Aspirin Monotherapy vs No Antiplatelet Therapy in Stable Patients With Coronary Stents Undergoing Low-to-Intermediate Risk Noncardiac Surgery.

BACKGROUND: Current guidelines recommend the perioperative continuation of aspirin in patients with coronary drug-eluting stents (DES) undergoing noncardiac surgery. However, supporting evidence is limited. OBJECTIVES: This study aimed to compare continuing aspirin monotherapy vs temporarily holding all antiplatelet therapy before noncardiac surgery in patients with previous DES implantation. METHODS: We randomly assigned patients who had received a DES >1 year previously and were undergoing elective noncardiac surgery either to continue aspirin or to discontinue all antiplatelet agents 5 days before noncardiac surgery. Antiplatelet therapy was recommended to be resumed no later than 48 hours after surgery, unless contraindicated. The primary outcome was a composite of death from any cause, myocardial infarction, stent thrombosis, or stroke between 5 days before and 30 days after noncardiac surgery. RESULTS: A total of 1,010 patients underwent randomization. Among 926 patients in the modified intention-to-treat population (462 patients in aspirin monotherapy group and 464 patients in the no-antiplatelet therapy group), the primary composite outcome occurred in 3 patients (0.6%) in the aspirin monotherapy group and 4 patients (0.9%) in the no antiplatelet group (difference, -0.2 percentage points; 95% CI: -1.3 to 0.9; P > 0.99). There was no stent thrombosis in either group. The incidence of major bleeding did not differ significantly between groups (6.5% vs 5.2%; P = 0.39), whereas minor bleeding was significantly more frequent in the aspirin group (14.9% vs 10.1%; P = 0.027). CONCLUSIONS: Among patients undergoing low-to-intermediate risk noncardiac surgery >1 year after stent implantation primarily with a DES, in the setting of lower-than-expected event rates, we failed to identify a significant difference between perioperative aspirin monotherapy and no antiplatelet therapy with respect to ischemic outcomes or major bleeding. (Perioperative Antiplatelet Therapy in Patients With Drug-eluting Stent Undergoing Noncardiac Surgery [ASSURE-DES]; NCT02797548).

Vitamin C-induced CO2 capture enables high-rate ethylene production in CO2 electroreduction.

High-rate production of multicarbon chemicals via the electrochemical CO2 reduction can be achieved by efficient CO2 mass transport. A key challenge for C-C coupling in high-current-density CO2 reduction is how to promote *CO formation and dimerization. Here, we report molecularly enhanced CO2-to-*CO conversion and *CO dimerization for high-rate ethylene production. Nanoconfinement of ascorbic acid by graphene quantum dots enables immobilization and redox reversibility of ascorbic acid in heterogeneous electrocatalysts. Cu nanowire with ascorbic acid nanoconfined by graphene quantum dots (cAA-CuNW) demonstrates high-rate ethylene production with a Faradaic efficiency of 60.7% and a partial current density of 539 mA/cm2, a 2.9-fold improvement over that of pristine CuNW. Furthermore, under low CO2 ratio of 33%, cAA-CuNW still exhibits efficient ethylene production with a Faradaic efficiency of 41.8%. We find that cAA-CuNW increases *CO coverage and optimizes the *CO binding mode ensemble between atop and bridge for efficient C-C coupling. A mechanistic study reveals that ascorbic acid can facilitate *CO formation and dimerization by favorable electron and proton transfer with strong hydrogen bonding.

Fiber optic sensor based on ZnO nanowires decorated by Au nanoparticles for improved plasmonic biosensor.

Fiber-optic-based localized surface plasmon resonance (FO-LSPR) sensors with three-dimensional (3D) nanostructures have been developed. These sensors were fabricated using zinc oxide (ZnO) nanowires and gold nanoparticles (AuNPs) for highly sensitive plasmonic biosensing. The main achievements in the development of the biosensors include: (1) an extended sensing area, (2) light trapping effect by nanowires, and (3) a simple optical system based on an optical fiber. The 3D nanostructure was fabricated by growing the ZnO nanowires on the cross-section of optical fibers using hydrothermal synthesis and via immobilization of AuNPs on the nanowires. The proposed sensor outputted a linear response according to refractive index changes. The 3D FO-LSPR sensor exhibited an enhanced localized surface plasmon resonance response of 171% for bulk refractive index changes when compared to the two-dimensional (2D) FO-LSPR sensors where the AuNPs are fixed on optical fiber as a monolayer. In addition, the prostate-specific antigen known as a useful biomarker to diagnose prostate cancer was measured with various concentrations in 2D and 3D FO-LSPR sensors, and the limits of detection (LODs) were 2.06 and 0.51 pg/ml, respectively. When compared to the 2D nanostructure, the LOD of the sensor with 3D nanostructure was increased by 404%.

