Disturbed flow increases endothelial inflammation and permeability via a Frizzled-4-ß-catenin-dependent pathway.

Multidirectional or disturbed flow promotes endothelial dysfunction and is associated with early atherogenesis. Here we investigated the role of Wnt signalling in flow-mediated endothelial dysfunction. The expression of Frizzled-4 was higher in cultured human aortic endothelial cells (ECs) exposed to disturbed flow compared to that seen for undisturbed flow, obtained using an orbital shaker. Increased expression was also detected in regions of the porcine aortic arch exposed to disturbed flow. The increased Frizzled-4 expression in cultured ECs was abrogated following knockdown of R-spondin-3. Disturbed flow also increased the nuclear localisation and activation of ß-catenin, an effect that was dependent on Frizzled-4 and R-spondin-3. Inhibition of ß-catenin using the small-molecule inhibitor iCRT5 or knockdown of Frizzled-4 or R-spondin-3 resulted in reduced expression of pro-inflammatory genes in ECs exposed to disturbed flow, as did inhibition of WNT5A signalling. Inhibition of the canonical Wnt pathway had no effect. Inhibition of ß-catenin also reduced endothelial paracellular permeability; this was associated with altered junctional and focal adhesion organisation and cytoskeletal remodelling. These data suggest the presence of an atypical Frizzled-4-ß-catenin pathway that promotes endothelial dysfunction in response to disturbed flow.

Satisfaction among Cancer Patients Undergoing Radiotherapy during the COVID-19 Pandemic: An Institutional Experience.

The COVID-19 pandemic has shifted oncology practices to prioritize patient safety while maintaining necessary treatment delivery. We obtained patient feedback on pandemic-based practices in our radiotherapy department to improve quality of patient care and amend policies as needed. We developed a piloted questionnaire which quantitatively and qualitatively assessed patients' pandemic-related concerns and satisfaction with specific elements of their care. Adult patients who were treated at our Centre between 23 March and 31 May 2020, had initial consultation via telemedicine, and received at least five outpatient fractions of radiotherapy were invited to complete the survey by telephone or online. Relative frequencies of categorical and ordinal responses were then calculated. Fifty-three (48%) out of 110 eligible patients responded: 32 patients by phone and 21 patients online. Eighteen participants (34%) admitted to feeling anxious about hospital appointments, and only five (9%) reported treatment delays. Forty-eight patients (91%) reported satisfaction with their initial telemedicine appointment. The majority of patients indicated that healthcare workers took appropriate precautions, making them feel safe. Overall, all 53 patients (100%) reported being satisfied with their treatment experience during the pandemic. Patient feedback is needed to provide the highest quality of patient care as we adapt to the current reality.