bluuebunny/crossref_metadata_2025_split huggingface dataset:
Redrawing the Map of the World? Reflections on the World Development Report 2009
Authors: Hart Gillian 
Published: September 2010

abstractThe World Development Report 2009 focuses on the role of markets for land, labor, and tradable goods in reshaping economic geography, but it pays little or no attention to financial markets. While analytically convenient, this abstraction from financial markets is deeply problematic. Especially since the late 1970s, the dynamics of finance capital have played a major role in redrawing the economic map of the world and will continue to do so. In addition, this review underscores the limits of the unilinear model of rural‐urban transition that underpins the report.
Developing and testing a patient information booklet for thrombolysis used in acute stroke
Authors: Knapp Peter , Wanklyn Peter , Raynor D K , Waxman Robin 
Published: September 2010

Abstract

Objective
Thrombolysis decreases the chance of post-stroke dependence, although its use carries significant risk, notably of intra-cerebral haemorrhage. Patients (and families) face an important risk/benefit decision before consenting. We drafted a patient information booklet for this purpose, and applied performance-based readability testing with the aim that the most important information in the booklet could be found and understood.

Methods
The booklet was developed with reference to best practice in information writing and design. We User-Tested its performance on 56 people without prior experience of stroke. After reading the booklet they were asked to find and explain 15 pieces of information. The booklet was revised according to its performance and re-tested, until each item was found and understood by at least 80% of participants.

Key findings
The four-page information booklet contained approximately 900 words, organised into six sections. A risk-palette graphic showed the chance of positive and negative outcomes. The booklet was tested on four participant cohorts and revised, including more bold text, re-wording, changing the title and changing the graphic to a coloured bar chart. Testing the final version on the fourth cohort of 20 people showed that each of the 15 tested items of information met the target of at least 80% participants being able to find and understand it.

Conclusions
The use of information design and User Testing produced a booklet that is understandable by people with no prior experience of stroke. User Testing is an inexpensive and quick method to ensure that information intended for patients is usable.
Mutually Exclusive Genotypes for Pyrazinamide and 5-Chloropyrazinamide Resistance Reveal a Potential Resistance-Proofing Strategy
Authors: Baughn Anthony D. , Deng Jiaoyu , Vilchèze Catherine , Riestra Angelica , Welch John T. , Jacobs William R. , Zimhony Oren 
Published: September 2010

ABSTRACT

The pyrazinamide (PZA) analog 5-chloropyrazinamide (5-Cl PZA) is active against mycobacterial species, including PZA-resistant strains of
Mycobacterium tuberculosis
. In
M. smegmatis
, overexpression of the type 1 fatty acid synthase (FAS I) confers resistance to 5-Cl PZA, a potent FAS I inhibitor. Since
M. tuberculosis
and
M. bovis
cannot tolerate FAS I overexpression, 5-Cl PZA resistance mutations have yet to be described for tubercle bacilli. In an attempt to identify other factors that govern the activity of 5-Cl PZA, we selected for 5-Cl PZA-resistant isolates from a library of transposon-mutagenized
M. smegmatis
isolates. Here, we report that increased expression of the
M. smegmatis
pyrazinamidase PzaA confers resistance to 5-Cl PZA and susceptibility to PZA in
M. smegmatis
,
M. tuberculosis
, and
M. bovis
. In contrast, while ectopic overexpression of the
M. tuberculosis
pyrazinamidase PncA increases PZA susceptibility, this amidase does not mediate resistance to 5-Cl PZA. We conclude that PncA-independent turnover of 5-Cl PZA represents a potential mechanism of resistance to this compound for
M. tuberculosis
, which will likely translate into enhanced PZA susceptibility. Thus, countersusceptibility can be manipulated as a resistance-proofing strategy for PZA-based compounds when these agents are used simultaneously.
Oritavancin Disrupts Membrane Integrity of
Staphylococcus aureus
and Vancomycin-Resistant Enterococci To Effect Rapid Bacterial Killing
Authors: Belley Adam , McKay Geoffrey A. , Arhin Francis F. , Sarmiento Ingrid , Beaulieu Sylvain , Fadhil Ibthihal , Parr Thomas R. , Moeck Gregory 
Published: September 2010

