FGFR3 and TP53 mutation analysis in inverted urothelial papilloma: incidence and etiological considerations

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Phenanthrene-Based Tylophorine-1 (PBT-1) Inhibits Lung Cancer Cell Growth through the Akt and NF-κB Pathways

Tylophorine and related natural compounds exhibit potent antitumor activities. We previously showed that PBT-1, a synthetic C9-substituted phenanthrene-based tylophorine (PBT) derivative, significantly inhibits growth of various cancer cells. In this study, we further explored the mechanisms and potential of PBT-1 as an anticancer agent. PBT-1 dose-dependently suppressed colony formation, induced cell cycle G2/M arrest and apoptosis. DNA microarray and pathway analysis showed that PBT-1 activated the apoptosis pathway and mitogen-activated protein kinase signaling. In contrast, PBT-1 suppressed the nuclear factor kappaB (NF-κB) pathway and focal adhesion. We further confirmed that PBT-1 suppressed Akt activation accelerated RelA degradation via IκB kinase-α, and downregulated NF-κB target gene expression. The reciprocal recruitment of RelA and RelB on COX-2 promoter region led to downregulation of transcriptional activity. We conclude that PBT-1 induces cell cycle G2/M arrest and apoptosis by inactivating Akt and by inhibiting the NF-κB signaling pathway. PBT-1 may be a good drug candidate for anticancer chemotherapy

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Contemporary approaches for processing and handling of radical prostactomy specimens

Standardized protocols for processing radicalprostatectomy specimens are critical for superior patientmanagement. It provides accurate information to theclinician in a reliable and consistent format to enhancepatient care and prognosis. In recent years, processingprotocols have been proposed by various authoritativegroups, with similar suggestions for most parts of thepractice guidelines; however, discrepancy in processingapproaches still exists. Standardization improves thequality and consistency of pathology reports. In thisreview article, we incorporate the processing schemesfor radical prostatectomy addressed in literature andpropose a comprehensively standardized approach toevaluate radical prostatectomy specimens

Ligand-dependent active-site closure revealed in the crystal structure of Mycobacterium tuberculosis MenB complexed with product analogues

1,4-Dihydroxy-2-naphthoyl coenzyme A (DHNA-CoA) synthase catalyzes an essential intramolecular Claisen condensation in menaquinone biosynthesis and is an important target for the development of new antibiotics. This enzyme in Mycobacterium tuberculosis is cofactor-free and is classified as a type II DHNA-CoA synthase, differing from type I enzymes, which rely on exogenous bicarbonate for catalysis. Its crystal structures in complex with product analogues have been determined at high resolution to reveal ligand-dependent structural changes, which include the ordering of a 27-residue active-site loop (amino acids 107-133) and the reorientation of the carboxy-terminal helix (amino acids 289-301) that forms part of the active site from the opposing subunit across the trimer-trimer interface. These structural changes result in closure of the active site to the bulk solution, which is likely to take place through an induced-fit mechanism, similar to that observed for type I DHNA-CoA synthases. These findings demonstrate that the ligand-dependent conformational changes are a conserved feature of all DHNA-CoA synthases, providing new insights into the catalytic mechanism of this essential tubercular enzyme

Why do customers utilize the internet as a retailing platform?: A view from consumer perceived value

This study investigates the impact of perceived value on customer intention to use the internet as a retailing platform and, more specifically, the impact that perceived value (comprising functional, social, emotional and epistemic values) has on Taiwanese customer intention to conduct the two distribution channel functions, i.e. information collection and order placement, through the internet. A total of 295 usable survey responses were collected in the main commuter district of Taipei, Taiwan. The findings indicate that both functional and epistemic values have a significant impact on information collection and order placement. Nevertheless, social value has an impact only on information collection, whereas emotional value has a significant impact only on order placement. The aforementioned issue has rarely been researched but is essential to the development of a channel of distribution theory and is of immediate relevance to marketing practices. The paper pioneers the study of the impact of perceived value in this context work that empirically investigated such an issue

The complete mitochondrial genome of Neotermes koshunensis (Shiraki, 1909) (Blattodea: Termitoidae: Kalotermitidae) and its phylogenetic implications

In this article, we describe the complete mitochondrial genome of Neotermes koshunensis from the Pingtung County, Taiwan. This mitogenome is 15,589 bp long, containing 13 protein-coding genes, 22 tRNA genes, and 2 rDNA genes. Nucleotide composition of the whole mitogenome is 42.86% for A, 25.42% for T, 19.65% for C, and 12.07% for G. The AT and GC skewness of mitogenomic sequences are 0.255 and −0.239, showing the A-skew and C-skew. Neotermes koshunensis grouped within the clade including the other nine Kalotermitidae species was well supported. The phylogenetic position of Kalotermitidae is sister to Neoisoptera (including Termitidae, Rhinotermitidae, Serritermitidae, and Stylotermitidae) in the current phylogenetic analysis. Mitogenomic data from this study will provide useful information for further studies on the phylogeny of Kalotermitidae

Characterization of the complete mitochondrial genome of Euwallacea fornicatus (Eichhoff, 1868) (Coleoptera: Curculionidae: Scolytinae) and its phylogenetic implications

In the present report, we described the complete mitochondrial genome of Euwallacea fornicatus from Sindien, New Taipei City, Taiwan. The length of the complete mitogenome of E. fornicatus is 15,743 bp and the mitogenome contains 13 protein-coding, 22 tRNA and two rDNA genes. Nucleotide compositions of the whole mitogenome are 39.41% for A, 33.84% for T, 16.64% for C, and 10.11% for G. The AT and GC skewness of mitogenome sequence was 0.076 and −0.244, showing the A-skew and C-skew. The reconstructed phylogenetic relationships of 33 Curculionid species based on 13 mitochondrial protein-coding genes received absolute support (100%). Euwallacea fornicates is sister to the rest species in Xyleborini. The phylogenetic position of Scolytinae is sister to the clade including Cucurlioninae, Molytinae and Cryptorhynchinae. Mitogenomic data from this study will provide useful information for further studies for the population genetics, invasive history and pest control of E. fornicatus in the future