bluuebunny/crossref_metadata_2025_split huggingface dataset:
What is the current practice of medicines reconciliation in children nationally in the UK?
Authors: Huynh Chi , Jani Yogini , Wong Ian Chi Kei , Dewchand Bhavika , Tomlin Stephen 
Published: June 2012

Abstract

Introduction
The National Institute for Health and Clinical Excellence/National Patient Safety Agency (NICE/NPSA) guidelines for medicines reconciliation (MR) on admission to hospital in adult inpatients were introduced in 2007, but they excluded children less than 16 years of age.

Method
We conducted a survey of 98 paediatric pharmacists (each from a different hospital) to find out what the current practice of MR in children is in the UK.

Key findings
Responses showed that 67% (43/64) of pharmacists surveyed carried out MR in all children at admission and only a third 34% (22/64) had policies for MR in children. Of the respondents who did not carry out MR in all children, 80% (4/5) responded that they did so in selected children. Pharmacists considered themselves the most appropriate profession for carrying out MR. When asked whether the NICE guidance should be expanded to include children, 98% (54/55) of the respondents answered ‘yes’.

Conclusion
In conclusion, the findings suggest that MR is being conducted inconsistently in children and most paediatric pharmacists would like national guidance to be expanded to include children.
The influence of evidence-based medicine training on decision-making in relation to over-the-counter medicines: a qualitative study
Authors: Hanna Lezley-Anne , Hughes Carmel 
Published: June 2012

Abstract

Objectives
To explore the role of evidence of effectiveness when making decisions about over-the-counter (OTC) medication and to ascertain whether evidence-based medicine training raised awareness in decision-making. Additionally, this work aimed to complement the findings of a previous study because all participants in this current study had received training in evidence-based medicine (unlike the previous participants).

Methods
Following ethical approval and an e-mailed invitation, face-to-face, semi-structured interviews were conducted with newly registered pharmacists (who had received training in evidence-based medicine as part of their MPharm degree) to discuss the role of evidence of effectiveness with OTC medicines. Interviews were recorded and transcribed verbatim. Following transcription, all data were entered into the NVivo software package (version 8). Data were coded and analysed using a constant comparison approach.

Key findings
Twenty-five pharmacists (7 males and 18 females; registered for less than 4 months) were recruited and all participated in the study. Their primary focus with OTC medicines was safety; sales of products (including those that lack evidence of effectiveness) were justified provided they did no harm. Meeting patient expectation was also an important consideration and often superseded evidence. Despite knowledge of the concept, and an awareness of ethical requirements, an evidence-based approach was not routinely implemented by these pharmacists. Pharmacists did not routinely utilize evidence-based resources when making decisions about OTC medicines and some felt uncomfortable discussing the evidence-base for OTC products with patients.

Conclusions
The evidence-based medicine training that these pharmacists received appeared to have limited influence on OTC decision-making. More work could be conducted to ensure that an evidence-based approach is routinely implemented in practice.
Nonlinear Bifurcation Analysis of a Single-DoF Model of a Robotic Arm Subject to Digital Position Control
Authors: Habib Giuseppe , Rega Giuseppe , Stepan Gabor 
Published: June 2012

Abstract
Precision and stability in position control of robots are critical parameters in many industrial applications where high accuracy is needed. It is well known that digital effect is destabilizing and can cause instabilities. In this paper, we analyze a single DoF model of a robotic arm and we present the stability limits in the parameter space of the control gains. Furthermore we introduce a nonlinearity relative to the saturation of the control force in the model, reduce the dynamics of the nonlinear map to its local center manifold, study the bifurcation along the stability border and identify conditions under which a supercritical or subcritical bifurcation occurs. The obtained results explain some of the typical instabilities occurring in industrial applications. We verify the obtained results through numerical simulations.
A Three-Stage Symbiosis Forms the Foundation of Seagrass Ecosystems
Authors: van der Heide Tjisse , Govers Laura L. , de Fouw Jimmy , Olff Han , van der Geest Matthijs , van Katwijk Marieke M. , Piersma Theunis , van de Koppel Johan , Silliman Brian R. , Smolders Alfons J. P. , van Gils Jan A. 
Published: June 2012

