bluuebunny/crossref_metadata_2025 huggingface dataset:
Active volcanism on Venus in the Ganiki Chasma rift zone
Authors: Shalygin E. V. , Markiewicz W. J. , Basilevsky A. T. , Titov D. V. , Ignatiev N. I. , Head J. W.
Published: May 2015

Venus is known to have been volcanically resurfaced in the last third of solar system history and to have undergone a significant decrease in volcanic activity a few hundred million years ago. However, fundamental questions remain: Is Venus still volcanically active today, and if so, where and in what geological and geodynamic environment? Here we show evidence from the Venus Express Venus Monitoring Camera for transient bright spots that are consistent with the extrusion of lava flows that locally cause significantly elevated surface temperatures. The very strong spatial correlation of the transient bright spots with the extremely young Ganiki Chasma, their similarity to locations of rift‐associated volcanism on Earth, provide strong evidence for their volcanic origin and suggests that Venus is currently geodynamically active.
Observations of the relationship between ionospheric central polar cap and dayside throat convection velocities, and solar wind/IMF driving
Authors: Bristow W. A. , Amata E. , Spaleta J. , Marcucci M. F.
Published: May 2015

Convection observations from the Southern Hemisphere Super Dual Auroral Radar Network are presented and examined for their relationship to solar wind and interplanetary magnetic field (IMF) conditions, restricted to periods of steady IMF. Analysis is concentrated on two specific regions, the central polar cap and the dayside throat region. An example time series is discussed in detail with specific examples of apparent direct control of the convection velocity by the solar wind driver. Closer examination, however, shows that there is variability in the flows that cannot be explained by the driving. Scatterplots and histograms of observations from all periods in the year 2013 that met the selection criteria are given and their dependence on solar wind driving is examined. It is found that on average the flow velocity depends on the square root of the rate of flux entry to the polar cap. It is also found that there is a large level of variability that is not strongly related to the solar wind driving.
35th Annual David W Smith Workshop on Malformations and Morphogenesis: Abstracts of the 2014 Annual Meeting
Authors: Braddock Stephen R. , Lipinski Robert J. , Williams Marc S. , Carey John C.
Published: May 2015

The 35th Annual David W Smith Workshop on Malformations and Morphogenesis was held on July 25–30, 2014 at the University of Wisconsin, Madison, Wisconsin. The conference, which honors the legacy of David Smith, brought together over 130 clinicians and researchers interested in congenital malformations and their underlying mechanisms of morphogenesis. As is the tradition of the meeting, the Workshop highlighted five themes besides mechanisms of morphogenesis: Evolution and Development, Minor Malformations, CHARGE syndrome, Craniofacial Development/ Malformations, and Disorders of Chromatin Remodeling. This Conference Report includes the abstracts presented at the Workshop. © 2015 Wiley Periodicals, Inc.
Investigation of the role of TCF4 rare sequence variants in schizophrenia
Authors: Basmanav F. Buket , Forstner Andreas J. , Fier Heide , Herms Stefan , Meier Sandra , Degenhardt Franziska , Hoffmann Per , Barth Sandra , Fricker Nadine , Strohmaier Jana , Witt Stephanie H. , Ludwig Michael , Schmael Christine , Moebus Susanne , Maier Wolfgang , Mössner Rainald , Rujescu Dan , Rietschel Marcella , Lange Christoph , Nöthen Markus M. , Cichon Sven
Published: May 2015

Transcription factor 4 (TCF4) is one of the most robust of all reported schizophrenia risk loci and is supported by several genetic and functional lines of evidence. While numerous studies have implicated common genetic variation at TCF4 in schizophrenia risk, the role of rare, small‐sized variants at this locus‐such as single nucleotide variants and short indels which are below the resolution of chip‐based arrays requires further exploration. The aim of the present study was to investigate the association between rare TCF4 sequence variants and schizophrenia. Exon‐targeted resequencing was performed in 190 German schizophrenia patients. Six rare variants at the coding exons and flanking sequences of the TCF4 gene were identified, including two missense variants and one splice site variant. These six variants were then pooled with nine additional rare variants identified in 379 European participants of the 1000 Genomes Project, and all 15 variants were genotyped in an independent German sample (n = 1,808 patients; n = 2,261 controls). These data were then analyzed using six statistical methods developed for the association analysis of rare variants. No significant association (P < 0.05) was found. However, the results from our association and power analyses suggest that further research into the possible involvement of rare TCF4 sequence variants in schizophrenia risk is warranted by the assessment of larger cohorts with higher statistical power to identify rare variant associations. © 2015 Wiley Periodicals, Inc.
Synthesis and Morphology of a Shape‐Persistent Macrocycle with endo‐Amines and an Inner Tetraethylene Glycol Ether Bridge
Authors: Nie Hui , Geng Yanfang , Luo Dapeng , Liu Miaoqing , Wang Yifei , Liu Zhenyu , Zeng Qingdao , Shu Lijin
Published: May 2015

A shape‐persistent macrocycle consisting of 2,6‐disubstituted aniline linked by acetylene, butadiyne, and an inner tetraethylene glycol bridge was prepared by Pd/Cu homocoupling oxidation reaction. The morphology of the resulting macrocycle was demonstrated and discussed, indicating the establishment of channels with amine functional groups inside the pores. Polarized optical microscopy (POM) observation of the macrocycle indicated the formation of liquid crystals (LCs) in the heating and cooling processes.
Chiral‐Squaramide‐Catalyzed Sulfa‐Michael/Aldol Cascade Reactions for Asymmetric Synthesis of Spirothiochromanones
Authors: Zhao Bo‐Liang , Du Da‐Ming
Published: May 2015

