bluuebunny/crossref_metadata_2025 huggingface dataset:
Nacrelike Nanocomposite Films from Fluorescent Hyperbranched Poly(amido amine)s and Clay Nanosheets
Authors: Hao Wentao , Ding Songyan , Zhang Liang , Liu Wei , Yang Wen
Published: December 2013

Inspired by the hierarchical structure of nacre, lots of functional nanocomposite films have been fabricated through finely tuning the composition and structure. To broaden their application in biological and biomedical research, it is highly demanded to develop a new strategy to fabricate nanocomposite films that are both biocompatible and functional. Herein, hyperbranched poly(amido amine)s (HPAMAMs) have been assembled with clay nanosheets. The obtained nanocomposite films show good mechanical performance and fluorescence properties. Analysis of the structure of the nanocomposite films indicates that the HPAMAMs and the clay nanosheets are stacked together in an orderly manner. The clay nanosheets align in the direction parallel to the film surface. Because of the inherent biocompatibility and autofluorescence property of the HPAMAMs, such composite films are thought to be very promising in applications requiring biocompatibility, fluorescence, and good mechanical performance. The method should provide a new route to the fabrication of functional nacrelike composite materials.
Access to Ultra‐High‐Molecular Weight Poly(ethylene) and Activity Boost in the Presence of Cyclopentene With Group 4 Bis‐Amido Complexes
Authors: Narayana Gurram Venkata , Xu Guangjuan , Wang Dongren , Frey Wolfgang , Buchmeiser Michael R.
Published: December 2013

ZrIV complexes of the type [Me2Si{(NR)(6‐{2‐(diethylboryl)phenyl}pyridyl‐2‐yl‐N)}ZrCl2⋅thf] (R=tBu (4), adamantyl (7 a); thf=tetrahydrofuran), [Me2Si{(NAd)(6‐{2‐(diphenylboryl)phenyl}pyridyl‐2‐yl‐N)}ZrCl2] (Ad=adamantyl (7 b)), the nonbridged half‐titanocene complexes of the type [(N‐{6‐(2‐diethylborylphenyl)pyrid‐2‐yl}‐NR)Cp′TiCl2] (R=Me, Cp′=C5H5 (12), Cp′=C5Me5 (13)), and the titanium(IV)‐based metallocene‐type complex [bis{N‐(6‐{2‐(diethylboryl)phenyl}pyrid‐2‐yl)NMe}TiCl2] (14) have been synthesized. The structures of complexes 7 b, 12, and 13 were determined by single‐crystal X‐ray diffraction analysis. In solution, complex 4 slowly rearranges to [Me2Si{(N‐tBu)(6‐{2‐(diethylboryl)phenyl}pyridyl‐2‐yl‐N)}2Zr] (4 a), the structure of which was unambiguously confirmed by single‐crystal X‐ray crystallography. Similarly, reaction of HfCl4 with Me2Si({RNLi}{6‐[2‐(diethylboryl)phenyl]pyridyl‐2‐ylNLi}) yielded the corresponding HfIV complexes [Me2Si{(NR)(6‐{2‐(diethylboryl)phenyl}pyridyl‐2‐ylN)}2Hf] (R=tBu (8) and Ad (9)). Upon activation of these complexes with methylalumoxane (MAO), complexes 4, 7 a, 7 b, and 12–14 showed activities up to 750 kg of polyethylene (PE)/molcat. bar h in the homopolymerization of ethylene (E), producing mainly linear PE (high‐density PE, HDPE) with molecular weights in the range of 1 800 000<Mn<4×106 g mol−1. In the copolymerization of E with cyclopentene (CPE), the polymerization activities of complexes 4, 7 a, and 7 b can be enhanced by a factor of 140 up to 7500 kg PE/molcat. bar h, which produced PE‐co‐poly(CPE) containing 3.5 mol % of CPE. This dramatic increase in polymerization activity for E in the presence of CPE can be attributed to an involvement of CPE in the polymerization process rather than to solvent polarity.
Gold Nanoparticles Embedded within Mesoporous Cobalt Oxide Enhance Electrochemical Oxygen Evolution
Authors: Lu Xunyu , Ng Yun Hau , Zhao Chuan
Published: December 2013

Gold nanoparticles incorporated in mesoporous cobalt oxides (Au/mCo3O4) are fabricated by a nanocasting method using porous silica as the hard template. The Au/mCo3O4 material exhibits enhanced catalytic activity towards water oxidation compared to bulk mCo3O4 in both alkaline and neutral solutions. The superior catalytic performance is ascribed to the synergistic effect of electronegative metal gold, which facilitates the generation of active CoIV sites, as well as the large specific surface area and the preferential exposure of catalytic active crystalline lattice.
Cannabis use: a perspective in relation to the proposed UK drug‐driving legislation
Authors: Wolff Kim , Johnston Atholl
Published: December 2013

With regard to THC (Δ9‐tetrahydrocannabinol), the main psychoactive constituent identified in the plant Cannabis sativa L, several facts are indisputable. Cannabis remains the most commonly used drug in the UK among those who reported driving under the influence of illegal drugs in the previous 12 months. There is a significant dose‐related decrement in driving performance following cannabis use; raised blood THC concentrations are significantly associated with increased traffic crash and death risk. When cannabis and alcohol are detected together, there is a greater risk to road safety than when either drug is used alone. Patterns of use are important when interpreting blood concentration data: Smoking infrequently a single cannabis cigarette leads to peak plasma THC concentrations (21‐267 µg/L) causing acute intoxication. In habitual, daily users, plasma THC concentrations range from 1.0 to 11.0 µg/L and are maintained by sequestration of the drug from the tissues. These facts undoubtedly make setting thresholds for drug‐driving legislation difficult but there is clearly a case for cannabis. Determining minimum blood THC concentrations at which a driver becomes sufficiently impaired to be unable to safely drive a vehicle is of particular concern given the increasing medicinal use of the drug. Internationally legislation for driving under the influence of drugs (DUID) is based on either a proof of impairment or a per se approach. For the latter this can be either zero‐tolerance or based on concentration limits such as those used for alcohol. The different approaches are considered against current scientific evidence. Copyright © 2013 John Wiley & Sons, Ltd.
Ecohydrology of the inland river basins in the Northwestern Arid Region of China
Authors: Shen Yanjun , Chen Yaning , Liu Changming , Smettem Keith
Published: December 2013

