Better sexual acceptability of agomelatine (25 and 50 mg) compared to escitalopram (20 mg) in healthy volunteers. A 9-week, placebo-controlled study using the PRSexDQ scale

The present double-blind, placebo-controlled study evaluates the effects of agomelatine and the selective serotonin reuptake inhibitor escitalopram on sexual dysfunction in healthy men and women

Evidence for Cognitive Impairment in Mastocytosis: Prevalence, Features and Correlations to Depression

Mastocytosis is a heterogeneous disease characterized by mast cells accumulation in one or more organs. We have reported that depression is frequent in mastocytosis, but although it was already described, little is known about the prevalence and features of cognitive impairment. Our objective was to describe the prevalence and features of cognitive impairment in a large cohort of patients with this rare disease (n = 57; mean age = 45) and to explore the relations between memory impairment and depression. Objective memory impairment was evaluated using the 3rd edition of the Clinical Memory scale of Wechsler. Depression symptoms were evaluated using the Hamilton Depression Rating Scale. Age and education levels were controlled for all patients. Patients with mastocytosis presented high levels of cognitive impairment (memory and/or attention) (n = 22; 38.6%). Cognitive impairment was moderate in 59% of the cases, concerned immediate auditory (41%) and working memory (73%) and was not associated to depression (p≥0.717). In conclusion, immediate auditory memory and attention impairment in mastocytosis are frequent, even in young individuals, and are not consecutive to depression. In mastocytosis, cognitive complaints call for complex neuropsychological assessment. Mild-moderate cognitive impairment and depression constitute two specific but somewhat independent syndromes in mastocytosis. These results suggest differential effects of mast-cell activity in the brain, on systems involved in emotionality and in cognition

Developmental Splicing Deregulation in Leukodystrophies Related to EIF2B Mutations

Leukodystrophies (LD) are rare inherited disorders that primarily affect the white matter (WM) of the central nervous system. The large heterogeneity of LD results from the diversity of the genetically determined defects that interfere with glial cells functions. Astrocytes have been identified as the primary target of LD with cystic myelin breakdown including those related to mutations in the ubiquitous translation initiation factor eIF2B. EIF2B is involved in global protein synthesis and its regulation under normal and stress conditions. Little is known about how eIF2B mutations have a major effect on WM. We performed a transcriptomic analysis using fibroblasts of 10 eIF2B-mutated patients with a severe phenotype and 10 age matched patients with other types of LD in comparison to control fibroblasts. ANOVA was used to identify genes that were statistically significantly differentially expressed at basal state and after ER-stress. The pattern of differentially expressed genes between basal state and ER-stress did not differ significantly among each of the three conditions. However, 70 genes were specifically differentially expressed in eIF2B-mutated fibroblasts whatever the stress conditions tested compared to controls, 96% being under-expressed. Most of these genes were involved in mRNA regulation and mitochondrial metabolism. The 13 most representative genes, including genes belonging to the Heterogeneous Nuclear Ribonucleoprotein (HNRNP) family, described as regulators of splicing events and stability of mRNA, were dysregulated during the development of eIF2B-mutated brains. HNRNPH1, F and C mRNA were over-expressed in foetus but under-expressed in children and adult brains. The abnormal regulation of HNRNP expression in the brain of eIF2B-mutated patients was concomitant with splicing dysregulation of the main genes involved in glial maturation such as PLP1 for oligodendrocytes and GFAP in astrocytes. These findings demonstrate a developmental deregulation of splicing events in glial cells that is related to abnormal production of HNRNP, in eIF2B-mutated brains

Impact of comorbidity on the short- and medium-term risk of revision in total hip and knee arthroplasty

