Prussian blue analogues improves the microenvironment after spinal cord injury by regulating Zn.

Mitochondrial injury, neuronal apoptosis and phenotypic transformation of macrophages are the main mechanisms of spinal cord injury. Based on the Prussian blue nanomase's strong ability to clear free radicals, the treatment of spinal cord injury with nano-zirconium (Pb-Zr) was carried out. The disease treatment strategy based on nanomaterials has excellent therapeutic effect, and Prussian blue analogs have good therapeutic properties, so the application prospects of Prussian blue analogs is broad. From the point of view of Prussian blue content, improving the presence of zirconium in the microenvironment significantly increased the activity of Prussian blue. Prussian Blue zirconium significantly improved lipopolysaccharide (LPS) and interferon (IFN-γ) induced neuronal cell (pc12 cells) and macrophage dysfunction by improving oxidative stress, inflammation, and apoptosis in the microenvironment. It can promote the recovery of motor function after spinal cord injury. In vivo experiments, it shows that Prussian blue zirconium can improve inflammation, apoptosis and oxidative stress of spinal cord tissue, promote regenerative therapy after spinal cord injury, and improve motor function. Moreover, it has been reported that high-priced Zr4+ cations can regulate the deposition and nucleation behavior of Zn2+ in high-performance zinc metal anodes. Therefore, we propose the hypothesis that Pb-Zr modulates Zn2+ be used to promote recovery from spinal cord injury. The results show that nanomaterial is beneficial in the treatment of spinal cord injury. This study provides a good prospect for the application of spinal cord injury treatment. It also provides an important feasibility for subsequent clinical conversions.

Zirconia dental implants; the relationship between design and clinical outcome: A systematic review.

OBJECTIVE: To evaluate the clinical outcome of different designs of zirconia dental implants. DATA: This systematic review adhered to the PRISMA checklist and followed the PICO framework. The protocol is registered in PROSPERO (CRD42022337228). SOURCES: The search was conducted in March 2023 through four databases (PubMed, Web of Science, Cochrane Library, and Google Scholar) along with a search of references in the related reviews. Three authors reviewed on title, and abstract level and analysed the risk of bias, and all authors reviewed on a full-text level. STUDY SELECTION: Clinical studies excluding case reports for patients treated with different designs of zirconia dental implants were included. From a total of 2728 titles, 71 full-text studies were screened, and 27 studies were included to assess the risk of bias (ROBINS-I tool) and data extraction. After quality assessment, four studies were included, and the remaining 23 excluded studies were narratively described. RESULT: The included prospective studies with moderate risk of bias reported success and survival rates of one-piece implants that ranged between 95 and 98.4 % with no difference between different lengths and diameters. The acid-etched roughened surface showed higher clinical outcomes compared to other surface roughness designs. CONCLUSION: Promising 5-year clinical outcomes were found for one-piece zirconia implants with no difference between different diameters and lengths. Concerning surface roughness, better outcomes were found when using the acid-etched implant surface. However, due to the limited available studies, further high-quality clinical studies comparing zirconia one-piece and two-piece implants with different diameters, lengths, and surface roughness are needed. CLINICAL SIGNIFICANCE: Based on this systematic review, under suitable clinical situations, the one-piece zirconia implants with diameters of 4.0 mm, 4.5 mm, or 5.5 mm and lengths of 8 mm, 10 mm, 12 mm, or 14 mm have similar promising clinical outcomes. Additionally, the acid-etched roughened implant surface may be preferable.

A Fluorinated BODIPY-Based Zirconium Metal-Organic Framework for In Vivo Enhanced Photodynamic Therapy.

