Hydrated Calcium Silicate in Resin Composites for Prevention of Secondary Caries.

INTRODUCTION AND AIMS: The gaps at the margins of restorative composite resin can increase as the carious process occurs underneath the materials, causing further demineralization along the tooth cavity wall. The aim of this study was to evaluate the effects of restorative resin composite containing hydrated calcium silicate (hCS) filler on enamel protection against demineralization by simulating microleakage between the test material and teeth in a cariogenic environment. METHODS: The experimental resin composites were composed of 70 wt.% filler, which was mixed with a glass filler and hCS in a weight ratio of 70.0% glass (hCS 0), 17.5% hCS + 52.5% glass (hCS 17.5), 35.0% hCS + 35.0% glass (hCS 35.0), and 52.5% hCS + 17.5% glass (hCS 52.5). A light-cured experimental resin composite disk was positioned over a polished bovine enamel disk, separated by a 30-µm gap, and immersed in artificial saliva with pH 4.0 for 15, 30, and 60 days. After the immersion period, the enamel disk was separated from the resin composite disk and evaluated using a microhardness tester, atomic force microscopy, and polarized light microscopy. The opposing sides of the enamel and resin composite disks were observed using scanning electron microscopy/energy dispersive X-ray spectrometry. RESULTS: The enamel surface showed a significant increase in microhardness, decreased roughness, and remineralization layer as the proportion of hCS increased (P < .05). In the scanning electron microscopy image, the enamel surface with hCS 35.0 and 52.5 after all experimental immersion periods, showed a pattern similar to that of a sound tooth. CONCLUSIONS: The results demonstrated that increasing the hCS filler level of restorative resin composites significantly decreased enamel demineralization. CLINICAL RELEVANCE: Hydrated calcium silicate laced restorative resin composites may be a promising dental biomaterial for protecting teeth against demineralization and preventing secondary caries around restorations.

Using computed tomogram atrial myocardial thickness maps in high-power short-duration radiofrequency pulmonary vein isolation: UTMOST AF.

Background: High-power short-duration (HPSD) ablation creates wide, shallow lesions using radiofrequency (RF) heating. It is uncertain if adjusting RF energy based on atrial wall thickness provides extra benefits. We studied the safety and effectiveness of tailored HPSD energy based on left atrial (LA) wall thickness (LAWT) for circumferential pulmonary vein isolation (CPVI) in patients with paroxysmal atrial fibrillation (PAF). Methods: We enrolled 212 patients (68.4% male, mean age: 59.5 ± 11.0 years) and randomly assigned them to two groups: LAWT-guided CPVI (WT, n = 108) and conventional CPVI (control, n = 104). Both groups used an open irrigated-tip deflectable catheter to apply 50 W for 10 s to the posterior LA, while controls used 60 W for 15 s on other LA regions. RF delivery time in WT was titrated (15 s at LAWT > 2.1 mm, 13 s at 1.4-2.1 mm, and 11 s at <1.4 mm) according to the computed tomogram-myocardial thickness color map. Results: After a mean follow-up of 13.4 ± 7.0 months, the WT and control groups showed no significant difference regarding clinical recurrence rate (13.9% vs. 5.8%, respectively; p = .061) and major complication rate (4.6% vs. 3.8%, respectively; p > .999). The total procedure time, cardioversion rate, and post-procedural AAD prescription rates did not significantly differ between the groups. Conclusions: The LAWT-guided energy titration strategy did not result in improved procedural safety and efficacy compared to the conventional 50-60 W-HPSD CPVI in patients with PAF.

Color stability, surface, and physicochemical properties of three-dimensional printed denture base resin reinforced with different nanofillers.

