Publications by authors named "Elodie Petit"

12 Publications

  • Page 1 of 1

Plasma neurofilament light chain predicts cerebellar atrophy and clinical progression in spinocerebellar ataxia.

Neurobiol Dis 2021 Jun 23;153:105311. Epub 2021 Feb 23.

Sorbonne Université, ICM (Paris Brain Institute), AP-HP, INSERM, CNRS, University Hospital Pitié-Salpêtrière, Paris, France; APHP Department of Genetics, Pitié-Salpêtrière University Hospital, Paris, France. Electronic address:

Neurofilament light chain (NfL) is a marker of brain atrophy and predictor of disease progression in rare diseases such as Huntington Disease, but also in more common neurological disorders such as Alzheimer's disease. The aim of this study was to measure NfL longitudinally in autosomal dominant spinocerebellar ataxias (SCAs) and establish correlation with clinical and imaging parameters. We enrolled 62 pathological expansions carriers (17 SCA1, 13 SCA2, 19 SCA3, and 13 SCA7) and 19 age-matched controls in a prospective biomarker study between 2011 and 2015 and followed for 24 months at the Paris Brain Institute. We performed neurological examination, brain 3 T MRI and plasma NfL measurements using an ultrasensitive single-molecule array at baseline and at the two-year follow-up visit. We evaluated NfL correlations with ages, CAG repeat sizes, clinical scores and volumetric brain MRIs. NfL levels were significantly higher in SCAs than controls at both time points (p < 0.001). Age-adjusted NfL levels were significantly correlated at baseline with clinical scores (p < 0.01). We identified optimal NfL cut-off concentrations to differentiate controls from carriers for each genotype (SCA1 16.87 pg/mL, SCA2, 19.1 pg/mL, SCA3 16.04 pg/mL, SCA7 16.67 pg/mL). For all SCAs, NfL concentration was stable over two years (p = 0.95) despite a clinical progression (p < 0.0001). Clinical progression between baseline and follow-up was associated with higher NfL concentrations at baseline (p = 0.04). Of note, all premanifest carriers with NfL levels close to cut off concentrations had signs of the disease at follow-up. For all SCAs, the higher the observed NfL, the lower the pons volume at baseline (p < 0.01) and follow-up (p = 0.02). Higher NfL levels at baseline in all SCAs predicted a decrease in cerebellar volume (p = 0.03). This result remained significant for SCA2 only among all genotypes (p = 0.02). Overall, plasma NfL levels at baseline in SCA expansion carriers predict cerebellar volume change and clinical score progression. NfL levels might help refine inclusion criteria for clinical trials in carriers with very subtle signs.
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http://dx.doi.org/10.1016/j.nbd.2021.105311DOI Listing
June 2021

Estimating disease prevalence and temporal dynamics using biased capture serological data in a wildlife reservoir: The example of brucellosis in Alpine ibex (Capra ibex).

Prev Vet Med 2021 Feb 26;187:105239. Epub 2020 Dec 26.

OFB - Office Français de la Biodiversité - Direction de la Recherche et Appui Scientifique - Unité Sanitaire de la Faune, Gap, France.

The monitoring of the disease prevalence in a population is an essential component of its adaptive management. However, field data often lead to biased estimates. This is the case for brucellosis infection of ibex in the Bargy massif (France). A test-and-cull program is being carried out in this area to manage the infection: captured animals are euthanized when seropositive, and marked and released when seronegative. Because this mountainous species is difficult to capture, field workers tend to focus the capture effort on unmarked animals. Indeed, marked animals are less likely to be infected, as they were controlled and negative during previous years. As the proportion of marked animals in the population becomes large, captured animals can no longer be considered as an unbiased sample of the population. We designed an integrated Bayesian model to correct this bias, by estimating the seroprevalence in the population as the combination of the separate estimates of the seroprevalence among unmarked animals (estimated from the data) and marked animals (estimated with a catalytic infection model, to circumvent the scarcity of the data). As seroprevalence may not be the most responsive parameter to management actions, we also estimated the proportion of animals in the population with an active bacterial infection. The actual infection status of captured animals was thus inferred as a function of their age and their level of antibodies, using a model based on bacterial cultures carried out for a sample of animals. Focusing on the population of adult females in the core area of the massif, i.e. with the highest seroprevalence, this observational study shows that seroprevalence has been divided by two between 2013 (51%) and 2018 (21%). Moreover, the likely estimated proportion of actively infected females in the same population, though very imprecise, has decreased from a likely estimate of 34% to less than 15%, suggesting that the management actions have been effective in reducing infection prevalence.
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http://dx.doi.org/10.1016/j.prevetmed.2020.105239DOI Listing
February 2021

Informing about genetic risk in families with Huntington disease: comparison of attitudes across two decades.

