Scaffolding competence-based learning design in the dental simulation curriculum.

INTRODUCTION: Learning in a clinical domain in dentistry is complex and learners may face uncertain clinical scenarios. A simulation curriculum can be designed to have simple clinical scenarios and learning activities which progress in complexity and employ competence assessments of simulated clinical practice before students can undertake authentic practice on patients. This paper presents how scaffolding of competence can be used for designing learning with simulators (haptics and phantom head) demonstrated in a specific domain in restorative dentistry. METHODS: A collaborative workshop as a research approach was undertaken to inform the iterative analysis, development, and discussion on scaffolding the learning design with respect to competence assessments of learning cavity preparation with simulation-based learning technologies. A workshop was conducted, which was collaborative and involved design negotiations between researchers, technologists, and teachers/practitioners in developing the simulation curriculum. RESULTS: A competence assessment with feedback in a specific domain in preparing interproximal caries was used as a context to describe how the learning activities and outcomes were designed to meet assessment of competence with varied levels of simple to complex learning activities and structured sessions. CONCLUSION: Simulation curriculum can be designed and implemented by scaffolding the level of competence that can be learned using simulation between haptics and phantom-head. This brings impetus to the need in meeting the relevant competence criteria in context to a specific affordance of the simulation-based learning technologies to provide optimal patient-centred holistic care.

The combined effect of light-illuminating direction and enamel rod orientation on color adjustment at the enamel borders of composite restorations.

OBJECTIVES: To investigate the effect of light-illuminating direction (from composite or enamel side) on color adjustment at the coronal and cervical enamel borders in composite restorations. MATERIALS AND METHODS: Forty cylindrical holes (3.0-mm diameters) were prepared in bovine enamel disks (1.0-mm thickness). After application of a one-step self-etch adhesive, one of four resin composites (Estelite Asteria, EA; Estelite Pro, EP; Kalore, KA; Clearfil Majesty ES-2 Premium, MJ) was restored in the holes. After 24-h storage, the colors (L*, C*, or h* values) at the restored enamel disks over a black background were measured in a black box using a CIE XYZ camera, spotted with D65 standard illuminant either from coronal or cervical side at 45°/0° geometry. The color shifting rate was calculated at the coronal and cervical enamel borders of the composite restorations, and analyzed by three-way ANOVA with Dunnett's T3 and t test for post hoc analysis (p < 0.05). RESULTS: The light-illuminating directions significantly affected the L* shifting rate at the cervical enamel border in EP and MJ (p < 0.05), and the C* shifting rate at the coronal enamel border in EA, EP, and MJ (p < 0.05). CONCLUSIONS: The color appearance at the border of the composite restoration was influenced by the light-illuminating direction in conjunction with the enamel rod orientation in the coronal or cervical enamel border. CLINICAL RELEVANCE: The line-of-vision angle would affect the perception of color adaptation at the enamel borders in the composite restorations.

BTBR ob/ob mouse model of type 2 diabetes exhibits early loss of retinal function and retinal inflammation followed by late vascular changes.

AIMS/HYPOTHESIS: Diabetic retinopathy is increasing in prevalence worldwide and is fast becoming a global epidemic and a leading cause of visual loss. Current therapies are limited, and the development of effective treatments for diabetic retinopathy requires a greater in-depth knowledge of disease progression and suitable modelling of diabetic retinopathy in animals. The aim of this study was to assess the early pathological changes in retinal morphology and neuronal, inflammatory and vascular features consistent with diabetic retinopathy in the ob/ob mouse model of type 2 diabetes, to investigate whether features similar to those in human diabetic retinopathy were present. METHODS: Male and female wild-type (+/+), heterozygous (+/-) and homozygous (-/-) BTBR ob/ob mice were examined at 6, 10, 15 and 20 weeks of age. Animals were weighed and blood glucose was measured. TUNEL and brain-specific homeobox/POU domain protein 3A (BRN3A) markers were used to examine retinal ganglion cells. We used immunostaining (collagen IV and platelet endothelial cell adhesion molecule [PECAM]/CD31) to reveal retinal vessel degeneration. Spectral domain optical coherence tomography was used to reveal changes in the thickness and structure of the retinal layer. Vitreous fluorophotometry was used to investigate vascular permeability. A-waves, b-waves and oscillatory potentials were measured under photopic and scotopic conditions. Concanavalin A leucostasis and immunostaining with glial fibrillary acidic protein (GFAP) and ionised calcium-binding adapter molecule 1 (IBA-1) identified differences in inflammatory status. Paraffin sections and transmission electron microscopy were used to reveal changes in the thickness and structure of the retinal layer. RESULTS: Following the development of obesity and hyperglycaemia in 2-week-old and 3-week-old ob-/ob- mice, respectively (p < 0.001), early functional deficits (p < 0.001) and thinning of the inner retina (p < 0.001) were identified. Glial activation, leucostasis (p < 0.05) and a shift in microglia/macrophage phenotype were observed before microvascular degeneration (p < 0.05) and elevated vascular permeability occurred (p < 0.05). CONCLUSIONS/INTERPRETATION: The present characterisation of the development of diabetic retinopathy in the ob/ob mouse represents a platform that will enable the development of new therapies, particularly for the early stages of disease.

