bluuebunny/crossref_metadata_2025_split huggingface dataset:
Becoming Bluestockings: Contextualising Hannah More's ‘The Bas Bleu’
Authors: HASLETT MOYRA 
Published: September 2009

AbstractHannah More's poem ‘The Bas Bleu’ was the first account of the Bluestockings to be published from within the Bluestocking circle itself. It remained the most significant defence of Bluestocking ideals for many decades thereafter, years in which satirical depictions of the Bluestockings would predominate. This essay locates More's poem in the contexts of its original composition (1783), manuscript circulation and eventual publication (1786). The poem's transformation from a manuscript to a published poem exemplifies its particular significance as a public statement in which the Bluestockings attained prominence and celebrity.
The need and total cost of Finnish eyecare services: a simulation model for 2005–2040
Authors: Tuulonen Anja , Salminen Hannu , Linna Miika , Perkola Markku 
Published: September 2009

Abstract.Purpose:  The aims of this study were: (i) to create a structural simulation model capable of predicting the future need and cost of eyecare services in Finland; and (ii) to test and rank different policy alternatives for access to care and the required physician workforce.Methods:  Using the system dynamics approach, the number and cost of patients with cataract, glaucoma, diabetic retinopathy and age‐related macular degeneration (AMD) were described with causal‐loop diagrams and were then translated into a set of mathematical equations to build a computer simulation model. Mathematically, the problem was formulated as a set of differential equations that were solved numerically with specialized software. The validity of the model was tested against prevalence and administrative historical data. The costs covered by the public sector in Finland were obtained from 2003 from the Finnish Hospital Discharge Register (including outpatient care), the Finnish Social Insurance Institution and a survey of hospital price lists. Different levels of access to public care were then simulated in four eye diseases, for which the model estimated the need for services and resources and their costs in the years 2005–2040.Results:  The model forecasted that the adoption of the 2005 national ‘access to care’ criteria for cataract surgery would shorten waiting lists. If the workload of Finnish ophthalmologists were kept at the 2003 level, the graduation rate of new ophthalmologists would have to increase by 75% from the current level. If all glaucoma patients were followed in the public sector in future, even this increase in training would not meet the demand for physician workforce. The current model indicated that the screening frequency of diabetes can be increased without large sacrifices in terms of costs. AMD therapy has a significant role in the allocation of future resources in eyecare. The modelling study predicted that ageing alone will increase the costs of eyecare during the next four decades in Finland by about 1% per year in real terms (undiscounted and without inflation of unit costs). The increases in total yearly costs were on average 8.6% between 2001 and 2003.Conclusions:  The results of this modelling study indicate that policy initiatives, such as defining criteria for access to care, can have substantial implications on the demand for care and waiting times whereas the effect of ageing alone was relatively small. Measures to control several other factors – such as the adoption and price level of new technologies, treatments and practice patterns – will be at least equally important in order to restrain healthcare costs effectively.
The Large Mechanosensitive Channel MscL Determines Bacterial Susceptibility to the Bacteriocin Sublancin 168
Authors: Kouwen Thijs R. H. M. , Trip Erik N. , Denham Emma L. , Sibbald Mark J. J. B. , Dubois Jean-Yves F. , van Dijl Jan Maarten 
Published: September 2009

ABSTRACT

Bacillus subtilis
strain 168 produces the extremely stable and broad-spectrum lantibiotic sublancin 168. Known sublancin 168-susceptible organisms include important pathogens, such as
Staphylococcus aureus
. Nevertheless, since its discovery, the mode of action of sublancin 168 has remained elusive. The present studies were, therefore, aimed at the identification of cellular determinants for bacterial susceptibility toward sublancin 168. Growth inhibition and competition assays on plates and in liquid cultures revealed that sublancin 168-mediated growth inhibition of susceptible
B. subtilis
and
S. aureus
cells is affected by the NaCl concentration in the growth medium. Added NaCl did not influence the production, activity, or stability of sublancin 168 but, instead, lowered the susceptibility of sensitive cells toward this lantibiotic. Importantly, the susceptibility of
B. subtilis
and
S. aureus
cells toward sublancin 168 was shown to depend on the presence of the large mechanosensitive channel of conductance MscL. In contrast, MscL was not involved in susceptibility toward the bacteriocin nisin or Pep5. Taken together, our unprecedented results demonstrate that MscL is a critical and specific determinant in bacterial sublancin 168 susceptibility that may serve either as a direct target for this lantibiotic or as a gate of entry to the cytoplasm.
Pharmacological Inhibition of Transforming Growth Factor β Signaling Decreases Infection and Prevents Heart Damage in Acute Chagas' Disease
Authors: Waghabi Mariana C. , de Souza Elen M. , de Oliveira Gabriel M. , Keramidas Michelle , Feige Jean-Jacques , Araújo-Jorge Tania C. , Bailly Sabine 
Published: September 2009

