Impact of proton pump inhibitor use on clinical outcomes in East Asian patients receiving clopidogrel following drug-eluting stent implantation.

BACKGROUND: Concomitant use of clopidogrel and proton pump inhibitor (PPI) is common, but PPI may reduce the antiplatelet effects of clopidogrel in patients undergoing percutaneous coronary intervention (PCI). We evaluated the impact of PPI use on clinical outcomes in post-PCI patients, by incorporating P2Y12 reaction unit (PRU) and CYP2C19 genotyping results. METHODS: From a multicenter registry of patients who underwent PCI with drug-eluting stent implantation and received clopidogrel-based dual antiplatelet therapy (DAPT), patients who were prescribed a PPI at the time of PCI (PPI users) were compared to those who were not (non-users). The primary outcome included all-cause death, myocardial infarction, stent thrombosis, or cerebrovascular accident at 12 months. Major bleeding (Bleeding Academic Research Consortium [BARC] types 3-5) and gastrointestinal (GI) bleeding (BARC types 3-5) were important secondary outcomes. The adjusted outcomes were compared using a 1:1 propensity-score (PS) matching and competing risk analysis. RESULTS: Of 13,160 patients, 2,235 (17.0%) were prescribed PPI, with an average age of 65.4 years. PPI users had higher on-treatment PRU levels than non-users. After PS matching, the primary outcome occurred in 51 patients who were PPI users (cumulative incidence, 4.7%) and 41 patients who were non-users (cumulative incidence, 3.7%; log-rank p = 0.27). In carriers of both CYP2C19 loss-of-function alleles, PPI use was linked to an increased risk of the primary outcome (hazard ratio, 3.22; 95% confidence interval, 1.18-8.78). The incidence of major bleeding and GI bleeding (BARC types 3-5) was comparable between PPI users and non-users in the PS-matched cohort. CONCLUSIONS: In post-PCI patients receiving clopidogrel-based DAPT, PPI use was not linked to an increased risk of adverse cardiac and cerebrovascular events, but there was a small but significant increase in on-treatment PRU. Future research using a more individualized approach would further elucidate these interactions and guide evidence-based clinical practices.

Fully automated quantitative coronary angiography versus optical coherence tomography guidance for coronary stent implantation (FLASH): Study protocol for a randomized controlled noninferiority trial.

BACKGROUND: Artificial intelligence-based quantitative coronary angiography (AI-QCA) has been developed to provide a more objective and reproducible data about the severity of coronary artery stenosis and the dimensions of the vessel for intervention in real-time, overcoming the limitations of significant inter- and intraobserver variability, and time-consuming nature of on-site QCA, without requiring extra time and effort. Compared with the subjective nature of visually estimated conventional CAG guidance, AI-QCA guidance provides a more practical and standardized angiography-based approach. Although the advantage of intravascular imaging-guided PCI is increasingly recognized, their broader adoption is limited by clinical and economic barriers in many catheterization laboratories. METHODS: The FLASH (fully automated quantitative coronary angiography versus optical coherence tomography guidance for coronary stent implantation) trial is a randomized, investigator-initiated, multicenter, open-label, noninferiority trial comparing the AI-QCA-assisted PCI strategy with optical coherence tomography-guided PCI strategy in patients with significant coronary artery disease. All operators will utilize a novel, standardized AI-QCA software and PCI protocol in the AI-QCA-assisted group. A total of 400 patients will be randomized to either group at a 1:1 ratio. The primary endpoint is the minimal stent area (mm2), determined by the final OCT run after completion of PCI. Clinical follow-up and cost-effectiveness evaluations are planned at 1 month and 6 months for all patients enrolled in the study. RESULTS: Enrollment of a total of 400 patients from the 13 participating centers in South Korea will be completed in February 2024. Follow-up of the last enrolled patients will be completed in August 2024, and primary results will be available by late 2024. CONCLUSION: The FLASH is the first clinical trial to evaluate the feasibility of AI-QCA-assisted PCI, and will provide the clinical evidence on AI-QCA assistance in the field of coronary intervention. CLINICAL TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov. Unique identifier: NCT05388357.

