sandwich

  • 文章类型: Journal Article
    开发了一种新型的自供电且灵活的基于酶促生物燃料电池(EBFC)的aptasensor,用于灵敏和选择性地检测17β-雌二醇(E2)。用金纳米粒子(AuNP)和巯基化适体1(Apt1)修饰柔性聚乙烯醇(PVA)-单宁酸-碳纳米管/还原氧化石墨烯(PTCR)基底,以产生Apt1@AuNP/PTCR。具有过氧化物酶模拟活性的铜基金属有机骨架(Cu-MOF)用于锚定葡萄糖氧化酶(GOD)和Apt2,形成Cu-MOF@GOD/Apt2标签。当E2被Apt1识别时,锚定的E2定量识别Cu-MOF@GOD/Apt2以创建Cu-MOF@GOD/Apt2-E2-Apt1夹心结构,用于葡萄糖氧化以产生电力。增加的E2浓度增强了Cu-MOF@GOD/Apt2捕获并放大了电信号。随着E2浓度从1.0μM增加到1.0nM,电功率线性增加。该传感器已成功应用于各种食品样品和血清检测。这项工作促进了新型自供电生物传感器在食品安全分析中的应用。
    A novel self-powered and flexible enzymatic biofuel cell (EBFC)-based aptasensor was developed for the sensitive and selective detection of 17 β-estradiol (E2). A flexible polyvinyl alcohol (PVA)-tannic acid‑carbon nanotube/reduced graphene oxide (PTCR) substrate was modified with gold nanoparticles (AuNPs) and thiolated aptamer 1 (Apt1) to yield Apt1@AuNPs/PTCR. A copper-based metal-organic framework (Cu-MOF) with peroxidase mimicking activity was employed to anchor glucose oxidase (GOD) and Apt2, forming the Cu-MOF@GOD/Apt2 tag. When E2 was recognized by Apt1, the anchored E2 quantitatively recognized Cu-MOF@GOD/Apt2 to create a Cu-MOF@GOD/Apt2-E2-Apt1 sandwich structure for glucose oxidation to generate electrical power. Increased E2 concentrations enhanced Cu-MOF@GOD/Apt2 capture and amplified the electrical signal. The electrical power increased linearly as the E2 concentration increased from 1.0 pM to 1.0 nM. The sensor was successfully applied to various food samples and blood serum detection. This work promoted the application of novel self-powered biosensors for food safety analysis.
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  • 文章类型: Journal Article
    陀螺结构是在蝴蝶翅膀中发现的生物启发结构。蝴蝶翅膀的陀螺结构的几何设计提供了强度和灵活性的独特组合。这项研究调查了由3D打印的陀螺结构核心和碳纤维增强聚合物(CFRP)面向皮肤组成的夹芯板。使用灯丝熔融制造3D打印机来打印具有三种不同相对密度的陀螺芯,即10%,15%,和20%。使用聚乳酸(PLA)作为陀螺的打印材料。然后在CFRP层压板之间夹住并通过环氧树脂连接该陀螺结构。将聚氨酯泡沫(PUF)填充到陀螺芯中以填充用于另一组样品的芯上的空腔。对样品进行弯曲和压缩测试以研究三明治的机械行为。此外,采用双参数Weibull分布对结果进行统计学评价.因此,复合材料三点弯曲试验的夹层比面应力和核心剪切强度随夹层密度的增加而增加。芯密度控制夹层的弯曲特性。添加PUF改善了最大应力下的挠度和夹层断裂后的持续载荷。压缩强度,模数,在相同的三明治密度下,陀螺芯三明治吸收的能量及其特定特性高于PUF填充的陀螺芯三明治。
    The gyroid structure is a bio-inspired structure that was discovered in butterfly wings. The geometric design of the gyroid structure in butterfly wings offers a unique combination of strength and flexibility. This study investigated sandwich panels consisting of a 3D-printed gyroid structure core and carbon fiber-reinforced polymer (CFRP) facing skin. A filament fused fabrication 3D printer machine was used to print the gyroid cores with three different relative densities, namely 10%, 15%, and 20%. Polylactic acid (PLA) was used as the printing material for the gyroid. The gyroid structure was then sandwiched and joined by an epoxy resin between CFRP laminates. Polyurethane foam (PUF) was filled into the gyroid core to fill the cavity on the core for another set of samples. Flexural and compression tests were performed on the samples to investigate the mechanical behavior of the sandwiches. Moreover, the two-parameter Weibull distribution was used to evaluate the results statistically. As a result, the sandwich-specific facing stress and core shear strength from the three-point bending test of the composites increased with the increase in sandwich density. Core density controls the flexural characteristics of the sandwich. Adding PUF improves the deflection at the maximum stress and the sustained load after fracture of the sandwich. Compression strength, modulus, and energy absorbed by gyroid core sandwiches and their specific properties are higher than the PUF-filled gyroid core sandwiches at equal sandwich density.
