bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overcorrection of iodinated contrast attenuation in SPECT‐CT: Phantom studies
Authors: Bonta Dacian V. , Wahl Richard L. 
Published: August 2010

Purpose:The authors investigated the effects of iodinated contrast agents on the quantification of radioactivity obtained using a combined single photon emission tomography (SPECT) and high resolution 16 slice computed tomography (CT) scanner.Methods:Two conditions were evaluated: Contrast media mixed with radioisotope and the contrast media, and the radioisotope solution confined in adjacent but distinct volumes. Phantoms containing combinations of, , and solutions in normal saline and contrast solutions in normal saline corresponding to the two conditions were prepared and scanned. Images were reconstructed by iterative reconstruction (ordered subset expectation maximization), with and without CT‐derived attenuation maps. The reconstructed counts encoded in the reconstructed images were compared.Results:Compared to normal saline, the presence of an iodinated contrast agent resulted in the underestimation of reconstructed counts in all nonattenuation corrected SPECT images. Compared to normal saline, the presence of a contrast agent resulted in the overestimation of reconstructed counts in all attenuation corrected SPECT images. The largest underestimation of reconstructed counts was 12.8% and the largest overestimation value was 35.9%.Conclusions:High concentrations of a contrast agent caused errors in the measurement of actual radiotracer reconstructed counts in phantoms. These errors could have important consequences for the use of oral and intravenous contrast in both diagnostic (qualitative) and dosimetric (quantitative) SPECT‐CT imaging. The authors’ findings suggest that noncontrast imaging or alternative contrast‐specific attenuation correction approaches should be considered for optimal SPECT activity quantification.
Prevalence of Antimicrobial-Resistant Pathogens in Canadian Hospitals: Results of the Canadian Ward Surveillance Study (CANWARD 2008)
Authors: Zhanel George G. , DeCorby Melanie , Adam Heather , Mulvey Michael R. , McCracken Melissa , Lagacé-Wiens Philippe , Nichol Kimberly A. , Wierzbowski Aleksandra , Baudry Patricia J. , Tailor Franil , Karlowsky James A. , Walkty Andrew , Schweizer Frank , Johnson Jack , Hoban Daryl J. 
Published: August 2010

ABSTRACT

A total of 5,282 bacterial isolates obtained between 1 January and 31 December 31 2008, inclusive, from patients in 10 hospitals across Canada as part of the Canadian Ward Surveillance Study (CANWARD 2008) underwent susceptibility testing. The 10 most common organisms, representing 78.8% of all clinical specimens, were as follows:
Escherichia coli
(21.4%), methicillin-susceptible
Staphylococcus aureus
(MSSA; 13.9%),
Streptococcus pneumoniae
(10.3%),
Pseudomonas aeruginosa
(7.1%),
Klebsiella pneumoniae
(6.0%), coagulase-negative staphylococci/
Staphylococcus epidermidis
(5.4%), methicillin-resistant
S. aureus
(MRSA; 5.1%),
Haemophilus influenzae
(4.1%),
Enterococcus
spp. (3.3%),
Enterobacter cloacae
(2.2%). MRSA comprised 27.0% (272/1,007) of all
S. aureus
isolates (genotypically, 68.8% of MRSA were health care associated [HA-MRSA] and 27.6% were community associated [CA-MRSA]). Extended-spectrum β-lactamase (ESBL)-producing
E. coli
occurred in 4.9% of
E. coli
isolates. The CTX-M type was the predominant ESBL, with CTX-M-15 the most prevalent genotype. MRSA demonstrated no resistance to ceftobiprole, daptomycin, linezolid, telavancin, tigecycline, or vancomycin (0.4% intermediate intermediate resistance).
E. coli
demonstrated no resistance to ertapenem, meropenem, or tigecycline. Resistance rates with
P. aeruginosa
were as follows: colistin (polymyxin E), 0.8%; amikacin, 3.5%; cefepime, 7.2%; gentamicin, 12.3%; fluoroquinolones, 19.0 to 24.1%; meropenem, 5.6%; piperacillin-tazobactam, 8.0%. A multidrug-resistant (MDR) phenotype occurred frequently in
P. aeruginosa
(5.9%) but uncommonly in
E. coli
(1.2%) and
K. pneumoniae
(0.9%). In conclusion,
E. coli
,
S. aureus
(MSSA and MRSA),
P. aeruginosa
,
S. pneumoniae
,
K. pneumoniae
,
H. influenzae
, and
Enterococcus
spp. are the most common isolates recovered from clinical specimens in Canadian hospitals. The prevalence of MRSA was 27.0% (of which genotypically 27.6% were CA-MRSA), while ESBL-producing
E. coli
occurred in 4.9% of isolates. An MDR phenotype was common in
P. aeruginosa.
In Vitro
Profiling of Pramiconazole and
In Vivo
Evaluation in
Microsporum canis
Dermatitis and
Candida albicans
Vaginitis Laboratory Models
Authors: de Wit Kelly , Paulussen Caroline , Matheeussen An , van Rossem Koen , Cos Paul , Maes Louis 
Published: August 2010

