Life-Threatening Adverse Reaction after Self-Initiated, Off-Label Use of High Dose Nicotinamide for the Treatment of Friedreich’s Ataxia

A 40-year old woman, previously known for Friedreich’s ataxia, presented with shock, profound lactic acidosis and hepatic failure after ingestion of a high dose of nicotinamide, the amide form of vitamin B3. On her own initiative, she was taking up to 4.4 g per day of nicotinamide, after having learned the results of a phase 2 study suggesting a potential benefit in Friedreich’s ataxia. The outcome was good with supportive care and withdrawal of nicotinamide

COCHLEAR IMPLANTS AND PSYCHIATRIC ASSESSMENTS: A NORRIE DISEASE CASE REPORT

Background: It is important to perform psychiatric assessments of adult patients who are candidates for cochlear implants both to screen them for psychiatric disorders and to assess their understanding and compliance with the procedure. Deafness is a factor of difficulty for conducting in-depth psychiatric interviews, but concomitant blindness may make it impossible. Subjects and method: After a description of Norrie disease, a rare disease in which blindness and deafness may occur together, we propose a case report of a patient suffering from the disease and who consulted in view of a cochlear implant. Results: Early information on cochlear implants appears to be necessary before total deafness occurs in patients suffering from Norrie disease. An inventory of digital communication tools that can be used by the patient is also highly valuable. Conclusions: Research should be supported for a more systematic use of psychiatric assessments prior to cochlear implants. In the special case of Norrie disease, we recommend early screening for mental retardation and related psychotic disorders and, depending on the patient’s level of understanding, preventive information on the benefits and limits of cochlear implants before total deafness occurs

Source localization using Poisson integrals

International audienceThis paper deals with the problem of source localization in diffusion processes via several sensor devices providing pointwise concentration measures; sensors are assumed to be arranged in circular arrays, they can be fixed along the array or they can turn along a circular path defined by the array. The originality of the proposed source localization solution lies in the computation of the gradient and of higher-order derivatives (i. e., the Hessian) from Poisson integrals; in opposition to other solutions published in the literature, this computation does neither require specific knowledge of the solution of the difiusion process, nor the use of probing signals, but only exploits properties of the PDE. The Laplacian of the measured value is null on the studied domain; such an assumption is justified for isotropic diffusive sources in steady-state. The paper also presents some simulation results of a source-seeking torque control law for mobile non-holonomic robots looking for a heat source in a room, where the source is modeled as a small circular region

Le développement agricole au Sahel. Tome 2. Recherches et techniques

Ce deuxième tome de la Synthèse sur le Développement agricole au Sahel esquisse un bilan des résultats de plus de trente ans de recherche agricole au Sahel: évaluer les acquis en matière d'amélioration variétale, réfléchir à la problématique de l'eau, aborder les enjeux de l'artificialisation des milieux sahéliens, proposer, au vu des acquis techniques, de nouvelles orientations pour raisonner globalement les systèmes d'élevage au plan régional... L'idée généralement répandue est que l'insuffisance des résultats opérationnels expliquerait, en partie, la situation précaire des économies agricoles sahéliennes. Les constats présentés démontrent, au contraire, que les propositions d'innovations de la recherche sont nombreuses et qu'elles peuvent servir de base à l'élaboration d'actions de développement, qui devront cependant tenir compte des évolutions récentes des systèmes de production et de leur environnement économiqu

Individual based SIS models on (not so) dense large random networks

Starting from a stochastic individual-based description of an SIS epidemic spreading on a random network, we study the dynamics when the size n of the network tends to infinity. We recover in the limit an infinite-dimensional integro-differential equation studied by Delmas, Dronnier and Zitt (2022) for an SIS epidemic propagating on a graphon. Our work covers the case of dense and sparse graphs, provided that the number of edges grows faster than n, but not the case of very sparse graphs with O(n) edges. In order to establish our limit theorem, we have to deal with both the convergence of the random graphs to the graphon and the convergence of the stochastic process spreading on top of these random structures: in particular, we propose a coupling between the process of interest and an epidemic that spreads on the complete graph but with a modified infection rate. Keywords: random graph, mathematical models of epidemics, measure-valued process, large network limit, limit theorem, graphon.Comment: Acknowledgments: This work was financed by the Labex B\'ezout (ANR-10-LABX-58) and the COCOON grant (ANR-22-CE48-0011), and by the platform MODCOV19 of the National Institute of Mathematical Sciences and their Interactions of CNRS. 32 pages, including an appendix of 6 page

Selective Neurofilament (SMI-32, FNP-7 and N200) Expression in Subpopulations of Layer V Pyramidal Neurons In Vivo and In Vitro

There are two main types of layer V pyramidal neurons in rat cortex. Type I neurons have tufted apical dendrites extending into layer I, produce bursts of action potentials and project to subcortical targets (spinal cord, superior colliculus and pontine nuclei). Type II neurons have apical dendrites, which arborize in layers II-IV, do not produce bursts of action potentials and project to ipsilateral and contralateral cortex. The specific expression of different genes and proteins in these two distinct layer V neurons is unknown. To distinguish between distinct subpopulations, fluorescent microspheres were injected into subcortical targets (labeling type I neurons) or primary somatosensory cortex (labeling type II neurons) of adult rats. After transport, cortical sections were processed for immunohistochemistry using various antibodies. This study demonstrated that antigens recognized by SMI-32, N200 and FNP-7 antibodies were only expressed in subcortical (type I) — but not in contralateral (type II) — projecting neurons. NR1, NR2a/b, PLCβ1, BDNF, NGF and TrkB antigens were highly expressed in all neuronal subpopulations examined. Organotypic culture experiments demonstrated that the development of neurofilament expression and laminar specificity does not depend on the presence of the subcortical targets. This study suggests specific markers for the subcortical projecting layer V neuron subpopulation