Photodynamic therapy (PDT), an emergent noninvasive cancer treatment, is largely dependent on the presence of efficient photosensitizers (PSs) and a sufficient oxygen supply. However, the therapeutic efficacy of PSs is greatly compromised by poor solubility, aggregation tendency, and oxygen depletion within solid tumors during PDT in hypoxic microenvironments. Despite the potential of PS-based metal-organic frameworks (MOFs), addressing hypoxia remains challenging. Boron dipyrromethene (BODIPY) chromophores, with excellent photostability, have exhibited great potential in PDT and bioimaging. However, their practical application suffers from limited chemical stability under harsh MOF synthesis conditions. Herein, we report the synthesis of the first example of a Zr-based MOF, namely, 69-L2, exclusively constructed from the BODIPY-derived ligands via a single-crystal to single-crystal post-synthetic exchange, where a direct solvothermal method is not applicable. To increase the PDT performance in hypoxia, we modify 69-L2 with fluorinated phosphate-functionalized methoxy poly(ethylene glycol). The resulting 69-L2@F is an oxygen carrier, enabling tumor oxygenation and simultaneously acting as a PS for reactive oxygen species (ROS) generation under LED irradiation. We demonstrate that 69-L2@F has an enhanced PDT effect in triple-negative breast cancer MDA-MB-231 cells under both normoxia and hypoxia. Following positive results, we evaluated the in vivo activity of 69-L2@F with a hydrogel, enabling local therapy in a triple-negative breast cancer mice model and achieving exceptional antitumor efficacy in only 2 days. We envision BODIPY-based Zr-MOFs to provide a solution for hypoxia relief and maximize efficacy during in vivo PDT, offering new insights into the design of promising MOF-based PSs for hypoxic tumors.

Long-term clinical outcome of three-unit fixed-fixed posterior zirconia ceramic inlay-retained FDPs with a modified design.

OBJECTIVES: To assess the long-term clinical outcome of posterior inlay-retained fixed dental prostheses (IRFDPs) with a modified design made from zirconia ceramic. METHODS: In 30 patients thirty 3-unit IRFDPs were placed to replace 7 premolars (4 in the maxilla, 3 in the mandible), and 23 first molars (15 in the maxilla, 8 in the mandible). Preparations were accomplished in agreement with the general principles for ceramic inlay restorations and modified with a short retainer-wing bevel preparation within the enamel at the buccal and oral sides. The frameworks were milled from 3Y-TZP ceramic, and the pontics were veneered with feldspathic ceramic. All IRFDPs were bonded with a phosphate monomer containing luting resin after air-abrasion of the intaglio surfaces. The patients were recalled 6-12 months after placement, and then annually. Kaplan-Meier analysis was used to calculate the survival and complication rates of the IRFDPs. RESULTS: The mean observation time was 10.6 ± 1.5 years. The 10-year cumulative survival rate was 89% with 4 failures, two of them were due to deep secondary caries with loss of retention, one due to repeated debonding with enamel fractures, and one due to generalized progressive periodontitis. The most common complication was chipping of the veneering ceramic (20.1%). Eighteen IRFDPs were free of any type of complication up to 15.4 years, which corresponds to a 10-year cumulative success rate of 70.4%. CONCLUSION: The long-term clinical performance of modified IRFDPs made of veneered zirconia ceramics was favorable after 10 years, therefore, they represent a treatment alternative to replace posterior single missing teeth. CLINICAL SIGNIFICANCE: Zirconia-based IRFDPs fabricated in the modified design may represent a substance-preserving alternative to conventional posterior FDPs to replace posterior single missing teeth, particularly in cases where implants cannot be placed, and when the adjacent teeth already have small restorations or defects.

Clinical Performance of Minimally Invasive Monolithic Ultratranslucent Zirconia Veneers: A Case Series up to Five Years of Follow-up.

There is a lack of reports in the literature on the long-term clinical performance of ultratranslucent zirconia, especially considering its use in manufacturing monolithic veneers. The purpose of this case series is to describe the aesthetic treatment steps of three patients with minimally invasive ultratranslucent zirconia veneers and to report the clinical findings up to five years. Three patients (woman: 2, man: 1; mean age: 30 years) unsatisfied with their dental aesthetics sought dental treatment. The treatment plan involved cementing ultratranslucent zirconia veneers. Air-abrasion was performed on the internal surface of zirconia with alumina particles coated by silica (silicatization), followed by silane and adhesive applications for the adhesive cementation. All veneers were adhesively cemented to enamel with resin cement (Variolink Esthetic, Ivoclar). The patients were clinically evaluated annually considering the Ryge modified/ California Dental Association criteria. After a mean follow-up of 4.33 years (4-5 years), a survival rate of 100% was detected for the 28 minimally invasive ultratranslucent zirconia veneers cemented in the 3 patients. There were no absolute failures such as debonding, veneer fracture, or secondary caries. Superficial marginal discoloration was observed in one element (maxillary left lateral incisor) of one patient. Ultratranslucent zirconia is a viable option for manufacturing veneers due to its excellent clinical performance and longevity. However, further long-term clinical studies are essential to consolidate this material as an option for esthetic restorations.

