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OBJECTIVE: To evaluate current studies to establish and compare the efficacy of traditional and laser acupuncture in reducing the signs and symptoms of temporomandibular disorders (TMD). METHODS: PubMed, Cochrane, Scopus, and Web of Science databases were searched. Clinical, controlled, and randomized trials written in English and having used traditional or laser acupuncture as therapy for TMD and RDC/TMD or DC/TMD as a diagnostic criterion for TMD were included. RESULTS: Six studies that evaluated the intensity of pain and the level of mouth opening of the patients submitted to acupuncture were selected, and all showed improvement. However, similar results were also observed in the groups treated with occlusal splint and placebo acupuncture. Only one study evaluated laser acupuncture and showed a higher proportion of patients with remission of symptoms in the experimental group. CONCLUSION: The traditional acupuncture seems to relieve the signs and symptoms of TMD, as well as laser acupuncture when associated with occlusal splint. However, more rigorous and high-quality clinical trials are needed.

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OBJETIVE: To evaluate the effects of Chinese scalp acupuncture in patients diagnosed with temporomandibular disorders (TMD) on pain, sleep, and quality of life (QOL), and compare these results with the results from traditional therapies. METHODS: Sixty patients diagnosed with TMD using the research diagnostic criteria for temporomandibular disorders (RDC/TMD) were allocated into four treatment groups: counseling (C = 15), occlusal splint (OS = 15), scalp acupuncture (SA = 15), and manual therapy (MT = 15). Participants were re-evaluated within 1 month. Three questionnaires were used to access sleep disorders, QOL, and pain: The Pittsburgh Sleep Quality Index (PSQI), World Health Organization Quality of Life (WHOQOL-bref), and the Visual Analogue Scale (VAS), respectively. The data obtained were analyzed using the Statistical Package for the Social Science program (SPSS 22.0). RESULTS: The SA group significantly improved pain (P = .015), as well as the OS (P = .01) and MT groups (P = .014). Only the OS (P = .002) and MT (P = .029) groups improved sleep. MT group significantly improved QOL in terms of the physical domain of the WHOQOL-bref (P = .011) and the OS group in the psychological domain (P = .012). CONCLUSIONS: The scalp acupuncture proved to be another alternative for pain relief in patients with TMD, demonstrating positive results in the short term. However, it was not as effective in improving quality of life and sleep.

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Objective: To evaluate, in the short term, the effectiveness of conservative therapies in pain, quality of life, and sleep in TMD patients.Methods: Eighty-nine TMD patients diagnosed by RDC-TMD were distributed in occlusal splints (OS; n= 24), manual therapy (MT; n= 21), counseling (C; n= 19), and OS associated with C (OSC; n= 25) therapy groups. Data collection was performed at baseline and within one month by VAS (pain), PSQI (sleep quality -SQ), WHOQOL-BREF (Quality of life - QL) and OHIP-14 (quality of life related to oral health -QLOH). The Split Plot ANOVA test was used to observe the difference between groups and over time.Results: All therapies were effective over time, improving pain (p< .001), SQ (p=.001), QLOH (p< .001), and QL (p= .006), but not between them.Discussion: The therapies were effective in improving pain, SQ, and quality of life; however, no therapeutic group was superior to the other.

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INTRODUCTION: Temporomandibular dysfunction (TMD) is a condition that affects the stomatognathic system. OBJECTIVE: To determine the effect of treatment with an occlusal splint (OS), manual therapy (MT), counselling (CS) and the combination of an occlusal splint and counselling (OSCS) on pain and anxiety in patients with TMD. MATERIALS AND METHODS: A randomised clinical trial was conducted with 89 patients diagnosed with TMD through RDC/TMD (Research Diagnostic Criteria for Temporomandibular Disorders) and divided into four groups of treatment: OSCS (n = 25); OS (n = 24); MT (n = 21); and CS (n = 19). Participants were assessed before and after 1 month of therapy for pain, anxiety and TMD diagnosis. Pain was measured by a visual analogue scale. To assess anxiety, Hospital Anxiety and Depression Scale (HADS), Beck Anxiety Inventory (BAI) and the State-Trait Anxiety Inventory (STAI-S and T) were used. The data were analysed using SPSS (Statistical Package for Social Science) 22.0. RESULTS: The four groups obtained a significant reduction (P < 0.001) in the pain after 1 month of treatment. Treatment in all groups promoted a significant reduction in anxiety symptoms 1 month after completion, HADS (P < 0.001), BAI (P < 0.001), STAI-T (P = 0.006). Thus, no group was superior to the other in reducing the studied variables. CONCLUSION: The therapies used were effective in reducing pain and anxiety in patients diagnosed with TMD. However, no treatment was superior to the other in reducing the studied variables.

