1,720,959 research outputs found
Repurposing High-Throughput Screening Reveals Unconventional Drugs with Antimicrobial and Antibiofilm Potential Against Methicillin-Resistant Staphylococcus aureus from a Cystic Fibrosis Patient
Full text linkBackground/Objectives: Antibiotic therapy faces challenges from rising acquired and biofilm-related antibiotic resistance rates. High resistance levels to commonly used antibiotics have been observed in methicillin-resistant Staphylococcus aureus (MRSA) strains among cystic fibrosis (CF) patients, indicating an urgent need for new antibacterial agents. This study aimed to identify potential novel therapeutics with antibacterial and antibiofilm activities against an MRSA CF strain by screening, for the first time, the Drug Repurposing Compound Library (MedChem Express). Methods/Results: Among the 3386 compounds, a high-throughput screening-based spectrophotometric approach identified 2439 (72%), 654 (19.3%), and 426 (12.6%) drugs active against planktonic cells, biofilm formation, and preformed biofilm, respectively, although to different extents. The most active hits were 193 (5.7%), against planktonic cells, causing a 100% growth inhibition; 5 (0.14%), with excellent activity against biofilm formation (i.e., reduction ≥ 90%); and 4, showing high activity (i.e., 60% ≤ biofilm reduction < 90%) against preformed biofilms. The potential hits belonged to several primary research areas, with “cancer” being the most prevalent. After performing a literature review to identify other, already published biological properties that could be relevant to the CF lung environment (i.e., activity against other CF pathogens, and anti-inflammatory and anti-virulence potential), the most interesting hits were the following: 5-(N,N-Hexamethylene)-amiloride (diuretic), Toremifene (anticancer), Zafirlukast (antiasthmatic), Fenretide (anticancer), and Montelukast (antiasthmatic) against planktonic S. aureus cells; Hemin against biofilm formation; and Heparin, Clemastine (antihistaminic), and Bromfenac (nonsteroidal anti-inflammatory) against established biofilms. Conclusions: These findings warrant further in vitro and in vivo studies to confirm the potential of repurposing these compounds for managing lung infections caused by S. aureus in CF patients
Impact of Growth Conditions on High-Throughput Identification of Repurposing Drugs for <i>Pseudomonas aeruginosa</i> Cystic Fibrosis Lung Infections
No full textPseudomonas aeruginosa lung infections in cystic fibrosis (CF) patients represent a therapeutic challenge due to antibiotic resistance. Repurposing existing drugs is a promising approach for identifying new antimicrobials. A crucial factor in successful drug repurposing is using assay conditions that mirror the site of infection. Here, the impact of growth conditions on the anti-P. aeruginosa activity of a library of 3386 compounds was evaluated. To this, after 24 h exposure, the survival rate of CF P. aeruginosa RP73 planktonic cells was assessed spectrophotometrically under “CF-like” (artificial CF sputum, pH 6.8, 5% CO2) and enriched (Tryptone Soya Broth, pH 7.2, and aerobiosis) conditions. Among non-antibiotic compounds (n = 3127), 13.4% were active regardless of growth conditions, although only 3.2% had comparable activity; 4% and 6.2% were more active under CF-like or enriched conditions, respectively. Interestingly, 22.1% and 26.6% were active exclusively under CF-like and enriched conditions, respectively. Notably, 7 and 12 hits caused 100% killing under CF-like and enriched conditions, respectively. Among antibiotics (n = 234), 42.3% were active under both conditions, although only 18.4% showed comparable activity; 9.4% and 14.5% were more active under CF-like and enriched conditions, respectively. Interestingly, 23% and 16.6% were active exclusively under CF-like and enriched conditions, respectively. Sulphonamides showed higher activity under CF-like conditions, whereas tetracyclines, fluoroquinolones, and macrolides were more effective under enriched settings. Our findings indicated that growth conditions significantly affect the anti-P. aeruginosa activity of antibiotics and non-antibiotic drugs. Consequently, repurposing studies and susceptibility tests should be performed under physicochemical conditions that the pathogen tackles at the site of infection
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
Cell-free supernatants from Lactobacillus strains exert antibacterial, antibiofilm, and antivirulence activity against Pseudomonas aeruginosa from cystic fibrosis patients
No full text: Chronic lung infections caused by Pseudomonas aeruginosa play a significant role in the mortality and morbidity of cystic fibrosis (CF) patients. The widespread bacterial resistance to conventional antimicrobials demands identifying new strategies to complement or replace current antibiotic therapies. In this study, we evaluated the antibacterial, antibiofilm, and antivirulence properties of cell-free supernatants (CFS) from several Lactobacillus probiotic strains against P. aeruginosa isolated from the sputum of CF patients. A strong and fast antibacterial activity of CFS from different strains of lactobacilli was observed at acidic pH towards P. aeruginosa, both in planktonic and biofilm mode of growth, in conditions mimicking CF lung. Interestingly, although when adjusted at pH 6.0, CFS lost most of their antibacterial potential, they retained some antivirulence activity towards P. aeruginosa, largely dependent on the dose, exposure time, and the Lactobacillus-P. aeruginosa strain combination. In vivo testing in the invertebrate Galleria mellonella model disclosed the lack of toxicity of acidic CFS and their ability to prevent P. aeruginosa infection. For the first time, the results revealed lactobacilli postbiotic activities in the context of the pulmonary environment, pointing to innovative postbiotics' uses in anti-infective therapy
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
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
- …
