1,720,982 research outputs found
Pyridine-2-thiol 1-oxide derivatives and their use for treatment of mammalian infections caused by Mycobacterium or fungi
No full textThe present invention relates to pyridine-2-thiol 1-oxide derivatives and their use as antimicrobial agents in infectious diseases of mammals (humans and animals) caused by fungi or bacteria, in particular belonging to the Mycobacteriaceae family, especially diseases caused by Mycobacterium abscessus or Mycobacterium tuberculosis
A pharmaceutical combination for the treatment of lung infections in subjects with cystic fibrosis
No full textThe present invention relates to a combination therapy for treating infections caused by Mycobacterium abscessus and other microbial pathogens in subjects with cystic fibrosis comprising the sequential, simultaneous or separate administration of pyridine-2-thiol 1-oxides or their salts and cystic fibrosis transmembrane conductance regulator (CFTR) modulators
Nitric oxide-releasing compounds for the treatment of lung infections
No full textThe spread of acquired drug resistance and of microorganisms naturally resistant to antibiotics is a major threat to global health, leading to an urgent need for novel antimicrobial compounds. Exogenous nitric oxide (NO) represents an attractive and promising antimicrobial approach, showing both bactericidal and biofilm dispersal activities. Numerous studies have been performed to develop NO donor scaffolds, including small molecules, macromolecular compounds, nanoparticles (NPs), and polymeric materials. This approach has resulted in successful outcomes, with some NO-releasing compounds entering clinical practice. In this review, we highlight the importance of this strategy, with a focus on lung infections
Azole resistance in Mycobacterium tuberculosis is mediated by the MmpS5-MmpL5 efflux system.
No full textTuberculosis (TB) remains the leading cause of mortality due to a bacterial pathogen, Mycobacterium tuberculosis. Moreover, the recent isolation of M. tuberculosis strains resistant to both first- and second-line antitubercular drugs (XDR-TB) threatens to make the treatment of this disease extremely difficult and becoming a threat to public health worldwide. Recently, it has been shown that azoles are potent inhibitors of mycobacterial cell growth and have antitubercular activity in mice, thus favoring the hypothesis that these drugs may constitute a novel strategy against tuberculosis disease. To investigate the mechanisms of resistance to azoles in mycobacteria, we isolated and characterized several spontaneous azoles resistant mutants from M. tuberculosis and Mycobacterium bovis BCG. All the analyzed resistant mutants exhibited both increased econazole efflux and increased transcription of mmpS5-mmpL5 genes, encoding a hypothetical efflux system belonging to the resistance-nodulation-division (RND) family of transporters. We found that the up-regulation of mmpS5-mmpL5 genes was linked to mutations either in the Rv0678 gene, hypothesized to be involved in the transcriptional regulation of this efflux system, or in its putative promoter/operator region
In vitro Study of Bedaquiline Resistance in Mycobacterium tuberculosis Multi-Drug Resistant Clinical Isolates.
Full text linkTuberculosis (TB) is one of the major causes of death related to antimicrobial resistance worldwide because of the spread of Mycobacterium tuberculosis multi- and extensively drug resistant (multi-drug resistant (MDR) and extensively drug-resistant (XDR), respectively) clinical isolates. To fight MDR and XDR tuberculosis, three new antitubercular drugs, bedaquiline (BDQ), delamanid, and pretomanid were approved for use in clinical setting. Unfortunately, BDQ quickly acquired two main mechanisms of resistance, consisting in mutations in either atpE gene, encoding the target, or in Rv0678, coding for the repressor of the MmpS5-MmpL5 efflux pump. To better understand the spreading of BDQ resistance in MDR- and XDR-TB, in vitro studies could be a valuable tool. To this aim, in this work an in vitro generation of M. tuberculosis mutants resistant to BDQ was performed starting from two MDR clinical isolates as parental cultures. The two M. tuberculosis MDR clinical isolates were firstly characterized by whole genome sequencing, finding the main mutations responsible for their MDR phenotype. Furthermore, several M. tuberculosis BDQ resistant mutants were isolated by both MDR strains, harboring mutations in both atpE and Rv0678 genes. These BDQ resistant mutants were further characterized by studying their growth rate that could be related to their spreading in clinical settings. Finally, we also constructed a data sheet including the mutations associated with BDQ resistance that could be useful for the early detection of BDQ-resistance in MDR/XDR patients with the purpose of a better management of antibiotic resistance in clinical settings
Mycobacterium abscessus, an Emerging and Worrisome Pathogen among Cystic Fibrosis Patients.
No full textNontuberculous mycobacteria (NTM) have recently emerged as important pathogens among cystic fibrosis (CF) patients worldwide. Mycobacterium abscessus is becoming the most worrisome NTM in this cohort of patients and recent findings clarified why this pathogen is so prone to this disease. M. abscessus drug therapy takes up to 2 years and its failure causes an accelerated lung function decline. The M. abscessus colonization of lung alveoli begins with smooth strains producing glycopeptidolipids and biofilm, whilst in the invasive infection, "rough" mutants are responsible for the production of trehalose dimycolate, and consequently, cording formation. Human-to-human M. abscessus transmission was demonstrated among geographically separated CF patients by whole-genome sequencing of clinical isolates worldwide. Using a M. abscessus infected CF zebrafish model, it was demonstrated that CFTR (cystic fibrosis transmembrane conductance regulator) dysfunction seems to have a specific role in the immune control of M. abscessus infections only. This pathogen is also intrinsically resistant to many drugs, thanks to its physiology and to the acquisition of new mechanisms of drug resistance. Few new compounds or drug formulations active against M. abscessus are present in preclinical and clinical development, but recently alternative strategies have been investigated, such as phage therapy and the use of β-lactamase inhibitors
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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