ABSTRACT

The triazole antifungal pramiconazole (Stiefel, a GSK company) was compared with itraconazole, miconazole, and terbinafine
in vitro
and
in vivo
. Potent
in vitro
activities against
Candida
spp. (50% inhibitory concentration [IC
50
], 0.04 to 1.83 μM) and
Microsporum
and
Trichophyton
spp. (IC
50
, 0.15 to 1.34 μM) were obtained but not, however, against other filamentous molds and zygomycetes. In the
M. canis
guinea pig model and
C. albicans
vulvovaginitis rat model, pramiconazole was superior to the reference compounds after oral and topical administration.
Loss of the Group A
Streptococcus
Regulator Srv Decreases Biofilm Formation
In Vivo
in an Otitis Media Model of Infection
Authors: Roberts Amity L. , Connolly Kristie L. , Doern Christopher D. , Holder Robert C. , Reid Sean D. 
Published: August 2010

ABSTRACT

Group A
Streptococcus
(GAS) is a common causative agent of pharyngitis, but the role of GAS in otitis media is underappreciated. In this study, we sought to test the hypothesis that GAS colonizes the middle ear and establishes itself in localized, three-dimensional communities representative of biofilms. To test this hypothesis, the middle ears of chinchillas were infected with either a strain of GAS capable of forming biofilms
in vitro
(MGAS5005) or a strain deficient in biofilm formation due to the lack of the transcriptional regulator Srv (MGAS5005 Δ
srv
). Infection resulted in the formation of large, macroscopic structures within the middle ears of MGAS5005- and MGAS5005 Δ
srv
-infected animals. Plate counts, scanning electron microscopy, LIVE/DEAD staining, and Gram staining revealed a difference in the distributions of MGAS5005 versus MGAS5005 Δ
srv
in the infected samples. High numbers of CFU of MGAS5005 Δ
srv
were isolated from the middle ear effusion, and MGAS5005 Δ
srv
was found randomly distributed throughout the excised macroscopic structure. In contrast, MGAS5005 was found in densely packed microcolonies indicative of biofilms within the excised material from the middle ear. CFU levels of MGAS5005 from the effusion were significantly lower than that of MGAS5005 Δ
srv
early during the course of infection. Allelic replacement of the chromosomally encoded streptococcal cysteine protease (
speB
) in the MGAS5005 Δ
srv
background restored biofilm formation
in vivo
. Interestingly, our results suggest that GAS naturally forms a biofilm during otitis media but that biofilm formation is not required to establish infection following transbullar inoculation of chinchillas.
Vascular Endothelial Growth Factor Receptor 1 Contributes toEscherichia coliK1 Invasion of Human Brain Microvascular Endothelial Cells through the Phosphatidylinositol 3-Kinase/Akt Signaling Pathway
Authors: Zhao Wei-Dong , Liu Wei , Fang Wen-Gang , Kim Kwang Sik , Chen Yu-Hua 
Published: August 2010

ABSTRACTEscherichia coliis the most common Gram-negative organism causing neonatal meningitis. Previous studies demonstrated thatE. coliK1 invasion of brain microvascular endothelial cells (BMEC) is required for penetration into the central nervous system, but the microbe-host interactions that are involved in this process remain incompletely understood. Here we report the involvement of vascular endothelial growth factor receptor 1 (VEGFR1) expressed on human brain microvascular endothelial cells (HBMEC) inE. coliK1 invasion of HBMEC. Our results showed that treatment of confluent HBMEC with pan-VEGFR inhibitors significantly inhibitedE. coliK1 invasion of HBMEC. Immunofluorescence results indicated the colocalization of VEGFR1 withE. coliK1 during bacterial invasion of HBMEC. TheE. coli-induced actin cytoskeleton rearrangements in HBMEC were blocked by VEGFR inhibitors but not by VEGFR2-specific inhibitors. The small interfering RNA (siRNA) knockdown of VEGFR1 in HBMEC significantly attenuatedE. coliinvasion and the concomitant actin filament rearrangement. Furthermore, we found an increased association of VEGFR1 with the p85 subunit of phosphatidylinositol 3-kinase (PI3K) in HBMEC infected withE. coliK1 and thatE. coliK1-triggered Akt activation in HBMEC was blocked by VEGFR1 siRNA and VEGFR inhibitors. Taken together, our results demonstrate that VEGFR1 contributes toE. coliK1 invasion of HBMEC via recruitment of the PI3K/Akt signaling pathway.
Transcriptional Response ofLeptospira interrogansto Iron Limitation and Characterization of a PerR Homolog
Authors: Lo Miranda , Murray Gerald L. , Khoo Chen Ai , Haake David A. , Zuerner Richard L. , Adler Ben 
Published: August 2010