The arid region in northwestern China covers 2·02 million square kilometres and is one of the most arid regions in the world. Positioned at the central part of the Eurasian Continent, this region experiences little influence from the Eastern and Southern Asian Monsoons and precipitation is formed mostly from westerly vapour. With a hyper arid climate, the annual precipitation in this region ranges from less than 20 mm at the oasis area to around 600 mm in the mountain regions, whereas potential evaporation can amount to 2000–3000 mm per annum. It is reported that strong evapotranspiration characterizes and dominates the water cycle in the arid basins. Nearly all the water resources of the oasis, where the human society exists, come from the mountain areas as river discharge from glacier/snow melting water, rainfall and subsurface flow from bedrock cracks. As a result, the hydrographs of the arid basins are affected by climate change via changes in precipitation partitioning (the ratio of rainfall and snowfall) and changes to seasonal distributions of precipitation and air temperature. These changes in turn directly affect the water yield and the vegetation response. Copyright © 2013 John Wiley & Sons, Ltd.
Groundwater depth and topography correlate with vegetation structure of an upland peat swamp, Budderoo Plateau, NSW, Australia
Authors: Hose Grant C. , Bailey Jane , Stumpp Christine , Fryirs Kirstie
Published: December 2013

Swamps, bogs and fens are diverse wetland ecosystems found worldwide. Within each region, different ecological processes and species dominate them, yet water levels and saturation of sediments appear key to the maintenance of vegetation and the ecosystem as a whole. Consequently, understanding how vegetation responds to water levels in these ecosystems is critical to their future management. This paper describes the floristic patterns observed in an upland swamp on the Budderoo Plateau, Southern Highlands, NSW, and relates the distribution of the vegetation communities to groundwater depth, soil type and site attributes. Three distinct vegetation assemblages were identified associated with (1) the main swamp axis, (2) the swamp margin and (3) the adjacent hillslopes. Elevation above the central swamp axis was the variable most strongly related to vegetation structure. Relative changes in elevation create a drainage gradient that allows higher elevation areas (hillslope and swamp marginal zones) to drain more readily than areas in the main swamp axis. Variation in vegetation was also related to median groundwater depth. Finally, soil organic matter content was a contributing factor with the swamp axis and marginal zones mostly having fibric, highly organic soils in contrast to the sandy, loamy soils on the hillslopes. Copyright © 2014 John Wiley & Sons, Ltd.
Ytterbium(III)‐Catalyzed Addition Reaction of Alkynyltrifluoroborate Salts to α‐Imino Esters: Efficient Synthesis of β‐Unsaturated α‐Amino Esters
Authors: Stefani Hélio A. , Manarin Flávia , Khan Amna N. , Vasconcelos Stanley N. S.
Published: December 2013

We describe the development of a mild and efficient method for the preparation of β‐unsaturated α‐amino esters through the ytterbium triflate catalyzed addition of potassium alkynyltrifluoroborate salts to imino esters. The synthetic viability of this protocol was supported by its high yields, short reaction times, and efficiency with regard to the scope of the substrates.
Ligand‐Free Copper‐Catalyzed One‐Pot Synthesis of Indole‐2‐carboxylic Esters
Authors: Zhu Zhiqiang , Yuan Jiangjun , Zhou Yirong , Qin Yang , Xu Jingshi , Peng Yiyuan
Published: December 2013

A simple, efficient, and facile synthetic route for the preparation of indole‐2‐carboxylic esters was described. The cascade reactions of 2‐bromobenzaldehyde and glycine ester hydrochloride were promoted by Cu2O and a base to provide the corresponding products in good yields. Commercially available, inexpensive substrates and reagents were employed under mild reaction conditions in this one‐pot operation, which is complementary to existing methods for access to 2‐substituted indoles.
Sourcing Olive Jars Using U‐Pb Ages of Detrital Zircons: A Study of 16th Century Olive Jars Recovered from the Solomon Islands
Authors: Kelloway Sarah J. , Craven Steven , Pecha Mark , Dickinson William R. , Gibbs Martin , Ferguson Timothy , Glascock Michael D.
Published: December 2013

We present U‐Pb ages of zircons extracted from olive jars recovered from two sites associated with Alvaro de Mendaña y Neyra's colonising expedition to the Solomon Islands, c. 1595–1596 A.D. The olive jars were previously associated with Panamanian and Peruvian origins based on petrological and geochemical studies. To further define provenance, 143 zircons were extracted from five olive jar sherds, analyzed and dated. The resultant U‐Pb ages range from the Archaean to the Cenozoic (2977.2 ± 29.0–3.2 ± 4.0 Ma), but the dominance of Cretaceous and Palaeogene ages (∼ 90% of the total age population is between ∼ 145 and 23 Ma) supports a Peruvian origin based on comparative geology, with the Coastal Batholith of Peru a prime candidate area of ceramic production. These results are significant for the characterization of 16th Century Peruvian‐made pottery and our understanding of its production and trade.
Cycloadducts of 1‐Alkyl‐1,2‐diphospholes with N‐Phenylmaleimide: Synthesis, Structure, Oxidation, and Thionation Reactions
Authors: Zagidullin Almaz , Miluykov Vasili , Sinyashin Oleg , Lönnecke Peter , Hey‐Hawkins Evamarie
Published: December 2013