ABSTRACT
Oritavancin is an investigational lipoglycopeptide in clinical development for the treatment of acute bacterial skin and skin structure infections. In this study, we demonstrate that oritavancin causes bacterial membrane depolarization and permeabilization leading to cell death of Gram-positive pathogens and that these effects are attributable to the 4′-chlorobiphenylmethyl group of the molecule.
Independent Behavior of Commensal Flora for Carriage of Fluoroquinolone-Resistant Bacteria in Patients at Admission
Authors: de Lastours Victoire , Chau Françoise , Tubach Florence , Pasquet Blandine , Ruppé Etienne , Fantin Bruno 
Published: September 2010

ABSTRACT

The important role of commensal flora as a natural reservoir of bacterial resistance is now well established. However, whether the behavior of each commensal flora is similar to that of other floras in terms of rates of carriage and risk factors for bacterial resistance is unknown. During a 6-month period, we prospectively investigated colonization with fluoroquinolone-resistant bacteria in the three main commensal floras from hospitalized patients at admission, targeting
Escherichia coli
in the fecal flora, coagulase-negative
Staphylococcus
(CNS) in the nasal flora, and α-hemolytic streptococci in the pharyngeal flora. Resistant strains were detected on quinolone-containing selective agar. Clinical and epidemiological data were collected. A total of 555 patients were included. Carriage rates of resistance were 8.0% in
E. coli
, 30.3% in CNS for ciprofloxacin, and 27.2% in streptococci for levofloxacin; 56% of the patients carried resistance in at least one flora but only 0.9% simultaneously in all floras, which is no more than random. Risk factors associated with the carriage of fluoroquinolone-resistant strains differed between fecal
E. coli
(i.e., colonization by multidrug-resistant bacteria) and nasal CNS (i.e., age, coming from a health care facility, and previous antibiotic treatment with a fluoroquinolone) while no risk factors were identified for pharyngeal streptococci. Despite high rates of colonization with fluoroquinolone-resistant bacteria, each commensal flora behaved independently since simultaneous carriage of resistance in the three distinct floras was uncommon, and risk factors differed. Consequences of environmental selective pressures vary in each commensal flora according to its local specificities (clinical trial NCT00520715 [
http://clinicaltrials.gov/ct2/show/NCT00520715
]).
Uptake ofHelicobacter pyloriOuter Membrane Vesicles by Gastric Epithelial Cells
Authors: Parker Heather , Chitcholtan Kenny , Hampton Mark B. , Keenan Jacqueline I. 
Published: September 2010

ABSTRACTHelicobacter pyloribacteria colonize the human stomach where they stimulate a persistent inflammatory response.H. pyloriis considered noninvasive; however, lipopolysaccharide (LPS)-enriched outer membrane vesicles (OMV), continuously shed from the surface of this bacterium, are observed within gastric epithelial cells. The mechanism of vesicle uptake is poorly understood, and this study was undertaken to examine the roles of bacterial VacA cytotoxin and LPS in OMV binding and cholesterol and clathrin-mediated endocytosis in vesicle uptake by gastric epithelial cells. OMV association was examined using a fluorescent membrane dye to label OMV, and a comparison was made between the associations of vesicles from a VacA+strain and OMV from a VacA−isogenic mutant strain. Within 20 min, essentially all associated OMV were intracellular, and vesicle binding appeared to be facilitated by the presence of VacA cytotoxin. Uptake of vesicles from the VacA+strain was inhibited byH. pyloriLPS (58% inhibition with 50 μg/ml LPS), while uptake of OMV from the VacA−mutant strain was less affected (25% inhibition with 50 μg/ml LPS). Vesicle uptake did not require cholesterol. However, uptake of OMV from the VacA−mutant strain was inhibited by a reduction in clathrin-mediated endocytosis (42% with 15 μg/ml chlorpromazine), while uptake of OMV from the VacA+strain was less affected (25% inhibition with 15 μg/ml chlorpromazine). We conclude that VacA toxin enhances the association ofH. pyloriOMV with cells and that the presence of the toxin may allow vesicles to exploit more than one pathway of internalization.
Listeria monocytogenes
Uses Listeria Adhesion Protein (LAP) To Promote Bacterial Transepithelial Translocation and Induces Expression of LAP Receptor Hsp60
Authors: Burkholder Kristin M. , Bhunia Arun K. 
Published: September 2010