Various materials have been introduced for the three-dimensional (3D) printing of dentures. In this study, the color stability and surface and physicochemical properties of 3D-printed denture base resins with four types of nanofiller particles were evaluated. Al2O3, ZnO, CeZr, and SiO2 nanofillers were added to a 3D printable denture base-resin matrix and subjected to digital light processing. The specimens were immersed in Coke, coffee, black tea, or distilled water for 6 days. For the assessment of color differences, 6 samples were analyzed using a spectrophotometer. In a separate investigation, surface properties of 10 samples were examined, while a different set of 6 samples was used to analyze water sorption and solubility. All experimental groups exhibited higher color stability in Coke than the control group. However, the groups containing ZnO and CeZr had lower color stability in coffee and black tea than the control group. Moreover, they had agglomerated nanofillers and lower gloss than the control group. Compared with that of the control group, the contact angle of the CeZr group and microhardness of the ZnO group were not significantly different. Water sorption was higher in the Al2O3 group, whereas the solubility of the experimental and control groups was not statistically significant. The results demonstrated the significant effect of ZnO and CeZr nanofillers on the color stability of the dentures when exposed to discoloring beverages. These results will facilitate the development of fillers that enhance the resistance of 3D printed denture base resins to discoloration in the oral environment.

Efficacy and safety of acupuncture in post-stroke constipation: a systematic review and meta-analysis.

Background and objective: Post-stroke constipation (PSC) is a common complication of strokes that seriously affects the recovery and quality of life of patients, and effective treatments are needed. Acupuncture is a viable treatment option, but current evidence is insufficient to support its efficacy and safety. This study aims to evaluate the efficacy and safety of acupuncture in the treatment of PSC. Methods: A systematic search of eight databases was conducted to identify PSC-related randomized clinical trials from the inception of each database through May 2023. Methodological quality assessment was conducted by RoB 2.0, meta-analysis was conducted by RevMan 5.3 and Stata 15.1, and evidence quality was evaluated by GRADE. Moreover, reporting quality of acupuncture interventions was assessed using the Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA). Results: Thirty RCTs involving 2,220 patients were identified. We found that acupuncture was superior to conventional treatment (CT) in improving total responder rate [risk ratio (RR): 1.16, 95% confidence interval (CI): 1.09 to 1.25, p < 0.0001], decreasing constipation symptom scores [standardized mean difference (SMD): -0.65, 95% CI: -0.83 to -0.46, p < 0.00001], increasing serum P substance (SP) levels (SMD: 1.92, 95% CI: 0.47 to 3.36, p = 0.009), reducing the time to first bowel movement (BM) (SMD: -1.19, 95% CI: -2.13 to -0.25, p = 0.01), and lowing serum vasoactive intestinal peptide (VIP) levels (SMD: -2.11, 95% CI: -3.83 to -0.38, p = 0.02). Furthermore, acupuncture plus CT was superior regarding total responder rate (RR: 1.26, 95% CI: 1.17 to 1.35, p < 0.00001), serum SP levels (SMD: 2.00, 95% CI: 1.65-2.35, p < 0.00001), time to first BM (SMD: -2.08, 95% CI: -2.44 to -1.71, p < 0.00001), and serum VIP levels (SMD: -1.71, 95% CI: -2.24 to -1.18, p < 0.00001). However, regarding Bristol Stool Scale (BSS) score, acupuncture plus CT was superior to CT (SMD: -2.48, 95% CI: -3.22 to -1.73, p < 0.00001), while there was no statistically significant difference between acupuncture and CT (SMD: 0.28, 95% CI: -0.02 to 0.58, p = 0.07). Acupuncture causes fewer AEs than CT (RR: 0.13, 95% CI: 0.06 to 0.26, p < 0.00001), though there was no statistically significant difference between acupuncture plus CT vs. CT (RR: 1.30, 95% CI: 0.60 to 2.84, p = 0.51). Conclusion: Acupuncture may be an effective and safe therapy for PSC. However, given the inferior quality of clinical data, additional well-designed RCTs are required to confirm these findings.

Carbamate JNK3 Inhibitors Show Promise as Effective Treatments for Alzheimer's Disease: In Vivo Studies on Mouse Models.

