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Glioblastoma (GBM) remains the most lethal and untreatable central nervous system malignancy. The challenges to devise novel and effective anti-tumor therapies include difficulty in locating the precise tumor border for complete surgical resection, and rapid regrowth of residual tumor tissue after standard treatment. Repeatable and non-invasive intranasal application of neural stem cells (NSCs) was recently shown to enable clinically relevant delivery of therapy to tumors. Treatment with chemotactic NSCs demonstrated significant survival benefits when coupled with radiation and oncolytic virotherapy in preclinical models of GBM. In order to further augment the clinical applicability of this novel therapeutic platform, we postulate that the FDA-approved compound, methimazole (MT), can be safely utilized to delay the nasal clearance and improve the ability of NSCs to penetrate the olfactory epithelium for robust in vivo brain tumor targeting and therapeutic actions. METHODS : To examine the role of reversible reduction of the olfactory epithelial barrier in non-invasive intranasal delivery, we explored the unique pharmacologic effect of MT at a single dosage regimen. In our proof-of-concept studies, quantitative magnetic resonance imaging (MRI), immunocytochemistry, and survival analysis were performed on glioma-bearing mice treated with a single dose of MT prior to intranasal anti-GBM therapy using an oncolytic virus (OV)-loaded NSCs. RESULTS: Based on histology and in vivo imaging, we found that disrupting the olfactory epithelium with MT effectively delays clearance and allows NSCs to persist in the nasal cavity for at least 24 h. MT pretreatment amplified the migration of NSCs to the tumor. The therapeutic advantage of this enhancement was quantitatively validated by tissue analysis and MRI tracking of NSCs loaded with superparamagnetic iron oxide nanoparticles (SPIOs) in live animals. Moreover, we observed significant survival benefits in GBM-bearing mice treated with intranasal delivery of oncolytic virus-loaded NSCs following MT injection. Conclusion: Our work identified a novel pharmacologic strategy to accelerate the clinical application of the non-invasive NSCs-based therapeutic platform to tackle aggressive brain tumors.

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Background The COVID-19 pandemic has disproportionately affected more socioeconomically disadvantaged persons and areas. We sought to determine how certain sociodemographic factors were correlated to adolescents’ COVID-19 vaccination rates in towns and cities (“communities”) in the Commonwealth of Massachusetts. Methods Data on COVID-19 vaccination rates were obtained over a 20-week period from March 30, 2021 to August 10, 2021. Communities’ adolescent (ages 12-19) vaccination rates were compared across quintiles of community-level income, COVID-19 case rate, and proportion of non-Hispanic Black or Hispanic individuals. Other variables included population density and earlier COVID-19 vaccination rates of adolescents and adults, averaged from March 30 to May 11 to determine their effects on vaccination rates on August 10. Linear and logistic regression was used to estimate individual effects of variables on adolescent vaccination rates. Results Higher median household income, lower proportion of Black or Hispanic individuals, higher early adolescent COVID-19 vaccination rates, and higher early adult COVID-19 vaccination rates were associated with higher later adolescent COVID-19 vaccination rates. Income per $10,000 (adjusted odds ratio=1.01 [95% confidence interval=1.01-1.02]), proportion of Hispanic individuals (1.33 [1.13-1.56]), early adolescent COVID-19 vaccination rates (5.28 [4.67-5.96]), and early adult COVID-19 vaccination rates (2.31 [2.02-2.64]) were associated with higher adolescent COVID-19 vaccination on August 10, while proportion of Black individuals approached significance (1.26 [0.98-1.61]). Conclusions Vaccination efforts for adolescents in Massachusetts should focus on boosting vaccination rates early in communities with the lowest incomes and greatest proportion of Hispanic individuals and consider targeting communities with a greater proportion of Black individuals.

in EMCD 2,4,5 and immune complexes consisting of IgM, IgA, C3, and fibrin deposited in cutaneous vasculature found in EM. 4 Limitations of this systematic review include small sample sizes, lack of high-quality randomized controlled trials, and lack of follow-up data. In addition, confirmation of EMCD in all included cases is difficult to determine. However, positive patch testing confirmed 95.1% (n = 116/122) of allergens, EM-like histology was confirmed by biopsy in 92.7% (n = 38/41) of patients, and targeted lesions were reported in 78.5% (n = 84/107) of patients. Despite these limitations, our findings provide important conclusions to guide EMCD management, showing that 99.0% cases (n = 98/99) of EMCD achieved CoR with allergen withdrawal or allergen withdrawal and corticosteroids.