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International audience; Three lanthanide complexes (Ln=Gd, Eu) based on a DO3 A ([Ln(L$_1$)]) or DO2 A ([Ln(L$_{2-3}$)]$^+$) platform appended by a redox active TEMPO-based arm were prepared. Complex [Ln(L$_2$)]$^+$) shows an alkyne arm, offering the possibility of postfunctionalization by click reaction to yield [Ln(L$_3$)]$^+$). The complexes demonstrate a redox response whereby the hydroxylamine, nitroxide and oxoammonium forms of the arm can be obtained in turn. Luminescence measurements on the europium complexes support an octadentate (L$_1$, L$_3$) or heptadentate (L$_2$) chelation by the ligand, with one water molecule in the inner coordination sphere. The relaxivity was determined from 20 kHz to 30 MHz by fast-field cycling NMR. The three Gd-III complexes under their hydroxylamine form [Gd(L$_1$)] and [Gd(L$_{2-3}$)]$^+$) show $r_1$ values of 7.0, 5.1 and 5.0 mM$^{-1}$ s$^{-1}$ (30 KHz), which increase to 8.8, 5.5 and 6.1 mM$^{-1}$ s$^{-1}$ in the nitroxide form. The radical complexes are not toxic against M21 cell lines, at least up to 40 $\mu$M. By using EPR spectroscopy we establish that they do not penetrate the cells with the exception of [Eu(L$_2$)]$^+$.

Lanthanides complexes are indispensable in fields related to medicine and biology. Their success lies in the great number of unpaired electrons (4f7 configuration of the Gd3+ ion) that makes them ideal contrasts agents for magnetic resonance imaging. On the other hand their narrow emission bands and long lifetime of their excited state provide them unique luminescence properties. The aqueous solution chemistry of the lanthanides is dominated by the (+III) oxidation state under oxygenated atmosphere. This severely limits their use as redox probes, and not surprisingly very few redox-switches employing lanthanide ions were reported until 2010. A very promising approach based on redox-reactive and redox non-innocent ligands has recently emerged in the literature, which overcomes this limitation and expands the application of lanthanides to redox monitoring. Herein the ligand acts as a redox-sensor by either changing its oxidation state or reacting with reactive oxygen (or nitrogen) species (ROS/RNS). Its response induces changes in the environment of the lanthanide ion, which acts as a reporter of the redox status. The detection is based on a modification of the magnetic or optical properties of the complexes, with detection by conventional spectroscopic techniques. We summarize in this review article the recent advances in this burgeoning field, with special emphasis on the detection of biological relevant ROS, RNS and redox status.

