Age-related Purkinje cell death is steroid dependent: RORα haplo-insufficiency impairs plasma and cerebellar steroids and Purkinje cell survival

A major problem of ageing is progressive impairment of neuronal function and ultimately cell death. Since sex steroids are neuroprotective, their decrease with age may underlie age-related neuronal degeneration. To test this, we examined Purkinje cell numbers, plasma sex steroids and cerebellar neurosteroid concentrations during normal ageing (wild-type mice, WT), in our model of precocious ageing (Rora+/sg, heterozygous staggerer mice in which expression of the neuroprotective factor RORα is disrupted) and after long-term hormone insufficiency (WT post-gonadectomy). During normal ageing (WT), circulating sex steroids declined prior to or in parallel with Purkinje cell loss, which began at 18 months of age. Although Purkinje cell death was advanced in WT long-term steroid deficiency, this premature neuronal loss did not begin until 9 months, indicating that vulnerability to sex steroid deficiency is a phenomenon of ageing Purkinje neurons. In precocious ageing (Rora+/sg), circulating sex steroids decreased prematurely, in conjunction with marked Purkinje cell death from 9 months. Although Rora+/sg Purkinje cells are vulnerable through their RORα haplo-insufficiency, it is only as they age (after 9 months) that sex steroid failure becomes critical. Finally, cerebellar neurosteroids did not decrease with age in either genotype or gender; but were profoundly reduced by 3 months in male Rora+/sg cerebella, which may contribute to the fragility of their Purkinje neurons. These data suggest that ageing Purkinje cells are maintained by circulating sex steroids, rather than local neurosteroids, and that in Rora+/sg their age-related death is advanced by premature sex steroid loss induced by RORα haplo-insufficiency

Collins and Sivers asymmetries in muonproduction of pions and kaons off transversely polarised protons

Measurements of the Collins and Sivers asymmetries for charged pions and charged and neutral kaons produced in semi-inclusive deep-inelastic scattering of high energy muons off transversely polarised protons are presented. The results were obtained using all the available COMPASS proton data, which were taken in the years 2007 and 2010. The Collins asymmetries exhibit in the valence region a non-zero signal for pions and there are hints of non-zero signal also for kaons. The Sivers asymmetries are found to be positive for positive pions and kaons and compatible with zero otherwise. © 2015

Impact of spinal fusion on severity health status in scoliotic adolescents with polyhandicap.

BackgroundScoliosis constitutes a prevalent comorbidity in adolescents with polyhandicap and frequently leads to other severe impairments, impacting abilities and requiring complex caregiving strategies. Therefore, spinal fusion surgeries are commonly performed to alleviate pain and provide more comfort. However, spine stabilization has not previously been proven to improve the severity health status of adolescents with polyhandicap according to specific clinical scales.ObjectiveThis study describes and compares the severity health status of adolescents with polyhandicap before and after they underwent spinal fusion.MethodsA monocentric retrospective observational study was conducted in the university hospital centre of Saint-Etienne, France. We included between 2009 to 2020, 30 scoliotic adolescents with polyhandicap who underwent spinal fusion performed with the same surgical technique and the same surgeon. The main outcome was the variation in the Polyhandicap Severity Scale (PSS) score after surgery. Secondary outcomes were variations in PSS subscores, quality of life scores, fronto-sagittal X-ray parameters, and measures of surgical complication rates and lengths of stay.ResultsAmong 30 adolescents, 27 PSS analyses were performed. We found a significant improvement between pre- and postoperative PSS scores, mainly for pain and respiratory, digestive, and skin disabilities. These improvements were accompanied by significant reductions in pelvic obliquity, in frontal and sagittal curves. The mean hospital length of stay was 45 days. During postoperative period, patients received a personalized postoperative rehabilitation procedure with spasticity and pain treatments, physiotherapy, and verticalization (wheelchair sitting and positioning devices such as contoured seat intended to increase postural stability). The mortality rate was estimated at 7%. At least 1 complication per patient occurred.ConclusionsWe show that spinal fusion surgeries confer a significant improvement in the severity health status in scoliotic adolescents with polyhandicap

Combined dating of goethites and kaolinites from ferruginous duricrusts. Deciphering the Late Neogene erosion history of Central Amazonia

International audienceThis study focuses on the dating of millimetric pisoliths from ferruginous duricrusts located in central Amazonia (Brazil), by coupling detailed mineralogy and two relevant dating methods: (i) (U-Th)/He analysis of goethites by mass spectrometry; (ii) analysis of radiation-induced defects of kaolinites embedded in duricrusts by electron paramagnetic resonance spectroscopy (EPR). Three samples collected at different elevations in the landscape were selected. The goethite corrected ages range from 1.1–15.2 Ma and consistently increase with elevation. EPR was performed on kaolinites after several cycles of a deferration procedure. Considering extreme geochemical scenarii, the ages of kaolinites are 1.7–7.1 Ma for a closed system and 4.0–16.7 Ma for an open system with 100% Rn loss. Ages of goethites and kaolinites are close, in the limit of the uncertainty of the methods. They show important periods of duricrust formation at Middle Miocene and at Late Miocene/Pliocene. Data allow the estimation of lowering rates between 3 and 8 m/Ma, in agreement with independent data available in the literature for the central Amazonia region or even for erosion of other cratons in the world. The two dating methods can be compared on common duricrust samples. By revealing single or multi-step weathering/erosion episodes related to relictual paleosurfaces, they also bring promising contributions to an advanced knowledge of ancient and complex lateritic geosystems

The nuclear receptor RORα exerts a bi-directional regulation of IL-6 in resting and reactive astrocytes