The [4+2] cycloaddition reaction of 1‐alkyl‐1,2‐diphospholes (1) with N‐phenylmaleimide proceeds at 25°С in toluene to give 1,7‐diphosphanorbornenes (2) as anti‐endo isomer only. Oxidation of 2 with air at room temperature or thionation with excess of sulfur at 80°С results in the formation of mixed valent PIII, PV 7‐oxo(thia)‐1,7‐diphosphanorbornenes (3, 4) in high yield. The polycyclic compounds 3 and 4 are air stable and have small sums of valence angles at the phosphorus atoms.
MEASURING THE DISPLACEMENT AND REPLACEMENT OF GOVERNMENT HEALTH EXPENDITURE
Authors: Dieleman Joseph L. , Hanlon Michael
Published: December 2013

Research assessing the relationship between government health expenditure and development assistance for health channeled to governments (DAHG) has not considered that this relationship may depend on whether DAHG is increasing or decreasing. We explore this issue using general method of moments estimation and a panel of financial flows data spanning 119 countries and 16 years. Our primary concern is how DAHG affects government health expenditure as source (GHES). We disaggregate the average effect of DAHG and separately identify the effects of increases versus decreases in DAHG. We find that a $1 year‐over‐year increase in DAHG leads to a $0.62 (90% confidence interval (CI): 0.15, 1.09) decrease in GHES, whereas a $1 year‐over‐year decrease in DAHG does not have an effect on GHES that is statistically different from zero (CI: −0.67, 1.17). Simulation shows that the displacement of GHES between 1995 and 2010 reduced total government health expenditure by $152.8 billion (CI: 46.9, 277.6). Moreover, the irregular disbursement of DAHG reduced total government expenditure by $96.9 billion (CI: 0.5, 212.4). Thus, this research shows that health aid is fungible and highlights the cost of displacement and erratic aid disbursement. © 2013 The Authors. Health Economics published by John Wiley & Sons, Ltd.
Stem Cell Gene SALL4 in Aggressive Hepatocellular Carcinoma: A Cancer Stem Cell-Specific Target?
Authors: Yakaboski Elizabeth , Jares Alexander , Ma Yupo
Published: December 2013

Abstract

Background:

Hepatocellular carcinoma is the third leading cause of cancer-related deaths worldwide. In the heterogeneous group of hepatocellular carcinomas, those with characteristics of embryonic stem-cell and progenitor-cell gene expression are associated with the worst prognosis. The oncofetal gene

SALL4,

a marker of a subtype of hepatocellular carcinoma with progenitor-like features, is associated with a poor prognosis and is a potential target for treatment.

Methods:

We screened specimens obtained from patients with primary hepatocellular carcinoma for the expression of SALL4 and carried out a clinicopathological analysis. Loss-of-function studies were then performed to evaluate the role of SALL4 in hepatocarcinogenesis and its potential as a molecular target for therapy. To assess the therapeutic effects of a peptide that targets SALL4, we used in vitro functional and in vivo xenograft assays.

Results:

SALL4 is an oncofetal protein that is expressed in the human fetal liver and silenced in the adult liver, but it is reexpressed in a subgroup of patients who have hepatocellular carcinoma and an unfavorable prognosis. Gene-expression analysis showed the enrichment of progenitor-like gene signatures with overexpression of proliferative and metastatic genes in

SALL4-positive

hepatocellular carcinomas. Loss-of-function studies confirmed the critical role of SALL4 in cell survival and tumorigenicity. Blocking SALL4-corepressor interactions released suppression of PTEN (the phosphatase and tensin homologue protein) and inhibited tumor formation in xenograft models in vivo.

Conclusions:

SALL4 is a marker for a progenitor subclass of hepatocellular carcinoma with an aggressive phenotype. The absence of SALL4 expression in the healthy adult liver enhances the potential of SALL4 as a treatment target in hepatocellular carcinoma.
Ergostane Steroids from Dysoxylum lukii
Authors: Hu Jiang , Song Yan , Shi Xiao‐Dong , Mao Xia , Chen Jian‐Gang , Zhu Lei
Published: December 2013

Phytochemical investigation of the 70% EtOH extract from the stem bark of Dysoxylum lukii led to the isolation of three new ergostane steroids, (3β)‐3,20‐dihydroxyergosta‐5,24(28)‐dien‐7‐one (1), (3β,4β,7α)‐ergosta‐5,24(28)‐diene‐3,4,7‐triol (2), and (3β,7α)‐3,20‐dihydroxyergosta‐5,24(28)‐dien‐7‐yl acetate (3), together with the known compound (3β,4β)‐ergosta‐5,24(28)‐diene‐3,4,20‐triol (4). Their structures were elucidated on the basis of extensive 1D‐ and 2D‐NMR (COSY, HMQC, HMBC, and NOESY) analyses.
Concise Stereoselective Total Synthesis of Leiocarpin C
Authors: Chandra Rao Dasireddi , Shekhar Vanam , Kumar Reddy Dorigondla , Chinnababu Baggu , Venkateswarlu Yenamandra
Published: December 2013

A simple and highly concise strategy has been developed for the stereoselective total synthesis of leiocarpin C starting from commercially available mandelic ester. The strategy utilizes the OsO4‐catalyzed cis‐hydroxylation and selective reduction with K‐Selectride as key steps.
Ultrasound‐Assisted Synthesis of Highly Functionalized Cyclopentadienes via an Isocyanide‐Based Three‐Component Reaction
Authors: Emtiazi Hamideh , Ali Amrollahi Mohammad
Published: December 2013

This report provides a description of an efficient and simple procedure for the synthesis of substituted cyclopentadienes via a one‐pot three‐component reaction of cyclohexyl isocyanide, diethyl acetylenedicarboxylate and (arylmethylidene)malononitriles in H2O under ultrasonic irradiation. The remarkable advantages are the simplicity of the experimental procedures, high yields, short reaction times, and avoidance of organic solvents.
A Copper‐Catalyzed Multicomponent Reaction and ‘Click Strategy’ for the Stereoselective Synthesis of a New Series of Oxazolone Peptidomimetics withα‐Acylamino Amide andβ‐Amido Ketone Structures
Authors: Balan Biny , Bahulayan Damodaran
Published: December 2013