ABSTRACTLeptospirosis is a globally significant zoonosis caused byLeptospiraspp. Iron is essential for growth of most bacterial species. Since iron availability is low in the host, pathogens have evolved complex iron acquisition mechanisms to survive and establish infection. In many bacteria, expression of iron uptake and storage proteins is regulated by Fur.L. interrogansencodes four predicted Fur homologs; we have constructed a mutation in one of these,la1857. We conducted microarray analysis to identify iron-responsive genes and to study the effects ofla1857mutation on gene expression. Under iron-limiting conditions, 43 genes were upregulated and 49 genes were downregulated in the wild type. Genes encoding proteins with predicted involvement in inorganic ion transport and metabolism (including TonB-dependent proteins and outer membrane transport proteins) were overrepresented in the upregulated list, while 54% of differentially expressed genes had no known function. There were 16 upregulated genes of unknown function which are absent from the saprophyteL. biflexaand which therefore may encode virulence-associated factors. Expression of iron-responsive genes was not significantly affected by mutagenesis ofla1857, indicating that LA1857 is not a global regulator of iron homeostasis. Upregulation of heme biosynthetic genes and a putative catalase in the mutant suggested that LA1857 is more similar to PerR, a regulator of the oxidative stress response. Indeed, thela1857mutant was more resistant to peroxide stress than the wild type. Our results provide insights into the role of iron in leptospiral metabolism and regulation of the oxidative stress response, including genes likely to be important for virulence.
Interaction between Pathogenic Bacteria and Intrauterine Leukocytes Triggers Alternative Molecular Signaling Cascades Leading to Labor in Women
Authors: Estrada-Gutierrez Guadalupe , Gomez-Lopez Nardhy , Zaga-Clavellina Veronica , Giono-Cerezo Silvia , Espejel-Nuñez Aurora , Gonzalez-Jimenez Marco Antonio , Espino y Sosa Salvador , Olson David M. , Vadillo-Ortega Felipe 
Published: August 2010

ABSTRACT

Increased risk of preterm labor has been linked to cervicovaginal infection with
Ureaplasma urealyticum
and group B streptococci. Although various experimental models have been developed to study the role of amniochorion infection in preterm labor, they typically exclude the initial interaction between intrauterine leukocytes (recruited from decidual vessels into the avascular fetal membranes) and infecting bacteria. In this work, we ascertained whether inflammatory molecules secreted by bacterium-activated intrauterine leukocytes stimulate the amniochorion production of mediators involved in human labor. Using a two-step process beginning with placental circulating leukocytes as a proxy for intrauterine leukocytes, we found that coincubation of amniochorion explants with plasma from placental whole blood preincubated with group B streptococci resulted in a significant increase in tumor necrosis factor alpha (TNF-α) and matrix metalloproteinase 9 (MMP-9) levels in tissue. Extensive changes in the connective tissue arrangement and a decrease in collagen content demonstrated the degradation of the extracellular matrix following this treatment. In contrast, plasma from blood preconditioned with
U. urealyticum
induced a highly significant secretion of interleukin-1β (IL-1β) and prostaglandin E
2
(PGE
2
) by the amniochorion without changes in the extracellular matrix organization or content. These data demonstrate that group B streptococci induce degradation of the amniochorion as a result of MMP-9 production, probably via TNF-α, whereas
U. urealyticum
stimulates the secretion of PGE
2
, probably via IL-1β, potentially stimulating myometrial contraction. Our study provides novel evidence that the immunological cells circulating within the uterine microenvironment respond differentially to an infectious agent, triggering alternative molecular signaling pathways leading to human labor.
Validation of two child passenger safety questionnaires
Authors: Uherick Lisa , Gorelick Marc H , Biechler Robert , Brixey Suzanne N , Melzer-Lange Marlene 
Published: August 2010