Astrocytes and one of their products, IL-6, not only support neurons but also mediate inflammation in the brain. Retinoid-related orphan receptor-α (RORα) transcription factor has related roles, being neuro-protective and, in peripheral tissues, anti-inflammatory. We examined the relation of RORα to astrocytes and IL-6 using normal and RORα loss-of-function mutant mice. We have shown RORα expression in astrocytes and its up-regulation by pro-inflammatory cytokines. We have also demonstrated that RORα directly trans-activates the Il-6 gene. We suggest that this direct control is necessary to maintain IL-6 basal level in the brain and may be a link between the neuro-supportive roles of RORα, IL-6, and astrocytes. Furthermore, after inflammatory stimulation, the absence of RORα results in excessive IL-6 up-regulation, indicating that RORα exerts an indirect repression probably via the inhibition of the NF-κB signaling. Thus, our findings indicate that RORα is a pluripotent molecular player in constitutive and adaptive astrocyte physiology

Management of Severe Bleeding in Patients Treated with Direct Oral Anticoagulants

International audienceThe use of prothrombin complex concentrates and the role of plasma concentration of anticoagulants in the management of bleeding in patients treated with direct oral anticoagulants are still debated. Our aim was to describe management strategies and outcomes of severe bleeding events in patients treated with direct oral anticoagulants.METHODS:We performed a prospective cohort study of 732 patients treated with dabigatran, rivaroxaban, or apixaban hospitalized for severe bleeding, included prospectively in the registry from June 2013 to November 2015.RESULTS:Bleeding was gastrointestinal or intracranial in 37% (212 of 732) and 24% (141 of 732) of the cases, respectively. Creatinine clearance was lower than 60 ml/min in 61% (449 of 732) of the cases. The plasma concentration of direct oral anticoagulants was determined in 62% (452 of 732) of the cases and was lower than 50 ng/ml or higher than 400 ng/ml in 9.2% (41 of 452) and in 6.6% (30 of 452) of the cases, respectively. Activated or nonactivated prothrombin complex concentrates were administered in 38% of the cases (281 of 732). Mortality by day 30 was 14% (95% CI, 11 to 16).CONCLUSIONS:Management of severe bleeding in patients treated with direct oral anticoagulants appears to be complex. The use of prothrombin complex concentrates differs depending on bleeding sites and direct oral anticoagulant plasma concentrations. Mortality differs according to bleeding sites and was similar to previous estimates

Piezoelectric, dielectric and pyroelectric properties of 0-3 ceramic-polymer composites

The circular samples of composites were made from PZT ceramic grains dispersed in polymers (epoxy or rubber). Pressure dependencies of the hydrostatic piezoelectric coefficient dh and permittivity ε were measured in the range up to 60 MPa. The hydrostatic strain coefficient dh, the hydrostatic voltage coefficient gh and figure of merit dh·gh were determined using the static method. The pressure dependence of the hydrostatic coefficients was measured for several successive cycles. Experimental dependence of the charge on pressure and temperature was fitted by multi parameter function. The pressure and temperature dependencies of the hydrostatic dh and pyroelectric p3 coefficients were determined. It was found that the hydrostatic strain coefficient dh and hydrostatic voltage coefficient gh decreased and pyroelectric coefficient p3 increased with pressure at constant temperature.DFG [1102]; ICTP programme for Training and Research in Italian Laboratories (TRIL); German Bundesministerium fur Bildung und Forschung; Czech Republic MEYS Grants [ME492, LA242]; SAIL (CSR), Govt. of India; CERN-RFBR Grants [08-02-91009, 12-02-91500]; Portuguese FCT - Fundacao para a Ciencia e Tecnologia [CERN/FP/109323/2009, CERN/FP/116376/2010, CERN/FP/123600/2011]; MEXT; JSPS [18002006, 20540299, 18540281]; Daiko Foundation; Yamada Foundation; DFG cluster of excellence 'Origin and Structure of the Universe'; EU FP7 (HadronPhysics3) [283286]; Israel Science Foundation; Polish NCN Grant [DEC-2011/01/M/ST2/02350

Odd and even partial waves of eta pi(-) and eta 'pi(-) in pi(-) p -> eta(('))pi(-)p at 191 GeV/c

Exclusive production of eta pi(-) and eta'pi(-) in has been studied with a 191 GeV/c pi(-) beam impinging on a hydrogen target at COMPASS (CERN). Partial-wave analyses reveal different odd/even angular momentum (L) characteristics in the inspected invariant mass range up to 3 GeV/c(2). A striking similarity between the two systems is observed for the L = 2, 4, 6 intensities (scaled by kinematical factors) and the relative phases. The known resonances a(2)(1320) and a(4)(2040) are in line with this similarity. In contrast, a strong enhancement of eta'pi(-) over eta pi(-) is found for the L = 1, 3, 5 waves, which carry non-qq quantum numbers. The L = 1 intensity peaks at 1.7 GeV/c(2) in in and at 1.4 GeV/c(2) in eta pi(-), the corresponding phase motions with respect to L = 2 are different. (C) 2014 The Authors. Published by Elsevier B.V.DFG [1102]; German Bundesministerium fur Bildung und Forschung; Czech Republic MEYS [ME492, LA242]; SAIL (CSR), Govt. of India; CERN-RFBR [08-02-91009, 12-02-91500]; Portuguese FCT - Fundacao para a Ciencia e Tecnologia [CERN/FP/109323/2009, CERN/FP/116376/2010, CERN/FP/123600/2011]; MEXT; JSPS [18002006, 20540299, 18540281]; Daiko Foundation; Yamada Foundation; DFG; EU [283286]; Israel Science Foundation; Polish NCN [DEC-2011/01/M/ST2/02350