A Global Review of the Impacts of the Coronavirus (COVID-19) Pandemic on Radiology Practice, Finances, and Operations.

The Coronavirus Disease 2019 (COVID-19) pandemic ushered in rapid changes in healthcare, including radiology, globally. This review discusses the impact of the pandemic on various radiology departments globally. We analyze the implications of the COVID-19 pandemic on the imaging volumes, finances, and clinical operations of radiology departments in 2020. Studies from health systems and outpatient imaging centers were analyzed, and the activity throughout 2020 was compared to the pre-pandemic activity, including activity during similar timeframes in 2019. Imaging volumes across modalities, including MRI and CT scans, were compared, as were the Relative Value Units (RVUs) for imaging finances. Furthermore, we compared clinical operations, including staffing and sanitation procedures. We found that imaging volumes in private practices and academic centers decreased globally. The decreases in volume could be attributed to delayed patient screenings, as well as the implementation of protocols, such as the deep cleaning of equipment between patients. Revenues from imaging also decreased globally, with many institutions noting a substantial decline in RVUs and revenue compared with pre-COVID-19 levels. Our analysis thus found significant changes in the volumes, finances, and operations of radiology departments due to the COVID-19 pandemic.

ß-Lactam TRPM8 Antagonist RGM8-51 Displays Antinociceptive Activity in Different Animal Models.

Transient receptor potential melastatin subtype 8 (TRPM8) is a cation channel extensively expressed in sensory neurons and implicated in different painful states. However, the effectiveness of TRPM8 modulators for pain relief is still a matter of discussion, since structurally diverse modulators lead to different results, depending on the animal pain model. In this work, we described the antinociceptive activity of a ß-lactam derivative, RGM8-51, showing good TRPM8 antagonist activity, and selectivity against related thermoTRP channels and other pain-mediating receptors. In primary cultures of rat dorsal root ganglion (DRG) neurons, RGM8-51 potently reduced menthol-evoked neuronal firing without affecting the major ion conductances responsible for action potential generation. This compound has in vivo antinociceptive activity in response to cold, in a mouse model of oxaliplatin-induced peripheral neuropathy. In addition, it reduces cold, mechanical and heat hypersensitivity in a rat model of neuropathic pain arising after chronic constriction of the sciatic nerve. Furthermore, RGM8-51 exhibits mechanical hypersensitivity-relieving activity, in a mouse model of NTG-induced hyperesthesia. Taken together, these preclinical results substantiate that this TRPM8 antagonist is a promising pharmacological tool to study TRPM8-related diseases.

Selective Inhibition of Cysteine-Dependent Enzymes by Bioorthogonal Tethering.

A general approach for the rapid and selective inhibition of enzymes in cells using a common tool compound would be of great value for research and therapeutic development. We previously reported a chemogenetic strategy that addresses this challenge for kinases, relying on bioorthogonal tethering of a pan inhibitor to a target kinase through a genetically encoded non-canonical amino acid. However, pan inhibitors are not available for many enzyme classes. Here, we expand the scope of the chemogenetic strategy to cysteine-dependent enzymes by bioorthogonal tethering of electrophilic warheads. For proof of concept, selective inhibition of two E2 ubiquitin-conjugating enzymes, UBE2L3 and UBE2D1, was demonstrated in biochemical assays. Further development and optimization of this approach should enable its use in cells as well as with other cysteine-dependent enzymes, facilitating the investigation of their cellular function and validation as therapeutic targets.

Using genetically incorporated unnatural amino acids to control protein functions in mammalian cells.

Genetic code expansion allows unnatural (non-canonical) amino acid incorporation into proteins of interest by repurposing the cellular translation machinery. The development of this technique has enabled site-specific incorporation of many structurally and chemically diverse amino acids, facilitating a plethora of applications, including protein imaging, engineering, mechanistic and structural investigations, and functional regulation. Particularly, genetic code expansion provides great tools to study mammalian proteins, of which dysregulations often have important implications in health. In recent years, a series of methods has been developed to modulate protein function through genetically incorporated unnatural amino acids. In this review, we will first discuss the basic concept of genetic code expansion and give an up-to-date list of amino acids that can be incorporated into proteins in mammalian cells. We then focus on the use of unnatural amino acids to activate, inhibit, or reversibly modulate protein function by translational, optical or chemical control. The features of each approach will also be highlighted.