bluuebunny/crossref_metadata_2025_split huggingface dataset:
Greek kindergarten teachers' beliefs and practices in early literacy
Authors: Stellakis Nektarios 
Published: May 2011

AbstractThis work describes a survey conducted in Syros Island in Greece. The intention was to ascertain kindergarten teachers' perceptions about early literacy and the skills and knowledge they consider as important for pre‐school aged children. The participants were all the kindergarten teachers of the island (N = 19) and the data were collected during a workshop where three groups tried to make a conceptual map of ‘literacy’. The results show that, overall, kindergarten teachers adopt a very broad definition of literacy as communication ability but restrict their practices to phonics instruction. Because this attitude differs significantly from the provisions of the official curriculum, which is based on emergent literacy perspective, it is obvious that due to the lack of specialised education and support the participants prefer a hidden curriculum, which is based on the assumption that mere acquaintance with graphophonemic relations is enough for the initial level of education. The findings of this research show that teachers lack awareness of recent research and pedagogy concerning early literacy development and demonstrate the urgent need for development of specialised educational programmes for in‐service kindergarten teachers.
Designing and Engineering of a Site‐specific Incorporation of a Keto Group in Uricase
Authors: Fang Zhengzhi , Liu Yaguang , Liu Jingxian , Sun Renhua , Chen Hai , Gao Xiangdong , Yao Wenbing 
Published: May 2011

Urate oxidase is a potential therapeutic protein in the prevention and treatment of tumor lysis syndrome and hyperuricemia. However, its severe immunogenicity limits its clinical application. In our work, several strides have been made toward engineering site‐specific modifications of keto groups in urate oxidase by using evolved Methanocaldococcus jannaschii aminoacyl‐tRNA synthetase(s)/suppressor tRNA pairs to reduce its antigenicity. Our approach, described here, consisted of designing a M. jannaschii tyrosyl‐tRNA synthetase library based on the homology modeling and molecular docking model of the species‐specific TyrRS‐Tyr complex. The active mutation was picked, and pBR‐RS series vectors were constructed to define the relationship between the expression of aaRS and the efficiency of the orthogonal amber suppressor tRNA/synthetase system. Two sites based on the 3D structure of the Candida utilis uricase, Lys21 and Lys248, were substituted for p‐acetyl‐l‐phenylalanine, and the yields were optimized. The products were purified, and their enzyme activities and antigenic properties were analyzed. The mutated uricase exhibited decreased antigenic properties, while its catalytic activities remained unchanged. This method imparts new insights into structure–function relationship research and provides a means by which site‐specific modifications may be achieved by using PEG derivates to improve pharmacological properties of urate oxidase.
Choroidal thickness following extrafoveal photodynamic treatment with verteporfin in patients with central serous chorioretinopathy
Authors: Pryds Anders , Larsen Michael 
Published: May 2011

Abstract.Purpose:  To evaluate the effect of verteporfin photodynamic treatment (PDT) on choroidal thickness in patients with central serous chorioretinopathy (CSC).Methods:  Choroidal thickness was measured with enhanced depth imaging– optical coherence tomography (EDI–OCT) before and after verteporfin PDT (full‐dose verteporfin, half‐light dose) in 16 eyes in 16 patients with serous detachment of the fovea secondary to extrafoveal angiographic fluorescein leakage. Treatment was confined to the area of leakage, whereas choroidal thickness before and after treatment was assessed over a larger area of the fundus using OCT.Results:  Complete resolution of the serous detachment was seen in all 16 eyes within 1 month of extrafoveal PDT, while choroidal thickness in the area where PDT was applied decreased from 407 μm [mean; 95% confidence interval (CI95) 356–458 μm] to 349 μm (mean; CI95 300–399 μm; p < 0.0001), and subfoveal choroidal thickness was reduced from 421 μm (mean; CI95 352–489 μm) to 346 μm (mean; CI95 278–414 μm; p = 0.0001). Initially, subfoveal choroidal thickness was significantly increased in the treated eye compared with the healthy fellow eye (mean 324 μm; CI95 273–376 μm; p = 0.0003), but after treatment, the difference was not significant.Discussion:  Photodynamic therapy of active CSC was followed by choroidal thickness reduction, not only locally but also at considerable distance from the treated area. Thus, the process that causes choroidal thickening in CSC appears to spread laterally within the choroid.
Common dental disorders in the donkey
Authors: du Toit N. , Dixon P. M. 
Published: May 2011