Eur J Hum Genet 2021 Apr 9;29(4):672-679. Epub 2020 Dec 9.

Sorbonne Université, Paris Brain Institute (ICM), AP-HP, INSERM, CNRS, Pitié-Salpêtrière University Hospital, Paris, France.

The low uptake of presymptomatic testing in Huntington disease prompted us to question family members on how they handle the transmission of information regarding genetic risk. We hypothesised that in 2019, parents would inform their at-risk children about their genetic risk more and at a younger age than in 2000, given the availability of prenatal diagnosis, French legislation changes since 2011, and recent therapeutic advances. We made a questionnaire available about the transmission of genetic information within families with Huntington disease in 2000 and 2019. We obtained 443 questionnaires (295 in 2019 and 148 in 2000). Participants were mainly at-risk for Huntington disease (n = 113), affected (n = 85), and spouses (n = 154). In 2019, participants had a higher mean education level (p < 0.01) and a mean age of 44.1 ± 15.1 years (vs 48.1 ± 11.4 years in 2000, p < 0.01). They had been informed about the risk of being a carrier at around 30 years of age (29.0 ± 14.2 in 2019 vs 32.2 ± 13.8 in 2000, p = 0.09). However, they would inform at an earlier age (≤18 years, 67% vs 59%, p = 0.16). Information on transmission risk had been given primarily by parents (45% vs 30%, p = 0.06). In addition, genetic testing for relatives unaware of their status was recommended more frequently in 2019 (46% vs 32%, p < 0.001). Respondents in 2019 recommended genetic testing more often but overall attitudes towards information and testing have not changed significantly over the 19-year time period since the questionnaire was first delivered even despite recent clinical trials potential disease modifying therapies.
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http://dx.doi.org/10.1038/s41431-020-00776-8DOI Listing
April 2021

Genetic epidemiology of the Alpine ibex reservoir of persistent and virulent brucellosis outbreak.

Sci Rep 2020 03 10;10(1):4400. Epub 2020 Mar 10.

Université de Lyon, VetAgro Sup - Campus vétérinaire de Lyon, Marcy l'Étoile, France.

While it is now broadly accepted that inter-individual variation in the outcomes of host-pathogen interactions is at least partially genetically controlled, host immunogenetic characteristics are rarely investigated in wildlife epidemiological studies. Furthermore, most immunogenetic studies in the wild focused solely on the major histocompatibility complex (MHC) diversity despite it accounts for only a fraction of the genetic variation in pathogen resistance. Here, we investigated immunogenetic diversity of the Alpine ibex (Capra ibex) population of the Bargy massif, reservoir of a virulent outbreak of brucellosis. We analysed the polymorphism and associations with disease resistance of the MHC Class II Drb gene and several non-MHC genes (Toll-like receptor genes, Slc11A1) involved in the innate immune response to Brucella in domestic ungulates. We found a very low neutral genetic diversity and a unique MHC Drb haplotype in this population founded few decades ago from a small number of individuals. By contrast, other immunity-related genes have maintained polymorphism and some showed significant associations with the brucellosis infection status hence suggesting a predominant role of pathogen-mediated selection in their recent evolutionary trajectory. Our results highlight the need to monitor immunogenetic variation in wildlife epidemiological studies and to look beyond the MHC.
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http://dx.doi.org/10.1038/s41598-020-61299-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7064506PMC
March 2020

Potential Sustainable Slow-Release Fertilizers Obtained by Mechanochemical Activation of MgAl and MgFe Layered Double Hydroxides and K₂HPO₄.

Nanomaterials (Basel) 2019 Feb 1;9(2). Epub 2019 Feb 1.

Institut de chimie de Clermont-Ferrand (ICCF), Université Clermont Auvergne, Centre National Recherche Scientifique (CNRS), Sigma Clermont, F-63000 Clermont-Ferrand, France.

