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Sol?ne Moulin - Top 30 Publications

Microbleeds, Cerebral Hemorrhage, and Functional Outcome After Stroke Thrombolysis: Individual Patient Data Meta-Analysis.

We assessed whether the presence, number, and distribution of cerebral microbleeds (CMBs) on pre-intravenous thrombolysis MRI scans of acute ischemic stroke patients are associated with an increased risk of intracerebral hemorrhage (ICH) or poor functional outcome.

In-hospital ischaemic stroke treated with intravenous thrombolysis or mechanical thrombectomy.

Patients with in-hospital strokes (IHS) may be eligible for recanalization therapies. The objective of this study is to compare outcomes in patients with IHS and community-onset strokes (COS) treated by recanalization therapy. We analysed data prospectively collected in consecutive patients treated by thrombolysis, thrombectomy, or both for cerebral ischemia at the Lille University Hospital. We compared four outcomes measures at 3 months in patients with IHS and COS: (1) modified Rankin scale (mRS) 0-1, (2) mRS 0-2, (3) death, and (4) symptomatic intracranial haemorrhage (ECASS 2 definition). Of 1209 patients, 64 (5.3%) had IHS, with an increasing proportion over time (p = 0.001). Their median onset-to-needle time was 128 min vs. 145 in COS (p < 0.001). They were more likely to have had a recent TIA [odds ratio (OR) 30.1; 95% confidence interval (CI) 11.5-78.7], to have been treated by vitamin K antagonist before (OR 4.2; 95% CI 1.4-12.0) and to undergo mechanical thrombectomy (45 vs. 10%, p < 0.001). They were less likely to have a pre-stroke mRS 0-1 (OR 0.22; 95% CI 0.09-0.50). After adjustment, IHS was not associated with any of the four outcome measures. Patients with IHS are treated 17 min earlier than patients with COS, but, taking into account that they were already in the hospital, delays are still too long. Their outcome does not differ from that of patients with COS, suggesting room for improvement if delays can be reduced. IHS being frequent, pre-specified pathways should be organised.

Glutaric Aciduria Type 1 and Acute Renal Failure: Case Report and Suggested Pathomechanisms.

Glutaric aciduria type 1 (GA1) is caused by deficiency of the mitochondrial matrix enzyme glutaryl-CoA dehydrogenase (GCDH), leading to accumulation of glutaric acid (GA) and 3-hydroxyglutaric acid (3OHGA) in tissues and body fluids. During catabolic crises, GA1 patients are prone to the development of striatal necrosis and a subsequent irreversible movement disorder during a time window of vulnerability in early infancy. Thus, GA1 had been considered a pure "cerebral organic aciduria" in the past. Single case reports have indicated the occurrence of acute renal dysfunction in children affected by GA1. In addition, growing evidence arises that GA1 patients may develop chronic renal failure during adulthood independent of the previous occurrence of encephalopathic crises. The underlying mechanisms are yet unknown. Here we report on a 3-year-old GA1 patient who died following the development of acute renal failure most likely due to haemolytic uraemic syndrome associated with a pneumococcal infection. We hypothesise that known GA1 pathomechanisms, namely the endothelial dysfunction mediated by 3OHGA, as well as the transporter mechanisms for the urinary excretion of GA and 3OHGA, are involved in the development of glomerular and tubular dysfunction, respectively, and may contribute to a pre-disposition of GA1 patients to renal disease. We recommend careful differential monitoring of glomerular and tubular renal function in GA1 patients.

Treatment of radioactive liquid effluents by reverse osmosis membranes: From lab-scale to pilot-scale.

The recent use of the reverse osmosis (RO) process at the damaged Fukushima-Daiichi nuclear power plant generated a growing interest in the application of this process for decontamination purposes. This study focused on the development of a robust RO process for decontamination of two kinds of liquid effluents: a contaminated groundwater after a nuclear disaster and a contaminated seawater during a nuclear accident. The SW30 HR membrane was selected among other in this study due to higher retentions (96% for Cs and 98% for Sr) in a true groundwater. Significant fouling and scaling phenomenon, attributed to calcium and strontium precipitation, were evidenced in this work: this underscored the importance of the lab scale experiment in the process. Validation of the separation performances on trace radionuclides concentration was performed with similar retention around 96% between surrogates Cs (inactive) and (137)Cs (radioactive). The scale up to a 2.6 m(2) spiral wound membrane led to equivalent retentions (around 96% for Cs and 99% for Sr) but lower flux values: this underlined that the hydrodynamic parameters (flowrate/cross-flow velocity) should be optimized. This methodology was also applied on the reconstituted seawater effluent: retentions were slightly lower than for the groundwater and the same hydrodynamic effects were observed on the pilot scale. Then, ageing of the membrane through irradiation experiments were performed. Results showed that the membrane active layer composition influenced the membrane resistance towards γ irradiation: the SW30 HR membrane performances (retention and permeability) were better than the Osmonics SE at 1 MGy. Finally, to supplement the scale up approach, the irradiation of a spiral wound membrane revealed a limited effect on the permeability and retention. This indicated that irradiation conditions need to be controlled for a further development of the process.