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  • 文章类型: Journal Article
    作为阿尔茨海默病的典型生物标志物,快速、特异地检测tau蛋白有助于提高疾病的早期诊断和预后。在这项研究中,开发了一种简单的夹心电化学免疫传感器,用于快速检测tau蛋白。针对tau蛋白中间结构域(氨基酸189-195)的一级单克隆抗体(mAb1)通过3,3'-二硫代双(磺基琥珀酰亚胺丙酸酯)的自组装单层(SAM)固定在金电极表面上(DTSSP)。然后通过抗原和抗体之间的特异性吸附捕获tau蛋白,导致阻抗的变化。使用针对tau蛋白的N-末端区域的第二单克隆抗体(mAb2)用于进一步扩增mAbl与tau蛋白之间的结合反应。从2×10-6mgmL-1到2×10-3mgmL-1,发现阻抗总变化与tau浓度对数之间存在线性关系,检出限低至1×10-6mgmL-1。从人血清白蛋白没有观察到显著的干扰。此外,制作的夹心免疫传感器成功检测到人工脑脊液(aCSF)样品中的目标tau蛋白,预示着未来临床应用的良好潜力。
    As a typical biomarker of Alzheimer\'s disease, rapid and specific detection of tau protein can help improve the early diagnosis and prognosis of the disease. In this study, a simple sandwich electrochemical immunosensor was developed for rapid detection of tau protein. Primary monoclonal antibodies (mAb1) against the middle domain of tau protein (amino acids 189-195) were immobilized on the gold electrode surface through a self-assembled monolayer (SAM) of 3,3\'-dithiobis (sulfosuccinimidyl propionate) (DTSSP). Then the tau protein was captured through the specific adsorption between the antigen and the antibody, resulting in a change in the impedance. Secondary monoclonal antibodies (mAb2) against the N-terminal region of tau protein were used for further amplification of the binding reaction between mAb1 and tau protein. A linear correlation between the total change in impedance and the logarithm of tau concentration was found from 2 × 10-6 mg mL-1 to 2 × 10-3 mg mL-1, with a detection limit as low as 1 × 10-6 mg mL-1. No significant interference was observed from human serum albumin. Furthermore, the fabricated sandwich immunosensor successfully detected target tau protein in artificial cerebrospinal fluid (aCSF) samples, indicating good potential for clinical applications in the future.
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  • 文章类型: Journal Article
    这项研究的重点是通过开发用于结构应用的中空玻璃微球/纳米粘土混合芯和香蕉纤维面板的环氧基夹层复合板来改善夹层复合材料的机械性能。这项工作研究了用中空玻璃微球(HGM)/纳米粘土混合芯与香蕉纤维面片复合板制成的夹层复合板的力学性能。在夹层复合材料面板中,芯的HGM含量从1重量%到3重量%不等。而芯的纳米粘土含量在每个HGM填充系列的夹层复合板中从1重量%变化到5重量%,这些夹层复合板是用传统的树脂浇铸方法制造的。在这次调查中,机械,吸水,和浮力行为进行了深入研究,研究结果表明,具有香蕉纤维面板的混合芯配方的三明治复合材料比没有混合芯配方的三明治复合材料有更好的改善。这表明,具有环氧树脂的香蕉纤维在没有混合芯的情况下使用时具有有限量的强度,但是当HGM和粘土颗粒混合作为混合芯时,由于混合芯和基质之间优异的界面粘合性,提供更好的性能。改进的机械性能可以表明该材料可以适用于需要轻质且具有良好机械性能的夹层结构的工业中。这项研究通过使用混合芯和香蕉纤维增强机械性能,显示了三明治结构发展的新领域。
    This study focuses on improving the mechanical properties of sandwich composites by developing epoxy-based sandwich composite panels with hollow glass microspheres/nanoclay hybrid core and banana fiber facesheets for structural applications. The mechanical performance of sandwich composite panels made with hollow glass microspheres (HGM)/nanoclay hybrid core with banana fibers face-sheet composites panel is investigated in this work. The HGM content of the core was varied from 1 wt% to 3 wt% in the sandwich composites panel, while the nanoclay content of the core was varied from 1 wt% to 5 wt% in each of the HGM-filled series of the sandwich composite panel, these sandwich composite panels were fabricated using a conventional resin casting method. In this investigation, the mechanical, water absorption, and buoyancy behavior are thoroughly studied and the findings revealed better improvement at the sandwich composites with hybrid core formulation with banana fiber facesheets than the sandwich composites without hybrid core formulation. This demonstrates that banana fiber with epoxy resin has a limited amount of strength when used without a hybrid core but delivers better performance when HGM and clay particles are mixed as the hybrid core because of excellent interfacial adhesion between the hybrid core and the matrix. The improved mechanical properties could suggest that this material may be suitable for application in industries where sandwich structures that are lightweight with good mechanical properties are required. This study showed a new area of sandwich structure development by enhancing mechanical properties using hybrid core and banana fibers.