ABSTRACT

Chagas' disease induced by
Trypanosoma cruzi
infection is an important cause of mortality and morbidity affecting the cardiovascular system for which presently available therapies are largely inadequate. We previously reported that transforming growth factor β (TGF-β) is implicated in several regulatory aspects of
T
.
cruzi
invasion and growth and in host tissue fibrosis. This prompted us to evaluate the therapeutic action of an inhibitor of TGF-β signaling (SB-431542) administered during the acute phase of experimental Chagas' disease. Male Swiss mice were infected intraperitoneally with 10
4
trypomastigotes of
T
.
cruzi
(Y strain) and evaluated clinically for the following 30 days. SB-431542 treatment significantly reduced mortality and decreased parasitemia. Electrocardiography showed that SB-431542 treatment was effective in protecting the cardiac conduction system. By 14 day postinfection, enzymatic biomarkers of tissue damage indicated that muscle injury was decreased by SB-431542 treatment, with significantly lower blood levels of aspartate aminotransferase and creatine kinase. In conclusion, inhibition of TGF-β signaling in vivo appears to potently decrease
T
.
cruzi
infection and to prevent heart damage in a preclinical mouse model. This suggests that this class of molecules may represent a new therapeutic agent for acute and chronic Chagas' disease that warrants further clinical exploration.
Influence of Inoculum Size and Marbofloxacin Plasma Exposure on the Amplification of Resistant Subpopulations of
Klebsiella pneumoniae
in a Rat Lung Infection Model
Authors: Kesteman Anne-Sylvie , Ferran Aude A. , Perrin-Guyomard Agnès , Laurentie Michel , Sanders Pascal , Toutain Pierre-Louis , Bousquet-Mélou Alain 
Published: September 2009

ABSTRACT

We tested the hypothesis that the bacterial load at the infection site could impact considerably on the pharmacokinetic/pharmacodynamic (PK/PD) parameters of fluoroquinolones. Using a rat lung infection model, we measured the influence of different marbofloxacin dosage regimens on selection of resistant bacteria after infection with a low (10
5
CFU) or a high (10
9
CFU) inoculum of
Klebsiella pneumoniae
. For daily fractionated doses of marbofloxacin, prevention of resistance occurred for an area-under-the-concentration-time-curve (AUC)/MIC ratio of 189 h for the low inoculum, whereas for the high inoculum, resistant-subpopulation enrichment occurred for AUC/MIC ratios up to 756 h. For the high-inoculum-infected rats, the AUC/MIC ratio,
C
max
/MIC ratio, and time within the mutant selection window (
T
MSW
) were not found to be effective predictors of resistance prevention upon comparison of fractionated and single administrations. An index corresponding to the ratio of the time that the drug concentrations were above the mutant prevention concentration (MPC) over the time that the drug concentrations were within the MSW (
T
>
MPC
/
T
MSW
) was the best predictor of the emergence of resistance: a
T
>
MPC
/
T
MSW
ratio of 0.54 was associated with prevention of resistance for both fractionated and single administrations. These results suggest that the enrichment of resistant bacteria depends heavily on the inoculum size at the start of an antimicrobial treatment and that classical PK/PD parameters cannot adequately describe the impact of different dosage regimens on enrichment of resistant bacteria. We propose an original index, the
T
>
MPC
/
T
MSW
ratio, which reflects the ratio of the time that the less susceptible bacterial subpopulation is killed over the time that it is selected, as a potentially powerful indicator of prevention of enrichment of resistant bacteria. This ratio is valid only if plasma concentrations achieve the MPC.
In Vitro Activity of Ceftaroline against Methicillin-Resistant
Staphylococcus aureus
and Heterogeneous Vancomycin-Intermediate
S. aureus
in a Hollow Fiber Model
Authors: Vidaillac Céline , Leonard Steve N. , Rybak Michael J. 
Published: September 2009

