The "5Ts" screening tool: Enhancements and threshold values for effective TMD identification.

OBJECTIVE: This study aimed to enhance the quintessential "five temporomandibular disorder (TMD) symptoms" (5Ts) screener by incorporating frequency options and distinguishing between TMJ and muscle pain. The diagnostic accuracy along with cut-off points for the effective identification of TMDs was also established. METHODS: Participants, aged ≥18 years, were recruited from a university-based hospital. After completing surveys encompassing demographic data and the enhanced 5Ts (with frequency options [5Ts-F] and differentiation of TMJ/muscle pain [6Ts-F]), protocolized interviews and clinical examinations were performed following DC/TMD. The diagnostic accuracy and best cut-off points were determined with the area under the receiver operating characteristic curves (AUCs). RESULTS: 324 participants were recruited (mean age 30.0 ± 11.4 years). Among these, 86.4% had TMDs. 5Ts exhibited high diagnostic accuracy for detecting all TMDs (AUC = 0.92) with sensitivity/specificity values of 83.9%/88.6%. Both 5Ts-F and 6Ts-F had slightly better accuracy (AUCs = 0.95/0.96), comparable sensitivity, and superior specificity (97.7%) compared to 5Ts. The best cut-off points were 1.5 for 5Ts and 2.5 for 5Ts-F/6Ts-F. CONCLUSIONS: Although all three TMD screeners presented high diagnostic accuracy, 5Ts-F/6Ts-F had notably improved specificity. 5Ts scores of >1.5 and 5Ts-F/6Ts-F scores of >2.5 are to be applied for screening the presence of TMDs.

Access to COVID-19 vaccination by socio-economic status in older Singaporean adults: a population-based cohort study.

OBJECTIVES: Socio-economic status (SES) disparities exist in the uptake of COVID-19 vaccination; however, most studies were conducted during the initial pandemic wave when vaccination was less discretionary, limiting generalizability. We aimed to determine whether differences in vaccination uptake across SES strata widened after the removal of vaccination-differentiated measures prior to the rollout of the second boosters, in a nationwide cohort of older Singaporeans at higher risk of severe-COVID-19. STUDY DESIGN: Retrospective population-based cohort study. METHODS: Retrospective population-based cohort study of all Singaporeans aged ≥60 years from 22nd February 2021-14th February 2023. Cox regression models controlling for demographics and comorbidities were used to estimate hazard-ratios (HRs) for the uptake of primary vaccination as well as first/second boosters, as recorded in the national vaccination registry, according to SES (housing type). RESULTS: 836,170 individuals were included for completion of a primary vaccine series; 784,938 individuals for completion of the first booster and 734,206 individuals for the completion of the second booster. Differences in vaccination uptake by SES strata were observed (e.g. vaccination uptake in lowest-SES [1-2 room public-housing] versus highest-SES [private housing]: second booster, 47.6% vs. 58.1%; first booster, 93.9% vs. 98.0%). However, relative differences did not markedly widen during second booster rollout when vaccination was more discretionary (e.g. amongst those aged 60-69 years: 0.75 [95% CI = 0.73-0.76] for the first booster; 0.81 [95% CI = 0.79-0.84] for the second booster). CONCLUSION: While differences in vaccination uptake across SES strata by housing type persisted during the rollout of primary vaccination and subsequent boosters in a nationwide cohort of older Singaporeans, differences did not widen substantially when vaccination was made more discretionary.

Microstructural abnormalities found in uncinate fasciculus and superior cerebellar tracts in children with global developmental delay: a feasibility study.

