bluuebunny/crossref_metadata_2025 huggingface dataset:
Sildenafil reverses cardiac dysfunction in the
mdx
mouse model of Duchenne muscular dystrophy
Authors: Adamo Candace M. , Dai Dao-Fu , Percival Justin M. , Minami Elina , Willis Monte S. , Patrucco Enrico , Froehner Stanley C. , Beavo Joseph A.
Published: October 2010

Duchenne muscular dystrophy (DMD) is a progressive and fatal genetic disorder of muscle degeneration. Patients with DMD lack expression of the protein dystrophin as a result of mutations in the X-linked dystrophin gene. The loss of dystrophin leads to severe skeletal muscle pathologies as well as cardiomyopathy, which manifests as congestive heart failure and arrhythmias. Like humans, dystrophin-deficient mice (
mdx
mice) show cardiac dysfunction as evidenced by a decrease in diastolic function followed by systolic dysfunction later in life. We have investigated whether sildenafil citrate (Viagra), a phosphodiesterase 5 (PDE5) inhibitor, can be used to ameliorate the age-related cardiac dysfunction present in the
mdx
mice. By using echocardiography, we show that chronic sildenafil treatment reduces functional deficits in the cardiac performance of aged
mdx
mice, with no effect on normal cardiac function in WT controls. More importantly, when sildenafil treatment was started after cardiomyopathy had developed, the established symptoms were rapidly reversed within a few days. It is recognized that PDE5 inhibitors can have cardioprotective effects in other models of cardiac damage, but the present study reports a prevention and reversal of pathological cardiac dysfunction as measured by functional analysis in a mouse model of DMD. Overall, the data suggest that PDE5 inhibitors may be a useful treatment for the cardiomyopathy affecting patients with DMD at early and late stages of the disease.
T-cell receptor-driven lymphomagenesis in mice derived from a reprogrammed T cell
Authors: Serwold Thomas , Hochedlinger Konrad , Swindle John , Hedgpeth Joe , Jaenisch Rudolf , Weissman Irving L.
Published: October 2010

The conversion of mature somatic cells into pluripotent stem cells, both by nuclear transfer and transduction with specific “reprogramming” genes, represents a major advance in regenerative medicine. Pluripotent stem cell lines can now be generated from an individual's own cells, facilitating the generation of immunologically acceptable stem cell-based therapeutics. Many cell types can undergo nuclear reprogramming, leading to the question of whether the identity of the reprogrammed cell of origin has a biological consequence. Peripheral blood, containing a mixture of T, B, NK, and myeloid cell types, represents one potential source of reprogrammable cells. In this study, we describe the unique case of mice derived from a reprogrammed T cell. These mice have prerearranged T-cell receptor (TCR) genes in all cells. Surprisingly, ≈50% of mice with prerearranged TCR genes develop spontaneous T cell lymphomas, which originate in the thymus. The lymphomas arise from developing T cells, and contain activated Notch1, similar to most human and mouse T-cell acute lymphoblastic lymphomas. Furthermore, lymphomagenesis requires the expression of both prerearranged TCRα and TCRβ genes, indicating a critical role for TCR signaling. Furthermore, inhibitors of multiple branches of TCR signaling suppress lymphoma growth, implicating TCR signaling as an essential component in lymphoma proliferation. The lymphomagenesis in mice derived from a reprogrammed T cell demonstrates the deleterious consequences of misregulation of the TCR rearrangement and signaling pathways and illustrates one case of cellular reprogramming where the identity of the cell of origin has profound consequences.
Vaccination with a synthetic peptide from the influenza virus hemagglutinin provides protection against distinct viral subtypes
Authors: Wang Taia T. , Tan Gene S. , Hai Rong , Pica Natalie , Ngai Lily , Ekiert Damian C. , Wilson Ian A. , García-Sastre Adolfo , Moran Thomas M. , Palese Peter
Published: October 2010

Current influenza virus vaccines protect mostly against homologous virus strains; thus, regular immunization with updated vaccine formulations is necessary to guard against the virus' hallmark remodeling of regions that mediate neutralization. Development of a broadly protective influenza vaccine would mark a significant advance in human infectious diseases research. Antibodies with broad neutralizing activity (nAbs) against multiple influenza virus strains or subtypes have been reported to bind the stalk of the viral hemagglutinin, suggesting that a vaccine based on this region could elicit a broadly protective immune response. Here we describe a hemagglutinin subunit 2 protein (HA2)-based synthetic peptide vaccine that provides protection in mice against influenza viruses of the structurally divergent subtypes H3N2, H1N1, and H5N1. The immunogen is based on the binding site of the recently described nAb 12D1, which neutralizes H3 subtype viruses, demonstrates protective activity in vivo, and, in contrast to a majority of described nAbs, appears to bind to residues within a single α-helical portion of the HA2 protein. Our data further demonstrate that the specific design of our immunogen is integral in the induction of broadly active anti-hemagglutinin antibodies. These results provide proof of concept for an HA2-based influenza vaccine that could diminish the threat of pandemic influenza disease and generally reduce the significance of influenza viruses as human pathogens.
B-cell activating factor and v-Myc myelocytomatosis viral oncogene homolog (c-Myc) influence progression of chronic lymphocytic leukemia
Authors: Zhang Weizhou , Kater Arnon P. , Widhopf George F. , Chuang Han-Yu , Enzler Thomas , James Danelle F. , Poustovoitov Maxim , Tseng Ping-Hui , Janz Siegfried , Hoh Carl , Herschman Harvey , Karin Michael , Kipps Thomas J.
Published: October 2010

