👤 Michel Lagarde

An emerging approach in surgery is to propose prehabilitation programs to strengthen the patient's functional abilities before surgical interventions, thus helping them cope better with its consequences. In drug-resistant language-dominant temporal lobe epilepsy (LdTLE), surgical treatment carries a risk of increasing cognitive deficits, notably word-finding difficulties (anomia) and verbal memory difficulties that negatively impact personal, social, and occupational activities. In this study, we invited 15 LdTLE patients to enroll in a speech and language prehabilitation program adapted to the specifics of their difficulties, organized daily during the preoperative period. Naming performance (for trained and untrained words) was studied twice before prehabilitation, during prehabilitation, and 1 week and 6 months after surgery. Results were analyzed using a generalized linear mixed effects model. We found a significant effect of prehabilitation on trained items before surgery. Postoperatively, trained items showed a slight and nonsignificant performance increase compared to baseline, whereas untrained items showed a significant decline in the same comparison. We conclude that trained words were better protected from postsurgical decline than untrained words. Our research can contribute to patient support during surgical decision-making; ultimately, prehabilitation might be considered as part of individualized care. These encouraging results lay the groundwork for more detailed or powerful examinations of the protective effect of prehabilitation on language skills. Show less

Determination of lipoprotein lipase (LPL) activity is important for hyperchylomicronemia diagnosis, but remains both unreliable and cumbersome with current methods. Consequently by using human VLDL as substrate we developed a new LPL assay which does not require sonication, radioactive or fluorescent particles. Post-heparin plasma was added to the VLDL substrate prepared by ultracentrifugation of heat inactivated normolipidemic human serums, diluted in buffer, pH 8.15. Following incubation at 37°c, the NEFA (non esterified fatty acids) produced were assayed hourly for 4 hours. LPL activity was expressed as µmol/l/min after subtraction of hepatic lipase (HL) activity, obtained following LPL inhibition with NaCl 1.5 mmol/l. Molecular analysis of LPL, GPIHBP1, APOA5, APOC2, APOE genes was available for 62 patients. Our method was reproducible (coefficient of variation (CV): intra-assay 5.6%, inter-assay 7.1%), and tightly correlated with the conventional radiolabelled triolein emulsion method (n = 26, r = 0.88). Normal values were established at 34.8 ± 12.8 µmol/l/min (mean ± SD) from 20 control subjects. LPL activities obtained from 71 patients with documented history of major hypertriglyceridemia showed a trimodal distribution. Among the 11 patients with a very low LPL activity (< 10 µmol/l/min), 5 were homozygous or compound heterozygous for LPL or GPIHBP1 deleterious mutations, 3 were compound heterozygous for APOA5 deleterious mutations and the p.S19W APOA5 susceptibility variant, and 2 were free of any mutations in the usual candidate genes. No homozygous gene alteration in LPL, GPIHBP1 and APOC2 genes was found in any of the patients with LPL activity > 10 µmol/l/min. This new reproducible method is a valuable tool for routine diagnosis and reliably identifies LPL activity defects. Show less

Determination of lipoprotein lipase (LPL) activity is important for hyperchylomicronemia diagnosis, but remains both unreliable and cumbersome with current methods. Consequently by using human VLDL as substrate we developed a new LPL assay which does not require sonication, radioactive or fluorescent particles. Post-heparin plasma was added to the VLDL substrate prepared by ultracentrifugation of heat inactivated normolipidemic human serums, diluted in buffer, pH 8.15. Following incubation at 37°c, the NEFA (non esterified fatty acids) produced were assayed hourly for 4 hours. LPL activity was expressed as µmol/l/min after subtraction of hepatic lipase (HL) activity, obtained following LPL inhibition with NaCl 1.5 mmol/l. Molecular analysis of LPL, GPIHBP1, APOA5, APOC2, APOE genes was available for 62 patients. Our method was reproducible (coefficient of variation (CV): intra-assay 5.6%, inter-assay 7.1%), and tightly correlated with the conventional radiolabelled triolein emulsion method (n = 26, r = 0.88). Normal values were established at 34.8 ± 12.8 µmol/l/min (mean ± SD) from 20 control subjects. LPL activities obtained from 71 patients with documented history of major hypertriglyceridemia showed a trimodal distribution. Among the 11 patients with a very low LPL activity (<10 µmol/l/min), 5 were homozygous or compound heterozygous for LPL or GPIHBP1 deleterious mutations, 3 were compound heterozygous for APOA5 deleterious mutations and the p.S19W APOA5 susceptibility variant, and 2 were free of any mutations in the usual candidate genes. No homozygous gene alteration in LPL, GPIHBP1 and APOC2 genes was found in any of the patients with LPL activity >10 µmol/l/min. This new reproducible method is a valuable tool for routine diagnosis and reliably identifies LPL activity defects. Show less

Endosomal signature phospholipid bis(monoacylglycero)phosphate (BMP) has been involved in the regulation of cellular cholesterol homeostasis. Accumulation of BMP is a hallmark of lipid storage disorders and was recently reported as a noticeable feature of oxidized low-density lipoprotein-laden macrophages. This study was designed to delineate the consequences of macrophage BMP accumulation on intracellular cholesterol distribution, metabolism, and efflux and to unravel the underlying molecular mechanisms. We have developed an experimental design to specifically increase BMP content in RAW 264.7 macrophages. After BMP accumulation, cell cholesterol distribution was markedly altered, despite no change in low-density lipoprotein uptake and hydrolysis, cholesterol esterification, or total cell cholesterol content. The expression of cholesterol-regulated genes sterol regulatory element-binding protein 2 and hydroxymethylglutaryl-coenzyme A reductase was decreased by 40%, indicative of an increase of endoplasmic reticulum-associated cholesterol. Cholesterol delivery to plasma membrane was reduced as evidenced by the 20% decrease of efflux by cyclodextrin. Functionally, BMP accumulation reduced cholesterol efflux to both apolipoprotein A1 and high-density lipoprotein by 40% and correlated with a 40% decrease in mRNA contents of ATP-binding cassette transporter A1, ATP-binding cassette transporter G1, and liver-X receptor α and β. Foam cell formation induced by oxidized low-density lipoprotein exposure was exacerbated in BMP-enriched cells. The present work shows for the first time a strong functional link between BMP and cholesterol-regulating genes involved in both intracellular metabolism and efflux. We propose that accumulation of cellular BMP might contribute to the deregulation of cholesterol homeostasis in atheromatous macrophages. Show less

Postprandial hypertriglyceridemia is considered as a risk factor for cardiovascular disease in Type 2 diabetes. However, little is known about the underlying mechanisms. Since the recently discovered apolipoprotein (apo) AV was identified as a modulator of triglyceride (TG) metabolism, the aim of the study was to determine the postprandial apoAV profile of Type 2 diabetic patients. We compared data from 11 patients with Type 2 diabetes mellitus to that of 12 non-diabetic normolipidemic subjects following the ingestion of a lipid-rich cream. Postprandial apoAV was elevated in diabetic patients but no correlation was observed either with plasma TG concentration or with the intensity of lipoprotein lipase-dependent lipolysis. These data obtained in human subjects suggest that plasma apoAV concentration does not play an acute or a direct role in the regulation of plasma TG in the postprandial state. Show less