565 research outputs found

    Needle Electrode-Based Electromechanical Reshaping of Cartilage

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    Electromechanical reshaping (EMR) of cartilage provides an alternative to the classic surgical techniques of modifying the shape of facial cartilages. The original embodiment of EMR required surface electrodes to be in direct contact with the entire cartilage region being reshaped. This study evaluates the feasibility of using needle electrode systems for EMR of facial cartilage and evaluates the relationships between electrode configuration, voltage, and application time in effecting shape change. Flat rabbit nasal septal cartilage specimens were deformed by a jig into a 90° bend, while a constant electric voltage was applied to needle electrodes that were inserted into the cartilage. The electrode configuration, voltage (0–7.5 V), and application time (1–9 min) were varied systematically to create the most effective shape change. Electric current and temperature were measured during voltage application, and the resulting specimen shape was assessed in terms of retained bend angle. In order to demonstrate the clinical feasibility of EMR, the most effective and practical settings from the septal cartilage experimentation were used to reshape intact rabbit and pig ears ex vivo. Cell viability of the cartilage after EMR was determined using confocal microscopy in conjunction with a live/dead assay. Overall, cartilage reshaping increased with increased voltage and increased application time. For all electrode configurations and application times tested, heat generation was negligible (<1 °C) up to 6 V. At 6 V, with the most effective electrode configuration, the bend angle began to significantly increase after 2 min of application time and began to plateau above 5 min. As a function of voltage at 2 min of application time, significant reshaping occurred at and above 5 V, with no significant increase in the bend angle between 6 and 7.5 V. In conclusion, electromechanical reshaping of cartilage grafts and intact ears can be effectively performed with negligible temperature elevation and spatially limited cell injury using needle electrodes

    Serratamolide is a hemolytic factor produced by Serratia marcescens

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    Serratia marcescens is a common contaminant of contact lens cases and lenses. Hemolytic factors of S. marcescens contribute to the virulence of this opportunistic bacterial pathogen. We took advantage of an observed hyper-hemolytic phenotype of crp mutants to investigate mechanisms of hemolysis. A genetic screen revealed that swrW is necessary for the hyper-hemolysis phenotype of crp mutants. The swrW gene is required for biosynthesis of the biosurfactant serratamolide, previously shown to be a broad-spectrum antibiotic and to contribute to swarming motility. Multicopy expression of swrW or mutation of the hexS transcription factor gene, a known inhibitor of swrW expression, led to an increase in hemolysis. Surfactant zones and expression from an swrW-transcriptional reporter were elevated in a crp mutant compared to the wild type. Purified serratamolide was hemolytic to sheep and murine red blood cells and cytotoxic to human airway and corneal limbal epithelial cells in vitro. The swrW gene was found in the majority of contact lens isolates tested. Genetic and biochemical analysis implicate the biosurfactant serratamolide as a hemolysin. This novel hemolysin may contribute to irritation and infections associated with contact lens use. © 2012 Shanks et al

    Gender Differences in Publication Output: Towards an Unbiased Metric of Research Performance

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    We examined the publication records of a cohort of 168 life scientists in the field of ecology and evolutionary biology to assess gender differences in research performance. Clear discrepancies in publication rate between men and women appear very early in their careers and this has consequences for the subsequent citation of their work. We show that a recently proposed index designed to rank scientists fairly is in fact strongly biased against female researchers, and advocate a modified index to assess men and women on a more equitable basis

    The Florey Adelaide Male Ageing Study (FAMAS): Design, procedures & participants

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    <p>Abstract</p> <p>Background</p> <p>The Florey Adelaide Male Ageing Study (FAMAS) examines the reproductive, physical and psychological health, and health service utilisation of the ageing male in Australia. We describe the rationale for the study, the methods used participant response rates, representativeness and attrition to date.</p> <p>Methods</p> <p>FAMAS is a longitudinal study involving approximately 1200 randomly selected men, aged 35–80 years and living in the north – west regions of Adelaide. Respondents were excluded at screening if they were considered incapable of participating because of immobility, language, or an inability to undertake the study procedures. Following a telephone call to randomly selected households, eligible participants were invited to attend a baseline clinic measuring a variety of biomedical and socio-demographic factors. Beginning in 2002, these clinics are scheduled to reoccur every five years. Follow-up questionnaires are completed annually. Participants are also invited to participate in sub-studies with selected collaborators.</p> <p>Results</p> <p>Of those eligible to participate, 45.1% ultimately attended a clinic. Non-responders were more likely to live alone, be current smokers, have a higheevalence of self-reported diabetes and stroke, and lower levels of hypercholesterolemia. Comparisons with the Census 2001 data showed that participants matched the population for most key demographics, although younger groups and never married men were under-represented and elderly participants were over-represented. To date, there has been an annual loss to follow-up of just over 1%.</p> <p>Conclusion</p> <p>FAMAS allows a detailed investigation into the effects of bio-psychosocial and behavioural factors on the health and ageing of a largely representative group of Australian men.</p