SummaryNormal dental anatomy and the range of dental disorders found in donkeys are largely similar to those described in horses. Recent studies have shown dental disease to have a high prevalence in donkeys. Some dental disorders, such as diastemata, displaced teeth and wave mouth can have serious clinical consequences by causing oral pain and weight loss and even predispose to colic. Many of these signs can be prevented by regular dental treatment that can slow down or even prevent the progression of these disorders.
Phosphoethanolamine Modification of Lipid A in Colistin-Resistant Variants of Acinetobacter baumannii Mediated by the pmrAB Two-Component Regulatory System
Authors: Beceiro Alejandro , Llobet Enrique , Aranda Jesús , Bengoechea José Antonio , Doumith Michel , Hornsey Michael , Dhanji Hiran , Chart Henrik , Bou Germán , Livermore David M. , Woodford Neil 
Published: May 2011

ABSTRACT

Colistin resistance is rare in
Acinetobacter baumannii
, and little is known about its mechanism. We investigated the role of PmrCAB in this trait, using (i) resistant and susceptible clinical strains, (ii) laboratory-selected mutants of the type strain ATCC 19606 and of the clinical isolate ABRIM, and (iii) a susceptible/resistant pair of isogenic clinical isolates, Ab15/133 and Ab15/132, isolated from the same patient.
pmrAB
sequences in all the colistin-susceptible isolates were identical to reference sequences, whereas resistant clinical isolates harbored one or two amino acid replacements variously located in PmrB. Single substitutions in PmrB were also found in resistant mutants of strains ATCC 19606 and ABRIM and in the resistant clinical isolate Ab15/132. No mutations in PmrA or PmrC were found. Reverse transcriptase (RT)-PCR identified increased expression of
pmrA
(4- to 13-fold),
pmrB
(2- to 7-fold), and
pmrC
(1- to 3-fold) in resistant versus susceptible organisms. Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry showed the addition of phosphoethanolamine to the hepta-acylated form of lipid A in the resistant variants and in strain ATCC 19606 grown under low-Mg
2+
induction conditions.
pmrB
gene knockout mutants of the colistin-resistant ATCC 19606 derivative showed >100-fold increased susceptibility to colistin and 5-fold decreased expression of
pmrC
; they also lacked the addition of phosphoethanolamine to lipid A. We conclude that the development of a moderate level of colistin resistance in
A. baumannii
requires distinct genetic events, including (i) at least one point mutation in
pmrB
, (ii) upregulation of
pmrAB
, and (iii) expression of
pmrC
, which lead to addition of phosphoethanolamine to lipid A.
SugE, a New Member of the SMR Family of Transporters, Contributes to Antimicrobial Resistance in
Enterobacter cloacae
Authors: He Gui-Xin , Zhang Chu , Crow Robert R. , Thorpe Conner , Chen Huizhong , Kumar Sanath , Tsuchiya Tomofusa , Varela Manuel F. 
Published: May 2011

ABSTRACT

We cloned a gene,
sugE
, from the chromosome of
Enterobacter cloacae
ATCC 13047. Analysis of the susceptibilities of the
sugE
-containing strain (
Escherichia coli
KAM32/pSUGE28) and
sugE
-deficient
E. cloacae
(
Ec
Δ
sugE
) showed that SugE confers resistance to cetyltrimethylammonium bromide, cetylpyridinium chloride, tetraphenylphosphonium, benzalkonium chloride, ethidium bromide, and sodium dodecyl sulfate. We also investigated expression of
sugE
. We confirm here that SugE from
E. cloacae
is an SMR family transporter as determined by observing its energy-dependent drug efflux activity.
Analysis of PBP5 of Early U.S. Isolates of Enterococcus faecium: Sequence Variation Alone Does Not Explain Increasing Ampicillin Resistance over Time
Authors: Galloway-Peña Jessica R. , Rice Louis B. , Murray Barbara E. 
Published: May 2011

