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Background: Antiplatelet treatment is an important component in optimizing the clinical outcomes after percutaneous coronary intervention (PCI) especially in patients with acute coronary syndrome (ACS). Prasugrel, which is a new P2Y12 inhibitor, has been confirmed as efficacious in a large trial in Western countries, and a similar trial is also to be launched in Asian countries. Although a 60-mg loading dose of prasugrel followed by 10 mg per day should be acceptable, there have been no data regarding the optimal dose in Asian patients. Furthermore, serum levels of prasugrel and the rates of platelet inhibition are known to be higher in Asians than Caucasians with the same dose of the drug. Polymer, a key component of drug-eluting stents (DES), has been suggested as the cause of inflammation leading to late complications, and has driven many companies to develop biodegradable-polymer DES. Currently, there are limited data regarding the head-to-head comparison between BP-BES and the biostable polymer CoCr-EES or the newest platinum-chromium everolimus-eluting stent (PtCr-EES). Furthermore, the polymer issue may be more important in ACS where there is ruptured thrombotic plaque where polymer-induced inflammation may affect the local milieu of the stented artery. Therefore, the present study dedicated only to ACS patients, will offer important information on the optimal prasugrel dose in the Asian population by comparing a 10-mg versus a 5-mg maintenance dose beyond 1 month after PCI, as well as giving important insight into the polymer issue by comparing BP-BES versus biostable-polymer PtCr-EES.Method/design: Harmonizing Optimal Strategy for Treatment of coronary artery diseases--comparison of REDUCtion of prasugrEl dose or POLYmer TECHnology in ACS patients (HOST-REDUCE-POLYTECH-ACS) trial is a multicenter, randomized and open-label clinical study with a 2 × 2 factorial design, according to the type of stent (PtCr-EES versus BP-BES) and prasugrel maintenance dose (5 mg versus 10 mg), to demonstrate non-inferiority of PtCr-EES relative to BP-BES or the reduced prasugrel dose relative to conventional dose in an Asian all-comers PCI population presenting with ACS. Approximately 3400 patients will undergo prospective, random assignment separately to either stent or prasugrel arm (1:1 ratio, respectively). When the patients have contraindications to prasugrel, they are categorized into an antiplatelet observation group after stent-randomization. The primary endpoint is the patient-oriented composite outcome, which is a composite of all-cause mortality, any myocardial infarction (MI), any repeat revascularization in the stent arm at 12 months after index PCI. In the prasugrel arm, primary endpoint is any major adverse cardiovascular event, which is a composite of all-cause mortality, any MI, any stent thrombosis (Academic Research Consortium (ARC)-defined), any repeat revascularization, stroke, or bleeding (BARC class ≥ 2).Discussion: The HOST-REDUCE-POLYTECH-ACS RCT is the first study exploring the optimal maintenance dose of prasugrel beyond 1 month after PCI for ACS in Asian all-comers. In addition, this is the largest study dedicated only to ACS patients to evaluate the polymer issue in the situation of ACS by directly comparing biostable-polymer PtCr-EES versus BP-BES.Trial Registration: ClinicalTrials.gov (ID: NCT02193971, 13 July 2014). [ABSTRACT FROM AUTHOR]

OBJECTIVES: A Bayesian network meta-analysis was performed comparing the efficacy and safety of drug-eluting balloons (DEB), drug-eluting stents (DES), or plain old balloon angioplasty (POBA) for treatment of in-stent restenosis (ISR). BACKGROUND: Optimal treatment options for ISR have not been well established. METHODS: Randomized, controlled trials comparing DEB, DES, and POBA for the treatment of ISR after percutaneous coronary intervention with bare metal stent or DES were included. The primary outcome was target lesion revascularization (TLR). The pairwise posterior median odds ratio (OR) with 95% credible interval (CrI) was the effect measure. RESULTS: This analysis included 2,059 patients from 11 RCTs. The risk of TLR was markedly lower in patients treated with DEB (OR: 0.22,95%CrI: 0.10 to 0.42) or DES (OR: 0.24, 95%CrI: 0.11 to 0.47) than in those treated with POBA in a randomeffects model. In a comparison of DEB and DES, the risk of TLR (OR: 0.92, 95% CrI: 0.43 to 1.90) was similar. The risk of MI or all-cause mortality was lowest in the DEB group compared with the DES and POBA groups, which did not meet statistical significance. The risk of major adverse cardiac events, which was mainly driven by TLR, was also significantly lower in the DEB or and DES group (OR: 0.28,95% CrI: 0.14 to 0.53) than in the POBA group, but it was similar between the DEB and DES groups (OR: 0.84, 95% CrI: 0.45 to 1.50). The probability of being ranked as the best treatment was 59.9% (DEB), 40.1% (DES), and 0.1% (POBA) in terms of TLR, whereas it was 63.0% (DEB), 35.3% (POBA), and 1.7% (DES) in terms of MI. CONCLUSIONS: Local drug delivery by DEB or DES for ISR lesions was markedly better than POBA in preventing TLR, but not for MI or mortality. Among the 2 different strategies of drug delivery for ISR lesions, treatment with DEB showed a trend of less development of MI than did treatment with DES. [ABSTRACT FROM AUTHOR]

