141 research outputs found

    Les manifestations violentes

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    Abstract. An automatic human shape-motion analysis method based on a fusion architecture is proposed for human action recognition in videos. Robust shape-motion features are extracted from human points detection and tracking. The features are combined within the Transferable Belief Model (TBM) framework for action recognition. The TBMbased modelling and fusion process allows to take into account imprecision, uncertainty and conflict inherent to the features. Action recognition is performed by a multilevel analysis. The sequencing is exploited for feedback information extraction in order to improve tracking results. The system is tested on real videos of athletics meetings to recognize four types of jumps: high jump, pole vault, triple jump and long jump.

    International Perspectives on Joint Hypermobility: A Synthesis of Current Science to Guide Clinical and Research Directions

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    There is exponential clinical and research interest in joint hypermobility due to recognition of the complexity of identification, assessment, and its appropriate referral pathways, ultimately impacting management. This state-of-the-science review provides an international, multidisciplinary perspective on the presentation, etiology, and assessment of joint hypermobility, as it presents in those with and without a systemic condition. We synthesize the literature, propose standardizing the use of terminology and outcome measures, and suggest potential management directions. The major topics covered are (i) historical perspectives; (ii) current definitions of hypermobility, laxity, and instability; (iii) inheritance and acquisition of hypermobility; (iv) traditional and novel assessments; (v) strengths and limitations of current assessment tools; (vi) age, sex, and racial considerations; (vii) phenotypic presentations; (viii) generalized hypermobility spectrum disorder and hypermobility Ehlers-Danlos syndrome; and (ix) clinical implications and research directions. A thorough understanding of these topics will equip the reader seeking to manage individuals presenting with joint hypermobility, while mindful of its etiology. Management of generalized joint hypermobility in the context of a complex, multisystem condition will differ from that of acquired hypermobility commonly seen in performing artists, specific athletic populations, posttrauma, and so on. In addition, people with symptomatic hypermobility present predominantly with musculoskeletal symptoms and sometimes systemic symptoms including fatigue, orthostatic intolerance, and gastrointestinal or genitourinary issues. Some also display skeletal deformities, tissue and skin fragility, and structural vascular or cardiac differences, and these warrant further medical follow-up. This comprehensive review on the full spectrum of joint hypermobility will assist clinicians, coaches/sports trainers, educators, and/or researchers in this area

    Selective PDE4 subtype inhibition provides new opportunities to intervene in neuroinflammatory versus myelin damaging hallmarks of multiple sclerosis

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    Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system (CNS) characterized by focal inflammatory lesions and prominent demyelination. Even though the currently available therapies are effective in treating the initial stages of disease, they are unable to halt or reverse disease progression into the chronic progressive stage. Thus far, no repair-inducing treatments are available for progressive MS patients. Hence, there is an urgent need for the development of new therapeutic strategies either targeting the destructive immunological demyelination or boosting endogenous repair mechanisms. Using in vitro, ex vivo, and in vivo models, we demonstrate that selective inhibition of phosphodiesterase 4 (PDE4), a family of enzymes that hydrolyzes and inactivates cyclic adenosine monophosphate (cAMP), reduces inflammation and promotes myelin repair. More specifically, we segregated the myelination-promoting and anti-inflammatory effects into a PDE4D- and PDE4B-dependent process respectively. We show that inhibition of PDE4D boosts oligodendrocyte progenitor cells (OPC) differentiation and enhances (re)myelination of both murine OPCs and human iPSC-derived OPCs. In addition, PDE4D inhibition promotes in vivo remyelination in the cuprizone model, which is accompanied by improved spatial memory and reduced visual evoked potential latency times. We further identified that PDE4B-specific inhibition exerts anti-inflammatory effects since it lowers in vitro monocytic nitric oxide (NO) production and improves in vivo neurological scores during the early phase of experimental autoimmune encephalomyelitis (EAE). In contrast to the pan PDE4 inhibitor roflumilast, the therapeutic dose of both the PDE4B-specific inhibitor A33 and the PDE4D-specific inhibitor Gebr32a did not trigger emesis-like side effects in rodents. Finally, we report distinct PDE4D isoform expression patterns in human area postrema neurons and human oligodendroglia lineage cells. Using the CRISPR-Cas9 system, we confirmed that pde4d1/2 and pde4d6 are the key targets to induce OPC differentiation. Collectively, these data demonstrate that gene specific PDE4 inhibitors have potential as novel therapeutic agents for targeting the distinct disease processes of MS

