bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis and Characterisation of Selected Group 4 Metallocene Complexes with 1,2‐Bis(4′,4′,5′,5′‐tetramethyl[1′,3′,2′]dioxaborolan‐2′‐yl)acetylene
Authors: Altenburger Kai , Arndt Perdita , Spannenberg Anke , Baumann Wolfgang , Rosenthal Uwe
Published: May 2013

The reactions of the metallocene generators Cp′2M(L)(η2‐Me3SiC≡CSiMe3) [1a‐Ti: Cp′ = Cp = η5‐cyclopentadienyl, M = Ti, L = none; 1b‐Ti: Cp′ = Cp* = η5‐pentamethylcyclopentadienyl, M = Ti, L = none; 1c‐Ti: Cp′2 = rac‐(ebthi) = rac‐ethylenebistetrahydroindenyl, M = Ti, L = none; 1a‐Zr: Cp′ = Cp, M = Zr, L = pyridine; 1b‐Zr: Cp′ = Cp*, M = Zr, L = none; 1c‐Zr: Cp′2 = rac‐(ebthi), M = Zr, L = none] with 1,2‐bis(4′,4′,5′,5′‐tetramethyl[1′,3′,2′]dioxaborolan‐2′‐yl)acetylene (bPinBA, 2) as a di‐heteroatom‐substituted alkyne were investigated. A slightly special reaction of 1a‐Ti with 2 produced no titanacyclopropene or titanacyclopentadiene, but instead complex 3 was produced by the coupling of two alkyne units with one of the Cp ligands to form a six‐membered ring annelated to a five‐membered one. The titanocene complexes 1b‐Ti and 1c‐Ti reacted with 2 to form the titanacylopropenes 4 and 5. The complex 1a‐Zr reacts with 2 to the corresponding zirconacyclopropene 6 as a byproduct, in which the pyridine ligand remains coordinated. If the pyridine ligand dissociates, a coupling with a second alkyne yields the zirconacyclopentadiene 7 as the main product. The reaction of the sterically more demanding zirconocene precursor 1c‐Zr also yielded the zirconacyclopentadiene 8, whereas 1b‐Zr did not react with 2. The complex rac‐(ebthi)Ti(η2‐bPinBA) (5) reacts with gaseous dry CO2 directly to form the titanafuranone 9. The molecular structures of complexes 5 and 6 were characterised by single‐crystal X‐ray crystallography.
Reduction of fat content during frying using dried egg white and fiber solutions
Authors: Brannan Robert G. , Myers Andrew S. , Herrick Christopher S.
Published: May 2013

Producers of deep‐fried foods seek new methods to lower the fat content of these foods. The effectiveness of edible films of proteins and carbohydrates and the addition of prefrying dips of egg white lower fat absorption. Common additions of chemicals to films called plasticizers allow them to improve distribution when coating a substrate and improve their water vapor permeability and mechanical properties. The purpose of this study was to determine whether the addition of corn or oat fiber to an egg albumin solution will increase fat absorption inhibition that occurs in deep‐fat frying compared to an egg albumin solution alone. Dipping chicken fritters in an egg white dip with no fiber present produced samples with the highest lipid reductions compared to the control. The addition of fiber to any of the dips did not produce a synergistic effect to reduce lipid absorption. The egg dip, 1%, and 2% fiber dip amounts were successful in reducing the lipid content compared to control, but not the 5% fiber dip amount. As the fiber dip concentration decreased for corn and oat fiber, lipid levels decreased. The addition of egg white, corn fiber, or oat fiber affected the color and texture of the fritters.

Practical applications: Reducing the oil content of chicken fritters could provide lower fat alternatives to normal deep fried foods that still retain the desirable characteristics that full fat foods provide. If fat reduction below 35% calories from fat can be achieved, markets such as schools and healthcare that are currently restricted to these types of products could be opened.
Scalable Synthesis of Enantiomerically Pure cis‐1,2‐Cyclohexanediamine Derivatives and Conformationally Rigid 7‐Aza­bi­cyclo[2.2.1]heptan‐2‐amines
Authors: Pandey Ganesh , Dey Debasis , Fernandes Rushil
Published: May 2013

A scalable approach to the syntheses of enantiomerically pure cis‐1,2‐cyclohexanediamines as well as exo‐ and endo‐7‐azabicyclo[2.2.1]heptan‐2‐amines is reported that utilizes meso‐tert‐butyl 2,3‐bis(phenylsulfonyl)‐7‐azabicyclo[2.2.1]hept‐2‐ene‐7‐carboxylate as a starting material.
Phenolphthalein induces centrosome amplification and tubulin depolymerization in vitro
Authors: Heard Pamela L. , Rubitski Elizabeth E. , Spellman Richard A. , Schuler Maik J.
Published: May 2013

Aneuploidy is a major cause of human reproductive failure and plays a large role in cancer. Phenolphthalein (PHT) induces tumors in rodents but its primary mechanism does not seem to be DNA damage. In heterozygous TSG‐p53® mice, PHT induces lymphomas and also micronuclei (MN), many containing kinetochores (K), implying chromosome loss (aneuploidy). The induction of aneuploidy would be compatible with the loss of the normal p53 gene seen in the lymphomas. In this study, we confirm PHT's aneugenicity and determine the aneugenic mechanism of PHT by combining traditional genetic toxicology assays with image and flow cytometry methods. The data revealed that PHT induces tubulin polymerization abnormalities and deregulates the centrosome duplication cycle causing centrosome amplification. We also show that one of the consequences of these events is apoptosis. Environ. Mol. Mutagen. 54:308–316, 2013. © 2013 Wiley Periodicals, Inc.
A role for Myh1 in DNA repair after treatment with strand‐breaking and crosslinking chemotherapeutic agents
Authors: Jansson Kristina , Alao John P. , Viktorsson Kristina , Warringer Jonas , Lewensohn Rolf , Sunnerhagen Per
Published: May 2013