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To evaluate the stress behavior of ceramic fragment restoration, varying the thickness of the cement layer and intraoral temperature variation. A solid model of a upper lateral incisor was obtained and a defect at enamel distal/incisal edge was restored with a ceramic fragment. Based on this initial model, 4 different models (M) were built: M1 - absence of cement layer (CL) (0 µm of thickness); M2 - CL with an uniform thickness of 50 µm; M3 - CL with 50 µm at the margin of ceramics and 100 µm in the inner area far from margins; M4 - CL with 50 µm at the margin of ceramics and 200 µm in the inner area far from margins. The environment temperature changed from 5 °C to 50 °C in 4 increments. The finite element analysis was performed. Increase the cement layer thickness generated higher stress levels on ceramic surface in all temperatures, as well as on cement interface. In general hot temperature was the worst scenario for ceramic fragments integrity, since tensile and compressive stress were more intense. The maximum principal stress on ceramic fragment was found 90 MPa for M4 at 50 °C, followed for M3 (87 Mpa). For CL, the peak of stress was found for M3 at 5 °C (47 MPa). Is it possible to conclude that thick resin cement layer contribute to higher stress concentration on ceramic fragment, and extremely hot temperatures increase the risk of structural failure, since both ceramic and \cl are exposed to higher compressive and tensile stresses.

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Veneer fracture is the most common complication in zirconia-based restorations. The aim of this study was to evaluate the mechanical behavior of a zirconia-based crown in a lower canine tooth supporting removable partial denture (RPD) prosthesis, varying the bond quality of the veneer/coping interface. Microtomography (µCT) data of an extracted left lower canine were used to build the finite element model (M) varying the core material (gold core - MAu; zirconia core - MZi) and the quality of the veneer/core interface (complete bonded - MZi; incomplete bonded - MZi-NL). The incomplete bonding condition was only applied for zirconia coping by using contact elements (Target/Contact) with 0.3 frictional coefficients. Stress fields were obtained using Ansys Workbench 10.0. The loading condition (L = 1 N) was vertically applied at the base of the RPD prosthesis metallic support towards the dental apex. Maximum principal (σmax) and von Mises equivalent (σvM) stresses were obtained. The σmax (MPa) for the bonded condition was similar between gold and zirconia cores (MAu, 0.42; MZi, 0.40). The incomplete bonded condition (MZi-NL) raised σmax in the veneer up to 800% (3.23 MPa) in contrast to the bonded condition. The peak of σvM increased up to 270% in the MZi-NL. The incomplete bond condition increasing the stress in the veneer/zirconia interface.

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The aim of this study was to evaluate stress distribution on the peri-implant bone, simulating the influence of Nobel Select implants with straight or angulated abutments on regular and switching platform in the anterior maxilla, by means of 3-dimensional finite element analysis. Four mathematical models of a central incisor supported by external hexagon implant (13 mm × 5 mm) were created varying the platform (R, regular or S, switching) and the abutments (S, straight or A, angulated 15°). The models were created by using Mimics 13 and Solid Works 2010 software programs. The numerical analysis was performed using ANSYS Workbench 10.0. Oblique forces (100 N) were applied to the palatine surface of the central incisor. The bone/implant interface was considered perfectly integrated. Maximum (σmax) and minimum (σmin) principal stress values were obtained. For the cortical bone the highest stress values (σmax) were observed in the RA (regular platform and angulated abutment, 51 MPa), followed by SA (platform switching and angulated abutment, 44.8 MPa), RS (regular platform and straight abutment, 38.6 MPa) and SS (platform switching and straight abutment, 36.5 MPa). For the trabecular bone, the highest stress values (σmax) were observed in the RA (6.55 MPa), followed by RS (5.88 MPa), SA (5.60 MPa), and SS (4.82 MPa). The regular platform generated higher stress in the cervical periimplant region on the cortical and trabecular bone than the platform switching, irrespective of the abutment used (straight or angulated).