ABSTRACT

Listeria monocytogenes
interaction with the intestinal epithelium is a key step in the infection process. We demonstrated that
Listeria
adhesion protein (LAP) promotes adhesion to intestinal epithelial cells and facilitates extraintestinal dissemination
in vivo
. The LAP receptor is a stress response protein, Hsp60, but the precise role for the LAP-Hsp60 interaction during
Listeria
infection is unknown. Here we investigated the influence of physiological stressors and
Listeria
infection on host Hsp60 expression and LAP-mediated bacterial adhesion, invasion, and transepithelial translocation in an enterocyte-like Caco-2 cell model. Stressors such as heat (41°C), tumor necrosis factor alpha (TNF-α) (100 U), and
L. monocytogenes
infection (10
4
to 10
6
CFU/ml) significantly (
P
< 0.05) increased plasma membrane and intracellular Hsp60 levels in Caco-2 cells and consequently enhanced LAP-mediated
L. monocytogenes
adhesion but not invasion of Caco-2 cells. In transepithelial translocation experiments, the wild type (WT) exhibited 2.7-fold more translocation through Caco-2 monolayers than a
lap
mutant, suggesting that LAP is involved in transepithelial translocation, potentially via a paracellular route. Short hairpin RNA (shRNA) suppression of Hsp60 in Caco-2 cells reduced WT adhesion and translocation 4.5- and 3-fold, respectively, while adhesion remained unchanged for the
lap
mutant. Conversely, overexpression of Hsp60 in Caco-2 cells enhanced WT adhesion and transepithelial translocation, but not those of the
lap
mutant. Furthermore, initial infection with a low dosage (10
6
CFU/ml) of
L. monocytogenes
increased plasma membrane and intracellular expression of Hsp60 significantly, which rendered Caco-2 cells more susceptible to subsequent LAP-mediated adhesion and translocation. These data provide insight into the role of LAP as a virulence factor during intestinal epithelial infection and pose new questions regarding the dynamics between the host stress response and pathogen infection.
The Coupling Protein Cagβ and Its Interaction Partner CagZ Are Required for Type IV Secretion of the
Helicobacter pylori
CagA Protein
Authors: Jurik Angela , Haußer Elisabeth , Kutter Stefan , Pattis Isabelle , Praßl Sandra , Weiss Evelyn , Fischer Wolfgang 
Published: September 2010

ABSTRACT

Bacterial type IV secretion systems are macromolecule transporters with essential functions for horizontal gene transfer and for symbiotic and pathogenic interactions with eukaryotic host cells.
Helicobacter pylori
, the causative agent of type B gastritis, peptic ulcers, gastric adenocarcinoma, and mucosa-associated lymphoid tissue (MALT) lymphoma, uses the Cag type IV secretion system to inject its effector protein CagA into gastric cells. This protein translocation results in altered host cell gene expression profiles and cytoskeletal rearrangements, and it has been linked to cancer development. Interactions of CagA with host cell proteins have been studied in great detail, but little is known about the molecular details of CagA recognition as a type IV secretion substrate or of the translocation process. Apart from components of the secretion apparatus, we previously identified several CagA translocation factors that are either required for or support CagA translocation. To identify protein-protein interactions between these translocation factors, we used a yeast two-hybrid approach comprising all
cag
pathogenicity island genes. Among several other interactions involving translocation factors, we found a strong interaction between the coupling protein homologue Cagβ (HP0524) and the Cag-specific translocation factor CagZ (HP0526). We show that CagZ has a stabilizing effect on Cagβ, and we demonstrate protein-protein interactions between the cytoplasmic part of Cagβ and CagA and between CagZ and Cagβ, using immunoprecipitation and pull-down assays. Together, our data suggest that these interactions represent a substrate-translocation factor complex at the bacterial cytoplasmic membrane.
Surface Immunolabeling and Consensus Computational Framework To Identify Candidate Rare Outer Membrane Proteins ofTreponema pallidum
Authors: Cox David L. , Luthra Amit , Dunham-Ems Star , Desrosiers Daniel C. , Salazar Juan C. , Caimano Melissa J. , Radolf Justin D. 
Published: September 2010