We have been developing new inhibitors for c-Jun N-terminal kinase 3 (JNK3) as a potential treatment for Alzheimer's disease (AD). We identified potential JNK3 inhibitors through pharmacodynamic optimization studies, including benzimidazole compounds 2 and 3, but their unreliable pharmacokinetic properties led us to develop carbamate inhibitors 2h and 3h. In vitro studies validated carbamate inhibitors 2h and 3h as potent and highly selective JNK3 inhibitors with favorable pharmacokinetic profiles. Oral administration of 2h and 3h to both APP/PS1 and 3xTg AD mouse models improved cognitive function, indicating their potential as effective treatments for Alzheimer's disease. Carbamate JNK3 inhibitor 3h, in particular, restored cognitive function to near-normal levels in the 3xTg mice model of AD and led to pTau reduction in the hippocampal tissues of 3xTg-AD mice during in vivo behavioral evaluations. We intend to further develop these carbamate JNK3 inhibitors in preclinical studies as a potential first-in-class treatment for AD.

Novel antibacterial and apatite forming restorative composite resin incorporated with hydrated calcium silicate.

BACKGROUND: White Portland cement is a calcium silicate material. It exhibits antibacterial properties and is biocompatible. In addition, calcium silicate-based materials are known to release calcium ions and form apatite. The purpose of this study was to develop a novel bioactive restorative resin composite with antibacterial and apatite forming properties to prevent tooth caries at the interface of teeth and restorative materials, by incorporation of hydrated calcium silicate (hCS) derived from white Portland cement. METHODS: To prepare the experimental composite resins, a 30 wt% light-curable resin matrix and 70 wt% filler, which was mixed with hCS and silanized glass powder were prepared in following concentrations: 0, 17.5, 35.0, and 52.5 wt% hCS filler. The depth of cure, flexural strength, water sorption, solubility, and antibacterial effect were tested. After immersion in artificial saliva solution for 15, 30, 60, and 90 days, ion concentration by ICP-MS and apatite formation using SEM-EDS, Raman spectroscopy and XRD from experimental specimens were analyzed. RESULTS: All experimental groups showed clinically acceptable depths of cure and flexural strength for the use as the restorative composite resin. Water sorption, solubility, released Ca and Si ions increased with the addition of hCS to the experimental composite resin. Experimental groups containing hCS showed greater antibacterial effects compared with the 0 wt% hCS filler group (p < 0.05). The 52.5 wt% hCS filler group produced precipitates mainly composed of Ca and P detected as hydroxyapatite after immersion in artificial saliva solution for 30, 60, and 90 days. CONCLUSIONS: This results show that composite resins containing hCS filler is effective in antibacterial effects. hCS has also apatite formation ability for reducing gap size of microleakage by accumulating hydroxyapatite precipitates at the restoration-tooth interface. Therefore, novel composite resin containing hCS is promising bioactive resin because of its clinically acceptable physiochemical properties, antibacterial properties, and self-sealing potential for prevention of microleakage for longer usage of restorations.

Effect of Zinc Oxide Incorporation on the Antibacterial, Physicochemical, and Mechanical Properties of Pit and Fissure Sealants.

This study aimed to evaluate the antibacterial, physicochemical, and mechanical properties of pit and fissure sealants containing different weight percentages of zinc oxide nanoparticles (ZnO NPs). The following amounts of ZnO NPs were added to a commercially available pit and fissure sealant (BeautiSealant, Shofu, Japan) to prepare the experimental materials: 0 wt.% (commercial control (CC)), 0.5 wt.% (ZnO 0.5), 1 wt.% (ZnO 1.0), 2 wt.% (ZnO 2.0), and 4 wt.% (ZnO 4.0). The antibacterial effect against S. mutans was confirmed by counting the colony-forming units (CFUs) and observing live/dead bacteria. In addition, ion release, depth of cure, water sorption and solubility, and flexural strength tests were conducted. When compared with the CC, the experimental groups containing ZnO NPs showed zinc ion emission and significantly different CFUs (p < 0.05) with fewer live bacteria. ZnO NP addition reduced the depth of cure and water solubility and increased water sorption in comparison with the CC (p < 0.05). However, all groups showed similar flexural strength (p > 0.05). The pit and fissure sealants containing ZnO NPs exhibited antibacterial activity against S. mutans with no negative effects on physicochemical and mechanical properties, and thus, these sealants can be ideal secondary caries prevention material.