Effect of rosuvastatin 20 mg versus rosuvastatin 5 mg plus ezetimibe on statin side-effects in elderly patients with atherosclerotic cardiovascular disease: Rationale and design of a randomized, controlled SaveSAMS trial.

BACKGROUND: Current guidelines recommend that patients with established atherosclerotic cardiovascular disease (ASCVD) use high-intensity statin therapy to lower low-density lipoprotein (LDL)-cholesterol levels by at least 50%, irrespective of age. However, in real-world practice, there is reluctance to maintain statin use in response to side-effects, particularly statin-associated muscle symptoms (SAMS). Moreover, no randomized trial has been conducted on the safety of statin therapy in elderly patients. TRIAL DESIGN: This investigator-initiated, multicenter, randomized clinical trial aimed to investigate the incidence of SAMS and its effect on LDL-cholesterol levels in elderly patients with established ASCVD. Eligible patients were aged 70 years or older with established ASCVD. Consecutive patients who met the inclusion criteria were randomized in a 1:1 fashion to receive either intensive statin monotherapy (rosuvastatin 20 mg) or combination therapy (rosuvastatin/ezetimibe, 5/10 mg). The primary endpoint of the study is SAMS at 6 months with regard to treatment strategy. Positive SAMS results are defined as patients with a proposed statin myalgia index score of 7 or higher. The key secondary end-points are target LDL-cholesterol achievement (LDL < 70 mg/dL), incidence of myopathy, rhabdomyolysis, frequency of drug discontinuation, and creatinine kinase, aspartate transaminase, alanine transaminase, total cholesterol, LDL-cholesterol, high-density lipoprotein-cholesterol, triglyceride, and highly sensitive C-reactive protein levels at 6 months. CONCLUSIONS: The SaveSAMS study is a multicenter, randomized trial that will compare the incidence of SAMS in patients with established ASCVD who are 70 years or older on intensive statin monotherapy to that combination therapy.

Cardioprotective effects of genetically engineered cardiac stem cells by spheroid formation on ischemic cardiomyocytes.

BACKGROUND: Sca-1+ cardiac stem cells and their limited proliferative potential were major limiting factors for use in various studies. METHODS: Therefore, the effects of sphere genetically engineered cardiac stem cells (S-GECS) inserted with telomerase reverse transcriptase (TERT) were investigated to examine cardiomyocyte survival under hypoxic conditions. GECS was obtained from hTERT-immortalized Sca-1+ cardiac stem cell (CSC) lines, and S-GECS were generated using poly-HEMA. RESULTS: The optimal conditions for S-GECS was determined to be 1052 GECS cells/mm2 and a 48 h culture period to produce spheroids. Compared to adherent-GECS (A-GECS) and S-GECS showed significantly higher mRNA expression of SDF-1α and CXCR4. S-GECS conditioned medium (CM) significantly reduced the proportion of early and late apoptotic cardiomyoblasts during CoCl2-induced hypoxic injury; however, gene silencing via CXCR4 siRNA deteriorated the protective effects of S-GECS against hypoxic injury. As downstream pathways of SDF-1α/CXCR4, the Erk and Akt signaling pathways were stimulated in the presence of S-GECS CM. S-GECS transplantation into a rat acute myocardial infarction model improved cardiac function and reduced the fibrotic area. These cardioprotective effects were confirmed to be related with the SDF-1α/CXCR4 pathway. CONCLUSIONS: Our findings suggest that paracrine factors secreted from transplanted cells may protect host cardiomyoblasts in the infarcted myocardium, contributing to beneficial left ventricle (LV) remodeling after acute myocardial infarction (AMI).

Design optimization of a 6.4†mm-diameter electromagnetic 2D scanning micromirror.

We present the design optimization, fabrication, and analysis of an electromagnetic biaxial scanning micromirror with 6.4 mm-diameter. The scanner is composed of a micromirror supported by two concentric gimbal structures with unique single turn coil. A cylindrical permanent magnet assembly is placed under the micromirror to provide a radial magnetic field for actuation. Lumped element model parameters and magnetic circuit have been optimized to maximize the driving torque. Fabricated micromirror has been actuated at 300 Hz and 1,010 Hz and maximum optical scan angle of 25.6° and 35.3° have been obtained for the vertical and horizontal scans, respectively. Crosstalk during the actuation has been analyzed, and improved models have been proposed to reduce the crosstalk.

