bluuebunny/crossref_metadata_2025 huggingface dataset:
On the “Tertiary Structure” of Poly‐Carbenes; Self‐Assembly of sp3‐Carbon‐Based Polymers into Liquid‐Crystalline Aggregates
Authors: Franssen Nicole M. G. , Ensing Bernd , Hegde Maruti , Dingemans Theo J. , Norder Ben , Picken Stephen J. , Alberda van Ekenstein Gert O. R. , van Eck Ernst R. H. , Elemans Johannes A. A. W. , Vis Mark , Reek Joost N. H. , de Bruin Bas
Published: July 2013

The self‐assembly of poly(ethylidene acetate) (st‐PEA) into van der Waals‐stabilized liquid‐crystalline (LC) aggregates is reported. The LC behavior of these materials is unexpected, and unusual for flexible sp3‐carbon backbone polymers. Although the dense packing of polar ester functionalities along the carbon backbone of st‐PEA could perhaps be expected to lead directly to rigid‐rod behavior, molecular modeling reveals that individual st‐PEA chains are actually highly flexible and should not reveal rigid‐rod induced LC behavior. Nonetheless, st‐PEA clearly reveals LC behavior, both in solution and in the melt over a broad elevated temperature range. A combined set of experimental measurements, supported by MM/MD studies, suggests that the observed LC behavior is due to self‐aggregation of st‐PEA into higher‐order aggregates. According to MM/MD modeling st‐PEA single helices adopt a flexible helical structure with a preferred trans‐gauche syn‐syn‐anti‐anti orientation. Unexpectedly, similar modeling experiments suggest that three of these helices can self‐assemble into triple‐helical aggregates. Higher‐order assemblies were not observed in the MM/MD simulations, suggesting that the triple helix is the most stable aggregate configuration. DLS data confirmed the aggregation of st‐PEA into higher‐order structures, and suggest the formation of rod‐like particles. The dimensions derived from these light‐scattering experiments correspond with st‐PEA triple‐helix formation. Langmuir–Blodgett surface pressure–area isotherms also point to the formation of rod‐like st‐PEA aggregates with similar dimensions as st‐PEA triple helixes. Upon increasing the st‐PEA concentration, the viscosity of the polymer solution increases strongly, and at concentrations above 20 wt % st‐PEA forms an organogel. STM on this gel reveals the formation of helical aggregates on the graphite surface–solution interface with shapes and dimensions matching st‐PEA triple helices, in good agreement with the structures proposed by molecular modeling. X‐ray diffraction, WAXS, SAXS and solid state NMR spectroscopy studies suggest that st‐PEA triple helices are also present in the solid state, up to temperatures well above the melting point of st‐PEA. Formation of higher‐order aggregates explains the observed LC behavior of st‐PEA, emphasizing the importance of the “tertiary structure” of synthetic polymers on their material properties.
An Endoperoxide‐Based Hybrid Approach to Deliver Falcipain Inhibitors Inside Malaria Parasites
Authors: Oliveira Rudi , Newton Ana S. , Guedes Rita C. , Miranda Daniela , Amewu Richard K. , Srivastava Abhishek , Gut Jiri , Rosenthal Philip J. , O'Neill Paul M. , Ward Stephen A. , Lopes Francisca , Moreira Rui
Published: July 2013

The emergence of artemisinin‐resistant Plasmodium falciparum malaria in Southeast Asia has reinforced the urgent need to discover novel chemotherapeutic strategies to treat and control malaria. To address this problem, we prepared a set of dual‐acting tetraoxane‐based hybrid molecules designed to deliver a falcipain‐2 (FP‐2) inhibitor upon activation by iron(II) in the parasite digestive vacuole. These hybrids are active in the low nanomolar range against chloroquine‐sensitive and chloroquine‐resistant P. falciparum strains. We also demonstrate that in the presence of FeBr2 or within infected red blood cells, these molecules fragment to release falcipain inhibitors with nanomolar protease inhibitory activity. Molecular docking studies were performed to better understand the molecular interactions established between the tetraoxane‐based hybrids and the cysteine protease binding pocket residues. Our results further indicate that the intrinsic activity of the tetraoxane partner compound can be masked, suggesting that a tetraoxane‐based delivery system offers the potential to attenuate the off‐target effects of known drugs.
A meshless boundary method for Stokes flows with particles: Application to canalithiasis
Authors: Boselli F. , Obrist D. , Kleiser L.
Published: July 2013

We propose to couple the method of fundamental solutions (MFS) to the force coupling method (FCM). The resulting method is an efficient, easy to program, meshless method for flows at low Reynolds numbers with finite‐size particles. In such an approach, the flow domain is extended across the solid particle phase, and the flow is approximated by a superposition of singular Stokeslets positioned outside the flow domain and finite‐size multipoles collocated with the particle. To improve the efficiency of the coupling, we propose new MFS quadratures for the computation of the volume integrals required for the FCM. These are exact and do not require the expensive evaluation of Stokeslets. The proposed method has been developed in the context of investigations of the fluid dynamics of canalithiasis, that is, a pathological condition of the semicircular canals of the inner ear. Numerical examples are presented to illustrate the applicability of the method. Copyright © 2013 John Wiley & Sons, Ltd.
Commentary on ‘Prophylactic drug management for febrile seizures in children’
Authors: Robertson Jeanette
Published: July 2013

This is a commentary on a Cochrane review, published in this issue of EBCH, first published as: Offringa M, Newton R. Prophylactic drug management for febrile seizures in children. Cochrane Database of Systematic Reviews 2012, Issue 4. Art. No.: CD003031. DOI: 10.1002/14651858.CD003031.pub2.
Commentary on ‘Glucocorticoids for the treatment of anaphylaxis’
Authors: Santos Alexandra F. , Lack Gideon
Published: July 2013

