Education thérapeutique à l'insulinothérapie fonctionnelle au CHU d'Angers au sein d'une cohorte de 124 diabétiques de type 1 (évaluation de l'impact sur les paramètres clinico-biologiques et sur la qualité de vie à 6 mois)

L'insulinothérapie fonctionnelle (IF) est un modèle d'éducation thérapeutique qui a pour objectif d'améliorer l'équilibre glycémique et de restaurer une bonne qualité de vie, en offrant au patient une plus grande souplesse dans le maniement de son traitement. L IF a considérablement amélioré la prise en charge thérapeutique des diabétiques de type 1. Matériel et méthodes : Depuis 2008, un programme d'éducation à l'IF est proposé au CHU d'Angers et a conduit à l'élaboration d'une cohorte de 124 diabétiques de type 1 éduqués à l'IF. Notre travail a consisté à étudier l'évolution de l'équilibre métabolique et de la qualité de vie au sein de cette cohorte. L'hémoglobine glyquée, la fréquence des hypoglycémies sévères et non sévères et le poids ont été analysés. Les questionnaires utilisés pour apprécier la qualité de vie sont l'ADDQoL et le DTSQ. Résultats : Les patients les plus déséquilibrés réduisent leur hémoglobine glyquée de plus de 0,5 %. De plus, les patients dont l'objectif personnalisé est de rééquilibrer leur diabète améliorent également leur HbA1C. Nous ne retrouvons pas de différence significative concernant les hypoglycémies, le poids ou la qualité de vie. Conclusion : Notre étude démontre que l'IF permet d'améliorer l'HbA1C des patients très déséquilibrés. Les patients ayant pour objectif personnalisé de rééquilibrer leur diabète améliorent également leur HbA1C. Ces résultats soulignent l'importance du diagnostic éducatif au sein d'un programme d'ETP, car il permet de susciter la motivation du patient et d'atteindre ainsi les objectifs définis avec l'équipe médicale.Functional intensified insulin therapy (FIT) is a model of structured education program, which objective is to improve glycemic control and to restaure a good quality of life. Giving the patient an easier way to manage his treatment, FIT has improved therapeutic management of type 1 diabetic persons. Material & methods : A structured education program to FIT is proposed in the diabetology unit of the Hospital of Angers since 2008. We followed a cohort of 124 type 1 diabetic patients trained to IIT during 6 months. Our aim is to assess the changes in glycemic control, biomedical outcomes and quality of life of these patients. The questionnaires used to assess quality of life are ADDQoL and DTSQ. Results : Patients with poor glycemic control improve their HbA1C, better than 0,5 % (main outcome). Moreover, patients whose personal objective was improving their metabolic control reach a significant value of HbA1C decrease. There is no difference regarding hypoglycemias, weight or quality of life. Conclusion : Our study show a better improvement of HbA1C among patients with poorer glycemic control, and in patients who attempt to improve their HbA1C. These results highlight the importance of the "shared educational assessment" within structured education programs, which define patients' needs and allow him to achieve this goal, by exploring his motivation to change.ANGERS-BU Médecine-Pharmacie (490072105) / SudocSudocFranceF

Temporal cross talk between endoplasmic reticulum and mitochondria regulates oxidative stress and mediates microparticle-induced endothelial dysfunction

Aims: Circulating microparticles (MPs) from metabolic syndrome patients and those generated from apoptotic T-cells induce endothelial dysfunction; however, the molecular and cellular mechanism(s) underlying in the effects of MPs remain to be elucidated. Results: Here, we show that both types of MPs increased expression of endoplasmic reticulum (ER) stress markers XBP-1, p-eIF2alpha and CHOP and nuclear translocation of ATF6 on human aortic endothelial cells. MPs decreased in vitro nitric oxide release by human aortic endothelial cells, whereas in vivo MP injection into mice impaired the endothelium-dependent relaxation induced by acetylcholine. These effects were prevented when ER stress was inhibited suggesting that ER stress is implicated in the endothelial effects induced by MPs. MPs affected mitochondrial function and evoked sequential increase of cytosolic and mitochondrial reactive oxygen species (ROS). Pharmacological inhibition of ER stress and silencing of neutral sphingomyelinase with siRNA abrogated all MP-mediated effects. Neutralization of Fas-Ligand carried by MPs abolished effects induced by both MP types, whereas neutralization of low density lipoprotein-receptor on endothelial cells prevented T-lymphocyte MP-mediated effects. Innovation and Conclusion: Collectively, endothelial dysfunction triggered by MPs involves temporal cross-talk between ER and mitochondria with respect to spatial regulation of ROS via the neutral sphingomyelinase and interaction of MPs with Fas and/or low density lipoprotein-receptor. These results provide a novel molecular insight into the manner MPs mediate vascular dysfunction and allow identification of potential therapeutic targets to treat vascular complications associated with metabolic syndrome.Institut National de la Santé et de la Recherche Médicale, Université dʼAngers and Centre Hospitalo-Universitaire dʼAngers

