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Polyneuropathy is a disease involving multiple peripheral nerves injuries. Axon regrowth remains the major prerequisite for plasticity, regeneration, circuit formation, and eventually functional recovery and therefore, regulation of neurite outgrowth might be a candidate for treating polyneuropathies. In a recent study, we synthesized and established the methylene-cycloalkylacetate (MCAs) pharmacophore as a lead for the development of a neurotropic drug (inducing neurite/axonal outgrowth) using the PC12 neuronal model. In the present study we extended the characterizations of the in vitro neurotropic effect of the derivative 3-(3-allyl-2-methylenecyclohexyl) propanoic acid (MCA-13) on dorsal root ganglia and spinal cord neuronal cultures and analyzed its safety properties using blood biochemistry and cell counting, acute toxicity evaluation in mice and different in vitro "off-target" pharmacological evaluations. This MCA derivative deserves further preclinical mechanistic pharmacological characterizations including therapeutic efficacy in in vivo animal models of polyneuropathies, toward development of a clinically relevant neurotropic drug.

Cholesterol crystallization from mixtures of unesterified cholesterol with phospholipids and cholesterol esters is believed to be a key event in atherosclerosis progression. Not much is understood, however, about the influence of the lipid environment on cholesterol crystallization. Here we study cholesterol monohydrate crystal formation from mixed bilayers with palmitoyl-oleoyl-phosphatidylcholine (POPC), dipalmitoyl-phosphatidylcholine (DPPC) and sphingomyelin. We show that disordered phospholipids and sphingomyelin stabilize the formation of crystal plates of the triclinic cholesterol monohydrate polymorph, whereas saturated glycerolipids stabilize helical and tubular crystals of the metastable monoclinic polymorph. We followed the subsequent transformation of these helical crystals into the stable triclinic plates. Discovering the relations between membrane lipid composition and cholesterol crystal polymorphism may provide important clues to the understanding of cholesterol crystal formation in atherosclerosis.

Abstract Background Changes in transcranial magnetic stimulation motor map parameters can be used to quantify plasticity in the human motor cortex. The golden standard uses a counting analysis of motor evoked potentials (MEPs) acquired with a predefined grid. Recently, digital reconstruction methods have been proposed, allowing MEPs to be acquired with a faster pseudorandom procedure. However, the reliability of these reconstruction methods has never been compared to the golden standard. Objective To compare the absolute reliability of the reconstruction methods with the golden standard. Methods In 21 healthy subjects, both grid and pseudorandom acquisition were performed twice on the first day and once on the second day. The standard error of measurement was calculated for the counting analysis and the digital reconstructions. Results The standard error of measurement was at least equal using digital reconstructions. Conclusion Pseudorandom acquisition and digital reconstruction can be used in intervention studies without sacrificing reliability.

Abstract Objectives It has been previously demonstrated that healthcare professionals would like additional education on medical cannabis. However, there has not yet been a review of the status of medical cannabis curriculum for medical and allied healthcare trainees worldwide, even though future healthcare workers will be placed on the forefront of patient care and must be prepared to counsel patients. This study was designed to address this gap in knowledge. Design A search syntax was generated and databases PubMed, ERIC, CINAHL, and Web of Science were searched for relevant articles. A grey literature search of Google Scholar, MedEd, Medline, and the Proquest Dissertations and Theses section was also performed. All titles and abstracts were screened. Selected articles were subsequently screened using predetermined inclusion and exclusion criteria. Results Allied healthcare trainees lacked sufficient knowledge about medical cannabis and did not feel prepared to counsel patients on this subject. Additionally, they expressed a growing interest in medical cannabis and would like more standardized education on the topic. Finally, faculty and deans in various institutions agreed on the need to educate students on the subject, and aimed to implement courses on medical cannabis or expand their existing curricula. Conclusions While the medical cannabis landscape is developing, medical and allied health students are not properly educated and knowledgeable on this emerging field of clinical care. The findings suggest that the implementation of competencies-based curricula on medical cannabis is essential for medical and allied healthcare trainees to have the appropriate level of knowledge to counsel and educate their patients.