At-Risk Phenotype of Neurofibromatose-1 Patients: A Multicentre Case-Control Study

<p>Abstract</p> <p>Objectives</p> <p>To assess associations between subcutaneous neurofibromas (SC-NFs) and internal neurofibromas in patients with neurofibromatosis type 1 (NF-1) and to determine whether the association between SC-NFs and peripheral neuropathy was ascribable to internal neurofibromas.</p> <p>Patients and methods</p> <p>Prospective multicentre case-control study. Between 2005 and 2008, 110 NF-1 adults having two or more SC-NFs were individually matched for age, sex and hospital with 110 controls who had no SC-NF. Patients underwent standardized MRI of the spinal cord, nerve roots and sciatic nerves and an electrophysiological study. Analyses used adjusted multinomial logistic regression (ORa) to estimate the risk of the presence of internal neurofibromas or peripheral neuropathies associated with patients presented 2 to 9 SC-NFs, at least 10 SC-NFs as compared to patients without any (referential category).</p> <p>Results</p> <p>Cases had a mean age of 41 (± 13) years; 85 (80%) had two to nine SC-NFs and 21 (19%) at least ten SC-NFs. SC-NFs were more strongly associated with internal neurofibromas in patients with ten or more SC-NFs than in patients with fewer NF-SCs (e.g., sciatic nerve, aOR = 29.1 [8.5 to 100] vs. 4.3 [2.1 to 9.0]). The association with SC-NFs was stronger for diffuse, intradural, and > 3 cm internal neurofibromas than with other internal neurofibromas. Axonal neuropathy with slowed conduction velocities (SCV) was more strongly associated with having at least ten SC-NFs (aOR = 29.9, 5.5 to 162.3) than with having fewer SC-NFs (aOR = 4.4, 0.9 to 22.0). Bivariate analyses showed that the association between axonal neuropathy with SCV and sciatic neurofibromas was mediated by the association between SC-NFs and sciatic neurofibromas.</p> <p>Conclusion</p> <p>The at-risk phenotype of NF-1 patients (i.e. NF-1 patients with SC-NFs) is ascribable to associations linking SC-NFs to internal neurofibromas at risk for malignant transformation and to axonal neuropathies with slowed conduction velocities. Axonal neuropathies with SCV are particularly common in patients with at least ten SC-NFs.</p> <p>Registration details</p> <p>ORPHA86301</p

Cities and their water socio-footprint: a dynamic socio-technical network

International audienceThrough examples of interactions among urban and rural areas we have built the concept of urban water socio-footprint, on the basis of concepts of water and urban footprints. This urban water socio-footprint entails making explicit the socio-technical network which disseminates the impact of urban activities on water system or due to their specific needs towards water system. Animating this footprint with people, their dynamics and migration, their concerns about various places leads to couple the dynamics of water system and land use in the whole urban systems, including built and non built, cultivated and non cultivated areas. This raises the issue of the existence of institutions to take in charger the links which are emerging through these multiple sources of interdependences

A2 gene of Old World cutaneous Leishmania is a single highly conserved functional gene

BACKGROUND: Leishmaniases are among the most proteiform parasitic infections in humans ranging from unapparent to cutaneous, mucocutaneous or visceral diseases. The various clinical issues depend on complex and still poorly understood mechanisms where both host and parasite factors are interacting. Among the candidate factors of parasite virulence are the A2 genes, a family of multiple genes that are developmentally expressed in species of the Leishmania donovani group responsible for visceral diseases (VL). By contrast, in L. major determining cutaneous infections (CL) we showed that A2 genes are present in a truncated form only. Furthermore, the A2 genomic sequences of L. major were considered subsequently to represent non-expressed pseudogenes [1]. Consequently, it was suggested that the structural and functional properties of A2 genes could play a role in the differential tropism of CL and VL leishmanias. On this basis, it was of importance to determine whether the observed structural/functional particularities of the L. major A2 genes were shared by other CL Leishmania, therefore representing a proper characteristic of CL A2 genes as opposed to those of VL isolates. METHODS: In the present study we amplified by PCR and sequenced the A2 genes from genomic DNA and from clonal libraries of the four Old World CL species comparatively to a clonal population of L. infantum VL parasites. Using RT-PCR we also amplified and sequenced A2 mRNA transcripts from L. major. RESULTS: A unique A2 sequence was identified in Old World cutaneous Leishmania by sequencing. The shared sequence was highly conserved among the various CL strains and species analysed, showing a single polymorphism C/G at position 58. The CL A2 gene was found to be functionally transcribed at both parasite stages. CONCLUSION: The present study shows that cutaneous strains of leishmania share a conserved functional A2 gene. As opposed to the multiple A2 genes described in VL isolates, the CL A2 gene is unique, lacking most of the nucleotide repeats that constitute the variable region at the 5'end of the VL A2 sequences. As the variable region of the VL A2 gene has been shown to correspond to a portion of the protein which is highly immunogenic, the present results support the hypothesis of a possible role of the A2 gene in the differential tropism of CL and VL leishmania parasites