bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antifungal Susceptibility Testing of
Candida
Isolates from the Candida Surveillance Study
Authors: Lyon G. Marshall , Karatela Sulaiman , Sunay Susan , Adiri Yaffa 
Published: February 2010

ABSTRACT

Candida
species are a common cause of nosocomial bloodstream infections. Recent surveillance has shown an increase in the relative proportion of infections caused by
Candida glabrata
, which has reduced susceptibility to fluconazole. We undertook sentinel surveillance with antifungal susceptibility testing to monitor the trends in the proportions of various
Candida
species causing invasive disease. Forty-one institutions participated in the Candida Surveillance Study. All isolates were submitted to a central laboratory for identification and susceptibility testing. Susceptibility testing was performed in compliance with CLSI guidelines using a custom, broth dilution, microtiter system. There were 5,900 isolates submitted for identification and antifungal susceptibility testing. The distribution of species was as follows:
C. albicans
, 2,567 (43.5%) isolates;
C. glabrata
, 1,464 (24.8%) isolates;
C. parapsilosis
, 1,048 (17.8%) isolates;
C. tropicalis
, 527 (8.9%) isolates;
C. krusei
, 109 (1.9%) isolates;
C. lusitaniae
, 76 (1.3%) isolates; and other
Candida
species, 109 (1.9%) isolates. Resistance to fluconazole occurred in 1.2% of
C. albicans
isolates, 5.9% of
C. glabrata
isolates, 0.3% of
C. parapsilosis
isolates, and 0.4% of
C. tropicalis
isolates. Resistance to fluconazole was highly predictive of resistance to voriconazole. Resistance to echinocandins was rarely found, occurring in only 0.2% of all isolates. The rate of fluconazole susceptibility increased significantly from 87.5% in 2005 to 97.4% in 2007. The proportion of cases of disease caused by various
Candida
species did not change appreciably between 2004 and 2007, and the rate of antifungal susceptibility was high.
A Chimeric Alphavirus Replicon Particle Vaccine Expressing the Hemagglutinin and Fusion Proteins Protects Juvenile and Infant Rhesus Macaques from Measles
Authors: Pan Chien-Hsiung , Greer Catherine E. , Hauer Debra , Legg Harold S. , Lee Eun-Young , Bergen M. Jeff , Lau Brandyn , Adams Robert J. , Polo John M. , Griffin Diane E. 
Published: February 2010

ABSTRACTMeasles remains a major cause of child mortality, in part due to an inability to vaccinate young infants with the current live attenuated virus vaccine (LAV). To explore new approaches to infant vaccination, chimeric Venezuelan equine encephalitis/Sindbis virus (VEE/SIN) replicon particles were used to express the hemagglutinin (H) and fusion (F) proteins of measles virus (MV). Juvenile rhesus macaques vaccinated intradermally with a single dose of VEE/SIN expressing H or H and F proteins (VEE/SIN-H or VEE/SIN-H+F, respectively) developed high titers of MV-specific neutralizing antibody and gamma-interferon (IFN-γ)-producing T cells. Infant macaques vaccinated with two doses of VEE/SIN-H+F also developed neutralizing antibody and IFN-γ-producing T cells. Control animals were vaccinated with LAV or with a formalin-inactivated measles vaccine (FIMV). Neutralizing antibody remained above the protective level for more than 1 year after vaccination with VEE/SIN-H, VEE/SIN-H+F, or LAV. When challenged with wild-type MV 12 to 17 months after vaccination, all vaccinated juvenile and infant monkeys vaccinated with VEE/SIN-H, VEE/SIN-H+F, and LAV were protected from rash and viremia, while FIMV-vaccinated monkeys were not. Antibody was boosted by challenge in all groups. T-cell responses to challenge were biphasic, with peaks at 7 to 25 days and at 90 to 110 days in all groups, except for the LAV group. Recrudescent T-cell activity coincided with the presence of MV RNA in peripheral blood mononuclear cells. We conclude that VEE/SIN expressing H or H and F induces durable immune responses that protect from measles and offers a promising new approach for measles vaccination. The viral and immunological factors associated with long-term control of MV replication require further investigation.
Pathogenesis of a Model Gammaherpesvirus in a Natural Host
Authors: Hughes David J. , Kipar Anja , Sample Jeffery T. , Stewart James P. 
Published: February 2010