ABSTRACT

Recent studies have shown that ampicillin resistance has increased steadily over the past 3 decades within U.S.
Enterococcus faecium
isolates. Analysis of the predicted PBP5 protein of 41 isolates showed a consensus PBP5 pattern for the 9 isolates with MICs of <4 μg/ml that is distinctly different from the PBP5 consensus of the 32 isolates with MICs of >4 μg/ml with ∼5% difference between these; however, there were no consistent amino acid changes that correlated with specific increases in the MICs of ampicillin within the latter group. Analysis of three other genes encoding cell wall/surface proteins also showed that there are two distinct evolutionary groups for each gene, but with occasional mixing of genes, consistent with a species that evolves by recombination.
Discovery of Potent Hepatitis C Virus NS5A Inhibitors with Dimeric Structures
Authors: Lemm Julie A. , Leet John E. , O'Boyle Donald R. , Romine Jeffrey L. , Huang Xiaohua Stella , Schroeder Daniel R. , Alberts Jeffrey , Cantone Joseph L. , Sun Jin-Hua , Nower Peter T. , Martin Scott W. , Serrano-Wu Michael H. , Meanwell Nicholas A. , Snyder Lawrence B. , Gao Min 
Published: May 2011

ABSTRACTThe exceptionalin vitropotency of the hepatitis C virus (HCV) NS5A inhibitor BMS-790052 has translated into anin vivoeffect in proof-of-concept clinical trials. Although the 50% effective concentration (EC50) of the initial lead, the thiazolidinone BMS-824, was ∼10 nM in the replicon assay, it underwent transformation to other inhibitory species after incubation in cell culture medium. The biological profile of BMS-824, including the EC50, the drug concentration required to reduce cell growth by 50% (CC50), and the resistance profile, however, remained unchanged, triggering an investigation to identify the biologically active species. High-performance liquid chromatography (HPLC) biogram fractionation of a sample of BMS-824 incubated in medium revealed that the most active fractions could readily be separated from the parental compound and retained the biological profile of BMS-824. From mass spectral and nuclear magnetic resonance data, the active species was determined to be a dimer of BMS-824 derived from an intermolecular radical-mediated reaction of the parent compound. Based upon an analysis of the structural elements of the dimer deemed necessary for anti-HCV activity, the stilbene derivative BMS-346 was synthesized. This compound exhibited excellent anti-HCV activity and showed a resistance profile similar to that of BMS-824, with changes in compound sensitivity mapped to the N terminus of NS5A. The N terminus of NS5A has been crystallized as a dimer, complementing the symmetry of BMS-346 and allowing a potential mode of inhibition of NS5A to be discussed. Identification of the stable, active pharmacophore associated with these NS5A inhibitors provided the foundation for the design of more potent inhibitors with broad genotype inhibition. This culminated in the identification of BMS-790052, a compound that preserves the symmetry discovered with BMS-346.
Inhibition of Herpes Simplex Virus Type 1 and Type 2 Infections by Peptide-Derivatized Dendrimers
Authors: Luganini Anna , Nicoletto Silvia Fabiole , Pizzuto Lorena , Pirri Giovanna , Giuliani Andrea , Landolfo Santo , Gribaudo Giorgio 
Published: May 2011