Retention of zirconia crown to oxidized titanium base abutment: Experimental research.

STATEMENT OF PROBLEM: To separate the crown from the titanium base abutment, by using heat, caused oxidization of the titanium base abutment. The effect of this procedure on the retention of a crown is unclear. PURPOSE: To compare the resin bond strength and failure type between zirconia crowns and titanium base abutments utilizing four different surface treatments. Surface roughness and morphology of each surface treatment were also investigated. MATERIAL AND METHODS: Forty titanium base abutments (Variobase®) were divided into four groups, 1. Control, 2. Air abraded, 3. Oxidized, and 4. Oxidized-air abraded. Oxidized and oxidized-air abraded groups were debonded from zirconia crowns using constant dry heat at 500 ˚C. For air abraded and oxidized-air abraded groups (after oxidization), the titanium base abutments were air abraded with Al3O2. After cleaning, one specimen of each group was investigated under a non-contact profilometer (50x), then the same samples were investigated under SEM at 25,300,500,1000 magnification and EDS at 30kV of accelerated voltage. All specimens were then cemented (RelyX Ultimate). After aging, with thermocycling under 5C° to 55C°,120 seconds dwell time for 5,000 cycles, bond strength was tested and statistical differences were calculated with One-way ANOVA (p-value <0.05) follow by Tukey test. All separated crowns and titanium base abutments were investigated under a light microscope (20x), using fisher's exact test for correlation of the failure types. RESULTS: There was a significant difference in the mean value of tensile bond strength among the control and test groups. Comparisons between control(237.6±46.3N) and oxidized(241.7±46.3N) showed statistically different values from air abraded(372.9±113.2N) when assembled using different surface treatments of the titanium-based abutments. (p-value<0.005) As for failure type, there were statistically significant differences between control versus air abraded, control versus oxidized-air abraded, oxidized versus air abraded, and oxidized versus oxidized-air abraded. (p-value<0.001) The titanium surface morphology shown from the profilometer and SEM was coordinated. Control (Ra 333.8nm) and oxidized (Ra 321.0nm) groups surfaces showed smooth, corrugated surfaces, meanwhile air abraded (Ra 476.0nm) and oxidized-air abraded (Ra 423.8nm) groups showed rough, rugged surfaces. CONCLUSION: Heat oxidization of titanium-based abutments did not adversely affect tensile bond strength or the failure mode and surface roughness between titanium base abutments and zirconia crowns. However, air abrasion of the titanium surface increased surface roughness and retentive strength. CLINICAL IMPLICATIONS: The titanium base abutments that were oxidized under heat treatment did not have an effect on crown retention. Thoroughly air abraded the titanium abutment prior to cementation can increase cement bond strength.

Current classification of zirconia in dentistry: an updated review.

Zirconia, a crystalline oxide of zirconium, holds good mechanical, optical, and biological properties. The metal-free restorations, mostly consisting of all-ceramic/zirconia restorations, are becoming popular restorative materials in restorative and prosthetic dentistry choices for aesthetic and biological reasons. Dental zirconia has increased over the past years producing wide varieties of zirconia for prosthetic restorations in dentistry. At present, literature is lacking on the recent zirconia biomaterials in dentistry. Currently, no article has the latest information on the various zirconia biomaterials in dentistry. Hence, the aim of this article is to present an overview of recent dental zirconia biomaterials and tends to classify the recent zirconia biomaterials in dentistry. This article is useful for dentists, dental technicians, prosthodontists, academicians, and researchers in the field of dental zirconia.

Different Designs of Deep Marginal Elevation and Its Influence on Fracture Resistance of Teeth with Monolith Zirconia Full-Contour Crowns.