A Proinflammatory Function of Toll-Like Receptor 2 in the Retinal Pigment Epithelium as a Novel Target for Reducing Choroidal Neovascularization in Age-Related Macular Degeneration.

Current treatments for choroidal neovascularization, a major cause of blindness for patients with age-related macular degeneration, treat symptoms but not the underlying causes of the disease. Inflammation has been strongly implicated in the pathogenesis of choroidal neovascularization. We examined the inflammatory role of Toll-like receptor 2 (TLR2) in age-related macular degeneration. TLR2 was robustly expressed by the retinal pigment epithelium in mouse and human eyes, both normal and with macular degeneration/choroidal neovascularization. Nuclear localization of NF-κB, a major downstream target of TLR2 signaling, was detected in the retinal pigment epithelium of human eyes, particularly in eyes with advanced stages of age-related macular degeneration. TLR2 antagonism effectively suppressed initiation and growth of spontaneous choroidal neovascularization in a mouse model, and the combination of anti-TLR2 and antivascular endothelial growth factor receptor 2 yielded an additive therapeutic effect on both area and number of spontaneous choroidal neovascularization lesions. Finally, in primary human fetal retinal pigment epithelium cells, ligand binding to TLR2 induced robust expression of proinflammatory cytokines, and end products of lipid oxidation had a synergistic effect on TLR2 activation. Our data illustrate a functional role for TLR2 in the pathogenesis of choroidal neovascularization, likely by promoting inflammation of the retinal pigment epithelium, and validate TLR2 as a novel therapeutic target for reducing choroidal neovascularization.

Effect of Water Aging of Adherend Composite on Repair Bond Strength of Nanofilled Composites.

PURPOSE: To evaluate the effect of water aging of adherend composite on repair bond strength to nanofilled composites with specific fillers using different bonding agents. MATERIALS AND METHODS: Three nanofilled composites - Beautifil II with S-PRG filler (BE) / Filtek Supreme ultra with nanocluster filler (SP) / Estelite Σ Quick (ES) - and one microhybrid composite, Clearfil APX (AP), were used in this study. The composite disks were immersed in water for different durations (immediate, 1 week, 2 weeks or 1 month), and then the polished surfaces were treated with one of three bonding agents - no treatment (control), application of Clearfil SE One (SE), application of Clearfil SE One plus Clearfil Porcelain Bond Activator (PB) - then filled with a repair composite. The bonded composite disks were subjected to the microshear bond strength (µSBS) test. Additionally, water sorption (Wsp) and solubility (Wsl) of the resin composite were measured. The µSBS data were was statistically analyzed using a three-way ANOVA and t-test with Bonferroni correction for multiple comparisons. RESULTS: Water aging of adherend composite affected the repair bond strength (p < 0.05). For BE, SP, and ES, application of an adhesive agent improved repair bond strengths to water-aged composites (p < 0.05), but adding a silane coupling agent could not (p > 0.05). For AP, the µSBS significantly increased, with control group < SE group < PB group (p < 0.05). CONCLUSION: Microhybrid composite was a more suitable material for composite repair than nanofilled composite, due to adhesion to exposed, larger silica fillers. S-PRG filler and nanocluster filler in the nanofilled composites played a slight role in improving their repair bonding performances with the bonding agents tested.

Effect of Polymerization Accelerator on Bond Strength to Eugenol-Contaminated Dentin.