A comparison between drug-eluting stent implantation and drug-coated balloon angioplasty in patients with left main bifurcation in-stent restenotic lesions.

BACKGROUND: The current guidelines recommend both repeat stenting and drug-coated balloons (DCB) for in-stent restenosis (ISR) lesions, if technically feasible. However, real-world clinical data on the interventional strategies in patients with left main bifurcation (LMB)-ISR have not been elucidated. METHODS: Seventy-five patients with LMB-ISR, who underwent percutaneous coronary intervention (PCI) between January 2009 and July 2015, were retrospectively reviewed for the present study (repeat drug eluting stent [DES] implantation [n = 51], DCB angioplasty [n = 24]). RESULTS: Analysis of the baseline characteristics showed that the patients in the DCB group had a lower incidence of non-ST segment elevation myocardial infarction/ST segment elevation myocardial infarction at the index PCI (8.3% vs. 25.5%; p = 0.12), higher low-density lipoprotein-cholesterol level (92.9 mg/dL vs. 81.7 mg/dL; p = 0.09), and more "stent-in-stent" lesions (25% vs. 7.8%; p = 0.07) than those in the DES group. A smaller post-procedural minimal target lesion lumen diameter was also noted in the DCB group than in the DES group (2.71 mm vs. 2.85 mm; p = 0.03). The cumulative incidence rates of major adverse cardiac events (MACEs) were similar between both groups (median follow-up duration, 868 days; MACE rate, 25% in the DCB group vs. 25.5% in the DES group; p = 0.96). The multivariate Cox regression analysis indicated that the true bifurcation of ISR was an independent risk predictor of MACEs (hazard ratio, 4.62; 95% confidence interval, 1.572-13.561; p < 0.01). CONCLUSIONS: DES and DCB showed comparable long-term clinical results in patients with LMB-ISR lesions.

Prospective partially randomized comparison of clopidogrel loading versus maintenance dosing to prevent periprocedural myocardial infarction after stenting for stable angina pectoris: Results from the "Method of Clopidogrel Pre-treatment Undergoing Conventional Coronary Angiogram in Angina Patients (MECCA)" study.

WHAT IS KNOWN AND OBJECTIVE: Pre-treatment of clopidogrel 600 mg is better than 300 mg loading for reducing periprocedural myocardial infarction (PMI). We aimed to evaluate pre-treatment methods for preventing PMI among patients undergoing conventional coronary angiography (CAG) for stable angina pectoris. MATERIALS AND METHODS: The study analyzed 402 patients who underwent percutaneous coronary intervention (PCI) during 2010 - 2011 at three Korean hospitals. Clopidogrel-naïve patients received routine maintenance therapy (75 mg/day for ≥ 5 days) and were randomly assigned to a 300-mg reload (RL) or only the maintenance dose (MD). Patients who received a loading dose (LD; 600 mg at 2 - 24 hours before the procedure) were entered into a non-randomized group. RESULTS: After excluding patients who showed an abnormal creatinine kinase myocardial band (CK-MB) level, the study included 233 patients in the LD group, 85 patients in the RL group and 84 patients in the MD group. The LD group had a significantly higher rate of PMI (LD: 21, RL: 3, MD: 0 cases; p = 0.007) and a significant increase in the mean CK-MB levels after 8 hours (p = 0.016) and 24 h (p = 0.01). However, there was no difference in PMI between the RL and MD groups. Furthermore, no significant differences between the three groups were observed in the P2Y12 reaction unit (PRU) values (p = 0.57). Albeit not significantly, the LD group had a higher rate of moderate-to-severe GUSTO bleeding within 7 days. WHAT IS NEW AND CONCLUSION: Clopidogrel maintenance is better than 600-mg loading for preventing PMI, and the RL protocol did not further prevent PMI.

Incidence of new-onset diabetes with 1 mg versus 4 mg pitavastatin in patients at high risk of developing diabetes during a 3-year follow-up.