Electrical and thermal transport on a fractional quantum Hall edge are determined by topological quantities inherited from the corresponding bulk state. While electrical transport is the standard method for studying edges, thermal transport appears more challenging. Here, we show that the shot noise generated on the edge provides a fully electrical method to probe the edge structure. In the incoherent regime, the noise falls into three topologically distinct universality classes: charge transport is always ballistic while thermal transport is either ballistic, diffusive, or "antiballistic". Correspondingly, the noise either vanishes, decays algebraically or is constant up to exponentially small corrections in the edge length. Published version: 6+7 pages, 3+3 figures

The human immunodeficiency virus enters its host cells by membrane fusion, initiated by the gp41 subunit of its envelope protein. gp41 has also been shown to bind T-cell receptor (TCR) complex components, interfering with TCR signaling leading to reduced T-cell activation. This immunoinhibitory activity is suggested to occur during the membrane fusion process and is attributed to various membranotropic regions of the gp41 ectodomain and to the transmembrane domain. Although extensively studied, the cytosolic region of gp41, termed the cytoplasmic tail (CT), has not been examined in the context of immune suppression. Here we investigated whether the CT inhibits T-cell activation in different T-cell models by utilizing gp41-derived peptides and expressed full gp41 proteins. We found that a conserved region of the CT, termed lentiviral lytic peptide 2 (LLP2), specifically inhibits the activation of mouse, Jurkat, and human primary T-cells. This inhibition resulted in reduced T-cell proliferation, gene expression, cytokine secretion, and cell surface expression of CD69. Differential activation of the TCR signaling cascade revealed that CT-based immune suppression occurs downstream of the TCR complex. Moreover, LLP2 peptide treatment of Jurkat and primary human T-cells impaired Akt but not NFκB and ERK1/2 activation, suggesting that immune suppression occurs through the Akt pathway. These findings identify a novel gp41 T-cell suppressive element with a unique inhibitory mechanism that can take place post-membrane fusion.

Optical imaging through scattering media is a fundamental challenge in many applications. Recently, breakthroughs such as imaging through biological tissues and looking around corners have been obtained via wavefront-shaping approaches. However, these require an implanted guidestar for determining the wavefront correction, controlled coherent illumination, and most often raster scanning of the shaped focus. Alternative novel computational approaches that exploit speckle correlations avoid guidestars and wavefront control but are limited to small two-dimensional objects contained within the “memory-effect” correlation range. Here, we present a new concept, image-guided wavefront shaping, allowing widefield noninvasive, guidestar-free, incoherent imaging through highly scattering layers, without illumination control. The wavefront correction is found even for objects that are larger than the memory-effect range, by blindly optimizing image quality metrics. We demonstrate imaging of extended objects through highly scattering layers and multicore fibers, paving the way for noninvasive imaging in various applications, from microscopy to endoscopy. Optical imaging through turbid samples and fibers is made possible by adaptive correction of scattering guided by image quality.

ABSTRACT Linear polarization has been measured in several gamma-ray burst (GRB) afterglows. After a few days, polarization arises from the forward shock emission that depends on the post-shock magnetic field. The latter can originate both from compression of existing fields, here the interstellar medium (ISM) magnetic field, and from shock-generated instabilities. For short GRBs, previous modelling of the polarization arising from the forward shock considered a random field fully or partially confined to the shock plane. However, the ISM magnetic field likely consists of both random and ordered components. Here we study the impact of a more realistic magnetic field having both ordered and random components. We present our semi-analytical model and compute polarization curves arising for different magnetic field configurations. We find that the presence of an ordered component, even significantly weaker than the random one, has distinct signatures that could be detectable. In the presence of an ordered component not in the observer plane, we show that (i) for an observer inside the jet, the polarization angle θp either remains constant during all the afterglow phase or exhibits variations smaller than the 90° swing expected from a random component solely; (ii) for an off-axis observer, the polarization angle evolves from $\theta _\mathrm{ p}^{\max }$, before the jet break to its opposite after the jet break. We also find that the upper limit polarization for GRB 170817 requires a random field not fully confined to the shock plane and is compatible with an ordered component as large as half the random one.