How to switch disease-modifying treatments in multiple sclerosis: Guidelines from the French Multiple Sclerosis Society (SFSEP)

BACKGROUND: Today, there are no recommendations on switching disease-modifying treatments (DMTs) in multiple sclerosis (MS). OBJECTIVES: To establish guidelines on switching DMTs MS. METHODS: A Steering Committee composed of seven MS experts from the French Group for Recommendations in Multiple Sclerosis (France4MS) defined 15 proposals. These proposals were then submitted to a Rating Group, composed of 48 French MS experts, for evaluation. The proposals were classified as 'appropriate', 'inappropriate' or 'uncertain'. RESULTS: Switching from a first-line therapy to another first-line therapy or a second-line therapy could be done without a washout period. Switching from a second-line therapy to a first-line therapy could be done without a washout period with fingolimod or natalizumab, after 3 months with ocrelizumab or mitoxantrone, and, if disease activity occurs with alemtuzumab or cladribine. The switch from a second-line therapy to another second-line therapy could be done after a washout period of 1 month with fingolimod or natalizumab, after 3 months with ocrelizumab, after 6 months with mitoxantrone, and, if disease activity occurs, with alemtuzumab or cladribine. CONCLUSION: This expert consensus approach provides physicians with some guidelines on optimizing the benefit/risk ratio when switching DMTs in patients with MS

Daily variations of Ostreopsis cf. ovata abundances in NW Mediterranean Sea

International audienceOstreopsis cf. ovata is a benthic dinoflagellate very common in tropical and temperate coastal areas, particularly in the Mediterranean Sea. This species is also found in the plankton, i.e. swimming in the water column or in aggregates floating at the sea surface. The potential links between the planktonic and benthic populations influencing their relative distribution in the water column and attached to the benthic substrate are poorly understood. To shed light on this question, a high-frequency temporal monitoring was conducted in the Villefranche bay (France) to determine the abundance of (1) epibenthic cells attached to macroalgae, (2) planktonic cells in the water column and (3) cells in aggregates floating at the sea water surface (hereafter, referred to sea surface cells) . This monitoring was realized over 3 consecutive years (2018, 2019 and 2020) and at different phases of the bloom (exponential phase – 2020, peak – 2019 and decline phase – 2018). Strong variations in benthic and planktonic O. cf. ovata abundances were observed over the 24 h sampling cycles conducted in three consecutive years. The three populations, planktonic, benthic and sea surface cells, exhibited the highest numbers during the day (light) hours and lowest values at night in 2018 and 2019. In 2020, however, benthic abundances did not differ significantly between light and dark periods. Moreover, epibenthic cells abundances peaked in the morning, followed by the peak of the cells in the plankton and in the surface aggregates during the afternoon.Monitoring of O. cf. ovata is often based on a single sampling per day without precise indications of sampling time and shows great variability in O. cf. ovata abundances. Our observations of daily variations in cell abundances along the water column clearly indicate that time and water column depth of sampling constitute a great source of variability and have to be considered when designing new monitoring strategies to reduce variability and to harmonize data acquisition and international comparisons

Rapport final d'opération

Le rapport présente les résultats de la campagne de fouille 2021 du système de fortification de l'éperon barré protohistorique sur le plateau de Blis à Eymet (Dordogne, France)

Deletion of lysophosphatidylcholine acyltransferase 3 in myeloid cells worsens hepatic steatosis after a high-fat diet

International audienceRecent studies have highlighted an important role for lysophosphatidylcholine acyltransferase 3 (LPCAT3) in controlling the PUFA composition of cell membranes in the liver and intestine. In these organs, LPCAT3 critically supports cell-membrane-associated processes such as lipid absorption or lipoprotein secretion. However, the role of LPCAT3 in macrophages remains controversial. Here, we investigated LPCAT3's role in macrophages both in vitro and in vivo in mice with atherosclerosis and obesity. To accomplish this, we used the LysMCre strategy to develop a mouse model with conditional Lpcat3 deficiency in myeloid cells (Lpcat3KOMac). We observed that partial Lpcat3 deficiency (approximately 75% reduction) in macrophages alters the PUFA composition of all phospholipid (PL) subclasses, including phosphatidylinositols and phosphatidylserines. A reduced incorporation of C20 PUFAs (mainly arachidonic acid [AA]) into PLs was associated with a redistribution of these FAs toward other cellular lipids such as cholesteryl esters. Lpcat3 deficiency had no obvious impact on macrophage inflammatory response or endoplasmic reticulum (ER) stress; however, Lpcat3KOMac macrophages exhibited a reduction in cholesterol efflux in vitro. In vivo, myeloid Lpcat3 deficiency did not affect atherosclerosis development in LDL receptor deficient mouse (Ldlr-/-) mice. Lpcat3KOMac mice on a high-fat diet displayed a mild increase in hepatic steatosis associated with alterations in several liver metabolic pathways and in liver eicosanoid composition. We conclude that alterations in AA metabolism along with myeloid Lpcat3 deficiency may secondarily affect AA homeostasis in the whole liver, leading to metabolic disorders and triglyceride accumulation