ABSTRACT

In response to the need for new antiviral agents, dendrimer-based molecules have been recognized as having a large number of potential therapeutic applications. They include peptide-derivatized dendrimers, which are hyperbranched synthetic well-defined molecules which consist of a peptidyl branching core and covalently attached surface functional peptides. However, few studies have addressed their applications as direct-acting antiviral agents. Here, we report on the ability of the peptide dendrimer SB105 and its derivative, SB105_A10, to directly inhibit herpes simplex virus 1 (HSV-1) and HSV-2
in vitro
replication, with favorable selective indexes discerned for both compounds. An analysis of their mode of action revealed that SB105 and SB105_A10 prevent HSV-1 and HSV-2 attachment to target cells, whereas SB104, a dendrimer with a different amino acid sequence within the functional group and minimal antiviral activity, was ineffective in blocking HSV attachment. Moreover, both SB105 and SB105_A10 retained their ability to inhibit HSV adsorption at pH 3.0 and 4.0 and in the presence of 10% human serum proteins, conditions mimicking the physiological properties of the vagina, a potential therapeutic location for such compounds. The inhibition of HSV adsorption is likely to stem from the ability of SB105_A10 to bind to the glycosaminoglycan moiety of cell surface heparan sulfate proteoglycans, thereby blocking virion attachment to target cells. Finally, when combined with acyclovir in checkerboard experiments SB105_A10 exhibited highly synergistic activity. Taken together, these findings suggest that SB105 and SB105_A10 are promising candidates for the development of novel topical microbicides for the prevention of HSV infections.
Is Neisseria gonorrhoeae Initiating a Future Era of Untreatable Gonorrhea?: Detailed Characterization of the First Strain with High-Level Resistance to Ceftriaxone
Authors: Ohnishi Makoto , Golparian Daniel , Shimuta Ken , Saika Takeshi , Hoshina Shinji , Iwasaku Kazuhiro , Nakayama Shu-ichi , Kitawaki Jo , Unemo Magnus 
Published: May 2011

ABSTRACT

Recently, the first
Neisseria gonorrhoeae
strain (H041) that is highly resistant to the extended-spectrum cephalosporin (ESC) ceftriaxone, the last remaining option for empirical first-line treatment, was isolated. We performed a detailed characterization of H041, phenotypically and genetically, to confirm the finding, examine its antimicrobial resistance (AMR), and elucidate the resistance mechanisms. H041 was examined using seven species-confirmatory tests, antibiograms (30 antimicrobials),
porB
sequencing,
N. gonorrhoeae
multiantigen sequence typing (NG-MAST), multilocus sequence typing (MLST), and sequencing of ESC resistance determinants (
penA
,
mtrR
,
penB
,
ponA
, and
pilQ
). Transformation, using appropriate recipient strains, was performed to confirm the ESC resistance determinants. H041 was assigned to serovar Bpyust, MLST sequence type (ST) ST7363, and the new NG-MAST ST4220. H041 proved highly resistant to ceftriaxone (2 to 4 μg/ml, which is 4- to 8-fold higher than any previously described isolate) and all other cephalosporins, as well as most other antimicrobials tested. A new
penA
mosaic allele caused the ceftriaxone resistance. In conclusion,
N. gonorrhoeae
has now shown its ability to also develop ceftriaxone resistance. Although the biological fitness of ceftriaxone resistance in
N. gonorrhoeae
remains unknown,
N. gonorrhoeae
may soon become a true superbug, causing untreatable gonorrhea. A reduction in the global gonorrhea burden by enhanced disease control activities, combined with wider strategies for general AMR control and enhanced understanding of the mechanisms of emergence and spread of AMR, which need to be monitored globally, and public health response plans for global (and national) perspectives are important. Ultimately, the development of new drugs for efficacious gonorrhea treatment is necessary.
Evaluation of Ceftaroline Activity versus Daptomycin (DAP) against DAP-Nonsusceptible Methicillin-Resistant Staphylococcus aureus Strains in an
In Vitro
Pharmacokinetic/Pharmacodynamic Model
Authors: Steed Molly , Vidaillac Celine , Rybak Michael J. 
Published: May 2011