Mice bearing a v-Myc myelocytomatosis viral oncogene homolog (
c-Myc
) transgene controlled by an Ig-alpha heavy-chain enhancer (i

Myc
Cα

mice) rarely develop lymphomas but instead have increased rates of memory B-cell turnover and impaired antibody responses to antigen. We found that male progeny of i

Myc
Cα

mice mated with mice transgenic (Tg) for CD257 (B-cell activating factor, BAFF) developed CD5
+
B-cell leukemia resembling human chronic lymphocytic leukemia (CLL), which also displays a male gender bias. Surprisingly, leukemic cells of
Myc/Baff
Tg mice expressed higher levels of
c-Myc
than did B cells of i

Myc
Cα

mice. We found that CLL cells of many patients with progressive disease also expressed high amounts of
c-MYC,
particularly CLL cells whose survival depends on nurse-like cells (NLC), which express high-levels of BAFF. We find that BAFF could enhance CLL-cell expression of
c-MYC
via activation the canonical IκB kinase (IKK)/NF-κB pathway. Inhibition of the IKK/NF-κB pathway in mouse or human leukemia cells blocked the capacity of BAFF to induce
c-MYC
or promote leukemia-cell survival and significantly impaired disease progression in
Myc/Baff
Tg mice. This study reveals an important relationship between BAFF and
c-MYC
in CLL which may affect disease development and progression, and suggests that inhibitors of the canonical NF-κB pathway may be effective in treatment of patients with this disease.
ALCHEMY: a reliable method for automated SNP genotype calling for small batch sizes and highly homozygous populations
Authors: Wright Mark H. , Tung Chih-Wei , Zhao Keyan , Reynolds Andy , McCouch Susan R. , Bustamante Carlos D.
Published: October 2010

Motivation: The development of new high-throughput genotyping products requires a significant investment in testing and training samples to evaluate and optimize the product before it can be used reliably on new samples. One reason for this is current methods for automated calling of genotypes are based on clustering approaches which require a large number of samples to be analyzed simultaneously, or an extensive training dataset to seed clusters. In systems where inbred samples are of primary interest, current clustering approaches perform poorly due to the inability to clearly identify a heterozygote cluster.

Results: As part of the development of two custom single nucleotide polymorphism genotyping products for Oryza sativa (domestic rice), we have developed a new genotype calling algorithm called ‘ALCHEMY’ based on statistical modeling of the raw intensity data rather than modelless clustering. A novel feature of the model is the ability to estimate and incorporate inbreeding information on a per sample basis allowing accurate genotyping of both inbred and heterozygous samples even when analyzed simultaneously. Since clustering is not used explicitly, ALCHEMY performs well on small sample sizes with accuracy exceeding 99% with as few as 18 samples.

Availability: ALCHEMY is available for both commercial and academic use free of charge and distributed under the GNU General Public License at http://alchemy.sourceforge.net/

Contact:  mhw6@cornell.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
High-throughput prediction of protein antigenicity using protein microarray data
Authors: Magnan Christophe N. , Zeller Michael , Kayala Matthew A. , Vigil Adam , Randall Arlo , Felgner Philip L. , Baldi Pierre
Published: October 2010

Motivation: Discovery of novel protective antigens is fundamental to the development of vaccines for existing and emerging pathogens. Most computational methods for predicting protein antigenicity rely directly on homology with previously characterized protective antigens; however, homology-based methods will fail to discover truly novel protective antigens. Thus, there is a significant need for homology-free methods capable of screening entire proteomes for the antigens most likely to generate a protective humoral immune response.

Results: Here we begin by curating two types of positive data: (i) antigens that elicit a strong antibody response in protected individuals but not in unprotected individuals, using human immunoglobulin reactivity data obtained from protein microarray analyses; and (ii) known protective antigens from the literature. The resulting datasets are used to train a sequence-based prediction model, ANTIGENpro, to predict the likelihood that a protein is a protective antigen. ANTIGENpro correctly classifies 82% of the known protective antigens when trained using only the protein microarray datasets. The accuracy on the combined dataset is estimated at 76% by cross-validation experiments. Finally, ANTIGENpro performs well when evaluated on an external pathogen proteome for which protein microarray data were obtained after the initial development of ANTIGENpro.

Availability: ANTIGENpro is integrated in the SCRATCH suite of predictors available at http://scratch.proteomics.ics.uci.edu.

Contact:  pfbaldi@ics.uci.edu
TURNIP: tracking unresolved nucleotide polymorphisms in large hard-to-assemble regions of repetitive DNA sequence
Authors: Davey Robert P. , James Stephen A. , Dicks Jo , Roberts Ian N.
Published: October 2010

Summary: TURNIP comprises a suite of Perl scripts and modules that facilitates the resolution of microheterogeneity within hard-to-assemble repetitive DNA sequences. TURNIP was originally developed for the Saccharomyces Genome Resequencing Project (SGRP) within which the ribosomal DNA (rDNA) of 36 strains of S.cerevisiae were analysed to investigate the occurrence of potential polymorphisms. Here, ‘partially resolved SNPs’, or pSNPs, as well as indels, were found to be far more prevalent than previously suspected. More generally, the TURNIP software ascertains degrees of variation between large tandem repeats within a single locus, offering insights into mechanisms of genome stability and gene conversion in any organism for which genome sequence data are available.

