bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of a portable prothrombin time analyzer (CoaguChek‐XS) in dogs
Authors: Kelmer Efrat , Segev Gilad , Codner Carolina , Bruchim Yaron , Klainbart Sigal , Aroch Itamar 
Published: July 2014

AbstractObjectivesTo assess the performance of a portable prothrombin time (PT) analyzer (CoaguChek‐XS) in dogs.AnimalsNinety‐seven dogs composed of 20 healthy dogs, 45 ill dogs, and 32 ill dogs with altered coagulation.ProceduresSamples were concurrently obtained and PT was measured using the CoaguChek‐XS and an automated coagulation analyzer. Agreement between methods was assessed using Spearman's correlation and Bland–Altman analysis.ResultsThe reference interval for PT using the CoaguChek‐XS was 9.6–11.5 s. The CoaguChek‐XS was easy to use, required a small volume of whole blood, and gave results within 1 min. The mean difference in PT between the 2 methods was 2.58 s (SD 3.10), and 94% of the samples fell within limits of agreement. The correlation was moderate, but significant (r = 0.35, P < 0.001). Sensitivity and specificity of the CoaguCheck‐XS PT compared to analyzer PT were 92% and 56%, respectively, and increased to 95% and 77% on intent to treat basis. The coefficient of variance was 0.72%.The CoaguChek‐XS identified all 8 dogs with anticoagulant rodenticide intoxication, although a discrepancy was noted from the analyzer results. In anemic dogs (PCV≤25%), the CoaguChek‐XS did not display accurate results.ConclusionsThe CoaguChek‐XS is a simple, user‐friendly, highly precise PT analyzer. Results had moderate correlation and good agreement with a standard method. It can be used reliably for screening dogs when the PT is normal. However, when the CoaguChek‐XS PT is prolonged or when the PCV is ≤25%, results should be confirmed using a standard method.
The effect of hetastarch 670/0.75 administered in vivo as a constant rate infusion on platelet closure time in the dog
Authors: Helmbold Kim A. , Mellema Matthew S. , Hopper Kate , Epstein Steven E. 
Published: July 2014

AbstractObjectiveTo evaluate the effects of hetastarch 670/0.75 on canine platelet function and clinical bleeding following its administration as a constant rate infusion (CRI) at 1 mL/kg/h and 2 mL/kg/h for 24 hours.DesignIn vivo, prospective, open‐label, crossover study.SettingResearch laboratory at a university veterinary facility.AnimalsEight healthy, adult male research dogs.InterventionsEach dog received 1 mL/kg/h hetastarch for 24 hours then 2 mL/kg/h with a washout period of 10 weeks between each experiment. Platelet closure time (CT) was measured using a platelet function analyzer with collagen adenosine diphosphate (ADP) cartridges. CT measurements were performed at baseline and 6, 12, and 24 hours following initiation of hetastarch infusion.Measurements and Main ResultsAt 1 mL/kg/h, mean CT was significantly increased at the 12‐ and 24‐hour time point relative to the baseline value, although mean CT never rose to a value above the reference interval during the 24‐hour infusion. At 2 mL/kg/h, median CT was also significantly increased at the 12‐ and 24‐hour time point relative to the baseline value. Administration of 2 mL/kg/h did progressively prolong the median CT value though only exceeded the reference interval at the 24‐hour time point. Despite the prolongation of median CT, there was no clinical evidence of spontaneous bleeding in any dog during the 24‐hour infusion at either CRI rate.ConclusionsHetastarch 670/0.75 when used as a 24‐hour CRI at 1 and 2 mL/kg/h prolongs CT in healthy dogs at 6, 12, and 24 hours. Median CT only exceeded the reference interval at 24 hours at 2 mL/kg/h.
Ceftaroline Is Active against Heteroresistant Methicillin-Resistant Staphylococcus aureus Clinical Strains despite Associated Mutational Mechanisms and Intermediate Levels of Resistance
Authors: Fernandez Regina , Paz Liliana I. , Rosato Roberto R. , Rosato Adriana E. 
Published: July 2014