ABSTRACT

Murine gammaherpesvirus 68 (MHV-68) infection of laboratory mice (
Mus musculus
) is an established model of gammaherpesvirus pathogenesis. The fact that
M. musculus
is not a host in the wild prompted us to reassess MHV-68 infection in wood mice (
Apodemus sylvaticus
), a natural host. Here, we report significant differences in MHV-68 infection in the two species: (i) following intranasal inoculation, MHV-68 replicated in the lungs of wood mice to levels approximately 3 log units lower than in BALB/c mice; (ii) in BALB/c mice, virus replication in alveolar epithelial cells was accompanied by a diffuse, T-cell-dominated interstitial pneumonitis, whereas in wood mice it was restricted to focal granulomatous infiltrations; (iii) within wood mice, latently infected lymphocytes were abundant in inducible bronchus-associated lymphoid tissue that was not apparent in BALB/c mice; (iv) splenic latency was established in both species, but well-delineated secondary follicles with germinal centers were present in wood mice, while only poorly delineated follicles were seen in BALB/c mice; and, perhaps as a consequence, (v) production of neutralizing antibody was significantly higher in wood mice. These differences highlight the value of this animal model in the study of MHV-68 pathogenesis.
Introduction of Virulence Markers in PB2 of Pandemic Swine-Origin Influenza Virus Does Not Result in Enhanced Virulence or Transmission
Authors: Herfst Sander , Chutinimitkul Salin , Ye Jianqiang , de Wit Emmie , Munster Vincent J. , Schrauwen Eefje J. A. , Bestebroer Theo M. , Jonges Marcel , Meijer Adam , Koopmans Marion , Rimmelzwaan Guus F. , Osterhaus Albert D. M. E. , Perez Daniel R. , Fouchier Ron A. M. 
Published: February 2010

ABSTRACT

In the first 6 months of the H1N1 swine-origin influenza virus (S-OIV) pandemic, the vast majority of infections were relatively mild. It has been postulated that mutations in the viral genome could result in more virulent viruses, leading to a more severe pandemic. Mutations E627K and D701N in the PB2 protein have previously been identified as determinants of avian and pandemic influenza virus virulence in mammals. These mutations were absent in S-OIVs detected early in the 2009 pandemic. Here, using reverse genetics, mutations E627K, D701N, and E677G were introduced into the prototype S-OIV A/Netherlands/602/2009, and their effects on virus replication, virulence, and transmission were investigated. Mutations E627K and D701N caused increased reporter gene expression driven by the S-OIV polymerase complex. None of the three mutations affected virus replication
in vitro
. The mutations had no major impact on virus replication in the respiratory tracts of mice and ferrets or on pathogenesis. All three mutant viruses were transmitted via aerosols or respiratory droplets in ferrets. Thus, the impact of key known virulence markers in PB2 in the context of current S-OIVs was surprisingly small. This study does not exclude the possibility of emergence of S-OIVs with other virulence-associated mutations in the future. We conclude that surveillance studies aimed at detecting S-OIVs with increased virulence or transmission should not rely solely on virulence markers identified in the past but should include detailed characterization of virus phenotypes, guided by genetic signatures of viruses detected in severe cases of disease in humans.
Bimolecular Complementation Defines Functional Regions of Herpes Simplex Virus gB That Are Involved with gH/gL as a Necessary Step Leading to Cell Fusion
Authors: Atanasiu Doina , Whitbeck J. Charles , de Leon Manuel Ponce , Lou Huan , Hannah Brian P. , Cohen Gary H. , Eisenberg Roselyn J. 
Published: February 2010

ABSTRACT
Herpes simplex virus (HSV) entry into cells requires four membrane glycoproteins: gD is the receptor binding protein, and gB and gH/gL constitute the core fusion machinery. Crystal structures of gD and its receptors have provided a basis for understanding the initial triggering steps, but how the core fusion proteins function remains unknown. The gB crystal structure shows that it is a class III fusion protein, yet unlike other class members, gB itself does not cause fusion. Bimolecular complementation (BiMC) studies have shown that gD-receptor binding triggers an interaction between gB and gH/gL and concurrently triggers fusion. Left unanswered was whether BiMC led to fusion or was a by-product of it. We used gB monoclonal antibodies (MAbs) to block different aspects of these events. Non-virus-neutralizing MAbs to gB failed to block BiMC or fusion. In contrast, gB MAbs that neutralize virus blocked fusion. These MAbs map to three functional regions (FR) of gB. MAbs to FR1, which contains the fusion loops, and FR2 blocked both BiMC and fusion. In contrast, MAbs to FR3, a region involved in receptor binding, blocked fusion but not BiMC. Thus, FR3 MAbs separate the BiMC interaction from fusion, suggesting that BiMC occurs prior to fusion. When substituted for wild-type (wt) gB, fusion loop mutants blocked fusion and BiMC, suggesting that loop insertion precedes BiMC. Thus, we postulate that each of the gB FRs are involved in different aspects of the path leading to fusion. Upon triggering by gD, gB fusion loops are inserted into target lipid membranes. gB then interacts with gH/gL, and this interaction is eventually followed by fusion.
Assessment of parental decision-making in neonatal cardiac research: a pilot study
Authors: Nathan Aruna T , Hoehn K Sarah , Ittenbach Richard F , Gaynor J William , Nicolson Susan , Wernovsky Gil , Nelson Robert M 
Published: February 2010