Availability: The TURNIP source code, results files and online help are available at http://www.ncyc.co.uk/software/turnip.html .

Contact:  robert.davey@bbsrc.ac.uk
Robust relationship inference in genome-wide association studies
Authors: Manichaikul Ani , Mychaleckyj Josyf C. , Rich Stephen S. , Daly Kathy , Sale Michèle , Chen Wei-Min
Published: October 2010

Motivation: Genome-wide association studies (GWASs) have been widely used to map loci contributing to variation in complex traits and risk of diseases in humans. Accurate specification of familial relationships is crucial for family-based GWAS, as well as in population-based GWAS with unknown (or unrecognized) family structure. The family structure in a GWAS should be routinely investigated using the SNP data prior to the analysis of population structure or phenotype. Existing algorithms for relationship inference have a major weakness of estimating allele frequencies at each SNP from the entire sample, under a strong assumption of homogeneous population structure. This assumption is often untenable.

Results: Here, we present a rapid algorithm for relationship inference using high-throughput genotype data typical of GWAS that allows the presence of unknown population substructure. The relationship of any pair of individuals can be precisely inferred by robust estimation of their kinship coefficient, independent of sample composition or population structure (sample invariance). We present simulation experiments to demonstrate that the algorithm has sufficient power to provide reliable inference on millions of unrelated pairs and thousands of relative pairs (up to 3rd-degree relationships). Application of our robust algorithm to HapMap and GWAS datasets demonstrates that it performs properly even under extreme population stratification, while algorithms assuming a homogeneous population give systematically biased results. Our extremely efficient implementation performs relationship inference on millions of pairs of individuals in a matter of minutes, dozens of times faster than the most efficient existing algorithm known to us.

Availability: Our robust relationship inference algorithm is implemented in a freely available software package, KING, available for download at http://people.virginia.edu/∼wc9c/KING.

Contact:  wmchen@virginia.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
GeneMANIA Cytoscape plugin: fast gene function predictions on the desktop
Authors: Montojo J. , Zuberi K. , Rodriguez H. , Kazi F. , Wright G. , Donaldson S. L. , Morris Q. , Bader G. D.
Published: October 2010

Summary: The GeneMANIA Cytoscape plugin brings fast gene function prediction capabilities to the desktop. GeneMANIA identifies the most related genes to a query gene set using a guilt-by-association approach. The plugin uses over 800 networks from six organisms and each related gene is traceable to the source network used to make the prediction. Users may add their own interaction networks and expression profile data to complement or override the default data.

Availability and Implementation: The GeneMANIA Cytoscape plugin is implemented in Java and is freely available at http://www.genemania.org/plugin/.

Contact:  gary.bader@utoronto.ca; quaid.morris@utoronto.ca
Pathway Activity Profiling (PAPi): from the metabolite profile to the metabolic pathway activity
Authors: Aggio Raphael B. M. , Ruggiero Katya , Villas-Bôas Silas Granato
Published: October 2010

Motivation: Metabolomics is one of the most recent omics-technologies and uses robust analytical techniques to screen low molecular mass metabolites in biological samples. It has evolved very quickly during the last decade. However, metabolomics datasets are considered highly complex when used to relate metabolite levels to metabolic pathway activity. Despite recent developments in bioinformatics, which have improved the quality of metabolomics data, there is still no straightforward method capable of correlating metabolite level to the activity of different metabolic pathways operating within the cells. Thus, this kind of analysis still depends on extremely laborious and time-consuming processes.

Results: Here, we present a new algorithm Pathway Activity Profiling (PAPi) with which we are able to compare metabolic pathway activities from metabolite profiles. The applicability and potential of PAPi was demonstrated using a previously published data from the yeast Saccharomyces cerevisiae. PAPi was able to support the biological interpretations of the previously published observations and, in addition, generated new hypotheses in a straightforward manner. However, PAPi is time consuming to perform manually. Thus, we also present here a new R-software package (PAPi) which implements the PAPi algorithm and facilitates its usage to quickly compare metabolic pathways activities between different experimental conditions. Using the identified metabolites and their respective abundances as input, the PAPi package calculates pathways' Activity Scores, which represents the potential metabolic pathways activities and allows their comparison between conditions. PAPi also performs principal components analysis and analysis of variance or t-test to investigate differences in activity level between experimental conditions. In addition, PAPi generates comparative graphs highlighting up- and down-regulated pathway activity.