PURPOSE: To evaluate the effect of a polymerization accelerator on the microtensile bond strength (µTBS) of etch-and-rinse and self-etch adhesives to eugenol-contaminated dentin. MATERIALS AND METHODS: Sixty flat dentin surfaces were prepared from human molars. Half of the specimens were restored with zinc oxide eugenol temporary cement (IRM) (eugenol-contaminated group) and the other half remained without restoration (control group). After 24-h storage, the cement was mechanically removed. Then the specimens in each group were further divided into three subgroups based on the application procedure of a polymerization accelerator (p-toluenesulfinic acid sodium salt; Accel): no application, 10-s application, or 30-s application. After air drying, the dentin surfaces were bonded with either a three-step etch-and-rinse adhesive (OptiBond FL) or a two-step self-etch adhesive (Clearfil SE Bond) and restored with composite. After 24-h water storage, the bonded specimens were subjected to the µTBS test. Data were analyzed by three-way ANOVA and Dunnett's T3 test (p < 0.05). RESULTS: The eugenol-contaminated groups had significantly lower µTBS than the control groups with both types of adhesives (p < 0.05), and the application of Accel significantly increased the compromised µTBS to eugenol-contaminated dentin. Optibond FL presented significantly higher µTBS to eugenol-contaminated dentin than did Clearfil SE Bond (p < 0.05). CONCLUSION: The application of a polymerization accelerator on eugenol-contaminated dentin prior to adhesive resin application increased the µTBS of both the three-step etch-and-rinse and two-step self-etch adhesive.

Bonding Durability of a Self-etch Adhesive to Normal Versus Smear-layer Deproteinized Dentin: Effect of a Reducing Agent and Plant-extract Antioxidant.

PURPOSE: To evaluate the effect of a reducing agent and plant-extract antioxidant on the bonding durability of a self-etch adhesive to normal and NaOCl-treated, smear-layer-deproteinized dentin. MATERIALS AND METHODS: Flat smear-layer-covered dentin surfaces from 60 extracted human molars were prepared by removing the occlusal enamel. The teeth were divided into two groups with or without NaOCl-deproteinizing treatment for 30 s, and further divided into three subgroups as follows: no application of antioxidant, application of Accel (p-toluenesulfinic acid sodium salt solution) for 5 s, or application of rosmarinic acid solution for 5 s. All treated dentin surfaces were bonded with a two-step self-etch adhesive (Clearfil SE Bond) and restored with composite (Clearfil AP-X). The bonded teeth were sectioned into a hourglass-shaped sticks with a composite-dentin bonded interface area of 1.0 mm2. After storage in artificial saliva for 24 h or 1 year, the specimens were subjected to the microtensile bond strength test (n = 15). Data were statistically analyzed with three-way ANOVA, Tukey's post-hoc test, and the t-test (p < 0.05). RESULTS: Without an antioxidant, 1-year storage significantly reduced the bond strengths of the self-etch adhesive to normal and smear-layer-deproteinized dentin compared with those after 24-h storage (p < 0.05). Application of Accel and rosmarinic acid restored the compromised initial bond strengths to smear-layer-deproteinized dentin (p < 0.05), and prevented long-term deterioration of bond strengths to both normal and smear-layer-deproteinized dentin (p > 0.05). CONCLUSION: Application of Accel and rosmarinic acid improved bonding durability of the self-etch adhesive to both normal and smear-layer-deproteinized dentin.

Dentin Bonding Durability of Two-step Self-etch Adhesives with Improved of Degree of Conversion of Adhesive Resins.

PURPOSE: To evaluate (1) the initial and long-term microtensile bond strengths of two-step self-etch adhesives with different degrees of conversion (DC); (2) the elastic modulus of the respective adhesive resins; (3) the water sorption of the respective adhesive resins. MATERIALS AND METHODS: Two two-step self-etch adhesives, Clearfil SE Bond (CSE) and Clearfil SE Bond 2 (CSE2) were used in this study. The DC was determined using ATR/FT-IR with a time-based spectrum analysis. Midcoronal flat dentin surfaces of 24 human molars were prepared with 600-grit SiC paper for microtensile bond strength (µTBS) testing. CSE and CSE2 were applied to the dentin surfaces according to the manufacturer's instructions, followed by composite buildups. The µTBS was measured after water storage for 24 h, 6 months, and 1 year. The elastic modulus (before and after 1 month of water immersion) was determined by the three-point flexural bending test and water sorption values by the water sorption test. RESULTS: CSE2 showed significantly higher DC than CSE. The µTBS of CSE2 was significantly higher than that of CSE in all water storage periods. One-year water storage decreased the µTBS of CSE; however, it did not decrease that of CSE2. Regarding the polymerized adhesive resins, the elastic modulus of CSE2 was significantly higher than that of CSE before and after water immersion (p < 0.001), and the water sorption of CSE was higher than that of CSE2. CONCLUSIONS: The higher DC of adhesive resins of two-step self-etch adhesives resists water aging and improves the initial bond strengths and durability of the resin-dentin bond.