An integrated analysis of surface velocities induced by rainfall in the Séchilienne landslide (Western Alps, France)

International audienceAn integrated analysis on the relationship between rainfall and displacement in the most active area of the Séchilienne unstable slope was performed. This study combines several techniques and models to adequately reproduce the landslide movement induced by the rainfall. The analysis of available time series shows a long term trend and seasonal variations in the displacement, respectively independent and synchronous to precipitations. In particular wavelet analysis highlights that the movement is rather linked to groundwater recharge than to precipitation (rainfall + snowfall), involving then the importance of groundwater process in the area. A first and simple relationship between the water input and the fluctuations of displacements apart from the general trend is shown using a tank model. Moreover, a seasonal analysis of this relationship was performed, showing that displacement rate follows the behavior of the hydrological cycle. Two different models were applied to the long temporal series of extensometric and precipitation data: the FLAME model, from BRGM and the FORESEES model, from Univ. Lausanne. These tools are based on a combined statistical-mechanical approach to predict changes in landslide displacement rates from observed changes in precipitation amounts. The forecasting tool FLAME associates 1) a statistical impulse response (IR) model to simulate the changes in landslide rates by computing a transfer function between the rainfall and the displacements, and 2) a 1D mechanical (ME) model (e.g. visco-plastic rheology), in order to take into account changes in pore water pressures. The performance of different combinations of models was evaluated against observed displacement rates at the selected pilot study area. Our results indicate that both models are able to reproduce, with a high degree of accuracy, the observed displacement pattern in the general kinematic regime. Finally the variability of the results, depending in particular on the input data, is discussed

An integrated analysis of surface velocities induced by rainfall in the Séchilienne landslide (Western Alps, France)

International audienceAn integrated analysis on the relationship between rainfall and displacement in the most active area of the Séchilienne unstable slope was performed. This study combines several techniques and models to adequately reproduce the landslide movement induced by the rainfall. The analysis of available time series shows a long term trend and seasonal variations in the displacement, respectively independent and synchronous to precipitations. In particular wavelet analysis highlights that the movement is rather linked to groundwater recharge than to precipitation (rainfall + snowfall), involving then the importance of groundwater process in the area. A first and simple relationship between the water input and the fluctuations of displacements apart from the general trend is shown using a tank model. Moreover, a seasonal analysis of this relationship was performed, showing that displacement rate follows the behavior of the hydrological cycle. Two different models were applied to the long temporal series of extensometric and precipitation data: the FLAME model, from BRGM and the FORESEES model, from Univ. Lausanne. These tools are based on a combined statistical-mechanical approach to predict changes in landslide displacement rates from observed changes in precipitation amounts. The forecasting tool FLAME associates 1) a statistical impulse response (IR) model to simulate the changes in landslide rates by computing a transfer function between the rainfall and the displacements, and 2) a 1D mechanical (ME) model (e.g. visco-plastic rheology), in order to take into account changes in pore water pressures. The performance of different combinations of models was evaluated against observed displacement rates at the selected pilot study area. Our results indicate that both models are able to reproduce, with a high degree of accuracy, the observed displacement pattern in the general kinematic regime. Finally the variability of the results, depending in particular on the input data, is discussed