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  • 文章类型: Journal Article
    由于小分子抗体的有限可用性和获得敏感信号的挑战,开发引入特异性识别元件的高度敏感和选择性方法对于检测小分子至关重要。在这项研究中,基于分子印迹聚合物(MIP)-适体夹心结构和纳米酶的协同作用,构建了一个通用的光电-比色双模传感平台。使用MIP官能化的过氧化物酶样Fe3O4(Fe3O4@MIPs)和碱性磷酸酶模拟物Zr-MOF标记的适体(Zr-mof@Apt)作为识别元素。通过选择性积累邻苯二甲酸二丁酯(DBP),小分子靶标模型,在Fe3O4@MIPs上,引发了Zr-MOF@Apt-DBP-Fe3O4@MIPs夹心结构的形成。Fe3O4@MIPs氧化TMB形成蓝色的oxTMB。然而,在选择性积累DBP后,Fe3O4@MIPs的催化活性受到抑制,导致通过比色法可检测到的较浅的颜色。此外,Zr-mof@Apt有效地催化了L-抗坏血酸2-磷酸倍半镁盐水合物(AAPS)的水解,产生抗坏血酸(AA),可以中和光生的空穴,以减少用于PEC感测的光电流信号,并减少用于比色测试的oxTMB。双模平台显示出对于从1.0μM至10μM(PEC)和0.1nM至0.5μM(比色法)的不同浓度的DBP的强线性。检测限为0.263nM(PEC)和30.1nM(比色法)(S/N=3),分别。双信号测量模式和夹心识别策略的集成为小分子的检测提供了灵敏、准确的平台。
    Developing highly sensitive and selective methods that incorporate specific recognition elements is crucial for detecting small molecules because of the limited availability of small molecule antibodies and the challenges in obtaining sensitive signals. In this study, a generalizable photoelectrochemical-colorimetric dual-mode sensing platform was constructed based on the synergistic effects of a molecularly imprinted polymer (MIP)-aptamer sandwich structure and nanoenzymes. The MIP functionalized peroxidase-like Fe3O4 (Fe3O4@MIPs) and alkaline phosphatase mimic Zr-MOF labeled aptamer (Zr-mof@Apt) were used as the recognition elements. By selectively accumulating dibutyl phthalate (DBP), a small molecule target model, on Fe3O4@MIPs, the formation of Zr-MOF@Apt-DBP- Fe3O4@MIPs sandwich structure was triggered. Fe3O4@MIPs oxidized TMB to form blue-colored oxTMB. However, upon selective accumulation of DBP, the catalytic activity of Fe3O4@MIPs was inhibited, resulting in a lighter color that was detectable by the colorimetric method. Additionally, Zr-mof@Apt effectively catalyzed the hydrolysis of L-Ascorbic acid 2-phosphate sesquimagnesium salt hydrate (AAPS), generating ascorbic acid (AA) that could neutralize the photogenerated holes to decrease the photocurrent signals for PEC sensing and reduce oxTMB for colorimetric testing. The dual-mode platform showed strong linearity for different concentrations of DBP from 1.0 pM to 10 μM (PEC) and 0.1 nM to 0.5 μM (colorimetry). The detection limits were 0.263 nM (PEC) and 30.1 nM (colorimetry) (S/N = 3), respectively. The integration of dual-signal measurement mode and sandwich recognition strategy provided a sensitive and accurate platform for the detection of small molecules.