An efficient, asymmetric sulfa‐Michael/aldol cascade reaction catalyzed by a chiral squaramide catalyst has been developed. This organocatalytic cascade reaction provides easy access to highly functionalized spirothiochromanones with three contiguous stereocenters, including one quaternary center, in excellent yields of up to 99 % with excellent diastereoselectivity up to >99:1 d.r. and enantioselectivity up to 98 % ee. In addition, the key to the present method is introducing indenones that are readily accessible as hydrogen‐bond acceptors with very low catalyst loading of 0.5 mol %.
A prospective randomized cohort study evaluating 3 weeks vs 6 weeks of oral antibiotic treatment in the setting of “maximal medical therapy” for chronic rhinosinusitis
Authors: Sreenath Satyan B. , Taylor Robert J. , Miller Justin D. , Ambrose Emily C. , Rawal Rounak B. , Ebert Charles S. , Senior Brent A. , Zanation Adam M.
Published: May 2015

Background

Surprisingly, little literature exists evaluating the optimal duration of antibiotic treatment in “maximal medical therapy” for chronic rhinosinusitis (CRS). As such, we investigated whether 3 weeks vs 6 weeks of antibiotic therapy resulted in significant differences in clinical response.

Methods

A prospective, randomized cohort study was performed with patients assigned to 3‐week or 6‐week cohorts. Our primary outcome was failure of “maximal medical therapy” and surgical recommendation. Secondary outcomes included changes in pretherapy and posttherapy scores for the Rhinosinusitis Disability Index (RSDI), Chronic Sinusitis Survey (CSS), and computed tomography (CT)‐based Lund‐Mackay (LM) evaluation. Analyses were substratified based on presence of nasal polyps.

Results

Forty patients were randomized to the 3‐week or 6‐week treatment cohorts, with near‐complete clinical follow‐up achieved. No significant difference was found between the proportion of patients who failed medical therapy and were deemed surgical candidates between the 2 cohorts (71% vs 68%, p = 1.000). No significant difference was found in the change of RSDI or CSS scores in the 3 vs 6 weeks of treatment groups (mean ± standard error of the mean [SEM]; RSDI: 9.62 ± 4.14 vs 1.53 ± 4.01, p = 0.868; CSS: 5.75 ± 4.36 vs 9.65 ± 5.34, p = 0.573). Last, no significant difference was found in the change of LM scores (3.35 ± 1.11 vs 1.53 ± 0.81, p = 0.829).

Conclusion

Based on this data, there is little difference in clinical outcomes between 3 weeks vs 6 weeks of antibiotic treatment as part of “maximal medical therapy” for CRS. Increased duration of antibiotic treatment theoretically may increase risk from side effects and creates higher healthcare costs.
Epidemiology and economic burden of asthma
Authors: Loftus Patricia A. , Wise Sarah K.
Published: May 2015

Background

The “asthma epidemic” is on the rise, with the Center for Disease Control (CDC) epidemiological studies reporting a 3.0% asthma prevalence in the United States in 1970, 5.5% in 1996, and 7.8% in 2006 to 2008. This results in an immense economic burden, with asthma costing an estimated $56 billion in the United States in 2007, which is a 6% increase from the $53 billion that was spent in 2002.

Methods

A review of the current literature and CDC reports were used to thoroughly examine and summarize the epidemiology and economic burden of asthma domestically and globally.

Results

Asthma shows a male predominance before puberty, and a female predominance in adulthood. Studies show Puerto Ricans to be the most commonly affected ethnicity, and a higher prevalence of asthma is found in lower income populations. Asthma is related to some of the more common otolaryngologic diseases such as allergy and obstructive sleep apnea. The condition results in significant morbidity, such as an increase in emergency department visits and a decrease in productivity due to missed school and works days.

Conclusion

Epidemiological statistics report an undisputable increase of asthma both domestically and worldwide, which means the economic burden of this disease is also on the rise. Better access to healthcare, improved asthma education, and bridging the gap between ethnic and racial disparities in the treatment and management of asthma may help to control this epidemic, promote better outcomes, and prevent continued rising costs related to the management of this widespread disease.
Effect of β‐glucan on MUC4 and MUC5B expression in human airway epithelial cells
Authors: Kim Yong‐Dae , Bae Chang Hoon , Song Si‐Youn , Choi Yoon Seok
Published: May 2015

Background

β‐Glucan is found in the cell walls of fungi, bacteria, and some plant tissues, and is detected by the innate immune system. Furthermore, this recognition is known to worsen respiratory symptoms in patients with allergic and inflammatory airway diseases. However, the means by which β‐glucan affects the secretion of major mucins by human airway epithelial cells has not been elucidated. Therefore, in this study, the effect and signaling pathway of β‐glucan on mucins MUC4 and MUC5B were investigated in human airway epithelial cells.

Methods

In NCI‐H292 cells and human normal nasal epithelial cells, the effect and signaling pathway of β‐glucan on MUC4 and MUC5B expression were investigated using reverse transcriptase–polymerase chain reaction (RT‐PCR), real‐time PCR, enzyme immunoassay, and immunoblot analysis with specific inhibitors and small interfering RNA (siRNA).

Results

β‐Glucan increased MUC4 and MUC5B expression and activated the phosphorylation of p38 mitogen‐activated protein kinase (MAPK) and nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB). SB203580 (a p38 MAPK inhibitor) and pyrrolidine dithiocarbamate (PDTC; a NF‐κB inhibitor) inhibited β‐glucan–induced MUC4 and MUC5B expression. In addition, siRNA knockdown of p38 MAPK blocked β‐glucan–induced MUC4 and MUC5B mRNA expression and β‐glucan–activated phosphorylation of NF‐κB. Furthermore, Toll‐like receptor 4 (TLR4) mRNA expression was increased by β‐glucan, and siRNA knockdown of TLR4 blocked β‐glucan–induced MUC4 and MUC5B mRNA expression and β‐glucan–activated phosphorylation of p38 MAPK and NF‐κB.