ObjectiveTo assess parental permission for a neonate's research participation using the MacArthur competence assessment tool for clinical research (MacCAT-CR), specifically testing the components of understanding, appreciation, reasoning and choice.Study DesignQuantitative interviews using study-specific MacCAT-CR tools.HypothesisParents of critically ill newborns would produce comparable MacCAT-CR scores to healthy adult controls despite the emotional stress of an infant with critical heart disease or the urgency of surgery. Parents of infants diagnosed prenatally would have higher MacCAT-CR scores than parents of infants diagnosed postnatally. There would be no difference in MacCAT-CR scores between parents with respect to gender or whether they did or did not permit research participation.ParticipantsParents of neonates undergoing cardiac surgery who had made decisions about research participation before their neonate's surgery.MethodsThe MacCAT-CR.Results35 parents (18 mothers; 17 fathers) of 24 neonates completed 55 interviews for one or more of three studies. Total scores: magnetic resonance imaging (mean 36.6, SD 7.71), genetics (mean 38.8, SD 3.44), heart rate variability (mean 37.7, SD 3.30). Parents generally scored higher than published subject populations and were comparable to published control populations with some exceptions.ConclusionsThe MacCAT-CR can be used to assess parental permission for neonatal research participation. Despite the stress of a critically ill neonate requiring surgery, parents were able to understand study-specific information and make informed decisions to permit their neonate's participation.
Attributes of a good physician: what are the opinions of first-year medical students?: Table 1
Authors: Sehiralti Mine , Akpinar Aslihan , Ersoy Nermin 
Published: February 2010

BackgroundUndergraduate medical education is beginning to concern itself with educating students about professional attributes as well as about clinical knowledge and skills. Defining these characteristics, and in particular seeking the help of the students themselves to define them, can be a useful starting point when considering how to incorporate aspects of professional behaviour into the medical curricula.MethodThis study explores the views of first-year medical students at Kocaeli University Faculty of Medicine in the 2007–8 academic year. The students were asked the open-ended question: ‘What, in your opinion, are the attributes a good physician should have?’ Four topics were defined by researchers based on the undergraduate and graduate education projects. The attributes expressed by the students were evaluated by the researchers according to these topics and compared with the topics covered in the undergraduate and graduate education projects.ResultsA total of 127 students responded, and between them suggested 756 attributes. The majority of these attributes (54.6%) were concerned with interpersonal relations and communication, whereas the category representing the fewest attributes (12.3%) was that involving scientific knowledge and medical practice. In general, students' perception corresponded to the concept of the ‘competent physician’ as described in the professionalism projects, but attributes reflecting their world-view were also expressed.ConclusionExperience suggests that the active participation of students in determining which attributes are necessary for a good physician is a positive way of ensuring they embrace the importance of such qualities and attributes in themselves.
Work-relatedHelicobacter pyloriinfection among sewage workers in municipal wastewater treatment plants in Belgium
Authors: Van Hooste Wim , Charlier Anne-Marie , Rotsaert Paul , Bulterys Simon , Moens Guido , van Sprundel Marc , De Schryver Antoon 
Published: February 2010