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  • 文章类型: Journal Article
    对于需要腹腔镜胃癌根治术的患者,淋巴结清扫术(LND)和外科手术的优化尤为重要。本研究介绍了顺时针模块化D2LND中的“象限三明治”方法,并评估了该方法的优点和安全性。
    回顾性分析2019年1月至2022年1月郑州大学附属肿瘤医院收治的108例腹腔镜全胃切除术患者的临床资料。基于不同的LND流程,55例患者被分配到观察组,使用“象限三明治法”进行顺时针模块化LND,53例患者被分配到对照组,经历了传统的LND。该方法在操作时间方面的有效性和安全性,失血,淋巴结产量,观察两组患者术后恢复情况及术后并发症发生情况。
    两组的基线数据之间没有统计学差异。关于手术,观察组手术时间为227.0±48.5分钟,术中出血100.0mL[四分位数间距(IQR),30.0-200.0mL],对照组手术时间为247±41.5分钟,术中出血180.0mL(IQR,130.0-245.0mL)。两组手术时间、术中出血量比较差异均有统计学意义(P=0.001,P=0.020)。关于LND,两组在每个分区的淋巴结总数方面没有统计学上的显著差异,和阳性淋巴结的数量。关于术后结果,两组术后病理分期差异无统计学意义,术后第一次口服喂养,术后住院时间,和术后并发症。
    使用“象限夹心法”顺时针模块化D2LND在腹腔镜全胃切除术中潜在安全可行。它不仅确保了LND的彻底性,而且还确保了高效和快速的手术过程,缩短手术时间,减少术中出血量。
    UNASSIGNED: For patients who need laparoscopic radical gastrectomy, lymph node dissection (LND) and optimization of surgical procedures are particularly important. This study introduces the \"quadrant-sandwich\" method in clockwise modular D2 LND and evaluates the advantages and safety of this method.
    UNASSIGNED: The clinical data of 108 laparoscopic total gastrectomy patients admitted to the Affiliated Cancer Hospital of Zhengzhou University from January 2019 to January 2022 were retrospectively analyzed. Based on the different LND processes, 55 patients were allocated to the observation group, which underwent clockwise modular LND using the \"quadrant-sandwich method\", and 53 patients were allocated to the control group, which underwent traditional LND. The effectiveness and safety of the approach in terms of operation time, blood loss, lymph node yield, postoperative recovery and postoperative complications were observed in the two groups.
    UNASSIGNED: There was no statistical difference between the baseline data of the two groups. In relation to the surgery, the observation group had an operation time of 227.0±48.5 minutes, and intraoperative bleeding of 100.0 mL [inter-quartile range (IQR), 30.0-200.0 mL], while the control group had an operation time of 247±41.5 minutes, and intraoperative bleeding of 180.0 mL (IQR, 130.0-245.0 mL). There were statistically significant differences between the two groups in terms of the operation time and intraoperative bleeding (P=0.001, P=0.020). In relation to the LND, there were no statistically significant differences between the two groups in terms of the total number of lymph nodes in each division, and the number of positive lymph nodes. In relation to the post-operative results, there were no statistically significant differences between the two groups in terms of the post-operative pathological stage, first postoperative oral feeding, post-operative hospitalization time, and post-operative complications.
    UNASSIGNED: Clockwise modular D2 LND using the \"quadrant-sandwich method\" is potentially safe and feasible in laparoscopic total gastrectomy. It not only ensures the thoroughness of the LND, but also ensures and efficient and fast surgical process, shortens the operation time, and reduces the amount of intraoperative bleeding.