Conclusion

These results demonstrate that in human airway epithelial cells β‐glucan induces MUC4 and MUC5B expression via the TLR4–p38 MAPK–NF‐κB signaling pathway.
D‐Glucosamine in iron‐catalysed cross‐coupling reactions of Grignards with allylic and vinylic bromides: application to the synthesis of a key sitagliptin precursor
Authors: Sova Matej , Frlan Rok , Gobec Stanislav , Stavber Gaj , Časar Zdenko
Published: May 2015

A sustainable D‐glucosamine ligand is successfully introduced into iron‐catalysed CC cross‐coupling reactions for the first time. The Fe(acac)2/D‐glucosamine·HCl/Et3N catalytic system was effective at 5 mol% loading in coupling reactions of Grignard reagents with organic bromides. Moderate to high efficiency was achieved with preserved stereochemistry when allyl (Csp3) or alkenyl (Csp2) bromides were coupled with phenylmagnesium (Csp2) or benzylmagnesium (Csp3) bromides. The catalytic system developed was also successfully applied for the novel and economic preparation of a Michael‐acceptor‐like starting material used in an alternative synthesis of the drug sitagliptin, a known blockbuster for the treatment of type II diabetes mellitus. Copyright © 2015 John Wiley & Sons, Ltd.
Evaluation of curing and thermal behaviors of konjac glucomannan–chitosan–polypeptide adhesive blends
Authors: Shang Jin , Liu Hongling , Qi Chusheng , Guo Kangquan , Tran Van Cuong
Published: May 2015

An environmentally friendly wood adhesive has been achieved through novel blending of konjac glucomannan and chitosan with polypeptide. Tensile tests reveal an optimal curing temperature of 130°C. Both viscoelastic properties of the adhesive blends during curing process, and the structural variation of chemical components induced by curing temperature, were defined by using dynamic rheometry, X‐ray photoelectron spectroscopy, and Fourier transform infrared spectroscopy. Results show both storage and loss modulus increase markedly from 90 to 105°C because of the reactions occurred between konjac glucomannan, chitosan, and polypeptide with formation of amide. Increased polypeptide content not only strengthens intermolecular hydrogen bonds but also enhances covalent reactions occurred between the components. Thermogravimetric and differential scanning calorimetry analyses indicate good miscibility of components in the adhesive blends and improved thermal stability with added polypeptide. Hydrogen bonds between polysaccharides and polypeptide break at 125 ± 10°C. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42202.
Effect of urea and formamide plasticizers on starch/PVA bioblend sheets
Authors: Yan Jiaan , Tian Huafeng , Zhang Yahui , Xiang Aimin
Published: May 2015

The starch/polyvinyl alcohol (PVA) bioblend sheets containing urea and formamide as plasticizers were prepared through melt processing in presence of water. The experiments indicated that urea and formamide plasticizers could form strong hydrogen bonds with starch/PVA molecules. Urea exhibited better plasticizing effect than formamide. Urea also could greatly destroy the crystal structures of PVA component in the blends, leading to the decreased crystallinity of the blends. Formamide was a good solvent for urea and could prevent urea separating from the blends, resulting in the improved stability of plasticizing systems. The blends exhibited good flexibility. Therefore, the incorporation of both urea and formamide into starch/PVA blends could exhibit synergistic effects to ensure the blends with both good plasticizing effect and the stability of the plasticizing systems. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42311.
Thermal, mechanical, and corrosion resistance properties of vinyl ester/clay nanocomposites for the matrix of carbon fiber‐reinforced composites exposed to electron beam
Authors: Razavi Seyed Mohammad , Dehghanpour Negar , Ahmadi Seyed Javad , Rajabi Hamaneh Mahdi
Published: May 2015

Vinyl ester/clay nanocomposites with 1, 3, and 5% nanoclay contents were prepared. X‐ray diffractography patterns and Scanning Electron micrographs showed that nanocomposites with the exfoliated structure were formed. Thermogravimetric analysis, water absorption test, and Tafel polarization method, respectively, revealed the improvements in thermal resistance, water barrier properties, and corrosion resistance properties of the samples with an increase in the amount of the incorporated nanoclay. Tensile tests showed that nanoclay also enhanced the mechanical properties of the polymer, so that the tensile strength of the samples with 5% nanoclay was more than 3 times higher than tensile strength of pure vinyl ester samples. Overall, the best properties were observed for the samples containing 5% nanoclay. Pure vinyl ester and nanocomposite with 5% nanoclay content were exposed to the electron beam radiation and their mechanical properties improved up to 500 kGy irradiation dose. Finally, pure vinyl ester and vinyl ester/nanoclay (5%) matrixes were reinforced with carbon fiber and the effect of electron beam irradiation on their mechanical properties was examined. The tensile strength and the modulus of the samples initially increased after exposure to the radiation doses up to 500 kGy and then a decrease was observed as the irradiation dose rose to 1000 kGy. Moreover, nanoclay moderated the effect of the irradiation. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42393.
Long‐Term Therapy With Omega‐3 Ameliorates Myonecrosis and Benefits Skeletal Muscle Regeneration in Mdx Mice
Authors: Apolinário Leticia Montanholi , De Carvalho Samara Camaçari , Santo Neto Humberto , Marques Maria Julia
Published: May 2015

In Duchenne muscle dystrophy (DMD) and in the mdx mouse model of DMD, a lack of dystrophin leads to myonecrosis and cardiorespiratory failure. Several lines of evidence suggest a detrimental role of the inflammatory process in the dystrophic process. Previously, we demonstrated that short‐term therapy with eicosapentaenoic acid (EPA), at early stages of disease, ameliorated dystrophy progression in the mdx mouse. In the present study, we evaluated the effects of a long‐term therapy with omega‐3 later in dystrophy progression. Three‐month‐old mdx mice received omega‐3 (300 mg/kg) or vehicle by gavage for 5 months. The quadriceps and diaphragm muscles were removed and processed for histopathology and Western blot. Long‐term therapy with omega‐3 increased the regulatory protein MyoD and muscle regeneration and reduced markers of inflammation (TNF‐α and NF‐kB) in both muscles studied. The present study supports the long‐term use of omega‐3 at later stages of dystrophy as a promising option to be investigated in DMD clinical trials. Anat Rec, 298:1589–1596, 2015. © 2015 Wiley Periodicals, Inc.
Carbon‐Centered Radical Addition to C=X Bonds for C−X Bond Formation
Authors: Liu Dong , Liu Chao , Lei Aiwen
Published: May 2015