The highly conserved DNA glycosylase MutY is implicated in repair of oxidative DNA damage, in particular in removing adenines misincorporated opposite 7,8‐dihydro‐8‐oxoguanine (8‐oxo‐G). The MutY homologues (MutYH) physically associate with proteins implicated in replication, DNA repair, and checkpoint signaling, specifically with the DNA damage sensor complex 9‐1‐1 proteins. Here, we ask whether MutYH could have a broader function in sensing and repairing different types of DNA damage induced by conventional chemotherapeutics. Thus, we examined if deletion of the Schizosaccharomyces pombe MutY homologue, Myh1, alone or in combination with deletion of either component of the 9‐1‐1 sensor complex, influences survival after exposure to different classes of DNA damaging chemotherapeutics that do not act primarily by causing 8‐oxoG lesions. We show that Myh1 contributes to survival on genotoxic stresses induced by the oxidizing, DNA double strand break‐inducing, bleomycins, or the DNA crosslinking platinum compounds, particularly in a rad1 mutant background. Exposure of cells to cisplatin leads to a moderate overall accumulation of Myh1 protein. Interestingly, we found that DNA damage induced by phleomycin results in increased chromatin association of Myh1. Further, we demonstrate that Myh1 relocalizes to the nucleus after exposure to hydrogen peroxide or chemotherapeutics, most prominently seen after phleomycin treatment. These observations indicate a wider role of Myh1 in DNA repair and DNA damage‐induced checkpoint activation than previously thought. Environ. Mol. Mutagen. 54:327–337, 2013. © 2013 Wiley Periodicals, Inc.
Brain microvessel cross‐presentation is a hallmark of experimental cerebral malaria
Authors: Howland Shanshan W. , Poh Chek Meng , Gun Sin Yee , Claser Carla , Malleret Benoit , Shastri Nilabh , Ginhoux Florent , Grotenbreg Gijsbert M. , Rénia Laurent
Published: May 2013

Cerebral malaria is a devastating complication of Plasmodium falciparum infection. Its pathogenesis is complex, involving both parasite‐ and immune‐mediated events. CD8+ T cells play an effector role in murine experimental cerebral malaria (ECM) induced by Plasmodium berghei ANKA (PbA) infection. We have identified a highly immunogenic CD8 epitope in glideosome‐associated protein 50 that is conserved across rodent malaria species. Epitope‐specific CD8+ T cells are induced during PbA infection, migrating to the brain just before neurological signs manifest. They are functional, cytotoxic and can damage the blood–brain barrier in vivo. Such CD8+ T cells are also found in the brain during infection with parasite strains/species that do not induce neuropathology. We demonstrate here that PbA infection causes brain microvessels to cross‐present parasite antigen, while non‐ECM‐causing parasites do not. Further, treatment with fast‐acting anti‐malarial drugs before the onset of ECM reduces parasite load and thus antigen presentation in the brain, preventing ECM death. Thus our data suggest that combined therapies targeting both the parasite and host antigen‐presenting cells may improve the outcome of CM patients.
Contribution of ADAMTS1 as a tumor suppressor gene in human breast carcinoma. Linking its tumor inhibitory properties to its proteolytic activity on nidogen‐1 and nidogen‐2
Authors: Martino‐Echarri Estefanía , Fernández‐Rodríguez Rubén , Rodríguez‐Baena Francisco Javier , Barrientos‐Durán Antonio , Torres‐Collado Antoni X. , del Carmen Plaza‐Calonge María , Amador‐Cubero Suyapa , Cortés Javier , Reynolds Louise E. , Hodivala‐Dilke Kairbaan M. , Rodríguez‐Manzaneque Juan Carlos
Published: May 2013

The extracellular protease ADAMTS1 (A disintegrin and metalloprotease with thrombospondin repeats 1) has been described as an anti‐angiogenic molecule and its role as a putative tumor protective molecule has also been suggested. Here, we have used a tumor xenograft model to determine the role of ADAMTS1 in tumor growth and angiogenesis. Increasing levels of the protease led to the complete inhibition of tumor growth. In an attempt to elucidate the mechanism of action of this protease, we focused our attention on its proteolytic activity on nidogens, one of the main components of the vascular basement membrane. The increased expression of ADAMTS1 was accompanied by increased proteolysis of nidogen‐1 and ‐2 and their almost complete removal from vascular structures, together with major morphological alterations of tumor blood vessels and a decreased vessel density. The clinical relevance of this work is supported by our observations that ADAMTS1 expression is decreased in breast tumor specimens when compared with healthy tissue. Our studies also reveal that the cleavage of nidogen‐1 and ‐2 is partially inhibited in human tumor samples. Moreover, the deposition of both nidogens surrounding vascular structures is drastically altered, implying a possible reduction in the maintenance of vessel integrity. Our studies reflect the requirement to explore the functional interactions between proteases and specific substrates in cancer biology.
Short‐term splenic impact of single‐strand DNA functionalized multi‐walled carbon nanotubes intraperitoneally injected in rats
Authors: Clichici Simona , Biris Alexandru Radu , Catoi Cornel , Filip Adriana , Tabaran Flaviu
Published: May 2013