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PURPOSE: To evaluate the stress distribution in peri-implant bone by simulating the effect of an implant with microthreads and platform switching on angled abutments through tridimensional finite element analysis. The postulated hypothesis was that the presence of microthreads and platform switching would reduce the stress concentration in the cortical bone. METHODS: Four mathematical models of a central incisor supported by an implant (5.0 mm × 13 mm) were created in which the type of thread surface in the neck portion (microthreaded or smooth) and the diameter of the angled abutment connection (5.0 and 4.1mm) were varied. These models included the RM (regular platform and microthreads), the RS (regular platform and smooth neck surface), the SM (platform switching and microthreads), and the SS (platform switching and smooth neck). The analysis was performed using ANSYS Workbench 10.0 (Swanson Analysis System). An oblique load (100N) was applied to the palatine surface of the central incisor. The bone/implant interface was considered to be perfectly integrated. Values for the maximum (σ(max)) and minimum (σ(min)) principal stress, the equivalent von Mises stress (σ(vM)), and the maximum principal elastic strain (ɛ(max)) for cortical and trabecular bone were obtained. RESULTS: For the cortical bone, the highest σ(max) (MPa) were observed for the RM (55.1), the RS (51.0), the SM (49.5), and the SS (44.8) models. The highest σ(vM) (MPa) were found for the RM (45.4), the SM (42.1), the RS (38.7), and the SS models (37). The highest values for σ(min) were found for the RM, SM, RS and SS models. For the trabecular bone, the highest σ(max) values (MPa) were observed in the RS model (6.55), followed by the RM (6.37), SS (5.6), and SM (5.2) models. CONCLUSION: The hypothesis that the presence of microthreads and a switching platform would reduce the stress concentration in the cortical bone was partially rejected, mainly because the microthreads increased the stress concentration in cortical bone. Only platform switching reduced the stress in cortical bone.

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PURPOSE: The aim of this study was to evaluate stress distribution on peri-implant bone simulating the influence of implants with different lengths on regular and switching platforms in the anterior maxilla by means of three-dimensional finite element analysis. MATERIALS AND METHODS: Four mathematical models of a central incisor supported by an external hexagon implant (diameter, 5.0 mm) were created, varying the length (15.0 mm for long implants [L] and 7.0 mm for short implants [S]) and the diameter of the abutment platform (5.0 mm for regular models [R] and 4.1 mm for switching models [S]). The models were created using the Mimics 11.11 (Materialise) and SolidWorks 2010 (Inovart) software. Numerical analysis was performed using ANSYS Workbench 10.0 (Swanson Analysis System). Oblique forces (100 N) were applied to the palatine surface of the central incisor. The bone/implant interface was considered perfectly integrated. Maximum (σ(max)) and minimum (σ(min)) principal stress values were obtained. RESULTS: For the cortical bone, the highest stress values (σ(max)) were observed in the SR (73.7 MPa) followed by LR (65.1 MPa), SS (63.6 MPa), and LS (54.2 MPa). For the trabecular bone, the highest stress values (σ(max)) were observed in the SS (8.87 MPa) followed by the SR (8.32 MPa), LR (7.49 MPa), and LS (7.08 MPa). CONCLUSIONS: The influence of switching platform was more evident for the cortical bone in comparison with the trabecular bone for the short and long implants. The long implants showed lower stress values in comparison to the short implants, mainly when the switching platform was used.

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PURPOSE: In view of reports in the literature on the benefits achieved with the use of platform switching, described as the use of an implant with a larger diameter than the abutment diameter, the goal being to prevent the (previously) normal bone loss down to the first thread that occurs around most implants, thus enhancing soft tissue aesthetics and stability and the need for implant inclination due to bone anatomy in some cases, the aim of this study was to evaluate bone stress distribution on peri-implant bone, by using three-dimensional finite element analysis to simulate the influence of implants with different abutment angulations (0 and 15 degrees) in platform switching. METHODS: Four mathematical models of an implant-supported central incisor were created with varying abutment angulations: straight abutment (S1 and S2) and angulated abutment at 15 degrees (A1 and A2), submitted to 2 loading conditions (100 N): S1 and A1-oblique loading (45 degrees) and S2 and A2-axial loading, parallel to the long axis of the implant. Maximum (σmax) and minimum (σmin) principal stress values were obtained for cortical and trabecular bone. RESULTS: Models S1 and A1 showed higher σmax in cortical and trabecular bone when compared with S2 and A2. The highest σmax values (in MPa) in the cortical bone were found in S1 (28.5), followed by A1 (25.7), S2 (11.6), and A2 (5.15). For the trabecular bone, the highest σmax values were found in S1 (7.53), followed by A1 (2.87), S2 (2.85), and A2 (1.47). CONCLUSIONS: Implants with straight abutments generated the highest stress values in bone. In addition, this effect was potentiated when the load was applied obliquely.