Poly (Methyl Methacrylate)-Containing Silver-Phosphate Glass Exhibits Potent Antimicrobial Activity without Deteriorating the Mechanical and Biological Properties of Dental Prostheses.

Poly (methyl methacrylate) (PMMA) is a commonly used denture material with poor antimicrobial effects. This study investigated the antimicrobial effects of PMMA-containing silver-phosphate glass. We fabricated a novel material comprising PMMA-containing silver-phosphate glass. Then, microhardness, flexural strength, and gloss unit were analyzed. Antimicrobial activity against Streptococcus mutans and Candida albicans was investigated. Colony-forming units were counted, and antimicrobial rates were measured. Biocompatibility tests were performed using a colorimetric MTT assay for evaluating cell metabolic activity. The microhardness, flexural strength, and gloss unit of the experimental groups (with silver-phosphate glass) were not significantly different from those of the control group (no silver-phosphate glass) (P > 0.05), which showed clinically valid values. With increasing proportions of silver-phosphate glass, the antimicrobial activity against the two microorganisms increased (P < 0.05). Furthermore, S. mutans showed more than 50% antimicrobial activity in 4%, 6%, and 8% experimental groups, C. albicans showed more than 50% antimicrobial activity in 6% and 8% groups, and a statistically significant difference in antimicrobial activity was observed compared to the control (P < 0.05). The cell viability of the experimental groups was not significantly different from that of the control group (P > 0.05). Both control and experimental groups showed approximately 100% cell viability. These results suggest that silver-phosphate glass is a promising antimicrobial material in dentistry.

Discovery of novel imidazole chemotypes as isoform-selective JNK3 inhibitors for the treatment of Alzheimer's disease.

Despite innumerable efforts to develop effective therapeutics, it is difficult to achieve breakthrough treatments for Alzheimer's disease (AD), and the main reason is probably the absence of a clear target. Here, we reveal c-Jun N-terminal kinase 3 (JNK3), a protein kinase explicitly expressed in the brain and involved in neuronal apoptosis, with a view toward providing effective treatment for AD. For many years, we have worked on JNK3 inhibitors and have discovered 2-aryl-1-pyrimidinyl-1H-imidazole-5-yl acetonitrile-based JNK3 inhibitors with superb potency (IC50 < 1.0 nM) and excellent selectivity over other protein kinases including isoforms JNK1 (>300 fold) and JNK2 (∼10 fold). Based on in vitro biological activity and DMPK properties, the lead compounds were selected for further in vivo studies. We confirmed that repeat administration of JNK3 inhibitors improved cognitive memory in APP/PS1 and the 3xTg mouse model. Overall, our results show that JNK3 could be a potential target protein for AD.

Ginkgolide injections in meglumine, combined with edaravone, significantly increases the efficacy in acute ischemic stroke: A meta-analysis.

Objective: This study aimed to evaluate the efficacy of combining diterpene ginkgolide meglumine injection (DGMI) with edaravone for the treatment of acute ischemic stroke. This is particularly relevant because Western drugs, excluding intravenous thrombolysis, have shown limited success. Methods: A comprehensive search was conducted using multiple databases, including PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure WanFang, VIP, and Chinese Biomedical Database (CBM) until June 2023. The data were analyzed using fixed-effects and random-effects models in Review Manager. The mean difference with 95% confidence interval was calculated for each outcome. Results: Eighteen studies involving 1,636 participants were included in the analysis. The DGMI group showed significant reductions in the National Institutes of Health Stroke Scale (NIHSS) score, modified Rankin Scale (mRS) score, and C-reactive protein (CRP) level, compared to the control group. Furthermore, the DGMI group showed a significant improvement in superoxide dismutase (SOD) levels and a reduction in malondialdehyde (MDA) levels. The combination of DGMI and edaravone was more effective in reducing neuron-specific enolase (NSE) levels following brain tissue injury than edaravone alone. Additionally, DGMI complemented edaravone in reducing rheological parameters associated with ischemic stroke, including hematocrit, plasma viscosity, platelet adhesion rate, and erythrocyte deformation index. Conclusion: The combination of DGMI and edaravone significantly improved the therapeutic efficacy in patients with acute ischemic stroke. However, more extensive and high-quality clinical trials are required to validate these underlying mechanisms. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=260215, identifier: PROSPERO (CRD42021260215).