ABSTRACTTreponema pallidumreacts poorly with the antibodies present in rabbit and human syphilitic sera, a property attributed to the paucity of proteins in its outer membrane. To better understand the basis for the syphilis spirochete's “stealth pathogenicity,” we used a dual-label, 3-step amplified assay in which treponemes encapsulated in gel microdroplets were probed with syphilitic sera in parallel with anti-FlaA antibodies. A small (approximately 5 to 10%) but reproducible fraction of intact treponemes bound IgG and/or IgM antibodies. Three lines of evidence supported the notion that the surface antigens were likely β-barrel-forming outer membrane proteins (OMPs): (i) surface labeling with anti-lipoidal (VDRL) antibodies was not observed, (ii) immunoblot analysis confirmed prior results showing thatT. pallidumglycolipids are not immunoreactive, and (iii) labeling of intact organisms was not appreciably affected by proteinase K (PK) treatment. With this method, we also demonstrate that TprK (TP0897), an extensively studied candidate OMP, and TP0136, a lipoprotein recently reported to be surface exposed, are both periplasmic. Consistent with the immunolabeling studies, TprK was also found to lack amphiphilicity, a characteristic property of β-barrel-forming proteins. Using a consensus computational framework that combined subcellular localization and β-barrel structural prediction tools, we generated ranked groups of candidate rare OMPs, the predictedT. pallidumouter membrane proteome (OMPeome), which we postulate includes the surface-exposed molecules detected by our enhanced gel microdroplet assay. In addition to underscoring the syphilis spirochete's remarkably poor surface antigenicity, our findings help to explain the complex and shifting balance between pathogen and host defenses that characterizes syphilitic infection.
Immunohistochemical assessment of respiratory viruses in necropsy samples from lethal non-pandemic seasonal respiratory infections
Authors: do Carmo Debur Maria , Raboni Sonia Mara , Flizikowski Fabiane B Z , Chong Débora C , Persicote Ana Paula , Nogueira Meri B , Rosele Luine V , de Almeida Sergio Monteiro , de Noronha Lucia 
Published: September 2010

Background/aimAcute respiratory infections are an important cause of childhood morbidity and mortality throughout the world, and viruses have often been reported to be an aetiological agent. This study aimed to identify respiratory viruses in paraffin-embedded samples of paediatric lung necropsy specimens, using immunohistochemistry on tissue microarray slides.MethodsRetrospective study in 200 lung tissue samples from children who had died from severe respiratory infections during 1985–2005. Immunoperoxidase assay was performed to detect the viruses that were most commonly associated with respiratory tract infections: influenza virus A (FLU A), influenza virus B (FLU B), respiratory syncytial virus (RSV), adenovirus (AdV) and parainfluenza virus (PIV) types 1, 2 and 3.ResultsViruses were detected in 71 (35.5%) cases. Most positive cases were observed in children younger than 6 months. In 42.3% of cases, only one virus was detected: 11 (36.7%) RSV; 7 (23.3%) AdV; 4 (13.3%) PIV2; 3 (10%) FLU A; 2 (6.7%) FLU B; 2 (6.7%) PIV3; and 1 (3.3%) PIV1. Co-infection with more than one virus was observed in 41 (57.7%) cases. No positive correlations were observed between the presence of viral antigens and seasonality of the infection, sex, age or histopathological findings.ConclusionsNon-pandemic seasonal respiratory viruses are involved in a significant number of deaths in paediatric patients; these findings highlight the importance of laboratory investigation of these agents in patients hospitalised with severe acute respiratory infections.
Assessment of malignant potential of oral submucous fibrosis through evaluation of p63, E-cadherin and CD105 expression
Authors: Das Raunak Kumar , Pal Mousumi , Barui Ananya , Paul Ranjan Rashmi , Chakraborty Chandan , Ray Ajoy Kumar , Sengupta Sanghamitra , Chatterjee Jyotirmoy 
Published: September 2010

BackgroundThe assessment of malignant potential of oral submucous fibrosis grades vis-à-vis their progression towards malignancy is associated with expression of possible multiple molecular markers.AimsTo analyse p63, E-cadherin and CD105 expression in this premalignant pathosis with a view to unravel and understand the expression of these molecules as markers.MethodsThe oral mucosal biopsies (normal, oral submucous fibrosis with and without dysplasia) were studied with routine H&E, and by immunohistochemistry for p63, E-cadherin and CD105 expression. p63 was assessed as percentage of positive nuclei. E-cadherin expression was estimated through (i) distance between basement membrane and E-cadherin expression initiation point, (ii) ratio between epithelial thickness and epithelial thickness displaying E-cadherin, and (iii) E-cadherin intensity variation along the expression path. CD105 expression was assessed qualitatively.ResultsThe p63+ cells were highest in severely dysplastic tissues followed by other dysplastic grades, normal oral mucosa and non-dysplastic conditions. However, the p63+ cells displayed the feature of progressive maturation only in normal mucosa. There was a loss of membranous E-cadherin in basal layers of all diseased conditions; it was highest in severe dysplasia. There was significant variation (p<0.0001) in E-cadherin intensity within and between the tissues (normal and diseased). CD105 expression increased abruptly in dysplasia.ConclusionsThe malignant potential of this pre-cancerous condition is likely to be correlated with an increase in p63 and CD105 expression and a concomitant loss of membranous E-cadherin. This may lead to marker identification through greater validation.
New double embedding technique for specimens of endoscopic submucosal dissection using agarose: comparison with other media
Authors: Zozumi Masataka , Nakai Mayumi , Ito Takashi , Matsuda Ikuo , Hao Hiroyuki , Tsukamoto Yoshitane , Hirota Seiichi 
Published: September 2010