Effect of Scrubbing Technique with Mild Self-etching Adhesives on Dentin Bond Strengths and Nanoleakage Expression.

PURPOSE: To evaluate the effect of a scrubbing technique with one-step self-etching adhesives on bond strengths and nanoleakage expression at the resin/dentin interface. MATERIALS AND METHODS: Flat human dentin surfaces bonded with one of two mild self-etching adhesives, SE One (SE) or Scotchbond Universal (SU) applied either with scrubbing or without scrubbing technique, were prepared (n = 5). The microtensile bond strengths (µTBS), SE micrographs of morphological changes on treated dentin surfaces, and expression of nanoleakage along the bonded dentin interfaces as shown with TEM were evaluated. µTBS data were analyzed using two-way ANOVA and the post-hoc t-test at the significance level of 0.05. RESULTS: The scrubbing technique had a significant positive effect on the µTBS of SU (p < 0.05), while it produced no significant difference for SE (p > 0.05). Morphological evaluation of the treated dentin surfaces demonstrated that SU with scrubbing showed the highest etching ability, followed by scrubbing SE > nonscrubbing SE > nonscrubbing SU. In the nonscrubbing groups, nanoleakage formation using SU exhibited a reticular pattern throughout the hybridized complex, whereas with SE, water-tree nanoleakage was only found in the adhesive layer at dentinal tubule orifices. The scrubbing groups of both adhesives did not exhibit any nanoleakage expression. CONCLUSION: Using a scrubbing technique when applying mild self-etching adhesives could improve resin monomer infiltration into dentin, chase water on adhesive surfaces, and facilitate smear layer removal.

VEGF-A is necessary and sufficient for retinal neuroprotection in models of experimental glaucoma.

Vascular endothelial growth factor A (VEGF-A) is a validated therapeutic target in several angiogenic- and vascular permeability-related pathological conditions, including certain cancers and potentially blinding diseases, such as age-related macular degeneration and diabetic retinopathy. We and others have shown that VEGF-A also plays an important role in neuronal development and neuroprotection, including in the neural retina. Antagonism of VEGF-A function might therefore present a risk to neuronal survival as a significant adverse effect. Herein, we demonstrate that VEGF-A acts directly on retinal ganglion cells (RGCs) to promote survival. VEGF receptor-2 signaling via the phosphoinositide-3-kinase/Akt pathway was required for the survival response in isolated RGCs. These results were confirmed in animal models of staurosporine-induced RGC death and experimental hypertensive glaucoma. Importantly, we observed that VEGF-A blockade significantly exacerbated neuronal cell death in the hypertensive glaucoma model. Our findings highlight the need to better define the risks associated with use of VEGF-A antagonists in the ocular setting.

An in vitro assessment of gutta-percha coating of new carrier-based root canal fillings.

The first aim of this paper was to evaluate the push-out bond strength of the gutta-percha coating of Thermafil and GuttaCore and compare it with that of gutta-percha used to coat an experimental hydroxyapatite/polyethylene (HA/PE) obturator. The second aim was to assess the thickness of gutta-percha around the carriers of GuttaCore and HA/PE obturators using microcomputed tomography ( µ CT). Ten (size 30) 1 mm thick samples of each group (Thermafil, GuttaCore, and HA/PE) were prepared. An orthodontic wire with a diameter of 0.5 mm was attached to the plunger of an Instron machine in order to allow the push-out testing of the gutta-percha coating. Five samples of (GuttaCore and HA/PE) were scanned using µ CT. The data obtained were analysed with one-way analysis of variance and Tukey post hoc test. HA/PE obturators exhibited significantly higher push-out bond strength (P < 0.001) determined at 6.84 ± 0.96 than those of Guttacore around 3.75 ± 0.75 and Thermafil at 1.5 ± 0.63. GuttaCore demonstrated significantly higher bond strength than Thermafil (P < 0.001). µ CT imaging revealed that the thickness of gutta-percha around the experimental HA/PE carrier was homogeneously distributed. The bondability and thickness of gutta-percha coating around HA/PE carriers were superior to those of GuttaCore and Thermafil obturators.

