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Aims Glycemic variability has been suggested as a risk factor for diabetes complications but the precise deleterious mechanisms remain poorly understood. Since mitochondria are the main source of energy in heart and cardiovascular diseases remain the first cause of death in patients with diabetes, the aim of the study was to evaluate the impact of glucose swings on mitochondrial functions in the cardiomyocyte cell line HL-1. Methods HL-1 cells were exposed to low (LG, 2.8 mmol/l), normal (NG, 5.5 mmol/l), high (HG, 25 mmol/l) or intermittent high glucose (IHG, swing between low and high) every 2h during 12h (short-time treatment) or every 12h during 72h (long-time treatment). Anaerobic catabolism of glucose was evaluated by measuring glucose consumption and lactate production, oxidative phosphorylation was evaluated by polarography and ATP measurement, mitochondrial superoxide anions and the mitochondrial membrane potential (MMP) were analysed using fluorescent probes, and the protein oxidation was measured by oxyblot. Results IHG and HG increased glucose consumption and lactate production compared to LG and NG but without any difference between short- and long-time treatments. After 72h and unlike to LG, NG and HG, we didn’t observe any increase of the mitochondrial respiration in the presence of succinate upon IHG treatment. IHG, and to a lesser extent HG, promoted a time-dependent decrease of the mitochondrial membrane potential compared to LG and NG treatments. HG and IHG also increased superoxide anion production compared to LG and NG both at 12 and 72h but with a higher increase for IHG at 72h. At last, both HG and IHG stimulated protein oxidation at 72h compared to LG and NG treatments. Conclusions Our results demonstrated that exposure of HL-1 cells to glucose swings promoted time-dependent mitochondrial dysfunctions suggesting a deleterious effect of such condition in patients with diabetes that could contribute to diabetic cardiomyopathy.

The chemokine receptor CXCR4 and its ligand CXCL12 regulate leukocyte trafficking, homeostasis and functions and are potential therapeutic targets in many diseases such as HIV-1 infection and cancers. Here, we identified new CXCR4 ligands in the CERMN chemical library using a FRET-based high-throughput screening assay. These are bis-imidazoline compounds comprising two imidazole rings linked by an alkyl chain. The molecules displace CXCL12 binding with submicromolar potencies, similarly to AMD3100, the only marketed CXCR4 ligand. They also inhibit anti-CXCR4 mAb 12G5 binding, CXCL12-mediated chemotaxis and HIV-1 infection. Further studies with newly synthesized derivatives pointed out to a role of alkyl chain length on the bis-imidazoline properties, with molecules with an even number of carbons equal to 8, 10 or 12 being the most potent. Interestingly, these differ in the functions of CXCR4 that they influence. Site-directed mutagenesis and molecular docking predict that the alkyl chain folds in such a way that the two imidazole groups become lodged in the transmembrane binding cavity of CXCR4. Results also suggest that the alkyl chain length influences how the imidazole rings positions in the cavity. These results may provide a basis for the design of new CXCR4 antagonists targeting specific functions of the receptor.

Background For the elderly population living at home, the implementation of professional services tends to mitigate the effect of loss of autonomy and increases their quality of life. While helping in avoiding social isolation, home services could also be associated to different healthcare pathways. For elderly patients, Emergency Departments (EDs) are the main entrance to hospital where previous loss of autonomy is associated to worst hospital outcomes. Part of elderly patients visiting EDs are still admitted to hospital for having difficulties coping at home without presenting any acute medical issue. There is a lack of data concerning elderly patients visiting EDs assisted by home services. Our aim was to compare among elderly patients visiting ED those assisted by professional home services to those who do not in terms of emergency resources’ use and patients’ outcome. Methods A multicenter, prospective cohort study was performed in 124 French EDs during a 24-h period on March 2016.Consecutive patients living at home aged ≥80 years were included. The primary objective was to assess the risk of mortality for patients assisted by professional home services vs. those who were not. Secondary objectives included admission rate and specific admission rate for “having difficulties coping at home”. The primary endpoint was in-hospital mortality. Cox proportional-hazards regression model was used to test the association between professional home services and the primary endpoint. Multi variables logistic regressions were performed to assess secondary endpoints. Results One thousand one hundred sixty-eight patients were included, median age 86(83–89) years old,32% were assisted by professional home services. The overall in-hospital mortality rate was 7%. Assisted patients had more investigations performed. Home services were not associated with increased in-hospital mortality (HR = 1.34;95%CI [0.68–2.67]), nor with the admission rate (OR = 0.92;95%CI [0.65–1.30]). Assisted patients had a lower risk of being admitted for “having difficulties coping at home” (OR = 0.59;95%CI [0.38–0.92]). Conclusion Professional home services which assist one-third of elderly patients visiting EDs, were not associated to lower in-hospital mortality or to an increased admission rate. Assisted patients were associated to a lower risk of being admitted for «having difficulties coping at home».Professional home services could result in avoiding some admissions and their corollary complications. Trial registration Clinicaltrial.gov - NCT02900391 , 09/14/2016, retrospectively registered

Yinde Zhang, Mo Yan, le lieu de la fiction (Mo Yan, the Place of Fiction), Paris, Seuil, 2014, 319 pp.

Review(s) of: The place of fiction, by Mo Yan, Paris, Seuil, 2014, 319 pp.