Among various kinds of radical reactions, the addition of carbon‐centered radicals to unsaturated bonds represents a powerful tool for the construction of different C−C and C−X (X=N, O, S, etc.) bonds, in which typically applied unsaturated bonds include alkenes, alkynes, imines, carbonyls, and even thiocarbonyls. When C=X bonds are utilized as the radical acceptors, reactions usually occur at the carbon position to generate a heteroatom radical, during which C−C coupling products are formed. This reaction mode has dominated this field for several decades. However, there is also another unconventional type of radical addition mode, in which carbon‐centered radicals attack the heteroatom position of C=X bonds to generate carbon radicals, during which selective C−X bond formation is achieved. This reaction mode demonstrates an effective method for the construction of different C−X bonds, such as C−O, C−N, and C−S bonds. This Focus Review gives an overview of recent advances in this unconventional field.
Metathesis of 1‐Butene to Propene over Mo/Al2O3@SBA‐15: Influence of Alumina Introduction Methods on Catalytic Performance
Authors: Zhang Dazhou , Li Xiujie , Liu Shenglin , Zhu Xiangxue , Chen Fucun , Xu Longya
Published: May 2015

A series of Mo‐based catalysts for 1‐butene metathesis to propene were prepared by supporting Mo species on SBA‐15 premodified with alumina. The effects of the method of introduction of the alumina guest to the host SBA‐15 on the location of the Mo species and the corresponding metathesis activity were studied. As revealed by N2 adsorption isotherms and TEM results, well‐dispersed alumina was formed on the pore walls of SBA‐15 if the ammonia/water vapor induced hydrolysis (NIH) method was employed. The Mo species preferentially interacted with alumina instead of SBA‐15, as evidenced by X‐ray photoelectron spectroscopy, time‐of‐flight secondary‐ion mass spectrometry, and IR spectroscopy of adsorbed pyridine. Furthermore, new Brønsted acid sites favorable for the dispersion of the Mo species and low‐temperature metathesis activity were generated as a result of the effective synergy between the alumina and SBA‐15. The Mo/Al2O3@SBA‐15 catalyst prepared by the NIH method showed higher metathesis activity and stability under the conditions of 120 °C, 0.1 MPa, and 1.5 h−1 than catalysts prepared by other methods.
Investigation on the Cyclability of Lithium‐Oxygen Cells in a Confined Potential Window using Cathodes with Pre‐filled Discharge Products
Authors: Geng Dongsheng , Ding Ning , Hor T. S. Andy , Chien Sheau Wei , Liu Zhaolin , Zong Yun
Published: May 2015

With new chemistry and advantageous configuration, the lithium‐oxygen (Li‐O2) battery promises a much higher specific energy than traditional lithium‐ion batteries. The limited understanding on the complicated battery reactions therein, however, has become a major bottleneck of its development for applications requiring a high energy efficiency and long cycle‐life. Herein, in a confined potential window with negligible electrolyte degradation, we studied the rechargeability of Li‐O2 cathodes with pre‐filled well‐defined discharge products of Li2O2, Li2CO3, LiOH, or their combinations. Our results suggest Li2CO3 as the most difficult species to be electrochemically decomposed among the three lithium compounds, whereas the presence of LiOH notably increases the initial charge potential. The clearly visible difference in the charge behavior and cycling stability of these artificially “discharged” electrodes provides a guideline for the development of future high‐performance Li‐O2 batteries.
Efficient and Stable MoS2/CdSe/NiO Photocathode for Photoelectrochemical Hydrogen Generation from Water
Authors: Dong Yuming , Chen Yanmei , Jiang Pingping , Wang Guangli , Wu Xiuming , Wu Ruixian , Zhang Chi
Published: May 2015

A novel CdSe/NiO heteroarchitecture was designed, prepared, and used as a photocathode for hydrogen generation from water. The composite films were structurally, optically, and photoelectrochemically characterized. The deposition of CdSe on the NiO film enhanced light harvesting in the visible‐light region and photoelectrochemical properties. Moreover, the CdSe/NiO photoelectrode showed superior stability both in nitrogen‐saturated and air‐saturated neutral environments. The CdSe/NiO photoelectrode after MoS2 modification retained the stability of the CdSe/NiO electrode and exhibited higher photocatalytic and photoelectrochemical performances than the unmodified CdSe/NiO electrode. In pH 6 buffer solution, an average hydrogen‐evolution rate of 0.52 μmol h−1 cm−2 at −0.131 V (versus reversible hydrogen electrode, RHE) was achieved on a MoS2/CdSe/NiO photocathode, with almost 100 % faradaic efficiency.
The Role of Intentionally Introduced Defects on Electrode Materials for Alkali‐Ion Batteries
Authors: Uchaker Evan , Cao Guozhong
Published: May 2015