A novel ‘click ligation’ strategy for the stereoselective synthesis of a medium‐size library of structurally complex and functionally diverse oxazolone peptidomimetics, which containα‐acylamino carboxamide orβ‐amido ketone residues, is presented. Most of these molecules have lipophilicity constant values (logP) in the qualifying range for cell permeability, and that indicates the possibilities of these new molecules to be used in the search for potential inhibitors for a broad spectrum of enzymes.
Stereoselective Synthesis of (Z)‐ and (E)‐Allyl Aryl Sulfides and Selenides from BaylisHillman Acetates under Neutral Conditions Using β‐Cyclodextrin in Water
Authors: Karnakar Konkala , Ramesh Katla , Narayana Murthy Sabbavarapu , Venkata Durga Nageswar Yadavalli
Published: December 2013

The first example of the stereoselective synthesis of (Z)‐ and (E)‐allyl aryl sulfides and selenides from BaylisHillman acetates under neutral conditions in H2O by supramolecular catalysis involving β‐cyclodextrin is reported. β‐Cyclodextrin can be recovered and reused. The reaction is very efficient in providing allyl aryl sulfides and selenides in good‐to‐excellent yields with clean reaction profiles under mild reaction conditions.
Synthesis of 5‐Aryl‐3‐(methylsulfanyl)‐1H‐pyrazoles via Three‐Component Reaction of 1,1‐Bis(methylsulfanyl)‐2‐nitroethene, Aromatic Aldehydes, and Hydrazine
Authors: Alizadeh Abdolali , Reza Esmaili zand Hamid , Saberi Vahid , Mokhtari Javad
Published: December 2013

An efficient approach for the preparation of functionalized 5‐aryl‐3‐(methylsulfanyl)‐1H‐pyrazoles 2 is described. This three‐component reaction between benzaldehydes 1, NH2NH2⋅H2O, and 1,1‐bis(methylsulfanyl)‐2‐nitroethene proceeds in EtOH under reflux conditions in good‐to‐excellent yields. The structures of 2 were corroborated spectroscopically (IR, 1H‐ and 13C‐NMR, and EI‐MS). A plausible mechanism for this type of reaction is proposed (Scheme 2).
Alkaloids from Ochrosia borbonica
Authors: Zhang Bing‐Jie , Yan Ju‐Ming , Wu Zi‐Kun , Liu Ya‐Ping , Bao Mei‐Fen , Cheng Gui‐Guang , Luo Xiao‐Dong , Cai Xiang‐Hai , Li Yan
Published: December 2013

Ten new monoterpenoid indole alkaloids, ochroborines A and B (1 and 2, resp.), 10‐hydroxyisovallesiachotamine (3), 10‐hydroxyisositsirikine (4), 10,11‐dimethoxysitsirikine (5), 10‐methoxyapoyohimbine (6), 10‐hydroxyakuammidine (7), akuammidine 17‐O‐β‐D‐glucoside (8), 15α‐hydroxyapparicine (9), and 15α‐hydroxy‐10‐methoxyapparicine (10), and 24 known alkaloids were isolated from leaves and twigs of Ochrosia borbonica J. F.Gmel. These structures were elucidated based on 1D‐ and 2D‐NMR, FT‐IR, UV, and MS data. 10‐Hydroxyisovallesiachotamine (3), ellipticine, and 10‐methoxyellipticine showed cytotoxic activities against five human cancer cell lines.
Two New Trijugin‐Type Limonoids from Cipadessa cinerascens
Authors: Zhang Zhi‐Guo , Cheng Yun‐Tao , Hu Gui‐Lin , Li Guo‐Neng
Published: December 2013

Two new trijugin‐type limonoids, cipatrijugins G and H (1 and 2, resp.) along with four known limonoids, were isolated from the leaves of Cipadessa cinerascens. All structures were elucidated on the basis of spectroscopic analyses, including IR, 1D‐ and 2D‐NMR, and ESI‐MS and HR‐ESI‐MS techniques.
Two New Rosane‐Type Diterpenoids from Euphorbia ebracteolataHayata
Authors: Mu Shu‐Zhen , Jiang Chun‐Rong , Huang Tao , Hao Xiao‐Jiang
Published: December 2013

Two new diterpeniods, euphebracteolatins A and B (1 and 2, resp.) were isolated from Euphorbia ebracteolata Hayata, along with two known ones (3R)‐ent‐rosa‐1(10),15‐dien‐3α‐ol (3) and yuexiandajisu D (4). The structures were established by extensive spectroscopic analyses and comparison with literature data.
A Chiron Approach for the Total Synthesis of Crassalactone A
Authors: Singh Yadav Jhillu , Maheswara Rao Gokada , Thirupathaiah Bodakuntala
Published: December 2013

The total synthesis of crassalactone A (1) has been achieved in twelve steps starting from commercially available 1,5‐D‐gluconolactone. StillGennari olefination, one‐pot deprotection, and lactonization are the key reactions involved in the synthesis.
Synthesis of 4‐Arylisocoumarins (=4‐Aryl‐1H‐2‐benzopyran‐1‐ones) through Acidic Hydrolysis of (Z)‐2‐(1‐Aryl‐2‐methoxyethenyl)benzaldehydes, Followed by Oxidation
Authors: Kobayashi Kazuhiro , Miyatani Wataru , Kuroda Minami
Published: December 2013