Availability: These datasets are available in http://www.4shared.com/file/hTWyndYU/extra.html and http://www.4shared.com/file/VbQIIDeu/intra.html. PAPi package is available in: http://www.4shared.com/file/s0uIYWIg/PAPi_10.html

Contact:  s.villas-boas@auckland.ac.nz

Supplementary information:  Supplementary data are available at Bioinformatics online.
Target-align: a tool for plant microRNA target identification
Authors: Xie Fuliang , Zhang Baohong
Published: October 2010

Motivation: MicroRNAs (miRNAs) are important regulatory molecules. A critical step in elucidating miRNA function is identifying potential miRNA targets. However, few reliable tools have been developed for identifying miRNA targets in plants.

Results: Here, we developed a Smith–Waterman-like alignment tool in order to accurately predict miRNA targets. Dynamic programming was used to build a score matrix based on the complementarity of nucleotides in order to trace the optimal local alignments. Important parameters, such as maximum mismatches and maximum consecutive mismatches between miRNAs and their targets, were also used for filtering the optimal local alignments. Almost all of the parameters in this alignment tool can be adjusted by users. Compared to other target prediction tools, Target-align exhibits strong sensitivity and accuracy for identifying miRNA targets. More importantly, Target-align can identify multi-target sites as well potential for non-cleaved targets sites by change the default settings. Windows, web and command-line versions were developed to better serve different users.

Availability:  http://www.leonxie.com/targetAlign.php.

Contact:  zhangb@ecu.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Pre-calculated protein structure alignments at the RCSB PDB website
Authors: Prlić Andreas , Bliven Spencer , Rose Peter W. , Bluhm Wolfgang F. , Bizon Chris , Godzik Adam , Bourne Philip E.
Published: October 2010

Summary: With the continuous growth of the RCSB Protein Data Bank (PDB), providing an up-to-date systematic structure comparison of all protein structures poses an ever growing challenge. Here, we present a comparison tool for calculating both 1D protein sequence and 3D protein structure alignments. This tool supports various applications at the RCSB PDB website. First, a structure alignment web service calculates pairwise alignments. Second, a stand-alone application runs alignments locally and visualizes the results. Third, pre-calculated 3D structure comparisons for the whole PDB are provided and updated on a weekly basis. These three applications allow users to discover novel relationships between proteins available either at the RCSB PDB or provided by the user.

Availability and Implementation: A web user interface is available at http://www.rcsb.org/pdb/workbench/workbench.do. The source code is available under the LGPL license from http://www.biojava.org. A source bundle, prepared for local execution, is available from http://source.rcsb.org

Contact:  andreas@sdsc.edu; pbourne@ucsd.edu
New approaches to scaling data measured on a CCD diffractometer
Authors: Dudka Alexander
Published: October 2010

New methods have been developed for scaling the intensities of diffraction reflections measured on a diffractometer with a CCD detector. The algorithm involves cyclic alternation of the refinement of a structure model from experimental data corrected for anisotropic effects with the refinement of anisotropic parameters from initial data for a fixed structure model. The first method consists of refining scale factors for the intensities after they have first been corrected for anisotropic effects of known physical nature (thermal diffuse scattering, absorption, extinctionetc.). It has been shown that the majority of the observed biases of intensities are caused by the characteristics of the CCD detector and the technique used for data collection on the diffractometer, rather than by the properties of the sample. The second (alternative) method of fixed scaling has been implemented here. This method does not require refinement of empirical scale factors but uses intensity correction maps obtained by averaging the results derived from several experiments with different crystals. The first map describes the non-uniformity of the response over the surface area of the detector. The second map accounts for distortions dependent on the setting angles of the goniometer. The methods were checked for data measured on an Oxford Diffraction Xcalibur Sapphire 3 CCD diffractometer. The proposed methods significantly improve the results of the refinement and make it possible to obtain a structure model that is reproduced in repeated investigations of samples of the same compound.
In-crystal chemical ligation for lead compound generation
Authors: Yamane Junji , Ohyabu Naoki , Yao Min , Takemoto Hiroshi , Tanaka Isao
Published: October 2010

A new fragment-based growth strategy for lead compound generation is proposed, which is based onin situchemical ligation and is operable in X-ray-based fragment screening format. The method involves two classes of bifunctional molecules, referred to as anchor molecules and tuning molecules. The anchor molecules are designed to form stable complexes with target proteins and to connect with the tuning molecules. The procedure begins with the introduction of the anchor molecule into the target protein, to which the tuning molecule is linked in the crystal. Proof-of-concept experiments using trypsin crystals charged withpara-aldehyde benzamidine showed that the crystals acted as a platform to select self-assembled ligation products. Furthermore, time-resolved crystallography allowed identification of the reaction field and direct visualization of the reaction pathway. The ability to rapidly gain an understanding of the relations between a set of chemical modifications and their interactions with target proteins would accelerate the hit-to-lead process. A potential crystallographic growth strategyviathe self-assembly technique and its biological implications are discussed.
Versatilein situpowder X-ray diffraction cells for solid–gas investigations
Authors: Jensen Torben R. , Nielsen Thomas K. , Filinchuk Yaroslav , Jørgensen Jens-Erik , Cerenius Yngve , Gray Evan MacA. , Webb Colin J.
Published: October 2010