In recent years, a great deal of studies have focused on the possible toxicity of carbon nanotubes (CNT), as a result of their potential applications in the field of nanotechnologies. The investigation of spleen toxicity is part of the carbon nanotubes‐induced toxicity assessment. In this study, we investigated the possible toxic effects of CNT on the rat spleen, after intraperitoneally (i.p.) administration of a single dose [1.5 ml; 2 mg multi‐walled (MW) CNT per body weight (bw)] of multi‐walled carbon nanotubes (exterior diameter 15–25 nm, interior diameter 10–15 nm, surface 88 m2 g–1) functionalized 1:1 with single‐strand DNA (ss‐DNA‐MWCNT, 270 mg l–1). CNT functionalization with DNA determines a stable dispersion in the body fluids. For the detection of carbon nanotubes in the spleen, Raman spectroscopy, histopathologic examination, confocal microscopy and transmission electron microscopy (TEM) were performed at different time points (1, 6, 24, 48 and 144 h) after MWCNT administration. The dynamics of oxidative stress parameters (malondialdehyde, protein carbonyls and reduced glutathione), along with nitrosative stress parameters (nitric oxide, inducible NO synthase), the pro‐inflammatory cytokines [interleukin‐(IL)‐1β] and the number of cells expressing caspase 3 and proliferating cell nuclear antigen (PCNA) were assessed. Our results indicate that, after i.p. administration, MWCNT translocate progressively in the spleen, with a peak of concentration after 48 h, and determine lymphoid hyperplasia and an increase in the number of cells which undergo apoptosis, in parallel with the enhancement of the mitosis in the white pulp and with transient alterations of oxidative stress and inflammation that need further investigations for a longer period of monitoring. Copyright © 2013 John Wiley & Sons, Ltd.
Photoacoustic and photothermal detection of circulating tumor cells, bacteria and nanoparticles in cerebrospinal fluid in vivo and ex vivo
Authors: Nedosekin Dmitry A. , Juratli Mazen A. , Sarimollaoglu Mustafa , Moore Christopher L. , Rusch Nancy J. , Smeltzer Mark S. , Zharov Vladimir P. , Galanzha Ekaterina I.
Published: May 2013

Circulating cells, bacteria, proteins, microparticles, and DNA in cerebrospinal fluid (CSF) are excellent biomarkers of many diseases, including cancer and infections. However, the sensitivity of existing methods is limited in their ability to detect rare CSF biomarkers at the treatable, early‐stage of diseases. Here, we introduce novel CSF tests based on in vivo photoacoustic flow cytometry (PAFC) and ex vivo photothermal scanning cytometry. In the CSF of tumor‐bearing mice, we molecularly detected in vivo circulating tumor cells (CTCs) before the development of breast cancer brain metastasis with 20‐times higher sensitivity than with current assays. For the first time, we demonstrated assessing three pathways (i.e., blood, lymphatic, and CSF) of CTC dissemination, tracking nanoparticles in CSF in vivo and their imaging ex vivo. In label‐free CSF samples, we counted leukocytes, erythrocytes, melanoma cells, and bacteria and imaged intracellular cytochromes, hemoglobin, melanin, and carotenoids, respectively. Taking into account the safety of PAFC, its translation for use in humans is expected to improve disease diagnosis beyond conventional detection limits. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Biocomposites reinforced by fibers or tubes as scaffolds for tissue engineering or regenerative medicine
Authors: Li Xiaoming , Yang Yu , Fan Yubo , Feng Qingling , Cui Fu‐zhai , Watari Fumio
Published: May 2013

As a dynamic and hierarchically organized composite, native extracellular matrix (ECM) not only supplies mechanical support, which the embedded cells need, but also regulates various cellular activities through interaction with them. On the basis of the ECM‐mimetic principle, good biocompatibility and appropriate mechanical properties are the two basic requirements that the ideal scaffolds for the tissue engineering or regenerative medicine need. Some fibers and tubes have been shown effective to reinforce scaffolds for tissue engineering or regenerative medicine. In this review, three parts, namely properties affected by the addition of fibers or tubes, scaffolds reinforced by fibers or tubes for soft tissue repair, and scaffolds reinforced by fibers or tubes for hard tissue repair are stated, which shows that tissue repair or regeneration efficacy was enhanced significantly by fiber or tube reinforcement. In addition, it indicates that these reinforcing agents can improve the biocompatibility and biodegradation of the scaffolds in most cases. However, there are still some concerns, such as the homogeneousness in structure or composition throughout the reinforced scaffolds, the adhesive strength between the matrix and the fibers or tubes, cytotoxicity of nanoscaled reinforcing agents, etc., which were also discussed in the conclusion and perspectives part. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 1580–1594, 2014.
XPS of oxygen atoms on Ag(111) and Ag(110) surfaces: Accurate study with SAC/SAC‐CI combined with dipped adcluster model
Authors: Ishikawa Atsushi , Nakatsuji Hiroshi
Published: May 2013

O1s core‐electron binding energies (CEBE) of the atomic oxygens on different Ag surfaces were investigated by the symmetry adapted cluster‐configuration interaction (SAC‐CI) method combined with the dipped adcluster model, in which the electron exchange between bulk metal and adsorbate is taken into account properly. Electrophilic and nucleophilic oxygens (Oelec and Onuc) that might be important for olefin epoxidation in a low‐oxygen coverage condition were focused here. We consider the O1s CEBE as a key property to distinguish the surface oxygen states, and series of calculation was carried out by the Hartree–Fock, Density functional theory, and SAC/SAC‐CI methods. The experimental information and our SAC/SAC‐CI results indicate that Oelec is the atomic oxygen adsorbed on the fcc site of Ag(111) and that Onuc is the one on the reconstructed added‐row site of Ag(110) and that one‐ and two‐electron transfers occur, respectively, to the Oelec and Onuc adclusters from the silver surface. © 2013 Wiley Periodicals, Inc.
Salt‐Dependence of Homology Searching Step by RecA Nucleoprotein Filaments
Authors: Liao Song‐Mao , Wu Hung‐Yi , Li Hung‐Wen
Published: May 2013

