Cervical artery dissection: An atypical presentation with Ehlers-Danlos-like collagen pathology?

The authors took skin biopsies of the macroscopically normal skin of seven consecutive patients with spontaneous cervical artery dissection (SCAD). Histologically, alterations of the collagen and elastic fiber networks were found in six patients. In five, the histologic, immunohistochemical, and ultrastructural changes were similar to those usually found in Ehlers-Danlos syndrome (EDS). This suggests that SCAD is frequently associated with the dermal alterations seen in EDS

Vital and functional outcomes of the first-ever hemispheric stroke, epidemiological comparative study between Kunming (China) and Limoges (France)

AbstractBackgroundClinical outcomes and socioeconomic consequences after a stroke may differ between regions.MethodsOne cohort was established prospectively in Kunming (China) to compare with a cohort of 156 stroke patients included in Limoges (France). During 1 year, patients hospitalized within 48hours for a first-ever hemispheric stroke were included. Demographic data and neurocardiovascular risk factors were registered. Hemiplegia was evaluated. Functional outcome was assessed using the Barthel Index (BI) after 3 months.ResultsOne hundred and eighteen patients were included in Kunming. Patients of Kunming were younger (61.4±13.4 vs 72.3±14.6 years in Limoges, P<0.0001), more involved in professional activity (36.4% vs 12.8%, P<0.0001). Survival analysis indicated that mortality did not differ between cohorts, but independently predicted by coma at the 2nd day (HR=9.33, 95% CI [4.39, 19.78]) and age>70 years (HR=6.29, 95% CI [2.36, 16.59]). Despite a better baseline BI for patients of Kunming (50.0±34.9 vs 37.4±34.2, P=0.0031), after adjustment for confusing, patients in Limoges had a 2.11 OR 95% CI [1.03, 4.31]) to reach a BI>80 at 3 months.ConclusionsFunctional recovery for patients of Kunming was not as good as expected. The socioeconomic consequences of stroke in Kunming are significant as they involved younger subjects who were still in work

The TRPV4 channel links calcium influx to DDX3X activity and viral infectivity

Ion channels are well placed to transduce environmental cues into signals used by cells to generate a wide range of responses, but little is known about their role in the regulation of RNA metabolism. Here we show that the TRPV4 cation channel binds the DEAD-box RNA helicase DDX3X and regulates its function. TRPV4-mediated Ca2+ influx releases DDX3X from the channel and drives DDX3X nuclear translocation, a process that involves calmodulin (CaM) and the CaM-dependent kinase II. Genetic depletion or pharmacological inhibition of TRPV4 diminishes DDX3X-dependent functions, including nuclear viral export and translation. Furthermore, TRPV4 mediates Ca2+ influx and nuclear accumulation of DDX3X in cells exposed to the Zika virus or the purified viral envelope protein. Consequently, targeting of TRPV4 reduces infectivity of dengue, hepatitis C and Zika viruses. Together, our results highlight the role of TRPV4 in the regulation of DDX3X-dependent control of RNA metabolism and viral infectivity

Loss of the receptor tyrosine kinase Axl leads to enhanced inflammation in the CNS and delayed removal of myelin debris during Experimental Autoimmune Encephalomyelitis

<p>Abstract</p> <p>Background</p> <p>Axl, together with Tyro3 and Mer, constitute the TAM family of receptor tyrosine kinases. In the nervous system, Axl and its ligand Growth-arrest-specific protein 6 (Gas6) are expressed on multiple cell types. Axl functions in dampening the immune response, regulating cytokine secretion, clearing apoptotic cells and debris, and maintaining cell survival. Axl is upregulated in various disease states, such as in the cuprizone toxicity-induced model of demyelination and in multiple sclerosis (MS) lesions, suggesting that it plays a role in disease pathogenesis. To test for this, we studied the susceptibility of Axl-/- mice to experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis.</p> <p>Methods</p> <p>WT and Axl-/- mice were immunized with myelin oligodendrocyte glycoprotein (MOG)_35-55peptide emulsified in complete Freund's adjuvant and injected with pertussis toxin on day 0 and day 2. Mice were monitored daily for clinical signs of disease and analyzed for pathology during the acute phase of disease. Immunological responses were monitored by flow cytometry, cytokine analysis and proliferation assays.</p> <p>Results</p> <p>Axl-/- mice had a significantly more severe acute phase of EAE than WT mice. Axl-/- mice had more spinal cord lesions with larger inflammatory cuffs, more demyelination, and more axonal damage than WT mice during EAE. Strikingly, lesions in Axl-/- mice had more intense Oil-Red-O staining indicative of inefficient clearance of myelin debris. Fewer activated microglia/macrophages (Iba1+) were found in and/or surrounding lesions in Axl-/- mice relative to WT mice. In contrast, no significant differences were noted in immune cell responses between naïve and sensitized animals.</p> <p>Conclusions</p> <p>These data show that Axl alleviates EAE disease progression and suggests that in EAE Axl functions in the recruitment of microglia/macrophages and in the clearance of debris following demyelination. In addition, these data provide further support that administration of the Axl ligand Gas6 could be therapeutic for immune-mediated demyelinating diseases.</p