This paper describes new sample cells and techniques forin situpowder X-ray diffraction specifically designed for gas absorption studies up toca300 bar (1 bar = 100 000 Pa) gas pressure. The cells are for multipurpose use, in particular the study of solid–gas reactions in dosing or flow mode, but can also handle samples involved in solid–liquid–gas studies. The sample can be loaded into a single-crystal sapphire (Al2O3) capillary, or a quartz (SiO2) capillary closed at one end. The advantages of a sapphire single-crystal cell with regard to rapid pressure cycling are discussed, and burst pressures are calculated and measured to be ∼300 bar. An alternative and simpler cell based on a thin-walled silicate or quartz glass capillary, connected to a gas sourceviaa VCR fitting, enables studies up to ∼100 bar. Advantages of the two cell types are compared and their applications are illustrated by case studies.
Diffraction study of protein crystals grown in cryoloops and micromounts
Authors: Berger Michael A. , Decker Johannes H. , Mathews Irimpan I.
Published: October 2010

Protein crystals are usually grown in hanging or sitting drops and generally get transferred to a loop or micromount for cryocooling and data collection. This paper describes a method for growing crystals on cryoloops for easier manipulation of the crystals for data collection. This study also investigates the steps for the automation of this process and describes the design of a new tray for the method. The diffraction patterns and the structures of three proteins grown by both the new method and the conventional hanging-drop method are compared. The new setup is optimized for the automation of the crystal mounting process. Researchers could prepare nanolitre drops under ordinary laboratory conditions by growing the crystals directly in loops or micromounts. As has been pointed out before, higher levels of supersaturation can be obtained in very small volumes, and the new method may help in the exploration of additional crystallization conditions.
The relationship between addiction and reward bundling: an experiment comparing smokers and non‐smokers
Authors: Hofmeyr Andre , Ainslie George , Charlton Richard , Ross Don
Published: October 2010

Aims Previous studies indicate that addicts show reduced preference for more delayed versus more immediate rewards compared to non‐addicts. This may reflect a lower propensity to view such decisions in terms of the larger sequences to which they typically belong (e.g. smoking is a frequently repeated act). Therefore, this study aims to test whether, in a sequence of decisions involving smaller, sooner (SS) versus larger, later (LL) rewards, suggesting or forcing people with a propensity to addiction to make the decision for the series as a whole would increase LL preference. It is hypothesized that people without a propensity to addiction should benefit less from being encouraged to think of reward sequences because they already tend to take that view.

Design Thirty regular smokers (as exemplars of addicted individuals) and 30 non‐smokers chose between small short‐term and larger long‐term monetary rewards over a sequence of four decisions spaced 2 weeks apart. Subjects were divided into three groups: one who made each decision independently with no suggestion that they be considered as a series (‘free’), a group to whom it was suggested from the start that they consider each decision as part of the series (‘suggested’) and a group who were told that their very first choice in the series would be used for the remaining decisions (‘forced’). All subjects were paid the amounts they had chosen.

Setting A laboratory room at the University of Cape Town (UCT).

Participants UCT undergraduate volunteers.

Analyses The proportion of LL choices in each subgroup was evaluated by χ2tests and a probit model.

Findings Smokers increased their preference for LL rewards when ‘bundling’ of individual decisions into a sequence was either suggested or forced. This preference increased with repeated experience. Non‐smokers showed neither pattern.

Conclusions The propensity of smokers to prefer small short‐term rewards over larger delayed rewards may be mitigated, over a sequence of decisions of this kind, by encouraging or forcing them to think of the sequence as a whole. If replicated, this finding may form the basis of an intervention that could attenuate the choice patterns characteristic of addiction.
A paramedic study comparing the use of the Airtraq®, Airway Scope and Macintosh laryngoscopes in simulated prehospital airway scenarios*
Authors: Lewis A. R. , Hodzovic I. , Whelan J. , Wilkes A. R. , Bowler I. , Whitfield R.
Published: October 2010

In a randomised, cross‐over study, we compared the use of the Airtraq®, Airway Scope and Macintosh laryngoscopes by paramedics for tracheal intubation in three simulated prehospital scenarios. Fifty‐four paramedics were invited to take part. When evaluated in a difficult airway manikin, median IQR [range] time to intubation with the Airtraq (21 (16–37 [6–80] s) and Airway Scope (16 (5–75 [12–23] s) was shorter than that with the Macintosh laryngoscope (39 (25–54 [7–120] s; p < 0.0001). The success rate within 30 s was greater with the Airtraq (61%) and Airway Scope (93%) than with the Macintosh laryngoscope (22%; p < 0.0001). When used for a standard intubation and in the sitting position, we found minimal differences among the three laryngoscopes. We conclude that the Airway Scope and Airtraq have significant advantages over the Macintosh laryngoscope and that of the two, the Airway Scope is the more effective device to use in the prehospital environment.
Comparison of the LMA Supreme vs the i‐gel™ in paralysed patients undergoing gynaecological laparoscopic surgery with controlled ventilation*
Authors: Teoh W. H. L. , Lee K. M. , Suhitharan T. , Yahaya Z. , Teo M. M. , Sia A. T. H.
Published: October 2010