This is a commentary on a Cochrane review, published in the issue of EBCH, first published as: Choo KJL, Simons FER, Sheikh A. Glucocorticoids for the treatment of anaphylaxis. Cochrane Database of Systematic Reviews 2012, Issue 4. Art. No.: CD007596. DOI: 10.1002/14651858.CD007596.pub3.
Commentary on ‘Propofol versus thiopental sodium for the treatment of refractory status epilepticus—Still no answer’
Authors: Buchhalter Jeffrey , Stang Antonia
Published: July 2013

This is a commentary on a Cochrane review, published in this issue of EBCH, first published as: Prabhakar H, Bindra A, Singh GP, Kalaivani M. Propofol versus thiopental sodium for the treatment of refractory status epilepticus. Cochrane Database of Systematic Reviews 2012, Issue 8. Art. No.: CD009202. DOI: 10.1002/14651858.CD009202.pub2.
A Comprehensive Study on Triplesalen‐Based [MnIII6FeIII]3+ and [MnIII6FeII]2+ Complexes: Redox‐Induced Variation of Molecular Magnetic Properties
Authors: Hoeke Veronika , Krickemeyer Erich , Heidemeier Maik , Theil Hubert , Stammler Anja , Bögge Hartmut , Weyhermüller Thomas , Schnack Jürgen , Glaser Thorsten
Published: July 2013

The synthesis and structural, mass spectrometric, FT‐IR, Mössbauer, and UV/Vis spectroscopic, electrochemical, and DC and AC magnetic properties of three [MnIII6FeIII]3+ (short for [{(talen)MnIII3}2{FeIII(CN)6}]3+) compounds {[MnIII6FeIII(MeOH)6]Cl3·11MeOH·H2O (1a), [MnIII6FeIII(MeOH)6]Cl3·3MeOH·H2O (1b), and [MnIII6FeIII(MeOH)6](PF6)2(OAc)·11MeOH (3)} and the one‐electron reduced congener [MnIII6FeII(MeOH)4](BPh4)2·3MeOH·toluene (2) are presented. The half‐wave potential of the FeIII/FeII couple in [MnIII6FeIII/II]3+/2+ is E1/2 = –0.06 V versus Fc/Fc+. The overall molecular structures of the complexes resemble those of the already published [MnIII6Mc]3+ compounds (Mc = CrIII, CoIII, MnIII, FeIII). The [MnIII6FeII]2+ dication, however, exhibits shorter Mn–NC≡N bonds than the tricationic [MnIII6Mc]3+ complexes, as well as a higher degree of aromaticity of the central benzene ring of the triplesalen ligand. The electronic absorption spectrum of [MnIII6FeII]2+ differs considerably from the superimposable spectra of tricationic [MnIII6Mc]3+ complexes in exhibiting lower‐energy ligand field transitions due to stronger π‐donation of the surrounding ligands and weaker absorption features in the 27000–35000 cm–1 region, due to a weaker keto‐enamine character of the central phloroglucinol unit. AC susceptibility measurements indicate single‐molecule magnet (SMM) behavior for 1a and 3. Analysis of the DC magnetic data (μeff vs. T, VTVH) of these compounds by a full‐matrix diagonalization of the spin‐Hamiltonian including isotropic exchange, zero‐field splitting with full consideration of the relative orientation of the D‐tensors, and Zeeman interaction reveals JMn,Mn = –1.00 to –1.15 cm–1 (Ĥex = –2JijŜi·Ŝj), JFe,Mn = +0.50 to +0.80 cm–1, and DMn = –3.5 cm–1. These values are similar to those previously found for [MnIII6FeIII][FeIII(CN)6]. For 2, the simulations indicate very weak antiferromagnetic MnIII–MnIII interactions within the trinuclear triplesalen subunits (JMn,Mn(1) = –0.20 cm–1) as well as across the central diamagnetic FeII ion (JMn,Mn(2,cis) = –0.06 cm–1, JMn,Mn(2,trans) = –0.18 cm–1), whereas DMn = –3.5 cm–1. The JMn,Mn(1) coupling in 2 is much less antiferromagnetic than in the tricationic [MnIII6Mc]3+ compounds; this is interpreted in terms of a stronger ferromagnetic contribution to the exchange interaction due to more efficient spin‐polarization through the central benzene ring, the aromatic nature of which is more pronounced.
Modified Fry Cyanation of a Chiral Pyridinium Salt: Asymmetric Syntheses of (–)‐Coniine and (–)‐Solenopsin A
Authors: Vu Van Ha , Jouanno Laurie‐Anne , Cheignon Adèle , Roisnel Thierry , Dorcet Vincent , Sinbandhit Sourisak , Hurvois Jean‐Pierre
Published: July 2013

The synthesis of chiral 2‐cyano‐Δ4‐tetrahydropyridine 5 was carried out in 85 % yield through a modified two‐step Fry reductive cyanation of pyridinium salt (+)‐3c that used lithium triethylborohydride as the hydride donor. An alkylation–reduction sequence provided 2‐alkyl‐substituted tetrahydropyridines (+)‐10a and (+)‐10b in 72–75 % yield after chromatographic purification. This protocol has been applied to the asymmetric syntheses of piperidine alkaloids (–)‐coniine and (–)‐solenopsin A.
BF3·OEt2‐Promoted Intramolecular Nucleophilic Substitution; Synthesis of Dibenzopyranones and Coumarins from Biaryltriazenes
Authors: Shang Xiaobo , Xu Lijun , Yang Weijun , Zhou Jun , Miao Maozhong , Ren Hongjun
Published: July 2013

A simple and highly efficient reaction promoted by Lewis acid has been demonstrated for the synthesis of dibenzopyranones. The metal‐free annulation can tolerate a series of functional groups and also allows the synthesis of coumarins and phenanthridinones in good to excellent yields.
Criminal victimisation fosters conservatism among people living in areas with high unemployment rates: A multilevel longitudinal study
Authors: Roccato Michele , Vieno Alessio , Russo Silvia
Published: July 2013