AIM: To evaluate the microstructural abnormalities of the white matter tracts (WMT) using diffusion tensor imaging (DTI) in children with global developmental delay (GDD). MATERIALS AND METHODS: Sixteen children with GDD underwent magnetic resonance imaging (MRI) and cross-sectional DTI. Formal developmental assessment of all GDD patients was performed using the Mullen Scales of Early Learning. An automated processing pipeline for the WMT assessment was implemented. The DTI-derived metrics of the children with GDD were compared to healthy children with normal development (ND). RESULTS: Only two out of the 17 WMT demonstrated significant differences (p<0.05) in DTI parameters between the GDD and ND group. In the uncinate fasciculus (UF), the GDD group had lower mean values for fractional anisotropy (FA; 0.40 versus 0.44), higher values for mean diffusivity (0.96 versus 0.91×10-3 mm2/s) and radial diffusivity (0.75 versus 0.68×10-3 mm2/s) compared to the ND group. In the superior cerebellar peduncle (SCP), mean FA values were lower for the GDD group (0.38 versus 0.40). Normal myelination pattern of DTI parameters was deviated against age for GDD group for UF and SCP. CONCLUSION: The UF and SCP WMT showed microstructural changes suggestive of compromised white matter maturation in children with GDD. The DTI metrics have potential as imaging markers for inadequate white matter maturation in GDD children.

Functional, physical and psychosocial impact of Temporomandibular Disorders in adolescents and young adults.

BACKGROUND: This community-based study investigated the functional, physical and psychosocial impact of Temporomandibular Disorders (TMDs) in adolescents and young adults. It also determined the discriminative capacity of a TMDs-specific oral health related quality of life (OHRQoL) instrument and compared three formats of appraising OHRQoL data. MATERIAL AND METHODS: Subjects were recruited from a local Polytechnic. The presence of TMDs was established with the Fonseca Anamnestic Index (FAI), whilst TMDs-specific OHRQoL was evaluated with the Oral Health Impact Profile-TMDs (OHIP-TMDs). Demographic information, FAI and OHIP-TMDs responses were gathered with an on-line questionnaire. Data was analysed using Mann-Whitney U-test, chi-square test and Spearman's rho correlation with significance level set at 0.05. RESULTS: Data from a total of 244 participants were compiled and examined. The "no TMDs" (NT) group consisted of 140 subjects (119 females; 21 males) with a mean age of 20.41±3.29 years, while the "with TMDs" (WT) group composed of 104 subjects (88 females; 16 males) aged 19.82±3.04 years. Significant differences in median severity scores were observed between subjects with and without TMDs for all OHIP-TMDs domains and total OHIP (p values < 0.001). For appraisal of extent and prevalence, significant differences were again observed (p values < 0.05) with the exception of the functional limitation and handicap domains. CONCLUSIONS: TMDs impacted physical and psychosocial well-being of adolescents and young adults. OHIP-TMDs, preferably appraised by severity, extent and prevalence, was able to discriminate between subjects with and without TMDs. It holds promise as a TMDs-specific OHRQoL instrument for epidemiological studies.

Effect of beta-blockers on cancer recurrence and survival: a meta-analysis of epidemiological and perioperative studies.

BACKGROUND: The biological perturbation associated with psychological and surgical stress is implicated in cancer recurrence. Preclinical evidence suggests that beta-blockers can be protective against cancer progression. We undertook a meta-analysis of epidemiological and perioperative clinical studies to investigate the association between beta-blocker use and cancer recurrence (CR), disease-free survival (DFS), and overall survival (OS). METHODS: Databases were searched until September 2017, reported hazard ratios (HRs) pooled, and 95% confidence intervals (CIs) calculated. Comparative studies examining the effect of beta-blockers (selective and non-selective) on cancer outcomes were included. The Newcastle Ottawa Scale was used to assess methodological quality and bias. RESULTS: Of the 27 included studies, nine evaluated the incidental use of non-selective beta-blockers, and ten were perioperative studies. Beta-blocker use had no effect on CR. Within subgroups of cancer, melanoma was associated with improved DFS (HR 0.03, 95% CI 0.01-0.17) and OS (HR 0.04, 95% CI 0.00-0.38), while endometrial cancer had an associated reduction in DFS (HR 1.40, 95% CI 1.10-1.80) and OS (HR 1.50, 95% CI 1.12-2.00). There was also reduced OS seen with head and neck and prostate cancer. Non-selective beta-blocker use was associated with improved DFS and OS in ovarian cancer, improved DFS in melanoma, but reduced OS in lung cancer. Perioperative studies showed similar variable effects across cancer types, albeit from a limited data pool. CONCLUSION: Beta-blocker use had no evident effect on CR. The beneficial effect of beta-blockers on DFS and OS in the epidemiological or perioperative setting remains variable, tumour-specific, and of low-level evidence at present.