RecA recombinase binds onto single‐stranded DNA (ssDNA) and searches for its homologous sequence along double‐stranded DNA (dsDNA). This homologous recombination process is required for repairing double‐stranded DNA breaks. Here, we applied lateral magnetic tweezers to stretch duplex DNA molecules (Lambda DNA, 48,502 bp) in order to monitor the homology searching step by RecA nucleoprotein filaments at the single‐molecule level. From individual searching events, the diffusion coefficient of the RecA nucleoprotein filament is determined to be ∼ 0.5‐1 μm2/s. The nearly salt‐independence of the diffusion coefficients of RecA nucleoprotein filaments implies that our observed RecA searching events were mainly carried out by the one‐dimensional sliding mode.
Population Pharmacokinetic Analysis of Orally‐Administered Ruxolitinib (INCB018424 Phosphate) in Patients With Primary Myelofibrosis (PMF), Post‐Polycythemia Vera Myelofibrosis (PPV‐MF) or Post‐Essential Thrombocythemia Myelofibrosis (PET MF)
Authors: Chen Xuejun , Williams William V. , Sandor Victor , Yeleswaram Swamy
Published: May 2013

Ruxolitinib is a selective inhibitor of Janus kinase 1 and 2, which is approved to treat intermediate or high‐risk myelofibrosis. The population pharmacokinetics for ruxolitinib were characterized by a modeling dataset of 272 subjects from a Phase 2 and a Phase 3 study and validated by an external validation dataset of 142 subjects from a second Phase 3 study. The PK of ruxolitinib was adequately described by a two‐compartment disposition model with first‐order absorption and linear elimination. All model parameters were estimated with good precision. Gender and body weight were identified as covariates for oral clearance (CL/F) and volume of distribution for central compartment (Vc/F), respectively. Apparent oral clearance was 22.1 and 17.7 L/h for a typical male and female subject, respectively, with 39.1% unexplained inter‐individual variability (IIV). The typical Vc/F for a subject with a median weight of 72.9 kg was estimated to be 58.6 L, with 28% unexplained IIV. The model predictive performance was validated by visual predictive check (VPC) and the external validation dataset. This analysis suggests that effects of gender and body weight on ruxolitinib PK are not clinically significant and hence no dose adjustment is needed based on gender and weight.
Variability of Histamine Pharmacodynamic Response in Children With Allergic Rhinitis
Authors: Jones Bridgette L. , Kearns Gregory , Neville Kathleen A. , Sherwin Catherine M.T. , Spigarelli Michael M.G. , Leeder J. Steven
Published: May 2013

Histamine iontophoresis with laser Doppler monitoring (HILD) is a robust and dynamic surrogate for histamine microvasculature response. We characterized histamine pharmacodynamics in children using HILD. HILD was performed in 54 children with allergic rhinitis. A non‐compartmental analysis and non‐linear mixed‐effects model with a linked effect PK/PD model was used to provide estimates for area under the effect curve (AUEC), maximal response over baseline (EffmaxNT), and time of EffmaxNT (Tmax). Data were placed in sub‐groups by visualization of time vs. response relationships. ANOVA and regression analyses were used for sub‐group comparisons. Three histamine response phenotypes were identified. One group demonstrated a hyper‐responsive phenotype (higher Tmax, EffmaxNt and AUEC, P < .01). AUEC and EffmaxNT were more strongly associated in this group (r2 = 0.86) than the entire cohort (r2 = 0.64). These data demonstrate a hyper‐responsive histamine phenotype via HILD. This finding is important to future pharmacologic studies of antihistamines.
Pharmacokinetic and Pharmacodynamic Interaction of Nadolol With Itraconazole, Rifampicin and Grapefruit Juice in Healthy Volunteers
Authors: Misaka Shingen , Miyazaki Nozomu , Yatabe Midori S. , Ono Tomoyuki , Shikama Yayoi , Fukushima Tetsuhito , Kimura Junko
Published: May 2013

To evaluate effects of itraconazole, rifampicin and grapefruit juice on pharmacokinetics and pharmacodynamics of a hydrophilic non‐selective β‐adrenoceptor blocker nadolol, we conducted an open‐label, four‐way crossover study in 10 healthy male volunteers. A single oral dose of 30 mg nadolol was administered with water (control), itraconazole (100 mg), or grapefruit juice (300 mL), or after a 6‐day pretreatment with rifampicin (450 mg/day). Plasma concentrations and urinary excretions of nadolol were measured over 48 hours after its dosing. Systolic and diastolic blood pressures and pulse rate were periodically recorded after nadolol administration as pharmacodynamic parameters. Itraconazole increased the peak plasma concentration and the area under the plasma concentration–time curve (AUC0−∞) of nadolol by 468% and 224% of control, respectively (P < .001). A slight, but not statistically significant, decrease in AUC0−∞ of nadolol was observed in rifampicin and grapefruit juice phases as compared to control. Elimination half‐life for nadolol did not differ among the four phases. During itraconazole phase, nadolol reduced pharmacodynamic parameters to a greater extent than the other phases. These results suggest that itraconazole substantially increases the oral availability of nadolol possibly by the inhibition of intestinal P‐glycoprotein, whereas grapefruit juice has little effect on nadolol pharmacokinetics.
Kinetic Alfvén wave instability driven by field‐aligned currents in a low‐β plasma
Authors: Chen L. , Wu D. J. , Huang J.
Published: May 2013

