First Evidence of Palytoxin and 42-Hydroxy-palytoxin in the Marine Cyanobacterium Trichodesmium

Marine pelagic diazotrophic cyanobacteria of the genus Trichodesmium (Oscillatoriales) are widespread throughout the tropics and subtropics, and are particularly common in the waters of New Caledonia. Blooms of Trichodesmium are suspected to be a potential source of toxins in the ciguatera food chain and were previously reported to contain several types of paralyzing toxins. The toxicity of water-soluble extracts of Trichodesmium spp. were analyzed by mouse bioassay and Neuroblastoma assay and their toxic compounds characterized using liquid chromatography coupled with tandem mass spectrometry techniques. Here, we report the first identification of palytoxin and one of its derivatives, 42-hydroxy-palytoxin, in field samples of Trichodesmium collected in the New Caledonian lagoon. The possible role played by Trichodesmium blooms in the development of clupeotoxism, this human intoxication following the ingestion of plankton-eating fish and classically associated with Ostreopsis blooms, is also discussed

DMTs and Covid-19 severity in MS: a pooled analysis from Italy and France

We evaluated the effect of DMTs on Covid-19 severity in patients with MS, with a pooled-analysis of two large cohorts from Italy and France. The association of baseline characteristics and DMTs with Covid-19 severity was assessed by multivariate ordinal-logistic models and pooled by a fixed-effect meta-analysis. 1066 patients with MS from Italy and 721 from France were included. In the multivariate model, anti-CD20 therapies were significantly associated (OR = 2.05, 95%CI = 1.39–3.02, p < 0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR = 0.42, 95%CI = 0.18–0.99, p = 0.047). This pooled-analysis confirms an increased risk of severe Covid-19 in patients on anti-CD20 therapies and supports the protective role of interferon

Rôle des cyanobactéries dans le développement des zones ciguatérigènes en lien avec les impacts anthropiques, pour une meilleure gestion du risque ciguatérique

Ciguatera, a marine intoxication, is caused by the consumption of tropical fish which accumulate toxins through their diet. Dinoflagellates are known to produce ciguatoxins (CTXs). Recently, cyanobacteria (Oscillatoriale) were also incriminated as potential progenitors of CTXs-like compounds. To understand better and to define management approaches that the involvement of these cyanobacteria poses to the risks of ciguatera outbreaks, surveys were undertaken at three representative sites. These include: (i) Lifou Island where ciguatera intoxications incidence have been recorded; (ii) the Prony Bay which is close to the site of a mineral mining plant in construction; and (iii) the lagoon of Ouvea that is reputed to be free of ciguatera. Studies on microorganisms (cyanobacteria and dinoflagellate) diversity, toxicological analyses of different trophic levels (cyanobacteria, fish and giant clams) and detection of toxic compounds were undertaken. These ecotoxicological studies highlight the presence of a toxic matrix of CTXs-like compounds and cyanotoxins in Oscillatoriales cyanobacteria, in fish and giant clams collected in damaged areas. For the first time, we are reporting the presence of homoanatoxin-a (a paralyzing neurotoxin), detected both in the cyanobacteria Hydrocoleum lyngbyaceum and the giant clam, and two palytoxins detected in cyanobacteria samples of Trichodesmium. Our findings emphasize the need of including the monitoring of marine cyanobacteria in management programs of ciguatera and also provide a new trophic link to the current ciguatera fish food chain. Consequently, we have named this new phenomenon as Ciguatera Seafood poisoning.La ciguatéra est une intoxication consécutive à l'ingestion de poissons porteurs de ciguatoxines. Classiquement liée à la prolifération des dinoflagellés ciguatérigènes, elle est favorisée par les perturbations naturelles ou anthropiques des écosystèmes coralliens. Or récemment, certaines cyanobactéries marines du groupe des Oscillatoriales (Hydrocoleum sp.) ont également été impliquées dans des intoxications de type ciguatéra. Dans ce contexte, l'objectif général de cette thèse est de mieux comprendre le déterminisme ciguatérique afin de mieux le prévenir. L'étude a constitué en un suivi écotoxicologique périodique de trois sites en Nouvelle-Calédonie : l'île de Lifou, réputée toxique ; la baie de Prony, en cours d'anthropisation ; l'atoll d'Ouvéa, réputé non ciguatérique, en ciblant spécifiquement l'étude de la diversité microbienne, l'évaluation de la toxicité à différents niveaux de la chaîne trophique (cyanobactéries, bénitiers, poissons) et la caractérisation des métabolites toxiques impliqués. Ce suivi environnemental a mis en évidence un complexe toxinique CTXs-like/cyanotoxines chez les Oscillatoriales dominant les écosystèmes dégradés, ainsi que les poissons et bénitiers inféodés à ces zones. Parmi les cyanotoxines détectées in situ, citons l'homoanatoxine-a (neurotoxine paralysante) présente à la fois chez Hydrocoleum lyngbyaceum et les bénitiers Tridacna maxima, et la palytoxine, révélée pour la première fois chez Trichodesmium erythraeum. Ces résultats originaux posent les bases d'un outil de surveillance sanitaire et écologique opérationnel d'un risque sanitaire en zone tropicale plus complexe que la ciguatéra telle qu'elle est connue actuellement

