efeitos dos fármacos , Poloxâmero/química , Rotaxanos/química , Sinvastatina , Animais , Humanos , Camundongos , Sinvastatina/química , Sinvastatina/farmacocinética , Sinvastatina/farmacologia , Crânio/diagnóstico por imagem , Crânio/efeitos dos fármacos , SolubilidadeRESUMO
Evaluating the cement space of various dental prostheses is important because it is related to the stability and retention of the prosthesis. However, a method for evaluating an overall cement space is complex. The purpose of this technique was to simplify the evaluation of prosthesis cement space by using a digital scanner. The form and thickness of the cement space could be simply recognized in any section the clinician or dental researcher wishes. Moreover, the cement space of several dental prostheses for the same abutment could also be precisely evaluated by superimposition. The method can be applied to various prosthodontic treatments.
Assuntos
Cimentos Dentários/uso terapêutico , Planejamento de Prótese Dentária/métodos , Prótese Dentária/métodos , Desenho Assistido por Computador , Retenção em Prótese Dentária/métodos , Humanos , Imageamento TridimensionalRESUMO
Zirconia (Zr) is also known as a biocompatible material with favorable mechanical properties as well as low plaque adhesion. In this study, we examined the efficacy of Zr coated with growth and differentiation factor-5 (GDF-5) bonded via click reaction as a substrate to support osteogenic differentiation of MC3T3-E1 cells. Pristine and surface-modified Zr surfaces were characterized by scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS), resulting that GDF-5 was successfully coated to the pristine Zr surface. GDF-5 coated to Zr surfaces was released for 28 days in a sustained manner. New bone formation onto GDF-5 coated Zr (Zr/GDF-5) surface was confirmed by in vitro test including cell proliferation, alkaline phosphatase activity and calcium deposition assays, and in vivo test including real-time polymerase chain reaction (qPCR) assay including osterix (OSX), runt-related transcription factor 2 (Runx 2), COL 1 (type I collagen) and osteocalcin (OC). Cell proliferation, alkaline phosphatase activity, and calcium deposition of MC3T3- E1 cells were significantly enhanced when the cells were cultured on Zr/GDF-5. Additionally, the results of qPCR revealed that genes related with osteogenic differentiation were up regulated when the cells were cultured on Zr/GDF-5. Our findings demonstrate that Zr/GDF-5 could be used as a material for enhancing the efficacy of osteogenic differentiation.
Assuntos
Diferenciação Celular/efeitos dos fármacos , Materiais Revestidos Biocompatíveis , Fator 5 de Diferenciação de Crescimento , Nanopartículas/química , Osteogênese/efeitos dos fármacos , Zircônio , Animais , Linhagem Celular , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Fator 5 de Diferenciação de Crescimento/química , Fator 5 de Diferenciação de Crescimento/farmacologia , Camundongos , Zircônio/química , Zircônio/farmacologiaRESUMO
PURPOSE: The aim of this study was to determine the stability of computer-aided design and manufacturing (CAD/CAM) and prefabricated abutment by measuring removal torque before and after cyclic loading. MATERIALS AND METHODS: Three types of fixture and 2 types of abutments were used. Removable torque was measured after cyclic loading for 5000 cycles between 25 and 250 N for each group. The same procedure was performed twice. RESULTS: First, removal torque values (Newton centimeter) were measured for stock versus custom abutments as follows: group 1: 27.17 versus 26.67, group 2: 26.27 versus 26.33, and group 3: 37.33 versus 36.67. Second removal torque values (Newton centimeter) were also measured: group 1: 23 versus 23.5, group 2: 22.5 versus 22.33, and group 3: 32.67 versus 32.5. There was no significant difference between the stock and custom abutments in either the first or second removal torque values and also no significant difference among initial tightening torque, first or second removal torque (P > 0.05). CONCLUSION: With precise control of CAD/CAM abutments, good screw joint stability can be achieved.