Kinetic Alfvén waves (KAWs) can play an important role in the energization of plasma particles and the formation of filamentous structures, which commonly are encountered and frequently accompanied by field‐aligned currents in various magneto‐plasmas, such as laboratory, auroral, and coronal plasmas. Based on a low‐frequency kinetic dispersion equation in frequency ω<ωci (the ion cyclotron frequency), KAW instability driven by a field‐aligned current, which is carried by the field‐aligned drift of electrons at velocity VD, is investigated in a low‐β plasma of β<Q≪1, where β is the kinetic‐to‐magnetic pressure ratio and Q (≡me/mi≪1) is the mass ratio of electrons to ions. An instability condition and the corresponding growth rate are obtained, which depends on the plasma β parameter as well as the drift velocity VD. The results show that the KAW instability occurs in the perpendicular wave number range of , in which the growth rate reaches its maximum at for fixed VD and β. As VD increases, this growing wave number range widens and the growth rate increases, but the maximal‐growing wave number decreases. On the other hand, as the plasma βparameter decreases, the growing wave number range also widens, and the maximal‐growing wave number and growth rate both increase. These results have potential importance in understanding the physics of the electric current dissipation and plasma active phenomena since the field‐aligned current is one of the most active factors in space and astrophysical plasmas.
Generation of continental rifts, basins, and swells by lithosphere instabilities
Authors: Fourel Loïc , Milelli Laura , Jaupart Claude , Limare Angela
Published: May 2013

Continents may be affected simultaneously by rifting, uplift, volcanic activity, and basin formation in several different locations, suggesting a common driving mechanism that is intrinsic to continents. We describe a new type of convective instability at the base of the lithosphere that leads to a remarkable spatial pattern at the scale of an entire continent. We carried out fluid mechanics laboratory experiments on buoyant blocks of finite size that became unstable due to cooling from above. Dynamical behavior depends on three dimensionless numbers, a Rayleigh number for the unstable block, a buoyancy number that scales the intrinsic density contrast to the thermal one, and the aspect ratio of the block. Within the block, instability develops in two different ways in an outer annulus and in an interior region. In the outer annulus, upwellings and downwellings take the form of periodically spaced radial spokes. The interior region hosts the more familiar convective pattern of polygonal cells. In geological conditions, such instabilities should manifest themselves as linear rifts striking at a right angle to the continent‐ocean boundary and an array of domal uplifts, volcanic swells, and basins in the continental interior. Simple scaling laws for the dimensions and spacings of the convective structures are derived. For the subcontinental lithospheric mantle, these dimensions take values in the 500–1000 km range, close to geological examples. The large intrinsic buoyancy of Archean lithospheric roots prevents this type of instability, which explains why the widespread volcanic activity that currently affects Western Africa is confined to post‐Archean domains.
Comparison of comfort and image quality with two endorectal coils in MRI of the prostate
Authors: Powell Daniel K. , Kodsi Karen L. , Levin Galina , Yim Angela , Nicholson Duane , Kagen Alexander C.
Published: May 2013

Purpose

To prospectively evaluate comfort and image quality of prostate MRI using two different endorectal (ER) coils.

Materials and Methods

Thirty consecutive patients were prospectively randomized to receive prostate MRI using either a prostate endocoil (PEC) or colorectal endocoil (CEC). Patients and operators were surveyed with regard to endocoil placement. Four Body MRI trained radiologists rated image quality for each examination and additional selected blinded coronal T2 weighted images.

Results

Average patient discomfort (on a 0–10 pain scale) was greater with the PEC (5.0 for PEC and 2.7 for CEC) with a statistically significant difference (P < 0.03). Ability to identify the neurovascular bundle (NVB) was 5.8 times more likely to be rated excellent with the CEC compared with the PEC (P < 0.003). Image quality with CEC was 3.5 times more highly rated (P < 0.04). In particular, signal‐to‐noise ratio (SNR) with the CEC was 3.0 times more highly rated than with the PEC (P < 0.05).

Conclusion

The smaller CEC was better tolerated by patients than the traditional PEC, and resulted in at least equivalent, and in some instances improved image quality. This may result in fewer aborted cases and lead to decreased procedural intolerance to endorectal coil MRI. J. Magn. Reson. Imaging 2014;39:419–426. © 2013 Wiley Periodicals, Inc.
Gadobutrol in the central nervous system at three doses: Results from a phase II, randomized, multicenter trial
Authors: Breuer Josy , Gutierrez Juan , Latchaw Richard , Lehr Robert , Sorensen A. Gregory
Published: May 2013

Purpose

To investigate the efficacy and safety of three doses of gadobutrol and determine the minimum effective dose for contrast‐enhanced MRI of the central nervous system (CNS).

Materials and Methods

This was a Phase II, multicenter, double‐blind, parallel‐group controlled study in subjects referred for contrast‐enhanced MRI of the CNS. Subjects were randomized to receive gadobutrol 0.03, 0.1, or 0.3 mmol/kg body weight, and underwent unenhanced, gadobutrol‐enhanced, and comparator‐enhanced MRI scans. Three blinded readers assessed the images. Primary efficacy variables were number of lesions detected, border delineation, contrast enhancement, and internal morphology.

Results

Of the 229 randomized subjects, 173 were evaluated for efficacy. Clinically meaningful improvements in lesion border delineation, contrast enhancement, and internal morphology were observed for 0.1 mmol/kg gadobutrol. Pair‐wise comparisons of a composite score of the four primary variables showed the 0.1 mmol/kg dose to be statistically superior to the 0.03 mmol/kg dose (P = 0.003). The 0.3 mmol/kg dose showed no statistically significant difference with the 0.1 mmol/kg dose. Twenty‐two (9.8%) subjects reported at least one treatment‐emergent adverse event (TEAE). No TEAE was reported at an incidence >3.5%.