AimsProcedure of endoscopic submucosal dissection (ESD) has been introduced widely for treatment of early gastric cancers. For such specimens, accurate pathological diagnosis, especially concerning depth of the invasion and exposure to margins, is essential to decide on the necessity of additional treatment. Therefore, easy and reliable tissue-processing method for multiple cut specimens is needed. The authors report here a new double embedding technique for specimens of ESD.MethodsFormalin-fixed whole specimen was superficially wrapped by agarose (the first embedding), and the tissue-agarose block was cut at 2–3 mm intervals. Each cut specimen was laid down with 90° rotation. This procedure permitted ‘on edge’ embedding of thin tissues in paraffin (the second embedding) and subsequent preparation of perpendicular section to the tissue surface. The authors compared the handleability and stainability among several media including various types of agar, agarose and gelatin for first embedding. A survey by questionnaire was carried out on handleability and/or impression on various tissue-processing steps from pathology technicians.ResultsAmong the media examined, agarose showed the best solubility in water and the best transparency on several representative stainings. According to the survey, pathology technicians seemed to feel that the present method was better than the usual tissue processing method, especially in shortened time consumption and accuracy of alignment of multiple tissues for ESD specimens.ConclusionsThe present new double embedding technique using agarose provides not only an easy and reliable embedding procedure for technicians but also accurate and exact diagnosis for pathologists.
Virtual microscopy for histology quality assurance of screen-detected polyps
Authors: Risio Mauro , Bussolati Gianni , Senore Carlo , Vigna Stefano , Frangipane Elena , Segnan Nereo , Cassoni Paola 
Published: September 2010

AimHistology quality assurance is crucial for screening programmes and can be performed by circulating glass slides, which has certain intrinsic disadvantages. The present study aimed to assess the accuracy of virtual microscopy in terms of reliability and diagnostic reproducibility in colorectal cancer screening programmes.Methods457 consecutive lesions detected in people undergoing colonoscopy were examined histologically in two pathology units, using both traditional optical microscopy and virtual microscopy (6–12 months later). Intra- and inter-observer agreement using the two approaches was determined using κ statistics.ResultsIntra- and inter-observer agreements were substantially unmodified by the use of the virtual microscopy approach compared with traditional optical microscopy; moreover, for some histological features critical for patient management in colorectal cancer screening programmes (such as the presence of a villous component within the adenoma), virtual microscopy increased interobserver agreement (κ statistics 0.66 versus 0.52).ConclusionsThis study shows that virtual microscopy can be an effective tool for diagnostic quality assurance in colorectal cancer screening programmes, and its accuracy is equivalent to or higher than that of optical microscopy in the validation of histological criteria (eg, advanced adenoma) crucial for patient management in screening programmes.
Surveillance of mesothelioma and workers' compensation in British Columbia, Canada
Authors: Kirkham Tracy L , Koehoorn Mieke W , McLeod Christopher B , Demers Paul A 
Published: September 2010

ObjectivesTo determine the rate of workers' compensation for mesothelioma cases in the Canadian province of British Columbia, examine trends in mesothelioma cases and compensation over time, and identify factors associated with compensation status for mesothelioma cases.MethodsMesothelioma cases in the provincial cancer registry were linked at the individual level with accepted claims for mesothelioma in the provincial workers' compensation system for the period 1970–2005.Results391 of the 485 workers' compensated claims were linked (81% match rate) with a record in the cancer registry for an overall mesothelioma compensation rate of 33% over the study period and a high of 49% in the last 5 years. Compensation rates were lower for women, older (retired) as well as younger workers, and sites other than the pleura.ConclusionsAlthough the workers' compensation rate for mesothelioma increased over time, the rate was much lower than anticipated for cases believed to be work-related cancers. Several key factors may significantly influence awareness by clinicians and workers of the work-relatedness of mesothelioma and of workers' compensation benefits. Regulatory agencies need to develop policies or effective notification systems to ensure that all newly diagnosed mesothelioma cases seek compensation benefits.