67 research outputs found

    Use of commercial sphagnum to estimate the geographic impact of a battery of recycling plant

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    International audienceA technique of biosurveillance (moss-bags) is used to evaluate thé heavy metal depositions (lead, cadmium, arsenic, barium and antimony) around an industrial source. The results are compared with those obtained by the use of gauges of sedimentation and by modelling of the emissions from stacks. The moss-bags prove to be as good qualitative tools as the gauges of sedimentation. It also appears that the moss-bags have a greater effectiveness to collect the atmospheric depositions than the gauges of sedimentation and that, in spite of a smaller surface of exposure. Fifteen days duration is sufficient to collect quantifiable levels of lead, cadmium, antimony and barium, in the moss-bags placed in the vicinity of the studied site. However, the speed of accumulation of heavy metals in the moss-bag does not seem to be constant in time. This makes delicate the comparison of results of campaigns carried out over different durations and perhaps periods. This study validates the use of sphagnum mosses of culture to make some moss-bag, thus mitigating the difficulty of provisioning related to the use of "natural" sphagnum mosses. The use of this technique, that requires a minimum number of measuring points, made possible a quick evaluation of the site's contribution in lead, cadmium, arsenic and antimony, deposition measured in its vicinity. In comparison, the modelling of exhaust gases and particulates of the site provided incomplete qualitative information because of the presence of diffuse sources. This tool of powerful qualitative survey (confidence interval reduced, cost effective, ease of use, discrete, light technique) can bring essential information where other approaches are more uncertain (modelling in degraded situation) or require to be optimised (standardized quantitative methods).Une technique de biosurveillance (moss-bag) est utilisée pour évaluer les retombées de métaux lourds (plomb, cadmium, arsenic, baryum et antimoine) autour d'une source industrielle. Les résultats sont comparés à ceux obtenus par l'utilisation de jauges de sédimentation et par modélisation des rejets canalisés. Ces essais sont réalisés en parallèle autour d'un même site de seconde fusion du plomb. Les moss-bag se révèlent être d'aussi bons outils qualitatifs que les jauges de sédimentation. Il apparaît également que les moss-bag ont une plus grande efficacité à capter les retombées atmosphériques que les jauges de sédimentation et cela, malgré une surface d'exposition plus faible. Une durée de quinze jours est suffisante pour recueillir des niveaux quantifiables de plomb, de cadmium, d'antimoine et de baryum, dans les moss-bag placés au voisinage du site étudié. De plus, la hiérarchisation des points de retombées obtenue est équivalente voire plus fine (plus de niveaux différenciés) que celle déterminée au moyen de jauges au bout de trente jours. Cependant, la vitesse d'accumulation des métaux lourds dans les moss-bag ne semble pas être constante dans je temps. Ceci rend donc délicate la comparaison de résultats de campagnes réalisées sur des durées différentes et peut-être même des périodes différentes. La coupure granulométrique et la sélectivité des moss-bag restent également mal connues. Cette étude permet également de valider l'utilisation de sphaignes de culture pour concevoir les moss-bag, palliant ainsi la difficulté d'approvisionnement liée à l'utilisation de sphaignes "naturelles ". L'utilisation de cette technique de cette technique a permis d'évaluer rapidement la contribution du site aux teneurs de plomb, cadmium, arsenic et antimoine, mesurées à son voisinage. En comparaison, la modélisation des rejets canalisés du site a fourni une information qualitative incomplète du fait de la présence de sources diffuses. Cet outil de sondage qualitatif performant (intervalle de confiance réduit, coût de mise en oeuvre faible, simplicité d'utilisation, technique discrète, légère) peut apporter une information essentielle là où d'autres approches sont plus fragiles (modélisation en situation dégradée) ou nécessitent d'être optimisées (méthodes quantitatives normalisées). Cependant, une campagne de mesure utilisant une méthode de biosurveillance active, doit intégrer, dès sa conception, un minimum de points de contrôle (blanc de site, témoin, détermination de l'intervalle de confiance)

    Does MPTP intoxication in mice induce metabolite changes in the nucleus accumbens? A 1H nuclear MRS study: A severe DA denervation in VTA induces metabolite changes in the NAc