Real-time measurements of vascular permeability in the mouse eye using vitreous fluorophotometry.

Breakdown of blood-retinal barrier integrity underpins pathological changes in numerous ocular diseases, including neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME). Whilst anti-vascular endothelial growth factor (VEGF) therapies have revolutionised disease treatment, novel therapies are still required to meet patients' unmet needs. To help develop new treatments, robust methods are needed to measure changes in vascular permeability in ocular tissues in animal models. We present here a method for detecting vascular permeability using fluorophotometry, which enables real-time measurements of fluorescent dye accumulation in different compartments of the mouse eye. We applied this method in several mouse models with different increased vascular leakage, including models of uveitis, diabetic retinopathy and choroidal neovascularization (CNV). Furthermore, in the JR5558 mouse model of CNV, we observed with anti-VEGF post-treatment a longitudinal reduction in permeability, in the same animal eyes. We conclude fluorophotometry is a useful method for measuring vascular permeability in the mouse eye, and can be used over multiple time points, without the need to sacrifice the animal. This method has the potential to be used in both basic research for studying the progression and factors underlying disease, but also for drug discovery and development of novel therapeutics.

How long does it take for the occlusion to re-establish following the placement of restorations at an increased occlusal vertical dimension? A literature review.

Purpose This literature review aimed to investigate predictability of re-establishment of the occlusion following placement of restorations at an increased OVD, duration and to assess the quality of the available evidence.Methods An electronic search of articles using MEDLINE (1946-01/2019), EMBASE (1974-01/2019) and the Cochrane databases was undertaken. Search terms included dental restoration, vertical dimension and time. Studies involving placement of restorations at an increased OVD and recorded the time taken for the occlusion to re-establish were included. Eligibility assessments were carried out independently by two reviewers who also undertook independent extraction of predefined data fields, including study quality indicators.Results The search provided 61 results with 11 being relevant. A further 5 papers were identified for full text analysis. 4 papers used similar data from previous studies and 3 were excluded after full text assessment.. A final total of 9 papers were included in the review. It was indicated that the technique of placing restorations at an increased OVD appears to be clinically predictable in terms of re-establishment of occlusion and appears to occur most rapidly in younger patients.Conclusions The time taken for the occlusion to re-establish was between 15 days to 24 months. However, there is a need for prospective studies to evaluate the process in terms of success, predictive variables and specifically how long the process takes and this information would be helpful for both clinicians and patients, so that they know what to expect before embarking on a treatment.

Critical thinking education for dental schools in Asia: Perceptions of educators.

Teaching competence in critical thinking is an important element of undergraduate dental curricula. The pedagogy for critical thinking education in Asia requires further discussion and neither the current situation nor the possible challenges are widely known from the perspectives of dental educators. Therefore, seven educators from four countries gathered online in the summer of 2021 to share the current situation and possible challenges. All the participants considered "critical thinking" was "important" (43%) or "very important" (57%), however, 86% mentioned that they faced challenges in delivering education in critical thinking. The challenges to delivering critical thinking education were insufficient time in the curriculum and lack of human resources; lack of information on appropriate teaching methods for the student population; and no established methods of assessment. How to teach and assess critical thinking therefore requires more brainstorming, and raising the awareness of educators to implement this education might be necessary.

In vitro remineralization assessment of enamel subsurface lesions using different percentages of surface reaction-type pre-reacted glass-ionomer containing gum-based material.

OBJECTIVE: To identify the remineralization activity of enamel subsurface lesions using different percentages of surface pre-reacted glass-ionomer (S-PRG) filler containing gum-base material. METHODS: Gum extracts from gum-base materials containing 0wt%, 5wt%, and 10wt% S-PRG filler were prepared as GE0, GE5, and GE10, respectively. A total of 50 bovine enamel specimens were used, and the polished enamel surface of a 3 × 3 mm2 window area was exposed. The specimens were then subjected to a demineralization solution for seven days to create a subsurface enamel lesion. Remineralization was then conducted for seven days using a protocol whereby the specimens were immersed three times a day in prepared gum extracts (0wt%, 5wt%, and 10wt%) and artificial saliva of pH 7 (Control) for 20 min at 37 °C. Thereafter, remineralization assessment was performed by using Swept Source Optical Coherence Tomography (SS-OCT) and micro-computed tomography (µCT). Surface morphology and elemental analysis were conducted by scanning electron microscopy (SEM) and energy-dispersive X-ray spectrometry (EDS). RESULTS: The depths of the demineralized lesions in the GE5 and GE10 groups were significantly lower than those of the Control and the GE0 groups. SEM observations of the enamel surface morphology of the GE5 and GE10 groups indicated remineralization with S-PRG filler-related elements present. CONCLUSION: The GE5 and GE10 S-PRG filler containing gum-base materials showed significantly improved surface remineralization and reduced demineralization of the enamel lesions. EDS analysis suggested that the released ions from the S-PRG filler might be responsible for surface remineralization. CLINICAL SIGNIFICANCE: The S-PRG filler containing gum-base material may have a significant remineralization effect and improve the surface morphology of enamel subsurface lesions.