Needle lift profile influence on the vapor phase penetration for a prototype diesel direct acting piezoelectric injector

In this study, Schlieren visualization tests have been performed for a prototype diesel common rail direct-acting piezoelectric injector, to understand the influence of fuel injection rate shaping on the vapor spray development under evaporative and non-reacting conditions. This state of the art injector presents a particular feature that permits full needle lift control through a parameter referred to as piezo stack charge level, enabling various fuel injection rate typologies. A fast camera and a two pass Schlieren visualization setup have been utilized to record high speed images of the injection event and later analyze, through the vapor phase, the transient evolution of the spray. The tests have been performed employing a novel continuous flow test vessel that provides an accurate control of ambient temperature and pressure up to 1000 K and 15 MPa respectively. The effect of ambient temperature, injection pressure, needle lift and needle lift profile were studied. Data obtained is correlated to previous liquid length and injection rate measurements of the same injector. Results show, as expected for all cases, that instant vapor penetration rate is closely related to instant injection rate. This is confirmed by the injection pressure test results, along with those obtained for the three different piezo stack charge levels, both affecting the vapor penetration in a similar way. Nevertheless, results obtained for the three different charge levels show that the influence of the charge level and the injection pressure differ in the very beginning of the injection event, where the spray development is largely determined by needle lift and not injection pressure. Ambient temperature alone seems not to have and important effect on vapor penetration. Finally, the effects of the needle lift profile in the instant injection rate and vapor penetration are presented, confirming the strong relation between these three parameters, and confirming also that the needle lift plays a determinant role in the spray development, especially at the early stages of the injection process. Both boot and ramp shaped injections proved the ability to strongly influence the vapor penetration rate. In comparison to the square shaped injection, the effect of the ramp shaped injection delays the vapor penetration right from the start of injection while the effect of the boot shaped injection takes considerably longer to become noticeable. From the results, the needle lift control feature has proven to be a very versatile tool for engine designers to control the injection process as desired, opening a new path with a plenty of room for improvement.he authors would like to thank general motors company for their financial support and its cooperation during the project and José Enrique del Rey* and Michele Bardi* for their collaboration in the experimental measurements and setup. (*) From CMT-Motores Térmicos. Universitat Politecnica de Valencia.Payri, R.; Gimeno, J.; Viera, JP.; Plazas Torres, AH. (2013). Needle lift profile influence on the vapor phase penetration for a prototype diesel direct acting piezoelectric injector. Fuel. 113:257-265. doi:10.1016/j.fuel.2013.05.057S25726511

Methodology for Phase Doppler Anemometry Measurements on a Multi-Hole Diesel Injector