IntroductionMost studies among sewage workers of wastewater treatment plants (WWTPs) have found a higher prevalence of gastrointestinal symptoms than among non-sewage exposed workers. Waterborne transmission ofHelicobacter pylori(H pylori) has been hypothesised, as the bacteria can survive into an aqueous environment and has been detected in sewage. A health and hygiene questionnaire has demonstrated a higher prevalence of peptic ulcers among Belgian WWTP operators and maintenance workers than among non-sewage exposed colleagues.ObjectivesTo assess the seroprevalence ofH pyloriinfection in Belgian sewage workers at municipal WWTPs, and to determine whether sewage exposure is an important risk factor for acquisition ofH pyloriand the possible association with gastrointestinal symptoms.MethodsA seroprevalence study ofH pyloriantibodies was conducted among 317 WWTP employees (operators, maintenance workers, laboratory personnel, other job). Information about demographic variables, possibleH pyloririsk factors, working history, and history of current gastrointestinal symptoms during last 3 months was obtained by a questionnaire. The presence ofH pyloriIgG was investigated with an ELISA. The results were compared with those of 250 employees of a pharmaceutical company (operators, maintenance workers, laboratory personnel).ResultsThe prevalence ofH pyloriIgG antibodies among sewage workers was 16.7% (95% CI 12.6 to 20.8%) compared to 13.6% (95% CI 9.4 to 17.8%) among the control group. In a logistic regression model with controlling for age and educational levels, OR study/control group was 1.02 (95% CI 0.58 to 1.80 with p=0.93). No significant associations were found between theH pyloristatus and gastrointestinal symptoms, occupational exposures in different tasks, nor with hygienic practices.ConclusionsOur results do not suggest thatH pyloriinfection is a probable cause of part of gastrointestinal symptoms among Flemish municipal sewage workers of WWTPs.
NEWS FRAMING OF POPULATION AND FAMILY PLANNING ISSUES VIA SYNTACTIC NETWORK ANALYSIS
Authors: LEGARA ERIKA , MONTEROLA CHRISTOPHER , DAVID CLARISSA , MAE ATUN JENNA 
Published: February 2010

Contentious political debates regarding the issues on population and family planning have been perennial over the past four decades especially in developing countries. While its prominence in the public agenda varies depending on other national issues vying for public attention, its presence in policy and political agendas is constant. Here, a computational approach to framing analysis is developed that examines the pattern of media coverage on the population issue in the Philippines. The content of 146 articles sampled from 1988 to 2007 in Manila Bulletin (one of the leading newspapers in the Philippines) is analyzed by creating a syntactic network of concept co-occurrences. The topological properties of the network indicates that the discussion of an article revolves around few central ideas. Moreover, cluster analysis of the network suggests three well-defined frame themes, namely: (1) Development Frame; (2) Maternal Health Frame; and (3) Framing by the Catholic Church. Our results support the thesis that the inability to fruitfully discuss points of contention to reach agreement about suitable population policies in the Philippines is due to the mismatched frames within which it is discussed.
Assessment of laboratory assays to measure rivaroxaban – an oral, direct factor Xa inhibitor
Authors: Martinoli Jean-Luc , LeFlem Léna , Guinet Céline , Plu-Bureau Geneviève , Depasse François , Perzborn Elisabeth , Samama Meyer Michel 
Published: February 2010

SummaryAlthough there is no need for routine coagulation monitoring with rivaroxaban – an oral, direct factor Xa inhibitor – a haemostasis assay might be valuable to measure its pharmacodynamic effects. This study aimed to find assays, among those commercially available, to measure rivaroxaban pharmacodynamics. Several global conventional clotting tests, as well as clotting or chromogenic assays to measure anti-factor Xa activity, were studied. A thrombin generation test using calibrated automated thrombogram was also done. Tests were performed with the indirect factor Xa inhibitor fondaparinux for comparison. A concentration-dependent prolongation of prothrombin time (PT), dilute PT, and activated partial thromboplastin time was observed with rivaroxaban. The results varied depending on the reagents. This variability cannot be standardised with the international normalised ratio system commonly used for vitamin K antagonists. Using a standard calibration curve, PT test results can be expressed in plasma concentrations of rivaroxaban rather than PT seconds or ratio. Standard methods for HepTest and two-step prothrombinase-induced clotting time (PiCT) resulted in a paradoxical response, with low concentrations of rivaroxaban reducing clotting times. This was not observed with shorter incubation times, or when antithrombin-deficient (immunodepleted) plasma was used. The chromogenic tests found a dose-dependent relationship between anti-factor Xa activity and rivaroxaban concentration. Modified specific factor Xa chromogenic assays are being further investigated. One-step PiCT and HepTest with shortened incubation times, as well as the widely available PT assay (using a rivaroxaban calibrator) could be useful to monitor the pharmacodynamic effects of rivaroxaban accurately. Finally, all clotting and chromogenic assays showed a concentration-dependent effect induced by rivaroxaban.
8-pCPT-conjugated cyclic AMP analogs exert thromboxane receptor antagonistic properties
Authors: Grandoch Maria , Börgermann Christof , Oude Weernink Paschal , Mahlke Yvonne , Schwindenhammer Benjamin , Weber Artur-Aron , Fischer Jens , Jakobs Karl , Sand Carsten , Schmidt Martina 
Published: February 2010