Assuntos
Desenho Assistido por Computador , Dente Suporte , Projeto do Implante Dentário-Pivô/métodos , Planejamento de Prótese Dentária/métodos , Parafusos Ósseos , Falha de Restauração Dentária , Análise do Estresse Dentário , Humanos , TorqueRESUMO
An obturator prosthesis with insufficient retention and support may be improved with implant placement. However, implant surgery in patients after maxillary tumor resection can be complicated because of limited visibility and anatomic complexity. Therefore, computer-guided surgery can be advantageous even for experienced surgeons. In this clinical report, the use of computer-guided surgery is described for implant placement using a bone-supported surgical template for a patient with maxillary defects. The prosthetic procedure was facilitated and simplified by using computer-aided design/computer-aided manufacture (CAD/CAM) technology. Oral function and phonetics were restored using a tooth- and implant-supported obturator prosthesis. No clinical symptoms and no radiographic signs of significant bone loss around the implants were found at a 3-year follow-up. The treatment approach presented here can be a viable option for patients with insufficient remaining zygomatic bone after a hemimaxillectomy.
Assuntos
Desenho Assistido por Computador , Planejamento de Prótese Dentária , Prótese Dentária Fixada por Implante/métodos , Maxila/cirurgia , Procedimentos Cirúrgicos Pré-Protéticos Bucais/métodos , Obturação do Canal Radicular/métodos , Cirurgia Assistida por Computador/métodos , Adulto , Implantação Dentária Endóssea/métodos , Humanos , MasculinoRESUMO
Melatonin's effect on hepatic differentiation of stem cells remains unclear. The aim of this study was to investigate the action of melatonin on hepatic differentiation as well as its related signaling pathways of human dental pulp stem cells (hDPSCs) and to examine the therapeutic effects of a combination of melatonin and hDPSC transplantation on carbon tetrachloride (CCl4 )-induced liver fibrosis in mice. In vitro hepatic differentiation was assessed by periodic acid-Schiff (PAS) staining and mRNA expression for hepatocyte markers. Liver fibrosis model was established by injecting 0.5 mL/kg CCl4 followed by treatment with melatonin (5 mg/kg, twice a week) and hDPSCs. In vivo therapeutic effects were evaluated by histopathology and by means of liver function tests including measurement of alanine transaminase (ALT), aspartate transaminase (AST), and ammonia levels. Melatonin promoted hepatic differentiation based on mRNA expression of differentiation markers and PAS-stained glycogen-laden cells. In addition, melatonin increased bone morphogenic protein (BMP)-2 expression and Smad1/5/8 phosphorylation, which was blocked by the BMP antagonist noggin. Furthermore, melatonin activated p38, extracellular signal-regulated kinase (ERK), and nuclear factor-κB (NF-κB) in hDPSCs. Melatonin-induced hepatic differentiation was attenuated by inhibitors of BMP, p38, ERK, and NF-κB. Compared to treatment of CCl4 -injured mice with either melatonin or hDPSC transplantation alone, the combination of melatonin and hDPSC significantly suppressed liver fibrosis and restored ALT, AST, and ammonia levels. For the first time, this study demonstrates that melatonin promotes hepatic differentiation of hDPSCs by modulating the BMP, p38, ERK, and NF-κB pathway. Combined treatment of grafted hDPSCs and melatonin could be a viable approach for the treatment of liver cirrhosis.