Corrigendum: Association of ZFHX3 genetic polymorphisms and extrapulmonary vein triggers in patients with atrial fibrillation who underwent catheter ablation.

[This corrects the article DOI: 10.3389/fphys.2021.807545.].

Clinical Usefulness of Virtual Ablation Guided Catheter Ablation of Atrial Fibrillation Targeting Restitution Parameter-Guided Catheter Ablation: CUVIA-REGAB Prospective Randomized Study.

BACKGROUND AND OBJECTIVES: We investigated whether extra-pulmonary vein (PV) ablation targeting a high maximal slope of the action potential duration restitution curve (Smax) improves the rhythm outcome of persistent atrial fibrillation (PeAF) ablation. METHODS: In this open-label, multi-center, randomized, and controlled trial, 178 PeAF patients were randomized with 1:1 ratio to computational modeling-guided virtual Smax ablation (V-Smax) or empirical ablation (E-ABL) groups. Smax maps were generated by computational modeling based on atrial substrate maps acquired during clinical procedures in sinus rhythm. Smax maps were generated during the clinical PV isolation (PVI). The V-Smax group underwent an additional extra-PV ablation after PVI targeting the virtual high Smax sites. RESULTS: After a mean follow-up period of 12.3±5.2 months, the clinical recurrence rates (25.6% vs. 23.9% in the V-Smax and the E-ABL group, p=0.880) or recurrence appearing as atrial tachycardia (11.1% vs. 5.7%, p=0.169) did not differ between the 2 groups. The post-ablation cardioversion rate was higher in the V-Smax group than E-ABL group (14.4% vs. 5.7%, p=0.027). Among antiarrhythmic drug-free patients (n=129), the AF freedom rate was 78.7% in the V-Smax group and 80.9% in the E-ABL group (p=0.776). The total procedure time was longer in the V-Smax group (p=0.008), but no significant difference was found in the major complication rates (p=0.497) between the groups. CONCLUSIONS: Unlike a dominant frequency ablation, the computational modeling-guided V-Smax ablation did not improve the rhythm outcome of the PeAF ablation and had a longer procedure time. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02558699.

Acid neutralizing and remineralizing orthodontic adhesive containing hydrated calcium silicate.

OBJECTIVES: The objective of this study was to evaluate an orthodontic adhesive containing hydrated calcium silicate (hCS) in terms of its bond strength with the enamel surface and its acid-neutralization and apatite-forming abilities. METHODS: The experimental orthodontic adhesives were composed of 30 wt.% resin matrix and 70 wt.% filler, which itself was a mixture of silanized glass filler and hCS in weight ratios of 100% glass filler (hCS 0), 17.5% hCS (hCS 17.5), 35% hCS (hCS 35.0), and 52.5% hCS (hCS 52.5). The degree of conversion (DC) and shear bond strength (SBS) of bovine enamel surfaces were tested. pH measurements were performed immediately upon submersion of the specimens in a lactic acid solution. The surface precipitates that formed on specimens immersed in phosphate-buffered saline (PBS) were analyzed by scanning electron microscopy with energy dispersive spectroscopy (SEM-EDS) and Raman spectroscopy after 15, 30, and 90 days. RESULTS: The experimental groups exhibited no significant differences in DC and had clinically acceptable SBS values. The hCS-containing groups showed increasing pH values as more hCS was added. hCS 52.5 produced Ca- and P-containing surface precipitates after PBS immersion, and hydroxyapatite deposition was detected after 15, 30, and 90 days. CONCLUSIONS: These results suggest that orthodontic adhesives containing hCS are effective for acid neutralization. Furthermore, hCS has an apatite-forming ability for enamel remineralization. CLINICAL SIGNIFICANCE: The novel orthodontic adhesive containing hCS exhibits a potential clinical benefit against demineralization and enhanced remineralization of the enamel surface around or beneath the orthodontic brackets.