Ancient AssociationsSubmarine seagrass meadows are critical to fisheries and coastline protection and provide feeding grounds for many endangered species, including dugongs and turtles, and serve as a nursery for coral reef fish. The persistence and maintenance of seagrass ecosystems have been mysterious, because accumulation of organic matter in the beds should rapidly lead to toxic sulphide levels in the sediment. Using a meta-analysis and a field study,van der Heideet al.(p.1432) atttribute the 100-million-year success of seagrasses to a three-stage symbiosis. Seagrass beds worldwide contain high densities of small lucinid bivalves that have symbiotic sulphide-oxidizing bacteria in their gills. This association appears to relieve any sulphide stress for seagrasses, while the lucinids and their symbionts profit from the accumulation of degradable organic matter and oxygen release from seagrass roots.
Enhanced Bovine Herpesvirus Type 1 Neutralization by Multimerized Single-Chain Variable Antibody Fragments Regardless of Differential Glycosylation
Authors: Pasman Yfke , Nagy Eva , Kaushik Azad K. 
Published: June 2012

ABSTRACTSingle-chain variable antibody fragments (scFvs) with a 2-amino-acid linker capable of multimerization as di-, tri-, or tetrabodies that neutralize bovine herpesvirus type 1 (BoHV-1)in vitrowere constructed and expressed inPichia pastoris. In contrast to the monomeric form, multimeric scFvs had a higher virus neutralization potency, as evidenced by a 2-fold increase in their ability to neutralize BoHV-1 due to avidity effects. Mass spectrum (quadrupole time of flight [Q-TOF]) analyses of multimeric scFv demonstrated extensive heterogeneity due to differential cleavage, variable glycosylation (1 to 9 mannose residues), and the incorporation of minor unidentified adducts. Regardless of the differential glycosylation patterns, the scFvs recognized non-gB or -gE target viral epitopes in the BoHV-1 envelope fraction in a Western blot and also neutralized BoHV-1 in infected Madin-Darby kidney (MDBK) cellsin vitro. Indirect evidence for the noncovalent multimerization of scFv was the presence of a major peak of multimerized scFv without a His tag (due to differential cleavage) in the Q-TOF profile, unlike monomeric scFv, which copurified with normally His-tagged scFv and recognized the target antigen. Overall, differentially glycosylated recombinant scFvs against BoHV-1 with a short linker (2 amino acids) are capable of assembly into functional multimers that confer high avidity, resulting in increased virus neutralizationin vitrocompared to that of monovalent scFv with a long (18-amino-acid) flexible linker. Overall, recombinant multimerized scFv5-2L potentially provides a high-potency therapeutic and immunodiagnostic reagent against BoHV-1, which is suitable for passive immunization and topical application.
IL23R(Arg381Gln) Functional Polymorphism Is Associated with Active Pulmonary Tuberculosis Severity
Authors: Ben-Selma Walid , Boukadida Jalel 
Published: June 2012

ABSTRACTThe purpose of our study was to investigate the association between a functional single nucleotide polymorphism (SNP) in the interleukin-23 receptor gene (IL23R; rs11209026, 1142 Gwild type→ Areduced function, Arg381Gln) and disease severity outcome in pulmonary tuberculosis (TB) in the Tunisian population. SNP was investigated in a population of 168 patients with active pulmonary TB (cases were stratified into patients with minimal/moderate lung involvement, i.e., patients with minimal/moderate disease [Pmd], and patients with extensive lung involvement, i.e., patients with active disease [Pad]) and 150 healthy subjects. Genotype analyses were carried out using the PCR-restriction fragment length polymorphism method. We have found that theIL23Rreduced-function allele 1142A and genotypes AA and AG were overrepresented, especially in the Pad subgroup compared with the control group (51% versus 18% [P= 10−8], 33% versus 5% [P= 10−8], and 36% versus 26% [P= 5 × 10−3], respectively). Additionally, comparison of the Pad and the Pmd groups showed that the A allele and AA genotype seemed to be associated with 2.79-fold (P= 4 × 10−5) and 7.74-fold (P= 10−5) increased risks of TB with minimal/moderate lung involvement, respectively. Our results demonstrate that the reduced-function polymorphism 1142G → A encoded byIL23Rinfluences the outcome of disease severity of active pulmonary TB in Tunisian patients.
Evaluation of Recombinant Proteins of Burkholderia mallei for Serodiagnosis of Glanders
Authors: Pal Vijai , Kumar Subodh , Malik Praveen , Rai Ganga Prasad 
Published: June 2012