Digitally Guided Direct Composite Injection Technique with a Bi-layer Clear Mini-Index for the Management of Extensive Occlusal Caries in a Pediatric Patient: A Case Report.

PURPOSE: This case report presents a direct composite inverse injection technique using a bi-layer clear mini-index fabricated with a digital workflow to restore extensive posterior occlusal cavities in a 13-year-old patient. MATERIALS AND METHODS: After a root canal treatment in the right mandibular first molar and step-wise excavation of deep caries in the left mandibular first molar, the extensive occlusal restorations were digitally designed using CAD software, upon which digital wax-ups were 3D-printed. Bi-layer clear mini-indices consisting of a hard outer plastic layer and an elastic inner silicone layer were prepared from the 3D-printed cast. The bonding surfaces were deproteinized using a 6% sodium hypochlorite solution, and an antioxidant (Clearfil DC Activator; Kuraray Noritake) was utilized to improve the dentin bonding durability of a 2-step self-etch adhesive (Clearfil SE Bond 2; Kuraray Noritake). Subsequently, a highly filled universal-shade flowable resin composite (RC) was incrementally placed into the cavities. To create the final occlusal morphology, the same RC was inversely injected through the opening of the bi-layer indices. RESULTS: The workflow was feasible, and the occlusal cavities were efficiently restored using the injection technique. Occlusal carving and adjustments of the morphology were not necessary, leading to less chair time. At the 1-year follow-up, the clinical outcome was excellent. CONCLUSION: The injection technique with a bi-layer clear mini-index accurately translated the digital wax-ups into large, final restorations. Precise morphology and shortened chair time enhanced patient satisfaction, but at the expense of multiple visits.

Delineating effects of angiopoietin-2 inhibition on vascular permeability and inflammation in models of retinal neovascularization and ischemia/reperfusion.

Introduction: Clinical trials demonstrated that co-targeting angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF-A) with faricimab controls anatomic outcomes and maintains vision improvements, with strong durability, through 2 years in patients with neovascular age-related macular degeneration and diabetic macular edema. The mechanism(s) underlying these findings is incompletely understood and the specific role that Ang-2 inhibition plays requires further investigation. Methods: We examined the effects of single and dual Ang-2/VEGF-A inhibition in diseased vasculatures of JR5558 mice with spontaneous choroidal neovascularization (CNV) and in mice with retinal ischemia/reperfusion (I/R) injuries. Results: In JR5558 mice, Ang-2, VEGF-A, and dual Ang-2/VEGF-A inhibition reduced CNV area after 1 week; only dual Ang-2/VEGF-A inhibition decreased neovascular leakage. Only Ang-2 and dual Ang-2/VEGF-A inhibition maintained reductions after 5 weeks. Dual Ang-2/VEGF-A inhibition reduced macrophage/microglia accumulation around lesions after 1 week. Both Ang-2 and dual Ang-2/VEGF-A inhibition reduced macrophage/microglia accumulation around lesions after 5 weeks. In the retinal I/R injury model, dual Ang-2/VEGF-A inhibition was statistically significantly more effective than Ang-2 or VEGF-A inhibition alone in preventing retinal vascular leakage and neurodegeneration. Discussion: These data highlight the role of Ang-2 in dual Ang-2/VEGF-A inhibition and indicate that dual inhibition has complementary anti-inflammatory and neuroprotective effects, suggesting a mechanism for the durability and efficacy of faricimab in clinical trials.

Polymerization shrinkage of light-cured conventional and bulk-fill composites -The effect of cavity depth and post-curing.