4‐Arylisocoumarins (=4‐aryl‐1H‐2‐benzopyran‐1‐ones) 6 were prepared from 2‐(1‐aryl‐2‐methoxyethenyl)‐1‐bromobenzenes 1. Successive treatment of these bromo styrenes with BuLi and 1‐formylpiperidine gave a mixture of (E)‐ and (Z)‐2‐(1‐aryl‐2‐methoxyethenyl)benzaldehydes 2. Hydrolysis of (Z)‐isomers with conc. HBr, followed by pyridinium chlorochromate (PCC) oxidation of the resulting 1H‐2‐benzopyran‐1‐ol derivatives 4 (and 5), afforded the desired products.
Filamin A interacting protein 1‐like inhibits WNT signaling and MMP expression to suppress cancer cell invasion and metastasis
Authors: Kwon Mijung , Lee Soo Jin , Wang Yarong , Rybak Yevangelina , Luna Alex , Reddy Srilakshmi , Adem Asha , Beaty Brian T. , Condeelis John S. , Libutti Steven K.
Published: December 2013

Identifying key mediators of cancer invasion and metastasis is crucial to the development of new and more effective therapies. We previously identified FILamin A Interacting Protein 1‐Like (FILIP1L) as an important inhibitor of cell migration and invasion. FILIP1L expression was inversely correlated with the invasive potential of ovarian tumors. In our study, we established an orthotopic ovarian cancer model, wherein FILIP1L expression can be regulated in vivo. Using this model, we observed that expression of FILIP1L in ovarian cancer cells inhibited spontaneous lung metastasis. Experimental lung metastases (established via tail vein injection of cancer cells) as well as the extravasation step of metastasis were not inhibited by FILIP1L, suggesting that FILIP1L inhibits the earlier steps of metastasis such as invasion and intravasation. FILIP1L inhibited matrix metalloproteinase (MMP)‐dependent invasion in vivo. MMP3, ‐7 and ‐9 were transcriptionally downregulated, and MMP9 protein expression and activity were inhibited in FILIP1L‐expressing tumors. Importantly, overexpression of MMP9 compensated for the anti‐invasive activity of FILIP1L. Furthermore, our studies suggest that FILIP1L regulates invasion and metastasis by inhibiting components of the WNT signaling pathway. FILIP1L expression reduced the induction of WNT target genes such as MMP3, ‐7 and ‐9, and β‐catenin‐directed transcriptional activity, suggesting inhibition of the canonical WNT pathway. Nuclear β‐catenin, an indicator of an active canonical WNT pathway, was reduced in FILIP1L‐expressing tumors. Overall, these findings suggest that FILIP1L reduces β‐catenin levels, which may lead to the transcriptional downregulation of WNT target genes such as MMPs, resulting in inhibition of metastasis. Modulation of FILIP1L expression has the potential to be a target for cancer therapy.
1H‐Observe 1H2H Dipolar Recoupling by REDOR and Rotary Resonance Recoupling
Authors: Karki Ichhuk , Mihaliuk Eugene , Gullion Terry
Published: December 2013

The measurement of heteronuclear dipolar couplings by solid‐state NMR is an important tool for determining structures in solids. 1H‐observe 1H2H REDOR and rotary resonance recoupling experiments with fast magic‐angle spinning are presented. These dipolar recoupling experiments show promise for measuring heteronuclear dipolar couplings with 1H nuclei. Potential limitations of the experiments include short transverse relaxation times of the 1H magnetization and BlochSiegert effects.
Drug Labeling and Risk Perceptions of Teratogenicity: A Survey of Pregnant Canadian Women and Their Health Professionals
Authors: Pole Meena , Einarson Adrienne , Pairaudeau Nicholas , Einarson Tom , Koren Gideon
Published: December 2013

There is a general perception that medicinal drugs are not safe in pregnancy despite the fact that fewer than 30 drugs have been shown to cause major malformations in humans. A large number of women need medications in pregnancy to treat pregnancy‐induced conditions, acute illnesses, and chronic diseases. The objectives of this study were the following: (1) to characterize the perception of teratogenic risk by pregnant women and their partners and by health professionals and (2) to examine the most reassuring way to present data on a drug for nausea and vomiting of pregnancy that has been proven to be safe to the fetus. A convenience sample of pregnant Canadian women and their partners, pharmacists, nurses, physicians, and hospital workers were asked to choose the “safest” among four drugs by statements describing their safety. Although the text of all four was similar, the title and narrative were modified to be more or less “reassuring” by the use of more or less terms such as malformations and abnormalities. Health professionals rated the teratogenic risk significantly lower than the parents, but even they rated the drugs as not safe, despite a scientifically reassuring text. Sixty percent of the 240 participants, regardless of their perception of teratogenic risk, believed the four drugs were of similar risks. However, in the other 40%, the less “reassuring” text led to higher teratogenic perception, and the more reassuring options tended to decrease the false perception of teratogenic risk. It was concluded that in general, four different versions of reassuring text describing a scientifically proven safe drug in pregnancy did not lead expecting parents to believe they were safe. Among those who did not rank the four drugs as having equal safety/risk, the less “reassuring” text led to a higher perception of teratogenic risk. Even health professionals reading the labels describing safe drugs rated them as unsafe. Presently, the perception of teratogenic risk is strong even for safe drugs and is difficult to change even with evidence‐based facts.
Pharmacodynamics and Pharmacokinetic‐Pharmacodynamic Relationships of Atorvastatin, an HMG‐CoA Reductase Inhibitor
Authors: Stern Ralph H. , Yang Bing‐Bing , Hounslow Neil J. , MacMahon Mark , Abel Robert B. , Olson Stephen C.
Published: December 2013