Recently, transcatheter aortic valve replacement (TAVR) has emerged as an alternative for the treatment of severe symptomatic aortic stenosis patients. Although experience with TAVR is increasing exponentially, few cases of post-TAVR endocarditis are reported. We present a case of 76-year-old man with infective endocarditis after TAVR who was definitely diagnosed by echocardiography. [ABSTRACT FROM AUTHOR]

Tight junctions (TJs) are a mode of cell-to-cell adhesion in epithelial or endothelial cells, and serve as a physical barrier to maintenance of homeostasis in body by controlling paracellular transport. Claudins are the most important molecules of the TJs, but paradoxically these proteins are frequently over-expressed in cancers and their overexpression is implicated in the invasive potential of cancer. Hence, we investigated the effects of flavonoids extracted from Orostachys japonicus A. Berger (FEOJ) on TJs and the expression of claudins as well as cancer invasion along with in LnCaP human prostate cancer. FEOJ suppressed cancer cell motility and invasiveness at the concentrations where FEOJ did not show anti-proliferative activity. FEOJ increased transepithelial electrical resistance (TER) associated with tightening TJs, and suppressed expression of claudin proteins. Furthermore, FEOJ suppressed the activities of MMP-2 and -9 in a dose-dependent manner, which came from the activation of tissue inhibitor of metalloproteinases (TIMPs) by FEOJ. FEOJ suppressed migration and invasion by suppressing PI3K/Akt signaling pathway. Taken together, this study suggest that FEOJ suppresses cancer migration and invasion by tightening TJs through the suppression of claudin expression, and by suppressing MMPs in LnCaP human prostate cancer cells, which at least in part results from the suppression of PI3K/Akt signaling pathway. [ABSTRACT FROM AUTHOR]

A large number of thioredoxins (Trxs), small redox proteins, have been identified from all living organisms. However, many of the physiological roles played by these proteins remain to be elucidated. We isolated a high Mr (HMW) form of h-type Trx from the heat-treated cytosolic extracts of Arabidopsis (Arabidopsis thaliana) suspension cells and designated it as AtTrx-h3. Using bacterially expressed recombinant AtTrx-h3, we find that it forms various protein structures ranging from low and oligomeric protein species to HMW complexes. And the AtTrx-h3 performs dual functions, acting as a disulfide reductase and as a molecular chaperone, which are closely associated with its molecular structures. The disulfide reductase function is observed predominantly in the low Mr forms, whereas the chaperone function predominates in the HMW complexes. The multimeric structures of AtTrx-h3 are regulated not only by heat shock but also by redox status. Two active cysteine residues in AtTrx-h3 are required for disulfide reductase activity, but not for chaperone function. AtTrx-h3 confers enhanced heat-shock tolerance in Arabidopsis, primarily through its chaperone function. [ABSTRACT FROM AUTHOR]

This article examines the relation of perceived career plateau to job satisfaction and organizational commitment and the moderating effects of career motivation and perceived supervisor support on the relationships between perceived career plateau and the two dependent variables. Data are collected from 209 whitecollar employees who are more than 30 years old and who come from a wide variety of organizations. The results of this study show that perceived career plateau is negatively correlated with job satisfaction and organizational commitment. The results of hierarchical multiple regression analyses indicate that career motivation plays a significant moderating role only on the relationship between perceived career plateau and organizational commitment. Perceived supervisor support moderates the relationships between perceived career plateau and the two dependent variables. Based on the results, the implications and limitations of this study and the directions for future research are discussed. [ABSTRACT FROM AUTHOR]