ABSTRACTGlanders is a contagious disease caused by the Gram-negative bacillusBurkholderia mallei. The number of equine glanders outbreaks has increased steadily during the last decade. The disease must be reported to the Office International des Epizooties, Paris, France. Glanders serodiagnosis is hampered by the considerable number of false positives and negatives of the internationally prescribed tests. The major problem leading to the low sensitivity and specificity of the complement fixation test (CFT) and enzyme-linked immunosorbent assay (ELISA) has been linked to the test antigens currently used, i.e., crude preparations of whole cells. False-positive results obtained from other diagnostic tests utilizing crude antigens lead to financial losses to animal owners, and false-negative results can turn a risk into a possible threat. In this study, we report on the identification of diagnostic targets using bioinformatics tools for serodiagnosis of glanders. The identified gene sequences were cloned and expressed as recombinant proteins. The purified recombinant proteins ofB. malleiwere used in an indirect ELISA format for serodiagnosis of glanders. Two recombinant proteins, 0375H and 0375TH, exhibited 100% sensitivity and specificity for glanders diagnosis. The proteins also did not cross-react with sera from patients with the closely related disease melioidosis. The results of this investigation highlight the potential of recombinant 0375H and 0375TH proteins in specific and sensitive diagnosis of glanders.
Field Application of Serodiagnostics To Identify Elephants with Tuberculosis prior to Case Confirmation by Culture
Authors: Lyashchenko Konstantin P. , Greenwald Rena , Esfandiari Javan , Mikota Susan , Miller Michele , Moller Torsten , Vogelnest Larry , Gairhe Kamal P. , Robbe-Austerman Suelee , Gai Jackie , Waters W. Ray 
Published: June 2012

ABSTRACTThree serologic methods for antibody detection in elephant tuberculosis (TB), the multiantigen print immunoassay (MAPIA), ElephantTB STAT-PAK kit, and DPP VetTB test, were evaluated using serial serum samples from 14 captive elephants infected withMycobacterium tuberculosisin 5 countries. In all cases, serological testing was performed prior to the diagnosis of TB by mycobacterial culture of trunk wash or tissue samples collected at necropsy. All elephants produced antibody responses toM. tuberculosisantigens, with 13/14 recognizing ESAT-6 and/or CFP10 proteins. The findings supported the high serodiagnostic test accuracy in detecting infections months to years beforeM. tuberculosiscould be isolated from elephants. The MAPIA and/or DPP VetTB assay demonstrated the potential for monitoring antimycobacterial therapy and predicting TB relapse in treated elephants when continuously used in the posttreatment period. History of exposure to TB and past treatment information should be taken into consideration for proper interpretation of the antibody test results. Data suggest that the more frequent trunk wash culture testing of seropositive elephants may enhance the efficiency of the TB diagnostic algorithm, leading to earlier treatment with improved outcomes.
Evaluation of the Efficacy of an Attenuated Live Vaccine against Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus in Young Pigs
Authors: Leng Xue , Li Zhenguang , Xia Mingqi , He Yanliang , Wu Hua 
Published: June 2012

ABSTRACTHighly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) is characterized by high fever and high mortality in pigs of all ages and has severely affected the pork industry of China in the last few years. An attenuated HP-PRRSV strain, TJM, was obtained by passaging HP-PRRSV strain TJ on MARC-145 cells for 92 passages. Porcine reproductive and respiratory syndrome virus (PRRSV)- and antibody-free pigs were inoculated intramuscularly with TJM (105.050% tissue culture infective doses [TCID50]) and challenged at 28, 60, 120, and 180 days postimmunization (dpi). The results showed that 5/5, 5/5, 5/5, and 4/5 immunized pigs were protected from the lethal challenge and did not develop fever and clinical diseases at each challenge, respectively. Compared to control pigs, vaccinated pigs showed much milder pathological lesions and gained significantly more weight (P< 0.01). Sequence analysis of different passages of strain TJ showed that the attenuation resulted in a deletion of a continuous 120 amino acids (aa), in addition to the discontinuous 30-aa deletion in the nsp2 region. The analysis also demonstrated that the 120-aa deletion was genetically stablein vivo. These results suggested that HP-PRRSV TJM was efficacious against a lethal challenge with a virulent HP-PRRSV strain, and effective protection could last at least 4 months. Therefore, strain TJM is a good candidate for an efficacious modified live virus vaccine as well as a useful molecular marker vaccine against HP-PRRSV.
Increased Antibody Affinity Confers Broad
In Vitro
Protection against Escape Mutants of Severe Acute Respiratory Syndrome Coronavirus
Authors: Rani Mridula , Bolles Meagan , Donaldson Eric F. , Van Blarcom Thomas , Baric Ralph , Iverson Brent , Georgiou George 
Published: June 2012

