Progress for ocular AAV gene therapy has been hindered by AAV-induced inflammation, limiting dose escalation and long-term efficacy. Broadly, the extent of inflammatory responses alters with age and sex, yet these factors are poorly represented in pre-clinical development of ocular AAV gene therapies. Here, we combined clinical imaging, flow cytometry and bulk-sequencing of sorted microglia to interrogate the longitudinal inflammatory response following intravitreal delivery of AAV2 in young (3-month), middle aged (9-month) and old (18-month) Cx3cr1-creER:R26tdTomato+/- mice of both sexes.
View Article and Find Full Text PDFVaccination strategies against HIV-1 aim to elicit broadly neutralizing antibodies (bnAbs) using prime-boost regimens with HIV envelope (Env) immunogens. Epitope mapping has shown that early antibody responses are directed to easily accessible nonneutralizing epitopes on Env instead of bnAb epitopes. Autologously neutralizing antibody responses appear upon boosting, once immunodominant epitopes are saturated.
View Article and Find Full Text PDFBotulinum toxin type A is a first line choice in the treatment of spastic muscle overactivity. However, targeting the muscles involved in the deformity with the appropriate dose as well as choosing the goal to achieve and predicting the expected results can be challenging. Diagnostic nerve block with anaesthetics rapidly and temporarily suppresses overactivity of the selected muscle allowing clinicians to identify the involved muscles and the potential improvement of botulinum toxin injections.
View Article and Find Full Text PDFObjective: To examine whether medical student empathy changes throughout the five years of a UK medical school.
Methods: Students completed an online version of the Jefferson Scale of Empathy (JSE-S) during the 2022-2023 academic year. Comparisons of empathy scores were made using analysis of variance (ANOVA), and independent -tests.