The ability of adeno-associated viruses (AAVs) to infect and deliver genetic material to a range of cell types makes them favorable gene therapy vectors. However, AAV vectors encounter a wide variety of host immune factors throughout the body, which can impede efficient gene delivery.
Intracellular bacterial pathogens often reprogram their mammalian host cells, including cell mechanical properties, to promote their own replication and spread. However, it is unclear whether mammalian host cells may modulate their biomechanics in response to infection in a way that would benefit the host by limiting bacterial infection. Inspired by this question, we monitored epithelial cell monolayers infected with low levels of Listeria monocytogenes. We found that, as the bacteria replicate and spread from cell to cell over several days, the infected host cells within the infection focus get progressively compressed by surrounding uninfected cells. Surrounding uninfected cells become highly polarized and move directionally towards the infection focus, squeezing the infected cells that eventually get extruded from the monolayer.Extruded cells continue adhering to the cellular monolayer, giving rise to a 3-dimensional (3D) mound of infected cells. We hypothesized that 3D mounding was driven by changes in the biomechanics of uninfected cells surrounding the mounds (surrounders) as well as the infected cells that eventually compose the mound (mounders). Indeed, we found that infected mounders, but not surrounders, become softer during infection and adhere more weakly on deformable matrices mimicking their natural environment. Through a combination of transcriptomics, pharmacological and genetic perturbations, we find that differentially upregulated innate immunity signaling, and downregulated cell-cell and cell-matrix adhesion pathways synergistically can drive the observed cellular competition between infected mounders and surrounders. Most importantly we find that activation of NF-κB is critical for mound formation, and show evidence that our findings extend to bacterial pathogens other than L. monocytogenes. Overall, our findings highlight the dynamic remodeling capability of epithelial tissue, and propose a novel biomechanical mechanism employed by host epithelial cells to eliminate bacterial infection.
Background
Online cardiologist reviews, such as those on the Yelp website, are a frequently used method for patients to find a cardiologist. It remains unknown how bias may influence such reviews. Our objectives for this study were to (1) determine which cardiologist‐ or practice‐related factors influence the overall rating of cardiologists and patient satisfaction and (2) discover any associations between sex and race with the overall rating of cardiologists or with cardiologist‐ or practice‐related factors.
Methods and Results
Cardiologist Yelp reviews from practices in the United States from 2007 to 2020 were analyzed. A total of 563 reviews were coded for positive and negative themes. Binary logistic regression was used to determine whether certain factors increased the likelihood of high ratings. Chi‐squared tests were used to determine associations between sex and race with certain factors and overall cardiologist ratings. Cardiologists were more likely to receive higher ratings when reviewers noted the characteristics of competency/knowledge base and thoroughness, positive interactions with staff, and when the cardiologist's name was mentioned in the review. Negative interactions with staff were associated with lower ratings. Female cardiologists received lower ratings and more negative mentions of cardiologist–patient communication than expected. White and Black cardiologists received lower ratings than expected compared with other racial groups.
Conclusions
Patient‐perceived cardiologist competency, thoroughness, and positive staff interactions were associated with positive reviews in online assessments. Sex and racial differences were also found. Further research must be done to confirm these findings and to understand the association of online reviews with clinical care and patient outcomes.
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