Fabrication of Localized Surface Plasmon Resonance Sensor Based on Optical Fiber and Micro Fluidic Channel.

This paper proposes Fiber-Optic Localized Surface Plasmon Resonance (FO LSPR) sensor combined with a micro fluidic channel, which enables continuous supply of fluid for bio-reaction. The proposed method prevents degradation of the sensing performance due to changes in measurement conditions. The feasibility of the FO LSPR sensor with a micro fluidic channel was demonstrated by computational fluid dynamics (CFD) simulation. Also, the proposed method was assessed by measuring the output intensity of the FO LSPR sensor at various refractive index solutions. Finally, a prostate-specific antigen (PSA) immunoassay was performed to evaluate the possibility of the fabricated sensor system as a biosensor.

Transplantation of Immortalized CD34+ and CD34- Adipose-Derived Stem Cells Improve Cardiac Function and Mitigate Systemic Pro-Inflammatory Responses.

Adipose-derived stem cells (ADSCs) have the potential to differentiate into various cell lineages and they are easily obtainable from patients, which makes them a promising candidate for cell therapy. However, a drawback is their limited life span during in vitro culture. Therefore, hTERT-immortalized CD34+ and CD34- mouse ADSC lines (mADSCshTERT) tagged with GFP were established. We evaluated the proliferation capacity, multi-differentiation potential, and secretory profiles of CD34+ and CD34- mADSCshTERT in vitro, as well as their effects on cardiac function and systemic inflammation following transplantation into a rat model of acute myocardial infarction (AMI) to assess whether these cells could be used as a novel cell source for regeneration therapy in the cardiovascular field. CD34+ and CD34- mADSCshTERT demonstrated phenotypic characteristics and multi-differentiation potentials similar to those of primary mADSCs. CD34+ mADSCshTERT exhibited a higher proliferation ability compared to CD34- mADSCshTERT, whereas CD34- mADSCshTERT showed a higher osteogenic differentiation potential compared to CD34+ mADSCshTERT. Primary mADSCs, CD34+, and CD34- mADSCshTERT primarily secreted EGF, TGF-ß1, IGF-1, IGF-2, MCP-1, and HGFR. CD34+ mADSCshTERT had higher secretion of VEGF and SDF-1 compared to CD34- mADSCshTERT. IL-6 secretion was severely reduced in both CD34+ and CD34- mADSCshTERT compared to primary mADSCs. Transplantation of CD34+ and CD34- mADSCshTERT significantly improved the left ventricular ejection fraction and reduced infarct size compared to AMI-induced rats after 28 days. At 28 days after transplantation, engraftment of CD34+ and CD34- mADSCshTERT was confirmed by positive Y chromosome staining, and differentiation of CD34+ and CD34- mADSCshTERT into endothelial cells was found in the infarcted myocardium. Significant decreases were observed in circulating IL-6 levels in CD34+ and CD34- mADSCshTERT groups compared to the AMI-induced control group. Transplantation of CD34- mADSCshTERT significantly reduced circulating MCP-1 levels compared to the AMI control and CD34+ mADSCshTERT groups. GFP-tagged CD34+ and CD34- mADSCshTERT are valuable resources for cell differentiation studies in vitro as well as for regeneration therapy in vivo.

Cyclosporin A induces cardiac differentiation but inhibits hemato-endothelial differentiation of P19 cells.

Little is known about the mechanisms underlying the effects of Cyclosporin A (CsA) on the fate of stem cells, including cardiomyogenic differentiation. Therefore, we investigated the effects and the molecular mechanisms behind the actions of CsA on cell lineage determination of P19 cells. CsA induced cardiomyocyte-specific differentiation of P19 cells, with the highest efficiency at a concentration of 0.32 µM during embryoid body (EB) formation via activation of the Wnt signaling pathway molecules, Wnt3a, Wnt5a, and Wnt8a, and the cardiac mesoderm markers, Mixl1, Mesp1, and Mesp2. Interestingly, cotreatment of P19 cells with CsA plus dimethyl sulfoxide (DMSO) during EB formation significantly increases cardiac differentiation. In contrast, mRNA expression levels of hematopoietic and endothelial lineage markers, including Flk1 and Er71, were severely reduced in CsA-treated P19 cells. Furthermore, expression of Flk1 protein and the percentage of Flk1+ cells were severely reduced in 0.32 µM CsA-treated P19 cells compared to control cells. CsA significantly modulated mRNA expression levels of the cell cycle molecules, p53 and Cyclins D1, D2, and E2 in P19 cells during EB formation. Moreover, CsA significantly increased cell death and reduced cell number in P19 cells during EB formation. These results demonstrate that CsA induces cardiac differentiation but inhibits hemato-endothelial differentiation via activation of the Wnt signaling pathway, followed by modulation of cell lineage-determining genes in P19 cells during EB formation.