Homologous Recombination Is Stimulated by a Decrease in dUTPase in Arabidopsis

Deoxyuridine triphosphatase (dUTPase) enzyme is an essential enzyme that protects DNA against uracil incorporation. No organism can tolerate the absence of this activity. In this article, we show that dUTPase function is conserved between E. coli (Escherichia coli), yeast (Saccharomyces cerevisiae) and Arabidopsis (Arabidopsis thaliana) and that it is essential in Arabidopsis as in both micro-organisms. Using a RNA interference strategy, plant lines were generated with a diminished dUTPase activity as compared to the wild-type. These plants are sensitive to 5-fluoro-uracil. As an indication of DNA damage, inactivation of dUTPase results in the induction of AtRAD51 and AtPARP2, which are involved in DNA repair. Nevertheless, RNAi/DUT1 constructs are compatible with a rad51 mutation. Using a TUNEL assay, DNA damage was observed in the RNAi/DUT1 plants. Finally, plants carrying a homologous recombination (HR) exclusive substrate transformed with the RNAi/DUT1 construct exhibit a seven times increase in homologous recombination events. Increased HR was only detected in the plants that were the most sensitive to 5-fluoro-uracils, thus establishing a link between uracil incorporation in the genomic DNA and HR. Our results show for the first time that genetic instability provoked by the presence of uracils in the DNA is poorly tolerated and that this base misincorporation globally stimulates HR in plants

Plos Med

Background The ε4 allele of apolipoprotein E (APOE) gene and increasing age are two of the most important known risk factors for developing Alzheimer disease (AD). The diagnosis of AD based on clinical symptoms alone is known to have poor specificity; recently developed diagnostic criteria based on biomarkers that reflect underlying AD neuropathology allow better assessment of the strength of the associations of risk factors with AD. Accordingly, we examined the global and age-specific association between APOE genotype and AD by using the A/T/N classification, relying on the cerebrospinal fluid (CSF) levels of β-amyloid peptide (A, β-amyloid deposition), phosphorylated tau (T, pathologic tau), and total tau (N, neurodegeneration) to identify patients with AD. Methods and findings This case–control study included 1,593 white AD cases (55.4% women; mean age 72.8 [range = 44–96] years) with abnormal values of CSF biomarkers from nine European memory clinics and the American Alzheimer’s Disease Neuroimaging Initiative (ADNI) study. A total of 11,723 dementia-free controls (47.1% women; mean age 65.6 [range = 44–94] years) were drawn from two longitudinal cohort studies (Whitehall II and Three-City), in which incident cases of dementia over the follow-up were excluded from the control population. Odds ratio (OR) and population attributable fraction (PAF) for AD associated with APOE genotypes were determined, overall and by 5-year age categories. In total, 63.4% of patients with AD and 22.6% of population controls carried at least one APOE ε4 allele. Compared with non-ε4 carriers, heterozygous ε4 carriers had a 4.6 (95% confidence interval 4.1–5.2; p < 0.001) and ε4/ε4 homozygotes a 25.4 (20.4–31.2; p < 0.001) higher OR of AD in unadjusted analysis. This association was modified by age (p for interaction < 0.001). The PAF associated with carrying at least one ε4 allele was greatest in the 65–70 age group (69.7%) and weaker before 55 years (14.2%) and after 85 years (22.6%). The protective effect of APOE ε2 allele for AD was unaffected by age. Main study limitations are that analyses were based on white individuals and AD cases were drawn from memory centers, which may not be representative of the general population of patients with AD. Conclusions In this study, we found that AD diagnosis based on biomarkers was associated with APOE ε4 carrier status, with a higher OR than previously reported from studies based on only clinical AD criteria. This association differs according to age, with the strongest effect at 65–70 years. These findings highlight the need for early interventions for dementia prevention to mitigate the effect of APOE ε4 at the population level

Etude des déterminants génétiques de l'obésité humaine dans la population française

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

Etude des facteurs pronostiques de récidive des adénomes hypophysaires gonadotropes opérés (analyse immunohistochimique de Ki-67)

ANGERS-BU Médecine-Pharmacie (490072105) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

De la génétique à l’épigénétique : une révolution « post-génomique » à l’usage des sociologues

International audienceCette note critique étudie l’impact de la révolution dite « post-génomique » pour les sciences sociales à partir de cinq ouvrages publiés entre 2016 et 2017. Il s’agit non seulement d’introduire le lecteur français à l’actualité des débats dans les pays anglo-saxons sur la redéfinition en cours des frontières entre sociologie et biologie, mais également et surtout de contribuer à la réflexion sur l’évolution des pratiques de recherche interdisciplinaires. Une attention particulière est accordée au domaine émergent de l’épigénétique et à la manière dont il est représenté par ces ouvrages comme le lieu par excellence de la révolution post-génomique. L’article souligne l’importance pour les sociologues de prendre conscience des opportunités associées à cette révolution, tout comme de s’affranchir d’un certain nombre d’idées reçues. Il insiste également sur la nécessité de maintenir une distance critique suffisante par rapport à un domaine de recherche « prometteur »