Effect of staining beverages on color and translucency of CAD/CAM composites.

This study investigated the color (ΔE) and translucency changes (ΔTP) of CAD/CAM composites after exposure to staining solutions using both spectrophotometer and shade-matching device. Direct (Filtek Z350XT [ZT]), indirect (Shofu Ceramage [CE]) and CAD/CAM (Shofu HC Block [HC], Lava Ultimate [LU], Vita Enamic [EN]) composite specimens measuring 12 × 14 × 1.5 mm were fabricated, divided into five groups (n = 8), and immersed in cola, tea, coffee, red wine, distilled water (control) at 37°C for 7 days. Color parameters were determined with both spectrophotometer and shade-taking device at baseline and 1 week. Delta E (ΔE) with white and black backgrounds, and Delta TP (ΔTP) were computed. Statistical testing was performed with ANOVA and Tukey post hoc test (P < .05). Mean ΔE (white) values ranged from 0.20 ± 0.06 to 12.26 ± 1.95 while mean ΔE (black) varied from 0.22 ± 0.11 to 14.21 ± 2.37. Mean ΔTP values ranged from 0.13 ± 0.17 to -3.87 ± 2.16. CAD/CAM composites fared better in red wine than direct and indirect materials. Clinically perceptible color changes (ΔE > 3.3) were observed for almost all materials when exposed to wine, coffee and tea. Direct, indirect, and CAD/CAM composites are all susceptible to various degrees of discoloration and translucency changes after exposure to staining beverages. Red wine caused the most discoloration and translucency changes. Limitations of these materials must be considered when placing an aesthetic restoration. CLINICAL SIGNIFICANCE: Direct, indirect, and CAD/CAM composites are all susceptible to various degrees of discoloration and translucency changes after exposure to staining beverages. Red wine generally caused the most discoloration and translucency changes. Although CAD/CAM composites were more color stable than direct and indirect materials when exposed to red wine, color changes were still clinically perceptible.

Physiological effects of anterior repositioning splint on temporomandibular joint disc displacement: a quantitative analysis.

Anterior repositioning splints (ARS) are used primarily for the management of temporomandibular joint (TMJ) anterior disc displacement with reduction (ADDwR). However, the exact physiological effects of ARS are still unclear. This study investigated the short and long-term effects of ARS on disc and condyle angles/positions by metric analysis. Twenty-two subjects diagnosed with ADDwR were recruited. Maxillary full-coverage ARS were fabricated, and MRI of TMJs was obtained before splint treatment, immediate post-insertion and 6 months after splint treatment. Disc-condyle relationship was determined by disc-condyle angle measurement. Disc and condyle positions were described as X-Y coordinates with the summit of glenoid fossa as the origin of the coordinates. Thirty-two TMJs were classified as ADDwR and 12 were normal. Upon ARS insertion, all TMJs with ADDwR got normal disc-condyle relationships. The condyles moved significantly forward and downward, while the discs moved significantly backward and upward. MRI at 6 months after treatment (without ARS insertion) indicated that only 40·6% (13/32) of the joints were maintained in the normal disc-condyle relationship. The majority of condyles returned to their pre-treatment positions, while the discs generally moved anteriorly again. The use of ARS resulted in forward and downward condyle movement, and a concurrent backward movement of the disc resulting in ideal spatial disc-condyle relationship. The stability of this relationship, however, could not be maintained in the majority of TMJs upon ARS removal. Findings explain the good short-term clinical outcomes with ARS and their relatively lower efficacy in the long term.

Surface Degradation of Ion-releasing Restorative Materials With Cariogenic Challenge.