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PURPOSE: This study aimed to evaluate stress distribution on peri-implant bone simulating the influence of platform switching in external and internal hexagon implants using three-dimensional finite element analysis. MATERIALS AND METHODS: Four mathematical models of a central incisor supported by an implant were created: External Regular model (ER) with 5.0 mm × 11.5 mm external hexagon implant and 5.0 mm abutment (0% abutment shifting), Internal Regular model (IR) with 4.5 mm × 11.5 mm internal hexagon implant and 4.5 mm abutment (0% abutment shifting), External Switching model (ES) with 5.0 mm × 11.5 mm external hexagon implant and 4.1 mm abutment (18% abutment shifting), and Internal Switching model (IS) with 4.5 mm × 11.5 mm internal hexagon implant and 3.8 mm abutment (15% abutment shifting). The models were created by SolidWorks software. The numerical analysis was performed using ANSYS Workbench. Oblique forces (100 N) were applied to the palatal surface of the central incisor. The maximum (σ(max)) and minimum (σ(min)) principal stress, equivalent von Mises stress (σ(vM)), and maximum principal elastic strain (ε(max)) values were evaluated for the cortical and trabecular bone. RESULTS: For cortical bone, the highest stress values (σ(max) and σ(vm) ) (MPa) were observed in IR (87.4 and 82.3), followed by IS (83.3 and 72.4), ER (82 and 65.1), and ES (56.7 and 51.6). For ε(max), IR showed the highest stress (5.46e-003), followed by IS (5.23e-003), ER (5.22e-003), and ES (3.67e-003). For the trabecular bone, the highest stress values (σ(max)) (MPa) were observed in ER (12.5), followed by IS (12), ES (11.9), and IR (4.95). For σ(vM), the highest stress values (MPa) were observed in IS (9.65), followed by ER (9.3), ES (8.61), and IR (5.62). For ε(max) , ER showed the highest stress (5.5e-003), followed by ES (5.43e-003), IS (3.75e-003), and IR (3.15e-003). CONCLUSION: The influence of platform switching was more evident for cortical bone than for trabecular bone, mainly for the external hexagon implants. In addition, the external hexagon implants showed less stress concentration in the regular and switching platforms in comparison to the internal hexagon implants.

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PURPOSE: This three-dimensional finite element analysis study evaluated the effect of different material combinations on stress distribution within metal-ceramic and all-ceramic single implant-supported prostheses. MATERIALS AND METHODS: Three-dimensional finite element models reproducing a segment of the maxilla with a missing left first premolar were created. Five groups were established to represent different superstructure materials: GP, porcelain fused to gold alloy; GR, modified composite resin fused to gold alloy; TP, porcelain fused to titanium; TR, modified composite resin fused to titanium; and ZP, porcelain fused to zirconia. A 100-N vertical force was applied to the contact points of the crowns. All models were fixed in the superior region of bone tissue and in the mesial and distal faces of the maxilla section. Stress maps were generated by processing with finite element software. RESULTS: Stress distribution and stress values of supporting bone were similar for the GP, GR, TP, and ZP models (1,574.3 MPa, 1,574.3 MPa, 1,574.3 MPa, and 1,574.2 MPa, respectively) and different for the TR model (1,838.3 MPa). The ZP model transferred less stress to the retention screw (785 MPa) than the other groups (939 MPa for GP, 961 MPa for GR, 1,010 MPa for TP, and 1,037 MPa for TR). CONCLUSION: The use of different materials to fabricate a superstructure for a single implant-supported prosthesis did not affect the stress distribution in the supporting bone. The retention screw received less stress when a combination of porcelain and zirconia was used.

