Safe and neuroprotective vectors for long-term traumatic brain injury gene therapy.

Traumatic brain injury (TBI) is a complex and progressive brain injury with no approved treatments that needs both short- and long-term therapeutic strategies to cope with the variety of physiopathological mechanisms involved. In particular, neuroinflammation is a key process modulating TBI outcome, and the potentiation of these mechanisms by pro-inflammatory gene therapy vectors could contribute to the injury progression. Here, we evaluate in the controlled cortical impact model of TBI, the safety of integrative-deficient lentiviral vectors (IDLVs) or the non-viral HNRK recombinant modular protein/DNA nanovector. These two promising vectors display different tropisms, transduction efficiencies, short- or long-term transduction or inflammatory activation profile. We show that the brain intraparenchymal injection of these vectors overexpressing green fluorescent protein after a CCI is not neurotoxic, and interestingly, can decrease the short-term sensory neurological deficits, and diminish the brain tissue loss at 90 days post lesion (dpl). Moreover, only IDLVs were able to mitigate the memory deficits elicited by a CCI. These vectors did not alter the microglial or astroglial reactivity at 90 dpl, suggesting that they do not potentiate the on-going neuroinflammation. Taken together, these data suggest that both types of vectors could be interesting tools for the design of gene therapy strategies targeting immediate or long-term neuropathological mechanisms of TBI.

Mobile phone use, sleep disorders and obesity in a social exclusion zone.

INTRODUCTION: There is little information on the impact of mobile phone overuse (MPO) in areas in need of social transformation (ANST). Our objective was to estimate the prevalence of MPO in an ANST and its association with sleep disorders, academic performance and obesity. PATIENTS AND METHODS: Consecutive sampling of patients aged 10-17 years who visited a primary care centre in an ARST between October 2019 and March 2020. The study involved performance of a clinical interview with collection of anthropometric, sociodemographic, mobile phone use and sleep data. RESULTS: The analysis included 214 participants. The prevalence of MPO during weekdays (more than 2 h a day) was 37.5% in children aged 10-12 years and 65.2% in 13- to 17-year-olds; in the weekend, the prevalence increased to 66.6% and 81.3%, respectively. In weekdays, MPO was associated with an increased prevalence of obesity, lower maternal educational attainment, greater difficulty waking up, daytime sleepiness and higher frequency of school failure. The adjusted risk was double for excess weight (odds ratio [OR] 1.90, 95% confidence interval [95% CI] 1.04-3.47), obesity (OR 2.45, 95% CI 1.23-4.89) and sleep disorders or sleep duration of less than 7 h (OR 2.26; 95% CI 1.31-3.92). Weekend MPO was associated with sleep disorders or sleep duration of less than 7 h (OR 2.68; 95% CI 1.40-5.11). CONCLUSIONS: The prevalence of mobile phone overuse is high in areas of social exclusion and is associated with sleep disorders, school failure and obesity.

Thy1-YFP-H Mice and the Parallel Rod Floor Test to Evaluate Short- and Long-Term Progression of Traumatic Brain Injury.

Traumatic brain injury (TBI) is a leading cause of death and disability and is a risk factor for the later development of neuropsychiatric disorders and neurodegenerative diseases. Many models of TBI have been developed, but their further refinement and a more detailed long-term follow-up is needed. We have used the Thy1-YFP-H transgenic mouse line and the parallel rod floor test to produce an unbiased and robust method for the evaluation of the multiple effects of a validated model of controlled cortical injury. This approach reveals short- and long-term progressive changes, including compromised biphasic motor function up to 85 days post-lesion, which correlates with neuronal atrophy, dendrite and spine loss, and long-term axonal pathology evidenced by axon spheroids and fragmentation. Here we present methods for inducing a controlled cortical injury in the Thy1-YFP-H transgenic mouse line and for evaluating the resulting deficits in the parallel rod floor test. This technique constitutes a new, unbiased, and robust method for the evaluation of motor and behavioral alterations after TBI. © 2018 by John Wiley & Sons, Inc.