The objective of this study is to determine the relationships between plasma atorvastatin concentrations, LDL (low‐density lipoprotein) cholesterol reduction, and atorvastatin dose; the earliest time at which lipid levels change when atorvastatin treatment is initiated or discontinued; and alterations in LDL particle composition. Twenty‐four subjects with elevated LDL‐cholesterol were treated with escalating daily doses of 5, 20, and 80 mg atorvastatin for 6 weeks each. Serial plasma lipid and lipoprotein analyses were performed during the initiation and discontinuation of atorvastatin therapy, as well as at steady state. LDL‐apolipoprotein B and LDL‐cholesterol were measured directly after ultracentrifugation, and LDL‐cholesterol also was estimated by the method of Friedewald. Steady‐state atorvastatin pharmacokinetic parameters were estimated on the last day of each dosing period. LDL‐cholesterol (Friedewald) reductions of 34%, 43%, and 57% were produced by atorvastatin doses of 5, 20, and 80 mg, respectively. The mean dose‐response relationship was log linear, and almost all individual dose‐response curves paralleled the mean curve. LDL‐apolipoprotein B reductions were slightly less than those of LDL‐cholesterol. Atorvastatin area under the curve (AUC(0.24)) values increased proportionally with dose, while values of Cmax (maximum concentration) increased more than proportionally, and Cmin (minimum concentration) increased less than proportionally. Following initiation of dosing, statistically significant decreases in total cholesterol, LDL‐cholesterol (beta quant), and LDL‐apolipoprotein B were observed within 24 hours and in LDL‐C (Friedewald) within 72 hours. Following discontinuation of drug dosing, statistically significant increases were observed in total cholesterol and LDL‐cholesterol (Friedewald) within 48 hours and in LDL‐cholesterol (beta quant) and LDL‐apolipoprotein B within 72 hours. At each dose, an individual's LDL‐cholesterol response was not correlated with AUC(0–24). In conclusion, atorvastatin produces marked LDL‐cholesterol reductions, the mean dose‐response relationship is log linear, almost all individual dose‐response curves parallel the mean dose‐response curve, onset and cessation of action are rapid, the estimated and measured LDL‐cholesterol are the same, LDL‐cholesterol and LDL‐Apo B reductions are similar, and plasma concentrations are not correlated with LDL‐cholesterol reduction at a given dose.
The Effect of 3‐Month Ingestion of Ginkgo biloba Extract on Pancreatic β‐Cell Function in Response to Glucose Loading in Normal Glucose Tolerant Individuals
Authors: Kudolo George B.
Published: December 2013

Ginkgo biloba extract is ingested on a chronic basis for enhancing mental focus and improving cognitive function in the elderly. This study was undertaken to determine the effect of Ginkgo biloba extract on glucose‐stimulated pancreatic β‐cell function in normal glucose‐tolerant individuals. Twenty individuals (14 females and 6 males, ages 21–57 years) underwent a 2‐hour 75 g oral glucose tolerance test (OGTT) before and after ingestion of Ginkgo biloba extract (120 mg/day at bedtime) for 3 months. Ginkgo biloba extract ingestion caused a decrease in systolic blood pressure from 125 ± 15 to 118 ± 12 mmHg (p < 0.05) and in diastolic blood pressure from 86 ± 10 to 68 ± 10 (p < 0.01). Fasting plasma insulin and C‐peptide were increased, and the insulin and C‐peptide areas under the curve during the OGTT changed from 136 ±55 to 162 ± 94 μU/ml/h (p = 0.1232) and 9.67 ± 5.34 to 16.88 ± 5.20 ng/ml/h (p < 0.001), respectively. The observed dissimilar insulin/C‐peptide response curves may be due to Ginkgo biloba‐induced increase of the rate of insulin metabolic clearance.
Real‐time monitoring of incision profile during laser surgery using shock wave detection
Authors: Bay Erwin , Deán‐Ben Xosé Luís , Pang Genny A. , Douplik Alexandre , Razansky Daniel
Published: December 2013

Lack of sensory feedback during laser surgery prevents surgeons from discerning the exact location of the incision, which increases duration and complexity of the treatment. In this study we demonstrate a new method for monitoring of laser ablation procedures. Real‐time tracking of the exact three dimensional (3D) lesion profile is accomplished by detection of shock waves emanating from the ablation spot and subsequent reconstruction of the incision location using time‐of‐flight data obtained from multiple acoustic detectors. Here, incisions of up to 9 mm in depth, created by pulsed laser ablation of fresh bovine tissue samples, were successfully monitored in real time. It was further observed that, by utilizing as little as 12 detection elements, the incision profile can be characterized with accuracy below 0.5 mm in all three dimensions and in good agreement with histological examinations. The proposed method holds therefore promise for delivering high precision real‐time feedback during laser surgeries. (© 2013 WILEY‐VCH Verlag GmbH &Co. KGaA, Weinheim)
Two-Year Results of a Randomized Placebo-Controlled Trial of Vertebroplasty for Acute Osteoporotic Vertebral Fractures
Authors: Kroon Féline , Staples Margaret , Ebeling Peter R , Wark John D , Osborne Richard H , Mitchell Peter J , Wriedt Chris HR , Buchbinder Rachelle
Published: December 2013

We previously reported the results of a randomized controlled trial that found no benefit of vertebroplasty over a sham procedure for acute osteoporotic vertebral fractures up to 6 months. We report here the 12-month and 24-month clinical outcomes of this trial. Eligible participants (n = 78) were randomly assigned to receive either vertebroplasty (n = 38) or a sham procedure (n = 40). Randomization was stratified by treatment center, sex, and symptom duration (<6 weeks or ≥6 weeks). Participants, investigators (except the treating radiologists), and outcome assessors were blinded to group assignments. Enrolment occurred between April 2004 and October 2008 with follow-up completed October 2010. The primary outcome was overall pain measured on a scale of 0 (no pain) to 10 (maximal imaginable pain). Secondary outcomes included pain at rest and at night, disability, quality of life, perceived recovery, and adverse events, including incident clinically apparent vertebral fractures. At 12 and 24 months, complete data were available for 67 (86%) and 57 (73%) participants, respectively. At 12 months participants in the active group improved by 2.4 ± 2.7 (mean ± SD) units in overall pain compared with 1.9 ± 2.8 units in the sham group, adjusted between-group mean difference (MD) 0.3 (95% confidence interval [CI], –0.9 to 1.5), whereas at 24 months participants in the active group had improved by 3.0 ± 3.1 units compared with 1.9 ± 3.0 units in the sham group, MD 1.1 (95% CI, –0.3 to 2.4). No significant between-group differences were observed for any of the secondary efficacy outcomes at 12 or 24 months. There were no between-group differences in incident clinical vertebral fractures up to 24 months (active: n = 14, sham: n = 13), although the study had inadequate power for this outcome. These results provide further evidence that the use of this treatment in routine care is unsupported. © 2014 American Society for Bone and Mineral Research.
Facilitating relational framing in children and individuals with developmental delay using the relational completion procedure
Authors: Walsh Sinead , Horgan Jennifer , May Richard J. , Dymond Simon , Whelan Robert
Published: December 2013