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Ceramics have been widely used for esthetic and functional improvements. The resin cement is the material of choice for bonding ceramics to dental substrate and it can also dictate the final esthetic appearance and strength of the restoration. The correct use of the wide spectrum of resin luting agents available depends on the dental tooth substrate. This article presents three-year clinical results of a 41 years old female patient B.H.C complaining about her unattractive smile. Two all-ceramic crowns and two laminates veneers were placed in the maxillary incisors and cemented with a self-adhesive resin luting cement and conventional resin luting cement, respectively. After a three-year follow-up, the restorations and cement/teeth interface were clinically perfect with no chipping, fractures or discoloration. Proper use of different resin luting cements shows clinical appropriate behavior after a three-year follow-up. Self-adhesive resin luting cement may be used for cementing all-ceramic crowns with high predictability of success, mainly if there is a large dentin surface available for bonding and no enamel at the finish line. Otherwise, conventional resin luting agent should be used for achieving an adequate bonding strength to enamel.

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STATEMENT OF PROBLEM: The fracture or chipping of ceramic veneers is a common problem for zirconia-based restorations. PURPOSE: This study evaluated the stress distribution in the veneer of a maxillary central incisor restored with a complete crown using a zirconia core with a feldspathic ceramic veneer, simulating an incomplete bond between the veneer and zirconia substructure. MATERIAL AND METHODS: Based on a microcomputed tomography of a maxillary central incisor, 3 finite element models (M) for a complete crown were developed: Mf, a complete crown based on feldspathic ceramic; Mlz, a zirconia-based complete crown with a complete bond at the zirconia/veneer interface; and Mnzl, similar to Mlz, but with an incomplete bond at the zirconia/veneer interface created by using a contact element with a frictional coefficient of 0.3. A distributed load of 1 N was applied to the lingual surface at 45 degrees to the long axis of the tooth. RESULTS: The zirconia core in the Mnzl model showed peak stresses for maximum principal stress (σ(max)) and shear stress of 9.02 and 8.81 MPa, respectively. The ceramic veneer in the Mnlz model showed peak stresses for σ(max), minimum principal stress (compressive), and von Mises stresses of 5.4 MPa, 61.23 MPa, and 35.19 MPa, respectively. CONCLUSIONS: The incomplete bond increased the σ(max) in the ceramic veneer in comparison to the perfect bond condition.

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OBJECTIVE: transitional implants are indicated for cases in which immediate loading is counterindicated because a healing period is necessary for osseointegration of the definitive implants. These provisional implants were developed to support an implant-supported fixed prosthesis or overdenture to provide retention, stability, and support. The aim of this article was to conduct a literature review on transitional implants to highlight the characteristics of the transitional implants and their advantages, indications, and contraindications, including the level of osseointegration of such implants according to the functional period. METHOD AND MATERIALS: the present literature review was based on the Old Medline and Medline databases from 1999 to 2010 using the key words "transitional implants" and "temporary implants." Fourteen articles were found: 11 clinical studies or techniques and three histologic and histomorphometric studies. RESULTS: the transitional immediate prostheses were worn by completely and partially edentulous patients. Advantages of transitional implants include complete denture retention, stability, and support; maintenance of chewing, phonetics, and patient comfort; protection of bone grafts; vertical stop during healing period; easy and fast surgical and prosthetic procedures; lower cost in comparison to the definitive implant; and reestablishment of esthetics. The success of transitional implants as conservative treatment for conventional immediate loading is a reality if correctly indicated. CONCLUSION: transitional implants are a provisional treatment alternative for completely and partially edentulous patients. However, additional studies are required to evaluate the level of remodeling and repair of the transitional implants under loading.