Background and objectives: Even with the demand for high esthetics, the strength of the material for esthetic applications continues to be important. In this study, monolith zirconia (MZi) crowns fabricated using CAD/CAM were tested for fracture resistance (FR) in teeth with class II cavity designs with varying proximal depths, restored through a deep marginal elevation technique (DME). Materials and Methods: Forty premolars were randomly divided into four groups of ten teeth. In Group A, tooth preparation was conducted and MZi crowns were fabricated. In Group B, mesio-occluso-distal (MOD) cavities were prepared and restored with microhybrid composites before tooth preparation and the fabrication of MZi crowns. In Groups C and D, MOD cavities were prepared, differentiated by the depth of the gingival seat, 2 mm and 4 mm below the cemento-enamel junction (CEJ). Microhybrid composite resin was used for DME on the CEJ and for the restoration of the MOD cavities; beforehand, tooth preparations were conducted and MZi crowns were and cemented using resin cement. The maximum load to fracture (in newtons (N)) and FR (in megapascals (MPa)) were measured using the universal testing machine. Results: The average scores indicate a gradual decrease in the load required to fracture the samples from Groups A to D, with mean values of 3415.61 N, 2494.11 N, 2108.25 N and 1891.95 N, respectively. ANOVA revealed highly significant differences between the groups. Multiple group comparisons using the Tukey HSD post hoc test revealed that Group D had greater DME depths and showed significant differences compared with Group B. Conclusions: FR in teeth decreased when more tooth structure was involved, even with MZi crowns. However, DME up to 2 mm below the CEJ did not negatively influence the FR. Strengthening the DME-treated teeth with MZi crowns could be a reasonable clinical option, as the force required to fracture the samples far exceeded the maximum recorded biting force for posterior teeth.

Zirconia-veneered polyetherketoneketone frameworks of implant-supported complete arch fixed dental prostheses: A report on 5 patients.

Metal frameworks have been used for implant-supported complete arch fixed dental prostheses (ISCFDPs) for maxillary or mandibular edentulous arches with a crown height space of more than 15 mm. However, technical difficulties in the casting, weight, and lack of passivity of the metal have led dentists and dental laboratory technicians to choose materials with different biomechanical properties, including polyetheretherketone (PEEK) and polyetherketoneketone (PEKK). This clinical report describes the design of ISCFDPs using PEKK frameworks, the number of cantilevers, the condition of the opposing dentition, and the incidence of complications, including zirconia crown or PEKK framework fracture, as well as the clinical outcomes of 5 patients observed prospectively over 8 to 65 months. No mechanical complications of PEKK-made ISCFDPs opposing removable prostheses occurred, regardless of the presence of cantilevers. The ISCFDPs that opposed natural dentition or a combination of the natural dentition and fixed prostheses showed different clinical outcomes depending on the length of cantilevers and the number and location of pontics.

An in vitro trial on the effect of arch form on connector size requirements in long span anterior zirconia fixed dental prostheses.

PURPOSE: To test the fracture resistance of maxillary canine to canine fixed partial denture with four missing incisors, with increasing anterior-cantilevers of the pontics and varying connector sizes. MATERIALS AND METHODS: Two 3D-printed titanium alloy (Ti6Al4V) models mimicking a maxillary canine to canine fixed partial denture (FPD) with four pontics replacing the incisors were used as master models. Zirconia FPDs were digitally designed and milled with two different connector sizes (9 and 12 mm2 ) each with three different anterior cantilevers (7, 10, and 13 mm) accounting for 6 test groups. Seven samples were milled for each group generating a total of 42 samples. The zirconia FPDs were cemented on the titanium model using resin modified glass ionomer cement and the model fixated to a variable angle vice. A sinusoidal cyclic waveform load from 50 to 280N was applied using a universal testing machine at a frequency of 30 cycles per second and a total of 5 million cycles. RESULTS: The results of Fisher's exact tests showed that the difference in the proportion of fractured versus nonfractured fixed partial dentures was not statistically significant when comparing the 9 with the 12 mm2 connector size (p = 1.00), as well as when comparing the six test groups (p = 0.2338); on the other hand, it proved to be statistically significant when comparing the 7 mm cantilever with the 10 and 13 mm cantilevers combined (p = 0.0407) indicating that a 7 mm anterior spread of the pontics showed a significantly greater proportion of fixed partial dentures that fractured. CONCLUSIONS: Fracture susceptibility was not a function of cantilever length in this testing configuration for anterior FPDs. Retainer crown thickness seems to be a more important parameter than connector size thickness. Based on the results, a smaller connector size (9 mm2 ) can be used to improve the esthetics of pontics in long span anterior FPDs.

