Evidence for a two-stage disability progression in multiple sclerosis

It is well documented that disability accumulation in multiple sclerosis is correlated with axonal injury and that the extent of axonal injury is correlated with the degree of inflammation. However, the interdependence between focal inflammation, diffuse inflammation and neurodegeneration, and their relative contribution to clinical deficits, remains ambiguous. A hypothesis might be that early focal inflammation could be the pivotal event from which all else follows, suggesting the consideration of multiple sclerosis as a two-stage disease. This prompted us to define two phases in the disease course of multiple sclerosis by using two scores on the Kurtzke Disability Status Scale as benchmarks of disability accumulation: an early phase, ‘Phase 1’, from multiple sclerosis clinical onset to irreversible Disability Status Scale 3 and a late phase, ‘Phase 2’, from irreversible Disability Status Scale 3 to irreversible Disability Status Scale 6. Outcome was assessed through five parameters: Phase 1 duration, age at Disability Status Scale 3, time to Disability Status Scale 6 from multiple sclerosis onset, Phase 2 duration and age at Disability Status Scale 6. The first three were calculated among all patients, while the last two were computed only among patients who had reached Disability Status Scale 3. The possible influence of early clinical markers on these outcomes was studied using Kaplan–Meier estimates and Cox models. The analysis was performed in the Rennes multiple sclerosis database (2054 patients, accounting for 26 273 patient-years) as a whole, and according to phenotype at onset (1609 relapsing/445 progressive onset). Our results indicated that the disability progression during Phase 2 was independent of that during Phase 1. Indeed, the median Phase 2 duration was nearly identical (from 6 to 9 years) irrespective of Phase 1 duration (<3, 3 to <6, 6 to <10, 10 to <15, ≥15 years) in the whole population, and in both phenotypes. In relapsing onset multiple sclerosis, gender, age at onset, residual deficit after the first relapse and relapses during the first 2 years of multiple sclerosis were found to be independent predictive factors of disability progression, but only during Phase 1. Our findings demonstrate that multiple sclerosis disability progression follows a two-stage process, with a first stage probably dependant on focal inflammation and a second stage probably independent of current focal inflammation. This concept has obvious implications for the future therapeutic strategy in multiple sclerosis

Challenges and Opportunities in Finfish Nutrition

Much of the criticism leveled at aquaculture (e.g., dependency on animal-derived feedstuffs, nutrient-laden effluent discharges, and increased organic contamination in edible products) can be traced to the feeds in use. Accordingly, finfish nutritionists are being challenged to formulate feeds that not only meet the nutritional requirements of livestock but also minimize production costs, limit environmental impacts, and enhance product quality. These challenges not only add considerable complexity to finfish nutrition but also afford opportunities to avoid some of the mistakes made by other industries in the past. From a review of the current status of finfish nutrition with respect to major nutrient classes, we comment on future opportunities and promising avenues of research. Alternative protein sources, specifically those derived from marine bycatch, plants, and microbes, are discussed, as well as methods to facilitate their implementation in finfish feeds. Dietary lipid, its role in fish bioenergetics and physiology, and quality of aquaculture products is reviewed with special emphasis on alternative lipid sources and finishing diets. Carbohydrates and fiber are discussed in terms of nutrient-sparing, least-cost diet formulation and digestive physiology. Micronutrients are reviewed in terms of current knowledge of requirements and, along with other dietary immunostimulants, are given further consideration in a review of nutriceuticals and application in finfish feeds. The status of nutritional research in new aquaculture species is also outlined. By integrating classical approaches with emerging technologies, dietary formulations, and species, finfish nutritionists may identify means to increase production efficiency and sustainability and provide for the continued success of aquaculture

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&nbsp;=&nbsp;2.05, 95%CI&nbsp;=&nbsp;1.39–3.02, p&nbsp;&lt;&nbsp;0.001) with Covid-19 severity, whereas interferon indicated a decreased risk (OR&nbsp;=&nbsp;0.42, 95%CI&nbsp;=&nbsp;0.18–0.99, p&nbsp;=&nbsp;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

A 400 fJ per-cycle frequency reference for internet of things

This work presents an ultra-low power oscillator designed to target different contexts, such as crystal-assisted timekeeping, reference oscillator to optimize the always on domain of a microcontroller or wake-up timer. This oscillator enables ultralow power operation in 0.18 μm CMOS technology; the core oscillator consumes 2.5 nW at room temperature, with a temperature stability of 14 ppm/°C [-40°C - 60°C] and 0.07 %/V supply sensitivity

Evaluation de l'effet de l'environnement et de l'alimentation sur l'apparition d'anomalies de développement chez l'alevin de bar (Dicentrarchus labrax)