Assuntos
Antioxidantes/farmacologia , Diferenciação Celular/efeitos dos fármacos , Polpa Dentária/metabolismo , Hepatócitos/metabolismo , Cirrose Hepática/terapia , Melatonina/farmacologia , Transplante de Células-Tronco , Células-Tronco/metabolismo , Animais , Antígenos de Diferenciação/biossíntese , Intoxicação por Tetracloreto de Carbono/metabolismo , Intoxicação por Tetracloreto de Carbono/patologia , Intoxicação por Tetracloreto de Carbono/terapia , Polpa Dentária/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Hepatócitos/patologia , Xenoenxertos , Humanos , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/metabolismo , Cirrose Hepática/patologia , Masculino , Camundongos , Camundongos Nus , Células-Tronco/patologiaRESUMO
The aim of this study is to determine the effects of the combination of recombinant human BMP-2 (rh-BMP-2) and dentin sialoprotein (rh-DSP) on growth and differentiation in human cementoblasts and determine the underlying signal transduction mechanism. Compared to treatment of cementoblasts with either rh-BMP-2 or rh-DSP alone, the combination of rh-BMP-2 and rh-DSP synergistically increased cell growth, ALP activity, nodule formation and expression of differentiation markers. The differentiation-promoting effect was also observed in periodontal ligament cells and an osteoblastic cell line. Likewise, combination of rh-DSP and rh-BMP-2 increased BMP-2 mRNA expression and Smad1/5/8 phosphorylation, which was blocked by the BMP antagonist noggin. The expression levels of α2ß1 integrin and RhoA, as well as the phosphorylation status of FAK and Akt, were increased by the combination of rh-BMP-2 and rh-DSP in a time-dependent manner. In addition, rh-BMP-2 and rh-DSP enhanced expression of Wnt ligands, ß-catenin activation and GSK-3ß phosphorylation, all of which were inhibited by the Wnt receptor antagonist DKK1. Furthermore, treatment with rh-DSP plus rh-BMP-2 resulted in phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 and also induced the nuclear translocation of the NF-κB p65 subunit, which was blocked by noggin. This study demonstrates for the first time that rh-DSP and rh-BMP-2 act synergistically, enhancing each other's ability to stimulate cementoblastic cell growth and differentiation in vitro via autocrine BMP, integrin, Wnt/ß-catenin, MAP kinase and NF-κB pathways. These results support the therapeutic potential of a combination strategy for aiding periodontal regeneration.
Assuntos
Proteína Morfogenética Óssea 2/farmacologia , Cemento Dentário/citologia , Cemento Dentário/efeitos dos fármacos , Proteínas da Matriz Extracelular/farmacologia , Fosfoproteínas/farmacologia , Sialoglicoproteínas/farmacologia , Fator de Crescimento Transformador beta/farmacologia , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Cemento Dentário/metabolismo , Humanos , Ligamento Periodontal/citologia , Ligamento Periodontal/efeitos dos fármacos , Ligamento Periodontal/metabolismo , Proteínas Recombinantes/farmacologia , Transdução de Sinais/efeitos dos fármacosRESUMO
With conventional fixed dental prostheses, the interim restoration is a valuable diagnostic tool in the evaluation of esthetics and function. To achieve predictable definitive esthetic results, information about the subgingival and the supragingival contour of a properly designed restoration should be communicated to the dental laboratory technician. The technique described enables the accurate transfer of the soft tissue morphology developed with an interim prosthesis to the definitive cast. This modified definitive cast allows the dental laboratory technician to fabricate a restoration with an emergence profile identical to that of the interim prosthesis.
