Variability in antifungal and antiviral use in hospitalized children

We analyzed antifungal and antiviral prescribing among high-risk children across freestanding children’s hospitals. Antifungal and antiviral days of therapy varied across hospitals. Benchmarking antifungal and antiviral use and developing antimicrobial stewardship strategies to optimize use of these high cost agents is needed.Infect Control Hosp Epidemiol2017;38:743–746</jats:p

Magnetic structure of Dy3+ in hexagonal multiferroic DyMnO3

Element specific x-ray resonant magnetic scattering (XRMS) investigations were undertaken to determine the magnetic structure of the multiferroic compound, hexagonal DyMnO3. In the temperature range from 68 K down to 8 K the Dy3+ moments are aligned and antiferromagnetically correlated in the c direction according to the magnetic representation Γ3. The temperature dependence of the observed intensity can be modeled assuming the splitting of ground-state doublet crystal-field levels of Dy3+ by the exchange field of Mn3+. XRMS together with magnetization measurements indicate that the magnetic representation is Γ2 below 8 K

Examining Signatures of Natural Selection in Antifungal Resistance Genes Across Aspergillus Fungi

Certain Aspergillus fungi cause aspergillosis, a set of diseases that typically affect immunocompromised individuals. Most cases of aspergillosis are caused by Aspergillus fumigatus, which infects millions of people annually. Some closely related so-called cryptic species, such as Aspergillus lentulus, can also cause aspergillosis, albeit at lower frequencies, and they are also clinically relevant. Few antifungal drugs are currently available for treating aspergillosis and there is increasing worldwide concern about the presence of antifungal drug resistance in Aspergillus species. Furthermore, isolates from both A. fumigatus and other Aspergillus pathogens exhibit substantial heterogeneity in their antifungal drug resistance profiles. To gain insights into the evolution of antifungal drug resistance genes in Aspergillus, we investigated signatures of positive selection in 41 genes known to be involved in drug resistance across 42 susceptible and resistant isolates from 12 Aspergillus section Fumigati species. Using codon-based site models of sequence evolution, we identified ten genes that contain 43 sites with signatures of ancient positive selection across our set of species. None of the sites that have experienced positive selection overlap with sites previously reported to be involved in drug resistance. These results identify sites that likely experienced ancient positive selection in Aspergillus genes involved in resistance to antifungal drugs and suggest that historical selective pressures on these genes likely differ from any current selective pressures imposed by antifungal drugs.RS was supported by the Brazilian São Paulo Research Foundation (FAPESP) grant numbers 2017/21983-3 and 2019/07526-4. JS and AR are supported by the Howard Hughes Medical Institute through the James H. Gilliam Fellowships for Advanced Study Program. AR’s laboratory received additional support from a Discovery grant from Vanderbilt University, the Burroughs Wellcome Fund, the National Science Foundation (DEB-1442113), and the National Institutes of Health/National Institute of Allergy and Infectious Diseases (R56AI146096). GHG was supported by FAPESP (2016/07870-9) and Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq).S

The Impact of Heterogeneity on Single-Cell Sequencing

The importance of diversity and cellular specialization is clear for many reasons, from population-level diversification, to improved resiliency to unforeseen stresses, to unique functions within metazoan organisms during development and differentiation. However, the level of cellular heterogeneity is just now becoming clear through the integration of genome-wide analyses and more cost effective Next Generation Sequencing (NGS). With easy access to single-cell NGS (scNGS), new opportunities exist to examine different levels of gene expression and somatic mutational heterogeneity, but these assays can generate yottabyte scale data. Here, we model the importance of heterogeneity for large-scale analysis of scNGS data, with a focus on the utilization in oncology and other diseases, providing a guide to aid in sample size and experimental design

Examination of Genome-Wide Ortholog variation in clinical and environmental isolates of the fungal pathogen Aspergillus fumigatus

Aspergillus fumigatus is a cosmopolitan species of fungus responsible for thousands of cases of invasive disease annually. Clinical and environmental isolates of A. fumigatus exhibit extensive phenotypic differences, including differences related to virulence and antifungal drug resistance. Aspergillus fumigatus is both an environmental saprobe and an opportunistic human fungal pathogen. Knowledge of genomic variation across A. fumigatus isolates is essential for understanding the evolution of pathogenicity, virulence, and resistance to antifungal drugs. Here, we investigated 206 A. fumigatus isolates (133 clinical and 73 environmental isolates), aiming to identify genes with variable presence across isolates and test whether this variation was related to the clinical or environmental origin of isolates. The PanOrtho genome of A. fumigatus consists of 13,085 ortholog groups, of which 7,773 (59.4\%) are shared by all isolates (core groups) and 5,312 (40.6\%) vary in their gene presence across isolates (accessory groups plus singletons). Despite differences in the distribution of orthologs across all isolates, no significant differences were observed among clinical versus environmental isolates when phylogeny was accounted for. Orthologs that differ in their distribution across isolates tend to occur at low frequency and/or be restricted to specific isolates; thus, the degree of genomic conservation between orthologs of A. fumigatus is high. These results suggest that differences in the distribution of orthologs within A. fumigatus cannot be associated with the clinical or environmental origin of isolates. IMPORTANCE Aspergillus fumigatus is a cosmopolitan species of fungus responsible for thousands of cases of invasive disease annually. Clinical and environmental isolates of A. fumigatus exhibit extensive phenotypic differences, including differences related to virulence and antifungal drug resistance. A comprehensive survey of the genomic diversity present in A. fumigatus and its relationship to the clinical or environmental origin of isolates can contribute to the prediction of the mechanisms of evolution and infection of the species. Our results suggest that there is no significant variation in ortholog distribution between clinical and environmental isolates when accounting for evolutionary history. The work supports the hypothesis that environmental and clinical isolates of A. fumigatus do not differ in their gene contents.We thank Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) 2020/10536-9 (M.A.C.H.) and 2016/07870-9 (G.H.G.) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) 301058/2019-9 and 404735/2018-5 (G.H.G.), both in Brazil, and National Institutes of Health/National Institute of Allergy and Infectious Diseases (R01AI153356) (A.R. and G.H.G.), in the United States.Peer ReviewedPostprint (published version

Алкогольные виртуальные реальности. Девиртуализация синдрома зависимости от алкоголя

Представлен новый взгляд на синдром зависимости от алкоголя с позиций виртуалистики как на параллельную виртуальную реальность. Подробно освещена рассматриваемая проблема, описан разработанный автором метод лечения алкоголизма ФорсажТМ и показана его высокая эффективность.A new idea about syndrome of alcohol addiction as a parallel virtual reality is presented. The problem is discussed in detail, the original method of treatment of alcoholism Forsazh(tm) is described, its high efficacy is shown