Une ponte naturelle de bar, obtenue dans les installations expérimentales de Palavas, est mise en élevage dans ce même laboratoire et dans celui de Brest, après un transport fictif ou réel. Les protocoles spécifiques de chacun des deux laboratoires sont utilisés sans changer le contexte d'élevage particulier de chacun des deux sites : mise à jeun à l'obscurité jusqu'à 160 degrés jours et première alimentation sur Artemia à Palavas en bacs de 500 litres et, première alimentation à 75 degrés jours sur rotifères à Brest en bacs de 250 litres et de 35 litres. Dans les conditions d'environnement comparables (bacs de 250 litres à Brest) une période de jeûne est également testée, de 75 à 160 degrés jours, soit en obscurité sans aération, soit sous éclairage continu avec aération. Les malformations des vertèbres, des maxillaires, des opercules (courts et soulevés), la non-inflation de la vessie natatoire et la présence de calculs urinaires sont relevées à 3 mois sur tous les lots. Plusieurs malformations apparaissent inféodées à un site ou un traitement particulier : cristaux urinaires à Palavas, vessies natatoires non fonctionnelles à Brest, maxillaires anormaux en bac de 35 litres. Les opercules soulevés sont observés dans deux installations utilisant des méthodologies différentes mais sont négligeables dans la ligne d'élevage où les tests méthodologiques ont été effectués. Les taux de survie sont significativement influencés par les traitements. La répartition des fréquences des lordoses entre les sites ou les différents traitements peut s'interpréter comme une conséquence de mortalités sélectives. L'association entre les lordoses et les vessies natatoires non fonctionnelles, déjà connue chez le bar, est observée. L'étude des fréquences croisées des malformations montre également que les opercules courts sont 10 fois plus fréquents chez les individus dont les vessies natatoires ne sont pas fonctionnelles. L'étude séparée des populations de juvéniles possédant ou non une vessie natatoire fonctionnelle montre que la répartition des fréquences des opercules courts est indépendante des traitements ou du site d'élevage. Les fréquences élevées des opercules courts sur la majorité des traitements du site de Brest ne peuvent être dissociées des taux importants de non-fonctionnalité des vessies natatoires

Besoins en vitamine C chez les poissons : existe-t-il des differences inter-specifiques ?

National audienc

'Clinically definite benign multiple sclerosis', an unwarranted conceptual hodgepodge: evidence from a 30-year observational study.

International audienceBACKGROUND: Benign multiple sclerosis (BMS) is a controversial concept which is still debated. However identification of this kind of patients is crucial to prevent them from unnecessary exposure to aggressive and/or long term medical treatments. OBJECTIVES: To assess two definitions of 'clinically definite benign multiple sclerosis' (CDBMS) using long-term follow-up data, and to look for prognostic factors of CDBMS. METHODS: In 874 patients with definite relapsing-remitting MS, followed up for at least 10 years, disability was assessed using the Disability Status Scale (DSS). CDBMS was defined by either DSS score≤2 (CDBMS1 group) or DSS score≤ 3 (CDBMS2 group) at 10 years. We estimated the proportion of patients who were still benign at 20 and 30 years after clinical onset. RESULTS: CDBMS frequency estimates were 57.7% and 73.9% when using CDBMS1 and CDBMS2 definitions, respectively. In the CDBMS1 group, only 41.7% (105/252) of cases were still benign 10 years later, and 41.1% (23/56) after an additional decade, while there were 53.8% (162/301) and 59.5% (44/74) respectively in the CDBMS2 group. CONCLUSIONS: This 30-year observational study, which is one of the largest published series, indicates that favourable 10-year disability scores of DSS 2 or 3 fail to ensure a long-term benign course of multiple sclerosis. After every decade almost half of the CDBMS were no longer benign. CDBMS, as currently defined, is an unwarranted conceptual hodgepodge. Other criteria using new biomarkers (genetic, biologic or MRI) should be found to detect benign cases of MS

Long-term survival of patients with multiple sclerosis in West France

International audienceIn France no data have been published about comparing survival in multiple sclerosis (MS) patients with the general French population. We estimated survival probabilities in MS patients from a major centre for MS in West France. We also compared MS survival with the general population and assessed prognostic parameters. All patients with MS onset after January 1976 and classified as dead or alive on 1 January 2004 were included. One thousand eight-hundred and seventy-nine patients (sex ratio W: M 2.3; relapsing/progressive onset 77.4%/22.6%) fulfilled these criteria, disease duration ranged from one to 28 years. By 2004, 68 patients died (51 due to MS) and the 15 and 25-year survival probabilities were 96% and 88%. Male gender, progressive course (either primary or secondary), polysymptomatic onset, and increased annual relapse rate during the first two years of MS were related to a worse prognosis. After a mean follow-up duration of 12.7 years since clinical onset, MS increased the number of deaths compared with the general population. However taking into account disability status, we found that less disabled MS patients had a better survival and highly disabled patients a worse survival (eight-fold increase of mortality) compared with the French population