Assuntos
Coroas , Planejamento de Prótese Dentária , Restauração Dentária Temporária , Gengiva/anatomia & histologia , Modelos Dentários , Materiais para Moldagem Odontológica/química , Técnica de Moldagem Odontológica , Técnicos em Prótese Dentária , Estética Dentária , Técnicas de Retração Gengival/instrumentação , Laboratórios Odontológicos , Metilmetacrilatos/química , Polivinil , SiloxanasRESUMO
BACKGROUND: Concussions are common among athletes, with the potential to cause memory-related, physical, cognitive, emotional, and behavioral damage. A concussion is an acceleration/deceleration injury resulting from direct and indirect biomechanical forces transmitted to the cerebral tissues. From a sports dentistry viewpoint, increased mastication muscle activity or clenching due to the presence of a mouthguard may enhance cervical muscle activity, thereby reducing damage following impact. This relationship has not been previously investigated in the context of rugby. The purpose of this study was to investigate the effect of voluntary clenching on indirect head acceleration during attack- and defense-related drills. MATERIALS AND METHODS: A total of 12 high school rugby players participated in the study. Linear acceleration of the head was measured using an accelerometer that took measurements in three axes. Masseter and sternocleidomastoid muscle activities were measured using wireless electromyography. These data were synchronized using digital video imaging software for analysis. The study protocol was approved by the Tokyo Dental College Ethics Committee. RESULTS AND CONCLUSIONS: Within the limitations of this study, the following results were obtained: the activities performed during rugby practice involved relatively small indirect head acceleration and masseter and sternocleidomastoid muscle activities. After the young male rugby players were instructed to clench their masseter muscles, a marked decrease in head acceleration was observed.
Assuntos
Aceleração , Concussão Encefálica/prevenção & controle , Futebol Americano/lesões , Cabeça/fisiologia , Músculo Masseter/fisiologia , Adolescente , Eletromiografia , Humanos , Masculino , Protetores BucaisRESUMO
BACKGROUND: The positive effects of wearing a mouthguard on shock absorption have been indicated in various papers. The ability of a mouthguard to protect against indirect injury, however, is not clear, and the thickness that a mouthguard would require to provide such protection remains to be determined. The primary aim of this study was to clarify the shock absorption potential of a mouthguard against forced, traumatic occlusion. The secondary objective was to compare the shock absorption ability of different thicknesses of mouthguard against this type of trauma. MATERIALS AND METHODS: An artificial skull (ZA20; 3B Scientific International, Co. Ltd, Niigata, Japan) with two-axis strain gages applied to the right buccal aspect of the mandible and the mandibular and maxillary teeth was used to measure shock absorption ability. Three different thicknesses of EVA mouthguard (1, 2, and 3 mm at the first molar) were tested. RESULTS AND CONCLUSIONS: Within the limitations of this laboratory study, the following results were obtained: the results showed that increasing the thickness of the mouthguard improved its shock absorption ability.
Assuntos
Mandíbula , Equipamentos de Proteção , Traumatismos Dentários/prevenção & controle , HumanosRESUMO
A rugby player who had frequently experienced soft tissue injuries while playing rugby and wearing a conventional custom-made mouthguard came to the hospital clinic. The patient had suffered traumatic soft tissue injuries such as lip lacerations and bite trauma. Severe crowding due to ectopic maxillary and mandibular canines was observed. In response to the patient's request for better protection, a set of maxillary and mandibular mouthguards was designed: one covering the entire maxillary dentition and the other the mandibular front teeth only. The mouthguards were to be worn simultaneously. In this paper, we describe how these mouthguards were fabricated and discuss the results. The patient has experienced no injury to the stomatognathic system, including the lips, for five seasons since he began wearing this set of mouthguards. This new pairing of mouthguards appears to offer sufficient protection against injury, despite severe malalignment. We believe that this new type of paired maxillary and mandibular mouthguards has the potential to reduce sports-related dental injuries.
Assuntos
Futebol Americano/lesões , Mandíbula , Protetores Bucais , Traumatismos Dentários/prevenção & controle , Humanos , Masculino , Adulto JovemRESUMO
Cleidocranial dysplasia (CCD) is a rare congenital disorder characterized by skeletal and dental anomalies. This clinical report describes the prosthodontic approach to treating a CCD patient who presented with decreased facial height and relative mandibular protrusion due to maxillary hypoplasia after orthodontic treatment. Functional and esthetic rehabilitation was achieved using telescopic detachable prostheses in the maxilla and osseointegrated implants and metal-ceramic fixed dental prostheses in the mandible. These treatment approaches precluded the need for orthognathic surgical correction and presented a favorable prognosis during the 5-year observation period.