This study examined the influence of cariogenic environments on the surface roughness of ion-releasing restorative materials (IRMs). Custom-made stainless steel molds with holes of 5 mm × 2mm were used to fabricate 60 disc-shaped specimens of each of the following materials: Activa Bioactive (AV), Beautifil Bulk Restorative (BB), Cention N (Bulk-fill) (CN), and Filtek Z350XT (FZ) (Control). Baseline surface roughness (Ra) measurements were obtained using an optical 3D measurement machine (Alicona Imaging GmbH, Graz, Austria). The specimens were then randomly divided into five subgroups (n=12) and exposed to 10 ml of the following mediums at 37°C: distilled water (DW), demineralization solution (DM), remineralization solution (RM), pH cycling (PC) and air (AR) (control). Ra measurements were again recorded after one week and one month, followed by statistical evaluations with two-way analysis of variance (ANOVA) to determine interactions between materials and mediums. One-way ANOVA and post hoc Games Howell tests were performed for intergroup comparisons at a significance level of 0.05. Mean Ra values ranged from 0.085 ± 0.004 (µm) to 0.198 ± 0.001 µm for the various material-medium combinations. All IRMs showed significant differences in Ra values after exposure to the aqueous mediums. The smoothest surfaces were observed in the AR for all materials. When comparing materials, AV presented the roughest surfaces for all mediums. All IRM materials showed increased surface roughness over time in all cariogenic environments but were below the threshold value for bacterial adhesion, except for AV 1-month post immersion with pH cycling. Therefore, besides AV, the surface roughness of IRMs did not deteriorate to an extent that it is clinically relevant.

Flexural Properties of Contemporary Bioactive Restorative Materials: Effect of Environmental pH.

This study investigated the effects of environmental pH on the flexural properties of ion-releasing restorative materials (IRMs), including giomer (Beautifil-Bulk Restorative - BB), alkasite (Cention N - CN), bioactive composite (Activa - AB) and resin-modified glass ionomer (Riva Light Cure -RV) restoratives. A bio-inert resin-based composite (Filtek Bulk-fill Posterior - FB) served as the control. Stainless steel molds were used to fabricate 40 beam-shaped specimens (12mm × 2mm × 2mm) for each material. The specimens were finished, measured, and randomly distributed into four groups (n=10) and immersed in aqueous solutions of pH 3.0, pH 5.0, pH 6.8, and pH 10.0 at 37°C for 28 days. Specimens were then subjected to a uniaxial three-point bending flexural test with a load cell of 5 KN and a fixed deformation rate of 0.5 mm/min until fracture occurred. Flexural modulus and strength were statistically analyzed using analysis of variance/Dunnet T3's test (p=0.05). Mean flexural modulus varied from (2.40±0.41 to 9.65±1.21 GPa), while mean flexural strength ranged from (21.56±2.78 to 163.86±13.13 MPa). Significant differences in flexural properties were observed among the various pH values and materials. All materials immersed in artificial saliva (pH 6.8) presented the highest flexural properties, except AB. The flexural strength of AB was significantly better when exposed to acidic environments. FB had better flexural properties than IRMs after exposure to a range of environmental pH values.

Non-pharmacological management of dental fear and anxiety in children and adolescents: An umbrella review.

AIM: To synthesise knowledge on the relative efficacies of non-pharmacological strategies for managing dental fear and anxiety (DFA) in children and adolescents, specifically their effects on behaviour, anxiety levels and pain perception. METHODS: An umbrella review on non-pharmacological strategies used to manage DFA in children and adolescents was conducted based the Joanna Briggs Institute methodology. Searches were performed in 5 main electronic databases and the grey-literature. Two independent reviewers selected and appraised the included studies using the AMSTAR2 tool. Disagreements were resolved by a third reviewer. CONCLUSION: Audio-visual distraction was effective in reducing anxiety during a variety of dental procedures including those requiring local anaesthesia. A combination of techniques may be more effective in managing DFA in children and adolescents, possibly improving pain perception and cooperative behaviour.

Effect of resin coating on highly viscous glass ionomer cements: A dynamic analysis.