This study describes the behavior of potential slow-release fertilizers (SRF), prepared by the mechanochemical activation of calcined Mg₂Al-CO₃ or Mg₂Fe-CO₃ layered double hydroxides (LDH) mixed with dipotassium hydrogen phosphate (K₂HPO₄). The effects of LDH thermal treatment on P/K release behavior were investigated. Characterizations of the inorganic composites before and after release experiments combined X-Ray diffraction (XRD), Fourier-transform infra-red spectroscopy (FTIR), solid-state nuclear magnetic resonance (NMR), scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX). The best release profile (<75% in 28 days and at least 75% release) was obtained for MgAl/K₂HPO₄ (9 h milling, 2:1 molar ratio, MR). Compared to readily used K₂HPO₄, milling orthophosphate into LDH matrices decreases its solubility and slows down its release, with 60% and 5.4% release after 168 h for MgAl/K₂HPO₄ and MgFe/K₂HPO₄ composites, respectively. Mechanochemical addition of carboxymethylcellulose to the LDH/K₂HPO₄ composites leads to a noticeable improvement of P release properties.
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http://dx.doi.org/10.3390/nano9020183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6410234PMC
February 2019

Autosomal dominant cerebellar ataxias: Imaging biomarkers with high effect sizes.

Neuroimage Clin 2018 14;19:858-867. Epub 2018 Jun 14.

INSERM U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, F-75013 Paris, France; AP-HP, Pitié-Salpêtrière University Hospital, Department of Genetics, Paris, France; University Pierre and Marie Curie, Neurometabolic Research Group, Paris, France. Electronic address:

Objective: As gene-based therapies may soon arise for patients with spinocerebellar ataxia (SCA), there is a critical need to identify biomarkers of disease progression with effect sizes greater than clinical scores, enabling trials with smaller sample sizes.

Methods: We enrolled a unique cohort of patients with SCA1 ( = 15), SCA2 ( = 12), SCA3 ( = 20) and SCA7 ( = 10) and 24 healthy controls of similar age, sex and body mass index. We collected longitudinal clinical and imaging data at baseline and follow-up (mean interval of 24 months). We performed both manual and automated volumetric analyses. Diffusion tensor imaging (DTI) and a novel tractography method, called fixel-based analysis (FBA), were assessed at follow-up. Effect sizes were calculated for clinical scores and imaging parameters.

Results: Clinical scores worsened as atrophy increased over time ( < 0.05). However, atrophy of cerebellum and pons showed very large effect sizes (>1.2) compared to clinical scores (<0.8). FBA, applied for the first time to SCA, was sensitive to microstructural cross-sectional differences that were not captured by conventional DTI metrics, especially in the less studied SCA7 group. FBA also showed larger effect sizes than DTI metrics.

Conclusion: This study showed that volumetry outperformed clinical scores to measure disease progression in SCA1, SCA2, SCA3 and SCA7. Therefore, we advocate the use of volumetric biomarkers in therapeutic trials of autosomal dominant ataxias. In addition, FBA showed larger effect size than DTI to detect cross-sectional microstructural alterations in patients relative to controls.
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http://dx.doi.org/10.1016/j.nicl.2018.06.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6005808PMC
January 2019

High Shedding Potential and Significant Individual Heterogeneity in Naturally-Infected Alpine ibex () With .

Front Microbiol 2018 28;9:1065. Epub 2018 May 28.

Wildlife Diseases Unit, French Hunting and Wildlife Agency (ONCFS), Gap, France.