ABSTRACT

The objective of this study was to investigate the potential role of ceftaroline, a new broad-spectrum cephalosporin, as a therapeutic option for the treatment of daptomycin-nonsusceptible (DNS) methicillin-resistant
Staphylococcus aureus
(MRSA) infections. Four clinical DNS MRSA strains, R5717, R5563, R5996 (heteroresistant vancomycin-intermediate
S. aureus
) and R5995 (vancomycin-intermediate
S. aureus
) were evaluated in a two-compartment hollow-fiber
in vitro
pharmacokinetic/pharmacodynamic model at a starting inoculum of 10
7
CFU/ml for 96 h. Simulated regimens were ceftaroline at 600 mg every 12 h (q12h) (maximum free-drug concentration [
f
C
max
], 15.2 μg/ml; serum half-life [
t
1/2
], 2.3 h), daptomycin at 6 mg/kg q24h (
f
C
max
, 7.9 μg/ml;
t
1/2
, 8 h), and daptomycin at 10 mg/kg q24h (
f
C
max
, 15.2 μg/ml;
t
1/2
, 8 h). Differences in CFU/ml between 24 and 96 h were evaluated by analysis of variance with Tukey's post-hoc test. Bactericidal activity was defined as a ≥3-log
10
CFU/ml decrease in the colony count from the initial inoculum. The ceftaroline MIC values were 0.25, 0.5, 0.5, and 0.5 μg/ml, and the daptomycin MIC values were 2, 2, 4, and 4 μg/ml for R5717, R5563, R5996, and R5995, respectively. Ceftaroline displayed sustained bactericidal activity against 3 of the 4 strains at 96 h (R5717, −3.1 log
10
CFU/ml; R5563, −2.5 log
10
CFU/ml; R5996, −5.77 log
10
CFU/ml; R5995, −6.38 log
10
CFU/ml). Regrowth occurred during the daptomycin at 6-mg/kg q24h regimen (4 strains) and the daptomycin at 10-mg/kg q24h regimen (3 strains). At 96 h, ceftaroline was significantly more active, resulting in CFU/ml counts lower than those obtained with daptomycin at 6 mg/kg q24h (4 strains,
P
≤ 0.008) and daptomycin at 10 mg/kg q24 h (3 strains,
P
≤ 0.001). Isolates with increased MIC values for daptomycin (all 4 strains) but not for ceftaroline were recovered. Ceftaroline was effective against the 4 isolates tested and may provide a clinical option for the treatment of DNS MRSA infections.
Joint Population Pharmacokinetic Analysis of Zidovudine, Lamivudine, and Their Active Intracellular Metabolites in HIV Patients
Authors: Bazzoli C. , Bénech H. , Rey E. , Retout S. , Salmon D. , Duval X. , Tréluyer J. M. , Mentré F. ,   the COPHAR2-ANRS 111 Study Group
Published: May 2011

ABSTRACTThe population pharmacokinetic parameters of zidovudine (AZT), lamivudine (3TC), and their active intracellular metabolites in 75 naïve HIV-infected patients receiving an oral combination of AZT and 3TC twice daily as part of their multitherapy treatment in the COPHAR2-ANRS 111 trial are described. Four blood samples per patient were taken after 2 weeks of treatment to measure drug concentrations at steady state. Plasma AZT and 3TC concentrations were measured in 73 patients, and among those, 62 patients had measurable intracellular AZT-TP and 3TC-TP concentrations. For each drug, a joint population pharmacokinetic model was developed and we investigated the influence of different covariates. We then studied correlations between the mean plasma and intracellular concentrations of each drug. A one-compartment model with first-order absorption and elimination best described the plasma AZT concentration, with an additional compartment for intracellular AZT-TP. A similar model but with zero-order absorption was found to adequately described concentrations of 3TC and its metabolite 3TC-TP. The half-lives of AZT and 3TC were 0.81 h (94.8%) and 2.97 h (39.2%), respectively, whereas the intracellular half-lives of AZT-TP and 3TC-TP were 10.73 h (69%) and 21.16 h (44%), respectively. We found particularly a gender effect on the apparent bioavailability of AZT, as well as on the mean plasma and intracellular concentrations of AZT, which were significantly higher in females than in males. Relationships between mean plasma drug and intracellular metabolite concentrations were also highlighted both for AZT and for 3TC. Simulation with the model of plasma and intracellular concentrations for once- versus twice-daily regimens suggested that a daily dosing regimen with double doses could be appropriate.
bla
KPC
RNA Expression Correlates with Two Transcriptional Start Sites but Not Always with Gene Copy Number in Four Genera of Gram-Negative Pathogens
Authors: Roth Amanda L. , Kurpiel Philip M. , Lister Philip D. , Hanson Nancy D. 
Published: May 2011