Background: The impact of comorbidity on the risk of revision in patients undergoing Total Knee arthroplasty (TKA) and Total Hip Arthroplasty (THA) is not currently well known. The aim of this study was to analyze the impact of comorbidity on the risk of revision in TKA and THA. Methods: Patients recorded in the Catalan Arthroplasty Register (RACat) between 01/01/2005 and 31/12/2016 undergoing TKA (n = 49,701) and THA (n = 17,923) caused by osteoarthritis were included. As main explanatory factors, comorbidity burden was assessed by the Elixhauser index, categorized, and specific comorbidities from the index were taken into account. Descriptive analyses for comorbidity burden and specific conditions were done. Additionally, incidence at 1 and 5 years' follow-up was calculated, and adjusted Competing Risks models were fitted. Results: A higher incidence of revision was observed when the number of comorbidities was high, both at 1 and 5 years for THA, but only at 1 year for TKA. Of the specific conditions, only obesity was related to the incidence of revision at 1 year in both joints, and at 5 years in TKA. The risk of revision was related to deficiency anemia and liver diseases in TKA, while in THA, it was related to peripheral vascular disorders, metastatic cancer and psychoses. Conclusions: Different conditions, depending on the joint, might be related to higher revision rates. This information could be relevant for clinical decision-making, patient-specific information and improving the results of both TKA and THA.This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site.The present study was funded by CIBER Epidemiology and Public Health (CIBERESP) as part of the aid for short internships granted to Jorge Arias-de la Torre in 2017 and 2018.published version, accepted versio

Selective augmentation of striatal functional connectivity following NMDA receptor antagonism: implications for psychosis

The psychotomimetic effect of the N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine is thought to arise from a functional modulation of the brain's fronto-striato-thalamic (FST) circuits. Animal models suggest a pronounced effect on ventral ‘limbic' FST systems, although recent work in patients with psychosis and high-risk individuals suggests specific alterations of dorsal ‘associative' FST circuits. Here, we used functional magnetic resonance imaging to investigate the effects of a subanesthetic dose of ketamine on measures of functional connectivity as indexed by the temporal coherence of spontaneous neural activity in both dorsal and ventral FST circuits, as well as their symptom correlates. We adopted a placebo-controlled, double-blind, randomized, repeated-measures design in which 19 healthy participants received either an intravenous saline infusion or a racemic mixture of ketamine (100 ng/ml) separated by at least 1 week. Compared with placebo, ketamine increased functional connectivity between the dorsal caudate and both the thalamus and midbrain bilaterally. Ketamine additionally increased functional connectivity of the ventral striatum/nucleus accumbens and ventromedial prefrontal cortex. Both connectivity increases significantly correlated with the psychosis-like and dissociative symptoms under ketamine. Importantly, dorsal caudate connectivity with the ventrolateral thalamus and subthalamic nucleus showed inverse correlation with ketamine-induced symptomatology, pointing to a possible resilience role to disturbances in FST circuits. Although consistent with the role of FST in mediating psychosis, these findings contrast with previous research in clinical samples by suggesting that acute NMDAR antagonism may lead to psychosis-like experiences via a mechanism that is distinct from that implicated in frank psychotic illness

Numerical modeling of erosion and assimilation of sulfur-rich substrate by martian lava flows: implications for the genesis of massive sulfide mineralization on Mars

International audienceMantle-derived volcanic rocks on Mars display physical and chemical commonalities with mafic-ultramafic ferropicrite and komatiite volcanism on the Earth. Terrestrial komatiites are common hosts of massive sulfide mineralization enriched in siderophile-chalcophile precious metals (i.e., Ni, Cu, and the platinum-group elements). These deposits correspond to the batch segregation and accumulation of immiscible sulfide liquids as a consequence of mechanical/thermo-mechanical erosion and assimilation of sulfur-rich bedrock during the turbulent flow of high-temperature and low-viscosity komatiite lava flows. This study adopts this mineralization model and presents numerical simulations of erosion and assimilation of sulfide- and sulfate-rich sedimentary substrates during the dynamic emplacement of (channelled) mafic-ultramafic lava flows on Mars. For sedimentary substrates containing adequate sulfide proportions (e.g., 1 wt% S), our simulations suggest that sulfide supersaturation in low-temperature (1400°C). The precious-metals tenor in the derived immiscible sulfide liquids may be significantly upgraded as a result of their prolonged equilibration with large volumes of silicate melts along flow conduits. The influence of sulfate assimilation on sulfide supersaturation in martian lava flows is addressed by simulations of melt-gas equilibration in the C-H-O-S fluid system. However, prolonged sulfide segregation and deposit genesis by means of sulfate assimilation appears to be limited by lava oxidation and the release of sulfur-rich gas. The identification of massive sulfide endowments on Mars is not possible from remote sensing data. Yet the results of this study aid to define regions for the potential occurrence of such mineral systems, which may be the large canyon systems Noctis Labyrinthus and Valles Marineris, or the Hesperian channel systems of Mars’ highlands (e.g., Kasei Valles), most of which have been periodically draped by mafic-ultramafic lavas

