ABSTRACT
Background: Normal organ function is critically dependent on an intact three-dimensional architecture. Structural abnormalities induced by pathological situations instruct cells to behave abnormally and promoting disease progression oftentimes leading to organ failure. Current approaches do not allow for high-resolution (HR) threedimensional (3D) visualisation and analysis of human organ structure. Method(s): Here, we develop a method to perfuse human tissue segments to remove cells and study the 3D structural scaffold, which could be applied to any organ. Our approach enables HR-3D imaging of organ architecture, which we apply to study healthy and diseased human lung, specifically emphysema, usual interstitial pneumonia, pulmonary sarcoidosis, and COVID-19. Result(s): Our imaging reveals major structural abnormalities previously unseen by existing methodologies. Furthermore, we identify disease-specific patterns of structural remodelling using machine learning, including the altered spatial relationship between extracellular matrix (ECM) proteins collagen type IV, elastin and fibrillar collagen present across all diseases. Conclusion(s): Given the importance of organ structure on function, our approach opens the possibility to understand human physiology in a new way, which may assist in future disease diagnosis and explain the detrimental pulmonary effects of the diseases studied here.
ABSTRACT
The coronavirus severe acute respiratory syndrome (COVID-19) pandemic has placed increased stress on healthcare workers (HCWs). While anxiety and post-traumatic stress have been evaluated in HCWs during previous pandemics, moral injury, a construct historically evaluated in military populations, has not. We hypothesized that the experience of moral injury and psychiatric distress among HCWs would increase over time during the pandemic and vary with resiliency factors. From a convenience sample, we performed an email-based, longitudinal survey of HCWs at a tertiary care hospital between March and July 2020. Surveys measured occupational and resilience factors and psychiatric distress and moral injury, assessed by the Impact of Events Scale-Revised and the Moral Injury Events Scale, respectively. Responses were assessed at baseline, 1-month, and 3-month time points. Moral injury remained stable over three months, while distress declined. A supportive workplace environment was related to lower moral injury whereas a stressful, less supportive environment was associated with increased moral injury. Distress was not affected by any baseline occupational or resiliency factors, though poor sleep at baseline predicted more distress. Overall, our data suggest that attention to improving workplace support and lowering workplace stress may protect HCWs from adverse emotional outcomes.