Background Prior to the COVID-19 pandemic, urology was one of the specialties with the lowest rates of telemedicine and videoconferencing use. Common barriers to the implementation of telemedicine included a lack of technological literacy, concerns with reimbursement, and resistance to changes in the workplace. In response to the COVID-19 pandemic declared in March 2020, the delivery of urological services globally has quickly shifted to telemedicine to account for the mass clinical, procedural, and operative cancellations, inadequate personal protective equipment, and shortage of personnel. Objective The aim of this study was to investigate current telemedicine usage by urologists, urologists’ perceptions on the necessity of in-person clinic appointments, the usability of telemedicine, and the current barriers to its implementation. Methods We conducted a global, cross-sectional, web-based survey to investigate the use of telemedicine before and after the COVID-19 pandemic. Urologists’ perceived usability of telemedicine was assessed using a modified Delphi approach to create questions based on a modified version of the validated Telehealth Usability Questionnaire (TUQ). For the purposes of this study, telemedicine was defined as video calls only. Results A total of 620 urologists from 58 different countries and 6 continents participated in the survey. Prior to COVID-19, 15.8% (n=98) of urologists surveyed were using telemedicine in their clinical practices; during the pandemic, that proportion increased to 46.1% (n=283). Of the urologists without telemedicine experience, interest in telemedicine usage increased from 43.7% (n=139) to 80.8% (n=257) during the COVID-19 pandemic. Among urologists that used telemedicine during the pandemic, 80.9% (n=244) were interested in continuing to use it in their practice. The three most commonly used platforms were Zoom, Doxy.me, and Epic, and the top three barriers to implementing telemedicine were patients’ lack of technological comprehension, patients’ lack of access to the required technology, and reimbursement concerns. Conclusions This is the first study to quantify the use, usability, and pervading interest in telemedicine among urologists during the COVID-19 pandemic. In the face of this pandemic, urologists’ usage of telemedicine nearly tripled, demonstrating their ability to adopt and adapt telemedicine into their practices, but barriers involving the technology itself are still preventing many from utilizing it despite increasing interest.
As of June 2021, three vaccines have been issued Emergency Use Authorization (EUA) by the U.S. Food and Drug Administration (FDA) to combat SARS-CoV-2, with approximately 65% of U.S. adults over the age of 18 having received at least one vaccine dose (Hamel, Lopes, Kearney, et al., 2021). However, vaccine hesitancy rates have remained steady, with 10.2% of Americans stating they probably will not get a vaccine and 8.2% stating they would definitely not get a vaccine (Tram et al., 2021). With the emergence of the delta variant and COVID-19 cases on the rise nationwide, it is more important than ever to vaccinate the population. Thus, we evaluated the current reasons for COVID-19 vaccine hesitancy among the unvaccinated U.S. population.
The protein kinase D (PKD) family of proteins are important regulators of tumor growth, development, and progression. CRT0066101, an inhibitor of PKD, has antitumor activity in multiple types of carcinomas. However, the effect and mechanism of CRT0066101 in bladder cancer are not understood. In the present study, we show that CRT0066101 suppressed the proliferation and migration of four bladder cancer cell lines in vitro. We also demonstrate that CRT0066101 blocked tumor growth in a mouse flank xenograft model of bladder cancer. To further assess the role of PKD in bladder carcinoma, we examined the three PKD isoforms and found that PKD2 was highly expressed in eight bladder cancer cell lines and in urothelial carcinoma tissues from the TCGA database, and that short hairpin RNA (shRNA)-mediated knockdown of PKD2 dramatically reduced bladder cancer growth and invasion in vitro and in vivo, suggesting that the effect of the compound in bladder cancer is mediated through inhibition of PKD2. This notion was corroborated by demonstrating that the levels of phospho-PKD2 were markedly decreased in CRT0066101-treated bladder tumor explants. Furthermore, our cell cycle analysis by flow cytometry revealed that CRT0066101 treatment or PKD2 silencing arrested bladder cancer cells at the G2/M phase, the arrest being accompanied by decreases in the levels of cyclin B1, CDK1 and phospho-CDK1 (Thr161) and increases in the levels of p27 and phospho-CDK1 (Thr14/Tyr15). Moreover, CRT0066101 downregulated the expression of Cdc25C, which dephosphorylates/activates CDK1, but enhanced the activity of the checkpoint kinase Chk1, which inhibits CDK1 by phosphorylating/inactivating Cdc25C. Finally, CRT0066101 was found to elevate the levels of Myt1, Wee1, phospho-Cdc25C (Ser216), Gadd45α, and 14-3-3 proteins, all of which reduce the CDK1-cyclin B1 complex activity. These novel findings suggest that CRT0066101 suppresses bladder cancer growth by inhibiting PKD2 through induction of G2/M cell cycle arrest, leading to the blockade of cell cycle progression.
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