Effects of incorporating 45S5 bioactive glass into 30% hydrogen peroxide solution on whitening efficacy and enamel surface properties.

OBJECTIVES: This study aimed to evaluate the effects of 30% hydrogen peroxide (HP) solution containing various contents of 45S5 bioactive glass (BAG) on whitening efficacy and enamel surface properties after simulating the clinical bleaching procedure. MATERIALS AND METHODS: A total of 60 bovine enamel specimens discolored with black tea were divided into five groups treated with distilled water (DW), HP, 0.01 wt.% BAG + HP, 1.0 wt.% BAG + HP, and 20.0 wt.% BAG + HP (n = 12). The pH change was observed for 20 min immediately after mixing the experimental solutions, which were applied for 20 min/week, at 37 °C over 21 days. Color, gloss, roughness, microhardness, and micromorphology measurements were conducted before and after bleaching treatment. RESULTS: All groups containing BAG experienced an increase in pH from 3.5 to 5.5 in less than 1 min, and the final pH increased as the BAG content increased. The ΔE of all experimental groups was significantly higher than that of the DW group (p < 0.05), but there were no significant differences between different BAG contents (p > 0.05). Gloss significantly decreased in all experimental groups compared to the DW group, and the increased BAG content had significantly affected the decrease in gloss (p < 0.05). There was no statistical difference in surface roughness (p > 0.05), but hardness increased significantly with BAG content after bleaching treatment (p < 0.05). CONCLUSIONS: HP containing 45S5 BAG showed efficacy in tooth whitening. Also, the pH value of the HP remained acidic near 3.5 for 20 min, while the HP containing the 45S5 BAG showed an increase in pH, which inhibited the demineralization of the enamel surface, and maintained the surface morphology. CLINICAL RELEVANCE: These novel materials are promising candidates to minimize enamel surface damage caused by HP during bleaching procedure in dental clinic.

Cytotoxicity, Colour Stability and Dimensional Accuracy of 3D Printing Resin with Three Different Photoinitiators.

Biocompatibility is important for the 3D printing of resins used in medical devices and can be affected by photoinitiators, one of the key additives used in the 3D printing process. The choice of ingredients must be considered, as the toxicity varies depending on the photoinitiator, and unreacted photoinitiator may leach out of the polymerized resin. In this study, the use of ethyl (2,4,6-trimethylbenzoyl) phenylphosphinate (TPO-L) as a photoinitiator for the 3D printing of resin was considered for application in medical device production, where the cytotoxicity, colour stability, dimensional accuracy, degree of conversion, and mechanical/physical properties were evaluated. Along with TPO-L, two conventional photoinitiators, phenylbis (2,4,6-trimethylbenzoyl) phosphine oxide (BAPO) and diphenyl (2,4,6-trimethylbenzoyl) phosphine oxide (TPO), were considered. A total of 0.1 mol% of each photoinitiator was mixed with the resin matrix to prepare a resin mixture for 3D printing. The specimens were printed using a direct light processing (DLP) type 3D printer. The 3D-printed specimens were postprocessed and evaluated for cytotoxicity, colour stability, dimensional accuracy, degree of conversion, and mechanical properties in accordance with international standards and the methods described in previous studies. The TPO-L photoinitiator showed excellent biocompatibility and colour stability and possessed with an acceptable dimensional accuracy for use in the 3D printing of resins. Therefore, the TPO-L photoinitiator can be sufficiently used as a photoinitiator for dental 3D-printed resin.