ObjectiveTo measure the validity of a booster seat questionnaire and a car seat questionnaire so that they can be reliably used in future trials.DesignThe two child passenger safety questionnaires were created. Each underwent expert review to ensure face and content validity. Two reliability studies were conducted independently of each other. Care givers for children who were cared for in a paediatric emergency department were enrolled. Criterion validity was tested by direct observation, and inter-rater reliability was measured. Test–retest reliability and internal consistency were also measured on the booster seat questionnaire.ResultsBooster seat questionnaire: test–retest agreement was good, with 16 of the 18 questions having agreement of at least 80%. Agreement was acceptable (>70%) in all other questions in which agreement was expected when the answers of two different care givers were compared. All care givers were able to report booster seat use as it was found on direct observation, yielding a κ value of 1. Car seat questionnaire: the respondents showed 95% agreement between their reported type of child safety restraint and what was found on direct observation. Inter-rater agreement for the type of safety restraint was 77% or a κ value of 0.7.ConclusionBoth the booster seat questionnaire and the car seat questionnaire are valid and can be reliably used in future studies. The findings of this study need to be verified with larger studies and different populations.
Motor vehicle mismatch: a national perspective
Authors: Mandell Samuel P , Mack Christopher D , Bulger Eileen M 
Published: August 2010

ObjectiveTo determine the RR of the severe injury associated with light truck vehicle (LTV) versus passenger vehicle (PV) mismatch following motor vehicle collisions across the USA.MethodsThis was a retrospective cohort study with the primary outcomes of Injury Severity Score (ISS) >8 and body region Abbreviated Injury Score (AIS) >2. The National Automotive Sampling System Crashworthiness Data System (NASS CDS) was searched for occupants in frontal and side impact crashes from 1993 to 2007. Occupants in PVs struck by LTVs were compared to PV occupants struck by another PV. Poisson regression was used to estimate the RR of severe injury after adjusting for driver age, driver gender, and change in velocity during the crash (∆v). Because 21% of cases were missing ∆v, multiple imputation was used to estimate the missing values. NASS CDS weights were used to estimate the risk of severe injury nationally.ResultsPV occupants in front impact crashes with an LTV as the striking vehicle were at increased risk of severe injury compared to those struck by another PV (RR 1.37, 95% CI 1.09 to 1.73). A similar increase risk was observed in side impact crashes (RR 1.34, 95% CI 1.12 to 1.62). Increased risk of injury was also identified in several body regions.ConclusionsMotor vehicle mismatch crashes are associated with a significant increase in risk of severe injury for PV occupants in the USA. Addressing vehicle compatibility remains an important issue for occupant safety.
Formal specification of wireless and pervasive healthcare applications
Authors: Coronato Antonio , Pietro Giuseppe DE 
Published: August 2010

Wireless and pervasive healthcare applications typically present critical requirements from the point of view of functional correctness, reliability, availability, security, and safety. In contrast to the case of classic safety critical applications, the behavior of wireless and pervasive applications is affected by the movements and location of users and resources.
This article presents a methodology to formally express requirements in safety critical wireless and pervasive healthcare applications in order to achieve a higher degree of dependability. In particular, it will be shown how it is possible to formalize and constrict mobility characteristics by combining, and in some cases extending, several formal methods. The article also describes a rigorous specification process. Finally, it concludes with a case study of a real safety critical pervasive healthcare application that is going to be deployed in a city hospital.
Hypodysfibrinogenaemia due to production of mutant fibrinogen alpha-chains lacking fibrinopeptide A and polymerisation knob ‘A’
Authors: Vorjohann Silja , Fish Richard , Biron-Andreani Christine , Nagaswami Chandrasekaran , Weisel John , Boulot Pierre , Reyftmann Lionel , Moerloose Philippe de , Neerman-Arbez Marguerite 
Published: August 2010

SummaryInherited disorders of fibrinogen are rare and affect either the quantity (hypofibrinogenaemia and afibrinogenaemia) or the quality of the circulating fibrinogen (dysfibrinogenaemia) or both (hypodysfibrinogenaemia). Extensive allelic heterogeneity has been found for all these disorders: in congenital afibrinogenaemia for example more than 40 mutations, the majority in FGA, have been identified in homozygosity or in compound heterozygosity. Numerous mutations have also been identified in patients with hypofibrinogenaemia, many of these patients are in fact heterozygous carriers of afibrinogenaemia mutations. Despite the number of genetic analyses performed, the study of additional patients still allows the identification of novel mutations. Here we describe the characterization of a novel FGA intron 2 donor splice-site mutation (Fibrinogen Montpellier II) identified in three siblings with hypodysfibrinogenaemia. Functional analysis of RNA produced by the mutant minigene in COS-7 cells revealed that the mutation led to the in-frame skipping of exon 2. Western blot analysis of COS-7 cells expressing an exon 2 deleted FGA cDNA revealed that an alpha-chain lacking exon 2, which codes in particular for fibrinopeptide A and polymerisation knob ‘A’, has the potential to be assembled into a hexamer and secreted. Analysis of precipitated fibrinogen from patient plasma showed that the defect leads to the presence in the circulation of alpha-chains lacking knob ‘A’ which is essential for the early stages of fibrin polymerisation. Fibrin made from purified patient fibrinogen clotted with thrombin displayed thinner fibers with frequent ends and large pores.
Factor XII: New life for an old protein
Authors: LaRusch Gretchen , Schmaier Alvin 
Published: August 2010

