Publications by authors named "A F Pasternak"

In this article, we present an approach to maximizing the splicing regulatory properties of splice-switching oligonucleotide (SSO) designed to regulate alternative splicing of PKM pre-mRNA. The studied SSO interacts with the regulatory element in exon 10 of PKM pre-mRNA and contributes to a significant reduction of PKM2 level with a simultaneous increase of the PKM1 isoform. This SSO forms a duplex not only with the regulatory fragment of exon 10 but also with a similar RNA fragment of intron 9.

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DNA can self-assemble into G-quadruplexes and i-motifs non-canonical secondary structures that are formed by guanine-rich sequences and the cytosine-rich sequences, respectively. G-quadruplexes and i-motifs have been closely linked to cancer development since they can regulate genes expression in various promoter regions. Moreover, these structures have gained attention as viable targets for anticancer treatments because of their physicochemical properties and gene-regulatory functions.

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Pharmacogenetics promises to optimize treatment-related outcomes by informing optimal drug selection and dosing based on an individual's genotype in conjunction with other important clinical factors. Despite significant evidence of genetic associations with drug response, pharmacogenetic testing has not been widely implemented into clinical practice. Among the barriers to broad implementation are limited guidance for how to successfully integrate testing into clinical workflows and limited data on outcomes with pharmacogenetic implementation in clinical practice.

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Background: Pharmacogenomic testing can optimize drug efficacy and minimize adverse effects. CYP3A5 polymorphisms affect the metabolism of tacrolimus. We sought to estimate the budget impact of preemptive pharmacogenomic testing for CYP3A5 in pediatric heart transplantation patients from an institutional perspective.

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Article Synopsis
  • The study focuses on developing new sulfone analogues of known metallo-β-lactamase inhibitors (MBLis) and their antibacterial effectiveness.
  • The new compounds showed greater effectiveness in killing gram-negative bacteria when paired with antibiotics imipenem and relebactam.
  • Improved antibacterial activity is linked to stronger enzyme-inhibitor interactions and decreased bacterial cell efflux, as shown by experiments with different strains of Pseudomonas aeruginosa.
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