We compared the efficacy of the inflatable cuff of the LMA Supreme™ against the non‐inflatable i‐gel™ cuff in providing an adequate seal for laparoscopic surgery in the Trendelenburg position in 100 female patients. There was no difference in our primary outcome, oropharyngeal leak pressure, between the LMA Supreme and the i‐gel (mean (SD) 26.4 (5.1) vs 25.0 (5.7) cmH2O, respectively; p = 0.18). Forty‐seven (94%) LMA Supremes and 48 (96%) i‐gels were successfully inserted on the first attempt, with similar ease, and comparable times to the first capnograph trace (mean (SD) 14.3 (4.7) s for the LMA Supreme vs 15.4 (8.2) s for the i‐gel; p = 0.4). Gastric tube insertion was easier and achieved more quickly with the LMA Supreme vs the i‐gel (9.0 (2.5) s vs 15.1 (7.3) s, respectively; p < 0.001). After creation of the pneumoperitoneum, there was a smaller difference between expired and inspired tidal volumes with the LMA Supreme (21.5 (15.2) ml) than with the i‐gel (31.2 (23.5) ml; p = 0.009). There was blood on removal of two LMA Supremes and one i‐gel. Four patients in the LMA Supreme group and one patient in the i‐gel group experienced mild postoperative sore throat.
Molecular characterization of paediatric idiopathic hypereosinophilia
Authors: Rapanotti Maria Cristina , Caruso Roberta , Ammatuna Emanuele , Zaza Serena , Trotta Laura , Divona Mariadomenica , Cicconi Laura , Funaro Daria , Federici Giorgio , Amadori Sergio , De Rossi Giulio , Lo‐Coco Francesco
Published: October 2010

The hypereosinophilic syndromes (HES) include a group of heterogeneous diseases characterized by the persistent increase of the number of eosinophils in blood and bone marrow. Few cases of paediatric hypereosinophilia (pHES) have been described in the literature. Early identification of pHES that may evolve towards a lymphomyeloproliferative disease is relevant in light of prognostic and therapeutic implications. Molecular features of 10 pHES patients were analysed at presentation and during their clinical course, including analysis of BCR‐ABL1 and FIP1L1/PDGFRA fusion genes, quantitation of WT1 gene copy number and clonality of T‐cell receptor (TCR) and immunoglobulin heavy chain (IGH). All patients had normal karyotype and germline TCR configuration. Five children showed IGH clonality at presentation: of these, two developed a B non‐Hodgkin lymphoma and a B‐lineage acute lymphocytic leukaemia at six and 12 months respectively, two spontaneously reverted to a polyclonal IGH profile during the follow‐up, and the last one persisted with pHES without B‐clonal evolution after 19 months. One patient had a PDGFRA/FIP1L1 fusion and achieved hematologic and molecular remission after imatinib therapy. IGH rearrangement was observed to be a frequent molecular feature of pHES and may precede B‐cell clonal expansion and evolution into B‐cell malignancies in children.
A randomized phase II trial of Arginine Butyrate with standard local therapy in refractory sickle cell leg ulcers
Authors: McMahon Lillian , Tamary Hannah , Askin Melissa , Adams‐Graves Patricia , Eberhardt Robert T. , Sutton Millicent , Wright Elizabeth C. , Castaneda Serguei A. , Faller Douglas V. , Perrine Susan P.
Published: October 2010

Sickle cell leg ulcers are often debilitating, refractory to healing, and prone to recurrence. Healing of leg ulcers was incidentally observed during dose‐ranging trials of Arginine Butyrate in beta haemoglobinopathies. Here, a controlled Phase II trial was performed in sickle cell patients who had lower extremity ulcers refractory to standard care for at least 6 months. Patients were randomized to receive standard local care alone (Control Arm) or standard care with Arginine Butyrate administered 5 d/week (Treatment Arm), for 12 weeks. Ulcers were photographed weekly, traced, and ulcer areas were calculated by computerized planimetry and compared between the two study arms. Twenty‐seven study courses were evaluated. Control Arm subjects had 25 ulcers with a mean area of 25·7 cm2 initially and 23·2 cm2 after 12 weeks; 2/25 (8%) healed completely. Treatment Arm subjects had 37 ulcers with a mean area of 50·6 cm2 initially and 28·3 cm2 at 12 weeks; 11/37 of these (30%) healed completely. After 3 months, proportions of ulcers which healed were 6/25 (24%) and 29/37 (78%), in the Control and Treatment Arms respectively (P < 0·001). These findings strongly suggest that Arginine Butyrate merits further evaluation for the treatment of refractory sickle cell leg ulcers in larger trials.
Desensitization to hydroxycarbamide following long‐term treatment of thalassaemia intermedia as observed in vivo and in primary erythroid cultures from treated patients
Authors: Rigano Paolo , Pecoraro Alice , Calzolari Roberta , Troia Antonio , Acuto Santina , Renda Disma , Pantalone Gaetano Restivo , Maggio Aurelio , Marzo Rosalba Di
Published: October 2010