The birth of magnetic resonance imaging (MRI) marks a major advance in the history of radiology. For almost 50 years, MRI has become an indispensable imaging and diagnostic tool. One of the main objectives is now to obtain better contrast and sensitivity in order to understand the biochemical and biological phenomena for better patient diagnostics, this is called molecular imaging. The principle of this discipline is to detect specific molecules, such as DNA sequences, cell markers, enzymes, reactive species ... It will then be possible, for example, to detect nascent cancers. The specific molecules are often present in very small quantities in the tissues and require imaging techniques with very good sensitivity. MRI has very good resolution but suffers from a lack of sensitivity. This is why contrast agents are added in order to gain in sensitivity. Conversely, optical imaging benefits from increased sensitivity but does not allow in-depth study. By coupling these two techniques, it would then be possible to study with precision the molecular mechanisms deep within the tissues.This thesis project was born in order to develop contrast agents based on lanthanides and non-innocent ligands that specifically respond to oxidative stress. The detection of this oxidative stress by several different techniques could be achieved using a bimodal probe which would combine the benefits of MRI and optical imaging, as good resolution and high sensitivity. In order to gain even more sensitivity, a new technique derived from MRI, called "CEST" for Chemical Exchange Saturation Transfer was born.The aim of this thesis is to provide the proof of concept of bimodal probes for the detection of reactive oxygen species by magnetic imaging and optical imaging techniques. For this, new families of lanthanide complexes with a radical or pro-radical ligand have been chemically synthesized and have been studied by different spectroscopic and electrochemical techniques. These analyzes validated the proof of concept by creating a bimodal probe showing an alteration of the signal depending on the redox state of the ligand.Key words: Medical imaging– Coordination complexes – Organic radicals – Lanthanides - Spectroscopy, La naissance de l’imagerie par résonance magnétique (IRM) marque un progrès majeur dans l’histoire de la radiologie. Depuis bientôt 50 ans, l’IRM est devenu un outil d’imagerie et de diagnostic indispensable. Un des principaux objectifs actuels est d’obtenir un meilleur contraste et une meilleure sensibilité afin de comprendre les phénomènes biochimiques et biologiques pour de meilleurs diagnostiques des patients, on parle alors d’imagerie moléculaire. Le principe de cette discipline est de détecter les molécules spécifiques d’une cible à étudier telles que des séquences d’ADN, des marqueurs cellulaires, des enzymes, des espèces réactives… Il sera alors possible par exemple, de détecter des cancers naissant. Les espèces à étudier sont souvent présentes en très faibles quantités dans les tissus et nécessitent des techniques d’imageries ayant une très bonne sensibilité. L’IRM dispose d’une très bonne résolution mais souffre d’un manque de sensibilité. C’est pourquoi des agents de contraste sont ajoutés afin de gagner en sensibilité. A contrario, l’imagerie optique bénéficie d’une sensibilité accrue mais ne permet pas une étude en profondeur. En couplant ces deux techniques, il serait alors possible d’étudier avec précision les mécanismes moléculaires au plus profond des tissus.C’est dans cette optique que ces travaux de thèse sont nés, afin de mettre au point des agents de contraste à base de lanthanides et de ligands non innocents répondant spécifiquement au stress oxydant. La détection de ce stress oxydant par plusieurs techniques différentes pourrait être réalisée à l’aide de sonde bimodale qui allierait les bénéfices de l’IRM et de l’imagerie optique, à savoir une bonne résolution et une haute sensibilité. Afin de gagner encore plus en sensibilité, une nouvelle technique dérivée de l’IRM, appelée « CEST » pour transfert de saturation par échange chimique est née. L’objet de cette thèse est d’apporter la preuve de concept de sondes bimodales pour la détection d’espèces réactive de l’oxygène par des techniques d’imagerie magnétique et d’imagerie optique.Pour cela, des nouvelles familles de complexes de lanthanides portant un ligand radicalaire ou pro-radicalaire ont été synthétisés chimiquement et ont été étudiés par différentes techniques spectroscopiques, électrochimiques. Ces analyses ont permis de valider la preuve de concept par la création de sonde bimodale montrant une altération du signal en fonction de l’état rédox du ligand.

Mean Gradient (MG) elevation can be detected immediately after transcatheter aortic valve implantation (TAVI) or secondarily during follow-up. Comparisons and interactions between these two parameters and their impact on outcomes have not previously been investigated. This study aimed to identify incidence, influence on prognosis, and parameters associated with immediate high post-procedural mean transvalvular gradient (PPMG) and delayed mean gradient increase (6 to 12 months after TAVI, DMGI) in the FRANCE 2 (French Aortic National CoreValve and Edwards 2) registry. The registry includes all consecutive symptomatic patients with severe aortic stenosis who have undergone TAVI. Three groups were analyzed: (1) PPMG &lt, 20 mmHg without DMGI &gt, 10 mmHg (control), (2) PPMG &lt, 20 mmHg with DMGI &gt, 10 mmHg (Group 1), and (3) PPMG ≥ 20 mmHg (Group 2). From January 2010 to January 2012, 4201 consecutive patients were prospectively enrolled in the registry. Controls comprised 2078 patients. In Group 1(n = 131 patients), DMGI exceeded 10 mmHg in 5.6%, and was not associated with greater 4-years mortality than in controls (32.6% vs. 40.1%, p = 0.27). In Group 2 (n = 144 patients), PPMG was at least 20 mmHg in 6.1% and was associated with higher 4-year mortality (48.7% versus 40.1%, p = 0.005). A total of two-thirds of the patients with PPMG ≥ 20 mmHg had MG &lt, 20 mmHg at 1 year, with mortality similar to the controls (39.2% vs. 40.1%, p = 0.73). Patients with PPMG &gt, 20 mmHg 1 year post-TAVI had higher 4-years mortality than the general population of the registry, unlike patients with MG normalization.

Aortic valve surgery in non-elderly patients represents a very challenging patient population. The younger the patient is at the point of aortic valve intervention, the longer their anticipated life expectancy will be, with longer exposure to valve-related complications and risk for re-operation. Although the latest international guidelines recommend aortic valve repair in patients with aortic valve insufficiency, what we see in the real world is that the vast majority of these aortic valves are replaced. However, current prosthetic valves has now been shown to lead to significant loss of life expectancy for non-elderly patients up to 50% for patients in their 40s undergoing mechanical aortic valve replacement. Bioprostheses carry an even worse long-term survival, with higher rates of re-intervention. The promise of trans-catheter valve-in-valve technology is accentuating the trend of bioprosthetic implantation in younger patients, without yet the appropriate evidence. In contrast, aortic valve repair has shown excellent outcomes in terms of quality of life, freedom from re-operation and freedom from major adverse valve-related events with similar life expectancy to general population as it is also found for the Ross procedure, the only available living valve substitute. We are at a time when the paradigm of aortic valve surgery needs to change for the better. To better serve our patients, we must acquire high quality real-world evidence from multiple centers globally - this is the vision of the AVIATOR registry and our common responsibility.