Simple defect modification is a powerful means to improve material intercalation capabilities. It has received considerable interest lately as it can directly alter both the chemical and structural characteristics; techniques of note include cationic disordering, amorphization, doping, partial cation reduction, and manipulation of intrinsic defects. Defects can reduce the stress and the electrostatic repulsion between adjacent oxygen layers, which can directly alter the migration energy and diffusion barriers the alkali ion must overcome during intercalation. Complementary to experimental observations, theoretical predictions are paramount to developing a detailed understanding of material‐defect chemistry. This focus review aims to demonstrate that the optimized design of stable intercalation compounds could lead to substantial improvements in energy‐storage applications by overcoming intrinsic limitations.
Analysis of the metabolic profile of parishin by ultra‐performance liquid chromatography/quadrupole‐time of flight mass spectrometry
Authors: Tang Chunlan , Wang Li , Li Jiejiang , Liu Xinxin , Cheng Mengchun , Xiao Hongbin
Published: May 2015

Parishin is a dominant active ingredient originating from Gastrodia elata Blume, and has good neuroprotective effects against brain disorders. In the present study, the metabolic profile of parishin by in vitro and in vivo experiments was investigated using ultra‐high performance liquid chromatography coupled with quadrupole–time of flight mass spectrometry (UHPLC/Q‐TOF MS) combined with an automated MSE technique. By comparison with reference compounds, accurate mass measurement, the characteristic fragmentation patterns of the parent drug parishin and gastrodin and relevant bio‐transformation knowledge, 14 metabolites (seven hydrolyzates and seven derivatives of gastrodin) were detected and identified in rat plasma and urine after intragastric administration of parishin, including processes of hydrolyzation, oxidation, sulfation and glucuronidation. According to the proposed metabolic pathways of parishin, in vitro hydrolytic experiments and metabolic study of gastrodin in rat plasma, it can be inferred that parishin mainly functions as a prodrug and undergoes hydrolysis before being absorbed into the blood. The hydrolyzate, mainly gastrodin, was involved in further metabolism, which was responsible for pharmacological activities of parishin. In conclusion, this work provides valuable information on parishin metabolism using a rapid and reliable UHPLC/Q‐TOF MS method, which could be widely used for the metabolic investigation of natural product. Copyright © 2015 John Wiley & Sons, Ltd.
Simultaneous determination of four secoiridoid and iridoid glycosides in rat plasma by ultra performance liquid chromatography–tandem mass spectrometry and its application to a comparative pharmacokinetic study
Authors: Wu Yun , Ai Yu , Wang Fenrong , Ma Wen , Bian Qiaoxia , Lee David Y.‐W. , Dai Ronghua
Published: May 2015

A simple, reliable and rapid ultra‐performance liquid chromatography–tandem mass spectrometry method was developed and validated for the simultaneous quantification of four secoiridoid (gentiopicroside, swertiamarin, sweroside) and iridoid glycosides (loganic acid), the bio‐active ingredients in rat plasma. After liquid–liquid extraction, chromatographic separation was accomplished on a Shim‐pack XR‐ODS column with a mobile phase consisting of methanol and 0.1% formic acid in water. A triple quadrupole tandem mass spectrometry equipped with an electrospray ionization source was used as detector operating both in positive and negative ionization mode and operated by multiple‐reaction monitoring scanning. The lower limits of quantitation were 0.25–30 ng/mL for all the analytes. Both intra‐day and inter‐day precision and accuracy of analytes were well within acceptance criteria (±15%). The mean extraction recoveries of analytes and internal standard (amygdalin) from rat plasma were all >71.4%. The validated method was successfully applied to a comparative pharmacokinetic study of four analytes in rat plasma between normal and arthritic rats after oral administration of Huo Luo Xiao Ling Dan and Gentiana macrophylla extract, respectively. Results showed significant differences in pharmacokinetic properties of the analytes among the different groups. Copyright © 2015 John Wiley & Sons, Ltd.
Positional Scanning Synthesis of a Peptoid Library Yields New Inducers of Apoptosis that Target Karyopherins and Tubulin
Authors: Vendrell‐Navarro Glòria , Rúa Federico , Bujons Jordi , Brockmeyer Andreas , Janning Petra , Ziegler Slava , Messeguer Angel , Waldmann Herbert
Published: May 2015

We describe the synthesis of a library of 11 638 N‐alkylglycine peptoid trimers in a positional scanning format with adjustment of reaction conditions to account for different reactivities of the monomer building blocks. Evaluation of the library by high‐content phenotypic screening for modulators of the cytoskeleton and mitosis resulted in the identification of two apoptosis‐inducing peptoids, which, despite their structural similarity, target different proteins and cellular mechanisms. Whereas one peptoid binds to karyopherins, which mediate nuclear transport, the other N‐alkylglycine trimer binds tubulin at the vinca alkaloid binding site.
Glucose regulates heat shock factor 1 transcription activity via mTOR pathway in HCC cell lines
Authors: Ma Wanli , Zhang Yaqing , Mu Hongmei , Qing Xiaoming , Li Shulian , Cui Xiukun , Lou Qiang , Ma Yuanfang , Pu Hongmin , Hu Yanzhong
Published: May 2015

HSF1‐mediated heat shock response is activated in most tumors and plays important roles in regulating tumor homeostasis. However, the signals underlying HSF1 activation is still not completely understood. In this paper, we find that glucose, the dominant tumor energy supplement, participates in regulating HSF1's activation in HCC cell lines. The immunoblotting results indicate that the phosphorylation of HSF1/S326, a hallmark of HSF1 activation, varies between the HCC cell lines (e.g., SMMC7721, HapG2, plc/prf5, and Chang‐liver). Glucose, but not 2D‐glucose, can induce the phosphorylation of HSF1 at S326 and upregulate the expression of HSF1's downstream alpha B‐crystallin and Hsp70 as well as the none‐heat shock proteins CSK2 and RBM23 in two tested hepatocellular carcinoma cell lines (prl/prf5 and SMMC7721). Rapamycin, an inhibitor of mTOR, can suppress the glucose‐induced phosphorylation of HSF1/S326 and the expression of alpha B‐crystallin. Knockdown of HSF1 with shRNA enhances the glucose‐depletion‐mediated inhibition of plc/prf5 cell proliferation. Our data reveal that HSF1 can be activated by glucose‐mTOR pathway, providing an alternative pathway for targeting HSF1 in tumor therapy.
The SYNERGY biodegradable polymer everolimus eluting coronary stent: Porcine vascular compatibility and polymer safety study
Authors: Wilson Gregory J. , Marks Angela , Berg Kimberly J. , Eppihimer Michael , Sushkova Natalia , Hawley Steve P. , Robertson Kimberly A. , Knapp David , Pennington Douglas E. , Chen Yen‐Lane , Foss Aaron , Huibregtse Barbara , Dawkins Keith D.
Published: May 2015