Hydroxycarbamide (HC) is a pharmacological agent capable of stimulating fetal haemoglobin (HbF) production during adult life. High levels of HbF may ameliorate the clinical course of β‐thalassaemia and sickle cell disease. The efficacy of HC for the treatment of thalassaemia major and thalassaemia intermedia is variable. Although an increase of HbF has been observed in most patients, only some patients experience significant improvement in total haemoglobin levels. This study aimed to determine the effectiveness and safety of short‐ (1 year) and long‐term (mean follow‐up 68 months) HC treatment in 24 thalassaemia intermedia patients. Additionally, we evaluated if primary erythroid progenitor cells cultured from treated patients responded to HC treatment in a manner similar to that observed in vivo. Our results confirm a good response to HC after a short‐term follow‐up in 70% of thalassaemia intermedia patients and a reduction of clinical response in patients with a long follow‐up. Erythroid cultures obtained from patients during treatment reproduced the observed in vivo response. Interestingly, haematopoietic stem cells from long‐term treated patients showed reduced ability to develop into primary erythroid cultures some months before the reduction of the ‘in vivo’ response. The mechanism of this loss of response to HC remains to be determined.
HER2 molecular subtype is a dominant subtype of mammary Paget’s cells. An immunohistochemical study
Authors: Sek Piotr , Zawrocki Antoni , Biernat Wojciech , Piekarski Janusz H
Published: October 2010

Sek P, Zawrocki A, Biernat W & Piekarski J H (2010) Histopathology57, 564–571 HER2 molecular subtype is a dominant subtype of mammary Paget’s cells. An immunohistochemical study

Aims:  To test the hypothesis that the similarity of the molecular subtypes of Paget’s cells to the molecular subtypes of the underlying breast carcinomas favours the epidermotrophic theory of the origin of Paget’s cells.

Methods and results:  The immunohistochemical expression of markers that define particular molecular subtypes of breast carcinomas were analysed. The whole analysis was performed by means of tissue microarrays in mammary Paget’s disease and in the underlying breast carcinoma(s). Human epidermal growth factor receptor type 2 (HER2)‐overexpression subtype [oestrogen receptor (ER−); HER2+] was a dominant molecular subtype of Paget’s cells (37 of 43 analysed cases; 86%). Luminal B (ER+; HER2+) and luminal A (ER+; HER−) subtypes were identified in 12% and 2% of cases, respectively. None of the analysed tumours presented a basal‐like phenotype. A similar distribution of molecular subtypes was identified in the underlying in situ breast carcinomas (HER2 subtype, 82%; luminal A, 6%; luminal B, 6%; basal‐like, 6% of cases) and in the invasive component (HER2 subtype, 84%; luminal A, 8%; luminal B, 8%; basal‐like, 0% of cases).

Conclusions:  HER2 molecular subtype is the dominant, but not the sole subtype seen in Paget’s cells of the nipple. A similar distribution of molecular subtypes in both Paget’s cells and in the underlying carcinomas strongly suggests their common origin.
Emergency nurse practitioners: the views of patients and hospital staff at a major acute trust in the UK
Authors: Melby Vidar , Gillespie Mark , Martin Stephanie
Published: October 2010

Aim.  The study reported in this paper aimed at exploring the views of staff and patients of a potential emergency nurse practitioner service in an acute trust in the UK.

Background.  The role of the nurse in emergency care has changed considerably in recent years, and the evolution of the emergency nurse practitioner role has changed emergency service provision dramatically. The emergency nurse practitioner role is not uniformly defined across emergency care in the UK, and the resulting blurring of the role of emergency nurse practitioners with that of emergency department medical staff is not helpful to hospital staff or patients.

Design.  A quantitative and qualitative mixed method design was used that enabled exploration of an individual’s viewpoint within their own practice or natural surroundings.

Method.  Self‐completed questionnaires were used to determine health professionals’ opinions, and semi‐structured interviews were employed to explore patients’ views.

Results.  A total of 144 health professionals responded to the questionnaire survey giving a response rate of 28·5%, and 10 patients participated in qualitative interviews. Health professionals and patients alike were generally supportive of an emergency nurse practitioner service, but there were some concerns in relation to the role and functions of the emergency nurse practitioner and associated accountability issues.

Conclusions.  This paper contributes further data that demonstrate the inter‐professional and patient support of the advanced role of the emergency nurse practitioner and highlights potential conflictual issues and barriers to implementation that can and must be resolved successfully through proper consultation prior to the service being introduced.

Relevance to clinical practice.  This paper provides important information to health professionals and service providers that should help to facilitate the introduction and maintenance of a successful and effective emergency nurse practitioner service in any trust.
Nurses’ practice of blood transfusion in the United Arab Emirates: an observational study
Authors: Hijji Belal , Parahoo Kader , Hossain Mohammad M , Barr Owen , Murray Shirley
Published: October 2010

Aims.  The aim of this study was to document nurses’ practice of red blood cells transfusion.

Background.  In the United Arab Emirates hospitals, nurses are responsible for the administration of blood transfusions. The safety and effectiveness of the transfusion process is dependent, among others, on the knowledge and skills of nurses who perform the procedure. Poor practice may result in avoidable complications that may threaten patients’ safety. Published work indicated that nurses’ practice varied across contexts and highlighted that patients received suboptimal care and incorrect transfusion that culminated in death or morbidity. In the United Arab Emirates, publications related to nurses’ practice of blood transfusion are lacking.

Design.  Descriptive.

Methods.  Data were collected by means of non‐participant structured observation. Data collection was undertaken in two general public hospitals in the Emirate of Abu Dhabi, United Arab Emirates. A random sample of 50 nurses from both hospitals was selected. Each nurse was observed once, from 10 minutes prior to blood collection until 15 minutes after initiating a transfusion.

