5 research outputs found

    Parent and teacher-reported child outcomes seven years after mild traumatic brain Injury: A nested case control study

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    Background: Increasing evidence suggests potential lifetime effects following mild traumatic brain injury (TBI) in childhood. Few studies have examined medium-term outcomes among hospitalized and non-hospitalized samples. Study aims were to describe children's behavioral and emotional adjustment, executive function (EF), quality of life, and participation at 7-years following mild TBI using parents' and teachers' reports. Methods: Nested case control study of 86 children (68% male, mean age at assessment = 11.27 years; range 7–17 years) who sustained a mild TBI 7-years previously, identified from a prospective, population-based study. They were compared to 69 children free from TBI (61% male, mean age at assessment = 11.12 years; range 5–17 years). In addition to parent-reported socio-demographic details, parents (mild TBI n = 86, non-TBI n = 69) completed age-appropriate standardized questionnaires about children's health-related quality of life, behavioral and emotional adjustment, EF, and social participation. Parents own mood was assessed using the Hospital Anxiety and Depression Scale. Teachers (mild TBI n = 53, non-TBI n = 42) completed questionnaires about children's behavioral and emotional adjustment, and EF. Results: Parent reports showed median group-level scores for cases were statistically significantly greater than controls for emotional symptoms, conduct problems, hyperactivity/inattention, total behavioral difficulties, inhibitory control, shifting, planning/organizing, and Global Executive Composite (total) EF difficulties (p-values 0.001–0.029). Parent reports of child quality of life and social participation were similar, as were teacher reports of child behavioral and emotional adjustment, and EF (p > 0.05). When examining clinical cut-offs, compared to controls, cases had a higher risk of parent-reported total EF difficulties (odds ratio = 3.00) and, to a lesser extent, total behavior problems (odds ratio = 2.51). Conclusions: As a group, children with a history of mild TBI may be at elevated risk for clinically significant everyday EF difficulties in the medium-term compared to non-TBI controls, as judged by their parents. Further multi-informant longitudinal research is required, following larger samples. Aspects requiring particular attention include pre-injury characteristics, such as sleep disturbances and comorbidities (e.g., headaches), that may act as potential confounders influencing the association between mild TBI and child behavioral problems

    Taverna: a tool for building and running workflows of services

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    Taverna is an application that eases the use and integration of the growing number of molecular biology tools and databases available on the web, especially web services. It allows bioinformaticians to construct workflows or pipelines of services to perform a range of different analyses, such as sequence analysis and genome annotation. These high-level workflows can integrate many different resources into a single analysis. Taverna is available freely under the terms of the GNU Lesser General Public License (LGPL) fro

    Safinamide and flecainide protect axons and reduce microglial activation in models of multiple sclerosis

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    Axonal degeneration is a major cause of permanent disability in the inflammatory demyelinating disease multiple sclerosis, but no therapies are known to be effective in axonal protection. Sodium channel blocking agents can provide effective protection of axons in the white matter in experimental models of multiple sclerosis, but the mechanism of action (directly on axons or indirectly via immune modulation) remains uncertain. Here we have examined the efficacy of two sodium channel blocking agents to protect white matter axons in two forms of experimental autoimmune encephalomyelitis, a common model of multiple sclerosis. Safinamide is currently in phase III development for use in Parkinson’s disease based on its inhibition of monoamine oxidase B, but the drug is also a potent state-dependent inhibitor of sodium channels. Safinamide provided significant protection against neurological deficit and axonal degeneration in experimental autoimmune encephalomyelitis, even when administration was delayed until after the onset of neurological deficit. Protection of axons was associated with a significant reduction in the activation of microglia/macrophages within the central nervous system. To clarify which property of safinamide was likely to be involved in the suppression of the innate immune cells, the action of safinamide on microglia/macrophages was compared with that of the classical sodium channel blocking agent, flecainide, which has no recognized monoamine oxidase B activity, and which has previously been shown to protect the white matter in experimental autoimmune encephalomyelitis. Flecainide was also potent in suppressing microglial activation in experimental autoimmune encephalomyelitis. To distinguish whether the suppression of microglia was an indirect consequence of the reduction in axonal damage, or possibly instrumental in the axonal protection, the action of safinamide was examined in separate experiments in vitro. In cultured primary rat microglial cells activated by lipopolysaccharide, safinamide potently suppressed microglial superoxide production and enhanced the production of the anti-oxidant glutathione. The findings show that safinamide is effective in protecting axons from degeneration in experimental autoimmune encephalomyelitis, and that this effect is likely to involve a direct effect on microglia that can result in a less activated phenotype. Together, this work highlights the potential of safinamide as an effective neuroprotective agent in multiple sclerosis, and implicates microglia in the protective mechanism
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