The echinocandins are relatively new antifungal drugs that represent, together with the older azoles, the recommended and/or preferred agents to treat candidaemia and other forms of invasive candidiasis in human patients. If “time is of the essence” to reduce the mortality for these infections, the administration of appropriate antifungal therapy could be accelerated by the timely reporting of laboratory test results. In this study, we attempted to validate a MALDI-ToF mass spectrometry-based assay for the antifungal susceptibility testing (AFST) of the potentially multidrug-resistant pathogen Candida glabrata against anidulafungin and fluconazole. The practical applicability of the assay, reported here as MS-AFST, was assessed with a panel of clinical isolates that were selected to represent phenotypically and genotypically/molecularly susceptible or resistant strains. The data show the potential of our assay for rapid detection of antifungal resistance, although the MS-AFST assay performed at 3 h of the in vitro antifungal exposure failed to detect C. glabrata isolates with echinocandin resistance-associated FKS2 mutations. However, cell growth kinetics in the presence of anidulafungin revealed important cues about the in vitro fitness of C. glabrata isolates, which may lead to genotypic or phenotypic antifungal testing in clinical practice.
It has been shown that decisions and moral judgments differ when made using native languages compared to foreign languages. Cross-linguistic differences appeared in foreign languages that monolinguals typically acquired in school and used neither routinely nor extensively. We replicated these differences with two populations of proficient, native bilinguals (Italian-Venetian; Italian-Bergamasque). Venetian and Bergamasque are spoken in households and informal circles, unlike Italian, which is also used in more formal contexts. The findings reported in foreign languages for the Asian Disease Problem and the Footbridge Dilemma were reproduced in Venetian and Bergamasque. Our results show that language effects on decisionmaking and moral judgments are not restricted to foreign languages. The explanation proposed for foreign languages of cross-linguistic differences in emotion responses does not apply to our proficient, native bilinguals, who showed emotion responses of equal intensity in their languages. We propose that the contexts in which bilinguals use a language -either native, regional or foreign -could affect decisions.
BackgroundTo determine whether the functional effects of oral supplementation with Saffron, a natural compound that proved to be neuroprotective in early age-related macular degeneration, are influenced by complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2) risk genotypes.MethodsThirty-three early AMD patients, screened for CFH (rs1061170) and ARMS2 (rs10490924) polymorphisms and receiving Saffron oral supplementation (20 mg/day) over an average period of treatment of 11 months (range, 6–12), were longitudinally evaluated by clinical examination and focal electroretinogram (fERG)-derived macular (18°) flicker sensitivity estimate. fERG amplitude and macular sensitivity, the reciprocal value of the estimated fERG amplitude threshold, were the main outcome measures.ResultsAfter three months of supplementation, mean fERG amplitude and fERG sensitivity improved significantly when compared to baseline values (p < 0.01). These changes were stable throughout the follow-up period. No significant differences in clinical and fERG improvements were observed across different CFH or ARMS2 genotypes.ConclusionsThe present results indicate that the functional effect of Saffron supplementation in individual AMD patients is not related to the major risk genotypes of disease.
We tested 59 common and 27 uncommon Aspergillus species isolates for susceptibility to the mold-active azole antifungal agents itraconazole, voriconazole, and posaconazole using the Sensititre method. The overall essential agreement with the CLSI reference method was 96.5% for itraconazole and posaconazole and was 100% for voriconazole. By the Sensititre method as well as the CLSI reference method, all of 10 A. fumigatus isolates with a cyp51 mutant genotype were classified as being non-wild-type isolates (MIC Ͼ epidemiological cutoff value [ECV]) with respect to triazole susceptibility.KEYWORDS Aspergillus, Sensititre, antifungal susceptibility testing I n contrast to other but emerging molds (1), Aspergillus species, particularly Aspergillus fumigatus, remain the most common causes of invasive fungal diseases in both North America and Europe (2, 3). Because of the availability of (tri)azole antifungal agents, survival of immunocompromised patients with invasive aspergillosis has improved dramatically and could be further improved by optimizing antifungal treatments (4). A key component of this optimization should be the regular in vitro antifungal susceptibility testing of the patients' A. fumigatus isolates to detect azole resistance (5). Unfortunately, in most clinical microbiology laboratories, antifungal susceptibility testing of aspergilli (and other molds) is not routinely performed (6), thus underestimating the true prevalence of fungal resistance (4).The azole antifungal agents for clinical use include itraconazole, voriconazole, posaconazole, and, most recently, isavuconazole (7). Despite their role-unlike voriconazole, itraconazole and posaconazole are not approved as first-line agents-in treatment of invasive aspergillosis (4), the Clinical and Laboratory Standards Institute (CLSI) did not set clinical breakpoints (CBPs) for common Aspergillus species and mold-active triazoles, e.g., itraconazole and posaconazole (8), in contrast to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) (9). However, CLSI-based epidemiological cutoff values (ECVs) were established-instead of CBPs-for Aspergillus species (A. fumigatus, A. flavus, A. terreus, A. niger, A. nidulans, and A. versicolor) and for triazoles to aid in the early identification of clinical isolates with acquired resistance mechanisms (10, 11). Isolates of these six Aspergillus species for which triazole MICs exceed the ECV are considered to be non-wild type (non-WT) and may harbor mutations in the cyp51a gene-the best-known mechanism of triazole resistance in the A. fumigatus species-or other mutations (12). Interestingly, whereas the significance of ECVs in clinical practice needs to be understood, the ECVs defined to date-albeit mainly for Candida
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