    Plant-made polio type 3 stabilized VLPs—a candidate synthetic polio vaccine

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    Poliovirus (PV) is the causative agent of poliomyelitis, a crippling human disease known since antiquity. PV occurs in two distinct antigenic forms, D and C, of which only the D form elicits a robust neutralizing response. Developing a synthetically produced stabilized viruslike particle (sVLP)-based vaccine with D antigenicity, without the drawbacks of current vaccines, will be a major step towards the final eradication of poliovirus. Such a sVLP would retain the native antigenic conformation and the repetitive structure of the original virus particle, but lack infectious genomic material. In this study, we report the production of synthetically stabilized PV VLPs in plants. Mice carrying the gene for the human PV receptor are protected from wild-type PV when immunized with the plant-made PV sVLPs. Structural analysis of the stabilized mutant at 3.6 Å resolution by cryo-electron microscopy and single particle reconstruction reveals a structure almost indistinguishable from wild-type PV3

    Evaluation of sesamum gum as an excipient in matrix tablets

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    In developing countries modern medicines are often beyond the affordability of the majority of the population. This is due to the reliance on expensive imported raw materials despite the abundance of natural resources which could provide an equivalent or even an improved function. The aim of this study was to investigate the potential of sesamum gum (SG) extracted from the leaves of Sesamum radiatum (readily cultivated in sub-Saharan Africa) as a matrix former. Directly compressed matrix tablets were prepared from the extract and compared with similar matrices of HPMC (K4M) using theophylline as a model water soluble drug. The compaction, swelling, erosion and drug release from the matrices were studied in deionized water, 0.1 N HCl (pH 1.2) and phosphate buffer (pH 6.8) using USP apparatus II. The data from the swelling, erosion and drug release studies were also fitted into the respective mathematical models. Results showed that the matrices underwent a combination of swelling and erosion, with the swelling action being controlled by the rate of hydration in the medium. SG also controlled the release of theophylline similar to the HPMC and therefore may have use as an alternative excipient in regions where Sesamum radiatum can be easily cultivated

    Binding of glutathione to enterovirus capsids is essential for virion morphogenesis.

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    Contains fulltext : 137349.pdf (publisher's version ) (Open Access)Enteroviruses (family of the Picornaviridae) cover a large group of medically important human pathogens for which no antiviral treatment is approved. Although these viruses have been extensively studied, some aspects of the viral life cycle, in particular morphogenesis, are yet poorly understood. We report the discovery of TP219 as a novel inhibitor of the replication of several enteroviruses, including coxsackievirus and poliovirus. We show that TP219 binds directly glutathione (GSH), thereby rapidly depleting intracellular GSH levels and that this interferes with virus morphogenesis without affecting viral RNA replication. The inhibitory effect on assembly was shown not to depend on an altered reducing environment. Using TP219, we show that GSH is an essential stabilizing cofactor during the transition of protomeric particles into pentameric particles. Sequential passaging of coxsackievirus B3 in the presence of low GSH-levels selected for GSH-independent mutants that harbored a surface-exposed methionine in VP1 at the interface between two protomers. In line with this observation, enteroviruses that already contained this surface-exposed methionine, such as EV71, did not rely on GSH for virus morphogenesis. Biochemical and microscopical analysis provided strong evidence for a direct interaction between GSH and wildtype VP1 and a role for this interaction in localizing assembly intermediates to replication sites. Consistently, the interaction between GSH and mutant VP1 was abolished resulting in a relocalization of the assembly intermediates to replication sites independent from GSH. This study thus reveals GSH as a novel stabilizing host factor essential for the production of infectious enterovirus progeny and provides new insights into the poorly understood process of morphogenesis.1 april 201

    Inulin hydrogels. II. In vitro degradation study

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    Inulin hydrogels have been developed as potential new carriers for colonic drug targeting. Since site-specific drug release of this delivery system is based on its bacterial degradation in the colon, the enzymatic digestibility of the prepared inulin hydrogels was assessed by performing an in vitro study using an inulinase preparation derived from Aspergillus niger. The amount of fructose liberated from the inulin hydrogels by the action of inulinase was quantified using the anthrone method. The equilibrium swelling ratio as well as the mechanical strength of the hydrogels were studied before and after incubation in inulinase solutions. The data obtained by these different methods indicate that enzymatic digestion of the inulin hydrogels appeared to be enhanced by a prolonged degradation time, a higher inulinase concentration and a lower degree of substitution and feed concentration of the hydrogel polymer. The inulin hydrogels exhibited an increase in equilibrium swelling after degradation compared to the swelling before degradation, suggesting that inulinase enzymes are able to diffuse into the inulin hydrogel networks causing bulk degradation.status: publishe

    Development of picornavirus-like particle vaccines

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