Vγ9Vδ2 T cell activation by strongly agonistic nucleotidic phosphoantigens.

Human Vγ9Vδ2 T cells can sense through their TCR tumor cells producing the weak endogenous phosphorylated antigen isopentenyl pyrophosphate (IPP), or bacterially infected cells producing the strong agonist hydroxyl dimethylallyl pyrophosphate (HDMAPP). The recognition of the phosphoantigen is dependent on its binding to the intracellular B30.2 domain of butyrophilin BTN3A1. Most studies have focused on pyrophosphate phosphoantigens. As triphosphate nucleotide derivatives are naturally co-produced with IPP and HDMAPP, we analyzed their specific properties using synthetic nucleotides derived from HDMAPP. The adenylated, thymidylated and uridylated triphosphate derivatives were found to activate directly Vγ9Vδ2 cell lines as efficiently as HDMAPP in the absence of accessory cells. These antigens were inherently resistant to terminal phosphatases, but apyrase, when added during a direct stimulation of Vγ9Vδ2 cells, abrogated their stimulating activity, indicating that their activity required transformation into strong pyrophosphate agonists by a nucleotide pyrophosphatase activity which is present in serum. Tumor cells can be sensitized with nucleotide phosphoantigens in the presence of apyrase to become stimulatory, showing that this can occur before their hydrolysis into pyrophosphates. Whereas tumors sensitized with HDMAPP rapidly lost their stimulatory activity, sensitization with nucleotide derivatives, in particular with the thymidine derivative, induced long-lasting stimulating ability. Using isothermal titration calorimetry, binding of some nucleotide derivatives to BTN3A1 intracellular domain was found to occur with an affinity similar to that of IPP, but much lower than that of HDMAPP. Thus, nucleotide phosphoantigens are precursors of pyrophosphate antigens which can deliver strong agonists intracellularly resulting in prolonged and strengthened activity.

A Pilot Study on Ocular Safety and Efficacy of Infliximab as an Antifibrotic Agent After Experimental Glaucoma Filtration Surgery.

Tumor necrosis factor-α (TNF-α) is a multifunctional, proinflammatory cytokine that mediates pleiotropic biological functions, especially inflammation and immunoregulation. We hypothesized that blocking TNF-α with a monoclonal antibody would decrease inflammation and subconjunctival scarring in an animal model of experimental filtration surgery.

Lower Functional Connectivity of the Periaqueductal Gray Is Related to Negative Affect and Clinical Manifestations of Fibromyalgia.

Fibromyalgia (FM) syndrome is characterized by chronic widespread pain, muscle tenderness and emotional distress. Previous studies found reduced endogenous pain modulation in FM. This deficiency of pain modulation may be related to the attributes of chronic pain and other clinical symptoms experienced in patients with FM. Thus, we tested whether there is a link between the clinical symptoms of FM and functional connectivity (FC) of the periaqueductal gray (PAG), a key node of pain modulation. We acquired resting state 3T functional MRI (rsfMRI) data from 23 female patients with FM and 16 age- and sex- matched healthy controls (HC) and assessed FM symptoms with the Brief Pain Inventory (BPI), Fibromyalgia Impact Questionnaire (FIQ), Hospital Anxiety and Depression Scale (HADS) and Pain Catastrophizing Scale (PCS). We found that patients with FM exhibit statistically significant disruptions in PAG FC, particularly with brain regions implicated in negative affect, self-awareness and saliency. Specifically, we found that, compared to HCs, the FM patients had stronger PAG FC with the lingual gyrus and hippocampus but weaker PAG FC with regions associated with motor/executive functions, the salience (SN) and default mode networks (DMN). The attenuated PAG FC was also negatively correlated with FIQ scores, and positively correlated with the magnification subscale of the PCS. These alterations were correlated with emotional and behavioral symptoms of FM. Our study implicates the PAG as a site of dysfunction contributing to the clinical manifestations and pain in FM.

MicroRNA-29b Contributes to Collagens Imbalance in Human Osteoarthritic and Dedifferentiated Articular Chondrocytes.