ABSTRACTMethicillin-resistantStaphylococcus aureus(MRSA) is an important infectious human pathogen responsible for diseases ranging from skin and soft tissue infections to life-threatening endocarditis. β-Lactam resistance in MRSA involves acquisition of penicillin-binding protein 2a (PBP2a), a protein with low affinity for β-lactams that mediates cell wall assembly when the normal staphylococcal PBPs (PBP1 to -4) are blocked by these agents. Many MRSA strains display heterogeneous expression of resistance (HeR) against β-lactam antibiotics. The β-lactam-mediated homoresistant (HoR) phenotype is associated with both expression of themecAgene and activation of the LexA-RecA-mediated SOS response, a regulatory network induced in response to DNA damage. Ceftaroline (CPT) is the only FDA-approved cephalosporin targeting PBP2a. We investigated the mechanistic basis of CPT activity against HeR-MRSA strains, including a set of strains displaying an intermediate level of resistance to CPT. Mechanistically, we found that 1 exposure of HeR-MRSA to subinhibitory concentrations of CPT selected for the HoR derivative activated the SOS response and increased mutagenesis. Importantly, CPT-selected HoR cells remained susceptible to CPT while still being resistant to most β-lactams, and 2-CPT activity in HeR-MRSA resided in an attenuated induction ofmecAexpression in comparison to other β-lactams. In addition, 3-CPT intermediate-resistant strains displayed a significant increase in CPT-inducedmecAexpression accompanied by mutations in PBP2, which together may interfere with the complete repression by CPT of both PBP2a and PBP2a-PBP2 interactions and thus be a determining factor in the low level of CPT resistance in the absence ofmecAgene mutations. The present study provides mechanistic evidence that CPT represents an alternative therapeutic option for the treatment of heteroresistant MRSA strains.
Avibactam and Class C β-Lactamases: Mechanism of Inhibition, Conservation of the Binding Pocket, and Implications for Resistance
Authors: Lahiri S. D. , Johnstone M. R. , Ross P. L. , McLaughlin R. E. , Olivier N. B. , Alm R. A. 
Published: July 2014

ABSTRACT

Avibactam is a novel non-β-lactam β-lactamase inhibitor that inhibits a wide range of β-lactamases. These include class A, class C, and some class D enzymes, which erode the activity of β-lactam drugs in multidrug-resistant pathogens like
Pseudomonas aeruginosa
and
Enterobacteriaceae
spp. Avibactam is currently in clinical development in combination with the β-lactam antibiotics ceftazidime, ceftaroline fosamil, and aztreonam. Avibactam has the potential to be the first β-lactamase inhibitor that might provide activity against class C-mediated resistance, which represents a growing concern in both hospital- and community-acquired infections. Avibactam has an unusual mechanism of action: it is a covalent inhibitor that acts via ring opening, but in contrast to other currently used β-lactamase inhibitors, this reaction is reversible. Here, we present a high-resolution structure of avibactam bound to a class C β-lactamase, AmpC, from
P. aeruginosa
that provided insight into the mechanism of both acylation and recyclization in this enzyme class and highlighted the differences observed between class A and class C inhibition. Furthermore, variants resistant to avibactam that identified the residues important for inhibition were isolated. Finally, the structural information was used to predict effective inhibition by sequence analysis and functional studies of class C β-lactamases from a large and diverse set of contemporary clinical isolates (
P. aeruginosa
and several
Enterobacteriaceae
spp.) obtained from recent infections to understand any preexisting variability in the binding pocket that might affect inhibition by avibactam.
Revised Reference Broth Microdilution Method for Testing Telavancin: Effect on MIC Results and Correlation with Other Testing Methodologies
Authors: Farrell David J. , Mendes Rodrigo E. , Rhomberg Paul R. , Jones Ronald N. 
Published: July 2014