SummaryRatnoff and his coworkers recognised that factor XII (XII) stimulates cell growth and activates mitogen-activated protein kinase. We determined the receptor(s) for this function and the consequence of this signalling pathway. Investigations show that the urokinase plasminogen activator receptor serves as the XII binding site on cultured umbilical vein endothelial cells. When XII binds, it stimulates ERK1/2 and Akt S473 phosphorylation. These events are distinct because when cell mTORC2 is absent, XII phosphorylates ERK1/2 but not Akt S473. Zymogen XII is an equal stimulator of signalling as XIIa or inhibitor-treated XIIa. Peptides from uPAR domain 2 block XII binding and ERK1/2 and Akt phosphorylation. Furthermore, antibodies to the integrins β1 and α5 block XII signalling. Likewise, inhibitors to the EGFR block XII-induced phosphorylation events. XII stimulates cell growth and proliferation. XII induces angiogenesis ex vivo in normal aortic sprouts and in vivo in matrigel plugs in normal mice, but not in aorta from uPAR knockout mice or matrigel plugs placed into uPAR-deleted mice. Skin biopsies constitutively or in a wound nine days after injury show reduced CD31 antigen expression in specimens from XII knockout mice compared to wild-type mice. These studies indicate that XII stimulates angiogenesis, a physiologic function independent of contact activation.
Interaction of PF4 (CXCL4) with the vasculature: A role in atherosclerosis and angiogenesis
Authors: Aidoudi Sallouha , Bikfalvi Andreas 
Published: August 2010

SummaryPlatelet factor-4 (PF4), a platelet-derived chemokine, has two important functions in the vasculature. It has a pro-atherogenic role while also having anti-angiogenic effects. The activity of platelet factor-4 (PF4), unlike other chemokines that bind to specific receptors, depends on its unusually high affinity for proteoglycans and other negatively charged molecules. High affinity for heparan sulfates was thought to be central to all of PF4’s biological functions. However, other mechanisms have been described such as direct growth factor binding, activation of the CXCR3B chemokine receptor isoform that is present in some vascular cells or binding to lipoprotein-related protein-1 (LRP1). Furthermore, PF4 also binds to integrins with affinities similar to matrix molecules. These interactions may explain the effects of PF4 in healthy and pathological tissues. However, the mechanisms involved in PF4’s activity are complex and may depend on a given tissue or localisation. Overall, while much is already known about PF4, its specific role in atherosclerosis and angiogenesis remains still to be clarified.
Dynamic Norm-based Encoding for Unfamiliar Shapes in Human Visual Cortex
Authors: Panis Sven , Wagemans Johan , Op de Beeck Hans P. 
Published: August 2010

Abstract
Previous studies have argued that faces and other objects are encoded in terms of their deviation from a class prototype or norm. This prototype is associated with a smaller neural population response compared with nonprototype objects. However, it is still unclear (1) whether a norm-based representation can emerge for unfamiliar or novel object classes through visual experience at the time scale of an experiment and (2) whether the results from previous studies are caused by the prototypicality of a stimulus, by the physical properties of individual stimuli independent from the stimulus distribution, and/or by the trial-to-trial adaptation. Here we show with a combined behavioral and event-related fMRI study in humans that a short amount of visual experience with exemplars from novel object classes determines which stimulus is represented as the norm. Prototypicality effects were observed at the behavioral level by behavioral asymmetries during a stimulus comparison task. The fMRI data revealed that class exemplars closest to the prototypes—the perceived average of each class—were associated with a smaller response in the anterior part of the visual object-selective cortex compared with other class exemplars. By dissociating between the physical characteristics and the prototypicality status of the stimuli and by controlling for trial-to-trial adaptation, we can firmly conclude for the first time that high-level visual areas represent the identity of exemplars using a dynamic, norm-based encoding principle.