ABSTRACT

Ceftaroline is a broad-spectrum injectable cephalosporin exhibiting bactericidal activity against a variety of bacteria, including methicillin-resistant
Staphylococcus aureus
(MRSA). Using a two-compartment in vitro pharmacokinetic/pharmacodynamic (PK/PD) model, we evaluated the activity of ceftaroline at 600 mg every 8 h (q8h) and q12h in comparison with that of vancomycin at 1,000 mg q12h over a 72-h time period against six clinical MRSA isolates, including two heterogeneous vancomycin-intermediate
S. aureus
(hVISA) isolates. The MIC and minimum bactericidal concentration ranged between 0.125 to 2 and 0.5 to 2 μg/ml for ceftaroline and vancomycin, respectively. In the PK/PD model, ceftaroline was superior to vancomycin against all isolates (
P
< 0.05), except one to which it was equivalent. No difference in activity was observed between both q8 and q12h dosing regimens of ceftaroline. Bacterial regrowth was observed after 32 h for two isolates treated with ceftaroline. This regrowth was uncorrelated to resistance, instability of the drug, or tolerance. However, subpopulations with higher MICs to ceftaroline were found by population analysis for these two isolates. Finally, and in contrast to ceftaroline, MIC elevations up to 8 to 12 μg/ml were observed with vancomycin for the hVISA isolates. In conclusion, in addition to a lower potential to select resistant mutants, ceftaroline demonstrated activity equal to or greater than vancomycin against MRSA isolates. Although further in vitro and in vivo investigations are warranted, ceftaroline appears to be a promising alternative for the treatment of MRSA infections.
ATP Synthase Inhibition of
Mycobacterium avium
Is Not Bactericidal
Authors: Lounis Nacer , Gevers Tom , Van Den Berg Joke , Vranckx Luc , Andries Koen 
Published: September 2009

ABSTRACT

The efficacy of ATP synthase inhibitor TMC207 was assessed in early and late
Mycobacterium avium
infections in mice. In contrast to what was earlier observed for
M. tuberculosis
, a bacteriostatic effect was obtained. In vitro, the minimal bactericidal concentration (MBC)/MIC ratio was very high. The MBC was more relevant for assessment of pharmacokinetic/pharmacodynamic relationships than the MIC.
Case of Fatal
Blastoschizomyces capitatus
Infection Occurring in a Patient Receiving Empiric Micafungin Therapy
Authors: Chittick Paul , Palavecino Elizabeth L. , Delashmitt Brian , Evans James , Peacock James E. 
Published: September 2009

ABSTRACT

We report the first case, to our knowledge, of
Blastoschizomyces capitatus
infection occurring in a patient receiving empirical echinocandin therapy for neutropenic fevers. Clinicians should consider
B. capitatus
infection in those neutropenic patients who remain febrile despite echinocandin therapy or who develop yeast bloodstream infections while receiving an echinocandin.
Cross-Reactive Immunity to
Mycobacterium tuberculosis
DosR Regulon-Encoded Antigens in Individuals Infected with Environmental, Nontuberculous Mycobacteria
Authors: Lin May Young , Reddy T. B. K. , Arend Sandra M. , Friggen Annemieke H. , Franken Kees L. M. C. , van Meijgaarden Krista E. , Verduyn Marleen J. C. , Schoolnik Gary K. , Klein Michel R. , Ottenhoff Tom H. M. 
Published: September 2009

ABSTRACT

Mycobacterium tuberculosis
DosR regulon-encoded antigens are highly immunogenic in
M. tuberculosis
-infected humans and are associated with latent tuberculosis infection. We have investigated the hypothesis that infection with or exposure to nontuberculous mycobacteria (NTM) can induce cross-reactive immunity to
M. tuberculosis
DosR regulon-encoded antigens since responsiveness has been observed in non-
M. tuberculosis
-exposed but purified protein derivative-responsive individuals.
M. tuberculosis
DosR regulon-encoded antigen-specific T-cell responses were studied in peripheral blood mononuclear cells (PBMCs) of NTM-infected/exposed individuals. BLASTP was used to determine the presence of
M. tuberculosis
DosR regulon-encoded protein orthologs among environmental mycobacteria and nonmycobacteria. Significant gamma interferon production was observed in PBMCs from NTM-infected/exposed individuals in response to
M. tuberculosis
DosR regulon-encoded antigens. DosR regulon-encoded protein orthologs were prominently present in tuberculous and environmental mycobacteria and surprisingly also in nonmycobacteria. The ubiquitous presence of the highly conserved DosR master regulator protein Rv3133c suggests that this is a general adaptive bacterial response regulator. We report a first series of
M. tuberculosis
antigens to which cross-reactive immunity is induced by NTM infection/exposure. The high conservation of
M. tuberculosis
DosR regulon-encoded antigens most likely enables them to induce cross-reactive T-cell responses.
Molecular, Antigenic, and Functional Characteristics of Ferric Enterobactin Receptor CfrA in
Campylobacter jejuni
Authors: Zeng Ximin , Xu Fuzhou , Lin Jun 
Published: September 2009