Wildlife reservoirs of infectious diseases raise major management issues. In Europe, brucellosis has been eradicated in domestic ruminants from most countries and wild ruminants have not been considered important reservoirs so far. However, a high prevalence of infection has been recently identified in a French population of Alpine ibex (), after the emergence of brucellosis was confirmed in a dairy cattle farm and two human cases. This situation raised the need to identify the factors driving the persistence of infection at high prevalence levels in this ibex population. In the present paper, we studied the shedding pattern of in ibex from Bargy Massif, French Alps. Bacteriological examinations (1-15 tissues/samples per individual) were performed on 88 seropositive, supposedly infected and euthanized individuals. Among them, 51 (58%) showed at least one positive culture, including 45 ibex with at least one isolation from a urogenital sample or a lymph node in the pelvic area (active infection in organs in the pelvic area). Among these 45 ibex, 26 (30% of the total number of necropsied animals) showed at least one positive culture for a urogenital organ and were considered as being at risk of shedding the bacteria at the time of capture. We observed significant heterogeneity between sex-and-age classes: seropositive females were most at risk to excrete before the age of 5 years, possibly corresponding to abortion during the first pregnancy following infection such as reported in the domestic ruminants. The high shedding potential observed in young females may have contributed to the self-sustained maintenance of infection in this population, whereas males are supposed to play a role of transmission between spatial units through venereal transmission during mating. This heterogeneity in the shedding potential of seropositive individuals should be considered in the future to better evaluate management scenarios in this system as well as in others.
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http://dx.doi.org/10.3389/fmicb.2018.01065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5985404PMC
May 2018

Plasma oxysterols: biomarkers for diagnosis and treatment in spastic paraplegia type 5.

Brain 2018 01;141(1):72-84

APHP, La Pitié-Salpêtrière University Hospital, Reference Center for Adult Neurometabolic Diseases, Paris, France.

The hereditary spastic paraplegias are an expanding and heterogeneous group of disorders characterized by spasticity in the lower limbs. Plasma biomarkers are needed to guide the genetic testing of spastic paraplegia. Spastic paraplegia type 5 (SPG5) is an autosomal recessive spastic paraplegia due to mutations in CYP7B1, which encodes a cytochrome P450 7α-hydroxylase implicated in cholesterol and bile acids metabolism. We developed a method based on ultra-performance liquid chromatography electrospray tandem mass spectrometry to validate two plasma 25-hydroxycholesterol (25-OHC) and 27-hydroxycholesterol (27-OHC) as diagnostic biomarkers in a cohort of 21 patients with SPG5. For 14 patients, SPG5 was initially suspected on the basis of genetic analysis, and then confirmed by increased plasma 25-OHC, 27-OHC and their ratio to total cholesterol. For seven patients, the diagnosis was initially based on elevated plasma oxysterol levels and confirmed by the identification of two causal CYP7B1 mutations. The receiver operating characteristic curves analysis showed that 25-OHC, 27-OHC and their ratio to total cholesterol discriminated between SPG5 patients and healthy controls with 100% sensitivity and specificity. Taking advantage of the robustness of these plasma oxysterols, we then conducted a phase II therapeutic trial in 12 patients and tested whether candidate molecules (atorvastatin, chenodeoxycholic acid and resveratrol) can lower plasma oxysterols and improve bile acids profile. The trial consisted of a three-period, three-treatment crossover study and the six different sequences of three treatments were randomized. Using a linear mixed effect regression model with a random intercept, we observed that atorvastatin decreased moderately plasma 27-OHC (∼30%, P < 0.001) but did not change 27-OHC to total cholesterol ratio or 25-OHC levels. We also found an abnormal bile acids profile in SPG5 patients, with significantly decreased total serum bile acids associated with a relative decrease of ursodeoxycholic and lithocholic acids compared to deoxycholic acid. Treatment with chenodeoxycholic acid restored bile acids profile in SPG5 patients. Therefore, the combination of atorvastatin and chenodeoxycholic acid may be worth considering for the treatment of SPG5 patients but the neurological benefit of these metabolic interventions remains to be evaluated in phase III therapeutic trials using clinical, imaging and/or electrophysiological outcome measures with sufficient effect sizes. Overall, our study indicates that plasma 25-OHC and 27-OHC are robust diagnostic biomarkers of SPG5 and shall be used as first-line investigations in any patient with unexplained spastic paraplegia.
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http://dx.doi.org/10.1093/brain/awx297DOI Listing
January 2018

Vapor liquid solid-hydride vapor phase epitaxy (VLS-HVPE) growth of ultra-long defect-free GaAs nanowires: ab initio simulations supporting center nucleation.

J Chem Phys 2014 May;140(19):194706

Clermont Université, Université Blaise Pascal, Institut Pascal, BP 10448, F-63000 Clermont-Ferrand, France.