ABSTRACT

Klebsiella pneumoniae
carbapenemase (KPC)-producing organisms are therapeutically and diagnostically challenging. It is possible that
bla
KPC
gene expression plays a role in the variability observed in clinical susceptibility testing.
bla
KPC
transformants together with 10 clinical isolates representing four genera were evaluated for
bla
KPC
copy number and gene expression and correlated with β-lactam MIC data. The data suggest that mechanisms other than gene copy number and expression of
bla
KPC
contribute to variability in susceptibility when testing KPC-producing isolates.
Developmental Pharmacokinetics of Lamivudine in 580 Pediatric Patients Ranging from Neonates to Adolescents
Authors: Bouazza Naïm , Hirt Déborah , Blanche Stéphane , Frange Pierre , Rey Elisabeth , Tréluyer Jean-Marc , Urien Saik 
Published: May 2011

ABSTRACTLamivudine concentration-time courses were described for a very large range of ages to study the effects of body weight and maturation on lamivudine pharmacokinetics and to check the consistency of dosing recommendations. Lamivudine concentrations were monitored on a routine basis to produce concentrations similar to the known values in adults. Concentrations were measured in 580 children from 2 days to 18 years old. A total of 2,106 plasma lamivudine concentrations were measured, and a population pharmacokinetic analysis was performed using the stochastic approximation expectation maximization algorithm implemented in MONOLIX 3.1 software. A two-compartment model adequately described the data. After standardization for a mean standard body weight by using an allometric model, age also had a significant effect on clearance maturation. Typical population estimates (percent interindividual variability) standardized for 70 kg of the apparent clearance, including central and peripheral volumes of distribution, intercompartmental clearance, and absorption rate constant, were 31 liters·h−1(32%), 76.4 liters (77%), 129 liters, 5.83 liters·h−1, and 0.432 h−1, respectively. According to the model, elimination clearance (liters/h/70 kg) increases gradually during the first years of life. Theoretical doses needed to reach the range of 24 h of exposure observed in adults were calculated: to be closer to adult exposure, children should receive 4 mg/kg/day from birth to 8 weeks of age, 5 mg/kg/day from 8 to 16 weeks of age, 6 mg/kg from 16 to 25 weeks of age, 8 mg/kg/day from 25 weeks of age to 14 kg of body weight, 150 mg/day from 14 to 25 kg of body weight, 225 mg/day from 25 to 35 kg of body weight, and 300 mg/day thereafter.
Antifungal Therapy in an Athymic Murine Model of Chromoblastomycosis by
Fonsecaea pedrosoi
Authors: Calvo Enrique , Pastor F. Javier , Mayayo Emilio , Hernández Pilar , Guarro Josep 
Published: May 2011

ABSTRACT

We have compared the efficacy of terbinafine (TRB) and itraconazole (ITZ), the recommended drugs for the treatment of chromoblastomycosis, with that of posaconazole (PSC) and voriconazole (VRC) in athymic mice infected with the fungus
Fonsecaea pedrosoi
. Three weeks after challenge, mice were treated for 4 months with PSC at 10 or 20 mg/kg of body weight/day, with VRC at 10 or 20 mg/kg/day, with ITZ at 25 or 50 mg/kg/day, or with TRB at 150 or 250 mg/kg/day. The progress of the infection was evaluated by measuring the size of the lesions, by histopathological studies, and by cultures of the excised tissue. The two doses of PSC followed by the highest doses of ITZ and TRB showed the best results while VRC did not show efficacy. PSC could be an alternative in the treatment of chromoblastomycosis.