ABSTRACT

The ferric enterobactin receptor CfrA not only is responsible for high-affinity iron acquisition in
Campylobacter jejuni
but also is essential for
C. jejuni
colonization in animal intestines. In this study, we determined the feasibility of targeting the iron-regulated outer membrane protein CfrA for immune protection against
Campylobacter
colonization. Alignment of complete CfrA sequences from 15
Campylobacter
isolates showed that the levels of amino acid identity for CfrA range from 89% to 98%. Immunoblotting analysis using CfrA-specific antibodies demonstrated that CfrA was dramatically induced under iron-restricted conditions and was widespread and produced in 32
Campylobacter
primary strains from various sources and from geographically diverse areas. The immunoblotting survey results were highly correlated with the results of an enterobactin growth promotion assay and a PCR analysis using
cfrA
-specific primers. Inactivation of the
cfrA
gene also impaired norepinephrine-mediated growth promotion, suggesting that CfrA is required for
C. jejuni
to sense intestinal stress hormones during colonization. Complementation of the
cfrA
mutant with a wild-type
cfrA
allele in
trans
fully restored the production and function of CfrA. A growth assay using purified anti-CfrA immunoglobulin G demonstrated that specific CfrA antibodies could block the function of CfrA, which diminished ferric enterobactin-mediated growth promotion under iron-restricted conditions. The inhibitory effect of CfrA antibodies was dose dependent. Immunoblotting analysis also indicated that CfrA was expressed and immunogenic in chickens experimentally infected with
C. jejuni
. Amino acid substitution mutagenesis demonstrated that R327, a basic amino acid that is highly conserved in CfrA, plays a critical role in ferric enterobactin acquisition in
C. jejuni.
Together, these findings strongly suggest that CfrA is a promising vaccine candidate for preventing and controlling
Campylobacter
infection in humans and animal reservoirs.
Overexpression of CsrA (BB0184) Alters the Morphology and Antigen Profiles ofBorrelia burgdorferi
Authors: Sanjuan Eva , Esteve-Gassent Maria D. , Maruskova Mahulena , Seshu J. 
Published: September 2009

ABSTRACTBorrelia burgdorferi, the agent of Lyme disease, alters its gene expression in response to highly disparate environmental signals encountered in its hosts. Among the relatively few regulators of adaptive gene expression present in the borrelial genome is an open reading frame (ORF), BB0184, annotated as CsrA (carbonstorageregulatorA). CsrA, in several bacterial species, has been characterized as a small RNA binding protein that functions as a global regulator affecting mRNA stability or levels of translation of multiple ORFs. Consistent with known functions of CsrA, overexpression of CsrA fromB. burgdorferi(CsrABb) inEscherichia coliresulted in reduced accumulation of glycogen. We determined thatcsrABbis part of theflgKmotility operon and that the synthesis of CsrABbwas increased whenB. burgdorferiwas propagated under fed-tick conditions. Overexpression of CsrABbinB. burgdorferistrain B31 (ML23, lp25-negative clonal isolate) resulted in a clone, designated ES25, which exhibited alterations in colony morphology and a significant reduction in the levels of FlaB. Several lipoproteins previously characterized as playing a role in infectivity were also altered in ES25. Real-time reverse transcription-PCR analysis of RNA revealed significant differences in the transcriptional levels ofospCin ES25, while there were no such differences in the levels of other transcripts, suggesting posttranscriptional regulation of expression of these latter genes. These observations indicate that CsrABbplays a role in the regulation of expression of pathophysiological determinants ofB. burgdorferi, and further characterization of CsrABbwill help in better understanding of the regulators of gene expression inB. burgdorferi.
Genome-Wide Study of
Pseudomonas aeruginosa
Outer Membrane Protein Immunogenicity Using Self-Assembling Protein Microarrays
Authors: Montor Wagner R. , Huang Jin , Hu Yanhui , Hainsworth Eugenie , Lynch Susan , Kronish Jeannine-Weiner , Ordonez Claudia L. , Logvinenko Tanya , Lory Stephen , LaBaer Joshua 
Published: September 2009