Cet article étudie le rôle joué par la figure du cheval de Troie dans l’œuvre de Monique Wittig. J’y défends l’idée que, si la figure du cheval de Troie est si importante pour l’écrivaine, c’est non seulement parce qu’il s’agit d’un pilier de la tradition qu’elle veut renverser, mais aussi parce que, selon elle, c’est toujours de l’intérieur qu’il est possible d’opérer ce renversement, comme c’est de l’intérieur qu’Ulysse a pu renverser Troie. Je montre aussi comment le Cheval de Troie, à travers ce que Wittig appelle « l’universalisation » du point de vue lesbien, fonctionne dans l’œuvre de celle-ci comme une figure anti-essentialiste qui ruine les notions d’identité et de fondement., This paper studies the role played by the figure of the Trojan horse in the work of Monique Wittig. I argue that if this particular figure is so important to Wittig, it is not only because it is a pillar of tradition that they want to overthrow, but also because, according to them, it is always from within that this overthrow can take place, just as it was from within that Odysseus was able to overthrow Troy. I also argue that the Trojan horse, through what Wittig calls the “universalization” of the lesbian standpoint, functions in their work as an anti-essentialist figure that dismantles notions such as identity and foundation.

"Il s’agit de l’Odyssee d’Homere, et notamment du celebre episode du chant XII, ou Ulysse se ligote au mat de son navire pour pouvoir ecouter le chant des Sirenes sans craindre d’y succomber. Grâce a ce stratageme, Ulysse fait l’experience d’un abandon de l’esprit a ce qui l’affecte de l’exterieur, le fascinant et menacant de lui faire perdre la raison. Mais en meme temps, et dans un meme mouvement, il fait l’experience d’une maitrise des affects par la force de la raison. A la fois stoique et ouvert au debordement des affects, Ulysse incarne les extremes de l’esprit, le lieu ou la tension entre affect et raison est portee a son comble. En prenant l’exemple de deux textes du XXe siecle qui actualisent la figure d’Ulysse, « Le silence des Sirenes » de Kafka et Un apprentissage ou le livre des plaisirs de Clarice Lispector, je voudrais montrer comment les mises en scene du litteraire donnent lieu a une pensee qui n’est epuisee par aucun moment historique particulier ni reductible a aucune discipline institutionnalisee."

International audience

International audience; The lanthanide complexesEuL(3),GdL3,YbL(3)andLuL(3)of theN,N '-bis(2-hydroxy-di-3,5-tert-butylphenyl)amine were prepared. The X-Ray crystal structures ofGdL(3)andLuL(3)demonstrated a nine-coordinate sphere with three ligand molecules under their anionic diamagnetic form (Cat-N-BQ)(-). The complexes showed three oxidation events (Eox11/2 = 0.15-0.16 V,E-1/2(2)= 0.51-55 V, andE(1/2)(3)= 0.75-0.78 Vvs.Fc(+)/Fc)viacyclic voltammetry, corresponding to the successive oxidation of the aminophenolate moeities to iminosemiquinone species. The complexesGdL(3)andYbL(3)were characterized by EPR spectroscopy, allowing for the determination of the zero field splitting (ZFS) parameters in the first case. The monocations(LnL(3))(+)and monoanions(LnL(3))(-)were electrochemically generated (Ln = Eu, Gd, Yb, Lu), as well as the dicationsYbL(3)(2+)andLuL(3)(2+). The spins are antiferromagnetically exchange coupled in the diradical speciesLuL(3)(2+)(|D| = 260 MHz,E= 0). All the complexes (incl. neutral) possess a strong absorption band in the NIR region (730-840 nm,epsilon> 19 mM(-1)cm(-1)) corresponding to ligand-based transitions.

International audience; The DOTA-based ligand H3L (5) appended with a pro-nitroxide moiety has been synthesized. The europium and ytterbium complexes 5Ln show metal-centred luminescence. They react with ROS in aqueous media to give a transient iminonitroxide and a stable nitronylnitroxide radical authenticated by EPR, with change in luminescence.

International audience; Background and aim of the study Cardiac wounds have been described for centuries and still remain to be fatal. For a long period of time, the suturing of a myocardial laceration was thought to be absolutely impossible if not sacrilege. Methods It is only at the end of the 19th century that pioneers decided to defy such a dogma in desperate cases. Results Nowadays, it seems obvious that a cardiac stab wound requires emergent surgery whenever possible. Conclusions The story of cardiac wounds highlights nicely the change of mind that is required to accept progress and new procedures in medicine.

