Effects of Veliparib on Microglial Activation and Functional Outcomes after Traumatic Brain Injury in the Rat and Pig.

The inflammation response induced by brain trauma can impair recovery. This response requires several hours to develop fully and thus provides a clinically relevant therapeutic window of opportunity. Poly(ADP-ribose) polymerase inhibitors suppress inflammatory responses, including brain microglial activation. We evaluated delayed treatment with veliparib, a poly(ADP-ribose) polymerase inhibitor, currently in clinical trials as a cancer therapeutic, in rats and pigs subjected to controlled cortical impact (CCI). In rats, CCI induced a robust inflammatory response at the lesion margins, scattered cell death in the dentate gyrus, and a delayed, progressive loss of corpus callosum axons. Pre-determined measures of cognitive and motor function showed evidence of attentional deficits that resolved after three weeks and motor deficits that recovered only partially over eight weeks. Veliparib was administered beginning 2 or 24 h after CCI and continued for up to 12 days. Veliparib suppressed CCI-induced microglial activation at doses of 3 mg/kg or higher and reduced reactive astrocytosis and cell death in the dentate gyrus, but had no significant effect on delayed axonal loss or functional recovery. In pigs, CCI similarly induced a perilesional microglial activation that was attenuated by veliparib. CCI in the pig did not, however, induce detectable persisting cognitive or motor impairment. Our results showed veliparib suppression of CCI-induced microglial activation with a delay-to-treatment interval of at least 24 h in both rats and pigs, but with no associated functional improvement. The lack of improvement in long-term recovery underscores the complexities in translating anti-inflammatory effects to clinically relevant outcomes

Mobile app for personalized sleep–wake management for shift workers: A user testing trial

Objective Development of personalized sleep–wake management tools is critical to improving sleep and functional outcomes for shift workers. The objective of the current study was to test the performance, engagement and usability of a mobile app ( SleepSync ) for personalized sleep–wake management in shift workers that aid behavioural change and provide practical advice by providing personalized sleep scheduling recommendations and education. Methods Shift workers ( n  = 27; 20 healthcare and 7 from other industries) trialled the mobile app for two weeks to determine performance, engagement and usability. Primary outcomes were self-reported total sleep time, ability to fall asleep, sleep quality and perception of overall recovery on days off. Secondary performance outcomes included sleep disturbances (insomnia and sleep hygiene symptoms, and sleep-related impairments) and mood (anxiety, stress and depression) pre- and post-app use. Satisfaction with schedule management, integration into daily routine and influence on behaviour were used to determine engagement, while the usability was assessed for functionality and ease of use of features. Results Total sleep time ( P  = .04), ability to fall asleep ( P  < .001), quality of sleep ( P  = .001), insomnia ( P  = .02), sleep hygiene ( P  = .01), sleep-related impairments ( P  = .001), anxiety ( P  = .001), and stress ( P  = .006) were all improved, with non-significant improvements in recovery on days off ( P  = .19) and depression ( P  = .07). All measures of engagement and usability were scored positively by the majority of users. Conclusions This pilot trial provides preliminary evidence of the positive impact of the SleepSync app in improving sleep and mood outcomes in shift workers, and warrants confirmation in a larger controlled trial

Effects of Veliparib on Microglial Activation and Functional Outcomes after Traumatic Brain Injury in the Rat and Pig.

The inflammation response induced by brain trauma can impair recovery. This response requires several hours to develop fully and thus provides a clinically relevant therapeutic window of opportunity. Poly(ADP-ribose) polymerase inhibitors suppress inflammatory responses, including brain microglial activation. We evaluated delayed treatment with veliparib, a poly(ADP-ribose) polymerase inhibitor, currently in clinical trials as a cancer therapeutic, in rats and pigs subjected to controlled cortical impact (CCI). In rats, CCI induced a robust inflammatory response at the lesion margins, scattered cell death in the dentate gyrus, and a delayed, progressive loss of corpus callosum axons. Pre-determined measures of cognitive and motor function showed evidence of attentional deficits that resolved after three weeks and motor deficits that recovered only partially over eight weeks. Veliparib was administered beginning 2 or 24 h after CCI and continued for up to 12 days. Veliparib suppressed CCI-induced microglial activation at doses of 3 mg/kg or higher and reduced reactive astrocytosis and cell death in the dentate gyrus, but had no significant effect on delayed axonal loss or functional recovery. In pigs, CCI similarly induced a perilesional microglial activation that was attenuated by veliparib. CCI in the pig did not, however, induce detectable persisting cognitive or motor impairment. Our results showed veliparib suppression of CCI-induced microglial activation with a delay-to-treatment interval of at least 24 h in both rats and pigs, but with no associated functional improvement. The lack of improvement in long-term recovery underscores the complexities in translating anti-inflammatory effects to clinically relevant outcomes

Dielectric materials for electrowetting-on-dielectric actuation

10.1007/s00542-009-0933-zMicrosystem Technologies163449-46