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Candida auris is a globally emerging pathogenic fungus described in Japan in 2009. This fungus has been identified mainly in nosocomial environments, associated with a high frequency of multidrug-resistant strains, and mortality rates reach 60%. C. auris is divided into 6 biogeographic clades, and there is a correlation between the clades and resistance against antifungals. In the current report, 8 strains of C. auris isolated in the Montefiore Medical Center, Bronx were analyzed to assess their clade (via ClaID) and common molecular determinants of antifungal resistance. We assessed antifungal resistance as well as the efficacy of a novel nitric oxide-donating microparticle as an alternative approach against C. auris in vitro through microplate susceptibility tests. Virulence was also determined in a Galleria mellonella model. Our results indicate that 7 out of 8 strains, belonging to clade 1, were resistant to fluconazole, while clade 2 was susceptible. Additionally, the clade 2 strain was more susceptible to treatment with the microparticle, while also being more virulent in an invertebrate model of infection. Our findings were then correlated to visualize parallels between clade identification and resistance/virulence patterns. [ABSTRACT FROM AUTHOR]

Cutaneous lupus erythematosus (CLE) is a heterogeneous autoimmune skin disease which occurs independently and in conjunction with systemic lupus erythematosus. Drug development for CLE is severely lacking. Anandamide (AEA) is a primary endocannabinoid which exhibits immunomodulatory effects through mixed cannabinoid receptor agonism. We evaluated AEA as topical treatment for CLE and assessed benefits of nanoparticle encapsulation (AEA‐NP) on cutaneous drug penetration, delivery and biological activity. Compared to untreated controls, AEA‐NP decreased IL‐6 and MCP‐1 in UVB‐stimulated keratinocytes (p < 0.05) in vitro. In BALB/c mice, AEA‐NP displayed improved cutaneous penetration, extended release and persistence of AEA in the follicular unit extending to the base after 24 h. Utilizing the MRL‐lpr lupus murine model, twice weekly treatment of lesions with topical AEA‐NP for 10 weeks led to decreased clinical and histologic lesion scores compared to unencapsulated AEA and untreated controls (p < 0.05). Prophylactic application of AEA‐NP to commonly involved areas on MRL‐lpr mice similarly resulted in decreased clinical and histologic scores when compared to controls (p < 0.05), and reduced C3 and IBA‐1 in lesional tissue (p < 0.05). The demonstrated clinical and immunomodulatory effects of treatment with AEA support its potential as therapy for CLE. This work also suggests that encapsulation of AEA improves penetration and treatment efficacy. Future studies will be conducted to assess full therapeutic potential. [ABSTRACT FROM AUTHOR]

Analysis of time-resolved phosphorescence data from proteins presents certain problems. Care must be taken in establishing that the analysis is not confounded in the early part of the decay by other emitting species. These species may include tyrosine, impurities found in the solvent, or impurities bound to the protein. In this paper, analysis of the phosphorescence of simple mixtures of tryptophan, tyrosine, and tryptophan + tyrosine in glycerol-water solvent has demonstrated the necessity of accounting for tyrosine emission in the analysis of protein phosphorescence. The tyrosine emission is especially strong at cold temperatures and becomes negligible above approximately 185 K in this solvent. Two fitting procedures have been developed to describe the bimodal emission that results from a single-tryptophan protein that contains a significant number of tyrosine residues. The methods utilize either a maximum entropy method-derived lifetime distribution or the stretched exponential function. In both cases some prior information regarding the expected decay characteristics of the tryptophan residue is applied to guide the separation of the tryptophan component from the tyrosine component. This prior information is obtained by comparing the tail of the protein decay to decays of free-tryptophan in solvent at a variety of temperatures until a match is found having close overlap on a log-intensity decay plot.