1,720,960 research outputs found
Novel synthetic antimicrobial peptides with In-Vivo and In-Vitro activity against Streptococcus Pneumoniae / Le Cheng Foh
Full text linkStreptococcus pneumoniae is a major human bacterial pathogen causing life threatening diseases such as meningitis, bacteremia, and pneumonia. Younger children are heavily affected by pneumococcal infections. Pneumococcal conjugate vaccines (PCVs) are serotype-specific and require data on local serotype distribution to predict the coverage of PCVs. Moreover, the escalating incidence of antibiotic resistance S. pneumoniae has prompted the development of novel antimicrobial agents. Antimicrobial peptides (AMPs) have been increasingly recognized as the new generation antibiotics due to their potent antimicrobial activity. In this study, we sought to design novel synthetic antimicrobial peptides against S. pneumoniae and determine the in vitro and in vivo activities of the peptides.
A collection of 151 pneumococcal clinical isolates from University of Malaya Medical Centre, Kuala Lumpur were serotyped using multiplex PCR and the penicillin susceptibility was determined using agar dilution method. Biocomputational tools were employed to design the peptides based on the publicly available AMPs. The designed AMPs were tested for minimum inhibitory concentration, bacterial killing kinetics, and synergism activity. Broad spectrum antibacterial activity against eight common bacterial pathogens was also determined. Morphological changes of pneumococcal cells were observed using transmission electron microscopy. The designed AMPs were also assessed for hemolytic and cell cytotoxicity. In vivo therapeutic efficacy and acute toxicity of the peptides were assessed using an in-house mouse model.
Serotypes 19F and 23F were the two prevailing serotypes among Malaysian population with serotype 19F significantly associated with penicillin resistance. Penicillin-nonsusceptible S. pneumoniae constituted half (50.3%) of the total isolates. and as high as 87.5% of penicillin-resistant S. pneumoniae (PRSP) were PCV7-vaccine serotypes. From the peptide designs, antimicrobial testing showed that the five hybrid
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peptides (DM1-5) exhibited strong antipneumococcal activity irrespective of penicillin susceptibility of the isolates. These isolates included the highly prevalent serotype 19F. The pneumococcal killing rates were higher than penicillin by 38 – 64%, 54 – 76%, and 30 – 57% for penicillin-resistant, intermediate, and susceptible isolates at 30 min posttreatment, respectively. The DMs and other peptides produced synergism in combination with penicillin against S. pneumoniae and displayed broad spectrum antibacterial activities. The DMs induced overwhelming cellular damages leading to cell death. Besides, DMs exhibited low hemolytic activity (HC50 >250 μg/ml) with varying degrees of cell cytotoxicity against NL20 and A549 cell lines. Notably, DM3 (40 mg/kg) given via intraperitoneal route at 12 hrs interval for three dosing regimens protected 50% of mice from lethal systemic infection by a PRSP strain. Interestingly, combination therapy using low doses (10mg/kg and 20mg/kg) DM3 and penicillin showed therapeutic synergism with 20-50% higher survival rates than the sum of the standalone treatments. Complete protection (100%) was achieved with DM3 (20 mg/kg) – penicillin (20 mg/kg) combination.
Pneumococcal infections continue to affect humans and antibiotic-resistant S. pneumoniae would further complicate the treatment outcomes. The current study demonstrated that AMPs represent the promising new generation antibiotics as standalone therapeutics or in combination with conventional antibiotics. Novel designed AMPs candidates can be designed following careful designing approaches to generate peptides with high therapeutic potential to be further developed into clinically useful antibiotics
The epidemiology of pneumococcal carriage and infections in Malaysia
No full textIn Malaysia, various aspects of the epidemiology of pneumococcal carriage and disease remain largely unclear due to the lack of supporting data. Although a number of relevant studies have been documented, their individual discrete findings are not sufficient to inform experts on pneumococcal epidemiology at a national level. Therefore, in this review we aim to bring together and systematically evaluate the key information regarding pneumococcal disease epidemiology in Malaysia and provide a comprehensive overview of the data. Major aspects discussed include pneumococcal carriage, disease incidence and prevalence, age factors, invasiveness of pneumococci, serotypes, molecular epidemiology and antibiotic susceptibility. Penicillin resistance is increasingly prevalent and studies suggest that the majority of pneumococcal serotypes causing pneumococcal disease in Malaysia are covered by currently available conjugate vaccines. Continued surveillance is needed to provide a better understanding of pneumococcal epidemiology in Malaysia
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
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
Serotype distribution of invasive, non-invasive and carried Streptococcus pneumoniae in Malaysia: a meta-analysis
Full text linkBackground: pneumococcal pneumonia is the leading cause of under-five mortality globally. The surveillance of pneumococcal serotypes is therefore vital for informing pneumococcal vaccination policy and programmes. Pneumococcal conjugate vaccines (PCVs) have been available as an option in the private healthcare setting and beginning December 2020, PCV10 was incorporated as part of routine national immunisation programme (NIP) in Malaysia. We searched existing literature on pneumococcal serotype distribution across Malaysia to provide an overall view of this distribution before the implementation of PCV10.Methods: online databases (PubMed, Ovid MEDLINE and Scopus), reference lists of articles identified, and grey literature (Malaysian Ministry of Health website, WHO website) were systematically searched for relevant literature on pneumococcal serotype distribution across Malaysia up to 10th November 2020. No lower date limit was set to maximise the number of target reports returned. Results of serotypes were split by age categories, including ≤5 years, > 5 years and unreported for those that did not specify.Results: the search returned 18 relevant results, with a total of 2040 isolates. The most common serotypes across all disease types were 19F (n = 313, 15.3% [95%CI: 13.8-17.0]), 23F (n = 166, 8.1% [95%CI: 7.0-9.4]), 14 (n = 166, 8.1% [95%CI: 7.0-9.4]), 6B (n = 163, 8.0% [95%CI: 6.9-9.2]) and 19A (n = 138, 6.8% [95%CI: 5.8-7.9]).Conclusion: four of the most common serotypes across all isolate sources in Malaysia are covered by PCV10, while PCV13 provides greater serotype coverage in comparison to PCV10. There is still a need for surveillance studies, particularly those investigating serotypes in children under 5 years of age, to monitor vaccine effectiveness and pneumococcal population dynamic following implementation of PCV10 into routine immunisation.</p
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
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