Liquid exfoliation of ultrasmall zirconium carbide nanodots as a noninflammatory photothermal agent in the treatment of glioma.

Photothermal therapy (PTT), like other clinical translational tumor ablation techniques, requires a temperature increase above 50 °C to cause necrosis and death of tumor cells. Although the tumor can be eliminated rapidly by PTT, the inflammatory response is triggered by the large amounts of released reactive oxygen species (ROS). Therefore, liquid exfoliation was used to create ultrasmall zirconium carbide nanodots (NDs) with an average diameter of approximately 4.5 nm as noninflammatory/anti-inflammatory photosensitizers for PTT of glioma. Ultrasmall ZrC NDs showed excellent photothermal stability and biocompatibility but no obvious toxicity. Moreover, the ultrasmall ZrC NDs effectively ablated glioma at relatively low concentrations and inhibited tumor migration and proliferation in vitro and in vivo. Furthermore, the excellent ROS-scavenging ability of ultrasmall ZrC NDs suppressed the inflammatory response to PTT. Intriguingly, we found that ZrC had the capability of performing CT imaging. We demonstrated that the ultrasmall ZrC NDs created in this study could effectively and safely treat glioma without inflammation.

Preclinical Evaluation of 89Zr-Desferrioxamine-Bexmarilimab, a Humanized Antibody Against Common Lymphatic Endothelial and Vascular Endothelial Receptor-1, in a Rabbit Model of Renal Fibrosis.

Bexmarilimab is a new humanized monoclonal antibody against common lymphatic endothelial and vascular endothelial receptor-1 (CLEVER-1) and is in clinical trials for macrophage-guided cancer immunotherapy. In addition being associated with cancer, CLEVER-1 is also associated with fibrosis. To facilitate prospective human PET studies, we preclinically evaluated 89Zr-labeled bexmarilimab in rabbits. Methods: Bexmarilimab was conjugated with desferrioxamine (DFO) and radiolabeled with 89Zr. Retained immunoreactivity was confirmed by flow cytometry. The distribution kinetics of intravenously administered 89Zr-DFO-bexmarilimab (0.1 mg/kg) were determined for up to 7 d in a rabbit model of renal fibrosis mediated by unilateral ureteric obstruction. The in vivo stability of 89Zr-DFO-bexmarilimab was evaluated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis in combination with autoradiography. Additionally, we estimated the human radiation dose from data obtained in healthy rabbits. Results: 89Zr-DFO-bexmarilimab cleared rapidly from the blood circulation and distributed to the liver and spleen. At 24 h after injection, PET/CT, ex vivo γ-counting, and autoradiography demonstrated that there was significantly higher 89Zr-DFO-bexmarilimab uptake in unilateral ureteric obstruction-operated fibrotic renal cortex, characterized by abundant CLEVER-1-positive cells, than in contralateral or healthy kidneys. The estimated effective dose for a 70-kg human was 0.70 mSv/MBq. Conclusion: The characteristics of 89Zr-DFO-bexmarilimab support future human PET studies to, for example, stratify patients for bexmarilimab treatment, evaluate the efficacy of treatment, or monitor disease progression.

Clinical outcomes of single crown and 3-unit bi-layered zirconia-based fixed dental prostheses: An upto 6- year retrospective clinical study: Clinical outcomes of zirconia FDPs.