Simulation of substrate erosion and sulphate assimilation by Martian low-viscosity lava flows: implications for the genesis of precious metal-rich sulphide mineralisation on Mars

International audienceOn Earth, high temperature mafic to ultramafic lava flows, such as komatiites and ferropicrites of the Archean and Proterozic eons, can be hosts to Ni-Cu-PGE sulphide mineralisation. Mechanical/thermo-mechanical erosion and assimilation of sulphur-rich crustal rocks is ascribed as the principal mechanism that leads to sulphide supersaturation, batch segregation and subsequent accumulation of metal-enriched magmatic sulphides (e.g., Bekker et al., Science, 2009). In order to investigate the likelihood of the occurrence of similar sulphide mineralisation in extraterrestrial magmatic systems, we numerically modelled erosion and assimilation during the turbulent emplacement of Martian lavas, some of which display chemical and rheological analogies with terrestrial komatiites and ferropicrites, on a variety of consolidated sedimentary sulphate-rich substrates. The modelling approach relies on the integration of i) mathematical lava erosion models for turbulent flows (Williams et al., J. Geophys. Res., 1998), ii) thermodynamic volatile degassing models (Gaillard et al., Space Sci. Rev., 2013), and iii) formulations on the stability of sulphides (Fortin et al., Geochim. Cosmochim. Acta, 2015). A series of scenarios are examined in which various Martian mafic to ultramafic mantle-derived melts emplace over, and assimilate consolidated sulphate-rich substrates, such as the sedimentary lithologies (i.e., conglomerates, sandstones and mudstones) recently discovered at the Gale Crater landing site. Our modellings show that lavas emplacing over consolidated sedimentary substrate rather than stiff basaltic crust, are governed by relatively high cooling and substrate erosion rates. The rapid assimilation of sulphate, which serves as a strongly oxidising agent, could result in dramatic sulphur loss due to increased volatile degassing rates at fO2 ≳QFM-1. This effect is further enhanced with increased temperature. Nevertheless, sulphide supersaturation in the way of sulphate assimilation can be achieved in relatively reduced (i.e., fO2 <QFM-2) melts. We thus outline that reduced low-temperature melts of the Hesperian and Amazonian, such as those parental to the Adirondack-class basalts at Gusev Crater, rather than high-temperature melts of the Pre-Noachian and Noachian or those parental to some primitive Shergottite meteorites (Filiberto et al., J. Geophys. Res., 2015), are promising candidates for the presence of Ni-Cu-PGE sulphide mineralisation on Mars

Simulation of substrate erosion and sulphate assimilation by Martian low-viscosity lava flows: implications for the genesis of precious metal-rich sulphide mineralisation on Mars