Conclusion

The 0.1 mmol/kg dose of gadobutrol was effective and well tolerated for contrast‐enhanced MRI of the CNS. J. Magn. Reson. Imaging 2014;39:410–418. © 2013 Wiley Periodicals, Inc.
Whole‐body MR angiography: First experiences with the new TimCT technology with single contrast injection
Authors: Naguib Nagy N.N. , Bohrt Kevin , Nour‐Eldin Nour‐Eldin A. , Schulz Boris , Tawfik Ahmed M. , Siebenhandel Petra , Bodelle Boris , Eichler Katrin , Moritz Anton , Vogl Thomas J. , Zangos Stephan
Published: May 2013

Purpose

To assess image quality, presence of artifacts, arterial stenosis, and interobserver agreement of Tim‐CT in assessment of the arterial system using contrast‐enhanced whole‐body‐MRA (CE‐Wb‐MRA) with a single contrast‐medium injection in patients with arteriosclerosis.

Materials and Methods

The retrospective study included 18 patients (mean age, 68 years). A total of 468 arteries were evaluated. CE‐Wb‐MRA was performed using Tim‐CT technology on a 1.5 Tesla (T) MRI after injecting a single dose of Vasovist. Evaluations were independently performed by two radiologists. The arterial system was divided into seven anatomic locations. Each radiologist assessed the image quality, degree of artifacts, and arterial stenosis in different locations.

Results

All Wb‐MRA examinations were technically successful. Image quality: 28.42% arteries were excellent, 29.17% were good, 22.54% were satisfactory, 9.40% were poor, and 5.13% of insufficient quality. Occurrence of artifacts: 37.25% were free of artifacts, 49.44% minimal artifacts not affecting diagnosis, and 13.31% strong artifacts not permitting a diagnosis. A total of 60.00% arteries showed no stenosis, 8.76% were ≤50% stenotic, 5.17% were 51–75% stenotic, 4.38% were 76–99%, and 8.54% total occlusion. The interobserver agreement was good for supra‐aortic, pelvic, and upper and lower leg regions.

Conclusion

CE‐Wb‐MRA using the TimCT technology and with a single contrast injection is a feasible tool for whole‐body MRA. J. Magn. Reson. Imaging 2014;39:434–439. © 2013 Wiley Periodicals, Inc.
Endorectal MRI and MR spectroscopic imaging of prostate cancer: Developing selection criteria for MR‐guided focal therapy
Authors: Chang Stephanie T. , Westphalen Antonio C. , Jha Priyanka , Jung Adam J. , Carroll Peter R. , Kurhanewicz John , Coakley Fergus V.
Published: May 2013

Purpose

To investigate criteria that can identify dominant treatable prostate cancer foci with high certainty at endorectal magnetic resonance imaging (MRI) and MR spectroscopic (MRS) imaging, and thus facilitate selection of patients who are radiological candidates for MR‐guided focal therapy.

Materials and Methods

We retrospectively identified 88 patients with biopsy‐proven prostate cancer who underwent endorectal MRI and MRS imaging prior to radical prostatectomy with creation of histopathological tumor maps. Two independent readers noted the largest tumor foci at MRI, if visible, and the volume of concordant abnormal tissue at MRS imaging, if present. A logistic random intercept model was used to determine the association between clinical and MR findings and correct identification of treatable (over 0.5 cm3) dominant intraprostatic tumor foci.

Results

Readers 1 and 2 identified dominant tumor foci in 50 (57%) and 58 (65%) of 88 patients; 42 (84%) and 48 (83%) of these were dominant treatable lesions at histopathology, respectively. Within the statistical model, the volume of concordant spectroscopic abnormality was the only factor that predicted correct identification of a dominant treatable lesion on T2‐weighted images (odds ratio = 1.75; 95% confidence interval = 1.08 to 2.82; P value = 0.02). In particular, all visible lesions on T2‐weighted imaging associated with at least 0.54 cm3 of concordant spectroscopic abnormality were correctly identified dominant treatable tumor foci.

Conclusion

Patients with dominant intraprostatic tumor foci seen on T2‐weighted MRI and associated with at least 0.54 cm3 of concordant MRS imaging abnormality may be radiological candidates for MR‐guided focal therapy. J. Magn. Reson. Imaging 2014;39:519–525. © 2013 Wiley Periodicals, Inc.
Development of a new fluorescence immunochromatography strip for detection of chloramphenicol residues in chicken muscles
Authors: Bai Zhihong , Luo Yunbo , Xu Wentao , Gao Huafang , Han Pei , Liu Tao , Wang Hui , Chen Ailiang , Huang Kunlun
Published: May 2013

BACKGROUND

Chloramphenicol (CAP), an antimicrobial drug that is widely used in animal feed, would have a negative effect on human health due to its low elimination rate and relatively high residue in animal food. It is important to develop a rapid and economic method to determine CAP in animal food to ensure that human health is not affected.

RESULTS

A new fluorescence immunochromatography strip was developed and established for the detection of CAP residue in chicken muscles for the first time. A CAP–bovine serum albumin conjugate, monoclonal antibody and polyclonal antibody against CAP were applied to constitute a fluorescence immunochromatography strip. The fluorescence intensity was detected by a charge‐coupled device scanner and transformed to a digital value. The CAP linearity working range was from 0.1 ng mL−1 to 20 ng mL−1 with a limit of detection of 0.1 ng mL−1 within 10 min. The performance of the strip assay was compared with a commercial ELISA kit and the correlation coefficient was 0.99, which indicated that the new strip assay had a good quantification ability for CAP.

