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Abstract It is known that small extracellular vesicles (sEVs) are released from cancer cells and contribute to cancer progression via crosstalk with recipient cells. We have previously reported that sEVs expressing the αVβ3 integrin, a protein upregulated in aggressive neuroendocrine prostate cancer (NEPrCa), contribute to neuroendocrine differentiation (NED) in recipient cells. Here, we examine the impact of αVβ3 expression on sEV protein content, density and function. sEVs used in this study were isolated by iodixanol density gradients and characterized by nanoparticle tracking analysis, immunoblotting and single vesicle analysis. Our proteomic profile of sEVs containing αVβ3 shows downregulation of typical effectors involved in apoptosis and necrosis and an upregulation of tumour cell survival factors compared to control sEVs. We also show that the expression of αVβ3 in sEVs causes a distinct reposition of EV markers (Alix, CD81, CD9) to a low‐density sEV subpopulation. This low‐density reposition is independent of extracellular matrix (ECM) protein interactions with sEVs. This sEV subset contains αVβ3 and an αVβ3 downstream effector, NgR2, a novel marker for NEPrCa. We show that sEVs containing αVβ3 are loaded with higher amounts of NgR2 as compared to sEVs that do not express αVβ3. Mechanistically, we demonstrate that sEVs containing NgR2 do not affect the sEV marker profile, but when injected in vivo intratumorally, they promote tumour growth and induce NED. We show that sEVs expressing NgR2 increase the activation of focal adhesion kinase (FAK), a known promoter of cancer cell proliferation, in recipient cells. We also show that NgR2 mimics the effect of sEVs containing αVβ3 since it displays increased growth of NgR2 transfectants in vivo, as compared to control cells. Overall, our results describe the changes that occur in cargo, density and functions of cancer cell‐derived sEVs containing the αVβ3 integrin and its effector, NgR2, without affecting the sEV tetraspanin profiles.

Abstract Background This study examined the conflicts between different generations working in US emergency departments (ED). We sought to record generational differences involving communication preferences, perceived areas of conflict, work motivations, and attitudes regarding work-life balance. Methods We developed a survey to assess the physician perspective on generational conflict in the ED. The survey was distributed to members of the American College of Emergency Physicians, a professional organization comprising emergency medicine physicians in the USA. Results We received 696 completed responses. Men represented 60% of respondents and the largest proportion of respondents were emergency physicians working in community settings (53%); 11% were residents. Generation representation was smallest for Traditionalist (2%) and largest for Gen X (43%). Seventy percent reported observing conflict due to generational communication with the largest frequency being once a week (26%). In the associated open-ended questions, 247 (33%) provided 316 anecdotal descriptions of observed conflict. Responses clustered into seven themes (ordered by frequency): Work Ethic, Treatment Approach, Technology Application, Entitlement, Professionalism, Work Life/Balance, and Communication Style. Comparing Work Ethic responses, 52–70-year-olds reported that younger providers are less interested in “accomplishing anything” while 26–34-year-olds resented that attitude. Respondents completing the open-ended questions regarding preventing and responding to conflict provided some insight into helpful strategies including actions supportive of clear communication and standardized policies and expectations. Only 5% of respondents reported that they had discussed generational communication in department meetings with the odds of a woman reporting conflict being less than males (p = .01). Conclusion Conflicts in the ED in the USA can be attributed to how an individual views the values of someone from another generation. Understanding the frequency and areas of generational conflict in the ED can help medical leaders find strategies to mitigate negative workplace interactions.

Abstract Androgen deprivation therapies aimed to target prostate cancer (PrCa) are only partially successful given the occurrence of neuroendocrine PrCa (NEPrCa), a highly aggressive and highly metastatic form of PrCa, for which there is no effective therapeutic approach. Our group has demonstrated that while absent in prostate adenocarcinoma, the αVβ3 integrin expression is increased during PrCa progression toward NEPrCa. Here, we show a novel pathway activated by αVβ3 that promotes NE differentiation (NED). This novel pathway requires the expression of a GPI-linked surface molecule, NgR2, also known as Nogo-66 receptor homolog 1. We show here that NgR2 is upregulated by αVβ3, to which it associates; we also show that it promotes NED and anchorage-independent growth, as well as a motile phenotype of PrCa cells. Given our observations that high levels of αVβ3 and, as shown here, of NgR2 are detected in human and mouse NEPrCa, our findings appear to be highly relevant to this aggressive and metastatic subtype of PrCa. This study is novel because NgR2 role has only minimally been investigated in cancer and has instead predominantly been analyzed in neurons. These data thus pave new avenues toward a comprehensive mechanistic understanding of integrin-directed signaling during PrCa progression toward a NE phenotype.