    In silico approach to screen compounds active against parasitic nematodes of major socio-economic importance

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    Infections due to parasitic nematodes are common causes of morbidity and fatality around the world especially in developing nations. At present however, there are only three major classes of drugs for treating human nematode infections. Additionally the scientific knowledge on the mechanism of action and the reason for the resistance to these drugs is poorly understood. Commercial incentives to design drugs that are endemic to developing countries are limited therefore, virtual screening in academic settings can play a vital role is discovering novel drugs useful against neglected diseases. In this study we propose to build robust machine learning model to classify and screen compounds active against parasitic nematodes.A set of compounds active against parasitic nematodes were collated from various literature sources including PubChem while the inactive set was derived from DrugBank database. The support vector machine (SVM) algorithm was used for model development, and stratified ten-fold cross validation was used to evaluate the performance of each classifier. The best results were obtained using the radial basis function kernel. The SVM method achieved an accuracy of 81.79% on an independent test set. Using the model developed above, we were able to indentify novel compounds with potential anthelmintic activity.In this study, we successfully present the SVM approach for predicting compounds active against parasitic nematodes which suggests the effectiveness of computational approaches for antiparasitic drug discovery. Although, the accuracy obtained is lower than the previously reported in a similar study but we believe that our model is more robust because we intentionally employed stringent criteria to select inactive dataset thus making it difficult for the model to classify compounds. The method presents an alternative approach to the existing traditional methods and may be useful for predicting hitherto novel anthelmintic compounds.12 page(s

    Horizontal DNA transfer mechanisms of bacteria as weapons of intragenomic conflict

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    Horizontal DNA transfer (HDT) is a pervasive mechanism of diversification in many microbial species, but its primary evolutionary role remains controversial. Much recent research has emphasised the adaptive benefit of acquiring novel DNA, but here we argue instead that intragenomic conflict provides a coherent framework for understanding the evolutionary origins of HDT. To test this hypothesis, we developed a mathematical model of a clonally descended bacterial population undergoing HDT through transmission of mobile genetic elements (MGEs) and genetic transformation. Including the known bias of transformation toward the acquisition of shorter alleles into the model suggested it could be an effective means of counteracting the spread of MGEs. Both constitutive and transient competence for transformation were found to provide an effective defence against parasitic MGEs; transient competence could also be effective at permitting the selective spread of MGEs conferring a benefit on their host bacterium. The coordination of transient competence with cell-cell killing, observed in multiple species, was found to result in synergistic blocking of MGE transmission through releasing genomic DNA for homologous recombination while simultaneously reducing horizontal MGE spread by lowering the local cell density. To evaluate the feasibility of the functions suggested by the modelling analysis, we analysed genomic data from longitudinal sampling of individuals carrying Streptococcus pneumoniae. This revealed the frequent within-host coexistence of clonally descended cells that differed in their MGE infection status, a necessary condition for the proposed mechanism to operate. Additionally, we found multiple examples of MGEs inhibiting transformation through integrative disruption of genes encoding the competence machinery across many species, providing evidence of an ongoing "arms race." Reduced rates of transformation have also been observed in cells infected by MGEs that reduce the concentration of extracellular DNA through secretion of DNases. Simulations predicted that either mechanism of limiting transformation would benefit individual MGEs, but also that this tactic's effectiveness was limited by competition with other MGEs coinfecting the same cell. A further observed behaviour we hypothesised to reduce elimination by transformation was MGE activation when cells become competent. Our model predicted that this response was effective at counteracting transformation independently of competing MGEs. Therefore, this framework is able to explain both common properties of MGEs, and the seemingly paradoxical bacterial behaviours of transformation and cell-cell killing within clonally related populations, as the consequences of intragenomic conflict between self-replicating chromosomes and parasitic MGEs. The antagonistic nature of the different mechanisms of HDT over short timescales means their contribution to bacterial evolution is likely to be substantially greater than previously appreciated

