Successful cancer gene therapy requires a vector that systemically and specifically targets tumor cells throughout the body. Although several vectors have been developed to express cytotoxic genes via tumor-specific promoters or to selectively replicate in tumor cells, most are taken up and expressed by just a few targeted tumor cells. By contrast, we show here that blood-borne Sindbis viral vectors systemically and specifically infect tumor cells. A single intraperitoneal treatment allows the vectors to target most tumor cells, as demonstrated by immunohistochemistry, without infecting normal cells. Further, Sindbis infection is sufficient to induce complete tumor regression. We demonstrate systemic vector targeting of tumors growing subcutaneously, intrapancreatically, intraperitoneally and in the lungs. The vectors can also target syngeneic and spontaneous tumors in immune-competent mice. We document the anti-tumor specificity of a vector that systemically targets and eradicates tumor cells throughout the body without adverse effects.

Type 1 diabetes is an organ-specific autoimmune disease that is mediated by autoreactive T cells. We show here that administration of a soluble dimeric peptide-major histocompatibility complex (pMHC) class II chimera (DEF) to prediabetic double-transgenic mice prevents the onset of disease or, in animals that are already diabetic, restores normoglycemia. The antidiabetogenic effects of DEF rely on the induction of anergy in splenic autoreactive CD4+ T cells via alteration of early T cell receptor signaling and stimulation of interleukin 10-secreting T regulatory type 1 cells in the pancreas. Soluble dimeric pMHC class II may be useful in the development of immunospecific therapies for type 1 diabetes.

Background This study sought to assess the magnitude of and factors associated with mental health outcomes among frontline health care workers (FHCWs) providing care during the Spring 2020 COVID-19 pandemic surge in New York City. Methods A cross-sectional, survey-based study over 4 weeks during the Spring 2020 pandemic surge was used to assess symptoms of COVID-19-related posttraumatic stress disorder (PTSD), major depressive disorder (MDD), and generalized anxiety disorder (GAD) in 2,579 FHCWs at the Mount Sinai Hospital. Participants were additionally asked about their occupational and personal exposures to COVID-19. Multivariable logistic regression and relative importance analyses were conducted to identify factors associated with these outcomes. Results A total of 3,360 of 6,026 individuals completed the survey (55.8% participation), with 2,579 (76.8%) analyzed based on endorsing frontline responsibilities and providing information related to the three outcomes. 1,005 (39.0%) met criteria for symptoms of COVID-19-related PTSD, MDD, or GAD. 599 (23.3%) screened positively for PTSD symptoms, 683 (26.6%) for MDD symptoms, and 642 (25.0%) for GAD symptoms. Multivariable analyses revealed that past-year burnout was associated with the highest risk of developing symptoms for COVID-19-related PTSD (odds ratio [OR] = 2.10), MDD (OR = 2.83), and GAD (OR = 2.68). Higher perceived support from hospital leadership was associated with a lowest risk of all outcomes [PTSD (OR = 0.75), MDD (OR = 0.72), and GAD (OR = 0.76). Conclusion In this large sample of FHCWs providing care during the 2020 NYC pandemic surge, 39% experienced symptoms of COVID-19-related PTSD, MDD, and/or GAD and pre-pandemic burnout as well as leadership support were identified as the most highly associated factors. These findings suggest that interventions aimed at reducing burnout and augmenting support from hospital leadership may be appropriate targets to mitigate the risk for developing further psychopathology in this population and others working in the midst of crisis.

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Introduction Little is known about the relationship between moral distress and mental health problems. We examined moral distress in 2579 frontline healthcare workers (FHCWs) caring for coronavirus disease 2019 (COVID‐19) patients during the height of the spring 2020 pandemic surge in New York City. The goals of the study were to identify common dimensions of COVID‐19 moral distress; and to examine the relationship between moral distress, and positive screen for COVID‐19‐related posttraumatic stress disorder (PTSD) symptoms, burnout, and work and interpersonal functional difficulties. Method Data were collected in spring 2020, through an anonymous survey delivered to a purposively‐selected sample of 6026 FHCWs at Mount Sinai Hospital; 2579 endorsed treating COVID‐19 patients and provided complete survey responses. Physicians, house staff, nurses, physician assistants, social workers, chaplains, and clinical dietitians comprised the sample. Results The majority of the sample (52.7%–87.8%) endorsed moral distress. Factor analyses revealed three dimensions of COVID‐19 moral distress: negative impact on family, fear of infecting others, and work‐related concerns. All three factors were significantly associated with severity and positive screen for COVID‐19‐related PTSD symptoms, burnout, and work and interpersonal difficulties. Relative importance analyses revealed that concerns about work competencies and personal relationships were most strongly related to all outcomes. Conclusion Moral distress is prevalent in FHCWs and includes family‐, infection‐, and work‐related concerns. Prevention and treatment efforts to address moral distress during the acute phase of potentially morally injurious events may help mitigate risk for PTSD, burnout, and functional difficulties.