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Abstract: A reconstituted human tissue model was used to mimic Candida albicans and Candida parapsilosis infection in order to investigate the protective effects of acetylsalicylic acid (aspirin, ASA). We found that therapeutic concentrations of ASA reduced tissue damage in the in vitro infection model. We further evaluated the lipase inhibitory effects of ASA by investigating the growth of C. albicans, C. parapsilosis and C. parapsilosis lipase negative (Δcplip1-2/Δcplip1-2) mutants in a lipid rich minimal medium supplemented with olive oil and found that a therapeutic concentration of ASA inhibited the growth of wild type fungi. The lipase inhibitors quinine and ebelactone B were also shown to reduce growth and protect against tissue damage from Candida species, respectively. A lipolytic activity assay also showed that therapeutic concentrations of ASA inhibited C. antarctica and C. cylindracea purified lipases obtained through a commercial kit. The relationship between ASA and lipase was characterized through a computed structural model of the Lipase-2 protein from C. parapsilosis in complex with ASA. The results suggest that development of inhibitors of fungal lipases could result in broad-spectrum therapeutics, especially since fungal lipases are not homologous to their human analogues. [Copyright &y& Elsevier]

Background: Professional guidelines in the U.S. do not recommend routine screening mammography for women ≥75 years with limited life expectancy and/or poor health. Yet, routine mammography remains widely used in older women. We examined older women's experiences, beliefs, and opinions about screening mammography in relation to aging and health. Methods: We performed thematic analysis of transcribed semi‐structured interviews with 19 women who had a recent screening visit at a mammography clinic in New York City (average age: 75 years, 63% Hispanic, 53% ≤high school education). Results: Three main themes emerged: (1) older women typically perceive mammograms as a positive, beneficial, and routine component of care; (2) participation in routine mammography is reinforced by factors at interpersonal, provider, and healthcare system levels; and (3) older women do not endorse discontinuation of screening mammography due to advancing age or poor health, but some may be receptive to reducing screening frequency. Only a few older women reported having discussed mammography cessation or the potential harms of screening with their providers. A few women reported they would insist on receiving mammography even without a provider recommendation. Conclusions: Older women's positive experiences and views, as well as multilevel and frequently automated cues toward mammography are important drivers of routine screening in older women. These findings suggest a need for synergistic patient, provider, and system level strategies to reduce mammography overuse in older women. [ABSTRACT FROM AUTHOR]

Abstract: Neutral lipid storage in lipid droplets (LDs) is a conserved process across diverse species. Although significant attention has focused on LDs in the biology of obesity, diabetes, and atherosclerosis, there is limited information on the role of LDs in pathogenic fungi. We have disrupted the Fat storage-Inducing Transmembrane (FIT) protein 2 genes of the emerging pathogenic fungus Candida parapsilosis and demonstrated that LD formation is significantly reduced in the mutant cells. Disruption of FIT2 genes also reduced accumulation of triacylglycerols. The production of other lipids such as phospholipids and steryl esters were also affected in the mutant strain. Inhibition of de novo fatty acid biosynthesis by triclosan in the FIT2 disruptants reduced fungal growth in rich medium YPD, indicating that TAGs or fatty acids from the LDs could be important for cell proliferation. FIT2 disruption was associated with enhanced sensitivity to oxidative stress. Furthermore, we showed that FIT2 deletion yeast cells were significantly attenuated in murine infection models, suggesting an involvement of LDs in the pathobiology of the fungus. [Copyright &y& Elsevier]