OBJECTIVES: The aim of this retrospective clinical study was to evaluate the survival and the occurrence of technical and biological complications in bi-layered zirconia-based (Zi) single crown and 3-unit fixed dental prostheses (FDPs). Also, the study aimed to analyze the effects of tooth vitality (vital versus non-vital), abutment location (anterior versus posterior), and luting cement (self-adhesive resin versus resin-reinforced glass ionomer) on clinical outcomes. METHODS: A total of 147 prostheses (in 94 patients) placed by undergraduate dental students in a university dental center during the period 2015-2021 were examined clinically using modified United States Public Health Service (USPHS) and California Dental Association (CDA) criteria. The mean duration of follow-up was 37 months (range, 6 - 63 months) for the single crowns (n = 77) and 25 months (range, 6 - 68 months) for the 3-unit FDPs (n = 70). Data were descriptively analyzed to determine the types and rates of complications based on USPHS and CDA criteria. The Kaplan-Meier survival estimation method was used to determine the cumulative survival and success rates of the prostheses (α=0.05). Differences in clinical outcomes (survival or failure) according to tooth vitality, luting cement, and location were statistically analyzed using cross-tabulations and Ð¥2 test (α=0.05). RESULTS: The Kaplan-Meier cumulative survival rate was estimated as 96% for the Zi 3-unit FDPs after 5.5 years, and 90% for the Zi single crowns after 4.8 years. The 5-year estimated success rate was 68% for both 3-unit FDPs and single crowns. Seven (9.1%) 77Zi single crowns and 70 2 (2.9%) Zi 3-unit FDPs were recorded as failures with occlusal roughness being the most commonly-observed complication (crowns: 4 [5.6%]; 3-unit FDPs: 8 [11.4%]). In terms of clinical outcomes, statistically significant differences were found between all included vital and non-vital teeth (p = .006), and cement types (p = .028). Taking single crowns alone, significant differences in clinical outcomes according to tooth vitality were noted (p = .036), but not for PFDPs. The location of the prostheses did not produce any significant differences in the clinical outcomes, for both prostheses types independently or combined (p > .05). CONCLUSIONS: The estimated cumulative survival rates in this study for single crowns and 3-unit Zi FDPs concurred with the ranges reported in systematic reviews. Zi-based prostheses on vital teeth produced better clinical outcomes than those placed on non-vital teeth, and type of luting cement influenced the final clinical outcome. CLINICAL SIGNIFICANCE: Zi crowns and 3-unit PFDPs fabricated using the specific CAD-CAM system used in the controlled environment of this study showed good clinical performance with minimal veneer porcelain chipping. Root canal treated teeth seem to be at higher risk for failure of Zi prostheses compared with vital teeth.

Synthesis and Biomedical Applications of Zirconium Nanoparticles: Advanced Leaps and Bounds in the Recent Past.

Many synthetic routes manufacture zirconium nanoparticles in metal oxide, nitride, and other combination forms. Coupled with other variables such as concentration, pH, and form of precursor used, the various synthetic methods support synthesizing the zirconium metal oxide nanoparticles with changed features. Various synthetic methods were studied, such as sol-gel, hydrothermal, laser ablation, and precipitation. All have different synthetic routes, different precursors and solvents were sued, and the product was characterized by SEM, TEM, photo luminance spectroscopy, UV-absorption spectroscopy, and powder X-ray diffraction. X-ray diffraction determined the crystal structure by identifying the crystal shape, arrangement of atoms, and spacing between them. SEM and TEM studied the particle size and morphology of nanoparticles. UV-visible absorption spectroscopy and PL spectroscopy were used for the determination of optical properties of nanoparticles. Zirconium oxide nanoparticles have many applications in the medical field. The review study primarily focuses on the efficient combination of zirconium dioxide with other additive materials and functionalization techniques used to improve the material's properties, assisting the use of the material in hip arthroplasty and bone tissue applications. The development of sophisticated near-infrared (NIR) absorbing small molecules for useful phototheranostic applications was discussed in this paper.

Ceramic Dental Implants: An Overview of Materials, Characteristics, and Application Concepts.

The clinical application of modern bioceramics is no longer limited only to prosthetic restorations. Zirconia is also successfully used as a dental implant material, enabling a metal-free restoration concept in most cases. The demand for such metal-free solutions is steadily rising mainly because of patients' increased health awareness. With the development of new materials, microrough surfaces, and improved treatment protocols, implants made of zirconium dioxide are already achieving results comparable to those of titanium. This advancement will enable clinicians to leverage the clinical advantages of ceramic implants in daily practice as an additional reliable treatment alternative to titanium implants. However, to successfully use ceramic implants, practitioners should have knowledge of the background of zirconium dioxide material and its particular features in clinical application, as presented in this overview article.

Fracture load of zirconia crowns based on preparation and cement type.

