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关键词： Coronary artery disease   xanthine dehydrogenase   genetic variants   personalized treatment   molecular modelling   molecular dynamics simulation  

摘要： Xanthine dehydrogenase (XDH) contributes significantly to generating reactive oxygen species in coronary artery disease (CAD). XDH has been proposed as a therapeutic target, but its genetic variants could affect protein structure and drug response. We aimed to assess protein structure modification occur due to genetic variants and to screen 215 CAD drugs for their utility in personalized CAD treatment against the XDH variants. A series of computational methods were implemented to identify pathogenic variants that cause XDH structure instability localized at the conserved regions contributing to functional significance. Then, the XDH structures with the pathogenic variants were modeled using two different approaches to select the best models for docking with the CAD drugs. Finally, the stability of the docked complexes and their ability to transfer electrons were evaluated using molecular dynamics (MD) simulations and quantum mechanics/molecular mechanics (QM/MM) calculation. Among 751 variants examined;R149C and Q919R showed high pathogenicity, localized in conserved regions could alter protein structure and function. Further, docking of CAD drugs against XDH (native, R149C and Q919R) showed vericiguat with higher affinity, ranging from -7.95 kcal/mol to -10.41 kcal/mol, than the well-known XDH inhibitor (febuxostat, -5.73 kcal/mol to -8.35 kcal/mol). This indicates that vericiguat will be effective in CAD treatment, regardless of the XDH variants. Additionally, MD simulation and QM/MM confirmed vericiguat stability and electron transfer ability to form hydrogen bonds with the XDH protein. In conclusion, vericiguat will be beneficial for the personalized treatment of CAD by inhibiting XDH variants. Additional clinical studies are necessary to confirm our findings.

关键词： ceramic CAD-CAM crowns   fracture strength   hybrid composite CAD-CAM crown   preformed zirconia crown   primary molars   zirconia CAD-CAM crown  

摘要： Background: Paediatric-preformed zirconia crowns have been associated with several issues, primarily their inability to be crimped and the need for extensive tooth preparation. Additionally, the capacity to adjust the size, shape, and fit of these crowns is very limited. Aim: To evaluate and compare the fracture strength of four different types of dental crowns intended for paediatric patients. Design: The fracture resistance of four types of paediatric crowns was evaluated using the universal testing machine;freshly extracted primary molars received one of the following: preformed zirconia crowns, custom-made computer-aided design and computer-aided manufacturing (CAD-CAM) zirconia crowns, custom-made CAD-CAM ceramic crowns, and custom-made CAD-CAM hybrid composite crowns. Data were statistically compared using the Kruskal-Wallis test followed by the Bonferroni test, and the level of significance was set at 5%. Results: Results showed that there was a statistically significant difference among the four groups (p < .001). The highest value of fracture force was observed for the milled zirconia crown and the lowest for the prefabricated zirconia. Conclusion: The implementation of the CAD-CAM digital crown fabrication technique has the potential to address issues associated with preformed crowns in paediatric patients, particularly in terms of fracture resistance.

关键词： van Trees inequality   Cram & eacute   r-Rao bound   differentiability in quadratic mean   local asymptotic minimax theorem  

摘要： In honor of the 100th birth anniversary of Lucien Le Cam (November 18, 1924-April 24, 2000), we work out a version of the van Trees inequality in a H & aacute;jek-Le Cam spirit, that is, under minimal assumptions that, in particular, involve no direct pointwise regularity assumptions on densities but rather almost-everywhere differentiability in quadratic mean of the model. Surprisingly, it suffices that the latter differentiability holds along canonical directions-not along all directions. Also, we identify a (slightly stronger) version of the van Trees inequality as a very instance of a Cram & eacute;r- Rao bound, that is, the van Trees inequality is not just a Bayesian analog of the Cram & eacute;r-Rao bound. We provide, as an illustration, an elementary proof of the local asymptotic minimax theorem for quadratic loss functions, again assuming differentiability in quadratic mean only along canonical directions.

关键词： CAD/CAM   dental materials   dental internal adaptation   milling protocols   resin composite   lithium disilicate  

摘要： This study aimed to evaluate the marginal and internal adaptation of CAD/CAM crowns milled using two different milling protocols (fine or extra-fine) within a 4-axis milling machine. The crowns were fabricated from lithium disilicate ceramic (IPS *** CAD) and resin composite (Tetric CAD), assessing their fit in various regions. The crowns (N = 40, n = 10) were milled from lithium disilicate and resin composite using a CEREC Primemill unit. Four groups were formed based on the material and milling protocol: EFLD (extra-fine lithium disilicate), FLD (fine lithium disilicate), EFRC (extra-fine resin composite), and FRC (fine resin composite). The crowns were measured using the replica technique, evaluating internal and marginal adaptation in 18 measuring points per specimen. Data were statistically analyzed using ANOVA and Tukey's test. Resin composite crowns demonstrated a significantly better internal fit compared to lithium disilicate (p < 0.001). Marginal and internal measurements for resin composites were consistently smaller across regions compared to lithium disilicate. No significant differences were found between milling protocols except for the axial wall region (p = 0.001), where extra-fine milling resulted in smaller values. Resin composite crowns exhibited superior internal fit compared to lithium disilicate, regardless of milling protocol. Both the fine and extra-fine milling protocols had minimal impact on adaptation, except at the axial wall region, with both protocols promoting adequate results overall.

