49 research outputs found

    Usability of the SAFEWAY@SCHOOL system in children with cognitive disabilities

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    PurposeSAFEWAY2SCHOOL is a programme based on several systems for the enhancement of school transportation safety for children. The aim of the study was to explore whether children with cognitive disabilities will notice, realise, understand, trust and accept the SAFEWAY2SCHOOL system and act in accordance with its instructions. Methods Fourteen children with cognitive disabilities and a control group of 23 children were shown five videos of scenarios involving journeys to and from school. During the first viewing visual scanning patterns were recorded with an eye tracking device. After a second viewing the participant was asked ten questions per scenario. Five questions addressed what the children saw on the video, and the remaining five what they would need to know and/or do within the scenario. Additional ratings of trust, likability, acceptability and usability were also collected. Results Very few differences were found in the visual scanning patterns of children with disabilities compared to children who participated in the control group. Of the 50 questions regarding what children saw or needed to know and/or do, only one significant difference between groups was found. No significant differences were found regarding self-reported ratings of trust, acceptability or usability of the system. Despite some significant differences across five of the 11 likability aspects, ratings were consistently high for both groups. Conclusions Children with cognitive disabilities proved that the SAFEWAY2SCHOOL system is as useful for them as it was for children in the control group. However, a valid estimation of the full utility of SAFEWAY2SCHOOL requires in situ testing of the system with these children

    Preclinical evaluation of KIT/PDGFRA and mTOR inhibitors in gastrointestinal stromal tumors using small animal FDG PET

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    <p>Abstract</p> <p>Background</p> <p>Primary and secondary drug resistance to imatinib and sunitinib in patients with gastrointestinal stromal tumors (GISTs) has led to a pressing need for new therapeutic strategies such as drug combinations. Most GISTs are caused by mutations in the KIT receptor, leading to upregulated KIT tyrosine kinase activity. Imatinib and nilotinib directly inhibit the kinase activity of KIT, while RAD001 (everolimus) inhibits mTOR. We report a preclinical study on drug combinations in a xenograft model of GIST in which effects on tumor dimensions and metabolic activity were assessed by small animal PET imaging.</p> <p>Methods</p> <p>Rag2-/-; ╬│common -/- male mice were injected s.c. into the right leg with GIST 882. The animals were randomized into 6 groups of 6 animals each for different treatment regimens: No therapy (control), imatinib (150 mg/kg b.i.d.) by oral gavage for 6 days, then once/day for another 7 days, everolimus (10 mg/kg/d.) by oral gavage, everolimus (10 mg/kg/d.) + imatinib (150 mg/kg b.i.d.) by oral gavage for 6 days, then once/day for another 7 days, nilotinib (75 mg/kg/d.) by oral gavage, nilotinib (75 mg/kg/d.) + imatinib (150 mg/kg b.i.d) by oral gavage for 6 days, then once/day for another 7 days. Tumor growth control was evaluated by measuring tumor volume (cm<sup>3</sup>). Small animal PET (GE Explore tomography) was used to evaluate tumor metabolism and performed in one animal per group at base-line then after 4 and 13 days of treatment.</p> <p>Results</p> <p>After a median latency time of 31 days, tumors grew in all animals (volume 0,06-0,15 cm<sup>3</sup>) and the treatments began at day 38 after cell injection. Tumor volume control (cm3) after 13 days of treatment was > 0.5 for imatinib alone and nilotinib alone, and < 0.5 for the 2 combinations of drugs and for everolimus alone. The baseline FDG uptake was positive in all animals. FDG/SUV/TBR was strongly reduced over time by everolimus both as a single agent and in combination with imatinib respectively: 3.1 vs. 2.3 vs. 1.9 and 2.5 vs 2.3 vs 0.</p> <p>Conclusions</p> <p>As single agents, all drugs showed an anti-tumor effect in GIST xenografts but everolimus was superior. The everolimus plus imatinib combination appeared to be the most active regimen both in terms of inhibiting tumor growth and tumor metabolism. The integration of everolimus in GIST treatment merits further investigation.</p

    Spatiotemporal mapping of interictal spike propagation: a novel methodology applied to pediatric intracranial EEG recordings.