Cet article analyse la représentation de la musique punk dans les romans de Virginie Despentes à partir de la figure de Némésis. Conçue à la fois comme éclatement d’une violence excessive, démesurée, et comme châtiment venant punir la démesure, Némésis incarne la dialectique à l’œuvre dans la conception du punk développée par Despentes. De la cavale meurtrière de Nadine et Manu aux convergences de Vernon Subutex, l’expérience du punk, chez Despentes, est d’abord mise en scène comme explosion violente révélant les extrêmes du monde en un bref instant de lucidité, puis comme objet de nostalgie dans un monde qui en a balayé les dernières traces et, enfin, comme surgissement d’un nouvel horizon utopique dont l’hybris appelle sur lui le châtiment de l’histoire., This article analyzes the representation of punk music in the novels of Virginie Despentes based on the figure of Nemesis. Conceived both as a burst of excessive, disproportionate violence and as a punishment for the disproportionate, Nemesis embodies the dialectic at work in Despentes’ conception of punk. From Nadine and Manu’s murderous road trip to Vernon Subutex’s convergences, the experience of punk is first staged as a violent explosion revealing the extremes of the world in a brief moment of lucidity, then as an object of nostalgia in a world that has swept away its last traces, and finally as the emergence of a new utopian horizon whose hubris brings forth the punishment of history.

Working party approved by the French Society of Anaesthesia and Intensive Care Medicine (SFAR) and the French Society for the study of Diabetes (SFD); International audience; Follow on from continuous intravenous administration of insulin with an electronic syringe (IVES) is an important element in the postoperative management of a diabetic patient. The basal-bolus scheme is the most suitable taking into account the nutritional supply and variable needs for insulin, reproducing the physiology of a normal pancreas: (i) slow (long-acting) insulin (= basal) which should immediately take over from IVES insulin simulating basal secretion; (ii) ultra-rapid insulin to simulate prandial secretion (= bolus for the meal); and (iii) correction of possible hyperglycaemia with an additional ultra-rapid insulin bolus dose. A number of schemes are proposed to help calculate the dosages for the change from IV insulin to subcutaneous insulin and for the basal-bolus scheme. Postoperative resumption of an insulin pump requires the patient to be autonomous. If this is not the case, then it is mandatory to establish a basal-bolus scheme immediately after stopping IV insulin. Monitoring of blood sugar levels should be continued postoperatively. Hypoglycaemia and severe hyperglycaemia should be investigated. Faced with hypoglycaemia < 3.3 mmol/L (0.6 g/L), glucose should be administered immediately. Faced with hyperglycaemia > 16.5 mmol/L (3 g/L) in a T1D or T2D patient treated with insulin, investigations for ketosis should be undertaken systematically. In T2D patients, unequivocal hyperglycaemia should also call to mind the possibility of diabetic hyperosmolarity (hyperosmolar coma). Finally, the modalities of recommencing previous treatments are described according to the type of hyperglycaemia, renal function and diabetic control preoperatively and during hospitalisation.

In diabetic patients undergoing surgery, we recommend assessing glycaemic control preoperatively by assessing glycated haemoglobin (HbA1c) levels and recent capillary blood sugar (glucose) levels, and to adjust any treatments accordingly before surgery, paying particular attention to specific complications of diabetes. Gastroparesis creates a risk of stasis and aspiration of gastric content at induction of anaesthesia requiring the use of a rapid sequence induction technique. Cardiac involvement can be divided into several types. Coronary disease is characterised by silent myocardial ischaemia, present in 30-50% of T2D patients. Diabetic cardiomyopathy is a real cause of heart failure. Finally, cardiac autonomic neuropathy (CAN), although rarely symptomatic, should be investigated because it causes an increased risk of cardiovascular events and a risk of sudden death. Several signs are suggestive of CAN, and confirmation calls for close perioperative surveillance. Chronic diabetic kidney disease (diabetic nephropathy) aggravates the risk of perioperative acute renal failure, and we recommend measurement of the glomerular filtration rate preoperatively. The final step of the consultation concerns the management of antidiabetic therapy. Preoperative glucose infusion is not necessary if the patient is not receiving insulin. Non-insulin drugs are not administered on the morning of the intervention except for metformin, which is not administered from the evening before. The insulins are injected at the usual dose the evening before. The insulin pump is maintained until the patient arrives in the surgical unit. It should be remembered that insulin deficiency in a T1D patient leads to ketoacidosis within a few hours.