Alteration of Autophagy and Glial Activity in Nilotinib-Treated Huntington's Disease Patients.

Nilotinib is a tyrosine kinase inhibitor that is safe and tolerated in neurodegeneration, it achieves CSF concentration that is adequate to inhibit discoidin domain receptor (DDR)-1. Nilotinib significantly affects dopamine metabolites, including Homovanillic acid (HVA), resulting in an increase in brain dopamine. HD is a hereditary disease caused by mutations in the Huntingtin's (HTT) gene and characterized by neurodegeneration and motor and behavioral symptoms that are associated with activation of dopamine receptors. We explored the effects of a low dose of nilotinib (150 mg) on behavioral changes and motor symptoms in manifest HD patients and examined the effects of nilotinib on several brain mechanisms, including dopamine transmission and gene expression via cerebrospinal fluid (CSF) miRNA sequencing. Nilotinib, 150 mg, did not result in any behavioral changes, although it significantly attenuated HVA levels, suggesting reduction of dopamine catabolism. There was no significant change in HTT, phosphorylated neuro-filament and inflammatory markers in the CSF and plasma via immunoassays. Whole miRNA genome sequencing of the CSF revealed significant longitudinal changes in miRNAs that control specific genes associated with autophagy, inflammation, microglial activity and basal ganglia neurotransmitters, including dopamine and serotonin.

Covid-19 and Worker Issues: Lessons From a University-based Ad-Hoc Network.

The Covid-19 pandemic has made clear the central role of the workplace in public health. Workers and working families have been particularly impacted by a public health and economic crisis that has revealed both structural shortcomings and opportunities for future preparedness. In response to the pandemic, a group of scholars, labor and anti-poverty advocates, activists, union representatives, frontline workers, and public health professionals gathered to share observations and create a forum for information sharing and collaboration. Conversations evolved with the pandemic to include policy solutions aimed at addressing the pandemic's health and economic impacts. In this paper, we summarize key lessons from the "Covid-19 and Workers" calls and suggest that ongoing collaboration among labor activists and academic and public health advocates may help to prepare for new public health crises and protect the safety and health of workers and communities.