ABSTRACT

The reference broth microdilution (BMD) antimicrobial susceptibility testing method for telavancin was revised to include dimethyl sulfoxide (DMSO) as a solvent and diluent for frozen-form panel preparation, following the CLSI recommendations for water-insoluble agents. Polysorbate 80 (P-80) was also added to the test medium to minimize proven drug losses associated with binding to plastic surfaces. Four hundred sixty-two Gram-positive isolates, including a challenge set of organisms with reduced susceptibilities to comparator agents, were selected and tested using the revised method for telavancin, and the MIC results were compared with those tested by the previously established method and several Sensititre dry-form BMD panel formulations. The revised method provided MIC results 2- to 8-fold lower than the previous method when tested against staphylococci and enterococci, resulting in MIC
50
values of 0.03 to 0.06 μg/ml for staphylococci and 0.03 and 0.12 μg/ml for
Enterococcus faecium
and
Enterococcus faecalis
, respectively. Less-significant MIC decreases (1 to 2 log
2
dilution steps) were observed when testing streptococci in broth supplemented with blood, which showed similar MIC
50
values for both methods. However,
Streptococcus pneumoniae
had MIC
50
results of 0.008 and 0.03 μg/ml when tested by the revised and previous methods, respectively. Highest essential agreement rates (≥94.0%) were noted for one candidate dry-form panel formulation compared to the revised test. The revised BMD method provides lower MIC results for telavancin, especially when tested against staphylococci and enterococci. This is secondary to the use of DMSO for panel production and the presence of P-80, which ensure the proper telavancin testing concentration and result in a more accurate MIC determination. Moreover, earlier studies where the previous method was applied underestimated the
in vitro
drug potency.
Role for Streptococcal Collagen-Like Protein 1 in M1T1 Group A Streptococcus Resistance to Neutrophil Extracellular Traps
Authors: Döhrmann Simon , Anik Sabina , Olson Joshua , Anderson Ericka L. , Etesami Neelou , No Hyewon , Snipper Joshua , Nizet Victor , Okumura Cheryl Y. M. 
Published: July 2014

ABSTRACT

Streptococcal collagen-like protein 1 (Scl-1) is one of the most highly expressed proteins in the invasive M1T1 serotype group A
Streptococcus
(GAS), a globally disseminated clone associated with higher risk of severe invasive infections. Previous studies using recombinant Scl-1 protein suggested a role in cell attachment and binding and inhibition of serum proteins. Here, we studied the contribution of Scl-1 to the virulence of the M1T1 clone in the physiological context of the live bacterium by generating an isogenic strain lacking the
scl-1
gene. Upon subcutaneous infection in mice, wild-type bacteria induced larger lesions than the Δ
scl
mutant. However, loss of Scl-1 did not alter bacterial adherence to or invasion of skin keratinocytes. We found instead that Scl-1 plays a critical role in GAS resistance to human and murine phagocytic cells, allowing the bacteria to persist at the site of infection. Phenotypic analyses demonstrated that Scl-1 mediates bacterial survival in neutrophil extracellular traps (NETs) and protects GAS from antimicrobial peptides found within the NETs. Additionally, Scl-1 interferes with myeloperoxidase (MPO) release, a prerequisite for NET production, thereby suppressing NET formation. We conclude that Scl-1 is a virulence determinant in the M1T1 GAS clone, allowing GAS to subvert innate immune functions that are critical in clearing bacterial infections.
An Optimized, Synthetic DNA Vaccine Encoding the Toxin A and Toxin B Receptor Binding Domains of Clostridium difficile Induces Protective Antibody ResponsesIn Vivo
Authors: Baliban Scott M. , Michael Amanda , Shammassian Berje , Mudakha Shikata , Khan Amir S. , Cocklin Simon , Zentner Isaac , Latimer Brian P. , Bouillaut Laurent , Hunter Meredith , Marx Preston , Sardesai Niranjan Y. , Welles Seth L. , Jacobson Jeffrey M. , Weiner David B. , Kutzler Michele A. 
Published: July 2014

ABSTRACTClostridium difficile-associated disease (CDAD) constitutes a large majority of nosocomial diarrhea cases in industrialized nations and is mediated by the effects of two secreted toxins, toxin A (TcdA) and toxin B (TcdB). Patients who develop strong antitoxin antibody responses can clearC. difficileinfection and remain disease free. Key toxin-neutralizing epitopes have been found within the carboxy-terminal receptor binding domains (RBDs) of TcdA and TcdB, which has generated interest in developing the RBD as a viable vaccine target. While numerous platforms have been studied, very little data describes the potential of DNA vaccination against CDAD. Therefore, we created highly optimized plasmids encoding the RBDs from TcdA and TcdB in which any putativeN-linked glycosylation sites were altered. Mice and nonhuman primates were immunized intramuscularly, followed byin vivoelectroporation, and in these animal models, vaccination induced significant levels of both anti-RBD antibodies (blood and stool) and RBD-specific antibody-secreting cells. Further characterization revealed that sera from immunized mice and nonhuman primates could detect RBD protein from transfected cells, as well as neutralize purified toxins in anin vitrocytotoxicity assay. Mice that were immunized with plasmids or given nonhuman-primate sera were protected from a lethal challenge with purified TcdA and/or TcdB. Moreover, immunized mice were significantly protected when challenged withC. difficilespores from homologous (VPI 10463) and heterologous, epidemic (UK1) strains. These data demonstrate the robust immunogenicity and efficacy of a TcdA/B RBD-based DNA vaccine in preclinical models of acute toxin-associated and intragastric, spore-induced colonic disease.
Role of YpeB in Cortex Hydrolysis during Germination of Bacillus anthracis Spores
Authors: Bernhards Casey B. , Popham David L. 
Published: July 2014