CONCLUSION

The fluorescence immunochromatography strip was successfully applied to the detection of CAP residues in chicken samples. To our knowledge, it is the first report regarding the development of a fluorescence immunochromatography method for screening CAP in animal samples. © 2013 Society of Chemical Industry
Measuring psychotropic drug exposures in register‐based studies – validity of a dosage assumption of one unit per day in older Finns
Authors: Rikala Maria , Hartikainen Sirpa , Saastamoinen Leena K. , Korhonen Maarit Jaana
Published: May 2013

Pharmacoepidemiological studies provide valuable information on the relationships between psychotropic drug use and adverse outcomes in older people. To minimize the influence of misclassification bias in pharmacoepidemiological studies, more emphasis should be given to methodological aspects of exposure assessment. This study evaluated the validity of a dosage assumption of one unit per day for measuring legend duration of psychotropic drug exposures among older people. Using data from the Finnish Prescription Register, the study analysed 62,320 psychotropic drug prescriptions dispensed for people aged ≥ 75 years (n = 52,729) in September 2009. The proportions of prescriptions in which the prescribed dose deviated from one unit per day were assessed for categories and subcategories of psychotropic drugs. The prescription was considered misclassified (a) if the prescribed drug was intended for “as needed” use, (b) if the prescription included a dose range, or (c) if the prescribed dose was below or above one unit per day. Among antidepressants, less than every fourth (23.7%) prescription was misclassified. The proportions of misclassification varied substantially across subcategories, being 13.1% for selective serotonin reuptake inhibitors (SSRIs), 25.3% for other antidepressants and 53.8% for tricyclic antidepressants. Of the benzodiazepine and antipsychotic prescriptions, 79.9% and 57.6%, respectively, were misclassified. In conclusion, the dosage assumption of one unit per day is valid for measuring the legend duration of SSRI and other antidepressant exposures among older people. Among other psychotropic drugs, the dosage assumption is likely to lead to severe exposure misclassification. Copyright © 2013 John Wiley & Sons, Ltd.
Mental health care Monitor Older adults (MEMO): monitoring patient characteristics and outcome in Dutch mental health services for older adults
Authors: Veerbeek Marjolein , Oude Voshaar Richard , Depla Marja , Pot Anne Margriet
Published: May 2013

Information on which older adults attend mental health care and whether they profit from the care they receive is important for policy‐makers. To assess this information in daily practice, the “Mental health care Monitor Older adults” (MEMO) was developed in the Netherlands. The aim of this paper is to describe MEMO and the older adults who attend outpatient mental health care regarding their predisposing and enabling characteristics and need for care. In MEMO all patients referred to the division of old age psychiatry of the participating mental health care organisations are assessed at baseline and monitored at 4, 8 and 12‐month follow‐up. Primary outcomes are mental and social functioning, consumer satisfaction, and type of treatment provided (MEMO Basic). Over the years, MEMO Basic is repeated. In each cycle, additional information on specific patient groups is added (e.g. mood disorders). Data collection is supported by a web‐based system for clinicians, including direct feedback to monitor patients throughout treatment. First results at baseline showed that the majority of patients that entered the division of old age psychiatry was female (69%), had low education (83%), lived alone (53%), was depressed (42%) and had a comorbid condition (82%). It seemed that older immigrants were not sufficiently reached. The current study is the first in the Netherlands to evaluate patient characteristics and outcome in mental health care provided for older adults in day‐to‐day practice. If MEMO works out successfully, the method should be extended to other target groups. Copyright © 2013 John Wiley & Sons, Ltd.
SMA valiant trial: A prospective, double‐blind, placebo‐controlled trial of valproic acid in ambulatory adults with spinal muscular atrophy
Authors: Kissel John T. , Elsheikh Bakri , King Wendy M. , Freimer Miriam , Scott Charles B. , Kolb Stephen J. , Reyna Sandra P. , Crawford Thomas O. , Simard Louise R. , Krosschell Kristin J. , Acsadi Gyula , Schroth Mary K. , D'Anjou Guy , LaSalle Bernard , Prior Thomas W. , Sorenson Susan , Maczulski Jo Anne , Swoboda Kathryn J. ,   for the Project Cure Spinal Muscular Atrophy Investigators Network
Published: May 2013

Introduction: An open‐label trial suggested that valproic acid (VPA) improved strength in adults with spinal muscular atrophy (SMA). We report a 12‐month, double‐blind, cross‐over study of VPA in ambulatory SMA adults. Methods: There were 33 subjects, aged 20–55 years, included in this investigation. After baseline assessment, subjects were randomized to receive VPA (10–20 mg/kg/day) or placebo. At 6 months, patients were switched to the other group. Assessments were performed at 3, 6, and 12 months. The primary outcome was the 6‐month change in maximum voluntary isometric contraction testing with pulmonary, electrophysiological, and functional secondary outcomes. Results: Thirty subjects completed the study. VPA was well tolerated, and compliance was good. There was no change in primary or secondary outcomes at 6 or 12 months. Conclusions: VPA did not improve strength or function in SMA adults. The outcomes used are feasible and reliable and can be employed in future trials in SMA adults. Muscle Nerve 49: 187–192, 2014
Does vaccine dose predict response to the monovalent pandemic H1N1 influenza a vaccine in children with acute lymphoblastic leukemia? A single‐centre study
Authors: Leahy T. Ronan , Smith Owen P. , Bacon Christopher L. , Storey Lorna , Lynam Paul , Gavin Patrick J. , Butler Karina M. , O'Marcaigh Aengus S.
Published: May 2013

Background

Vaccination against influenza is an important strategy in preventing severe infection among children with acute lymphoblastic leukemia (ALL). Successful vaccination depends on both vaccine and host‐related factors. We conducted a study on factors predicting the immunogenicity of the monovalent pandemic H1N1 (pH1N1) influenza A vaccine in children with ALL.

Methods

Children with ALL in our hospital were recruited and received two doses of the inactivated split‐virion AS03‐adjuvanted vaccine. The serological response was measured before each vaccine dose (Day 0 and 28) and 3 months after the second dose. Antibody titres were measured using a hemagglutination–inhibition assay. Seroconversion was defined as a ≥fourfold increase in antibody titre and a post‐vaccination titre ≥1:40.