Using a multilevel, longitudinal model, we tested the mugging thesis, which states that ‘a conservative is a liberal who has been mugged’, in a national sample of Italians (N = 457, nested in 54 counties) surveyed four times between October 2002 and January 2007. We predicted participants' increase in conservatism as a function of the cross‐level interactions between criminal victimisation on the one hand and the unemployment and the crime rates for their areas of residence on the other. Conservatism increased among victimised participants living in areas characterised by high unemployment rates, but not among those living in areas with low unemployment rates. The cross‐level interaction between victimisation and crime rate did not influence our dependent variable. The strengths, implications and limitations of this research are discussed. Copyright © 2013 John Wiley & Sons, Ltd.
Meaning in music: Deviations from expectations in music prompt outgroup derogation
Authors: Maher Paul James , Van Tilburg Wijnand Adriaan Pieter , Van Den Tol Annemieke Johanna Maria
Published: July 2013

Encountering stimuli that violate expectations can elicit compensatory behavior. One notable result of such compensatory responses is the derogation of outgroups. The present research investigated for the first time if music that defies expectations fosters the derogation of outgroups. In Study 1, exposure to unconventional relative to conventional music increased wagers placed in favor of an ingroup winning a hypothetical rugby match against an outgroup. In extension of this finding, Study 2 revealed that unconventional music led to lower allocated budgets for support of a minority. Study 3 confirmed that music led to harsher punishments of a hypothetical outgroup offender after being exposed to an unconventional edit of a music piece relative to its regular version. The consequences of these findings are discussed in relation to intergroup relations and theories of meaning maintenance. Copyright © 2013 John Wiley & Sons, Ltd.
Depletion of the transcriptional coactivators megakaryoblastic leukaemia 1 and 2 abolishes hepatocellular carcinoma xenograft growth by inducing oncogene‐induced senescence
Authors: Hampl Veronika , Martin Claudia , Aigner Achim , Hoebel Sabrina , Singer Stephan , Frank Natalie , Sarikas Antonio , Ebert Oliver , Prywes Ron , Gudermann Thomas , Muehlich Susanne
Published: July 2013

Megakaryoblastic leukaemia 1 and 2 (MKL1/2) are coactivators of the transcription factor serum response factor (SRF). Here, we provide evidence that depletion of MKL1 and 2 abolishes hepatocellular carcinoma (HCC) xenograft growth. Loss of the tumour suppressor deleted in liver cancer 1 (DLC1) and the subsequent activation of RhoA were prerequisites for MKL1/2 knockdown‐mediated growth arrest. We identified oncogene‐induced senescence as the molecular mechanism underlying the anti‐proliferative effect of MKL1/2 knockdown. MKL1/2 depletion resulted in Ras activation, elevated p16 expression and hypophosphorylation of the retinoblastoma (Rb) protein in DLC1‐deficient HCC cells. Interestingly, reconstitution of HuH7 HCC cells with DLC1 also induced senescence. Evaluation of the therapeutic efficacy of MKL1/2 knockdown in vivo revealed that systemic treatment of nude mice bearing HuH7 tumour xenografts with MKL1/2 siRNAs complexed with polyethylenimine (PEI) completely abolished tumour growth. The regression of the xenografts was associated with senescence. Importantly, PEI‐complexed MKL1 siRNA alone was sufficient for complete abrogation of HCC xenograft growth. Thus, MKL1/2 represent promising novel therapeutic targets for the treatment of HCCs characterized by DLC1 loss.
A CWENO ghost fluid method for compressible multimaterial flow
Authors: Lahooti Mohsen , Pishevar Ahmadreza
Published: July 2013

In this work a new ghost fluid method (GFM) is introduced for multimaterial compressible flow with arbitrary equation of states. In previous researches, it has been shown that accurate wave decomposition at the interface by solving a Riemann problem alleviates the shortcomings of the standard GFM in dealing with the impingement of strong waves onto the interface but these Riemann‐based GFM are not consistent with the framework of the central WENO scheme in which the emphasis is to avoid solving Riemann problems at control volume faces and enjoy the black box property (being independent of equation of state). The aim of this work is to develop a new GFM that is completely consistent with the methodology behind central schemes; that is, it enjoys a black box property. The capabilities of the proposed GFM method is shown by solving various types of multimaterial compressible flows including gas–gas, gas–water and fluid–solid interfaces interacting with strong shock waves in one and two space dimensions. Copyright © 2013 John Wiley & Sons, Ltd.
A probabilistic framework for assessing drought recovery
Authors: Pan Ming , Yuan Xing , Wood Eric F.
Published: July 2013

A probabilistic framework is proposed to explore drought recovery and its uncertainty based on any ensemble forecast. First, the joint distribution between precipitation and drought index is established from the forecast ensemble using the copula method, which allows arbitrary marginal distributions and fine‐tuned correlation structure. Then, questions like “how much precipitation is needed for recovery and its uncertainty?” and “what is the likelihood that a specified drought index threshold be surpassed given specified cumulative precipitation over a fixed period?” are studied. The application investigates how the 2012–2013 drought over central United States may recover during the forecast period from February to July 2013. The ensemble streamflow prediction method is used to create the ensemble forecast, with soil moisture percentile against climatology as the drought index. We find significant uncertainty in drought recovery given the same precipitation, suggesting that a probabilistic analysis will offer important additional information about drought risk.
Precipitation scaling with temperature in warm and cold climates: An analysis of CMIP5 simulations
Authors: Li Guangqi , Harrison Sandy P. , Bartlein Patrick J. , Izumi Kenji , Colin Prentice I.
Published: July 2013