International audienceOn Earth, high temperature mafic to ultramafic lava flows, such as komatiites and ferropicrites of the Archean and Proterozic eons, can be hosts to Ni-Cu-PGE sulphide mineralisation. Mechanical/thermo-mechanical erosion and assimilation of sulphur-rich crustal rocks is ascribed as the principal mechanism that leads to sulphide supersaturation, batch segregation and subsequent accumulation of metal-enriched magmatic sulphides (e.g., Bekker et al., Science, 2009). In order to investigate the likelihood of the occurrence of similar sulphide mineralisation in extraterrestrial magmatic systems, we numerically modelled erosion and assimilation during the turbulent emplacement of Martian lavas, some of which display chemical and rheological analogies with terrestrial komatiites and ferropicrites, on a variety of consolidated sedimentary sulphate-rich substrates. The modelling approach relies on the integration of i) mathematical lava erosion models for turbulent flows (Williams et al., J. Geophys. Res., 1998), ii) thermodynamic volatile degassing models (Gaillard et al., Space Sci. Rev., 2013), and iii) formulations on the stability of sulphides (Fortin et al., Geochim. Cosmochim. Acta, 2015). A series of scenarios are examined in which various Martian mafic to ultramafic mantle-derived melts emplace over, and assimilate consolidated sulphate-rich substrates, such as the sedimentary lithologies (i.e., conglomerates, sandstones and mudstones) recently discovered at the Gale Crater landing site. Our modellings show that lavas emplacing over consolidated sedimentary substrate rather than stiff basaltic crust, are governed by relatively high cooling and substrate erosion rates. The rapid assimilation of sulphate, which serves as a strongly oxidising agent, could result in dramatic sulphur loss due to increased volatile degassing rates at fO2 ≳QFM-1. This effect is further enhanced with increased temperature. Nevertheless, sulphide supersaturation in the way of sulphate assimilation can be achieved in relatively reduced (i.e., fO2 <QFM-2) melts. We thus outline that reduced low-temperature melts of the Hesperian and Amazonian, such as those parental to the Adirondack-class basalts at Gusev Crater, rather than high-temperature melts of the Pre-Noachian and Noachian or those parental to some primitive Shergottite meteorites (Filiberto et al., J. Geophys. Res., 2015), are promising candidates for the presence of Ni-Cu-PGE sulphide mineralisation on Mars

Simulation of substrate erosion and sulphate assimilation by Martian low-viscosity lava flows: implications for the genesis of precious metal-rich sulphide mineralisation on Mars

International audienceOn Earth, high temperature mafic to ultramafic lava flows, such as komatiites and ferropicrites of the Archean and Proterozic eons, can be hosts to Ni-Cu-PGE sulphide mineralisation. Mechanical/thermo-mechanical erosion and assimilation of sulphur-rich crustal rocks is ascribed as the principal mechanism that leads to sulphide supersaturation, batch segregation and subsequent accumulation of metal-enriched magmatic sulphides (e.g., Bekker et al., Science, 2009). In order to investigate the likelihood of the occurrence of similar sulphide mineralisation in extraterrestrial magmatic systems, we numerically modelled erosion and assimilation during the turbulent emplacement of Martian lavas, some of which display chemical and rheological analogies with terrestrial komatiites and ferropicrites, on a variety of consolidated sedimentary sulphate-rich substrates. The modelling approach relies on the integration of i) mathematical lava erosion models for turbulent flows (Williams et al., J. Geophys. Res., 1998), ii) thermodynamic volatile degassing models (Gaillard et al., Space Sci. Rev., 2013), and iii) formulations on the stability of sulphides (Fortin et al., Geochim. Cosmochim. Acta, 2015). A series of scenarios are examined in which various Martian mafic to ultramafic mantle-derived melts emplace over, and assimilate consolidated sulphate-rich substrates, such as the sedimentary lithologies (i.e., conglomerates, sandstones and mudstones) recently discovered at the Gale Crater landing site. Our modellings show that lavas emplacing over consolidated sedimentary substrate rather than stiff basaltic crust, are governed by relatively high cooling and substrate erosion rates. The rapid assimilation of sulphate, which serves as a strongly oxidising agent, could result in dramatic sulphur loss due to increased volatile degassing rates at fO2 ≳QFM-1. This effect is further enhanced with increased temperature. Nevertheless, sulphide supersaturation in the way of sulphate assimilation can be achieved in relatively reduced (i.e., fO2 <QFM-2) melts. We thus outline that reduced low-temperature melts of the Hesperian and Amazonian, such as those parental to the Adirondack-class basalts at Gusev Crater, rather than high-temperature melts of the Pre-Noachian and Noachian or those parental to some primitive Shergottite meteorites (Filiberto et al., J. Geophys. Res., 2015), are promising candidates for the presence of Ni-Cu-PGE sulphide mineralisation on Mars

The freshwater moss Fontinalis antipyretica bioaccumulates oxolinic acid

International audienc