No abstract

evere infection with COVID-19 has been linked to immune dysregulation, including impaired or delayed production of type I and type III interferons 1-5 , marked lymphopenia [6][7][8][9][10] and a paradoxical increase in pro-inflammatory cytokines, such as TNF-α, IL-1β and IL-6 1,4,6,[11][12][13] . Alteration of T cell compartments include increases in effector and activated CD4 and CD8 T cells [14][15][16][17] , CD8 + T cells contribute to survival in patients with COVID-19 and hematologic cancer

Large-scale usage of antibiotics can generate seasonal patterns of resistance that fluctuate on a short time scale with changes in antibiotic retail sales, suggesting that use of antibiotics in the winter could have a significant effect on resistance. In addition, the strong correlation between community use of antibiotics and resistance isolated in the hospital indicates that restrictions imposed at the hospital level are unlikely to be effective unless coordinated with campaigns to reduce unnecessary antibiotic use at the community level.

Successful treatment of brain tumors such as glioblastoma multiforme (GBM) is limited in large part by the cumulative dose of Radiation Therapy (RT) that can be safely given and the blood-brain barrier (BBB), which limits the delivery of systemic anticancer agents into tumor tissue. Consequently, the overall prognosis remains grim. Herein, we report our pilot studies in cell culture experiments and in an animal model of GBM in which RT is complemented by PEGylated-gold nanoparticles (GNPs). GNPs significantly increased cellular DNA damage inflicted by ionizing radiation in human GBM-derived cell lines and resulted in reduced clonogenic survival (with dose-enhancement ratio of ∼1.3). Intriguingly, combined GNP and RT also resulted in markedly increased DNA damage to brain blood vessels. Follow-up in vitro experiments confirmed that the combination of GNP and RT resulted in considerably increased DNA damage in brain-derived endothelial cells. Finally, the combination of GNP and RT increased survival of mice with orthotopic GBM tumors. Prior treatment of mice with brain tumors resulted in increased extravasation and in-tumor deposition of GNP, suggesting that RT-induced BBB disruption can be leveraged to improve the tumor-tissue targeting of GNP and thus further optimize the radiosensitization of brain tumors by GNP. These exciting results together suggest that GNP may be usefully integrated into the RT treatment of brain tumors, with potential benefits resulting from increased tumor cell radiosensitization to preferential targeting of tumor-associated vasculature.