OBJECTIVES: This study determined the effects of self-adhesive resin coatings on viscoelastic properties of highly viscous glass ionomer cements (HVGICs) using dynamic mechanical analysis. MATERIALS AND METHODS: The HVGICs evaluated were Zirconomer [ZR] (Shofu), Equia Forte [EQ] (GC) and Riva [RV] (SDI). Sixty specimens (12mm x 2mm x 2mm) of each material were fabricated using customized Teflon molds. After initial set, the specimens were removed from their molds, finished, measured and randomly divided into 3 groups of 20. Half the specimens in each group were left uncoated while the remaining half was covered with the respective manufacturers' resin coating. The specimens were subsequently conditioned in distilled water, artificial saliva or citric acid at 37°C for 7 days. The uncoated and coated specimens (n=10) were then subjected to dynamic mechanical testing in flexure mode at 37°C with a frequency of 0.1 to 10Hz. Storage modulus, loss modulus and loss tangent data were subjected to normality testing and statistical analysis using one-way ANOVA/Scheffe's post-hoc test and Ttest at significance level p<0.05. RESULTS: Mean storage modulus ranged from 1.39 ± 0.36 to 10.80 ± 0.86 GPa while mean loss modulus varied from 0.13 ± 0.03 to 0.70 ± 0.14 GPa after conditioning in the different mediums. Values for loss tangent ranged from 39.4 ± 7.75 to 213.2 ± 20.11 (x10 -3 ). Significant differences in visco-elastic properties were observed between mediums and materials. When conditioned in distilled water and artificial saliva,storage modulus was significantly improved when ZR, EQ and RV were uncoated. Significantly higher values were, however, observed with resin coating when the materials were exposed to citric acid. CONCLUSION: The visco-elastic properties of HVGICs were influenced by both resin coating and chemical environment.

Flexural Properties of Bioactive Restoratives in Cariogenic Environments.

This study determined the mechanical performance of bioactive restoratives in cariogenic environments and compared the flexural properties of various bioactive materials. The materials evaluated included a conventional resin-based composite (Filtek Z350 [FZ]) and 3 bioactive restoratives, namely an alkasite (Cention N [CN]), a giomer (Beautifil-bulk Restorative [BB]), and an enhanced resin-modified glass ionomer (Activa Bioactive Restorative [AV]). Beam-shaped specimens (12 x 2 x 2 mm) were produced, randomly allocated to 4 groups (n=10), and conditioned in deionized solution, remineralizing solution, demineralizing solution (DE), or pH cycled for 14 days at 37°C. After conditioning/pH cycling, the specimens were subjected to 3-point flexural testing. Flexural data were subjected to statistical analysis using analysis of variance or Tukey's test (α=0.05). Mean flexural modulus and strength ranged from 3.54 ± 0.33 to 7.44 ± 0.28 GPa, and 87.07 ± 8.99 to 123.54 ± 12.37 MPa, respectively. While the flexural modulus of the bioactive restoratives was not affected by cariogenic/acidic conditions, flexural strength usually decreased, with the exception of CN. The strength of BB was significantly reduced by DE and pH cycling, while that of AV was lowered by DE. For all conditioning mediums, AV had a significantly lower modulus than the other materials. Apart from conditioning in DE, where differences in flexural strength was insignificant, FZ and AV were generally significantly stronger than BB and CN. The effect of cariogenic environments on flexural strength was found to be material dependent, and aside from the alkasite material (CN), cariogenic conditions were observed to significantly decrease the strength of bioactive restoratives.

Comparison of Flexural Properties of Bulk-fill Restorative/Flowable Composites and Their Conventional Counterparts.

The objectives of the study were to compare the flexural modulus and strength of restorative and flowable bulk-fill resin-based composites (RBCs) to their conventional counterparts and to determine the effects of conditioning environment on their flexural properties. The materials evaluated included three conventional RBCs (Filtek Z350, Tetric N Ceram, and Beautifil II), three restorative bulk-fill RBCs (Filtek Bulk-Fill Restorative, Tetric N Ceram Bulk-Fill, and Beautifil Bulk-fill Restorative), as well as three flowable bulk-fill RBCs (Filtek Bulk-Fill Flowable, Tetric N Flow Bulk-Fill, and Beautifil Bulk-Fill Flowable). Specimens were fabricated using customized stainless-steel molds, finished, measured, and randomly divided into four groups. The various RBCs were conditioned in the following mediums (n=10) for seven days at 37°C: air, artificial saliva (SAGF), 0.02 N citric acid, and 50% ethanol-water solution. After conditioning, the specimens were rinsed, blotted dry, measured, and subjected to flexural testing using a universal testing machine. Data were subjected to statistical analysis using analysis of variance and the Tukey test at a significance level of α = 0.05. Significant differences in flexural properties were observed between materials and conditioning mediums. Bulk-fill restorative RBCs exhibited higher flexural modulus than their bulk-fill flowable and conventional counterparts. With the exception of Filtek Bulk-Fill Flowable, bulk-fill flowable RBCs had significantly higher flexural strength than bulk-fill restorative and conventional RBCs. Flexural properties were highest when RBCs were conditioned in air and generally the lowest after exposure to ethanol.