Volumetric shrinkage (VS) of conventional, bulk-fill, and core build-up resin-based composites (RBCs) of various thickness (1-5 mm) was measured using the modified bonded-disk method with confocal laser scanning microscopy. Additionally, the bottom-to-top ratio of Vickers hardness (%VH) was measured. Conventional RBCs exhibited significantly higher VS than bulk-fill and core build-up RBCs (p<0.05). As specimen thickness increased, VS relative to volume (%VS) and difference in VS at each depth (VSdepth) decreased. For conventional RBCs, there was a significant drop in VSdepth between 1 mm and 2 mm (p<0.05), and another drop was observed between 3 mm and 4 mm (p<0.05) where %VH decreased below 90%. For bulk-fill and core build-up RBCs, VSdepth decreased significantly between 2 mm and 3 mm (p<0.05), but %VH exceeded 90% even in 5 mm deep cavities. These results indicated that post-curing contributed to lower shrinkage in deeper layers, and that conventional RBCs were not adequately polymerized at the depth of over 3 mm.

Involvement of Angiopoietin 2 and vascular endothelial growth factor in uveitis.

PURPOSE: Angiopoietin (Ang) 2 is released from vascular endothelial cells by the stimulation of vascular endothelial growth factor (VEGF)A. Ang2 increases the expression of leukocyte adhesion molecules on endothelial cells via nuclear factor κB. The aim of this study was to evaluate the effects of Ang2 and VEGFA on ocular autoimmune inflammation. METHODS: We measured the concentrations of Ang2 and VEGFA in vitreous samples among patients with uveitis. Vitreous samples were collected from 16 patients with idiopathic uveitis (uveitis group) and 16 patients with non-inflammatory eye disease (control group). Experimental autoimmune uveoretinitis (EAU) was induced in B10.BR mice with a human interphotoreceptor retinoid-binding protein-derived peptide. The retinochoroidal tissues of the EAU mice were removed, and the mRNA levels of Ang2 and VEGFA were examined. EAU mice treated with anti-Ang2, anti-VEGFA, a combination of anti-Ang2 and anti-VEGFA, anti-Ang2/VEGFA bispecific, or IgG control antibodies were clinically and histopathologically evaluated. RESULTS: The protein levels of Ang2 and VEGFA were significantly higher in the vitreous samples of patients with uveitis than in controls (P<0.05). The retinochoroidal mRNA levels of Ang2 and VEGFA were significantly upregulated in EAU mice compared to controls (n = 6, P<0.05). Although there was no significant difference, treatment with anti-VEGFA antibody reduced the clinical and histopathological scores. However, treatment with anti-Ang2 antibody reduced the clinical and histopathological scores (n = 18-20, P<0.05). Furthermore, these scores were further decreased when treated by inhibiting both Ang2 and VEGFA. CONCLUSIONS: Based on these results, VEGFA and Ang2 were shown to be upregulated locally in the eye of both uveitis patients and models of uveitis. Dual inhibition of Ang2 and VEGFA is suggested to be a new therapeutic strategy for uveitis.

Effect of surface topography and wettability on shear bond strength of Y-TZP ceramic.

Zirconia ceramics have been widely used as dental restorations due to their esthetic appearance and high flexural strength. The bonding of zirconia with resin cement should rely on both mechanical and chemical bonds. This study was performed to investigate the effect of zirconia surface topography and its wettability after surface pretreatments on the microshear bond strength (µSBS) of a resin cement. Zirconia slabs were prepared and randomly divided into 5 groups based on the surface treatment as follows: no treatment (control), air abrasion (AB), etching with hydrofluoric acid (F), the mixture of hydrofluoric acid and nitric acid (FN), or the mixture of hydrochloric acid and nitric acid (CN) for 10 min. The specimens were subjected to investigation of surface roughness characteristics [average roughness (Ra), peak-to-valley average distance (Rpv), skewness (Rsk), and kurtosis (Rku)] using atomic force microscopy (AFM) and measurements of surface contact angle (θc) and µSBS of a resin cement. In addition, the area % of the nanoscale surface irregularity (nSI%) was calculated from the AFM images. The effects of nSI%, Ra and θc on the µSBS were analyzed by multiple linear regression analysis (p < 0.05). Multiple regression analysis revealed that the nSI% was the most predominant factor for the µSBS (p < 0.001). A surface with larger nSI%, higher Ra and relatively lower θc was essential for establishing a reliable resin-zirconia bond.