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    Synchronized cortical activity is implicated in both normative cognitive functioning andmany neurological disorders. For epilepsy patients with intractable seizures, irregular patterns ofsynchronization within the epileptogenic zone (EZ) is believed to provide the network substratethrough which seizures initiate and propagate. Mapping the EZ prior to epilepsy surgery is critical fordetecting seizure networks in order to achieve post-surgical seizure control. However, automatedtechniques for characterizing epileptic networks have yet to gain traction in the clinical setting.Recent advances in signal processing and spike detection have made it possible to examine thespatiotemporal propagation of interictal spike discharges across the epileptic cortex. In this study, wepresent a novel methodology for detecting, extracting, and visualizing spike propagation anddemonstrate its potential utility as a biomarker for the epileptogenic zone. Eighteen pre-surgicalintracranial EEG recordings were obtained from pediatric patients ultimately experiencing favorable(i.e., seizure-free, n = 9) or unfavorable (i.e., seizure-persistent, n = 9) surgical outcomes. Novelalgorithms were applied to extract multi-channel spike discharges and visualize their spatiotemporalpropagation. Quantitative analysis of spike propagation was performed using trajectory clusteringand spatial autocorrelation techniques. Comparison of interictal propagation patterns revealed anincrease in trajectory organization (i.e., spatial autocorrelation) among Sz-Free patients compared toSz-Persist patients. The pathophysiological basis and clinical implications of these findings areconsidered

    Skeletal muscle mitochondria in the elderly: effects of physical fitness and exercise training.

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    Context: Sarcopenia is thought to be associated with mitochondrial (M) loss. It is unclear whether the decrease in M content is consequent to aging per se or to decreased physical activity. Objectives: To examine the influence of fitness on M content and function, and to assess whether exercise could improve M function in older adults. Design and subjects: Three distinct studies were conducted: 1) a cross-sectional observation comparing M content and fitness in a large heterogeneous cohort of older adults; 2) a case-control study comparing chronically endurance-trained older adults (A) and sedentary (S) subjects matched for age and gender; 3) a 4-month exercise intervention in S. Setting: University-based clinical research center Outcomes: M volume density (Mv) was assessed by electron microscopy from vastus lateralis biopsies, electron transport chain proteins (ETC) by western blotting, mRNAs for transcription factors involved in M biogenesis by qRT-PCR and in-vivo oxidative capacity (ATPmax) by (31)P-MR spectroscopy. Peak oxygen uptake (VO2peak) was measured by GXT. Results: VO2peak was strongly correlated with Mv in eighty 60-80 yo adults. Comparison of A vs. S revealed differences in Mv, ATPmax and some ETC complexes. Finally, exercise intervention confirmed that S are able to recover Mv, ATPmax and specific transcription factors. Conclusions: These data suggest that 1) aging per se is not the primary culprit leading to M dysfunction, 2) an aerobic exercise program, even at an older age, can ameliorate the loss in skeletal muscle M content and may prevent aging muscle comorbidities and 3) the improvement of M function is all about content

    Interaction of Bartonella henselae with the Murine Macrophage Cell Line J774: Infection and Proinflammatory Response

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    Bartonella henselae is the causative agent of cat scratch disease (CSD), a self-limiting condition characterized by a subacute regional lymphadenopathy that may develop into disseminated bartonellosis in immunocompromised subjects. Mice experimentally infected with B. henselae display typical liver and spleen granulomas rich in T cells and macrophages. So far there are no data on the interaction between bartonellae and macrophages. In order to clarify this topic, we investigated the interaction of B. henselae with J774, a mouse macrophage cell line. Analysis of bacterial uptake by functional assays and transmission electron microscopy indicates that bartonellae can enter and survive inside J774. Entry occurred within 30 min postinfection and reached a plateau at 160 min. Infection of J774 was followed by a dose-dependent release of the proinflammatory cytokines tumor necrosis factor alpha, interleukin 1╬▓ (IL-1╬▓), and IL-6. Bartonellae persisted intracellularly without loss of viability for at least 8 h, and their number slightly decreased 24 h postinfection. Gamma interferon (IFN-╬│) treatment of J774 significantly decreased the number of recoverable bacteria at 8 and 24 h. This enhancement of macrophage bactericidal activity was associated with nitric oxide (NO) release and was prevented by the addition of the competitive inhibitor of NO synthesis N(G)-monomethyl l-arginine. These findings suggest that IFN-╬│-mediated activation of macrophages may be important for the clearing of B. henselae infection and that anti-B. henselae microbicidal activity of IFN-╬│-activated macrophages is mediated to a large extent by NO production