ABSTRACT

The infectious agent of the disease anthrax is the spore of
Bacillus anthracis
. Bacterial spores are extremely resistant to environmental stresses, which greatly hinders spore decontamination efforts. The spore cortex, a thick layer of modified peptidoglycan, contributes to spore dormancy and resistance by maintaining the low water content of the spore core. The cortex is degraded by germination-specific lytic enzymes (GSLEs) during spore germination, rendering the cells vulnerable to common disinfection techniques. This study investigates the relationship between SleB, a GSLE in
B. anthracis
, and YpeB, a protein necessary for SleB stability and function. The results indicate that Δ
sleB
and Δ
ypeB
spores exhibit similar germination phenotypes and that the two proteins have a strict codependency for their incorporation into the dormant spore. In the absence of its partner protein, SleB or YpeB is proteolytically degraded soon after expression during sporulation, rather than escaping the developing spore. The three PepSY domains of YpeB were examined for their roles in the interaction with SleB. YpeB truncation mutants illustrate the necessity of a region beyond the first PepSY domain for SleB stability. Furthermore, site-directed mutagenesis of highly conserved residues within the PepSY domains resulted in germination defects corresponding to reduced levels of both SleB and YpeB in the mutant spores. These results identify residues involved in the stability of both proteins and reiterate their codependent relationship. It is hoped that the study of GSLEs and interacting proteins will lead to the use of GSLEs as targets for efficient activation of spore germination and facilitation of spore cleanup.
Systematic review on the primary and secondary reporting of the prevalence of ghostwriting in the medical literature
Authors: Stretton Serina 
Published: July 2014

BackgroundGhostwriting of industry-sponsored articles is unethical and is perceived to be common practice.ObjectiveTo systematically review how evidence for the prevalence of ghostwriting is reported in the medical literature.Data sourcesMEDLINE via PubMed 1966+, EMBASE 1966+, The Cochrane Library 1988+, Medical Writing 1998+, The American Medical Writers Association (AMWA) Journal 1986+, Council of Science Editors Annual Meetings 2007+, and the Peer Review Congress 1994+ were searched electronically (23 May 2013) using the search terms ghostwrit*, ghostauthor*, ghost AND writ*, ghost AND author*.Eligibility criteriaAll publication types were considered; only publications reporting a numerical estimate of possible ghostwriting prevalence were included.Data extractionTwo independent reviewers screened the publications; discrepancies were resolved by consensus. Data to be collected included a numerical estimate of the prevalence of possible ghostwriting (primary outcome measure), definitions of ghostwriting reported, source of the reported prevalence, publication type and year, study design and sample population.ResultsOf the 848 publications retrieved and screened for eligibility, 48 reported numerical estimates for the prevalence of possible ghostwriting. Sixteen primary publications reported findings from cross-sectional surveys or descriptive analyses of published articles; 32 secondary publications cited published or unpublished evidence. Estimates on the prevalence of possible ghostwriting in primary and secondary publications varied markedly. Primary estimates were not suitable for meta-analysis because of the various definitions of ghostwriting used, study designs and types of populations or samples. Secondary estimates were not always reported or cited correctly or appropriately.ConclusionsEvidence for the prevalence of ghostwriting in the medical literature is limited and can be outdated, misleading or mistaken. Researchers should not inflate estimates using non-standard definitions of ghostwriting nor conflate ghostwriting with other unethical authorship practices. Editors and peer reviewers should not accept articles that incorrectly cite or interpret primary publications that report the prevalence of ghostwriting.
Work outcomes of sickness absence related to mental disorders: a systematic literature review
Authors: Dewa Carolyn S , Loong Desmond , Bonato Sarah 
Published: July 2014