High aspect ratio, rod-like and single crystal phase GaAs nanowires (NWs) were grown by gold catalyst-assisted hydride vapor phase epitaxy (HVPE). High resolution transmission electron microscopy and micro-Raman spectroscopy revealed polytypism-free zinc blende (ZB) NWs over lengths of several tens of micrometers for a mean diameter of 50 nm. Micro-photoluminescence studies of individual NWs showed linewidths smaller than those reported elsewhere which is consistent with the crystalline quality of the NWs. HVPE makes use of chloride growth precursors GaCl of which high decomposition frequency after adsorption onto the liquid droplet catalysts, favors a direct and rapid introduction of the Ga atoms from the vapor phase into the droplets. High influxes of Ga and As species then yield high axial growth rate of more than 100 μm/h. The diffusion of the Ga atoms in the liquid droplet towards the interface between the liquid and the solid nanowire was investigated by using density functional theory calculations. The diffusion coefficient of Ga atoms was estimated to be 3 × 10(-9) m(2)/s. The fast diffusion of Ga in the droplet favors nucleation at the liquid-solid line interface at the center of the NW. This is further evidence, provided by an alternative epitaxial method with respect to metal-organic vapor phase epitaxy and molecular beam epitaxy, of the current assumption which states that this type of nucleation should always lead to the formation of the ZB cubic phase.
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http://dx.doi.org/10.1063/1.4874875DOI Listing
May 2014

Solid state NMR study of nanodiamond surface chemistry.

Solid State Nucl Magn Reson 2011 Nov 18;40(4):144-54. Epub 2011 Nov 18.

Clermont Université, UBP, Laboratoire des Matériaux Inorganiques (UMR CNRS 6002), 24, Avenue des Landais, 63177 Aubière, France.

Solid state NMR measurements using 13C, 1H and 19F nuclei (MAS, CP-MAS) underline the surface chemistry of nanodiamonds from different synthesis (detonation, high pressure high temperature and shock compression). The comparison of the spin-lattice relaxation times T1 and physicochemical characterization (spin densities of dangling bonds, specific surface area and Raman and infrared spectroscopies) for the various samples, as synthesized, chemically purified and fluorinated allows the nature and the location of the various groups, mainly C-OH, C-H and C-F to be investigated. C-OH groups are located only on the surface whereas C-H and dangling bonds seem to be distributed in the whole volume. Fluorination was studied as a chemical treatment for purification and change of the hydrophobicity through the conversion of the C-OH groups into covalent C-F bonds.
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http://dx.doi.org/10.1016/j.ssnmr.2011.10.003DOI Listing
November 2011

Differences in regulatory frameworks governing genetic laboratories in four countries.

J Law Med Ethics 2009 ;37(2):351-7

Bioethics Program, Department of Preventative and Social, Medicine, University of Montreal, Canada.

The purpose of this article is to determine how the heterogeneity of the different regulatory frameworks governing genetic laboratories in Australia, France, the United Kingdom, and the United States hinder the international availability of genetic tests. We conclude that a better understanding of the various national standards governing genetic laboratories may help health professionals choose laboratories for referral in an evidence based manner in order to protect the patient's best interests.
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http://dx.doi.org/10.1111/j.1748-720X.2009.00378.xDOI Listing
March 2010

The ovarioleukodystrophy.

Clin Neurol Neurosurg 2008 Dec 3;110(10):1035-7. Epub 2008 Aug 3.

University of Poitiers, CHU Poitiers, Department of Neurology, 2 rue de La Milétrie, 86021 Poitiers cedex 05, France.

The "ovarioleukodystrophies" comprise a group of rare leukodystrophies associated with primary or premature ovarian failure. Some of the patients have a variant of "vanishing white matter disease" with mutations in subunits of eukaryotic initiation factor 2B (EIF2B). A 32-year-old woman who developed neurological signs related to an extensive leukoencephalopathy on magnetic resonance imaging (MRI) in the context of amenorrhea since the age of 18 years was found to be homozygous for a mutation in the EIF2B5 gene: c.338G>A/p.Arg113His. She had a progressive disease with development of tetraparesia in less than 6 years. Our observation confirms that ovarian failure in the context of a leukodystrophy warrants mutational analysis of the genes encoding the subunits of EIF2B.
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http://dx.doi.org/10.1016/j.clineuro.2008.06.002DOI Listing
December 2008