Diffusion Tensor Imaging in Sport-Related Concussion: A Systematic Review Using an a priori Quality Rating System

Diffusion tensor imaging (DTI) of brain white matter (WM) may be useful for characterizing the nature and degree of brain injury after sport-related concussion (SRC) and assist in establishing objective diagnostic and prognostic biomarkers. This study aimed to conduct a systematic review using an a priori quality rating strategy to determine the most consistent DTI-WM changes post-SRC. Articles published in English (until June 2020) were retrieved by standard research engine and gray literature searches (N = 4932), using PRISMA guidelines. Eligible studies were non-interventional naturalistic original studies that conducted DTI within 6 months of SRC in current athletes from all levels of play, types of sports, and sex. A total of 29 articles were included in the review, and after quality appraisal by two raters, data from 10 studies were extracted after being identified as high quality. High-quality studies showed widespread moderate-to-large WM differences when SRC samples were compared to controls during the acute to early chronic stage (days to weeks) post-SRC, including both increased and decreased fractional anisotropy and axial diffusivity and decreased mean diffusivity and radial diffusivity. WM differences remained stable in the chronic stage (2-6 months post-SRC). DTI metrics were commonly associated with SRC symptom severity, although standardized SRC diagnostics would improve future research. This indicates that microstructural recovery is often incomplete at return to play and may lag behind clinically assessed recovery measures. Future work should explore interindividual trajectories to improve understanding of the heterogeneous and dynamic WM patterns post-SRC

Elevation of cell-associated HIV-1 transcripts in CSF CD4+ T cells, despite effective antiretroviral therapy, is linked to brain injury

Antiretroviral therapy (ART) can attain prolonged undetectable HIV-1 in plasma and cerebrospinal fluid (CSF), but brain injury remains prevalent in people living with HIV-1 infection (PLHIV). We investigated cell-associated (CA)-HIV-1 RNA transcripts in cells in CSF and blood, using the highly sensitive Double-R assay, together with proton Magnetic Resonance Spectroscopy (1H MRS) of major brain metabolites, in sixteen PLHIV. 14/16 CSF cell samples had quantifiable CA-HIV-1 RNA, at levels significantly higher than in their PBMCs (median 9,266 vs 185 copies /106 CD4+ T-cells; p<0.0001). In individual PLHIV, higher levels of HIV-1 transcripts in CSF cells were associated with greater brain injury in the frontal white matter (Std β=-0.73; p=0.007) and posterior cingulate (Std β=-0.61; p=0.03). 18-colour flow cytometry revealed that the CSF cells were 91% memory T-cells, equally CD4+ and CD8+ T-cells, but fewer B cells (0.4 %), and monocytes (3.1%). CXCR3+CD49d+integrin β7-, CCR5+CD4+ T-cells were highly enriched in CSF, compared with PBMC (p <0.001). However, CA-HIV-1 RNA could not be detected in 10/16 preparations of highly purified monocytes from PBMC, and was extremely low in the other six. Our data show that elevated HIV-1 transcripts in CSF cells were associated with brain injury, despite suppressive ART. The cellular source is most likely memory CD4+ T cells from blood, rather than trafficking monocytes. Future research should focus on inhibitors of this transcription to reduce local production of potentially neurotoxic and inflammatory viral products

µ-Calpain Conversion of Antiapoptotic Bfl-1 (BCL2A1) into a Prodeath Factor Reveals Two Distinct alpha-Helices Inducing Mitochondria-Mediated Apoptosis

Anti-apoptotic Bfl-1 and pro-apoptotic Bax, two members of the Bcl-2 family sharing a similar structural fold, are classically viewed as antagonist regulators of apoptosis. However, both proteins were reported to be death inducers following cleavage by the cysteine protease µ-calpain. Here we demonstrate that calpain-mediated cleavage of full-length Bfl-1 induces the release of C-terminal membrane active α-helices that are responsible for its conversion into a pro-apoptotic factor. A careful comparison of the different membrane-active regions present in the Bfl-1 truncated fragments with homologous domains of Bax show that helix α5, but not α6, of Bfl-1 induces cell death and cytochrome c release from purified mitochondria through a Bax/Bak-dependent mechanism. In contrast, both helices α5 and α6 of Bax permeabilize mitochondria regardless of the presence of Bax or Bak. Moreover, we provide evidence that the α9 helix of Bfl-1 promotes cytochrome c release and apoptosis through a unique membrane-destabilizing action whereas Bax-α9 does not display such activities. Hence, despite a common 3D-structure, C-terminal toxic domains present on Bfl-1 and Bax function in a dissimilar manner to permeabilize mitochondria and induce apoptosis. These findings provide insights for designing therapeutic approaches that could exploit the cleavage of endogenous Bcl-2 family proteins or the use of Bfl-1/Bax-derived peptides to promote tumor cell clearance

Synthesis of P-Stereogenic Phosphines Based on Chiral Aminoalcohols as Chiral Auxiliary.

Part XI, Chapter

Autonomous power supply for aeronautical health monitoring sensors

International audienceNew applications of embedded systems are envisioned in the context of aeronautics. However, the increasing burden of on-board cabling requires wireless solutions. Moreover, concerns such as safety or system lifetime often preclude the use of electrochemical energy storage. Ambient energy capture, storage and management are therefore key topics. In this paper we illustrate these concepts by describing an actual implementation in the engine harsh environment of an Airbus A380. A thermogenerator was used to harvest ambient energy and the electronics associated with it allows the local system being energy autonomous. All items were devised and tested in order to meet the criteria of DO-160G aeronautical standard. The set of equipment was mounted on aircraft, and submitted to tens of test flights during roughly a year, in very various flight conditions