ObjectivesThe purpose of this systematic literature review is to examine the current state of knowledge regarding the return-to-work outcomes of sickness absences related to mental disorders that increase costs borne by employers. We address two questions: (1) Based on the existing literature, from the employer's perspective, what are the relevant economic return-to-work outcomes for sickness absences related to mental disorders? and (2) From the employer's economic perspective, are there gaps in knowledge about the relevant return-to-work outcomes for sickness absences related to mental disorders?SettingThe included studies used administrative data from either an employer, insurer or occupational healthcare provider.ParticipantsStudies included working adults between 18 and 65 years old who had a sickness absence related to a mental disorder.Primary and secondary outcome measuresThe studies considered two general return-to-work outcome categories: (1) outcomes focusing on return-to-work and (2) outcomes focusing on sickness absence recurrence.ResultsA total of 3820 unique citations were identified. Of these, 10 studies were identified whose quality ranged from good to excellent. Half of the identified studies came from one country. The studies considered two characteristics of sickness absence: (1) whether and how long it took for a worker to return-to-work and (2) sickness absence recurrence. None of the studies examined return-to-work outcomes related to work reintegration.ConclusionsThe existing literature suggests that along with the incidence of sickness absence related to mental disorders, the length of sickness absence episodes and sickness absence recurrence (ie, number and time between) should be areas of concern. However, there also seems to be gaps in the literature regarding the work reintegration process and its associated costs.
Generalized Almost Convergence and Core Theorems of Double Sequences
Authors: Mohiuddine S. A. , Alotaibi Abdullah 
Published: July 2014

The idea of[λ, μ]-almost convergence (briefly,F[λ, μ]-convergence) has been recently introduced and studied by Mohiuddine and Alotaibi (2014). In this paper first we define a norm onF[λ, μ]such that it is a Banach space and then we define and characterize those four-dimensional matrices which transformF[λ, μ]-convergence of double sequencesx=(xjk)intoF[λ, μ]-convergence. We also define aF[λ, μ]-core ofx=(xjk)and determine a Tauberian condition for core inclusions and core equivalence.
Row-Based Dual Vdd Assignment, for a Level Converter Free CSA Design and Its Near-Threshold Operation
Authors: Saha Dipankar , Chatterjee Aanan , Chatterjee Sayan , Sarkar C. K. 
Published: July 2014

Subthreshold circuit designs are very much popular for some of the ultra-low power applications, where the minimum energy consumption is the primary concern. But, due to the weak driving current, these circuits generally suffer from huge performance degradation. Therefore, in this paper, we primarily targeted analyzing the performance of a near-threshold circuit (NTC), which retains the excellent energy efficiency of the subthreshold design, while improving the performance to a certain extent. A modified row-based dual Vdd 4-operand carry save adder (CSA) design has been reported in the present work using 45 nm technology. Moreover, to find out the effectiveness of the near-threshold operation of the 4-operand CSA design, it has been compared with the other design styles. From the simulation results, obtained for the frequency of 20 MHz, we found that the proposed scheme of CSA design consumes 3.009 ×10-7 Watt of average power (Pavg), which is almost 90.9% lesser than that of the conventional CSA design, whereas, looking at the perspective of maximum delay at output, the proposed scheme of CSA design provides a fair 44.37% improvement, compared to that of the subthreshold CSA design.
Molecular Pathways: Connecting Fibrosis and Solid Tumor Metastasis
Authors: Cox Thomas R. , Erler Janine T. 
Published: July 2014

Abstract
Pathologic organ fibrosis is a condition that can affect all major tissues and is typically ascribed to the excessive accumulation of extracellular matrix components, predominantly collagens. It typically leads to compromise of organ function and subsequent organ failure, and it is estimated that 45% of deaths in the developed world are linked to fibrotic disease. Fibrosis and cancer are known to be inextricably linked; however, we are only just beginning to understand the common and overlapping molecular pathways between the two. Here, we discuss what is known about the intersection of fibrosis and cancer, with a focus on cancer metastasis, and highlight some of the exciting new potential clinical targets that are emerging from analysis of the molecular pathways associated with these two devastating diseases. Clin Cancer Res; 20(14); 3637–43. ©2014 AACR.