SummaryMembrane-permeable 8-(4-chlorophenylthio)-2'-O-methyl cyclic AMP (8-pCPT-2'-O-Me-cAMP) has been shown to specifically activate cAMP-regulated Epac proteins, without direct effects on protein kinase A and protein kinase G. During isometric tension measurements in thoracic aortic rings from Wistar rats, we observed that 8-pCPT-2'-O-Me-cAMP selectively induced a rightward shift of the concentration response curve for the thromboxane mimetic U46619, without altering the contractile response to noradrenaline. We hypothesised that 8-pCPT-2'-O-Me-cAMP and similar compounds may function as direct thromboxane receptor antagonists. Indeed, in addition to 8-pCPT-2'-OMe-cAMP, also 8-pCPT-cAMP, 8-(4-chlorophenylthio)-adenosine-3',5'-cyclic monophosphorothioate, Rp-isomer (Rp-8-CPT-cAMPS) and 8-CPT-adenosine, but not 8-Bromo-2'-O-Me-cAMP, induced rightward shifts of the contractile response to U46619. Likewise, 8-pCPT-2'-O- Me-cAMP and Rp-8-CPT-cAMPS, but not 8-Bromo-2'-O-Me-cAMP, specifically reduced U46619-induced aggregation of human platelets. In addition, 8-pCPT-2'-O-Me-cAMP and Rp-8-CPT-cAMPS completely reversed U46619-induced reduction of intercellular adhesion molecule-1 expression and migration of human coronary artery endothelial cells. Most important, the cAMP analogs that reduced the contractile response to U46619 also concentration-dependently inhibited binding of the thromboxane receptor radioligand [5,6-3H]SQ29548 to human platelets. We conclude that 8-pCPT-conjugated cAMP analogs exert competitive thromboxane receptor antagonistic properties.
Adrenergic receptor polymorphisms and platelet reactivity after treatment with dual antiplatelet therapy with aspirin and clopidogrel in acute coronary syndrome
Authors: Cuisset Thomas , Hamilos Michalis , Delrue Leen , Frere Corinne , Verhamme Katia , Bartunek Jozef , Saut Noemie , Bonnet Jean Louis , Eijgelsheim Mark , Wijns William , Alessi Marie-Christine , Barbato Emanuele 
Published: February 2010

SummaryPlatelet response to clopidogrel shows inter-individual variability that is partially explained by genetic polymorphisms. This variability affects clinical outcome when clopidogrel is administered in patients with acute coronary syndrome (ACS). Catecholamines, released during ACS, contribute to platelet aggregation through platelet α2A- (α2A-AR) and β2-adrenergic receptor (β2-AR) stimulation. It was the objective of this study to assess the potential influence of α2A-AR and β2-AR gene polymorphisms on platelet reactivity after dual antiplatelet therapy with aspirin and clopidogrel in ACS. We screened 641 ACS patients for 6.3/6.7 kb α2A-AR polymorphism, and for Arg16Gly and Gln27Glu β2-AR polymorphism. After 600 mg clopidogrel, we assessed ADP 10 μmol-induced platelet aggregation (ADP-Ag) and vasoactive stimulated phosphoprotein (VASP). All single nucleotide polymorphisms were in Hardy-Weinberg equilibrium. A slight though negligible association was found between 6.3 kb allele of α2A-AR with platelet reactivity ADPAg induced (beta: –2.91 [-5.68;-0.14], p=0.04). A borderline not significant reduction in PRI VASP was observed in 6.3 kb α2A-AR carriers (beta: –3.81 [-0.09;7.72], p=0.06). No significant effect on platelet parameters was observed for the other tested polymorphisms. Common α2A- and β2-adrenergic receptor polymorphisms do not show any major impact on residual platelet reactivity in non-ST-elevation ACS when a dual antiplatelet therapy with 250 mg aspirin and 600 mg clopidogrel is administered.