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PURPOSE: To evaluate stress distribution in different horizontal mandibular arch formats restored by protocol-type prostheses using three-dimensional finite element analysis (3D-FEA). MATERIALS AND METHODS: A representative model (M) of a completely edentulous mandible restored with a prefabricated bar using four interforaminal implants was created using SolidWorks 2010 software (Inovart, São Paulo, Brazil) and analyzed by Ansys Workbench 10.0 (Swanson Analysis Inc., Houston, PA) to obtain the stress fields. Three mandibular arch sizes were considered for analysis, regular (M), small (MS), and large (ML). Three unilateral posterior loads (L) (150 N) were used: perpendicular to the prefabricated bar (L1); 30° oblique in a buccolingual direction (L2); 30° oblique in a lingual-buccal direction (L3). The maximum and minimum principal stresses (σ(max), σ(min)), the equivalent von Mises (σ(vM)), and the maximum principal strain (σ(max) ) were obtained for type I (M.I) and type II (M.II) cortical bones. RESULTS: Tensile stress was more evident than compression stress in type I and II bone; however, type II bone showed lower stress values. The L2 condition showed highest values for all parameters (σ(vM), σ(max), σ(min), ɛ(max)). The σ(vM) was highest for the large and small mandibular arches. CONCLUSION: The large arch model had a higher influence on σ(max) values than did the other formats, mainly for type I bone. Vertical and buccolingual loads showed considerable influence on both σ(max) and σ(min) stresses.

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PURPOSE: The aim of this study was to evaluate the influence of different Young moduli of the ceramic crown on the distribution of tensions in the region of the abutment-crown interface by making use of 2D finite element analysis. MATERIALS: Two representative models of a sagittally sectioned maxilla were built through AutoCad program showing an implant in the region of the upper central incisor and were restored by means of IPS e.max Press or Procera AllCeram on zircon abutment. Numerical analysis (Ansys 10.0) was performed under 2 loading conditions (50 N): on the lingual face, at 45 degrees with the implant's long axis (L1) and perpendicular to the incisal edge (L2). The von Mises equivalent stress (σvM) and maximum principal stress (σmax) were obtained. RESULTS: It was noticed that, independent of the restoring system, the maximum σvM values were in the incisal region of the cementation interface for both loading conditions. The IPS e.max Press system showed higher σvM on the adhesive interface with higher L1 influence. The same behavior was also observed as regards the σmax variation. CONCLUSIONS: It was concluded that a restoring system with a lower Young modulus shows higher stress concentration on the abutment-crown interface when cemented on an abutment with a high Young modulus. Thus, IPS e.max Press system provides higher stress concentration in the resin cement layer than Procera AllCeram system, suggesting that the resin cement layer shows lower failure risk when the Procera crown is used.

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The aim of the present study was to conduct a critical literature review about the technique of computer-guided surgery in implantology to highlight the indications, purposes, immediate loading of implants and complications, protocol of fabrication, and functioning of virtual planning software. This literature review was based on OLDMEDLINE and MEDLINE databases from 2002 to 2010 using the key words "computer-guided surgery" and "implant-supported prosthesis." Thirty-four studies regarding this topic were found. According to the literature review, it was concluded that the computer-assisted surgery is an excellent treatment alternative for patients with appropriate bone quantity for implant insertion in complete and partially edentulous arches. The Procera Nobel Guide software (Nobel Biocare) was the most common software used by the authors. In addition, the flapless surgery is advantageous for positioning of implants but with accurate indication. Although the computer-guided surgery may be helpful for virtual planning of cases with severe bone resorption, the conventional surgical technique is more appropriate. The surgical guide is important for insertion of the implants regardless of the surgical technique, and the success of immediate loading after computer-guided surgery depends on the accuracy of clinical and/or laboratorial steps.

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This clinical report describes a method to reduce the number of clinical sessions for the rehabilitation of implant-supported fixed dentures through a simplified and versatile procedure indicated mainly for immediate loading. According to this method, the immediate implant-supported fixed dentures for edentulous patients can be safely fabricated within 2 days. In this technique, the teeth in the wax are prepared on a base of light-polymerized resin, and both wax teeth and metallic superstructure trials are accomplished at the same session.

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This study aimed to evaluate the influence of loading on a maxillary central incisor with the periodontal ligament (PDL) represented by 2D elastic beam elements using a 2D finite element analysis. Two models (M) were built varying the PDL representation: Mh (homogeneous PDL) and Mht (heterogeneous PDL with beam3 elements). Stress and displacements were determined for three loading conditions (L): Ll, lingual face loading at 45° with the tooth long axis; Li, perpendicular to the incisal edge; and Lip, on the incisal edge, parallel to the tooth long axis. Evaluation was performed on ANSYS software. Lip provided lower stress variation on the tooth and support structures when compared to Ll and Li. PDL's influence on stress values was lower for Lip. Oblique loading showed stress and displacement not observed in parallel loading condition through PDL's heterogeneous representation and it is probably incompatible with the in vivo condition.

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