Are cyanobacteria involved in Ciguatera Fish Poisoning-like outbreaks in New Caledonia ?

From 2001 to 2005, numerous cases of seafood poisonings were reported in a tribe from Lifou (Loyalty Islands Province, New Caledonia) of which 35 were thoroughly examined. Observations outlined by the epidemiological and clinical data (including severity and rapid onset of certain symptoms following consumption of either giant clams (Tridacna spp.) or grazing and molluscivorous fish together with the apparent inefficacy of traditional remedies, were not in favour of a classical Ciguatera Fish Poisoning (CFP) outbreak. From 2005 onwards, an environmental offshore survey of the affected area was conducted. Screening of the damaged coral area revealed the presence of large populations of cyanobacteria identified as Hydrocoleum Kutzing, but the absence of Gambierdiscus spp., the well-known dinoflagellate causative agent of CFP. In vivo and in vitro toxicological studies of extracts obtained from cyanobacteria and giant clams, strongly suggested the co-occurrence of ciguatoxin-like, anatoxin-like and paralytic shellfish toxins in these samples. These new findings shed new light on the complexity of the CFP symptomatology and treatment and also on the diversity and origin of the CFP toxins. Furthermore they provide new evidence of the overall variability of seafood poisonings following the ingestion of different sea products living in a marine environment where significant harmful populations of microalgae and cyanobacteria coexist. This is the first report on the involvement of cyanobacteria in CFP-like outbreaks following the consumption of giant clams or fish specimens. Consequently, it is recommended that CFP risk assessment programs now include monitoring of cyanobacteria besides the obvious screening of CFP-promoting dinoflagellates

Multiple sclerosis clinical decision support system based on projection to reference datasets

International audienceObjective: Multiple sclerosis (MS) is a multifactorial disease with increasingly complicated management. Our objective is to use on-demand computational power to address the challenges of dynamically managing MS.Methods: A phase 3 clinical trial data (NCT00906399) were used to contextualize the medication efficacy of peg-interferon beta-1a vs placebo on patients with relapsing-remitting MS (RRMS). Using a set of reference patients (PORs), selected based on adequate features similar to those of an individual patient, we visualize disease activity by measuring the percentage of relapses, accumulation of new T2 lesions on MRI, and worsening EDSS during the clinical trial.Results: We developed MS Vista, a functional prototype of clinical decision support system (CDSS), with a user-centered design and distributed infrastructure. MS Vista shows the medication efficacy of peginterferon beta-1a versus placebo for each individual patient with RRMS. In addition, MS Vista initiated the integration of a longitudinal magnetic resonance imaging (MRI) viewer and interactive dual physician-patient data display to facilitate communication.Interpretation: The pioneer use of PORs for each individual patient enables personalized analytics sustaining the dialog between neurologists, patients and caregivers with quantified evidence

Results of a Phase 1b study to confirm safety and tolerability of olesoxime in multiple sclerosis patients

International audienc

Results of a Phase 1b study to confirm safety and tolerability of olesoxime in multiple sclerosis patients

International audienc