48 research outputs found

    Stoichiometry of a regulatory splicing complex revealed by single-molecule analyses

    Get PDF
    Splicing is regulated by complex interactions of numerous RNA-binding proteins. The molecular mechanisms involved remain elusive, in large part because of ignorance regarding the numbers of proteins in regulatory complexes. Polypyrimidine tract-binding protein (PTB), which regulates tissue-specific splicing, represses exon 3 of α-tropomyosin through distant pyrimidine-rich tracts in the flanking introns. Current models for repression involve either PTB-mediated looping or the propagation of complexes between tracts. To test these models, we used single-molecule approaches to count the number of bound PTB molecules both by counting the number of bleaching steps of GFP molecules linked to PTB within complexes and by analysing their total emissions. Both approaches showed that five or six PTB molecules assemble. Given the domain structures, this suggests that the molecules occupy primarily multiple overlapping potential sites in the polypyrimidine tracts, excluding propagation models. As an alternative to direct looping, we propose that repression involves a multistep process in which PTB binding forms small local loops, creating a platform for recruitment of other proteins that bring these loops into close proximity

    Cranial and ventricular size following shunting or endoscopic third ventriculostomy (ETV) in infants with aqueductal stenosis: further insights from the International Infant Hydrocephalus Study (IIHS)

    Get PDF
    Purpose: The craniometrics of head circumference (HC) and ventricular size are part of the clinical assessment of infants with hydrocephalus and are often utilized in conjunction with other clinical and radiological parameters to determine the success of treatment. We aimed to assess the effect of endoscopic third ventriculostomy (ETV) and shunting on craniometric measurements during the follow-up of a cohort of infants with symptomatic triventricular hydrocephalus secondary to aqueductal stenosis. Methods: We performed a post hoc analysis of data from the International Infant Hydrocephalus Study (IIHS)—a prospective, multicenter study of infants (\u3c 24 months old) with hydrocephalus from aqueductal stenosis who were treated with either an ETV or shunt. During various stages of a 5-year follow-up period, the following craniometrics were measured: HC, HC centile, HC z-score, and frontal-occipital horn ratio (FOR). Data were compared in an analysis of covariance, adjusting for baseline variables including age at surgery and sex. Results: Of 158 enrolled patients, 115 underwent an ETV, while 43 received a shunt. Both procedures led to improvements in the mean HC centile position and z-score, a trend which continued until the 5-year assessment point. A similar trend was noted for FOR which was measured at 12 months and 3 years following initial treatment. Although the values were consistently higher for ETV compared with shunt, the differences in HC value, centile, and z-score were not significant. ETV was associated with a significantly higher FOR compared with shunting at 12 months (0.52 vs 0.44; p = 0.002) and 3 years (0.46 vs 0.38; p = 0.03) of follow-up. Conclusion: ETV and shunting led to improvements in HC centile, z-score, and FOR measurements during long-term follow-up of infants with hydrocephalus secondary to aqueductal stenosis. Head size did not significantly differ between the treatment groups during follow-up, however ventricle size was greater in those undergoing ETV when measured at 1 and 3 years following treatment

    The management and outcome for patients with chronic subdural hematoma: a prospective, multicenter, observational cohort study in the United Kingdom

    Get PDF
    Symptomatic chronic subdural hematoma (CSDH) will become an increasingly common presentation in neurosurgical practice as the population ages, but quality evidence is still lacking to guide the optimal management for these patients. The British Neurosurgical Trainee Research Collaborative (BNTRC) was established by neurosurgical trainees in 2012 to improve research by combining the efforts of trainees in each of the United Kingdom (UK) and Ireland's neurosurgical units (NSUs). The authors present the first study by the BNTRC that describes current management and outcomes for patients with CSDH throughout the UK and Ireland. This provides a resource both for current clinical practice and future clinical research on CSDH

    Implications for sequencing of biologic therapy and choice of second anti-TNF in patients with inflammatory bowel disease: results from the IMmunogenicity to Second Anti-TNF Therapy (IMSAT) therapeutic drug monitoring study

    Get PDF

    Patient-Reported oral health outcome measurement for children and adolescents

    Get PDF
    BACKGROUND: Oral health is an important component of daily functioning and well-being. A comprehensive patient-reported oral health measure is needed to gauge the impact of oral health status on children and adolescents. This study aims to develop oral health item banks and associated short-form surveys for children and adolescents 2–17 year olds. METHODS: Using children and adolescents, ages 2–17 years, selected from diverse dental sites in Greater Los Angeles Area, we propose to develop state-of-the-science methods to create oral health item banks to effectively measure oral health outcomes for children and adolescents. Methods include a literature review of existing measures, focus groups, cognitive interviews, drafting and field testing of survey items, and evaluation of the psychometric properties of the measures. RESULTS: Based on the systematic literature search and focus groups, we identified core (physical health, mental health, and social function domains) and peripheral (e.g., need and access) oral health domains. We then drafted survey items and revised them based on 66 cognitive interviews (27 children/adolescents and 39 parents) with 39 families. The revised items will be administered in a field test of 500 children and adolescents ages 2–17, and their parents. CONCLUSIONS: The qualitative methods used in the initial phases of the project (focus group and cognitive interviews) are the initial steps in the development of oral health item banks and associated short-form surveys for children and adolescents. The oral health items can potentially be used to create effective computerized adaptive test and/or create ad hoc short forms targeting specific areas of oral health to survey large populations of children with much less cost compared with traditional clinical oral health examination
    corecore