Results

Pre and post‐vaccination titres were available from 45 children with ALL after one dose of the vaccine and 39 children after two doses. The seroconversion rate was 11.1% after one dose and 25.6% after the second dose. Univariate analysis demonstrated a significantly higher (P = 0.01) seroconversion rate among children who received the adult dose (0.5 ml) of the vaccine and a trend towards increased seroconversion (P = 0.07) by multivariate analysis. Factors including age, gender, lymphocyte count, treatment phase and regimen did not significantly affect the seroconversion rate. Children who received the adult dose demonstrated a significantly greater magnitude of serological response after both one dose (P = 0.04) and two doses (P = 0.001).

Conclusions

These data suggest that the immunogenicity of the pH1N1 vaccine among children with ALL is improved by repeated and adult doses of the vaccine. Pediatr Blood Cancer 2013;60:1656–1661. © 2013 Wiley Periodicals, Inc.
Do childhood cancer survivors with physical performance limitations reach healthy activity levels?
Authors: Rueegg Corina S. , Gianinazzi Micòl E. , Michel Gisela , von der Weid Nicolas X. , Bergstraesser Eva , Kuehni Claudia E. ,   for the Swiss Paediatric Oncology Group (SPOG)
Published: May 2013

Background

The extent to which physical performance limitations affect the ability of childhood cancer survivors to reach healthy activity levels is unknown. Therefore this study aims to describe the effect of different types of limitations on activity levels in survivors.

Procedure

Within the Swiss Childhood Cancer Survivor Study we sent a questionnaire to all survivors (≥16 years) registered in the Swiss Childhood Cancer Registry, who survived >5 years and were diagnosed 1976–2005 aged <16 years. We measured healthy activity levels using international guidelines and assessed different kinds of performance limitations (visual impairment, weight and endurance problems, cardiorespiratory, musculoskeletal, and neurological problems, pain and fatigue syndromes).

Results

The sample included 1,560 survivors (75% response rate), of whom 209 (13.5%) reported they have performance limitations. Forty‐two percent of survivors with limitations reached healthy activity levels, compared to 57% of survivors without limitations. Least active were survivors with vision impairments (25% active), weight and endurance problems (27.3%), cardiorespiratory problems (36.4%), and musculoskeletal problems (43.1%). After adjusting for socio‐demographic variables and type of cancer, we found that survivors with limitations were 1.4 (95%CI 1.0–2.0;P = 0.047) times more likely to be inactive.

Conclusions

Although many survivors with physical performance limitations maintain healthy activity levels, there is room for improvement. Adapted and targeted physical activity counseling for survivors with performance limitations might help them to raise level of activity and pursue a healthy lifestyle. Pediatr Blood Cancer 2013;60:1714–1720. © 2013 Wiley Periodicals, Inc.
Cancer survivors with self‐reported late effects: their health status, care needs and service utilisation
Authors: Treanor Charlene , Santin Olinda , Mills Moyra , Donnelly Michael
Published: May 2013

Objective

Cancer survivors (CSs) are at risk of developing late effects (LEs) associated with the disease and its treatment. This paper compares the health status, care needs and use of health services by CSs with LEs and CSs without LEs.

Methods

Cancer survivors (n = 613) were identified via the Northern Ireland Cancer Registry and invited to participate in a postal survey that was administered by their general practitioner. The survey assessed self‐reported LEs, health status, health service use and unmet care needs. A total of 289 (47%) CSs responded to the survey, and 93% of respondents completed a LEs scale.

Results

Forty‐one per cent (111/269) of CSs reported LEs. Survivors without LEs and survivors with LEs were comparable in terms of age and gender. The LEs group reported a significantly greater number of co‐morbidities, lower physical health and mental health scores, greater overall health service use and more unmet needs. Unadjusted logistic regression analysis found that cancer site, time since diagnosis and treatment were significantly associated with reporting of LEs. CSs who received combination therapies compared with CSs who received single treatments were over two and a half times more likely to report LEs (OR = 2.63, 95% CI = 1.32–5.25) after controlling for all other variables.

Conclusions

The CS population with LEs comprises a particularly vulnerable group of survivors who have multiple health care problems and needs and who require tailored care plans that take account of LEs and their impact on health‐related quality of life. Copyright © 2013 John Wiley & Sons, Ltd.
Structural representative of the protein family PF14466 has a new fold and establishes links with the C2 and PLAT domains from the widely distant Pfams PF00168 and PF01477
Authors: Serrano Pedro , Geralt Michael , Mohanty Biswaranjan , Wüthrich Kurt
Published: May 2013

The domain of unknown function (DUF) YP_001302112.1, a protein secreted by the human intestinal microbita, has been determined by NMR and represents the first structure for the Pfam PF14466. Its NMR structure is classified as a new fold, which, nonetheless, shows limited similarities with representatives of the PLAT/LH2 domains from PF01477 and the C2 domains from PF00168, both of which bind Ca2+ for their physiological functions. Further experiments revealed affinity of YP_001302112.1 for Ca2+, and the NMR structure in the presence of CaCl2 was better defined than that of the apo‐protein. Overall, these NMR structures establish a new connection between structural representatives from two widely different Pfams that include the calcium‐binding domain of a sialidase from Vibrio cholerae and the α‐toxin from Clostridium perfrigens, whereby these two proteins have only 7% sequence identity. Furthermore, it provides information toward the functional annotation of YP_001302112.1, based on its capacity to bind Ca2+, and thus adds to the structural and functional coverage of the protein sequence universe. © 2013 The Protein Society