    High resolution melting analysis for rapid and sensitive EGFR and KRAS mutation detection in formalin fixed paraffin embedded biopsies

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    <p>Abstract</p> <p>Background</p> <p>Epithelial growth factor receptor (<it>EGFR</it>) and <it>KRAS </it>mutation status have been reported as predictive markers of tumour response to <it>EGFR </it>inhibitors. High resolution melting (HRM) analysis is an attractive screening method for the detection of both known and unknown mutations as it is rapid to set up and inexpensive to operate. However, up to now it has not been fully validated for clinical samples when formalin-fixed paraffin-embedded (FFPE) sections are the only material available for analysis as is often the case.</p> <p>Methods</p> <p>We developed HRM assays, optimised for the analysis of FFPE tissues, to detect somatic mutations in <it>EGFR </it>exons 18 to 21. We performed HRM analysis for <it>EGFR </it>and <it>KRAS </it>on DNA isolated from a panel of 200 non-small cell lung cancer (NSCLC) samples derived from FFPE tissues.</p> <p>Results</p> <p>All 73 samples that harboured <it>EGFR </it>mutations previously identified by sequencing were correctly identified by HRM, giving 100% sensitivity with 90% specificity. Twenty five samples were positive by HRM for <it>KRAS </it>exon 2 mutations. Sequencing of these 25 samples confirmed the presence of codon 12 or 13 mutations. <it>EGFR </it>and <it>KRAS </it>mutations were mutually exclusive.</p> <p>Conclusion</p> <p>This is the first extensive validation of HRM on FFPE samples using the detection of <it>EGFR </it>exons 18 to 21 mutations and <it>KRAS </it>exon 2 mutations. Our results demonstrate the utility of HRM analysis for the detection of somatic <it>EGFR </it>and <it>KRAS </it>mutations in clinical samples and for screening of samples prior to sequencing. We estimate that by using HRM as a screening method, the number of sequencing reactions needed for <it>EGFR </it>and <it>KRAS </it>mutation detection can be reduced by up to 80% and thus result in substantial time and cost savings.</p

    Caenorhabditis elegans: a model to monitor bacterial air quality

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    <p>Abstract</p> <p>Background</p> <p>Low environmental air quality is a significant cause of mortality and morbidity and this question is now emerging as a main concern of governmental authorities. Airborne pollution results from the combination of chemicals, fine particles, and micro-organisms quantitatively or qualitatively dangerous for health or for the environment. Increasing regulations and limitations for outdoor air quality have been decreed in regards to chemicals and particles contrary to micro-organisms. Indeed, pertinent and reliable tests to evaluate this biohazard are scarce. In this work, our purpose was to evaluate the <it>Caenorhaditis elegans </it>killing test, a model considered as an equivalent to the mouse acute toxicity test in pharmaceutical industry, in order to monitor air bacterial quality.</p> <p>Findings</p> <p>The present study investigates the bacterial population in dust clouds generated during crop ship loading in harbor installations (Rouen harbor, Normandy, France). With a biocollector, airborne bacteria were impacted onto the surface of agar medium. After incubation, a replicate of the colonies on a fresh agar medium was done using a velvet. All the replicated colonies were pooled creating the "Total Air Sample". Meanwhile, all the colonies on the original plate were isolated. Among which, five representative bacterial strains were chosen. The virulence of these representatives was compared to that of the "Total Air Sample" using the <it>Caenorhaditis elegans </it>killing test. The survival kinetic of nematodes fed with the "Total Air Sample" is consistent with the kinetics obtained using the five different representatives strains.</p> <p>Conclusions</p> <p>Bacterial air quality can now be monitored in a one shot test using the <it>Caenorhaditis elegans </it>killing test.</p

    Treatment of substance abuse in dual diagnosis

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    Interventions for substance use–related problems are limited for individuals with intellectual disability (ID). This is problematic, as the lack of interventions can lead to substance use initiation, progression of substance use into substance use disorder, poorer outcomes of treatment, and stigmatization of individuals with dual diagnosis. Additionally, staff who work with individuals with ID and addiction treatment lack resources to effectively help substance use in individuals with ID. Nevertheless, there has been an increase in studies assessing the feasibility and outcomes of interventions for substance use and abuse in individuals with ID. This chapter reviews psychological and pharmacological interventions for individuals with dual diagnosis of substance abuse and ID
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