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  • 文章类型: Journal Article
    当(4n+2)π电子位于单个平面环时,它通常具有芳香性。根据Hückel的规则,拥有十个π电子的系统应该是芳香的。在这里,我们报告了一系列D5hLi6E5Li6夹层结构,代表具有十个π电子E510环(E=Si-Pb)的第一个全局最小值。然而,这些π电子定位为五个π孤对,而不是离域轨道。实现的高对称性结构是σ芳香性的直接结果,特别有利于从Si到Pb的元素,导致明显的各向异性环电流,有助于增强这些系统的稳定性。
    When (4n +2) π-electrons are located in single planar ring, it conventionally qualifies as aromatic. According Hückel\'s rule, systems possessing ten π-electrons should be aromatic. Herein we report a series of D5h  Li6 E5 Li6 sandwich structures, representing the first global minima featuring ten π-electrons E5 10- ring (E=Si-Pb). However, these π-electrons localize as five π-lone-pairs rather than delocalized orbitals. The high symmetry structure achieved is a direct consequence of σ-aromaticity, particularly favored in elements from Si to Pb, resulting in a pronounced diatropic ring current flow that contributes to the enhanced stability of these systems.
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  • 文章类型: Meta-Analysis
    目的:造口旁疝是造口形成后最常见的并发症,术后2年发生率接近50%。在过去的十年里,已经提出了不同的微创手术方法来治疗造口旁疝。然而,一种技术优于其他技术仍不清楚。我们的目标是更新和系统分析有关四种最流行的微创技术的术后结果的研究现状。
    方法:对三个数据库进行系统的文献检索(Medline,Scopus,GoogleScholar)适用于2015年1月至2022年11月发布的文章。包括来自先前关于该主题的荟萃分析的15项研究。
    结果:共纳入1289名患者的33项研究被认为符合纳入最终分析的条件。锁孔技术与术后并发症和复发的发生率最高(31.3%和24.1%,分别),其次是Sugarbaker技术(27.6%和9%,分别)。在使用3D网格技术进行手术的患者中,手术时间是最低的,而接受锁孔技术的患者住院时间最短(6天)。
    结论:每种技术都显示出独特的有效性特征,被发生术后并发症的倾向所抵消。虽然迄今为止还没有关于最佳技术的确凿证据,较新的微创技术显示出有希望的结果,尽管基于有限的数据。造口旁疝修补术的未来似乎依赖于高度个性化的方法,针对疝气和患者的独特特征量身定制。
    OBJECTIVE: Parastomal hernia is the most common complication after stoma formation with an incidence that approaches 50% at 2 years postoperatively. In the last decade, different approaches of minimally invasive procedures have been proposed for the treatment of parastomal hernia. Nevertheless, the superiority of one technique over the others remains still unclear. Our objective was to update and systematically analyze current state of research concerning the postoperative outcomes of the four most prevalent minimally invasive techniques.
    METHODS: A systematic literature search of three databases (Medline, Scopus, Google Scholar) was undertaken for articles published from January 2015 to November 2022. Fifteen studies from a previous meta-analysis on the topic were included.
    RESULTS: Thirty-three studies incorporating 1289 total patients were deemed eligible for inclusion in the final analysis. The keyhole technique was associated with the highest incidence of postoperative complications and recurrences (31.3% and 24.1%, respectively), followed by the Sugarbaker technique (27.6% and 9%, respectively). Operative time was among the lowest in patients operated with the 3D mesh technique, while patients undergoing the keyhole technique experienced the shortest cumulative length of hospital stay (6 days).
    CONCLUSIONS: Each technique demonstrates a unique profile of effectiveness offset by the propensity towards developing postoperative complications. While no conclusive evidence on the optimal technique exist to date, newer minimally invasive techniques show promising results, albeit based on limited data. The future of parastomal hernia repair seems to rely on a highly individualized approach, tailored to the distinctive characteristics of both the hernia and the patient.