We investigate the scaling between precipitation and temperature changes in warm and cold climates using six models that have simulated the response to both increased CO2 and Last Glacial Maximum (LGM) boundary conditions. Globally, precipitation increases in warm climates and decreases in cold climates by between 1.5%/°C and 3%/°C. Precipitation sensitivity to temperature changes is lower over the land than over the ocean and lower over the tropical land than over the extratropical land, reflecting the constraint of water availability. The wet tropics get wetter in warm climates and drier in cold climates, but the changes in dry areas differ among models. Seasonal changes of tropical precipitation in a warmer world also reflect this “rich get richer” syndrome. Precipitation seasonality is decreased in the cold‐climate state. The simulated changes in precipitation per degree temperature change are comparable to the observed changes in both the historical period and the LGM.
Structure and Dynamic of Three Indole Alkaloids from the Campylospermum Genus (Ochnaceae)
Authors: Njock Gaétan Bayiha Ba , Bartholomeusz Trixie Ann , Bikobo Dominique Ngono , Foroozandeh Mohammadali , Shivapurkar Rupali , Christen Philippe , Pegnyemb Dieudonné Emmanuel , Jeannerat Damien
Published: July 2013

A new indole alkaloid, calanthumindole (4), and three known biflavonoids, amentoflavone, sequoiaflavone, and podoscarpusflavone B, were isolated from Campylospermum calanthum (Ochnaceae). Calanthumindole is a new indole alkaloid of the serotobenine family characterized by the presence of a CC bond between atoms C(7′) and C(8′) of the furan ring. This is the first compound to have a fully unsaturated furan ring among the members of this family. The combination of NMR and DFT allowed the determination and comparison of the 3D structures and relevant conformational characteristics of serotobenine (1), flavumindole (2), and calanthumindole (4).
A Fused Benzocyclooctene Ring System via an Aromatic Cope Rearrangement: Thermal Reactions of trans‐1‐Aryl‐2‐ethenylcyclobutanecarbonitriles
Authors: Ávila‐Zárraga José Gustavo , Vázquez‐Sánchez Adrián , Maldonado Luis Ángel
Published: July 2013

The results of an aromatic Cope rearrangement of a trans‐1‐aryl‐2‐ethenylcyclobutanecarbonitrile are reported (Scheme). The use of this rearrangement for the construction of the fused benzocyclooctene ring system and a preliminary study of the electronic requirements to favor such a transformation are also described.
Highly Diastereoselective Total Syntheses of (+)‐7‐Epigoniodiol, (−)‐8‐Epigoniodiol, and (+)‐9‐Deoxygoniopypyrone
Authors: Kumaraswamy Gullapalli , Satish Kumar Rangaraju
Published: July 2013

An expedient concise total synthesis of (+)‐7‐epigoniodiol, (−)‐8‐epigoniodiol, and (+)‐9‐deoxygoniopypyrone is accomplished. The key transformations include a catalytic hydroxylation and base‐mediated N‐(acetyl)oxazolidinone addition reactions, which could set the consecutive OH motif that is either syn,syn or syn,anti with high diastereoselectivity. Moreover, this approach envisioned to facilitate the synthesis of other representatives of the family with structural and stereochemical variation.
New Cytotoxic Triterpenoids from the Aerial Parts of Euphorbia sieboldiana
Authors: Zhang Bei‐Bei , Jiang Qian , Liao Zhi‐Xin , Liu Chao , Liu Shi‐Jun
Published: July 2013

Phytochemical investigation of the EtOH extract of Euphorbia sieboldiana led to the isolation of four new oleanane‐type triterpenoids, (1β,2α,3β,19β)‐1,2,3,19‐tetrahydroxyolean‐12‐en‐28‐oic acid, (1β,3β,19β)‐1,3,19‐trihydroxyolean‐12‐en‐28‐oic acid, (1β,2α,3β,16β,19β)‐1,2,3,16,19‐pentahydroxyolean‐12‐en‐28‐oic acid, and (1β,2α,3β,19β,23)‐1,2,3,19,23‐pentahydroxyolean‐12‐en‐28‐oic acid, along with 16 known compounds. Their structures were established by extensive 1D‐ and 2D‐NMR, as well as other spectral analyses. Biological evaluation of the four new triterpenoids revealed potent cytotoxic activities against HeLa and Hep‐G2 cells.
Five New Nortriterpenoids from the Stems of Schisandra neglecta
Authors: Liang Cheng‐Qin , Hu Jing , Shi Yi‐Ming , Shang Shan‐Zhai , Du Xue , Zhan Rui , Wang Wei‐Guang , Xiong Wen‐Yong , Xiao Wei‐Lie , Zhang Hong‐Bin , Sun Han‐Dong
Published: July 2013

Five new nortriterpenoids, schicagenins D–F (1–3, resp.) and negleschidilactones A and B (4 and 5, resp.), together with eleven known ones, were isolated from the stems of Schisandra neglecta. Their structures were established on the basis of extensive spectroscopic analyses. All the compounds were evaluated for their activities regarding insulin sensitivity in 3T3‐L1 differentiated adipocytes. None of them showed a significant bioactivity at 10 μM concentration.
Efficient One‐Pot Synthesis of a Densely Functionalized Tetrahydropyridine in the Presence of [1,1′‐Binaphthalene]‐2,2′‐diol/Indium(III) Chloride (binol/InCl3) or Simple Brønsted Acids as Catalysts
Authors: Kończyk Anna A. , Szawkało Joanna , Maurin Jan K. , Czarnocki Zbigniew
Published: July 2013

The highly functionalized tetrahydropyridine 4 was obtained in an indium(III) chloride catalyzed multi‐component reaction from benzaldehyde, 4‐methoxyaniline, and ethyl acetoacetate (=ethyl 3‐oxobutanoate) in the presence of [1,1′‐binaphthalene]‐2,2′‐diol (binol). It was found that binol played a beneficial role in this reaction, allowing a substantial decrease of the amount of indium salt. Also, simple organic Brønsted acids may serve as effective organocatalysts in this process.
An Efficient Synthesis of Novel Benzo‐Fused Macrocyclic Dilactams
Authors: Mekky Ahmed E. M. , Ahmed Ahmed A. M. , Elwahy Ahmed H. M.
Published: July 2013