When the wideband complex permittivity of a liquid solution was measured by an open-ended coaxial probe, its accuracy was inherently degraded due to an inexact conversion model compared with the uncertainty of the associated vector network analyzer. In this paper, the accuracy of the converted wideband complex permittivity is evaluated indirectly and then enhanced significantly. Firstly, the measured wideband complex permittivity is fitted by a dispersive permittivity profile in the Debye formula. Secondly, the new reflection coefficients are calculated numerically by applying the dispersive permittivity profile to a 2D finite-difference time-domain model of our probe. Thirdly, the inaccuracy of the fitted complex permittivity profile is quantified indirectly by the root mean square (RMS) error of the numerically calculated reflection coefficients in comparison with the originally measured reflection coefficients. Finally, four parameters of the Debye formula involved in the initially converted complex permittivity profile were calibrated iteratively until the RMS error of the repeatedly calculated reflection coefficients could be minimized. The validity of the above calibration procedure is assured numerically for a given wideband complex permittivity profile. In the case of our actual measurement of the fabricated cancer-equivalent solution, an unknown complex permittivity profile, the RMS error of the numerically calculated reflection coefficients could be reduced from 0.0416 to 0.0093. This calibration results in both relative dielectric constant and conductivity profiles being gradually enhanced as the frequency increases up to 5000 MHz. [ABSTRACT FROM AUTHOR]

Human nuclear factor of kappa light chain gene enhancer in B cells inhibitor, alpha (NFKBIA) inhibits the action of NF-κB by forming a heterodimer with NF-κB, and preventing its translocation to the nucleus. We have sequenced a human NFKBIA full gene including -1000bp promoter region to identify its gene polymorphisms as a potential candidate gene for host genetic study of Hepatocellular Carcinoma (HCC). Nine novel single nucleotide polymorphisms (SNPs) and one GAA deletion were identified; two in promoter region (c.-673A>T, c.-642C>T), two in exon 1 (c.78G>A (Leu26Leu), c.81C>T (Asp27Asp)), three in introns (c.284T>A, c.1952A>G and c.2444C>T) and three in 3'UTR (c.2710-2712delGAA, c.2758G>A and c.3053G>A). Among ten identified variants, six were selected for larger scale genotyping (n=1,750) for association study based on frequencies and location. Haplotypes, their frequencies and linkage disequilibrium coefficients (∣D'∣) between SNP pairs were estimated. Allele frequencies of each SNPs and haplotypes were compared between patients with HCC and patients without HCC among HbsAg positives by logistic regression. As a conclusion, we could not find any significant association of NFKBIA variants with development of HCC among chronic hepatitis B patients. © 2003 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Background Studies have reported conflicting results regarding efficacy of mechanical hemodynamic support using intra-aortic balloon pump (IABP) or percutaneous ventricular assisted device (pVAD) in patients undergoing high-risk PCI. We performed a Bayesian network meta-analysis comparing the safety and efficacy of mechanical hemodynamic support devices and medical therapy (MT). Methods and results RCTs comparing overall mortality of IABP versus MT or IABP versus pVAD in high-risk PCI populations were included. The primary endpoint was overall mortality, using the longest available follow-up in each study. This analysis included 2843 patients from 13 trials. In network meta-analysis, overall survival benefit was not significant with IABP (RR 0.84, 95% CrI 0.56-1.24) or pVAD (RR 0.95, 95% CrI 0.42-2.06), compared with MT. IABP or pVAD also did not show early survival benefit compared with MT. In terms of bleeding, pVAD was the worst (versus IABP: RR 29.4, 95% CrI 5.99-221.0; versus MT: RR 41.7, 95% CrI 8.19-330.0), which was mainly driven by the higher incidence of bleeding in the ECMO and TandemHeart, while IABP was worse than MT (RR 1.41, 95% CrI 1.01-2.08). The incidence of acute limb ischemia or vascular complication was not different between treatment groups. Conclusions In this meta-analysis, routine elective use of IABP or pVAD did not reduce mortality, while it increased bleeding, compared with MT in high-risk PCI population or even in the patients with cardiogenic shock. Thoughtful selection of appropriate patients and balancing the risk and benefit should be the prerequisites to the use of mechanical hemodynamic support devices. [ABSTRACT FROM AUTHOR]