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  • 文章类型: Journal Article
    这项研究的重点是探索菌丝体作为拉挤玻璃纤维增强塑料(GFRP)夹层型材中木材或固体泡沫的可持续替代品的潜力。该研究通过机械测试和生命周期评估(LCA)评估了该复合材料的性能和环境可持续性潜力。用菌丝体拉挤三明治型材的分析和比较,聚氨酯(PUR)泡沫和刨花板表明,菌丝体在其性能和环境影响方面具有竞争力。LCA表明,88%的温室气体排放归因于菌丝生产,热压(实验室规模)是罪魁祸首。当使用油加热的实验室压力机生产具有密度为350和550kg/m3的菌丝体核心的拉挤型材时,全球变暖潜能值(GWP)为5.74和9.10kgCO2-eq。计算了每个功能单元,分别。使用电热机时,GWP降至1.50和1.78kgCO2-eq。与PUR泡沫相比,GWP降低23%是可能的。为了利用这种潜力,必须进一步提高材料性能和性能的可重复性。此外,通过拉挤成型过程中原位菌丝体失活来调整制造工艺可以进一步降低能耗。
    This research focuses on exploring the potential of mycelium as a sustainable alternative to wood or solid foam in pultruded glass fiber-reinforced plastic (GFRP) sandwich profiles. The study evaluates the performance and the environmental sustainability potential of this composite by mechanical tests and life cycle assessment (LCA). Analysis and comparison of pultruded sandwich profiles with mycelium, polyurethane (PUR) foam and chipboard demonstrate that mycelium is competitive in terms of its performance and environmental impact. The LCA indicates that 88% of greenhouse gas emissions are attributed to mycelium production, with the heat pressing (laboratory scale) being the main culprit. When pultruded profiles with mycelium cores of densities 350 and 550 kg/m³ are produced using an oil-heated lab press, a global warming potential (GWP) of 5.74 and 9.10 kg CO2-eq. per functional unit was calculated, respectively. When using an electrically heated press, the GWP decreases to 1.50 and 1.78 kg CO2-eq. Compared to PUR foam, a reduction of 23% in GWP is possible. In order to leverage this potential, the material performance and the reproducibility of the properties must be further increased. Additionally, an adjustment of the manufacturing process with in situ mycelium deactivation during pultrusion could further reduce the energy consumption.
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  • 文章类型: Journal Article
    目的:比较树脂复合材料后II类修复体的临床性能,该修复体用蚀刻和冲洗粘合剂或使用玻璃离聚物水门汀的开放式夹层技术放置。
    方法:从患者档案中收集了一位牙医在1990年至2016年之间放置的II类修复体的数据。包括龋齿风险,牙齿相关变量,申请的材料和最后一次检查访问和修复安置的日期。在2001年之前放置了开放式夹层修复体,而在2001年之后,在放置II类复合修复体时使用了使用蚀刻和冲洗3步粘合剂的全蚀刻技术。为了进行统计分析,进行Kaplan-Meier统计和多水平Cox回归(p<0.05)。计算年故障率(AFR)。
    结果:在91例患者中放置了675个II类修复体,491个全蚀修复体(观察时间2-18y),和184个开放式夹层修复体(观察时间19-29y),显示15年时总蚀刻的AFR为2.9%,开放式夹层修复体为9.7%。失败后的继发性龋齿在两组中均匀分布,开放式夹层组中27%的失败是由于玻璃离聚物水泥的近端变质所致。Cox回归显示,与全蚀刻II类复合修复体相比,开放式夹层技术的失败风险明显更高(HR=2.9;p<0.001)。
    结论:对于II类修复体,不推荐使用开放夹心技术应用玻璃离聚物水泥,因为它更复杂,临床表现较差。
    To compare clinical performance of resin composite posterior Class-II restorations placed with etch-and-rinse adhesive or open sandwich technique using glass-ionomer cement.
    Data on Class II restorations placed by one dentist between 1990 and 2016 were collected from patient files, including caries risk, tooth related variables, applied materials and dates of last check-up visit and restoration placement. Open sandwich restorations were placed before 2001, while after 2001, a total-etch technique using etch-and-rinse 3-step adhesive was used when placing a Class II composite restoration. For statistical analysis, Kaplan-Meier statistics and a multilevel Cox-Regression was conducted (p < 0.05). Annual Failures Rates (AFR) were calculated.
    675 Class II restorations were placed in 91 patients, 491 total-etch restorations (observation time 2-18 y), and 184 open sandwich restorations (observation time 19-29 y) showing AFRs at 15 years as 2.9 % for total-etch and 9.7 % for open sandwich restorations. Secondary caries as failure was equally distributed among the 2 groups and 27 % of the failures in the open sandwich group were due to proximal deterioration of glass-ionomer cement. The Cox-regression showed a significant higher risk for failure for the open sandwich technique compared to total-etch class-II composite restorations (HR = 2.9; p < 0.001).
    Application of glass-ionomer cement using the open sandwich technique cannot be recommended for class-II restorations as being more complex and showing poorer clinical performance.
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