A facile synthetic approach was adopted towards the synthesis of benzo‐fused macrocyclic lactams 2a–2g via the base‐catalyzed condensation reaction of 2,2′‐[alkanediylbis(oxy)]bis[benzaldehydes] 3a–3c with N,N′‐substituted bis[2‐cyanoacetamide] derivatives 7a–7c (Scheme 2). The latter compounds were obtained by the reaction of the appropriate diamines 6a–6c with ethyl 2‐cyanoacetate (4). Attempts to prepare the oxaaza macrocycles 2 by alternative pathways were also investigated. The novel pyrazolo‐fused macrocycles 13a and 13b were obtained in 48 and 52% yield, respectively, upon treatment of 2d and 2g with NH2NH2⋅H2O at 100° (Scheme 4).
Convenient Synthesis of Various Substituted Homotaurines from Alk‐2‐enamides
Authors: Nai Youfeng , Xu Jiaxi
Published: July 2013

Various substituted homotaurines (=3‐aminopropane‐1‐sulfonic acids) 6 were readily synthesized in satisfactory to good yields via the Michael addition of thioacetic acid to alk‐2‐enamides 3 (→4), followed by LiAlH4 reduction (→5) and performic acid oxidation (Scheme 1). The configuration of ‘anti’‐disubstituted homotaurine ‘anti’‐6h was deduced from the 3‐(acetylthio)alkanamide (=S‐(3‐amino‐1,2‐dimethyl‐3‐oxopropyl) ethanethioate)‘anti’‐4h formed in the Michael addition, which was identified via the Karplus equation analysis, and confirmed by X‐ray diffraction analysis. The current route is an efficient method to synthesize diverse substituted homotaurines, including 1‐, 2‐, and N‐monosubstituted, as well as 1,2‐, 1,N‐, 2,N‐, and N,N‐disubstituted homotaurines (Table).
Burrowing as a non‐reflex behavioural readout for analgesic action in a rat model of sub‐chronic knee joint inflammation
Authors: Rutten K. , Schiene K. , Robens A. , Leipelt A. , Pasqualon T. , Read S.J. , Christoph T.
Published: July 2013

Background

Innate responses against spontaneous pain are proposed to improve the predictive validity of preclinical analgesia models. Therefore, development and validation of novel readouts is necessary. To investigate whether innate rodent burrowing is a useful alternative behavioural readout for assessment of analgesic efficacy, a complete Freund's adjuvant (CFA)‐induced model of sub‐chronic inflammation was used to compare the effects of naproxen, ibuprofen and pregabalin in weight‐bearing (WB), open‐field (OF) and burrowing assays.

Methods

Male Sprague Dawley rats were injected with 150 μL of CFA (2 mg/mL) into the knee (hind leg) 3 days before testing. Naproxen, ibuprofen and pregabalin were administered at different doses 30, 90 and 60 min, respectively, before testing. WB was determined using a rat incapacitance tester; horizontal distance moved and vertical rearings were recorded in an OF; and burrowing was measured by the weight of gravel remaining in a hollow tube after 60 min.

Results

CFA‐induced arthritis reduced WB, OF activity and burrowing. Naproxen, pregabalin and ibuprofen treatment normalized WB; however, horizontal OF activity was not improved by any treatment; rearing behaviour was moderately reinstated by ibuprofen (100 mg/kg). In burrowing, naproxen (100 mg/kg), ibuprofen (31.6 and 100 mg/kg) and pregabalin (10 mg/kg) reversed CFA‐induced deficits.

Conclusions

Burrowing performance is an alternative non‐reflex readout relying on innate rodent behaviour that is affected by nociceptive behaviour and can be pharmacologically manipulated. The burrowing assay appears to be more sensitive than OF assays and is as sensitive as WB assays at distinguishing between analgesic doses and doses that impair locomotion.
Circulating Level of Lipocalin 2 As a Predictor of Severity in Patients With Community‐Acquired Pneumonia
Authors: Yeh Yuan‐Hung , Chang Junn‐Liang , Hsiao Pei‐Ching , Tsao Shih‐Ming , Lin Chien Huang , Kao Shang‐Jyh , Chou Ming‐Chih , Yang Shun‐Fa , Chien Ming‐Hsien
Published: July 2013

Background

The aim of this study was to investigate the differential plasma levels of lipocalin 2 (LCN2) and its complex with MMP‐9 (where MMP is matrix metalloproteinase) before and after antibiotic treatment in hospitalized adult patients with community‐acquired pneumonia (CAP).

Method

Plasma LCN2 and LCN2/MMP‐9 complex levels were measured in 61 adult patients with CAP and 60 healthy controls using commercial enzyme‐linked immunosorbent assay (ELISA).

Results

A decrease in the number of white blood cells (WBCs) and neutrophils and decreases in the levels of C‐reactive protein (CRP), LCN2, and LCN2/MMP‐9 complex were observed after antibiotic treatment. The plasma level of LCN2, but not that of CRP, was correlated with the severity of CAP based on the Pneumonia Severity Index (PSI; r = 0.333, P = 0.009), confusion, urea, respiratory rate and blood pressure (CURB)‐65 (r = 0.288, P = 0.024), and Acute Physiology And Chronic Health Evaluation II (APACHE II) scores (r = 0.328, P = 0.010). LCN2 levels were also significantly correlated with LCN2/MMP‐9 levels and the numbers of WBCs or neutrophils.

Conclusions

Plasma levels of LCN2 and the LCN2/MMP‐9 complex can act as adjuvant diagnostic biomarkers for CAP. Plasma LCN2 might play a further role in the clinical assessment of the severity of CAP, which could potentially guide the development of future treatment strategies.
Determination of Storage Time of Saliva Samples Obtained From Patients With and Without Chronic Periodontitis for the Comparison of Some Biochemical and Cytological Parameters
Authors: Emekli‐Alturfan Ebru , Yarat Aysen , Çalışkan‐Ak Esin , Pisiriciler Rabia , Kuru Bahar , Noyan Ülkü
Published: July 2013

Background

Salivary glutathione (GSH), malondialdehyde (MDA), protein, sialic acid (SA) levels, cytological parameters, and tissue factor activities (TFa) were investigated when fresh and after 3, 7, 11, 15, 21, and 30 days (d) of storage at −20°C both in the control and the periodontitis group. Moreover, the control and the periodontits groups were compared and continuity of the significances detected between the two groups were evaluated.