关键词： cats   robenacoxib   CAM   NSAIDs  

摘要： Robenacoxib is a selective non-steroidal anti-inflammatory drug indicated for pain control in felines. The objective was to evaluate the effect of robenacoxib on the minimum alveolar concentration of isoflurane in cats. There were 30 cats that used one of the 3 treatments through therapy: GM - meloxicam (0.2 mg/kg), GR - robenacoxib (2 mg/kg) or GC - 0.9% saline solution (0.1 ml/kg) kg). We waited 30 minutes, and the animals were induced to general anesthesia with isoflurane in an induction box, intubated and anesthetized with 1.5 V% isoflurane. All animals were secured to a supramaximal nociceptive stimulus (tail pinch). Positive response was defined as proposed movement of the head and/or limbs. The method for determining MAC was up and down to Dixon, and calculation of the average of crossover values according to Monteiro (2016). The mean and standard deviation of ISOMAC MAC was 2.10 +/- 0.15%, 1.95 +/- 0.14%, and 1.7 +/- 0.15% in GC, GM, and GR, respectively. Robenacoxib reduced to 19.1% and 12.8% ISOMAC MAC when compared to a control group and a group that received meloxicam, respectively.

关键词： Coronary artery disease   Computed tomography coronary angiography   Optimal medical therapy   Non-invasive functional imaging   Revascularisation  

摘要： BackgroundPatients with stable chest pain suspected of coronary artery disease (CAD) usually undergo multiple diagnostic tests to confirm or rule out obstructive CAD. Some tests may not effectively assess the presence of CAD, precluding optimal treatment. A diagnostic strategy of upfront computed tomography coronary angiography (CTCA) combined with optimal medical therapy (OMT) tailored to the extent of CAD may be superior to standard care in preventing major adverse cardiac *** designThe CLEAR-CAD trial is a prospective, open-label, multicentre, randomised, superiority trial of an upfront CTCA-guided strategy in 6444 patients presenting in an outpatient setting with suspected CAD compared with standard care, in approximately 30 participating centres in the Netherlands. The upfront CTCA-guided strategy consists of an initial CTCA which is assessed using the Coronary Artery Disease-Reporting and Data System (CAD-RADS 2.0). In patients without CAD (CAD-RADS 0) no specific cardiac medication is mandated. Patients with non-obstructive CAD (CAD-RADS 1-2) are treated with preventive OMT. Patients with obstructive CAD (CAD-RADS >= 3) are treated with preventive and anti-anginal OMT;in the presence of pharmacologically refractory symptoms patients undergo selective revascularisation after non-invasive functional imaging for myocardial ischaemia (>= 10%). Patients with significant left main or proximal left anterior descending coronary artery stenosis on CTCA undergo direct invasive coronary angiography and subsequent revascularisation. The primary endpoint is the composite of all-cause death and myocardial *** CLEAR-CAD trial is the first randomised study to investigate the efficacy of a combined upfront CTCA-guided medical and selective revascularisation strategy in an outpatient setting with suspected CAD compared with standard care.

关键词： AI   CAD eye function   colorectal polyps  

摘要： Purpose: To assess wear, fatigue, and fracture resistance of different CAD/CAM onlays milled from monolithic zirconia (ZR), hybrid ceramic (EN), and lithium disilicate (LS) when used as abutments for removable partial denture frameworks fabricated from acetal resin (AR) or cobalt-chromium (Co-Cr). Materials and Methods: Standard onlays and RPD framework were designed and milled using CAD/CAM. Onlays were cemented with resin cement to identical teeth models. The RPD's occlusal rest surface and the ceramic onlays' rest seats were both 3D scanned before and after 750,000 mechanical load cycles (50 N) and 8,000 thermal cycles (5 degrees to 55 degrees C) in a chewing simulator. The volumetric loss was measured using 3D-image processing software, and the failure of the samples was detected using a stereomicroscope. The fracture resistance was tested by loading to failure in a universal testing machine. The fatigue failure results were analyzed with Fisher exact probability test, and the wear and fracture resistance data were analyzed using twoway ANOVA and Bonferroni post-hoc test (P < .05). Results: A significant difference (P < .05) was found between the tested experimental groups in wear, fatigue, and fracture resistance. Zr/Co-Cr combinations exhibited the least wear and the highest fatigue and fracture resistance (P < .05), while the highest wear and least fatigue and fracture resistance were recorded for the EN/AR group (P < .05). Conclusions: Zr onlays demonstrated a conservative treatment option with superior mechanical behavior when used as an onlay abutment, regardless of the RPD framework material used. The AR framework is not recommended in the posterior region for removable partial dentures.

关键词： angiogenesis   bioengineering   neovascularization   regenerative medicine   tissue engineering  

摘要： Tissue engineering is a promising approach for generating or repairing living tissues. The development of innovative biomaterials for tissue engineering has the potential to address the unmet clinical needs in certain applications. However, before these biomaterials can be used in clinical settings, they must undergo preclinical testing to ensure safety and performance. The chicken chorioallantoic membrane (CAM) assay is a preferred screening tool for studying biocompatibility, angiogenesis, and inflammation induced by biomaterials owing to ethical and economic considerations. This CAM-based platform increased the throughput of biomaterial testing for tissue engineering before in vivo testing. In this paper, we discuss the advantages of the CAM model. We also provided a step-by-step guide for implementing the CAM model in a research laboratory, along with tips and tricks for successfully running CAM assays. Finally, we present examples of biomaterials screened using CAM assays. CAM assay is a powerful in vivo model for assessing the angiogenic potential of tissue-engineered scaffolds. This guide provides a framework for conducting the assay, but specific experimental conditions should be optimized based on the scaffold material and the research question.

关键词： Editorials   heart   myocardium   perfusion   positron-emission tomography