Background. In early 2020, the novel coronavirus pandemic forced communities around the globe to shut down and isolate. Routine graduate medical education activities have also been suspended as resident and fellow physicians-in-training have been re-deployed to support critical patient care services. Innovation. We developed a two-part hybrid telesimulation model to teach COVID-19 ventilator management strategies while physically separating a group of learners and an instructor from one another. Learners consisted of non-ICU health care providers with limited experience in ventilator management being redeployed to manage ICU level COVID-19 infected patients. In the first week, the video tutorial has been viewed over 500 times and we have facilitated 14 telesimulation sessions, including 48 participants comprised of hospitalists, emergency medicine physicians and physician assistants, pediatric residents, nurses, and a nurse educator. Conclusion. We believe that the combination of a video tutorial followed by an interactive telesimulation was successful in providing timely education during a coronavirus pandemic. Furthermore, it reinforced the value and flexibility in which simulation education could continue conveniently for learners despite significant restrictions in place during the coronavirus pandemic. Research is needed to assess the efficacy of this hybrid intervention in preparing healthcare workers and to determine if the knowledge is successfully transferred to the clinical setting.
Cullin-RING E3 ubiquitin ligases (CRL) control a myriad of biological processes by directing numerous protein substrates for proteasomal degradation. Key to CRL activity is the recruitment of the E2 ubiquitin-conjugating enzyme Cdc34 through electrostatic interactions between E3′s cullin conserved basic canyon and the acidic C terminus of the E2 enzyme. This report demonstrates that a smallmolecule compound, suramin, can inhibit CRL activity by disrupting its ability to recruit Cdc34. Suramin, an antitrypansomal drug that also possesses antitumor activity, was identified here through a fluorescence-based high-throughput screen as an inhibitor of ubiquitination. Suramin was shown to target cullin 1's conserved basic canyon and to block its binding to Cdc34. Suramin inhibits the activity of a variety of CRL complexes containing cullin 2, 3, and 4A. When introduced into cells, suramin induced accumulation of CRL substrates. These observations help develop a strategy of regulating ubiquitination by targeting an E2-E3 interface through small-molecule modulators.protein degradation | K48-polyubiquitination | E3 ligase | E2 enzyme | suramin
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