Evaluation of the time-dependent efficacy of commercial denture or orthodontic appliance cleansers: An in vitro study.

The aim of this study was to evaluate the antimicrobial, stain and protein removal efficacy of denture or orthodontic appliance cleansers using in vitro test methods. Experimental cleansers were applied for experimental time in each evaluation method. To evaluate the microorganism removal efficacy, C. albicans and S. mutans removal rate was calculated from the specimen surface. Stain and protein removal rate was calculated using the spectrophotometer. Experimental cleansers significantly affected the microorganism removal rate for both C. albicans and S. mutans, as well as the stain and protein removal rates, at each experimental time (p<0.05). As the application time increased, the stain and protein removal rates of all experimental cleansers significantly increased (p<0.05). The present study provided in vitro evaluation methods to assess the efficacy of denture or orthodontic appliance cleansers. Also, manufacturers and researchers can predict clinical outcomes and ensure proper hygiene management of dentures or orthodontic appliances.

Effects of 35% hydrogen peroxide solution containing hydrated calcium silicate on enamel surface.

OBJECTIVES: The objectives of this study were to develop a novel bleaching material containing hydrated calcium silicate (hCS) particles and investigate the effects of hCS on the bleaching efficacy, microhardness, and surface morphology of bovine enamel. MATERIALS AND METHODS: To prepare the hCS particles, white Portland cement was mixed with distilled water and ground into a fine powder. The particles in various proportions were then mixed with 35% hydrogen peroxide solution (HP), while HP without hCS was used as a control (HP), and teeth whitening gel was used as a commercial control (CC). Following the thrice application of experimental and control solutions on the discolored bovine enamel surface for 15 min, color change (n = 10), microhardness (n = 10), and micromorphology (n = 2) of the enamel surface were analyzed. RESULTS: The Δ E* of the enamel surface treated with the experimental solution containing hCS was significantly higher than that of the CC, but there were no significant differences between the different hCS contents. The experimental solution containing hCS reduced the percentage of microhardness loss on the enamel surface, and the percentage of microhardness loss significantly decreased as the content of hCS increased (p < 0.05). The erosion pattern was only observed on enamel surfaces treated with HP and CC. CONCLUSIONS: This study suggests that HP containing hCS is effective in bleaching efficacy. In addition, hCS could also minimize the microhardness loss of tooth structure caused by HP and maintain enamel surface morphology. CLINICAL RELEVANCE: This novel bleaching material is promising for inhibiting demineralization and promoting the remineralization of teeth during bleaching treatment in dental clinics.

Clinical Outcomes of Computational Virtual Mapping-Guided Catheter Ablation in Patients With Persistent Atrial Fibrillation: A Multicenter Prospective Randomized Clinical Trial.

Background: Clinical recurrence after atrial fibrillation catheter ablation (AFCA) still remains high in patients with persistent AF (PeAF). We investigated whether an extra-pulmonary vein (PV) ablation targeting the dominant frequency (DF) extracted from electroanatomical map-integrated AF computational modeling improves the AFCA rhythm outcome in patients with PeAF. Methods: In this open-label, randomized, multi-center, controlled trial, 170 patients with PeAF were randomized at a 1:1 ratio to the computational modeling-guided virtual DF (V-DF) ablation and empirical PV isolation (E-PVI) groups. We generated a virtual dominant frequency (DF) map based on the atrial substrate map obtained during the clinical AF ablation procedure using computational modeling. This simulation was possible within the time of the PVI procedure. V-DF group underwent extra-PV V-DF ablation in addition to PVI, but DF information was not notified to the operators from the core lab in the E-PVI group. Results: After a mean follow-up period of 16.3 ± 5.3 months, the clinical recurrence rate was significantly lower in the V-DF than with E-PVI group (P = 0.018, log-rank). Recurrences appearing as atrial tachycardias (P = 0.145) and the cardioversion rates (P = 0.362) did not significantly differ between the groups. At the final follow-up, sinus rhythm was maintained without any AADs in 74.7% in the V-DF group and 48.2% in the E-PVI group (P < 0.001). No significant difference was found in the major complication rates (P = 0.489) or total procedure time (P = 0.513) between the groups. The V-DF ablation was independently associated with a reduced AF recurrence after AFCA [hazard ratio: 0.51 (95% confidence interval: 0.30-0.88); P = 0.016]. Conclusions: The computational modeling-guided V-DF ablation improved the rhythm outcome of AFCA in patients with PeAF. Clinical Trial Registration: Clinical Research Information Service, CRIS identifier: KCT0003613.