Decreased expression of collagen type II in favour of collagen type I or X is one hallmark of chondrocyte phenotype changes in osteoarthritic (OA) cartilage. MicroRNA- (miR-) 29b was previously shown to target collagens in several tissues. We studied whether it could contribute to collagen imbalance in chondrocytes with an impaired phenotype.

Pain-related Activity Management Patterns and Function in Patients with Fibromyalgia Syndrome.

To clarify the importance of avoidance, pacing and overdoing pain-related activity management patterns as predictors of adjustment in patients with Fibromyalgia Syndrome (FMS).

The Utility of Gene Expression Profiling from Tissue Samples to Support Drug Safety Assessments.

Originally conceptualized as an integrated approach combining conventional toxicology methods with genome-wide expression profiling, toxicogenomics has promised to provide unequivocal relationships between the molecular changes elicited by a compound or a target pathway and the lesions that appear subsequently in the tissues. However, the discipline has only partially delivered on this promise, and the number of publications and submissions related to toxicogenomics is stagnating. The purpose of this article is to outline key factors contributing to a successful implementation of toxicogenomics in the drug discovery and development process. Paradigms and methods of toxicogenomics are briefly reviewed, and the prominence of biostatistics and its limitations in the particular context of nonclinical toxicology studies are discussed. We present specific approaches for pathophysiological contextualization of gene expression data derived from tissues with lesions at variable incidence and severity: "unmixing" (deconvolution) of molecular expression profiles from complex tissues, the invaluable contribution of reference data, the role of establishing causation between expression signals and pathologic changes (phenotypic anchoring), and especially molecular localization. These approaches compensate for the limitations of biostatistical analysis, which in turn, derive from tissue heterogeneity. Finally, impactful applications of toxicogenomics along the drug discovery and development process are exemplified, from the evaluation of potential target toxicities to the selection of candidate compounds and elucidation of the molecular and cellular mechanisms leading to chronic toxicity.

Real-life patterns of use, safety and effectiveness of sunitinib in first-line therapy of metastatic renal cell carcinoma: the SANTORIN cohort study.

To investigate sunitinib in the real-life first-line treatment of metastatic renal cell carcinoma (mRCC).

The cognitive effects of wearable cameras in Mild Alzheimer disease - An experimental study.

Wearable cameras are a new type of intervention aimed at stimulating memory in Alzheimer's disease (AD). Such passive external memory aids have started to be considered as alternatives to both more active external aids (such as writing in diaries, journals, and timetables) and to internal cognitive strategies (such as spaced retrieval, errorless learning).

Xenobiotic CAR activators induce Dlk1-Dio3 locus non-coding RNA expression in mouse liver.

Derisking xenobiotic-induced non-genotoxic carcinogenesis (NGC) represents a significant challenge during the safety assessment of chemicals and therapeutic drugs. The identification of robust mechanism-based NGC biomarkers has the potential to enhance cancer hazard identification. We previously demonstrated Constitutive Androstane Receptor (CAR) and WNT signaling-dependent up-regulation of the pluripotency associated Dlk1-Dio3 imprinted gene cluster non-coding RNAs (ncRNAs) in the liver of mice treated with tumor-promoting doses of phenobarbital (PB). Here, we have compared phenotypic, transcriptional and proteomic data from wild-type, CAR/PXR double knock-out and CAR/PXR double humanized mice treated with either PB or chlordane, and show that hepatic Dlk1-Dio3 locus long ncRNAs are upregulated in a CAR/PXR-dependent manner by two structurally distinct CAR activators. We further explored the specificity of Dlk1-Dio3 locus ncRNAs as hepatic NGC biomarkers in mice treated with additional compounds working through distinct NGC modes of action. We propose that up-regulation of Dlk1-Dio3 cluster ncRNAs can serve as an early biomarker for CAR activator-induced non-genotoxic hepatocarcinogenesis and thus may contribute to mechanism-based assessments of carcinogenicity risk for chemicals and novel therapeutics.

Selective Cannabinoids for Chronic Neuropathic Pain: A Systematic Review and Meta-analysis.

There is a lack of consensus on the role of selective cannabinoids for the treatment of neuropathic pain (NP). Guidelines from national and international pain societies have provided contradictory recommendations. The primary objective of this systematic review and meta-analysis (SR-MA) was to determine the analgesic efficacy and safety of selective cannabinoids compared to conventional management or placebo for chronic NP.

Discovery of Clinical Candidate 2-((2S,6S)-2-Phenyl-6-hydroxyadamantan-2-yl)-1-(3'-hydroxyazetidin-1-yl)ethanone BMS-816336, an Orally Active Novel Selective 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitor.