The Relational Completion Procedure is effective for establishing same, opposite and comparative derived relations in verbally able adults, but to date it has not been used to establish relational frames in young children or those with developmental delay. In Experiment 1, the Relational Completion Procedure was used with the goal of establishing two 3‐member sameness networks in nine individuals with Autism Spectrum Disorder (eight with language delay). A multiple exemplar intervention was employed to facilitate derived relational responding when required. Seven of nine participants in Experiment 1 passed tests for derived relations. In Experiment 2, eight participants (all of whom, except one, had a verbal repertoire) were given training with the aim of establishing two 4‐member sameness networks. Three of these participants were typically developing young children aged between 5 and 6 years old, all of whom demonstrated derived relations, as did four of the five participants with developmental delay. These data demonstrate that it is possible to reliably establish derived relations in young children and those with developmental delay using an automated procedure.
Radiolabeled antagonistic bombesin peptidomimetics for tumor targeting
Authors: Valverde Ibai E. , Huxol Elena , Mindt Thomas L.
Published: December 2013

The replacement of amide bonds in the backbone of peptides by proteolytically stable 1,2,3‐triazole isosteres can provide novel peptidomimetics with promising properties for the development of tumor‐targeting radiopeptides. On the basis of our previous work with radiolabeled agonistic bombesin (BBN) derivatives of the sequence [Nle14]BBN(7–14), we substituted selected amide bonds of the structurally closely related antagonistic peptide analog JMV594. With the exception of the C‐terminal modification, amide‐to‐triazole substitutions tolerated by [Nle14]BBN(7–14) without loss of biological function led to abolished receptor affinity in the case of JMV594. These findings provide an additional piece of evidence for the currently disputed differences in the modes of action of agonistic and antagonistic gastrin‐releasing peptide receptor (GRPR)‐targeting radiopeptides. Copyright © 2013 John Wiley & Sons, Ltd.
18F‐Fluorodeoxyglycosylamines: Maillard reaction of 18F‐fluorodeoxyglucose with biological amines†
Authors: Baranwal Aparna , Patel Himika H. , Mukherjee Jogeshwar
Published: December 2013

The Maillard reaction of sugars and amines resulting in the formation of glycosylamines and Amadori products is of biological significance, for drug delivery, role in central nervous system, and other potential applications. We have examined the interaction of 18F‐fluorodeoxyglucose (18F‐FDG) with biological amines to study the formation of 18F‐fluorodeoxyglycosylamines (18F‐FDGly). Respective amines N‐allyl‐2‐aminomethylpyrrolidine (NAP) and 2‐(4′‐aminophenyl)‐6‐hydroxybenzothiazole (PIB precursor) were mixed with FDG to provide glycosylamines, FDGNAP and FDGBTA. Radiosynthesis using 18F‐FDG (2–5 mCi) was carried out to provide 18F‐FDGNAP and 18F‐FDGBTA. Binding of FDGBTA and 18F‐FDGBTA was evaluated in human brain sections of Alzheimer's disease (AD) patients and control subjects using autoradiography. Both FDGNAP and FDGBTA were isolated as stable products. Kinetics of 18F‐FDGNAP reaction indicated a significant product at 4 h (63% radiochemical yield). 18F‐FDGBTA was prepared in 57% yield. Preliminary studies of FDGBTA showed displacement of 3H‐PIB (reduced by 80%), and 18F‐FDGBTA indicated selective binding to Aβ‐amyloid plaques present in postmortem AD human brain, with a gray matter ratio of 3 between the AD patients and control subjects. We have demonstrated that 18F‐FDG couples with amines under mild conditions to form 18F‐FDGly in a manner similar to click chemistry. Although these amine derivatives are stable in vitro, stability in vivo and selective binding is under investigation. Copyright © 2013 John Wiley & Sons, Ltd.
Rhenium and technetium tricarbonyl complexes of 1,4‐Substituted pyridyl‐1,2,3‐triazole bidentate ‘click’ ligands conjugated to a targeting RGD peptide
Authors: Connell Timothy U. , Hayne David J. , Ackermann Uwe , Tochon‐Danguy Henri J. , White Jonathan M. , Donnelly Paul S.
Published: December 2013

New 1,4‐substituted pyridyl‐1,2,3‐triazole ligands with pendent phenyl isothiocyanate functional groups linked to the heterocycle through a short methylene or longer polyethylene glycol spacers were prepared and conjugated to a peptide containing the arginine–glycine–aspartic acid peptide motif. Rhenium and technetium carbonyl complexes, [M(CO)3Lx(py)]+ (where M = ReI or 99mTcI; Lx = 1,4‐substituted pyridyl‐1,2,3‐triazole ligands and py = pyridine) were prepared. One rhenium complex has been characterized by X‐ray crystallography, and the luminescent properties of [M(CO)3Lx(py)]+ are reported.
Safety of elective colorectal cancer surgery: Non‐surgical complications and colectomies are targets for quality improvement
Authors: Henneman Daniel , ten Berge Martijn G. , Snijders Heleen S. , van Leersum Nicoline J. , Fiocco Marta , Wiggers Theo , Tollenaar Rob A.E.M. , Wouters Michel W.J.M. ,   on behalf of the Dutch Surgical Colorectal Audit Group
Published: December 2013

Background

Mortality following severe complications (failure‐to‐rescue, FTR) is targeted in surgical quality improvement projects. Rates may differ between colon‐ and rectal cancer resections.