BACKGROUND: Statin therapy reduces the risk of cardiovascular events across a broad spectrum of patients; however, it increases the risk of new-onset diabetes (NOD). Although the highest dose pitavastatin is considered to not be associated with NOD, there are limited data regarding the impact of long-term highest dose pitavastatin use on the development of NOD in patients at high risk of developing diabetes. Therefore, we prospectively compared the differences in the development of NOD between the lowest and the highest dose of pitavastatin in patients at high risk of developing diabetes during a 3-year follow-up. METHODS: This post hoc analysis of a prospective, single-blinded, randomized study compared the risk of NOD between the highest dose of pitavastatin (4 mg) and the lowest dose of pitavastatin (1 mg) over a 3-year follow-up in patients with acute coronary syndrome. Among 1044 patients of the original study, 667 patients at high risk of developing type 2 diabetes mellitus were in the subgroup analysis. The primary endpoint was a comparison of the differences in the cumulative incidence of NOD in the pitavastatin 1 mg and 4 mg groups during a 3-year follow-up. RESULTS: With propensity score matching, there were no significant differences in baseline demographic characteristics between the 2 groups. Incidence of NOD was similar between the pitavastatin 1 mg and 4 mg groups [12 of 289 patients (4.2%) and 8 of 289 patients (2.8%), respectively; p = 0.36]. In a prespecified analysis, there were no significant differences in NOD events according to sex, age, diagnosis, body mass index, glucose intolerance, or dyslipidemia. CONCLUSIONS: Administration of highest-dose pitavastatin did not increase the risk of NOD in patients at high risk of developing diabetes during the 3-year follow-up. Moreover, various risk factors for NOD such as metabolic syndrome components, glucose intolerance, dyslipidemia, obesity, or hypertension did not affect the development of NOD during pitavastatin administration. Thus, the highest dose pitavastatin can be safely used in patients with metabolic syndrome who are at high risk of developing diabetes. Trial registration Clinical Trial registration information. URL: https://clinicaltrials.gov/ct2/show/NCT02545231. Unique identifier: NCT02545231.

Effects of lowest-dose vs. highest-dose pitavastatin on coronary neointimal hyperplasia at 12-month follow-up in type 2 diabetic patients with non-ST elevation acute coronary syndrome: an optical coherence tomography analysis.

Current ACC/AHA guidelines recommend high-dose statin therapy after coronary stenting, especially in diabetic patients; however, pitavastatin 4 mg or pitavastatin 1 mg are frequently used after coronary stenting in Asia, even in patients with acute coronary syndrome. We compared the effects of highest-dose and lowest-dose pitavastatin therapy on coronary neointimal hyperplasia at 12-month follow-up in diabetic patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) using optical coherence tomography. A total of 72 diabetic patients with NSTE-ACS were randomized to lowest-dose pitavastatin [1 mg (n = 36)] or highest-dose pitavastatin [4 mg (n = 36)] after everolimus-eluting stent implantation. The primary endpoint was to compare the normalized neointimal volume at 12-month follow-up. Normalized neointimal volume was significantly lower in the pitavastatin 4 mg group (4.00 ± 2.80 vs. 8.24 ± 2.83 mm3/mm, p < 0.01) at 12-month follow-up. There was also significant difference in neointimal area between the pitavastatin 4 mg group and pitavastatin 1 mg group (0.41 ± 0.28 vs. 0.74 ± 0.23 mm2, p < 0.01). Improvement of brachial artery flow-mediated dilation (baFMD) was significantly higher in the pitavastatin 4 mg group than in pitavastatin 1 mg group (0.15 ± 0.15 vs. - 0.03 ± 0.19 mm, p < 0.001). In addition, the improvement of adiponectin levels was significantly greater in the pitavastatin 4 mg group than in the pitavastatin 1 mg group (2.97 ± 3.98 vs. 0.59 ± 2.80 µg/mL, p < 0.05). Pitavastatin 4 mg significantly improved inflammatory cytokines and lipid profiles compared to pitavastatin 1 mg during the 12-month follow-up, contributing to the reduction of neointimal hyperplasia and to the improvement of baFMD in diabetic patients with NSTE-ACS requiring coronary stenting. Thus, the administration of pitavastatin 4 mg can be safely and effectively used in high-risk patients requiring coronary stenting. Trial registration NCT02545231 (Clinical Trial registration information: https://clinicaltrials.gov/ct2/show/NCT02545231 ).