BMS-816336 (6n-2), a hydroxy-substituted adamantyl acetamide, has been identified as a novel, potent inhibitor against human 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme (IC50 3.0 nM) with >10000-fold selectivity over human 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2). 6n-2 exhibits a robust acute pharmacodynamic effect in cynomolgus monkeys (ED50 0.12 mg/kg) and in DIO mice. It is orally bioavailable (%F ranges from 20 to 72% in preclinical species) and has a predicted pharmacokinetic profile of a high peak to trough ratio and short half-life in humans. This ADME profile met our selection criteria for once daily administration, targeting robust inhibition of 11β-HSD1 enzyme for the first 12 h period after dosing followed by an "inhibition holiday" so that the potential for hypothalamic-pituitary-adrenal (HPA) axis activation might be mitigated. 6n-2 was found to be well-tolerated in phase 1 clinical studies and represents a potential new treatment for type 2 diabetes, metabolic syndrome, and other human diseases modulated by glucocorticoid control.

Simultaneous measurement of T2 and apparent diffusion coefficient (T2 +ADC) in the heart with motion-compensated spin echo diffusion-weighted imaging.

To evaluate a technique for simultaneous quantitative T2 and apparent diffusion coefficient (ADC) mapping in the heart (T2 +ADC) using spin echo (SE) diffusion-weighted imaging (DWI).

Prevalence and Psychosocial Correlates of ADHD Symptoms in Young Adulthood: A French Population-Based Study.

The scientific literature suggests that ADHD in adulthood is associated with a considerable psychosocial burden. However, most knowledge in this area relies on studies conducted in the United States or in North European nations, thereby limiting generalization to other countries.

Sensitivity of the DN4 in Screening for Neuropathic Pain Syndromes.

Several tools have been developed to screen for neuropathic pain. This study examined the sensitivity of the Douleur Neuropathique en 4 Questions (DN4) in screening for various neuropathic pain syndromes.

Eplerenone treatment alleviates the development of joint lesions in a new rat model of spontaneous metabolic-associated osteoarthritis.

Permanent Draft Genome Sequence of Rhizobium sp. Strain LCM 4573, a Salt-Tolerant, Nitrogen-Fixing Bacterium Isolated from Senegalese Soils.

The genus Rhizobium contains many species that are able to form nitrogen-fixing nodules on plants of the legume family. Here, we report the 5.5-Mb draft genome sequence of the salt-tolerant Rhizobium sp. strain LCM 4573, which has a G+C content of 61.2% and 5,356 candidate protein-encoding genes.

Calcified Non-Pigmented Choroidal Melanoma: Report of a Rare Case.

Are the results of intravenous thrombolysis trials reproduced in clinical practice? Comparison of observed and expected outcomes with the stroke-thrombolytic predictive instrument (STPI).

In patients with cerebral ischemia, intravenous (i.v.) recombinant tissue plasminogen activator (rt-PA) increases survival without handicap or dependency despite an increased risk of bleeding. This study evaluated whether the results of randomized controlled trials are reproduced in clinical practice.

Eddy current-nulled convex optimized diffusion encoding (EN-CODE) for distortion-free diffusion tensor imaging with short echo times.

To design and evaluate eddy current-nulled convex optimized diffusion encoding (EN-CODE) gradient waveforms for efficient diffusion tensor imaging (DTI) that is free of eddy current-induced image distortions.

Validation of SmartRank: A likelihood ratio software for searching national DNA databases with complex DNA profiles.

Searching a national DNA database with complex and incomplete profiles usually yields very large numbers of possible matches that can present many candidate suspects to be further investigated by the forensic scientist and/or police. Current practice in most forensic laboratories consists of ordering these 'hits' based on the number of matching alleles with the searched profile. Thus, candidate profiles that share the same number of matching alleles are not differentiated and due to the lack of other ranking criteria for the candidate list it may be difficult to discern a true match from the false positives or notice that all candidates are in fact false positives. SmartRank was developed to put forward only relevant candidates and rank them accordingly. The SmartRank software computes a likelihood ratio (LR) for the searched profile and each profile in the DNA database and ranks database entries above a defined LR threshold according to the calculated LR. In this study, we examined for mixed DNA profiles of variable complexity whether the true donors are retrieved, what the number of false positives above an LR threshold is and the ranking position of the true donors. Using 343 mixed DNA profiles over 750 SmartRank searches were performed. In addition, the performance of SmartRank and CODIS were compared regarding DNA database searches and SmartRank was found complementary to CODIS. We also describe the applicable domain of SmartRank and provide guidelines. The SmartRank software is open-source and freely available. Using the best practice guidelines, SmartRank enables obtaining investigative leads in criminal cases lacking a suspect.