Aims

SYNERGY is a novel platinum chromium alloy stent that delivers abluminal everolimus from an ultrathin poly‐lactide‐co‐glycide (PLGA) biodegradable polymer. This study evaluated the in vivo degradation of the polymer coating, everolimus release time course, and vascular compatibility of the SYNERGY stent.

Methods and Results

SYNERGY stents were implanted in arteries of domestic swine. Devices were explanted at predetermined time points (up to 120 days) and the extent of PLGA coating or everolimus remaining on the stents was quantified. Everolimus levels in the arterial tissue were also evaluated. A pathological analysis on coronary arteries of single and overlapping stents was performed at time points between 5 and 270 days. PLGA bioabsorption began immediately after implantation, and drug release was essentially complete by 90 days; PLGA absorption was substantially complete by 120 days (>90% of polymer was absorbed) leaving a bare metal SYNERGY stent. Vascular response was similar among SYNERGY and control stents (bare metal, polymer‐only, and 3× polymer‐only). Mild increases in para‐strut fibrin were seen for SYNERGY at an early time point with no significant differences in all other morphological and morphometric parameters through 270 days or endothelial function (eNOS immunostaining) at 90 or 180 days. Inflammation was predominantly minimal to mild for all device types.

Conclusion

In a swine model, everolimus was released by 90 days and PLGA bioabsorption was complete shortly thereafter. The SYNERGY stent and its biodegradable polymer, even at a 3× safety margin, demonstrated vascular compatibility similar to bare metal stent controls. © 2015 Wiley Periodicals, Inc.
“A bend in time”: Shaping the sheath facilitates left atrial appendage closure
Authors: Gafoor Sameer , Heuer Luisa , Schulz Philipp , Matic Predrag , Franke Jennifer , Bertog Stefan , Reinartz Markus , Vaskelyte Laura , Hofmann Ilona , Sievert Horst
Published: May 2015

Objectives

The purpose of this study is to determine feasibility, safety, and effectiveness of the “shape‐the‐sheath” method in left atrial appendage closure.

Background

LAA occlusion is often a difficult procedure, due to not just the learning curve but also the three‐dimensional variable nature of the left atrial appendage. Multiple sheaths have been created for various takeoffs. The purpose of this article is to show the feasibility of the “shape‐the‐sheath” method in left atrial appendage closure.

Methods

Ten consecutive patients undergoing LAA occlusion without the “shape‐the‐sheath” method were compared to 10 consecutive patients undergoing LAA occlusion with the “shape‐the‐sheath” method using the Amplatzer Cardiac Plug (ACP) system and the Amplatzer TorqVue 45 × 45 sheath.

Results

The “shape‐the‐sheath” method resulted in significant decreases in fluoroscopy time (7.2 ± 3.0 min vs. 13.7 ± 6.7 min, P < 0.05), number of partial recaptures (0% vs. 50%, P < 0.05), with a trend toward decrease in the number of complete recaptures (0 vs. 40%, P = 0.09) compared to conventional sheath use.

Conclusions

Shaping‐the‐sheath is a simple, elegant way to help conform delivery systems to better access the LAA and ensure stable position. Further experience with this procedure optimization step is warranted. © 2015 Wiley Periodicals, Inc.
Guidewire‐Induced coronary perforation successfully treated with subcutaneous fat embolisation: A simple technique available to all
Authors: George Sudhakar , Cotton James , Wrigley Ben
Published: May 2015

A 62‐year‐old man presented with an anterior ST elevation myocardial infarction and underwent primary percutaneous coronary intervention to an occluded diagonal artery. Following stenting, a type III distal guidewire‐induced coronary perforation of the diagonal branch was recognized with extravasation of contrast into the pericardial space. Prolonged balloon inflations proximal to the site of the perforation were unsuccessful. Subcutaneous fat was therefore harvested from the patients upper thigh under local anesthetic and embolized through an Export catheter into the distal diagonal vessel, resulting in the immediate cessation of leak through the site of perforation. We discuss the technical aspects of this technique as well as alternative methods of distal embolization and the potential complications that must be considered. © 2015 Wiley Periodicals, Inc.
A pathway to earlier discharge following TAVI: Assessment of safety and resource utilization
Authors: Noad Rebecca L. , Johnston Nicola , McKinley Andrew , Dougherty Mark , Nzewi O.C. , Jeganathan Reuben , Manoharan Ganesh , Spence Mark S.
Published: May 2015

Introduction

There is considerable variability within the population of patients treated with transcatheter aortic valve implantation (TAVI), the procedural approach and time to discharge. In Belfast, from the commencement of our program, our approach has been to perform TAVI by the least invasive approach, where feasible, utilizing a percutaneous transfemoral route and local anesthetic. By analyzing our Belfast TAVI database we identified factors that predicted shorter admission times without impacting adversely on patient safety. Following this, we developed an early discharge pathway. The aim of this current study was to perform a prospective analysis of outcomes in our unit since implementation of this pathway assessing discharge time, mortality, serious adverse events, readmission, and resource implications for patients according to time to discharge.

Methods

Consecutive patients who underwent TAVI and were successfully discharged from 2013 to 2014 over a 14 month period were included, and analyzed according to time to discharge. Baseline and procedural characteristics, mortality, serious adverse events, readmission, and cost were assessed.

