1,720,974 research outputs found
Decontamination of prions, prion-associated amyloid and inefectivity from surgical stainless steel - implications for the risk of iatrogenic transmission of CJD
No full textThe physicochemical nature of the infectious agent in prion diseases creates asignificant challenge for decontamination services. It has been shown to be both resistant tostandard methods of decontamination, used to inactivate viruses and bacteria, and to associateavidly with surgical stainless steel. Moreover, the pathophysiology of the variant, iatrogenicand sporadic forms of Creutzfeldt-Jakob Disease (CJD) suggests deposition of the infectiousagent across a wide range of extraneural, lymphoid tissues, as well as in the skeletal muscleand blood. Coupled with the potential for asymptomatic carriers, there is a significant risk ofiatrogenic transmission of CJD through both neurosurgical procedures and standard surgery.This PhD study was undertaken in order to improve methods of instrumentdecontamination and to evaluate prion detection techniques and their applicability for theassessment of prion inactivation and removal. The project has provided relevant, criticalassessment of hospital decontamination procedures, in addition to guidance on how workingprotocols should be improved to provide a cleaner and safer end product for the patient.Moreover, laboratory studies have been performed to evaluate current methods of priondecontamination in the context of hospital procedures for instrument reprocessing. Challengesfaced by sterile service departments, such as soil drying and surface degradation, have beenaddressed and their impact on the risk of iatrogenic transmission of prions has beeninvestigated. Critically, the use of a fluorescent amyloid fluorophore for the detection of prionassociatedamyloid as a marker for disease permitted the investigation of the role of amyloidin infectious disease under denaturing conditions. Correlation of this detection technique withthe identification of PrPres by Western blot and infectious disease suggested that, whilstfluorescent detection of prion-associated amyloid was more sensitive than Western blot, PrPresdetection was more specific relative to infectivity. Improved fluorophores, with greatersensitivity, have been evaluated which will enhance in situ detection of prions in the future
Targeting biofilms: Current and prospective therapeutics
No full textBiofilm formation is now recognized as a key virulence factor for a wide range of chronic microbial infections. While it has been well known for decades that bacteria and fungi in biofilms become highly tolerant of antibiotics, the development of effective therapeutics has lagged behind our growing understanding of biofilm biology. The multifactorial nature of biofilm development and drug tolerance imposes significant challenges to conventional antimicrobials, and indicates the need for multi-targeted or combinatorial therapies. In light of the discrepancy between the explosion of papers presenting multitude of methods to control biofilms and the sparsity of biofilm specific treatments available to the clinician, in this review, we focus on current therapeutic strategies and those in development for the treatment of biofilm infections, which target vital structure-function traits and drug tolerance mechanisms, including the extracellular matrix and dormant cells. We emphasize strategies that are supported by in vivo or ex vivo studies, highlight emerging anti-biofilm technologies, and provide a rationale for multi-targeted therapies aimed at disrupting the complex biofilm microenvironment
A novel application of Gini coefficient for the quantitative measurement of bacterial aggregation
No full textNon-surface attached bacterial aggregates are frequently found in clinical settings associated with chronic infections. Current methods quantifying the extent to which a suspended bacterial population is aggregated mainly rely on: (1) cell size distribution curves that are difficult to be compared numerically among large-scale samples; (2) the average size/proportion of aggregates in a population that do not specify the aggregation patterns. Here we introduce a novel application of Gini coefficient, herein named Aggregation Coefficient (AC), to quantify the aggregation levels of cystic fibrosis Pseudomonas aeruginosa (CF-PA) isolates in vitro using 3D micrographs, Fiji and MATLAB. Different aggregation patterns of five strains were compared statistically using the numerical AC indexes, which correlated well with the size distribution curves plotted by different biovolumes of aggregates. To test the sensitivity of AC, aggregates of the same strains were treated with nitric oxide (NO), a dispersal agent that reduces the biomass of surface attached biofilms. Strains unresponsive to NO were reflected by comparable AC indexes, while those undergoing dispersal showed a significant reduction in AC index, mirroring the changes in average aggregate sizes and proportions. Therefore, AC provides simpler and more descriptive numerical outputs for measuring different aggregation patterns compared to current approaches
Comparing PMMA and calcium sulfate as carriers for the local delivery of antibiotics to infected surgical sites
No full textAntibiotic-loaded bone cement is a primary option for treatment of orthopedic infections. Poly(methyl methacrylate) (PMMA) is a widely used cement that, when loaded with antibiotics in spacer or bead form, has been shown to reduce infection rates. However, PMMA is not resorbable and requires a second surgery for removal, while also acting as a potential foreign body for bacterial colonization. Alternatively, resorbable bone cements, such as calcium sulfate, have been proposed and present the advantage of being completely reabsorbed. It is unknown whether the antibiotic elution characteristics of absorbable bone cements are similar to PMMA. This study (1) characterized antibiotic elution from synthetic, highly purified calcium sulfate cement beads of varying sizes against pathogenic bacteria both in liquid culture and seeded on agar plates, (2) tested calcium sulfate beads against PMMA beads loaded with the same antibiotics, and (3) analyzed the structural differences between how PMMA and calcium sulfate bind to antibiotics. In every assay, the calcium sulfate beads performed as well as, or better than, the PMMA beads in inhibition of bacterial growth and elution of vancomycin in vitro with complete elution observed from calcium sulfate within three days. These data suggest that calcium sulfate, functions, as well as PMMA in the patient setting for infection control
Antibiofilm efficacy of antibiotic-loaded synthetic calcium sulphate beads in a P. aeruginosa/S. aureus co-culture model for prosthetic infections
No full textBacterial biofilms play a key role in prosthetic infection (PI) pathogenesis. Establishment of the biofilm phenotype confers the bacteria with significant tolerance to systemic antibiotics and the host immune system meaning thorough debridement and prosthesis removal often remain the only possible course of treatment. Protection of the prosthesis and dead-space management may be achieved through the use of antibiotic loaded cements and beads to release high concentrations of antibiotics at the surgical site. The antibacterial and antibiofilm efficacy of these materials is poorly understood in the context of mixed species models, such as are often encountered clinically
Dataset: Proteomic response of S. aureus to HT61
No full textDataset supports: Frapwell, C.J. et al (2020). Antimicrobial activity of the quinoline derivative HT61 against Staphylococcus aureus biofilms. Antimicrobial Agents and Chemotherapy.
Data set containing mass spectrometry results for S. aureus UAMS-1 planktonic and biofilm cultures, before and after treatment with HT61.</span
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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