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Abstract Plasmodium falciparum malaria contributes to a significant global disease burden. Circumsporozoite protein (CSP), the most abundant sporozoite stage antigen, is a prime vaccine candidate. Inhibitory monoclonal antibodies (mAbs) against CSP map to either a short junctional sequence or the central (NPNA)n repeat region. We compared in vitro and in vivo activities of six CSP-specific mAbs derived from human recipients of a recombinant CSP vaccine RTS,S/AS01 (mAbs 317 and 311); an irradiated whole sporozoite vaccine PfSPZ (mAbs CIS43 and MGG4); or individuals exposed to malaria (mAbs 580 and 663). RTS,S mAb 317 that specifically binds the (NPNA)n epitope, had the highest affinity and it elicited the best sterile protection in mice. The most potent inhibitor of sporozoite invasion in vitro was mAb CIS43 which shows dual-specific binding to the junctional sequence and (NPNA)n. In vivo mouse protection was associated with the mAb reactivity to the NANPx6 peptide, the in vitro inhibition of sporozoite invasion activity, and kinetic parameters measured using intact mAbs or their Fab fragments. Buried surface area between mAb and its target epitope was also associated with in vivo protection. Association and disconnects between in vitro and in vivo readouts has important implications for the design and down-selection of the next generation of CSP based interventions.

Abstract Background Powered exoskeletons provide a way to stand and walk for people with severe spinal cord injury. Here, we used the ReWalk exoskeleton to determine the training dosage required for walking proficiency, the sensory and motor changes in the nervous system with training, and the functionality of the device in a home-like environment. Methods Participants with chronic (> 1 yr) motor complete or incomplete spinal cord injury, who were primarily wheelchair users, were trained to walk in the ReWalk for 12 weeks. Measures were taken before, during, immediately after, and 2–3 months after training. Measures included walking progression, sitting balance, skin sensation, spasticity, and strength of the corticospinal tracts. Results Twelve participants were enrolled with 10 completing training. Training progression and walking ability: The progression in training indicated about 45 sessions to reach 80% of final performance in training. By the end of training, participants walked at speeds of 0.28–0.60 m/s, and distances of 0.74–1.97 km in 1 h. The effort of walking was about 3.3 times that for manual wheelchair propulsion. One non-walker with an incomplete injury became a walker without the ReWalk after training. Sensory and motor measures: Sitting balance was improved in some, as seen from the limits of stability and sway speed. Neuropathic pain showed no long term changes. Change in spasticity was mixed with suggestion of differences between those with high versus low spasticity prior to training. The strength of motor pathways from the brain to back extensor muscles remained unchanged. Adverse events: Minor adverse events were encountered by the participants and trainer (skin abrasions, non-injurious falls). Field testing: The majority of participants could walk on uneven surfaces outdoors. Some limitations were encountered in home-like environments. Conclusion For individuals with severe SCI, walking proficiency in the ReWalk requires about 45 sessions of training. The training was accompanied by functional improvements in some, especially in people with incomplete injuries. Trial registration NCT02322125 Registered 22 December 2014.

Abstract Background Despite growing evidence of a critical link between neuromodulation technologies and neuroplastic recovery, the underlying mechanisms of these technologies remain elusive. Objective To investigate physiological evidence of central nervous system (CNS) changes in humans during translingual neurostimulation (TLNS). Methods We used high-density electroencephalography (EEG) to measure changes in resting brain activity before, during, and after high frequency (HF) and low frequency (LF) TLNS. Results Wavelet power analysis around Cz and microstate analysis revealed significant changes after 20 min of stimulation compared to baseline. A secondary effect of exposure order was also identified, indicating a differential neuromodulatory influence of HF TLNS relative to LF TLNS on alpha and theta signal power. Conclusions These results further our understanding of the effects of TLNS on underlying resting brain activity, which in the long-term may contribute to the critical link between clinical effect and changes in brain activity.

Using a longitudinal case study design, we have tracked the recovery of motor function following severe traumatic brain injury (TBI) through a multimodal neuroimaging approach. In 2006, Canadian Soldier Captain (retired) Trevor Greene (TG) was attacked with an axe to the head while on tour in Afghanistan. TG continues intensive daily rehabilitation, which recently included the integration of physical therapy (PT) with neuromodulation using translingual neurostimulation (TLNS) to facilitate neuroplasticity. Recent findings with PT + TLNS demonstrated that recovery of motor function occurred beyond conventional time limits, currently extending past 14-years post-injury. To investigate whether PT + TLNS similarly resulted in associated cognitive function improvements, we examined event-related potentials (ERPs) with the brain vital signs framework. In parallel with motor function improvements, brain vital signs detected significant increases in basic attention (as measured by P300 response amplitude) and cognitive processing (as measured by contextual N400 response amplitude). These objective cognitive improvements corresponded with TG’s self-reported improvements, including a noteworthy and consistent reduction in ongoing symptoms of post-traumatic stress disorder (PTSD). The findings provide valuable insight into the potential importance of non-invasive neuromodulation in cognitive rehabilitation, in addition to initial indications for physical rehabilitation.

The atypical antipsychotic drugs have enhanced the quality of life in many patients with schizophrenia. Their main advantage over conventional antipsychotic drugs is their propensity to cause fewer extrapyramidal adverse effects. However, there is increasing evidence that atypical antipsychotic drugs are associated with metabolic adverse effects including weight gain, new onset diabetes (both type 2 diabetes and diabetic ketoacidosis) and hypertriglyceridaemia. These problems are most common with clozapine. We discuss the mechanism of the association and recommendations for screening and monitoring in order that metabolic problems can be detected and treated early. Copyright © 2003 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]