A Low Frequency Vibration Energy Harvester Using ZnO Nanowires on Elastic Interdigitated Electrodes.

This paper presents a low frequency piezoelectric vibration energy harvester using ZnO nanowires on elastic interdigitated electrodes. The interdigitated electrodes are formed using electroplated Ni and have suspended parts at the edges that are elastic and deformable by applying external force. A spherical Ni ball is used as a proof mass, which transforms a low frequency mechanical vibration into the force applied to deform the elastic electrodes. The ZnO nanowires are grown selectively on the electrodes and can generate a piezoelectric potential when the elastic electrodes are deformed by the proof mass activated by the external mechanical vibration. The proposed operation concept is demonstrated using two different types of energy harvesters, which have simple suspended part and cantilever array structures added to the electrodes, respectively. The output voltage of the fabricated harvesters is measured using a vibration exciter at 6 Hz sinusoidal vibration with an acceleration of 0.5 g. Maximum output power of 12.8 pW and 18.8 pW was generated with a load resistance of 1 MΩ for the harvesters using the simple suspended structure and cantilever array, respectively.

Clinical outcomes of patients with coronary artery aneurysm after the first generation drug-eluting stent implantation.

OBJECTIVES: We sought to investigate the long-term clinical outcomes of patients with coronary artery aneurysm (CAA) after drug-eluting stent (DES) implantation, compared with patients without CAA. BACKGROUND: CAA developed after DES implantation is a rare but associated with poor clinical outcome. METHODS: We retrospectively compared 78 patients with CAA after DES implantation with 269 patients without CAA who underwent DES implantation for complex lesions (controls). The primary endpoint was defined as major adverse cardiac events (MACE), the composite of all-cause death, nonfatal myocardial infarction (MI), and target lesion revascularization (TLR). RESULTS: Morphologically, CAAs were saccular (32%), fusiform (13%), or microform (55%). The stent types involved were Cypher (n = 56, 71.8%) and Taxus (n = 22, 28.2%). During a median follow-up period of 1164 days, the incidence of MACE was significantly higher in the CAA group (26.9 vs. 2.2%, P < 0.001); the difference was driven mainly by nonfatal MI (11.5 vs. 0%, P < 0.001) and TLR (20.5 vs. 1.9%, P < 0.001). The incidence of stent thrombosis was higher in the CAA group (12.8 vs. 0.74%, P < 0.001), irrespective of the maintenance of dual antiplatelet therapy. In the CAA group, Cox regression analysis showed significantly higher hazard ratios of CAA for MACE during the follow-up period. Further analyses after propensity-score matching of 65 pairs also showed similar results. CONCLUSIONS: The incidence of MACE was higher in patients with CAA compared with patients without CAA after DES implantation. This difference was driven by TLR and nonfatal MI and widened over time.

Impact of hyperuricemia on clinical outcomes after percutaneous coronary intervention for in-stent restenosis.

BACKGROUND: There have been limited data on the impact of hyperuricemia on long-term clinical outcomes after percutaneous coronary intervention (PCI) for in-stent restenosis (ISR). METHODS: From January 2009 to July 2015, 317 patients who underwent repeat PCI for ISR were divided into two groups: patients with normal serum uric acid (UA) levels (normal UA group) and patients with higher serum UA levels (higher UA group). The higher UA group included patients with serum UA levels > 6.8 mg/dL or patients who were taking anti-hyperuricemic medication. RESULTS: During a median follow-up period of 1088 days, the cumulative incidence rates of major adverse event (MAE), including a composite of all-cause death, non-fatal myocardial infarction, and any revascularization, were similar between the two groups (higher UA 36.4% vs. normal UA 29.9%, p = 0.389, log-rank p = 0.367). Follow-up angiographic data showed similar outcomes of late lumen loss (0.8 ± 0.9 mm vs. 0.8 ± 1.1 mm, p = 0.895) and binary restenosis rate (28.1% vs. 34.7%, p = 0.622). Multivariate Cox regression analysis indicated higher levels of low-density lipoprotein cholesterol (hazard ratio [HR] 1.011, 95% confidence interval [CI] 1.003-1.019, p = 0.006) and lower left ventricular ejection fraction (HR 0.972, 95% CI 0.948-0.996, p = 0.022), but not UA levels, to be the independent risk predictors of MAE. CONCLUSION: Hyperuricemia is not associated with poor clinical outcomes after repeat PCI for ISR lesions.