Dynamic Viscoelastic Characterization of Bulk-fill Resin-based Composites and Their Conventional Counterparts.

This study compared the viscoelastic properties of restorative and flowable bulk-fill resin-based composites (RBCs) with their conventional counterparts and evaluated the impact of aqueous solutions on viscoelastic properties. The materials examined included three conventional RBCs (Filtek Z350, Tetric N Ceram, and Beautifil II), three restorative bulk-fill RBCs (Filtek Bulk-Fill Restorative, Tetric N Ceram Bulk-Fill, and Beautifil Bulk-Fill Restorative) in addition to three flowable bulk-fill RBCs (Filtek Bulk-Fill Flowable, Tetric N Flow Bulk-Fill, and Beautifil Bulk-Fill Flowable). Beam-shaped specimens (12×2×2 mm) were fabricated using customized stainless-steel molds, finished, and measured. The specimens were randomly divided into four groups and conditioned in air (control), artificial saliva, 0.02 N citric acid, and 50% ethanol-water solution for seven days at 37°C. They were then subjected to dynamic mechanical analysis (n = 10) in flexure mode at 37°C with a frequency of 0.1 to 10 Hz. Storage modulus, loss modulus, and loss tangent data were subjected to statistical analysis using one-way analysis of variance/Tukey post hoc test at a significance level of α = 0.05. Viscoelastic properties of the RBCs were found to be product and conditioning medium dependent. For most RBCs, exposure to aqueous solutions, particularly an ethanol-water solution, degraded viscoelastic properties. With the exception of Filtek Bulk-Fill Restorative, bulk-fill restorative and flowable RBCs generally had significantly lower storage and loss modulus than their conventional counterparts regardless of conditioning medium. Conventional RBCs are thus favored over their bulk-fill counterparts, particularly for high-stress-bearing areas.

Degradation of Computer-aided Design/Computer-aided Manufacturing Composites by Dietary Solvents: An Optical Three-dimensional Surface Analysis.

CLINICAL RELEVANCE: Computer-aided design/computer-aided manufacturing (CAD/CAM) composite resins are susceptible to degradation by dietary solvents. Dietary counselling is prudent when placing such CAD/CAM restorations. SUMMARY: This study determined the effect of dietary solvents on the surface roughness (Ra) of direct, indirect, and computer-aided design/computer-aided manufacturing (CAD/CAM) dental composites. The materials evaluated were a direct composite (Filtek Z350 XT [FZ]), an indirect composite (Shofu Ceramage [CM]), and four CAD/CAM composites (Lava Ultimate [LU], Shofu Block HC [HC], Cerasmart [CS], and Vita Enamic [VE]). Specimens (12×14×1.5 mm) of each material were prepared, measured for baseline Ra, ranked, divided into six groups (n=12), and conditioned in the following media for 1 week at 37°C: air (control), distilled water, 0.02 N citric acid, 0.02 N lactic acid, heptane, and 50% ethanol-water solution. The composite specimens were then subjected to postconditioning Ra testing using an optical three-dimensional surface analyzer (G4e, Alicona Imaging GmbH, Raaba, Austria). Inter-medium and inter-material comparisons were performed with one-way analysis of variance and post hoc Bonferroni test at a significance level of α=0.05. Mean Ra values ranged from 0.086 ± 0.004 µm to 0.153 ± 0.005 µm for the various material/medium combinations. For all materials, conditioning in air (control) and distilled water generally resulted in significantly lower mean Ra than exposure to other dietary solvents. Conditioning in citric acid presented the roughest surfaces for FZ, CM, and CS. For LU, HC, and VE, exposure to lactic acid, heptane, and ethanol solution resulted in the highest mean Ra. Regardless of conditioning media, FZ had the highest and VE the lowest mean Ra compared with other composites. The CAD/CAM composites remained susceptible to surface degradation by dietary solvents despite their industrial polymerization.

