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Invasive aspergillosis remains a potentially life-threatening infection, the incidence of which is increasing. Current methods used to determine the susceptibilities of Aspergillus strains to antifungal drugs are often unreliable. Nuclear magnetic resonance (NMR) spectroscopy can identify the metabolic complement of microorganisms while monitoring nutrient utilization from the incubation medium. We used 600-MHz 1 H NMR spectroscopy to monitor the metabolic responses of five Aspergillus species cultured in RPMI 1640-2% glucosemorpholinepropanesulfonate buffer to various concentrations of the antifungal drugs amphotericin B (AMB) and caspofungin. The metabolic endpoint (MEP) was determined from nutrient and metabolite resonances, measured as a function of the drug concentration, and was defined as a >50% reduction in nutrient consumption or metabolite production. MICs were evaluated by a modification of Clinical and Laboratory Standards Institute broth microdilution method M27-A, and minimal effective concentrations (MECs) were determined by microscopic examination of fungal hyphae. For AMB, the MEPs coincided with the MICs. For caspofungin, the MEPs agreed with the MECs for several Aspergillus strains, but the effect of drug pressure was more complex for others. Expansion of the MEP definition to include any significant changes in metabolite production resulted in agreement with the MEC in most cases. Paradoxical metabolic responses were observed for several Aspergillus strains at either high or low caspofungin concentrations and for one Aspergillus terreus strain with AMB. NMR spectroscopy proved to be a powerful tool for detecting the subtle effects of drug pressure on fungal metabolism and has the potential to provide an alternative method for determining the susceptibilities of Aspergillus species to antifungal drugs.

Introduction:Monitoring patients with acute myeloid leukemia can be implemented through various techniques such as multiparameter flow cytometry, real-time quantitative polymerase chain reaction, and next-generation sequencing. However, there is scarce studies when comparing the data of next-generation sequencing and flow cytometry for monitoring disease progression, particularly how they might supplement one another when used in tandem. Methods:We investigated 107 patients via retrospective analysis using follow-up MFC and NGS data with a total of 717 MFC and 247 NGS studies to compare these methods in monitoring minimal/measurable residual disease.Results: 197 instances were MFC + /NGS + , 3 were MFC − /NGS − , 44 were MFC − / NGS + , and 3 are MFC + /NGS − . The majority of the MFC − /NGS + cases occurred within 6 months during the post-treatment phase (64%). Among 44 MFC − /NGS + instances, 13 had similar NGS profiles to their original day 0 diagnosis. The remaining cases showed preleukemic clonal hematopoiesis mutations, "likely pathogenic mutations," or "variants of uncertain significance." Conclusion:Our findings show that flow cytometry has its advantages with comparable sensitivity in detecting minimal/measurable residual disease. Next-generation sequencing could be used in an increased and more regular capacity in conjunction with flow cytometry to achieve a more comprehensive surveillance of these patients, resulting in improved outcomes.

We present a novel NMR-based study of the molecular aspects of the "attack" on human red blood cells (RBCs) by growing bacteria. Staphylococcus aureus expresses virulence factors, including ␣-hemolysin, which contribute to the clinical condition known as septic shock. ␣-Hemolysin is a pore-forming toxin and its secretion increases the permeability of a range of mammalian cell types infected with S. aureus. 31 P NMR spectra of the probe molecules dimethyl methylphosphonate (

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