[EN] In this paper, a methodology for Phase Doppler Anemometry (PDPA) measurements on a multi-hole diesel injector is developed. Several key considerations were taken into account in this methodology: The windows for PDPA optical access must be clean, since fuel impregnated in these could preclude the droplets velocity acquisition. Some parts, including a device for spray isolation, were designed and manufactured to fulfill this goal. Taking into account that only one spray is measured, the isolation device captures all except three of the sprays (including the spray of interest). The two plumes accompanying the main spray were thought to conserve the actual air entrainment and thus the spray behavior. The spray of interest was aligned horizontally to ease the way that the PDPA measurements are carried out. The plume was lined up by means of the MIE-Scattering macroscopic optical technique. Images were acquired for several injection events and spray contours were detected and processed with a purpose-built Matlab tool. At each time step a spray axis inclination was estimated using the centroids from instantaneous contours. Also, preliminary droplet velocity measurements were made to check the effectiveness of the alignment and spray isolation strategies. Both geometrical characterization and spray alignment had very low measurement error. Radial velocity profiles show that PDPA measurements with this set-up configuration preserved the spray behavior.This research was performed in the frame of the project "Estudio de la interaccion chorro-pared en condiciones realistas de motor" reference TRA2015-67679-c2-1-R from Ministerio de Economia y Competitividad (Spanish Ministry of Economy). The equipment used in this work has been partially supported by FEDER Project funds "Dotacion de infraestructuras cientifico tectinas para el Centro Integral de Mejora Energetica y Medioambiental de Sistemas de Transporte (CiMeT), (FEDER-ICTS-2012-06)", framed in the operation program of unique scientific and technical infrastructure of the Ministry of Science and Innovation of Spain. Jhoan S. Giraldo was supported by a research grant from Generalitat Valenciana (Programa Santiago Grisolia, GRISOLIA/2013/007).Payri, R.; Gimeno, J.; Marti-Aldaravi, P.; Giraldo-Valderrama, JS. (2017). Methodology for Phase Doppler Anemometry Measurements on a Multi-Hole Diesel Injector. Experimental Techniques. 41(2):95-102. https://doi.org/10.1007/s40799-016-0154-1S95102412Lee J, Kang S, Rho B (2002) Intermittent atomization characteristics of multi-hole and single-hole diesel nozzle. KSME Int J 16(12):1693–1701Lee BH, Song JH, Chang YJ, Jeon CH (2010) Effect of the number of fuel injector holes on characteristics of combustion and emissions in a diesel engine. Int J Automot Technol 11(6):783– 791Lee J, Kaug S, Rho B (2003) Atomization characteristics of intermittent multi-hole diesel spray using time-resolved pdpa data. KSME Int J 17(5):766–775Zhou L-Y, Dong S-F, Cui H-F, Wu X-W, Xue F-Y, Luo F-Q (2016) Measurements and analyses on the transient discharge coefficient of each nozzle hole of multi-hole diesel injector. Sensors Actuators A Phys 244:198–205Payri R, Salvador FJ, Manin J, Viera A (2016) Diesel ignition delay and lift-off length through different methodologies using a multi-hole injector. Appl Energy 162:541–550Payri R, García-Oliver JM, Bardi M, Manin J (2012) Fuel temperature influence on diesel sprays in inert and reacting conditions. Appl Therm Eng 35:185–195Payri F, Payri R, Bardi M, Carreres M (2014) Engine combustion network: Influence of the gas properties on the spray penetration and spreading angle. Exp Thermal Fluid Sci 53:236– 243Payri R, Gimeno J, Bardi M, Plazas AH (2013) Study liquid length penetration results obtained with a direct acting piezo electric injector. Appl Energy 106(0):152–162Soare V (2007) Phase Doppler Measurements in Diesel Dense Sprays: Optimisation of Measurements and Study of the Orifice Geometry Influence over the Spray at Microscopic Level. PhD thesis, Universitat Politècnica de ValenciaAraneo L, Tropea C (2000) Improving phase doppler measurements in a diesel spray. SAE paperCoghe A, Cossali GE (2012) Quantitative optical techniques for dense sprays investigation: A survey. Optics and Lasers in Engineering 50(1):46–56. 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Protective role of chaperone-mediated autophagy against atherosclerosis

Significance Cardiovascular diseases remain the leading cause of death worldwide, with atherosclerosis being the most common source of clinical events. Metabolic changes with aging associate with concurrent increased risk of both type 2 diabetes and cardiovascular disease, with the former further raising the risk of the latter. The activity of a selective type of autophagy, chaperone-mediated autophagy (CMA), decreases with age or upon dietary excesses. Here we study whether reduced CMA activity increases risk of atherosclerosis in mouse models. We have identified that CMA is up-regulated early in response to proatherogenic challenges and demonstrate that reduced systemic CMA aggravates vascular pathology in these conditions. We also provide proof-of-concept support that CMA up-regulation is an effective intervention to reduce atherosclerosis severity and progression