Methods

GSH, MDA, SA, protein, and TFa were determined using the methods of Beutler, Yagi, Warren, Lowry, and Quick, respectively. Saliva imprint samples were stained with Giemsa and microscopically examined.

Results

When the continuity of the significances of differences between the two groups was investigated, differences continued to be significant for GSH and TFa on days 3, 7, 11, 15, 21, and 30. Cytologically, only the significance detected between leucocyte numbers continued to be significant for 30 d. However significance of differences in total protein, MDA, and SA levels on day 0, were interrupted on days 3, 7, and 11, respectively.

Conclusion

Saliva samples may be stored for 30 d for GSH and TFa analyses in patients with and without periodontitis. However, to compare salivary MDA, SA, and total protein levels in these groups we suggest fresh samples to be studied.
Analysis of β/α Globin Ratio by Using Relative qRT‐PCR for Diagnosis of Beta‐Thalassemia Carriers
Authors: Ranjbaran Reza , Okhovat Mohammad Ali , Mobarhanfard Arash , Aboualizadeh Farzaneh , Abbasi Mozhdeh , Moezzi Leili , Golafshan Habib Allah , Behzad‐Behbahani Abbas , Bagheri Mandana , Sharifzadeh Sedigheh
Published: July 2013

Background

Current routine tests for premarital screening of β‐thalassemia carriers are not applicable for diagnosis of rare atypical minor β‐thalassemia cases. A more specialized laboratory evaluation for them is the measurement of β/α chain synthesis ratio with the assistance of radioactive amino acids. This method is also no longer routinely accessible. Consequently it is required to establish a rapid, trouble‐free, and reliable method that encompasses all the cases of β‐thalassemia carriers. Therefore we have determined β/α‐globin mRNA ratio by applying relative qRT‐PCR in various β‐thalassemia patients.

Methods

Reticulocytes RNA extraction and subsequent cDNA synthesis were performed, followed by relative qRT‐PCR for α‐ and β‐globin chain genes and ‐actin gene as an endogenous reference. ‐Globin gene ratio was then evaluated with the Pfaffl method.

Results

The mean of β/α ratio was 0.99, 0.81, 0.69, and 0.69 for normal population, minor, intermediate, and major β‐thalassemia, respectively. Approximately 6% of cases with minor thalassemia RBC index and normal HbA2 and having a decreased β/α ratio were located in the minor β‐thalassemia group. The mean of β/α mRNA ratio in normal individuals and minor β‐thalassemia was significantly different with all other groups (P‐value < 0.05). Nevertheless, there was no such association between β/α mRNA ratio in major and intermediate β‐thalassemia.

Conclusion

According to the significant differences achieved, no overlapping between minor β‐thalassemia and normal group, capability of diagnosing atypical minor β‐thalassemia, and accessibility of this technique, we can declare that this method could be suggested as a routine premarital screening test for β‐thalassemia carriers.
Measurement of Serum Total Vitamin D (25‐OH) Using Automated Immunoassay in Comparision With Liquid Chromatography Tandem‐Mass Spectrometry
Authors: Shin Sang‐Yong , Kwon Min‐Jung , Song Junghan , Park Hyosoon , Woo Hee‐Yeon
Published: July 2013

Background

The associations of vitamin D deficiency with many nonskeletal diseases are still being discovered. We evaluated the use of an automated immunoassay to measure serum total vitamin D (25‐OH) and assessed vitamin D status in a Korean adult population.

Methods

We compared the Elecsys Vitamin D (25‐OH) Total Assay (Roche Diagnostics) with liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) using 300 serum samples. Total imprecision was calculated using three levels of quality control materials and serum samples. We also investigated the vitamin D status using data for 70,762 cases who had a routine health check‐up in our hospitals.

Results

The regression equation: Elecsys = 0.882 × LC‐MS/MS + 6.814 (r = 0.926). Total imprecision was within 10% for all quality control materials and serum samples. The prevalence of vitamin D deficiency using cut‐off values of <50 nmol/l (<20 ng/ml) were 70.3% in males and 86.4% in females, respectively. The prevalence of vitamin D deficiency was higher in younger subjects than in older subjects (P for linear‐by‐linear association was <0.001). Serum vitamin D levels were highest in September and lowest in February.

Conclusion

The Elecsys Vitamin D (25‐OH) Total Assay was comparable to LC‐MS/MS and appropriate for routine clinical use. Vitamin D deficiency is common in Korean adults.
PDE4D Gene Polymorphisms and Coronary Heart Disease: A Case‐Control Study in a North Indian Population
Authors: Sinha Ekata , Meitei Sanjenbam Yaiphaba , Garg Priyanka Rani , Saraswathy Kallur Nava
Published: July 2013

Background

The present study aims to assess the association of PDE4D gene polymorphisms (SNP83 and SNP87) with Coronary Heart Disease (CHD) in a single Mendelian population of Delhi.

Methods

A cross‐sectional study was carried out wherein intravenous blood samples were collected from 100 cases and 100 age, sex and ethnicity matched controls along with their demographic, life style, and clinical profiles.

Results

Genotypic frequencies of PDE4D gene variants 83 and 87 did not differ significantly between cases and controls. Odds ratio revealed a 1.4‐fold increased risk with PDE4D 83 C allele; though not significant. Both the SNPs showed significant association with serum triglyceride (TG) (P ≤ 0.05). A significant linkage disequilibrium was observed between the SNPs. The haplotype with mutant alleles of the two SNPs showed fivefold increased risk (though not significant) and that with normal allele of SNP 83 and mutant allele of SNP 87 (T‐T) was found to be significantly associated with the disease in the present population.

