Quality of life in patients with locked-in syndrome: Evolution over a 6-year period

International audienceBackground: Improved knowledge of the quality of life (QoL) of locked-in syndrome (LIS) patients have implications for managing their care, and assists clinicians in choosing the most appropriate interventions. We performed a survey of a population of LIS patients to describe the course of the QoL of LIS patients over a 6-year period and to determine the potential predictive factors of QoL changes over time. Method: This is a study performed over a 6-year period in patients with a LIS diagnosis. Questionnaires were sent in 2007 and 2013. The following data were recorded: i) sociodemographic data; ii) clinical data related to LIS, physical/handicap status, psychological status; iii) self-reported QoL: Anamnestic Comparative Self-Assessment (ACSA); iv) Integration in life: French Reintegration to Normal Living Index (RNLI). Results: Among the 67 patients included in 2007, 39 (58 %) patients returned their questionnaire in 2013. The LIS etiology was stroke in 51 individuals. The QoL of the patients was relatively satisfactory compared to populations in other severe conditions. Twenty-one (70 %) individuals reported a stable/improved QoL between 2007 and 2013. The physical/handicap statuses in 2007 and 2013 were not related to the QoL 6 years later, with the exception of one communication parameter: the individuals who used yes-no code reported significantly lower QoL levels than those who did not in 2013. Discussion: In opposition to a widespread opinion, LIS persons report a relatively satisfactory QoL level that stays stable over time, suggesting that life with LIS is worth living. Preservation of autonomy and communication may help them to live as normal life as possible

French Survey on Pain Perception and Management in Patients with Locked-In Syndrome.

peer reviewedPatients with locked-in syndrome (LIS) may suffer from pain, which can significantly affect their daily life and well-being. In this study, we aim to investigate the presence and the management of pain in LIS patients. Fifty-one participants completed a survey collecting socio-demographic information and detailed reports regarding pain perception and management (type and frequency of pain, daily impact of pain, treatments). Almost half of the LIS patients reported experiencing pain (49%) that affected their quality of life, sleep and cognition. The majority of these patients reported that they did not communicate their pain to clinical staff. Out of the 25 patients reporting pain, 18 (72%) received treatment (60% pharmacological, 12% non-pharmacological) and described the treatment efficacy as 'moderate'. In addition, 14 (56%) patients were willing to try other non-pharmacological treatments, such as hypnosis or meditation. This study provides a comprehensive characterization of pain perception in LIS patients and highlights the lack of guidelines for pain detection and its management. This is especially pertinent given that pain affects diagnoses, by either inducing fatigue or by using pharmacological treatments that modulate the levels of wakefulness and concentration of such patients

Modifications de la liaison peptidique (N-hydroxy-, N-acyloxy- et N-alkyloxy-peptides)

Une série de peptides présentant un ou deux motifs hydroxamate a été synthétisée, l'étape clé étant la N-acylation sélective de N-hydroxy-dipeptides terminaux. L'atome d'oxygène du groupe hydroxyle peut servir de point d'ancrage pour une autre chaîne et donne ainsi accès à de nouveaux pseudopeptides. D'une part, l'acylation de N-hydroxy-peptides a été réalisée dans différentes conditions permettant l'introduction de groupements variés, en particulier des acides aminés. Il est possible d'allonger ces N-acyloxy-peptides dans toutes les directions, même si dans certains cas des réarrangements intéressants peuvent avoir lieu. D'autre part, une réaction d'alkylation dans les conditions de Mitsunobu a permis de greffer des groupements allyle et homoallyle sur des N-hydroxy-tripeptides, conduisant notamment à la préparation d'un hexapeptide bis insaturé qui peut être cyclisé via une réaction de métathèse.GRENOBLE1-BU Sciences (384212103) / SudocSudocFranceF