Results.  Forty‐nine nurses (98%) were observed. The maximum obtained score was 13 points of a possible score of 21, and 75% of nurses scored below the 50% level. Practice deficiencies included improper patient identification, suboptimal vital signs documentation and invalid methods of blood warming.

Conclusions.  Patients in both hospitals were at risk of receiving incorrect blood, suffering unobserved transfusion reaction and acquiring bacterial infection.

Relevance to clinical practice.  This study revealed inadequate practices that nurses and hospitals should strive to change to provide a safer and more effective care that would, hopefully, minimise the risks and maximise the benefits of blood transfusion. These findings also have implications for clinical supervision and nurse education.
Urinary incontinence in pregnant women and their quality of life
Authors: Kocaöz Semra , Talas Melek S , Atabekoğlu Cem S
Published: October 2010

Aims and objectives.  The aim was to investigate the prevalence of urinary incontinence during pregnancy and the related risk factors as well as to assess its influence on the quality of life.

Background.  Although urinary incontinence is common during pregnancy and can have a substantial impact on quality of life, women rarely seek help for this symptom.

Design.  This study was designed as a cross‐sectional and descriptive survey.

Methods.  A total of 393 pregnant women participated in the study between March and June 2007. The data was collected using the International Consultation on Incontinence Questionnaire Short Form and Wagner’s quality of life scale. Potential risk factors were investigated through logistic regression analysis.

Results.  The prevalence of urinary incontinence was 27% (106/393). Factors significantly associated with urinary incontinence included age group, parity, previous urinary incontinence, constipation, urinary incontinence in mother and sister, previous urinary incontinence during pregnancy and postpartum.

Conclusion.  According to the results of our study, urinary incontinence is common in women during pregnancy. The quality of life of pregnant women was found to be either unaffected or affected very little by urinary incontinence.

Relevance to clinical practice.  This study reveals that the prevalence of urinary incontinence during pregnancy is very high. The findings will help increase the awareness of health care workers involved in the care of pregnant women about urinary incontinence and aid the design of more intensive education programmes directed towards the prevention of urinary incontinence during pregnancy.
Promoting oral health during pregnancy: current evidence and implications for Australian midwives
Authors: George Ajesh , Johnson Maree , Blinkhorn Anthony , Ellis Sharon , Bhole Sameer , Ajwani Shilpi
Published: October 2010

Aims and objectives.  The aim of this paper is to examine current evidence supporting the promotion of oral health during pregnancy and proffer aspects of a potential role for Australian midwives.

Background.  Research continues to show that poor oral health during pregnancy can have an impact on the health outcomes of the mother and baby. Poor maternal oral health increases the chances of infants developing early caries and is strongly associated with adverse pregnancy outcomes such as preterm and low birth‐weight babies. Unfortunately in Australia, no preventive strategies exist to maintain the oral health of pregnant women.

Design.  Systematic review.

Method.  This review examines all literature on oral health during pregnancy published to date in the English language and focuses on whether preventive oral health strategies during the prenatal period are warranted in Australia and if so, how they could be provided.

Results.  Maintaining oral health is important during pregnancy and many developed countries have implemented preventive strategies to address this issue using non‐dental professionals such as prenatal care providers. However, despite the positive international evidence, limited importance is being given to the oral health of pregnant women in Australia. It is also evident that the unique potential of prenatal care providers such as midwives to assess and improve maternal oral heath is not being thoroughly utilised. Compounding the issue in Australia, especially for pregnant women from socioeconomically disadvantaged backgrounds, is the limited access to public dental services and the high cost of private dental treatment.

Conclusion.  Promoting and maintaining oral health during pregnancy is crucial, and preventive prenatal oral health services are needed in Australia to achieve this.

Relevance to clinical practice.  Midwives have an excellent opportunity to offer preventive oral health services by providing oral health assessments, education and referrals for pregnant women attending antenatal clinics.
Navigating the unknown: model selection in phylogeography
Authors: CARSTENS BRYAN C. , KNOWLES L. L.
Published: October 2010

Despite the widespread use and obvious strengths of model‐based methods for phylogeographic study, a persistent concern for such analyses is related to the definition of the model itself. The study by Peter et al. (2010) in this issue of Molecular Ecology demonstrates an approach for overcoming such hurdles. The authors were motivated by a deceptively simple goal; they sought to infer whether a population has remained at a low and stable size or has undergone a decline, and certainly there is no shortage of software packages for such a task (e.g., see list of programs in Excoffier & Heckel 2006). However, each of these software packages makes basic assumptions about the underling population (e.g., is the population subdivided or panmictic); these assumptions are explicit to any model‐based approach but can bias parameter estimates and produce misleading inferences if the model does not approximate the actual demographic history in a reasonable manner. Rather than guessing which model might be best for analyzing the data (microsatellite data from samples of chimpanzees), Peter et al. (2010) quantify the relative fit of competing models for estimating the population genetic parameters of interest. Complemented by a revealing simulation study, the authors highlight the peril inherent to model‐based inferences that lack a statistical evaluation of the fit of a model to the data, while also demonstrating an approach for model selection with broad applicability to phylogeographic analysis.