Mixl1 and Flk1 Are Key Players of Wnt/TGF-ß Signaling During DMSO-Induced Mesodermal Specification in P19 cells.

Dimethyl sulfoxide (DMSO) is widely used to induce multilineage differentiation of embryonic and adult progenitor cells. To date, little is known about the mechanisms underlying DMSO-induced mesodermal specification. In this study, we investigated the signaling pathways and lineage-determining genes involved in DMSO-induced mesodermal specification in P19 cells. Wnt/ß-catenin and TGF-ß superfamily signaling pathways such as BMP, TGF-ß and GDF1 signaling were significantly activated during DMSO-induced mesodermal specification. In contrast, Nodal/Cripto signaling pathway molecules, required for endoderm specification, were severely downregulated. DMSO significantly upregulated the expression of cardiac mesoderm markers but inhibited the expression of endodermal and hematopoietic lineage markers. Among the DMSO-activated cell lineage markers, the expression of Mixl1 and Flk1 was dramatically upregulated at both the transcript and protein levels, and the populations of Mixl1+, Flk1+ and Mixl1+/Flk1+ cells also increased significantly. DMSO modulated cell cycle molecules and induced cell apoptosis, resulting in significant cell death during EB formation of P19 cells. An inhibitor of Flk1, SU5416 significantly blocked expressions of TGF-ß superfamily members, mesodermal cell lineage markers and cell cycle molecules but it did not affect Wnt molecules. These results demonstrate that Mixl1 and Flk1 play roles as key downstream or interacting effectors of Wnt/TGF-ß signaling pathway during DMSO-induced mesodermal specification in P19 cells.

Real-time label-free immunoassay of interferon-gamma and prostate-specific antigen using a Fiber-Optic Localized Surface Plasmon Resonance sensor.

A Fiber-Optic Localized Surface Plasmon Resonance (FO LSPR) sensor was fabricated using spherical gold nanoparticles (Au NPs) on a flattened end-face of the optical fiber. The Au NPs were easily synthesized by the Turkevich method and were immobilized on the end-face of the optical fiber by using a self-assembled monolayer (SAM). In order to examine the possibility of its application as a biosensor for label-free immunoassays, the fabricated FO LSPR sensor was used for the detection of the antibody-antigen reaction of interferon-gamma (IFN-γ) and the limit of detection (LOD) was approximately 2pg/ml. Herein, The antibodies and bovine serum albumins (BSAs) were immobilized on the Au NPs by physisorption. Also, the FO LSPR sensor was used for the detection of a prostate-specific antigen (PSA) and the LOD was 1pg/ml below. The fabricated FO LSPR sensor can be used for real-time label-free immunoassay having fast detection time, high resolution and sensitivity. In addition, the proposed sensor platform has the advantages of low cost, simple optical setup, remote sensing, simple fabrication, real-time detection, low sample volume, and potential application to in-vivo detection systems.

Peripheral arterial disease is associated with coronary artery spasm as assessed by an intracoronary acetylcholine provocation test.

1. Both peripheral arterial disease (PAD) and coronary artery spasm (CAS) are associated with endothelial dysfunction. Thus, a higher incidence of CAS may be expected in patients with PAD. In the present study, we evaluated the incidence and characteristics of CAS in patients with PAD. 2. A total of 78 patients with PAD and 241 age- and gender-matched patients without PAD who had chest pain with normal coronary appearance on coronary angiograms underwent intracoronary acetylcholine (ACh) provocation test. Acetylcholine was injected into the left coronary artery in incremental doses of 20, 50 and 100 microg/min. Significant CAS was defined as a transient > 70% luminal narrowing with concurrent chest pain and/or ST segment changes. 3. Patients with PAD had a significantly higher incidence of ACh-induced significant CAS than those without PAD (60.3 vs 34.0%, respectively P < 0.001), as well as chest pain and ST segment changes during the ACh provocation test. Patients with PAD were more sensitive to lower doses of ACh and had a higher incidence of multivessel spasm than those without PAD. Multivariable logistic analysis showed that age, current smoking, PAD and myocardial bridge were independent predictors of ACh-induced significant CAS. Moreover, of these factors, PAD was the strongest independent predictor (odds ratio 4.25; confidence interval 1.33-13.54; P = 0.014). 4. In patients with chest pain, the presence of arterial disease at another site should still push the clinician towards treating the chest pain as angina, even if the coronary anatomy is normal on a coronary angiogram.