1-OXY-2,3-DIHYDRO-IMIDAZOL-4-ONES : DES INTERMEDAIRES ET DES CIBLES

The present work deals with N-oxy-imidazolidinone type nitrones and the possible applications thereof. We developed an achiral nitrone, CYCNO, available in 3 stages from a glycine ester (66%) and a chiral nitrone, MiPNO. The latter was obtained in enantiopure form by a new optical resolution method; each enantiomer is accessible in 15 and 17% yield from the glycine ester. CYCNO was used as a model to study the reactivity of N-oxy-imidazolidinones toward aryl and heteroarylmagnesium halides, prepared by magnesium insertion or iodine-magnesium exchange. The reoxidation of the intermediate hydroxylamine led to a new family of nitrones, which may be used as spin traps. MiPNO was used for the preparation of unnatural amino acids, arylglycines and α-aryl,α-methylglycines. The sequence involves a totally diastereoselective addition of organomagnesium reagents. Seven arylglycine targets were prepared. In addition, 1,3-dipolar cycloaddition reactions between MiPNO and various alkenes led to isoxazolidines, in excellent regio- and diastereoselectivity. The cycloadduct can be converted into the corresponding α-amino-γ-lactone in a single operation, allowing the preparation of a new enantiopure γ-hydroxy-α-amino-acid.Les travaux présentés s'articulent autour de synthons nitrone de type N-oxy-imidazolidinone, pour lesquels nous avons exploré les applications possibles. Nous avons développé une nitrone achirale, CYCNO, accessible en 3 étapes depuis un ester de la glycine (66%) et une nitrone chirale, MiPNO. Celle-ci a été obtenue sous forme énantiopure par une méthode de résolution nouvelle ; chaque énantiomère est ainsi accessible avec des rendements de 15 et 17% depuis l'ester de la glycine. CYCNO a été utilisée comme modèle pour étudier la réactivité des N-oxy-imidazolidinones vis-à-vis des halogénures d'aryl- et hétéroarylmagnésium, préparés par insertion de magnésium ou par échange iode-magnésium. La réoxydation des hydroxylamines intermédiaires mène à une nouvelle série de nitrones, pouvant être utilisées comme pièges à radicaux libres. MiPNO a été utilisée pour la préparation d'acides aminés non naturels, arylglycines et α-aryl,α-méthylglycines. La séquence met en jeu une réaction d'addition d'organomagnésiens totalement diastéréosélective. Sept cibles arylglycines ont été préparées. De plus, des réactions de cycloaddition 1,3-dipolaire entre MiPNO et différents alcènes ont conduit à des isoxazolidines, obtenues de façon hautement régio- et diastéréosélective. Le cycloadduit peut être converti en l'α-amino-γ-lactone correspondante en une seule opération, ce qui a mené à la préparation d'un nouveau γ-hydroxy-α-amino-acide énantiopur

Straightforward Creation of Possibly Prebiotic Complex Mixtures of Thiol-Rich Peptides

At the origin of life, extremely diverse mixtures of oligomers and polymers could be obtained from relatively simple molecular bricks. Here, we present an example of the polymerization of two amidonitriles derived from cysteine, Cys-Ala-CN and Cys-Met-CN. The thiol function in a molecule adds onto the nitrile group of another one, allowing efficient condensation reactions and making available an extensive range of polymers containing amide bonds and/or five-membered heterocycles, namely thiazolines. Macrocycles were also identified, the biggest one containing sixteen residues (cyclo(Cys-Met)8). MALDI-TOF mass spectrometry was used to identify all the present species. What these examples show is that complex mixtures are likely to have formed on the primitive Earth and that, ultimately, the selection that must have followed may have been an even more crucial step towards life than the synthesis of the pre-biological species themselves

MiPNO, a new chiral nitrone for enantioselective amino acid synthesis: the cycloaddition approach.

International audienceThe resolution of chiral nitrones via derivatization of hydroxylamines was applied to MiPNO, a new, stable, easily prepared chiral cyclic nitrone. The application of MiPNO in totally regio- and diastereo- selective 1,3-dipolar cycloaddition reactions provides an expeditious enantioselective access to unusual γ-hydroxy α-aminoacids

Noncryogenic Preparation of Functionalized Arylboronic Esters through a Magnesium-Iodine Exchange with in Situ Quench

International audienceVarious functionalized aryl boronic esters derived from hexylene glycol and pinacol were prepared in excellent yields according to a simple, safe procedure. The metal-halogen exchange reaction between (PrMgCl)-Pr-i center dot LiCl and aryl iodides is performed at 0 degrees C in the presence of a cyclic borate ester ((MPBOPr)-Pr-i or PinBO(i)Pr); the organomagnesium intermediate is immediately trapped in situ so that no accumulation of hazardous reactive species can occur. The reaction is very selective, and particularly clean crude products are obtained. The scope of the procedure and the tuning of reaction parameters are investigated

Efficient borylation of reactive aryl halides with MPBH (4,4,6-trimethyl-1,3,2-dioxaborinane).

International audienceThe combination of 4,4,6-trimethyl-1,3,2-dioxaborinane, a particularly stable and inexpensive borylation reagent, and Buch-wald's palladium catalyst provides a simple, fast, cost-effective borylation of electron-rich, reactive iodides, bromides, and tri-flates, to produce stable, easily purified boronic esters

Totally diastereoselective addition of aryl Grignard reagents to the nitrone-based chiral glycine equivalent MiPNO.

International audienceThe reaction of the chiral nitrone MiPNO (2-isopropyl-2,3-dimethyl-1-oxy-2,3-dihydro-imidazol-4-one) with Grignard reagents is totally diastereoselective. Using simple and functionalized arylmagnesium reagents, enantiopure hydroxylamines were obtained in fair to good yields, which in turn could be easily transformed into new chiral ketonitrones. The prepn. of enantiopure L-phenylglycine derivs. is also described. [on SciFinder(R)