Methods

Analysis of patients undergoing elective colon and rectal cancer resections registered in the Dutch Surgical Colorectal Audit in 2011–2012. Severe complication‐ and FTR rates were compared between the groups in univariate and multivariate analysis.

Results

Colon cancer (CC) patients (n = 10,184) were older and had more comorbidity. Rectal cancer (RC) patients (n = 4,906) less often received an anastomosis and had more diverting stomas. Complication rates were higher in RC patients (24.8% vs. 18.3%, P < 0.001). However, FTR rates were higher in CC patients (18.6% vs. 9.4%, P < 0.001). Particularly, FTR associated with anastomotic leakage, postoperative bleeding, and infections was higher in CC patients. Adjusted for casemix, CC patients had a twofold risk of FTR compared to RC patients (OR 1.89, 95% CI 1.06–3.37).

Conclusions

Severe complication rates were lower in CC patients than in RC patients; however, the risk of dying following a severe complication was twice as high in CC patients, regardless of differences in characteristics between the groups. Efforts should be made to improve recognition and management of postoperative (non‐)surgical complications, especially in colon cancer surgery. J. Surg. Oncol. 2014 109:567–573. © 2013 Wiley Periodicals, Inc.
Carbohydrate analysis: From sample preparation to HPLC on different stationary phases coupled with evaporative light‐scattering detection
Authors: Dvořáčková Eva , Šnóblová Marie , Hrdlička Petr
Published: December 2013

After 20 years of development, evaporative light‐scattering detection (ELSD) has become the mainstream choice for the detection of various classes of natural products. ELSD continues to grow in popularity as a “quasi‐universal” technique because of the specificity of the detection method, which is based on the scattering of laser light from nonvolatile analyte particles. It represents an attractive alternative compared to other types of detection, such as refractive index detection and/or ultraviolet detection. This review presents issues concerned with the separation of carbohydrates in plant materials by HPLC and ELSD, as well as the advantages and limitations relating to the ELSD method. Additionally, an overview of possible ELSD applications in the analysis of carbohydrates in natural products is presented.
Socioeconomic disparities in the presentation of acute bacterial sinusitis complications in children
Authors: Sedaghat Ahmad R. , Wilke Claus O. , Cunningham Michael J. , Ishman Stacey L.
Published: December 2013

Objectives/Hypothesis

To identify characteristics and disparities associated with presentation of pediatric acute bacterial sinusitis (ABS) complications.

Study Design

A cross‐sectional study of the 2008 Nationwide Emergency Department Sample database.

Methods

A total of 101,660 children 18 years of age or younger diagnosed with ABS, 696 of whom had orbital or intracranial complications, were identified. Patient and hospital‐specific characteristics were investigated for association with childhood ABS complications.

Results

Orbital and intracranial complications occurred in 0.7% of children with ABS. Such complications were more common in boys (odds ratio [OR]: 1.65, P < .001) and children with chronic rhinosinusitis (OR: 7.89, P < .001), and were associated with presentation to metropolitan teaching (OR: 2.15, P < .001) and nonteaching (OR: 14.39, P< .001) hospitals. Orbital complications were associated with younger age (OR: 0.96, P < .001), whereas intracranial complications were associated with older age (OR: 1.11, P < .001). A dichotomy in socioeconomic background differentiated children with orbital ABS complications from those with intracranial complications. Although orbital complications were associated with higher income (OR: 2.13, P < .001) and private insurance (OR: 1.36, P = .003), intracranial complications were associated with Medicaid (OR: 2.96, P < .001) or no insurance at all (OR: 3.73, P = .001).

Conclusions

Socioeconomic disparities exist in presentation of ABS complications in children. Although hinted at by the association with urban/metropolitan hospitals, explicit evidence is provided by association of intracranial complications with markers of low socioeconomic status and poor access to healthcare. Efforts to aid early diagnosis and treatment should target providers in metropolitan areas who treat children of lower socioeconomic status. Such interventions will ideally improve outcomes and limit healthcare costs related to the high morbidity of pediatric ABS complications.

Level of Evidence

2b Laryngoscope, 124:1700–1706, 2014
Medical management of chronic rhinosinusitis in cystic fibrosis: A systematic review
Authors: Liang Jonathan , Higgins Thomas , Ishman Stacey L. , Boss Emily F. , Benke James R. , Lin Sandra Y.
Published: December 2013

Objectives/Hypothesis

To systematically review existing literature on the effectiveness of medical management of chronic rhinosinusitis (CRS) in cystic fibrosis (CF) patients.

Study Design

Systematic review.

Methods

We performed a literature search of PubMed, Embase, and Cochrane CENTRAL from 1987 to 2012. Inclusion criteria included English language as containing original data, with five or more subjects, measurable clinical outcomes, and readily available interventions. Data were systematically collected on study design, patient demographics, clinical characteristics and outcomes, and level of evidence. Two investigators independently reviewed all manuscripts and performed a comprehensive quality assessment.

Results

Of 415 abstracts identified, 12 articles were included. These 12 studies reported on 701 adult and pediatric CF patients who underwent medical therapy. Medical treatment included antibiotics (4/12), topical steroids (4/12), dornase alfa (3/12), and ibuprofen (1/12). Outcome measures included symptom scores (7/12), endoscopic findings (7/12), radiographic findings (4/12), pulmonary function testing (4/12), and rhinomanometry (2/12). Most studies found improvement in at least one of the outcome measures. There was statistical significance in clinical outcomes with dornase alfa, beclomethasone, and betamethasone. Most studies were level 3 or 4 evidence (9/12), but three studies were level 1 or 2 evidence (two dornase alfa studies, one betamethasone study).

Conclusions

Dornase alfa and, to a lesser extent, topical steroids demonstrated significant benefits in the medical treatment CRS in CF. There was a lack of evidence to support antibiotic therapy in the outcomes assessed. Further high‐quality studies should be carried out to determine the efficacy of various medical therapies for CRS in CF.

Level of Evidence

NA Laryngoscope, 124:1308–1313, 2014