Abnormalities in the Structure and Function of Cerebellar Neurons and Neuroglia in the Lc/+ Chimeric Mouse Model of Variable Developmental Purkinje Cell Loss.

Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders characterized by impaired and disordered language, decreased social interactions, stereotyped and repetitive behaviors, and impaired fine and gross motor skills. It has been well established that cerebellar abnormalities are one of the most common structural changes seen in the brains of people diagnosed with autism. Common cerebellar pathology observed in autistic individuals includes variable loss of cerebellar Purkinje cells (PCs) and increased numbers of reactive neuroglia in the cerebellum and cortical brain regions. The Lc/+ mutant mouse loses 100 % of cerebellar PCs during the first few weeks of life and provided a valuable model to study the effects of developmental PC loss on underlying structural and functional changes in cerebellar neural circuits. Lurcher (Lc) chimeric mice were also generated to explore the link between variable cerebellar pathology and subsequent changes in the structure and function of cerebellar neurons and neuroglia. Chimeras with the most severe cerebellar pathology (as quantified by cerebellar PC counts) had the largest changes in cFos expression (an indirect reporter of neural activity) in cerebellar granule cells (GCs) and cerebellar nucleus (CN) neurons. In addition, Lc chimeras with the fewest PCs also had numerous reactive microglia and Bergmann glia located in the cerebellar cortex. Structural and functional abnormalities observed in the cerebella of Lc chimeras appeared to be along a continuum, with the degree of pathology related to the number of PCs in individual chimeras.

Factors Affecting Delay in Filling Prescriptions for Dual Antiplatelet Therapy After Coronary Stenting.

Dual antiplatelet therapy (DAPT) is critical in preventing stent thrombosis after percutaneous coronary intervention (PCI). Delays in DAPT after PCI have been associated with stent thrombosis, reinfarction, and death. Cases of death, stent thrombosis, and reinfarction at our institution have been attributed to patient delays in accessing DAPT on discharge after PCI. We sought to determine the proportion of patients that delay filling their discharge prescription for DAPT after PCI and factors that influence delays in DAPT prescription-filling. We reviewed all patients who received PCI at St Paul's Hospital from April 1, 2015 to April 1, 2016 and determined the date of the first prescription filling of a P2Y12 antiplatelet agent after hospital discharge. The primary outcome was proportion of patients who delay filling their DAPT discharge prescription. Logistic regression analysis was performed to determine the relationship of various factors with delays in DAPT-filling. Six hundred fifty-one patients were included in the final analysis. Age, sex, and provincial drug coverage status were not associated with delays in DAPT prescription-filling. Distance of patient's residence to St Paul's Hospital was associated with a significant delay in DAPT prescription filling (adjusted odds ratio, 1.90; 95% confidence interval, 1.11-3.22). Hospital discharge processes to ensure timely access to DAPT after PCI should be established.