1,721,058 research outputs found
Fungal Drug Resistance and Pharmacologic Considerations of Dosing Newer Antifungal Therapies
No full textRecent advances in hematopoietic cell transplantation and a broadening array of salvage chemotherapy options have extended the survival of patients with hematological cancers, but can result in prolonged periods of immunosuppression and susceptibility to invasive fungal infections. Among these high-risk patient populations, systemic antifungal therapy is administered episodically or sometimes continuously for months or even years, increasing concerns for the development of antifungal resistance. As newer triazoles (voriconazole and posaconazole) and echinocandins (anidulafungin, caspofungin, and micafungin) have supplanted amphotericin B formulations as the preferred antifungal therapies for primary and secondary prophylaxis, pharmacokinetic variability inherent to the triazoles as well as emerging patterns of intrinsic and acquired antifungal resistance are becoming increasingly important factors in the long-term management of invasive fungal infections. In this chapter, we review recent data concerning antifungal drug resistance for these newer azoles and echinocandins, as well as key considerations in drug dosing
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
The Influence of Aspergillus fumigatus Fatty Acid Oxygenases PpoA and PpoC on Caspofungin Susceptibility
Get PDFAspergillus fumigatus can cause invasive pulmonary aspergillosis (IPA). Fungicidal azoles and fungistatic caspofungin (CAS) are the first- and second-line therapies, respectively, used to treat IPA. Treatment of A. fumigatus with CAS or micafungin induces the production of the oxylipin 5,8-diHODE by the fungal oxygenase PpoA. For this article, we investigated the influence of ppo genes, which encode the fatty acid oxygenases responsible for oxylipin biosynthesis, on CAS tolerance. The influence of PpoA and PpoC on CAS tolerance is mediated by MpkA phosphorylation and protein kinase A (PKA) activity. RNAseq transcriptional profiling and the label-free quantitative proteomics of the ppoA and ppoC mutants showed that differentially expressed genes and proteins are related to secondary metabolites and carbohydrate metabolism. We also characterized two clinical isolates, CM7555 and IFM61407, which decrease and increase susceptibility to CAS, respectively. CM7555 does not exhibit increased oxylipin production in the presence of CAS but oxylipin induction upon CAS exposure is increased in IFM61407, suggesting that oxylipins are not the only mechanism involved in CAS tolerance in these isolates. Upon CAS exposure, CM7555 has higher MpkA phosphorylation and PKA activity than IFM61407. Our results reveal the different aspects and genetic determinants involved in A. fumigatus CAS tolerance
Assessment of two new molecular based methods for identification of Candida parapsilosis sensu lato species
No full textCandida parapsilosis sensu stricto, C. orthopsilosis, and C. metapsilosis replaced C. parapsilosis groups I, II, and III in 2005. Since then, an increased interest in studying their epidemiology has arisen based on the observed differences in antifungal susceptibilities and virulence the three species. A strict differentiation of these species cannot be achieved by phenotypic methods. We evaluate two new molecular methodologies to differentiate among these species by the use of a collection of 293 bloodstream infection isolates of C. parapsilosis sensu lato. For the first method, the isolates were studied using PCR amplification of a fragment of the C. parapsilosis sensu lato FKS1 gene and a universal primer pair followed by EcoRI enzyme digestion. The other method used the allele discrimination ability of molecular beacons in a multiplex real-time PCR format. Both methods of identification showed 100% concordance with internal transcribed spacer 1 (ITS1)/ITS2 sequencing and proved to be effective for clinical applications, even with mixed-species DNAs.Fil: Garcia, Guillermo Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. New Jersey Medical School. Public Health Research Institute; Estados UnidosFil: Canton, Emilia. Hospital Universitario La Fe. Centro de Investigación. Unidad de Microbiología Experimental; EspañaFil: Pemán, Javier. Hospital Universitario La Fe. Servicio de Microbiología; EspañaFil: Dilger, Amanda. New Jersey Medical School. Public Health Research Institute; Estados UnidosFil: Romá, Eva. Hospital Universitario La Fe. Servicio de Farmacia; EspañaFil: Perlin, David S.. Public Health Research Institute; Estados Unido
Variations on the Author
Get PDF“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
Evaluation of fungal-specific fluorescent labeled echinocandin probes as diagnostic adjuncts
Get PDFThe diagnosis of invasive fungal infections from radiographic imaging is non-specific and problematic. As a first step toward increasing specificity, we describe the development of a broad-spectrum fungal-specific targeting molecule, which when modified with a fluorescent label fully retains its targeting properties, and provides a basis for future imaging applications.Fil: Pratt, Ayiasha. University of Medicine and Dentistry of New Jersey. New Jersey Medical School. Public Health Research Institute; Estados UnidosFil: Garcia, Guillermo Manuel. University of Medicine and Dentistry of New Jersey. New Jersey Medical School. Public Health Research Institute; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Santa Fe; ArgentinaFil: Zhao, Yanan. University of Medicine and Dentistry of New Jersey. New Jersey Medical School. Public Health Research Institute; Estados UnidosFil: Park, Steven . University of Medicine and Dentistry of New Jersey. New Jersey Medical School. Public Health Research Institute; Estados UnidosFil: Mustaev, Arkady. University of Medicine and Dentistry of New Jersey. New Jersey Medical School. Public Health Research Institute; Estados UnidosFil: Pillai, Shyamala. University of Medicine and Dentistry of New Jersey. New Jersey Medical School. Public Health Research Institute; Estados UnidosFil: Perlin, David S.. University of Medicine and Dentistry of New Jersey. New Jersey Medical School. Public Health Research Institute; Estados Unido
Machine Learning of Bacterial Transcriptomes Reveals Responses Underlying Differential Antibiotic Susceptibility
Get PDFAntibiotic resistance is an imminent threat to global health. Patient treatment regimens are often selected based on results from standardized antibiotic susceptibility testing (AST) in the clinical microbiology lab, but these
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