International and multidisciplinary expert recommendations for the use of biologics in systemic lupus erythematosus.

Despite conventional immunosuppressants, active and steroid-dependent systemic lupus erythematosus (SLE) represents a therapeutic challenge. Only one biologic, belimumab, has been approved, but other biologics are sometimes used off-label. Given the lack of evidence-based data in some clinical situations encountered in real life, we developed expert recommendations for the use of biologics for SLE.

Transvaginal ultrasound-guided embryo transfer in IVF.

To determine whether transvaginal ultrasound-guided embryo transfer is a technique that can be used routinely, whether it improves IVF outcomes and whether it makes difficult transfers easier and more successful.

Mitochondria: a central target for sex differences in pathologies.

It is increasingly acknowledged that a sex and gender specificity affects the occurrence, development, and consequence of a plethora of pathologies. Mitochondria are considered as the powerhouse of the cell because they produce the majority of energy-rich phosphate bonds in the form of adenosine tri-phosphate (ATP) but they also participate in many other functions like steroid hormone synthesis, reactive oxygen species (ROS) production, ionic regulation, and cell death. Adequate cellular energy supply and survival depend on mitochondrial life cycle, a process involving mitochondrial biogenesis, dynamics, and quality control via mitophagy. It appears that mitochondria are the place of marked sexual dimorphism involving mainly oxidative capacities, calcium handling, and resistance to oxidative stress. In turn, sex hormones regulate mitochondrial function and biogenesis. Mutations in genes encoding mitochondrial proteins are the origin of serious mitochondrial genetic diseases. Mitochondrial dysfunction is also an important parameter for a large panel of pathologies including neuromuscular disorders, encephalopathies, cardiovascular diseases (CVDs), metabolic disorders, neuropathies, renal dysfunction etc. Many of these pathologies present sex/gender specificity. Here we review the sexual dimorphism of mitochondria from different tissues and how this dimorphism takes part in the sex specificity of important pathologies mainly CVDs and neurological disorders.

Autoantibodies against GPIHBP1 as a Cause of Hypertriglyceridemia.

A protein that is expressed on capillary endothelial cells, called GPIHBP1 (glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1), binds lipoprotein lipase and shuttles it to its site of action in the capillary lumen. A deficiency in GPIHBP1 prevents lipoprotein lipase from reaching the capillary lumen. Patients with GPIHBP1 deficiency have low plasma levels of lipoprotein lipase, impaired intravascular hydrolysis of triglycerides, and severe hypertriglyceridemia (chylomicronemia). During the characterization of a monoclonal antibody-based immunoassay for GPIHBP1, we encountered two plasma samples (both from patients with chylomicronemia) that contained an interfering substance that made it impossible to measure GPIHBP1. That finding raised the possibility that those samples might contain GPIHBP1 autoantibodies.

Morel-Lavallée syndrome and post-traumatic nodular fat necrosis: Two post-traumatic complications mimicking cellulitis.

Dermal and subcutaneous inflammation following direct trauma is initially evocative of soft-tissue infection. However, two differential diagnoses must be considered: Morel-Lavallée syndrome and post-traumatic nodular fat necrosis.

Mycobacterium llatzerense, a waterborne Mycobacterium, that resists phagocytosis by Acanthamoeba castellanii.

Nontuberculous mycobacteria (NTM) are environmental bacteria increasingly associated to public health problems. In water systems, free-living amoebae (FLA) feed on bacteria by phagocytosis, but several bacteria, including many NTM, are resistant to this predation. Thus, FLA can be seen as a training ground for pathogenic bacteria. Mycobacterium llatzerense was previously described as frequently associated with FLA in a drinking water network. The present study aimed to characterize the interactions between M. llatzerense and FLA. M. llatzerense was internalised by phagocytosis and featured lipid inclusions, suggesting a subversion of host resources. Moreover, M. llatzerense survived and even multiplied in presence of A. castellanii. Using a genomic-based comparative approach, twelve genes involved in phagocytosis interference, described in M. tuberculosis, were identified in the M. llatzerense genome sequenced in this study. Transcriptomic analyses showed that ten genes were significantly upregulated during the first hours of the infection, which could partly explain M. llatzerense resistance. Additionally, M. llatzerense was shown to actively inhibit phagosome acidification. In conclusion, M. llatzerense presents a high degree of resistance to phagocytosis, likely explaining its frequent occurrence within FLA in drinking water networks. It underscores that NTM should be carefully monitored in water networks to prevent human health concerns.