16 research outputs found

    Brief Report: Maternal Opioid Prescription from Preconception Through Pregnancy and the Odds of Autism Spectrum Disorder and Autism Features in Children

    Get PDF
    Opioid use during pregnancy is associated with suboptimal pregnancy outcomes. Little is known about child neurodevelopmental outcomes. We examined associations between maternal opioid prescriptions preconception to delivery (peri-pregnancy) and child’s risk of ASD, developmental delay/disorder (DD) with no ASD features, or ASD/DD with autism features in the Study to Explore Early Development, a case-control study of neurodevelopment. Preconception opioid prescription was associated with 2.43 times the odds of ASD [95% confidence interval (CI) 0.99, 6.02] and 2.64 times the odds of ASD/DD with autism features (95% CI 1.10, 6.31) compared to mothers without prescriptions. Odds for ASD and ASD/DD were non-significantly elevated for first trimester prescriptions. Work exploring mechanisms and timing between peri-pregnancy opioid use and child neurodevelopment is needed

    Towards annotating potential incoherences in BioPortal mappings

    No full text
    BioPortal is a repository for biomedical ontologies that also includes mappings between them from various sources. Considered as a whole, these mappings may cause logical errors, due to incompatibilities between the ontologies or even erroneous mappings. We have performed an automatic evaluation of BioPortal mappings between 19 ontology pairs using the mapping repair systems of LogMap and AgreementMakerLight. We found logical errors in 11 of these pairs, which on average involved 22% of the mappings between each pair. Furthermore, we conducted a manual evaluation of the repair results to identify the actual sources of error, verifying that erroneous mappings were behind over 60% of the repairs. Given the results of our analysis, we believe that annotating BioPortal mappings with information about their logical conflicts with other mappings would improve their usability for semantic web applications and facilitate the identification of erroneous mappings. In future work, we aim to collaborate with BioPortal developers in extending BioPortal with these annotations.Copyright 2014 Springer International Publishing Switzerland. The final publication is available at http://link.springer.com/chapter/10.1007%2F978-3-319-11915-1_

    G.O.2: Mutations in LMOD3 cause severe nemaline myopathy by disrupting thin filament organisation in skeletal muscle

    No full text
    Nemaline myopathy (NM) is a disorder of the skeletal muscle thin filament characterised by muscle dysfunction and electron-dense protein accumulations (nemaline bodies). Pathogenic mutations have been described in nine genes to date, but the genetic basis remains unknown in many cases. We used whole exome sequencing (WES) in two families with NM and subsequent gene sequencing in over 540 additional genetically unresolved NM patients to identify and characterise a new genetic cause of NM. We developed a knock-down zebrafish model of this condition and used immunohistochemistry, western blotting, single-fibre contractility studies and recombinant protein studies to characterise the expression, localisation and biochemical functions of the new disease-related protein. We identified homozygous or compound heterozygous variants in LMOD3, which encodes leiomodin-3 (Lmod3) in 21 patients from 14 families. Affected individuals had severe generalised weakness and hypotonia, and most affected individuals died in the neonatal period. We demonstrated that Lmod3 is expressed from early muscle differentiation, localises to thin filaments with enrichment at the pointed ends, and has strong actin nucleating activity. Loss of Lmod3 in patient muscle results in shortening and disorganisation of thin filaments. Knockdown of lmod3 in the zebrafish replicates this phenotype. These findings define a new genetic subtype of congenital myopathy and demonstrate an essential, previously unrecognised role for Lmod3 in the regulation of sarcomeric thin filaments in skeletal muscle
    corecore