ABSTRACT
-To characterize the performance of the TUBB4A-related disorder population at traditional gross motor evaluations and adaptive behavior questionnaires. -To determine the functional performance of the population and confirm the existence of a functional genotype/phenotype correlation. Prospective study. Children were evaluated by providers trained in the administration of Gross Motor Function Measure-88 (GMFM-88), and Vineland Adaptive Behavior Scale 3rd edition (VABS-3) Parent/Caregiver Form. Motor function and adaptive behavior abilities were assessed with hybrid in-person/remote evaluations, due to COVID-19 pandemic constrains in travel. Fifty individuals with a clinical and molecular diagnosis of TUBB4A-related disorders. None. GMFM-88, VABS-3. Patients showed severe gross motor impairment, with floor effect performance at the GMFM-88. Impaired performance of motor abilities and daily living skills was observed at the VABS-3, while social and communicative abilities were relatively spared. A genotype-phenotype correlation was observed, with a lower overall functional level observed in the non-p.Asp249Asn subcohort. The severe motor impairment observed in this population makes challenging the administration of commonly administered gross motor assessments such as the GMFM-88, while the VABS-3 appears to describe better this population, being able to highlight functional differences associated with specific genotypes. The identification of outcome measures tailored on populations with rare disorders has the potential to be helpful in clinical prognostication as well as cohort selection for future clinical trials. None.
ABSTRACT
Background Cytomegalovirus (CMV) seropositivity has a significant immunomodulating over the life course, both with respect to responses to infections and responses to vaccines. For example, influenza vaccine response is known from multivariate analyses to be reduced by CMV seropositivity in elderly individuals. In patients with COVID-19, evidence suggests there are interactions between SARS-CoV-2 and CMV. CMV seropositives may have more severe COVID disease, and patients recovering from COVID often reactivate latent CMV, leading to end-organ CMV disease. This study aimed to test two hypotheses: 1) that vectored vaccines based on attenuated arenaviruses demonstrate equivalent immunogenicity to adjuvanted protein subunit spike (S) vaccines in a guinea pig vaccine model;2) that CMV seropositivity impacts the immune response to S protein-based vaccines. Method Guinea pigs (n=3 per group) were vaccinated with a 2-dose series of an attenuated arenavirus (Pichinde virus) S protein-vectored vaccine by intranasal (IN;n=4) or intramuscular (IM) route at a dose of 1x10