Limited research has been published evaluating the failure of zirconia crowns with less retentive tooth preparations. The purpose of this study was to evaluate the effect of axial wall height (AWH) and cement type on the fracture load of cubic phase-containing zirconia crowns. Standardized crown preparations with an AWH of 0, 2, or 4 mm (n = 10) were made in 90 extracted human maxillary third molars. The preparations were scanned, and crown restorations were designed. Cubic phase-containing zirconia crowns were milled and cemented with a resin-modified glass ionomer cement, a self-adhesive resin cement, or an adhesive resin cement. The specimens were subjected to thermocycling and cyclic loading. Each crown specimen was positioned in a universal testing machine so that the long axis of the tooth was at a 60° angle to the testing fixture and loaded until failure using a stainless steel rod resting on the buccal incline of the palatal cusp. Data were found to have a nonnormal distribution and were analyzed with Kruskal-Wallis and Mann-Whitney U tests (α = 0.05). Statistically significant differences in the median fracture loads of the groups were found based on both AWH and cement type (P < 0.05). Regardless of cement type, the median fracture loads were significantly lower in the 0-mm AWH groups than in the 2-mm and 4-mm AWH groups, which were not significantly different from each other. Compared to the other cement types, adhesive resin cement resulted in a significantly greater median fracture load when the AWH was 0 mm. The use of an adhesive resin cement with a cubic phase-containing zirconia crown may provide greater fracture resistance for preparations with minimal AWH.

Leveraging a physiologically-based quantitative translational modeling platform for designing B cell maturation antigen-targeting bispecific T cell engagers for treatment of multiple myeloma.

Bispecific T cell engagers (TCEs) are an emerging anti-cancer modality that redirects cytotoxic T cells to tumor cells expressing tumor-associated antigens (TAAs), thereby forming immune synapses to exert anti-tumor effects. Designing pharmacokinetically acceptable TCEs and optimizing their size presents a considerable protein engineering challenge, particularly given the complexity of intercellular bridging between T cells and tumor cells. Therefore, a physiologically-relevant and clinically-verified computational modeling framework is of crucial importance to understand the protein engineering trade-offs. In this study, we developed a quantitative, physiologically-based computational framework to predict immune synapse formation for a variety of molecular formats of TCEs in tumor tissues. Our model incorporates a molecular size-dependent biodistribution using the two-pore theory, extravasation of T cells and hematologic cancer cells, mechanistic bispecific intercellular binding of TCEs, and competitive inhibitory interactions by shed targets. The biodistribution of TCEs was verified by positron emission tomography imaging of [89Zr]AMG211 (a carcinoembryonic antigen-targeting TCE) in patients. Parameter sensitivity analyses indicated that immune synapse formation was highly sensitive to TAA expression, degree of target shedding, and binding selectivity to tumor cell surface TAAs over shed targets. Notably, the model suggested a "sweet spot" for TCEs' CD3 binding affinity, which balanced the trapping of TCEs in T-cell-rich organs. The final model simulations indicated that the number of immune synapses is similar (~55/tumor cell) between two distinct clinical stage B cell maturation antigen (BCMA)-targeting TCEs, PF-06863135 in an IgG format and AMG420 in a BiTE format, at their respective efficacious doses in multiple myeloma patients. This result demonstrates the applicability of the developed computational modeling framework to molecular design optimization and clinical benchmarking for TCEs, thus suggesting that this framework can be applied to other targets to provide a quantitative means to facilitate model-informed best-in-class TCE discovery and development.

Are zirconia crowns the superior choice when restoring primary posterior molars?