ABSTRACT

Even though the effect of antibody affinity on neutralization potency is well documented, surprisingly, its impact on neutralization breadth and escape has not been systematically determined. Here, random mutagenesis and DNA shuffling of the single-chain variable fragment of the neutralizing antibody 80R followed by bacterial display screening using anchored periplasmic expression (APEx) were used to generate a number of higher-affinity variants of the severe acute respiratory syndrome coronavirus (SARS-CoV)-neutralizing antibody 80R with equilibrium dissociation constants (

K
D

) as low as 37 pM, a >270-fold improvement relative to that of the parental 80R single-chain variable fragment (scFv). As expected, antigen affinity was shown to correlate directly with neutralization potency toward the icUrbani strain of SARS-CoV. Additionally, the highest-affinity antibody fragment displayed 10-fold-increased broad neutralization
in vitro
and completely protected against several SARS-CoV strains containing substitutions associated with antibody escape. Importantly, higher affinity also led to the suppression of viral escape mutants
in vitro
. Escape from the highest-affinity variant required reduced selective pressure and multiple substitutions in the binding epitope. Collectively, these results support the hypothesis that engineered antibodies with picomolar dissociation constants for a neutralizing epitope can confer escape-resistant protection.
Safer, Silencing-Resistant Lentiviral Vectors: Optimization of the Ubiquitous Chromatin-Opening Element through Elimination of Aberrant Splicing
Authors: Knight Sean , Zhang Fang , Mueller-Kuller Uta , Bokhoven Marieke , Gupta Abhinav , Broughton Thomas , Sha Sha , Antoniou Michael N. , Brendel Christian , Grez Manuel , Thrasher Adrian J. , Collins Mary , Takeuchi Yasuhiro 
Published: June 2012

ABSTRACT

Gammaretroviral and lentiviral vectors have been used successfully in several clinical gene therapy trials, although powerful enhancer elements have caused insertional mutagenesis and clonal dysregulation. Self-inactivating vectors with internal heterologous regulatory elements have been developed as potentially safer and more effective alternatives. Lentiviral vectors containing a ubiquitous chromatin opening element from the human
HNRPA2B1-CBX3
locus (A2UCOE), which allows position-independent, long-term transgene expression, are particularly promising. In a recently described assay, aberrantly spliced mRNA transcripts initiated in the vector A2UCOE sequence were found to lead to upregulation of growth hormone receptor gene (
Ghr
) expression in transduced murine Bcl-15 cells. Aberrant hybrid mRNA species formed between A2UCOE and a number of other cellular genes were also detected in transduced human PLB-985 myelomonocytic cells. Modification of the A2UCOE by mutation or deletion of recognized and potential cryptic splice donor sites was able to abrogate these splicing events and hybrid mRNA formation in Bcl-15 cells. This modification did not compromise A2UCOE regulatory activity in terms of resistance to CpG methylation and gene silencing in murine P19 embryonic carcinoma cells. These refined A2UCOE regulatory elements are likely to improve intrinsic biosafety and may be particularly useful for a number of clinical applications where robust gene expression is desirable.
Live-Attenuated Lentivirus Immunization Modulates Innate Immunity and Inflammation while Protecting Rhesus Macaques from Vaginal Simian Immunodeficiency Virus Challenge
Authors: Genescà Meritxell , Ma Zhong-Min , Wang Yichuan , Assaf Basel , Qureshi Huma , Fritts Linda , Huang Ying , McChesney Michael B. , Miller Christopher J. 
Published: June 2012