Clinical protocol for managing acute disc displacement without reduction: a magnetic resonance imaging evaluation.

This study investigated the efficacy of a sequential combination of arthrocentesis, mandibular manipulation, and anterior repositioning splint (ARS) in the management of acute temporomandibular joint (TMJ) disc displacement without reduction (DDwoR). Twenty-one consecutive patients diagnosed with acute DDwoR by Diagnostic Criteria for Temporomandibular Disorders and magnetic resonance imaging (MRI) were recruited and managed with this method. Clinical and MRI data were obtained before and at 1 week after treatment. The disc-condyle relationship was determined by disc-condyle angle measurement. Condyle/disc positions were described as x-y coordinates with the summit of the articular fossa as the coordinate origin. Statistical analyses including independent/paired samples t-tests were conducted; significance was set at P<0.05. Clinical success was observed in 95.2% of patients (20/21) with 22 joints affected by acute DDwoR. After combined treatment and ARS insertion, TMJs with DDwoR showed (a) normal disc-condyle relationships with substantial forward and downward condyle movement and significant disc reduction in closed position, and (b) discs with an intermediate zone located between the condylar head and articular eminence in open position. The combined approach was highly effective in 'unlocking' acute TMJ DDwoR and achieving spatial full disc reduction and a normal disc-condyle relationship. The duration of acute DDwoR appears to be critical for success.

Association between hypoplastic condyles and temporomandibular joint disc displacements: a cone beam computed tomography and magnetic resonance imaging metrical analysis.

This study investigated the association between hypoplastic condyles and disc displacements without reduction (DDw/oR). Consecutive patients with non-syndromic unilateral condylar hypoplasia were recruited and clinical, cone beam computed tomography (CBCT) and magnetic resonance imaging (MRI) data were acquired. Linear measurements including condylar head width, depth, height and condyle length were determined with CBCT while MRI was used to assess disc position, morphology and displacement. A total of 43 patients were enrolled of which 93.02% had a history of temporomandibular disorders (TMDs) and 83.72% presented with TMD signs and symptoms. Depth and height of the condylar head along with condyle length of hypoplastic joints (6.68±1.67mm, 4.97±1.25mm and 14.49±3.02mm, respectively) were significantly lesser than normal joints (7.77±1.26mm, 6.35±1.45mm and 18.20±3.18mm) (P<0.001). The prevalence of DDw/oR was significantly higher in hypoplastic joints (79.07% versus 13.95%) (P<0.001). Joints with hypoplastic condyles had shorter disc lengths (6.99 ± 2.16 mm vs, 8.45 ± 2.26 mm) (P=0.007). Furthermore, disc displacements were significantly more advanced (8.52 ± 2.84 mm) and severe (76.74% with severe translations) when compared to the contralateral side (4.77 ± 2.97 mm and 32.56%) (P<0.05). A significant association was observed between condylar hypoplasia and temporomandibular joint DDw/oR with hypoplastic joints exhibiting more severely displaced and deformed discs. DDw/oR coupled with repaired degenerative joint disease may mimic condylar hypoplasia radiographically.

The juxtamembrane region of the cadherin cytoplasmic tail supports lateral clustering, adhesive strengthening, and interaction with p120ctn.

Cadherin cell-cell adhesion molecules form membrane-spanning molecular complexes that couple homophilic binding by the cadherin ectodomain to the actin cytoskeleton. A fundamental issue in cadherin biology is how this complex converts the weak intrinsic binding activity of the ectodomain into strong adhesion. Recently we demonstrated that cellular cadherins cluster in a ligand-dependent fashion when cells attached to substrata coated with the adhesive ectodomain of Xenopus C-cadherin (CEC1-5). Moreover, forced clustering of the ectodomain alone significantly strengthened adhesiveness (Yap, A.S., W.M. Brieher, M. Pruschy, and B.M. Gumbiner. Curr. Biol. 7:308-315). In this study we sought to identify the determinants of the cadherin cytoplasmic tail responsible for clustering activity. A deletion mutant of C-cadherin (CT669) that retained the juxtamembrane 94-amino acid region of the cytoplasmic tail, but not the beta-catenin-binding domain, clustered upon attachment to substrata coated with CEC1-5. Like wild-type C-cadherin, this clustering was ligand dependent. In contrast, mutant molecules lacking either the complete cytoplasmic tail or just the juxtamembrane region did not cluster. The juxtamembrane region was itself sufficient to induce clustering when fused to a heterologous membrane-anchored protein, albeit in a ligand-independent fashion. The CT669 cadherin mutant also displayed significant adhesive activity when tested in laminar flow detachment assays and aggregation assays. Purification of proteins binding to the juxtamembrane region revealed that the major associated protein is p120(ctn). These findings identify the juxtamembrane region of the cadherin cytoplasmic tail as a functionally active region supporting cadherin clustering and adhesive strength and raise the possibility that p120(ctn) is involved in clustering and cell adhesion.