The Relationship between Pulse Wave Velocity and Coronary Artery Stenosis and Percutaneous Coronary Intervention: a retrospective observational study.

BACKGROUND: Arterial stiffness has been suggested as a valuable predictor of coronary artery stenosis (CAS). However, little data are available on aortic stiffness and CAS in patients who have previously undergone percutaneous coronary artery intervention (PCI). The aim of this study was to investigate the association of arterial stiffness to CAS in patients with a history of PCI and those without a history of PCI. METHODS: We retrospectively studied 1093 consecutive patients who had undergone coronary angiography (CAG). Arterial stiffness was determined by brachial-ankle pulse wave velocity (baPWV) measured prior to CAG. RESULTS: In patients without a history of PCI, baPWV significantly increased in patients with CAS compared to that in patients without CAS (p < 0.001). However, among patients with a history of PCI, there was no significant difference in baPWV. Multivariate logistic regression analysis demonstrated that baPWV was an independent risk predictor for CAS in patients without a history of PCI, but not in those with a history of PCI (OR 1.106, 95% CI 1.039-1.177, p = 0.002). In CAS patients without a history of PCI, increased baPWV was significantly associated with multiple cardiovascular risk factors, multivessel involvement, and anatomical severity. CONCLUSIONS: Prediction of CAS by baPWV is significantly attenuated in patients with a history of PCI.

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.

Novel microbial photobioelectrochemical cell using an invasive ultramicroelectrode array and a microfluidic chamber.

OBJECTIVE: To fabricate a novel microbial photobioelectrochemical cell using silicon microfabrication techniques. RESULTS: High-density photosynthetic cells were immobilized in a microfluidic chamber, and ultra-microelectrodes in a microtip array were inserted into the cytosolic space of the cells to directly harvest photosynthetic electrons. In this way, the microbial photobioelectrochemical cell operated without the aid of electron mediators. Both short circuit current and open circuit voltage of the microbial photobioelectrochemical cell responded to light stimuli, and recorded as high as 250 pA and 45 mV, respectively. CONCLUSION: A microbial photobioelectrochemical cell was fabricated with potential use in next-generation photosynthesis-based solar cells and sensors.

Efficacy and safety of endovascular treatment for femoropopliteal lesions of TASC II type C and D compared with TASC II type A and B in Korea.

Objective To compare the long-term safety and clinical efficacy of endovascular treatment for TASC-II type C/D femoropopliteal lesion compared with TASC-II type A/B femoropopliteal lesion in Korea. Methods A total of 179 limbs [TASC-II A/B femoropopliteal lesion (group I, n = 105 limbs) and TASC-II C/D (group II, n = 74 limbs)] were retrospectively analyzed from patients who underwent angioplasty with or without primary stent implantation between February 2008 and November 2012 at two medical centers in South Korea. The major adverse limb event was defined as a composite of target lesion revascularization, symptom relapse with abnormal ankle brachial index, and major amputation. Results Immediate procedural success rates were not significantly different (96.2% vs. 95.7%, p = 0.450). Although major adverse limb event, mainly driven by symptom relapse with abnormal ankle brachial index, were significantly higher in group II ( p = 0.013), the incidence of major amputation was very low and similar in both groups. Conclusion Even though there were higher incidences of overall procedural complication and major adverse limb event, the technical success rate of endovascular treatment for TASC-II C/D femoropopliteal lesion was comparable to endovascular treatment for TASC-II A/B FPL without an increase in major procedural complications or serious clinical events during follow-up.

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.

Electromagnetic biaxial microscanner with mechanical amplification at resonance.