Conclusions

PDE4D gene variants 83 and 87 did not show any significant association with CHD. However, their interaction with TG and the haplotypic association found in the present population is indicative of the population‐specific risk associated with CHD where majority of the individuals have high cholesterol and high Body Mass Index (BMI).
Vitamin D and Its Relationship with Markers of Bone Metabolism in Healthy Asian Women
Authors: Tan Karen M.L. , Saw Sharon , Sethi Sunil K.
Published: July 2013

Background

In this study, we aimed to determine the normal ranges of 25‐hydroxy‐vitamin D3 (25‐OHD3), parathyroid hormone (PTH), and the markers of bone turnover, procollagen type 1 N propeptide (P1NP) and C‐terminal cross‐linked telopeptide of type 1 collagen (CTX), in normal healthy women in Singapore, and to explore the relationship between vitamin D, PTH, and these markers of bone turnover in the women.

Methods

One hundred and ninety‐seven healthy women, aged 25 to 60, were selected from a hospital staff health screening program; 68% were Chinese, 18% Malay, and 14% Indian. P1NP, CTX, and 25‐OHD3 were measured using the Roche Cobas® electrochemiluminescence immunoassay. Serum PTH was measured using the Siemens ADVIA Centaur® immunoassay.

Results

Sixty‐five percent had 25‐OHD3 concentrations <50 nmol/l. Vitamin D insufficiency (25‐OHD3 < 50 nmol/l) was more prevalent in Malays (89%) and Indians (82%) compared to Chinese (56%). There was no correlation between vitamin D and age. PTH positively correlated with age, and Malays and Indians had higher PTH concentrations than Chinese. There was an inverse correlation between PTH and 25‐OHD3, but no threshold of 25‐OHD3 concentrations at which PTH plateaued. The bone turnover markers P1NP and CTX inversely correlated with age but were not different between ethnic groups. CTX and P1NP exhibited good correlation, however, there was no significant correlation between 25‐OHD3 or PTH concentrations and the bone turnover markers P1NP and CTX.

Conclusions

Healthy women in Singapore have a high prevalence of vitamin D insufficiency. Vitamin D insufficiency was more prevalent in Malays and Indians compared to Chinese.
Association of Tyrosyl‐DNA Phosphodiesterase 1 Polymorphism With Tourette Syndrome in Taiwanese Patients
Authors: Wu Bor‐Tsang , Lin Wei‐Yong , Chou I‐Ching , Liu Hsin‐Ping , Lee Cheng‐Chun , Tsai Yuhsin , Wu Wan‐Chen , Tsai Fuu‐Jen
Published: July 2013

Background

Genetic, environmental, immunological, and hormonal factors contribute to the etiology of Tourette syndrome (TS). From the genetic standpoint, TS is a heterogeneous disorder. In our previous study, we found that a single nucleotide polymorphism (SNP) of x‐ray repair cross‐complementing group 1 (XRCC1), a DNA repair gene, was associated with TS. Previous studies also showed that tyrosyl‐DNA phosphodiesterase 1 (TDP1) interacts with XRCC1 to repair damaged DNA. However, the relationship between TS and SNPs of TDP1 gene is unknown. Therefore, the aim of this study was to test the hypothesis that if the TDP1 SNP, rs28365054 (c.400G>A, Ala134Thr), was associated with TS or not.

Methods

A case‐control study was designed to test the hypothesis. A total of 122 TS children and 106 normal children participated in the study. We used polymerase chain reaction to identify the SNP, rs28365054, of the TDP1 gene in the TS patients and the normal children.

Results

A polymorphism at position rs28365054 in the TDP1 gene had a significant difference (P < 0.05) in the genotype distributions between the TS patients and the control group. The AG genotype was a risk factor for TS with an odds ratio of 2.26 for the AG versus AA genotype (95% CI 1.08–4.72).

Conclusion

The findings of this study suggested that variants in the TDP1 gene might play a role in TS susceptibility.
Investigation of an alternative generic model for predicting pharmacokinetic changes during physiological stress
Authors: Peng Henry T. , Edginton Andrea N. , Cheung Bob
Published: July 2013

Physiologically based pharmacokinetic models were developed using MATLAB Simulink® and PK‐Sim®. We compared the capability and usefulness of these two models by simulating pharmacokinetic changes of midazolam under exercise and heat stress to verify the usefulness of MATLAB Simulink® as a generic PBPK modeling software. Although both models show good agreement with experimental data obtained under resting condition, their predictions of pharmacokinetics changes are less accurate in the stressful conditions. However, MATLAB Simulink® may be more flexible to include physiologically based processes such as oral absorption and simulate various stress parameters such as stress intensity, duration and timing of drug administration to improve model performance. Further work will be conducted to modify algorithms in our generic model developed using MATLAB Simulink® and to investigate pharmacokinetics under other physiological stress such as trauma.
Extended range simulations of the extreme snow storms over southern China in early 2008 with the BCC_AGCM2.1 model
Authors: Huang Anning , Zhang Yaocun , Wang Zaizhi , Wu Tongwun , Huang Danqing , Zhou Yang , Zhao Yong , Huang Ying , Kuang Xueyuan , Zhang Lujun , Fang Yongjie , Guo Yan
Published: July 2013

