microRNA-219 Reduces Viral Load and Pathologic Changes in Theiler's Virus-Induced Demyelinating Disease.

Analysis of microRNA (miR) expression in the central nervous system white matter of SJL mice infected with the BeAn strain of Theiler's murine encephalomyelitis virus (TMEV) revealed a significant reduction of miR-219, a critical regulator of myelin assembly and repair. Restoration of miR-219 expression by intranasal administration of a synthetic miR-219 mimic before disease onset ameliorates clinical disease, reduces neurogliosis, and partially recovers motor and sensorimotor function by negatively regulating proinflammatory cytokines and virus RNA replication. Moreover, RNA sequencing of host lesions showed that miR-219 significantly downregulated two genes essential for the biosynthetic cholesterol pathway, Cyp51 (lanosterol 14-α-demethylase) and Srebf1 (sterol regulatory element-binding protein-1), and reduced cholesterol biosynthesis in infected mice and rat CG-4 glial precursor cells in culture.

SJL bone marrow-derived macrophages do not have IRF3 mutations and are highly susceptible to Theiler's virus infection.

It is well known that SJL mice are susceptible to Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease while C57BL6 (B6) and B10 mice are resistant, and H-2 on a B10 background (B10.S) contributes modestly to susceptibility. A recent study linked two IRF3 non-conservative mutations in SJL compared to B10.

Canadian Rural/Remote Primary Care Physicians Perspectives on Child/Adolescent Mental Health Care Service Delivery.

Introduction: Primary Care Physicians (PCP) play a key role in the recognition and management of child/adolescent mental health struggles. In rural and under-serviced areas of Canada, there is a gap between child/adolescent mental health needs and service provision.

Methods: From a Canadian national needs assessment survey, PCPs' narrative comments were examined using quantitative and qualitative approaches.