Data sources Electronic database searches were carried out using predefined search terms using Embase, Google Scholar, Medline, The Cochrane Library, The Cochrane Central Register of Controlled Trials and Latin American and Caribbean Health Sciences Literature. The Trip medical database was also used to identify randomised control trials investigating stainless steel and zirconia crowns. Studies published from 1 January 2000 until 6 June 2021 were included, and reference lists of included studies analysed to ensure data saturation along with grey literature searches.Study selection Inclusion criteria included research published in English only, randomised control trials investigating the clinical and radiographic effectiveness of zirconia crowns compared to stainless steel crowns, the rehabilitation of pulp-treated posterior primary teeth and randomised control trials with children in good health. Expert opinion, case reports and reviews were excluded. Studies with a follow-up period of less than 12 months, studies including children with special care requirements or non-compliant children were also excluded.Data extraction and synthesis Two reviewers (AKP, VKC) were involved with the primary search of abstracts and titles independently; both reviewers were involved in full text assessment. Disagreements were resolved by a third reviewer (NRV). The study characteristics, number of teeth evaluated, follow-up duration, type of zirconia and stainless steel crowns, outcome assessed and outcome results were extracted. Extracted data was analysed using Review Manager, Version 5.3 and dichotomous data was summarised as risk ratios with 95% confidence intervals. Continuous data was summarised as mean difference. Heterogeneity was summarised by I2 scores and a random-effects model and Mantel-Haenszel statistical test was used.Results From the initial 641 studies screened, six studies met the inclusion criteria for the systematic review and were included for analysis. Risk of bias assessment for the included studies was graded as 'low' for three of the six included studies and 'some concern' for the remaining three studies. This was based upon allocation concealment in the randomised control trials. Clinical failures were observed in 63 of 497 events. Rehabilitation with zirconia crowns may result in less clinical failures than stainless steel crowns: risk ratio 0.48; 95% CI (0.15-1.52) p = 0.021. Gingival health was better with zirconia rather than stainless steel crowns: risk ratio 0.32; 95% CI (-0.42-0.23) p <0.001.Conclusions Primary posterior teeth restored with zirconia crowns may have 52% less risk of experiencing clinical failures than teeth with stainless steel crowns and better gingival health than stainless steel crowns, observed after 12 months. However, due to the low quality of included studies and 'very low' grade rating of the evidence provided, further clinical trials are required to provide further evidence on the clinical and radiographic effectiveness of zirconia and stainless steel crowns.

89Zr-3,2-HOPO-Mesothelin Antibody PET Imaging Reflects Tumor Uptake of Mesothelin-Targeted 227Th-Conjugate Therapy in Mice.

The mesothelin (MSLN)-targeted 227Th conjugate is a novel α-therapy developed to treat MSLN-overexpressing cancers. We radiolabeled the same antibody-chelator conjugate with 89Zr to evaluate whether PET imaging with 89Zr-MSLN matches 227Th-MSLN tumor uptake, biodistribution, and antitumor activity. Methods: Serial PET imaging with protein doses of 4, 20, or 40 µg of 89Zr-MSLN and 89Zr-control was performed up to 168 h after tracer injection in human tumor-bearing nude mice with high (HT29-MSLN) and low (BxPc3) MSLN expression. 89Zr-MSLN and 227Th-MSLN ex vivo tumor uptake and biodistribution were compared at 6 time points in HT29-MSLN and in medium-MSLN-expressing (OVCAR-3) tumor-bearing mice. 89Zr-MSLN PET imaging was performed before 227Th-MSLN treatment in HT29-MSLN and BxPc3 tumor-bearing mice. Results: 89Zr-MSLN PET imaging showed an SUVmean of 2.2 ± 0.5 in HT29-MSLN tumors. Ex vivo tumor uptake was 10.6% ± 2.4% injected dose per gram at 168 h. 89Zr-MSLN tumor uptake was higher than uptake of 89Zr-control (P = 0.0043). 89Zr-MSLN and 227Th-MSLN showed comparable tumor uptake and biodistribution in OVCAR-3 and HT29-MSLN tumor-bearing mice. Pretreatment SUVmean was 2.2 ± 0.2 in HT29-MSLN tumors, which decreased in volume on 227Th-MSLN treatment. BxPc3 tumors showed an SUVmean of 1.2 ± 0.3 and remained similar in size after 227Th-MSLN treatment. Conclusion: 89Zr-MSLN PET imaging reflected MSLN expression and matched 227Th-MSLN tumor uptake and biodistribution. Our data support the clinical exploration of 89Zr-MSLN PET imaging together with 227Th-MSLN therapy, both using the same antibody-chelator conjugate.

Zirconium cyclosilicate: An oral sorbent for potassium, four decades in the making.

HemoCleanse collaborated with Dr. John Sherman and Union Carbide in the 1980s to develop a cation exchanger with high selectivity for potassium and ammonium, for use in a wearable artificial kidney. Synthetic zeolites had unexpected solubility in this application but by 2000, UOP (a sister company of Union Carbide) had developed zirconium cyclosilicate (SZC). HemoCleanse performed early animal studies of SZC as an oral sorbent. These showed remarkable binding characteristics. HemoCleanse then obtained the license for SZC for medical applications, helped to form ZS Pharma, and collaborated in further animal studies and clinical trials. AstraZeneca purchased ZS Pharma in 2015, and SZC (Lokelma®) has now become an effective treatment for hyperkalemia in patients with kidney failure and cardiac conditions.