Results

In total 120 patients were included, 26 (21.7%) were discharged the same/next day, 39 (32.5%) early (>1–4 days), and 55 (45.8%) discharged in the late group. There was no significant difference in baseline or preprocedural characteristics. The incidence of complications was low, and there was no difference in 30‐day mortality (P = 0.167) or readmission rates between groups (P = 0.952). Resource analysis revealed the late discharge group cost £3,091.6 more per patient per TAVI than same/next day discharge group.

Conclusion

Same/next day discharge can be performed safely in appropriately selected patients. Although this will be achieved in a minority of patients (21.7% in this study using an early discharge pathway) it has potential for resource and cost savings. © 2015 Wiley Periodicals, Inc.
Comparison of radiation dose between different fluoroscopy systems in the modern catheterization laboratory: Results from bench testing using an anthropomorphic phantom
Authors: Christopoulos Georgios , Christakopoulos Georgios E. , Rangan Bavana V. , Layne Ronald , Grabarkewitz Rebecca , Haagen Donald , Latif Faisal , Abu‐Fadel Mazen , Banerjee Subhash , Brilakis Emmanouil S.
Published: May 2015

Background

Variations in radiation dose between various X‐ray systems have received limited study.

Objective

We examined the impact of X‐ray system type on patient radiation dose during cardiac catheterization.

Methods

An anthropomorphic phantom was used in a series of standardized experiments that involved 15 sec of continuous cineangiography in 7 projections. Three to seven experiments were performed in four commonly used X‐ray systems: Innova IGS (GE Healthcare), Integris Allura FD20 (Philips), Allura Clarity (Philips), and Artis one (Siemens). Phantom radiation dose was measured with a dedicated X‐ray dosimetry system (Gafchromic radiology film and Film QA XR software, Ashland) that was precalibrated at 0, 1, 2, 3, and 4 Gray, and with the X‐ray system built‐in functions.

Results

Radiation dose was lowest with the Allura Clarity system [average film dose 4.2 ± 0.1 cGray, peak film dose 18.3 ± 1.6 cGray, Air Kerma (AK) dose 0.310 ± 0.002 Gray, Dose Area Product (DAP) dose 23.72 ± 0.84 Gray*cm2], intermediate with the Integris Allura FD20 (average film dose 4.4 ± 1.1 cGray, peak film dose 29.4 ± 15.5 cGray, AK 0.482 ± 0.189 Gray, DAP 45.18 ± 21.90 Gray*cm2), and highest with the Artis one system (average film dose 7.4 ± 0.8 cGray, peak film dose 66.9 ± 0.09 cGray, AK 0.746 ± 0.085 Gray, DAP 75.93 ± 9.11 Gray*cm2) and the Innova IGS system (average film dose 7.2 ± 1.0 cGray, peak film dose 49.3 ± 28.9 cGray, AK 0.874 ± 0.340 Gray, DAP 92.28 ± 14.73 Gray*cm2; P = 0.011 for average film dose, P = 0.019 for maximum film dose, P = 0.033 for AK, and P = 0.008 for DAP).

Conclusions

The X‐ray system type has significant impact on patient radiation dose during cardiac catheterization. © 2015 Wiley Periodicals, Inc.
Acquired aortic atresia: Catheter therapy using covered stents
Authors: Momenah Tarek S. , Khan Muhammad A. , Qureshi Shakeel , Hijazi Ziyad M.
Published: May 2015

Introduction

To maintain aortic continuity, aortic arch interruption is usually treated surgically. We present our experience of aortic arch reconstruction using percutaneous implantation of covered stents and mid‐term follow‐up.

Objective

To describe the feasibility, safety, and effectiveness using percutaneous placement of covered stents for functional aortic atresia and mid‐term follow‐up.

Methods

Nine patients (7 males), mean age of 30.8 ±16.2 years (range 13–58 years) and mean body weight of 65.7± 14.9 kg (range 52–95 kg), were investigated for systemic hypertension and found to have functional aortic interruption. All were treated with percutaneous perforation, combined with balloon dilation and implantation of covered stents. After stent implantation, control angiograms were performed.

Results

All the patients had functional aortic interruption and continuity was established by perforating the atretic segment with trans‐septal Brockenbrough needle or the stiff end of a guide wire. A covered Cheatham‐Platinum CP stent was used to establish the luminal continuity of the aortic arch. Angiograms after stent deployment showed good forward flow through the stent and hemodynamic assessment revealed minimal gradients across the stent. The mean invasive descending aortic systolic blood pressure before stenting was 86.6 ± 14.3 mm Hg, which increased to 116.5 ± 16.3 mm Hg, after stenting (P = 0.004). The mean invasive descending aortic diastolic blood pressure before stenting was 63.6 ± 8.1 mm Hg, which increased to 79.7 ± 13.3 mm Hg after stenting (P = 0.002).

Conclusion

Percutaneous treatment of functional aortic atresia with covered stents is feasible, safe, and effective alternative to surgery with excellent short‐ and mid‐term results. © 2015 Wiley Periodicals, Inc.
Impact of ultra‐long second‐generation drug‐eluting stent implantation
Authors: Honda Yohsuke , Muramatsu Toshiya , Ito Yoshiaki , Sakai Tsuyoshi , Hirano Keisuke , Yamawaki Masahiro , Araki Motoharu , Kobayashi Norihiro , Takimura Hideyuki , Sakamoto Yasunari , Mouri Shinsuke , Tsutumi Masakazu , Takama Takuro , Takafuji Hiroya , Tokuda Takahiro , Makino Kenji
Published: May 2015

Objectives

This study investigated the safety and prognosis of ultra‐long second DES (UL‐2nd DES) implantation in real‐world practice.

Background

Long stenting is a widely known predictor of stent thrombosis (ST) or target lesion revascularization (TLR) in first‐generation drug‐eluting stents (DES).