We present the design, fabrication, and measurement results of an electromagnetic biaxial microscanner with mechanical amplification mechanism. A gimbaled scanner with two distinct single-crystal silicon layer thicknesses and integrated copper coils has been fabricated with combination of surface and bulk micromachining processes. A magnet assembly consisting of an array of permanent magnets and a pole piece has been placed under the substrate to provide high strength lateral magnetic field oriented 45° to two perpendicular scanning axes. Micromirror has been supported by additional gimbal to implement a mechanical amplification. A 1.2mm-diameter mirror with aluminum reflective surface has been actuated at 60Hz for vertical scan and at 21kHz for horizontal scan. Maximum scan angle of 36.12° at 21.19kHz and 17.62° at 60Hz have been obtained for horizontal and vertical scans, respectively.

Pioglitazone increases circulating microRNA-24 with decrease in coronary neointimal hyperplasia in type 2 diabetic patients- optical coherence tomography analysis.

BACKGROUND: Aberrant expression of microRNAs is associated with neointimal hyperplasia (NIH) in type 2 diabetes. We prospectively compared the effects of pioglitazone on coronary NIH and changes in microRNAs according to NIH status in type 2 diabetic patients during 9-month follow-up. METHODS AND RESULTS: Type 2 diabetic patients were randomly assigned to the pioglitazone (n=36) or control groups (n=36) after coronary stenting. Primary endpoint was the comparison of changes in neointimal volume on OCT and in the level of circulating microRNA-17,-24,-92a,-126 and -145 during 9-month follow-up. Secondary endpoint was the comparison of changes in brachial artery flow-mediated dilation and inflammatory markers such as IL-6, TNF-α, hsCRP, adiponectin, sICAM-1, and sVCAM-1 between the 2 groups. Neointimal volume was significantly lower in the pioglitazone group (25.02±17.78 mm(3)vs. 55.10±30.01 mm(3), P<0.001) with significant increases in circulating microRNA-24 (0.264±0.084 vs. 0.006±0.030, P<0.001) during follow-up. FMD was significantly greater in the pioglitazone than control group at 9 months (0.47±0.14 mm vs. 0.28±0.18 mm, P<0.05, respectively). Decreases in inflammatory markers such as IL-6, TNF-α, and sVCAM-1 were significantly greater in the pioglitazone than the control group during the follow-up. CONCLUSIONS: Pioglitazone significantly decreased NIH with increases in circulating microRNA-24 at 9-month follow-up. The decrease in microRNA-24 could be used as a potential predictor of increases in NIH in type 2 diabetic patients.

Acute changes of left ventricular hemodynamics and function during percutaneous coronary intervention in patients with unprotected left main coronary artery disease.

Percutaneous coronary interventions (PCIs) are increasingly being used to treat unprotected left main coronary artery (ULMCA) lesions. However, research is sparse on the acute changes of left ventricular (LV) hemodynamics and function during PCI in patients with ULMCA stenosis. We aimed to assess the acute changes of LV function using speckle-tracking imaging during PCI in these patients. Fifteen consecutive patients who underwent elective PCI for ULMCA stenosis were enrolled. Echocardiographic studies and pressure measurement were performed at baseline, during PCI and after PCI. LMCA occlusion with a first balloon inflation induced a marked reduction in the peak positive derivative of LV pressure (dP/dt max), LV global longitudinal strain (GLS), and systolic and diastolic strain rates, and a marked increase in LV end-diastolic pressure (EDP) (all P < 0.01). During the second inflation, the degrees of LV hemodynamic and functional changes were similar to those of the first inflation, even with a higher inflation pressure. During the third inflation, the values of GLS and dP/dt max were higher than those of the second inflation (P = 0.03 and P = 0.05, respectively). After optimal PCI, dP/dt max, LVEDP, and strain parameters were improved to baseline values. LV hemodynamics and function were considerably impaired with the first ballooning during PCI for ULMCA stenosis. However, the degrees of LV hemodynamic and functional changes decreased with each successive balloon inflation, which can be explained by ischemic preconditioning. After all procedures were safely completed, LV systolic function was improved without LV diastolic stunning.