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    International audienceUsing in vivo 1H NMR spectroscopy in a mouse model of Parkinson's disease, we previously showed that glutamate concentrations in the dorsal striatum were highest after dopamine denervation associated with an increase in gamma-aminobutyric acid (GABA) and (Gln) glutamine levels. The aim of this study was to determine whether the changes previously observed in the motor part of the striatum were reproduced in a ventral part of the striatum, the nucleus accumbens (NAc). This study was carried out on controls and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated mice. In vivo spectra were acquired for a voxel (8 L) in the dorsal striatum, and in the NAc (1.56 L). NMR acquisitions were first performed 10 days after the last MPTP injection in a basal condition [after saline intraperitoneal (i.p.) injection] and then in the same animal the week after basal NMR acquisitions, after acute levodopa administration (200 mg kg1, i.p.). Immunohistochemistry was used to determine the levels of (Glu) glutamate, glutamine synthetase (GS) and glutamic acid decarboxylase (GAD) isoform 67 in these two structures. The Glu, Gln and GABA concentrations obtained in the basal state were higher in the NAc of MPTP-intoxicated mice which have the higher dopamine denervation in the ventral tegmental area (VTA) and in the dorsal striatum. Levodopa decreased the levels of these metabolites in MPTP-intoxicated mice to levels similar to those in controls. In parallel, immunohistochemical staining showed that glutamate, GS and GAD67 immunoreactivity increased in the dorsal striatum of MPTP-intoxicated mice and in the NAc for animals with a severe dopamine denervation in VTA. These findings strongly supported a hyperactivity of the glutamatergic cortico-striatal pathway and changes in glial activity when the dopaminergic denervation in the VTA and substantia nigra pars compacta (SNc) was severe. Copyright (c) 2012 John Wiley & Sons, Ltd

    Disease Severity and Progression in Progressive Supranuclear Palsy and Multiple System Atrophy: Validation of the NNIPPS – PARKINSON PLUS SCALE

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    BACKGROUND The Natural History and Neuroprotection in Parkinson Plus Syndromes (NNIPPS) study was a large phase III randomized placebo-controlled trial of riluzole in Progressive Supranuclear Palsy (PSP, n = 362) and Multiple System Atrophy (MSA, n = 398). To assess disease severity and progression, we constructed and validated a new clinical rating scale as an ancillary study. METHODS AND FINDINGS Patients were assessed at entry and 6-montly for up to 3 years. Evaluation of the scale's psychometric properties included reliability (n = 116), validity (n = 760), and responsiveness (n = 642). Among the 85 items of the initial scale, factor analysis revealed 83 items contributing to 15 clinically relevant dimensions, including Activity of daily Living/Mobility, Axial bradykinesia, Limb bradykinesia, Rigidity, Oculomotor, Cerebellar, Bulbar/Pseudo-bulbar, Mental, Orthostatic, Urinary, Limb dystonia, Axial dystonia, Pyramidal, Myoclonus and Tremor. All but the Pyramidal dimension demonstrated good internal consistency (Cronbach α ≥ 0.70). Inter-rater reliability was high for the total score (Intra-class coefficient = 0.94) and 9 dimensions (Intra-class coefficient = 0.80-0.93), and moderate (Intra-class coefficient = 0.54-0.77) for 6. Correlations of the total score with other clinical measures of severity were good (rho ≥ 0.70). The total score was significantly and linearly related to survival (p<0.0001). Responsiveness expressed as the Standardized Response Mean was high for the total score slope of change (SRM = 1.10), though higher in PSP (SRM = 1.25) than in MSA (SRM = 1.0), indicating a more rapid progression of PSP. The slope of change was constant with increasing disease severity demonstrating good linearity of the scale throughout disease stages. Although MSA and PSP differed quantitatively on the total score at entry and on rate of progression, the relative contribution of clinical dimensions to overall severity and progression was similar. CONCLUSIONS The NNIPPS-PPS has suitable validity, is reliable and sensitive, and therefore is appropriate for use in clinical studies with PSP or MSA. TRIAL REGISTRATION ClinicalTrials.gov NCT00211224

    Allons-nous vers une société plus responsable grâce à la pandémie de Covid-19 ?