Methods

Participants were 1,669 patients (2,763 lesions) who had undergone successful second DES implantation; they were assigned to one of three groups: ultra‐long 2nd DES (UL‐DES; >50 mm, 166 patients, 259 lesions), long second DES (L‐DES; 20–50 mm, 758 patients, 1,212 lesions), or short second DES (S‐DES; <20 mm, 745 patients, 1,292 lesions). The primary endpoint was TLR, and secondary endpoints were ST, cardiac death, and major adverse cardiac events (MACE; composite of TLR, ST and cardiac death). A Cox proportional hazards model was used to identify independent predictors of TLR.

Results

Patient characteristics including dual antiplatelet therapy duration were similar across groups. Follow‐up data were obtained from hospital charts, by contacting patients. Target lesion characteristics in the UL‐DES group showed higher right coronary artery and chronic total occlusion lesion rates. TLR rates (23.1 ± 13.2 months) were significantly higher in the UL‐DES group relative to other groups during follow up (P < 0.001). TLR rate was similar between S‐DES and L‐DES (P = 0.30). The incidence of ST was similar across groups (P = 0.40). MACE was significantly higher in the UL‐DES group relative to other groups due to higher TLR rates (P = 0.01). In a Cox proportional hazard model, hemodialysis (RR: 2.53, 95% CI: 1.69–3.67, P < 0.001) and total stent length of >50 mm (RR: 1.67, 95% CI: 1.07–2.55, P = 0.02) were independent predictors of TLR.

Conclusions

Ultra‐long DES implantation was associated with higher TLR rates but did not increase ST, while long DES implantation up to 50 mm was safe and acceptable. © 2015 Wiley Periodicals, Inc.
Vascular complications in steroid treated patients undergoing transfemoral aortic valve implantation
Authors: Fink Noam , Segev Amit , Barbash Israel , Bogdan Andrada , Hamdan Ashraf , Mazin Israel , Maor Elad , Hay Ilan , Guetta Victor , Fefer Paul
Published: May 2015

Objective

To assess the rate of Vascular complications in steroid treated patients undergoing transfemoral aortic valve implantation (TAVI).

Background

Steroid therapy has been associated with increased post‐surgical bleeding. Vascular complications are a major concern in patients undergoing TAVI. However, the effect of corticosteroids on vascular complications has not been assessed in these patients.

Methods

We conducted a retrospective analysis of 220 consecutive patients undergoing transfemoral TAVI at our institute between 2009 and 2013. Patients who were on steroids at the time of the procedure (n = 25) were compared with those who were not (n = 195).

Results

Baseline characteristics between groups were similar except for greater incidence of chronic renal failure (52 vs. 25%, P = 0.05) and lower left ventricular ejection fraction (50.3 vs. 55.8%, P = 0.037) in the steroid group. The rate of procedural success and nonvascular complication were similar in both groups with the exception of more temporary AV block in the steroid group (24 vs. 8%, P = 0.016). Patients treated with steroids had significantly more minor vascular complication (44 vs. 23%, P = 0.024), and significantly more femoral artery stenosis (16 vs. 5%, P = 0.036), occlusion (8 vs. 1%, P = 0.014), need for femoral artery percutaneous transluminal angioplasty (PTA) (32 vs. 12%, P = 0.009), and femoral artery PTA or stenting (32% vs. 15%, P = 0.031). On multivariate analysis steroid treatment was the only predictor of minor vascular complications (RR=2.65, 95% CI 1.04‐6.8, P = 0.042).

Conclusions

Concurrent corticosteroid treatment is associated with a higher rate of minor vascular complication following transfemoral TAVI. Operators should be aware of this risk when assessing patients for the procedure. © 2015 Wiley Periodicals, Inc.
Primary afferent neurons containing calcitonin gene‐related peptide but not substance P in forepaw skin, dorsal root ganglia, and spinal cord of mice
Authors: Kestell Garreth R. , Anderson Rebecca L. , Clarke Jennifer N. , Haberberger Rainer V. , Gibbins Ian L.
Published: May 2015

In mice dorsal root ganglia (DRG), some neurons express calcitonin gene–related peptide (CGRP) without substance P (SP; CGRP+SP‐). The projections and functions of these neurons are unknown. Therefore, we combined in vitro axonal tracing with multiple‐labeling immunohistochemistry to neurochemically define these neurons and characterize their peripheral and central projections. Cervical spinal cord, DRG, and forepaw skin were removed from C57Bl/6 mice and multiple‐labeled for CGRP, SP, and either marker for the sensory neuron subpopulations transient receptor potential vanilloid type 1 (TRPV1), neurofilament 200 (NF200), or vesicular glutamate transporter 2 (VGluT1). To determine central projections of CGRP+SP‐ neurons, Neurobiotin (NB) was applied to the C7 ventral ramus and visualized in DRG and spinal cord sections colabeled for CGRP and SP. Half (50%) of the CGRP‐immunoreactive DRG neurons lacked detectable SP and had a mean soma size of 473 ± 14 μm2 (n = 5); 89% of the CGRP+SP‐ neurons expressed NF200 (n = 5), but only 32% expressed TRPV1 (n = 5). Cutaneous CGRP+SP‐ fibers were numerous within dermal papillae and around hair shafts (n = 4). CGRP+SP‐ boutons were prevalent in lateral lamina I and in lamina IV/V of the dorsal horn (n = 5). NB predominantly labeled fibers penetrating lamina IV/V, 6 ± 3% contained CGRP (n = 5), and 21 ± 2% contained VGluT1 (n = 3). CGRP+SP‐ afferent neurons are likely to be non‐nociceptive. Their soma size, neurochemical profile, and peripheral and central targets suggest that CGRP+SP‐ neurons are polymodal mechanoceptors. J. Comp. Neurol. 523:2555–2569, 2015. © 2015 Wiley Periodicals, Inc.