Lateral dimerization is required for the homophilic binding activity of C-cadherin.

Regulation of cadherin-mediated adhesion can occur rapidly at the cell surface. To understand the mechanism underlying cadherin regulation, it is essential to elucidate the homophilic binding mechanism that underlies all cadherin-mediated functions. Therefore, we have investigated the structural and functional properties of the extracellular segment of Xenopus C-cadherin using a purified, recombinant protein (CEC 1-5). CEC 1-5 supported adhesion of CHO cells expressing C-cadherin. The extracellular segment was also capable of mediating aggregation of microspheres. Chemical cross-linking and gel filtration revealed that CEC 1-5 formed dimers in the presence as well as absence of calcium. Analysis of the functional activity of purified dimers and monomers demonstrated that dimers retained substantially greater homophilic binding activity than monomers. These results demonstrate that lateral dimerization is necessary for homophilic binding between cadherin extracellular segments and suggest multiple potential mechanisms for the regulation of cadherin activity. Since the extracellular segment alone possessed significant homophilic binding activity, the adhesive activity of the extracellular segment in a cellular context was analyzed. The adhesion of CHO cells expressing a truncated version of C-cadherin lacking the cytoplasmic tail was compared to cells expressing the wild-type C-cadherin using a laminar flow assay on substrates coated with CEC 1-5. CHO cells expressing the truncated C-cadherin were able to attach to CEC 1-5 and to resist detachment by low shear forces, demonstrating that tailless C-cadherin can mediate basic, weak adhesion of CHO cells. However, cells expressing the truncated C-cadherin did not exhibit the complete adhesive activity of cells expressing wild-type C-cadherin. Cells expressing wild-type C-cadherin remained attached to CEC 1-5 at high shear forces, while cells expressing the tailless C-cadherin did not adhere well at high shear forces. These results suggest that there may be two states of cadherin-mediated adhesion. The first, relatively weak state can be mediated through interactions between the extracellular segments alone. The second strong adhesive state is critically dependent on the cytoplasmic tail.

Recycling of E-cadherin: a potential mechanism for regulating cadherin dynamics.

E-Cadherin plays critical roles in many aspects of cell adhesion, epithelial development, and the establishment and maintenance of epithelial polarity. The fate of E-cadherin once it is delivered to the basolateral cell surface, and the mechanisms which govern its participation in adherens junctions, are not well understood. Using surface biotinylation and recycling assays, we observed that some of the cell surface E-cadherin is actively internalized and is then recycled back to the plasma membrane. The pool of E-cadherin undergoing endocytosis and recycling was markedly increased in cells without stable cell-cell contacts, i.e., in preconfluent cells and after cell contacts were disrupted by depletion of extracellular Ca2+, suggesting that endocytic trafficking of E-cadherin is regulated by cell-cell contact. The reformation of cell junctions after replacement of Ca2+ was then found to be inhibited when recycling of endocytosed E-cadherin was disrupted by bafilomycin treatment. The endocytosis and recycling of E-cadherin and of the transferrin receptor were similarly inhibited by potassium depletion and by bafilomycin treatment, and both proteins were accumulated in intracellular compartments by an 18 degrees C temperature block, suggesting that endocytosis may occur via a clathrin-mediated pathway. We conclude that a pool of surface E-cadherin is constantly trafficked through an endocytic, recycling pathway and that this may provide a mechanism for regulating the availability of E-cadherin for junction formation in development, tissue remodeling, and tumorigenesis.