ABSTRACT

Pseudomonas aeruginosa
is responsible for potentially life-threatening infections in individuals with compromised defense mechanisms and those with cystic fibrosis.
P. aeruginosa
infection is notable for the appearance of a humoral response to some known antigens, such as flagellin C, elastase, alkaline protease, and others. Although a number of immunogenic proteins are known, no effective vaccine has been approved yet. Here, we report a comprehensive study of all 262 outer membrane and exported
P. aeruginosa
PAO1 proteins by a modified protein microarray methodology called the nucleic acid-programmable protein array. From this study, it was possible to identify 12 proteins that trigger an adaptive immune response in cystic fibrosis and acutely infected patients, providing valuable information about which bacterial proteins are actually recognized by the immune system in vivo during the natural course of infection. The differential detections of these proteins in patients and controls proved to be statistically significant (
P
< 0.01). The study provides a list of potential candidates for the improvement of serological diagnostics and the development of vaccines.
Codependent and Independent Effects of Nitric Oxide-Mediated Suppression of PhoPQ andSalmonellaPathogenicity Island 2 on IntracellularSalmonella entericaSerovar Typhimurium Survival
Authors: Bourret Travis J. , Song Miryoung , Vázquez-Torres Andrés 
Published: September 2009

ABSTRACTHere we show that theSalmonella entericaserovar Typhimurium PhoQ sensor kinase lessens the cytotoxicity of reactive nitrogen species (RNS) generated by inducible nitric oxide synthase (iNOS) in the innate response of mononuclear phagocytic cells. This observation is consistent with the expression patterns of PhoP-activated genes during moderate nitrosative stress in the innate host response. In contrast, RNS synthesized during high-NO fluxes of gamma interferon (IFN-γ)-activated macrophages repress PhoP-activatedlpxO,pagP, andphoPgene transcription. Because PhoP-regulatedSalmonellapathogenicity island 2 (SPI2) genes are also repressed by high-order RNS (39), we investigated whether the NO-mediated inhibition of PhoPQ underlies the repression of SPI2. Our studies indicate that a third of the expression of the SPI2spiCgene recorded in nonactivated macrophages depends on PhoQ. Transcription ofspiCis repressed in IFN-γ-primed macrophages in an iNOS-dependent manner, irrespective of thephoQstatus of the bacteria. Transcription ofspiCis restored in IFN-γ-treated, iNOS-deficient macrophages to levels sustained by aphoQmutant in nonactivated phagocytes, suggesting that most NO-dependent repression ofspiCis due to the inhibition of PhoPQ-independent targets. Comparison of the intracellular fitness ofspiC,phoQ, andspiC phoQmutants revealed that PhoPQ and SPI2 have codependent and independent effects onS. Typhimurium survival during innate nitrosative stress. However, the intracellular survival of mostS.Typhimurium bacteria is conferred by the PhoPQ two-component regulator, and the SPI2 type III secretion system is repressed by high-order RNS of IFN-γ-activated macrophages.
Roles of age, length of service and job in work-related injury: a prospective study of 446 120 person-years in railway workers
Authors: Chau N , Wild P , Dehaene D , Benamghar L , Mur J M , Touron C 
Published: September 2009

ObjectivesBecause work-related injuries are common and yet the mechanisms through which various types of injuries relate to age, length of service and job remain unknown, this study assessed the role of age, length of service and job in work-related injury.MethodsProspective study of all 164 814 permanently employed male workers at the French national railway company during 1998–2000, based on the company's injury database: 446 120 person-years, 15 195 injuries with working days lost, coded using the company's injury classification, which is derived from that of the French health insurance scheme. We investigated the incidence of 10 types of injury: fall on same level, fall to lower level, handling materials/machine parts during assembly, handling objects, lifting/handling equipment, collision with/by moving objects, collision with/by vehicles, operating machines/equipment, using hand tools and other injuries. Data were analysed using negative binomial regression.ResultsWorkers aged <25 years were subject to a higher injury risk from handling materials/machine parts during assembly, and collision with/by moving objects or vehicles. Older workers, especially those aged 50–55 years, were subject to a higher risk of fall and injury resulting from lifting/handling materials/equipment/objects or from collision with/by moving objects/vehicles. Using hand tools was a risky task for workers aged <30 or ≥40 years. The relative risk decreased steadily with increasing length of service with the company, from 2.6 for 1 year to 1.0 for ≥30 years, and the slope of the trend is stronger for fall to lower level, lifting/handling materials/equipment and collision with/by moving objects.ConclusionYounger and older ages and shorter length of service are at risk for various types of injuries. Preventive measures should improve working conditions, especially for younger/older ages, provide knowledge through specific training during the first years in a job and help workers to be more aware of risks associated with their age, years of employment and job.