ABSTRACT

Immunization with attenuated lentiviruses is the only reliable method of protecting rhesus macaques (RM) from vaginal challenge with pathogenic simian immunodeficiency virus (SIV). CD8
+
lymphocyte depletion prior to SIVmac239 vaginal challenge demonstrated that a modest, Gag-specific CD8
+
T cell response induced by immunization with simian-human immunodeficiency virus 89.6 (SHIV89.6) protects RM. Although CD8
+
T cells are required for protection, there is no anamnestic expansion of SIV-specific CD8
+
T cells in any tissues except the vagina after challenge. Further, SHIV immunization increased the number of viral target cells in the vagina and cervix, suggesting that the ratio of target cells to antiviral CD8
+
T cells was not a determinant of protection. We hypothesized that persistent replication of the attenuated vaccine virus modulates inflammatory responses and limits T cell activation and expansion by inducing immunoregulatory T cell populations. We found that attenuated SHIV infection decreased the number of circulating plasmacytoid dendritic cells, suppressed T cell activation, decreased mRNA levels of proinflammatory mediators, and increased mRNA levels of immunoregulatory molecules. Three days after SIV vaginal challenge, SHIV-immunized RM had significantly more T regulatory cells in the vagina than the unimmunized RM. By day 14 postchallenge, immune activation and inflammation were characteristic of unimmunized RM but were minimal in SHIV-immunized RM. Thus, a modest vaccine-induced CD8
+
T cell response in the context of immunoregulatory suppression of T cell activation may protect against vaginal HIV transmission.
Detailed Mapping of Determinants within the Porcine Endogenous Retrovirus Envelope Surface Unit Identifies Critical Residues for Human Cell Infection within the Proline-Rich Region
Authors: Argaw Takele , Wilson Carolyn A. 
Published: June 2012

ABSTRACT

Replication-competent porcine endogenous retroviruses (PERVs) are either human cell tropic (PERV-A and PERV-B) or non-human cell tropic (PERV-C). We previously demonstrated that PERV
in vitro
cell tropism is modulated by 2 residues within the C terminus of SU and that the PERV receptor binding domain (RBD) extends beyond the variable regions A and B (VRA and VRB, respectively), to include the proline rich-region (PRR) of SU (M. Gemeniano et al., Virology 346:108–117, 2000; T. Argaw et al., J. Virol. 82:7483–7489, 2008). The present study aimed to identify the specific elements within the PERV RBD that interact with the C-terminal elements of SU to facilitate human cell infection. We constructed a series of chimeric and mutated envelopes between PERV-A and PERV-C and using pseudotyped retroviral vectors to map the human cell tropism-determining sequences within the PERV RBD. We show that the PRR from PERV-A is both necessary and sufficient to allow human cell infection when substituted into the homologous region of the PERV-C envelope carrying two C-terminal amino acid substitutions shown to influence human cell tropism, Q374R and I412V (PERV-Crv). Furthermore, substitution of a single amino acid residue in the PRR of the non-human-tropic PERV-Crv envelope allows vectors carrying this envelope to infect human cells. Receptor interference assays showed that these modified PERV-C envelopes do not bind either of the human PERV-A receptors, suggesting the presence of a distinct human PERV-C receptor. Finally, vectors carrying these modified PERV-C envelopes infect primary human endothelial cells, a cell type likely to be exposed to PERV in clinical use of certain porcine xenotransplantation products.
HMGB1 Protein Binds to Influenza Virus Nucleoprotein and Promotes Viral Replication
Authors: Moisy Dorothée , Avilov Sergiy V. , Jacob Yves , Laoide Brid M. , Ge Xingyi , Baudin Florence , Naffakh Nadia , Jestin Jean-Luc 
Published: June 2012

ABSTRACT
Influenza virus has evolved replication strategies that hijack host cell pathways. To uncover interactions between viral macromolecules and host proteins, we applied a phage display strategy. A library of human cDNA expression products displayed on filamentous phages was submitted to affinity selection for influenza viral ribonucleoproteins (vRNPs). High-mobility-group box (HMGB) proteins were found to bind to the nucleoprotein (NP) component of vRNPs. HMGB1 and HMGB2 bind directly to the purified NP in the absence of viral RNA, and the HMG box A domain is sufficient to bind the NP. We show that HMGB1 associates with the viral NP in the nuclei of infected cells, promotes viral growth, and enhances the activity of the viral polymerase. The presence of a functional HMGB1 DNA-binding site is required to enhance influenza virus replication. Glycyrrhizin, which reduces HMGB1 binding to DNA, inhibits influenza virus polymerase activity. Our data show that the HMGB1 protein can play a significant role in intranuclear replication of influenza viruses, thus extending previous findings on the bornavirus and on a number of DNA viruses.