Discovery of a Potent and Selective JNK3 Inhibitor with Neuroprotective Effect Against Amyloid ß-Induced Neurotoxicity in Primary Rat Neurons.

As members of the MAPK family, c-Jun-N-terminal kinases (JNKs) regulate the biological processes of apoptosis. In particular, the isoform JNK3 is expressed explicitly in the brain at high levels and is involved in the pathogenesis of neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). In this study, we prepared a series of five 6-dihydroxy-1H-benzo[d]imidazoles as JNK3 inhibitors and found them have potential as neuroprotective agents. Following a previous lead scaffold, benzimidazole moiety was modified with various aryl groups and hydroxylation, and the resulting compounds exhibited JNK3 inhibitory activity with improved potency and selectivity. Out of 37 analogues synthesized, (S)-cyclopropyl(3-((4-(2-(2,3-dihydrobenzo[b][1,4]dioxin -6-yl)-5,6-dihydroxy-1H-benzo[d]imidazol-1-yl)pyrimidin-2-yl)amino) piperidin-1-yl)methanone (35b) demonstrated the highest JNK3 inhibition (IC50 = 9.7 nM), as well as neuroprotective effects against Aß-induced neuronal cell death. As a protein kinase inhibitor, it also showed excellent selectivity over other protein kinases including isoforms JNK1 (>1000 fold) and JNK2 (-10 fold).

Efficacy and Safety of High-Power Short-Duration Radiofrequency Catheter Ablation of Atrial Fibrillation.

Introduction: Whereas, high-power short-duration (HPSD) radiofrequency (RF) ablation is generally used in atrial fibrillation (AF) catheter ablation (CA), its efficacy, safety, and influence on autonomic function have not been well established in a large population. This study compared HPSD-AFCA and conventional power (ConvP)-AFCA in propensity score matched-population. Methods: In 3,045 consecutive patients who underwent AFCA, this study included 1,260 patients (73.9% male, 59 ± 10 years old, 58.2% paroxysmal type) after propensity score matching: 315 in 50~60W HPSD group vs. 945 in the ConvP group. This study investigated the procedural factors, complication rate, rhythm status, and 3-month heart rate variability (HRV) between the two groups and subgroups. Results: Procedure time was considerably short in the HPSD group (135 min in HPSD vs. 181 min in ConvP, p < 0.001) compared to ConvP group, but there was no significant difference in the complication rate (2.9% in HPSD vs. 3.7% in ConvP, p = 0.477) and the 3-month HRV between the two groups. At the one-year follow-up, there was no significant difference in rhythm outcomes between the two groups (Overall, Log-rank p = 0.885; anti-arrhythmic drug free, Log-rank p = 0.673). These efficacy and safety outcomes were consistently similar irrespective of the AF type or ablation lesion set. The Cox regression analysis showed that the left atrium volume index estimated by computed tomography (HR 1.01 [1.00-1.02]), p = 0.003) and extra-pulmonary vein triggers (HR 1.59 [1.03-2.44], p = 0.036) were independently associated with one-year clinical recurrence, whereas the HPSD ablation was not (HR 1.03 [0.73-1.44], p = 0.887). Conclusion: HPSD-AFCA notably reduced the procedure time with similar rhythm outcomes, complication rate, and influence on autonomic function as ConvP-AFCA, irrespective of the AF type or ablation lesion set.