The 10–30 day extended range potential predictability of the Beijing Climate Center Atmospheric General Circulation Model version 2.1 (BCC_AGCM2.1) model with high horizontal resolution has been evaluated, and the associated influencing factors and possible physical mechanisms have been discussed through a case study of the long‐lasting extreme snow storms over southern China in early 2008. Comparison with meteorological observations suggests that the BCC_AGCM2.1 model forced by the real daily sea surface temperature (SST) well reproduced the extraordinarily frequent and long‐lasting heavy snow storm process over southern China in early 2008 including the spatial distribution and temporal evolution of the 2 m air temperature and snow rainfall but produced relatively larger errors in precipitation. Overall, the BCC‐AGCM2.1 model forced by the real daily SST shows good potential predictability on 10–30 day extended range time scale to some extent, at least from this extreme snow storm case study. Further analysis of the associated influencing factors and possible physical mechanisms indicates that the SST forcing is not as important as the initial conditions for the weather forecast within around 2 weeks in advance which is the upper limit of the daily weather forecast. However, the SST forcing with relatively larger day‐to‐day variability plays an important role in the potential predictability of the BCC_AGCM2.1 model on 10–30 day extended forecasting time scale through affecting the atmospheric variability. Results from this study provide us some necessary and valuable information for further development of an operational 10–30 day extended range forecasting system.
Long‐term and cross‐reactive immunogenicity of inactivated trivalent influenza vaccine in the elderly: MF59‐adjuvanted vaccine versus unadjuvanted vaccine
Authors: Song Joon Young , Cheong Hee Jin , Noh Ji Yun , Seo Yu Bin , Choi Won Suk , Cho Geum Joo , Hwang Taik Gun , Kim Woo Joo
Published: July 2013

Elderly people are at great risk for influenza‐related serious complications. However, influenza vaccine‐induced antibodies are believed to decline more rapidly in the elderly. This study was designed to evaluate the long‐term and cross‐reactive immunogenicity among those aged ≥65 years for two seasonal trivalent influenza vaccines during the 2009–2010 influenza season. One vaccine had the MF59 adjuvant, while the other did not contain an adjuvant. Serum hemagglutinin inhibition (HI) titers were determined pre‐vaccination and at 1 and 6 months post‐vaccination. Of the 100 subjects, 95 (95%) were followed‐up for 1 month after vaccination, and 76 (76%) were followed‐up for 6 months after vaccination. Both vaccines met the European Medicines Agency (EMA) criteria 1 month after vaccination. However, seroprotection for influenza B was not satisfactory, with a rate of 55.3% for the MF59 adjuvant vaccine and 47.9% for the vaccine without adjuvant. At 6 months post‐vaccination, the MF59‐adjuvanted vaccine showed a higher seroprotection rate than the unadjuvanted vaccine. At this point, the MF59‐adjuvanated vaccine still met the criteria of EMA for A/H1N1 (62.5% vs. 55.5%, P = 0.64) and A/H3N2 (72.5% vs. 47.2%, P = 0.04). Both vaccines showed excellent cross‐reactive immunogenicity for influenza A/Solomon Island/3/2006 (H1N1) and A/Wisconsin/67/2005 (H3N2), without significant differences. In comparison, cross‐reactive immunogenicity was not remarkable for the A/California/7/2009 (H1N1) and A/New Caledonia/20/1999 (H1N1) strains, which have a greater antigenic distance. In conclusion, the MF59‐adjuvanted influenza vaccine showed superior long‐term immunogenicity in the elderly compared to the unadjuvanted vaccine. However, cross‐reactive immunogenicity was not remarkably enhanced with the MF59 adjuvant. J. Med. Virol. 85:1591–1597, 2013. © 2013 Wiley Periodicals, Inc.
Human parechovirus and the risk of type 1 diabetes
Authors: Kolehmainen P. , Koskiniemi M. , Oikarinen S. , Veijola R. , Simell O. , Ilonen J. , Knip M. , Hyöty H. , Tauriainen S.
Published: July 2013

Human parechoviruses (HPeVs) are RNA viruses associated mainly with mild gastrointestinal and respiratory infections in children and also cause neonatal sepsis and CNS infections. Human enteroviruses, close relatives of HPeVs, associate with the development of type 1 diabetes. In this study, the potential role of HPeV infections in promoting beta cell autoimmunity was investigated by analyzing stool samples of 54 prediabetic case and 134 healthy control children for the presence of HPeV RNA and comparing the derived infection frequencies. All 188 children were participants of the Finnish prospective Diabetes Prediction and Prevention study. Viral RNA was screened for using an HPeV‐specific RT‐PCR method coupled to liquid hybridization of the PCR product. The overall HPeV infection frequency did not differ between prediabetic case and control children. However, case boys had more HPeV positive samples in the 6‐month period before becoming autoantibody positive, when compared to the matching time‐period in controls (P < 0.01). HPeV infection at a young age does not appear to play a major role in the development of beta‐cell autoimmunity. In boys, however, HPeVs showed time‐dependent association with the first detection of diabetes‐associated autoantibodies. Thus, in boys, HPeV infections cannot be excluded as a gender‐specific risk factor which promotes the development of type 1 diabetes. J. Med. Virol. 85:1619‐1623, 2013. © 2013 Wiley Periodicals, Inc.
Role of norovirus in acute gastroenteritis in the Northwest of Spain during 2010–2011
Authors: Manso Carmen F. , Torres Eva , Bou Germán , Romalde Jesús L.
Published: July 2013

A total of 2,643 samples from patients with gastroenteritis in Galicia (NW Spain) were tested for the presence of Norovirus (NoV). NoV genogroup GI was detected in 416 (15.7%) samples, while NoV genogroup GII was detected in 278 (10.5%) samples. Mixed infections of NoV GI and GII were observed in 53 (2%) samples. Total prevalence of NoV in the analyzed samples was 28.3%. Besides NoV diagnosis assay, all the specimens were also submitted to routine clinical bacteriology tests. Cryptosporidium spp. as well as adenovirus (AdV) and rotavirus (RV) were determined on some samples after specific request by hospital units. The results obtained allowed to determine the disease etiology in 14.4% of the patients. Taking into account all the microorganisms studied, the etiological agent was determined for 39.5% of the cases. The results indicated that NoVs are the leading cause of acute gastroenteritis in all age‐groups in Northwestern Spain, and that the lack of routine NoV diagnosis contributes to the underestimation of the importance of this virus, not only in outbreaks, but also in sporadic cases of acute gastroenteritis. J Med. Virol. 85:2009–2015, 2013.. © 2013 Wiley Periodicals, Inc.