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    La question traitée dans cet article porte sur le monde d’après la pandémie... Représente-t-elle un moment décisif qui va nous faire basculer vers une société plus responsable sur les plans sociaux et environnementaux ? De nouvelles habitudes et de nouveaux comportements responsables vont-ils se mettre en place de manière durable ? Pour répondre à ces enjeux, cet article mobilise des théories plurielles associées aux changements d’habitudes. Des préconisations s’adressant autant aux entreprises, qu’aux décideurs publics ou citoyens sont proposées pour dessiner les contours d’un après-Covid-19 socialement et écologiquement plus acceptable

    PTPA variants and impaired PP2A activity in early-onset parkinsonism with intellectual disability

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    The protein phosphatase 2A complex (PP2A), the major Ser/Thr phosphatase in the brain, is involved in a number of signalling pathways and functions, including the regulation of crucial proteins for neurodegeneration, such as alpha-synuclein, tau and LRRK2. Here, we report the identification of variants in the PTPA/PPP2R4 gene, encoding a major PP2A activator, in two families with early-onset parkinsonism and intellectual disability. We carried out clinical studies and genetic analyses, including genome-wide linkage analysis, whole-exome sequencing, and Sanger sequencing of candidate variants. We next performed functional studies on the disease-associated variants in cultured cells and knock-down of ptpa in Drosophila melanogaster. We first identified a homozygous PTPA variant, c.893T&gt;G (p.Met298Arg), in patients from a South African family with early-onset parkinsonism and intellectual disability. Screening of a large series of additional families yielded a second homozygous variant, c.512C&gt;A (p.Ala171Asp), in a Libyan family with a similar phenotype. Both variants co-segregate with disease in the respective families. The affected subjects display juvenile-onset parkinsonism and intellectual disability. The motor symptoms were responsive to treatment with levodopa and deep brain stimulation of the subthalamic nucleus. In overexpression studies, both the PTPA p.Ala171Asp and p.Met298Arg variants were associated with decreased PTPA RNA stability and decreased PTPA protein levels; the p.Ala171Asp variant additionally displayed decreased PTPA protein stability. Crucially, expression of both variants was associated with decreased PP2A complex levels and impaired PP2A phosphatase activation. PTPA orthologue knock-down in Drosophila neurons induced a significant impairment of locomotion in the climbing test. This defect was age-dependent and fully reversed by L-DOPA treatment. We conclude that bi-allelic missense PTPA variants associated with impaired activation of the PP2A phosphatase cause autosomal recessive early-onset parkinsonism with intellectual disability. Our findings might also provide new insights for understanding the role of the PP2A complex in the pathogenesis of more common forms of neurodegeneration.</p

    A new MRI rating scale for progressive supranuclear palsy and multiple system atrophy: validity and reliability

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    AIM To evaluate a standardised MRI acquisition protocol and a new image rating scale for disease severity in patients with progressive supranuclear palsy (PSP) and multiple systems atrophy (MSA) in a large multicentre study. METHODS The MRI protocol consisted of two-dimensional sagittal and axial T1, axial PD, and axial and coronal T2 weighted acquisitions. The 32 item ordinal scale evaluated abnormalities within the basal ganglia and posterior fossa, blind to diagnosis. Among 760 patients in the study population (PSP = 362, MSA = 398), 627 had per protocol images (PSP = 297, MSA = 330). Intra-rater (n = 60) and inter-rater (n = 555) reliability were assessed through Cohen's statistic, and scale structure through principal component analysis (PCA) (n = 441). Internal consistency and reliability were checked. Discriminant and predictive validity of extracted factors and total scores were tested for disease severity as per clinical diagnosis. RESULTS Intra-rater and inter-rater reliability were acceptable for 25 (78%) of the items scored (≥ 0.41). PCA revealed four meaningful clusters of covarying parameters (factor (F) F1: brainstem and cerebellum; F2: midbrain; F3: putamen; F4: other basal ganglia) with good to excellent internal consistency (Cronbach α 0.75-0.93) and moderate to excellent reliability (intraclass coefficient: F1: 0.92; F2: 0.79; F3: 0.71; F4: 0.49). The total score significantly discriminated for disease severity or diagnosis; factorial scores differentially discriminated for disease severity according to diagnosis (PSP: F1-F2; MSA: F2-F3). The total score was significantly related to survival in PSP (p<0.0007) or MSA (p<0.0005), indicating good predictive validity. CONCLUSIONS The scale is suitable for use in the context of multicentre studies and can reliably and consistently measure MRI abnormalities in PSP and MSA. Clinical Trial Registration Number The study protocol was filed in the open clinical trial registry (http://www.clinicaltrials.gov) with ID No NCT00211224
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