Search

We report two members of a French family who are carriers of a rare hemoglobin (Hb) variant leading to erythrocytosis: Hb Saint Nazaire [β103(G5)Phe→Ile

International audience; We describe the clinical, hematologic and genetic characteristics of a retrospective series of 126 subjects from 64 families with hereditary xerocytosis. Twelve patients from six families carried a KCNN4 mutation, five had the recurrent p.Arg352His mutation and one had a new deletion at the exon 7-intron 7 junction. Forty-nine families carried a PIEZO1 mutation, which was a known recurrent mutation in only one-third of the cases and private sequence variation in others; 12 new probably pathogenic missense mutations were identified. The two dominant features leading to diagnosis were hemolysis that persisted after splenectomy and hyperferritinemia, with an inconstant correlation with liver iron content assessed by magnetic resonance imaging. PIEZO1-hereditary xerocytosis was characterized by compensated hemolysis in most cases, perinatal edema of heterogeneous severity in more than 20% of families and a major risk of post-splenectomy thrombotic events, including a high frequency of portal thrombosis. In KCNN4-related disease, the main symptoms were more severe anemia, hemolysis and iron overload, with no clear sign of red cell dehydration; therefore, this disorder would be better described as a ‘Gardos channelopathy’. These data on the largest series to date indicate that PIEZO1-hereditary xerocytosis and Gardos channelopathy are not the same disease although they share hemolysis, a high rate of iron overload and inefficient splenectomy. They demonstrate the high variability in clinical expression as well as genetic bases of PIEZO1-hereditary xerocytosis. These results will help to improve the diagnosis of hereditary xerocytosis and to provide recommendations on the clinical management in terms of splenectomy, iron overload and pregnancy follow-up.

International audience; 4,4-Diisothiocyanostilbene-2,2-disulfonic acid (DIDS) is a well-known ion-exchange inhibitor targeting cardiac functions and indirectly impeding both radio- and chemo-resistance. A joint computational and experimental study is presented to provide deeper insights into DIDS and other members of this family of compounds. To this end, we applied state-of-the-art density functional theory (DFT) and time-dependent DFT methods, in addition to measuring the optical properties. The experimental data show that such compounds are highly sensitive to their environment and that the optical properties change within as little time as 7h. However, the optical properties of DIDS are similar in various acidic/basic environments, which were confirmed by pK(a) computations on both cis and trans isomers. The protonation analysis also highlights that the singly protonated form of DIDS behaves like a proton sponge compound. The experimentally observed redshift that can be seen when going from water to DMSO was reproduced solely by using the solvation model based on density, although the polarization continuum model and implicit/explicit hybrid schemes were also tested. The characteristic broadening of the absorption peak in water and the vibronic fine structure in DMSO were also reproduced thanks to vibronic coupling simulations associated with the solvent reorganization energy. For other stilbene derivatives, a correlation is found between the maximum absorption wavelength and the Hammett parameters.

Resume Introduction Le recours a une transfusion de culots de globules rouges chez un patient drepanocytaire majeur est parfois indispensable. L’hemolyse post-transfusionnelle retardee est une complication rare mais potentiellement grave. Cette manifestation peut survenir a tout âge. Elle est probablement sous-diagnostiquee du fait du peu de signes specifiques. Observations Nous decrivons dans cet article, les signes cliniques, biologiques et les aleas de la prise en charge therapeutique de trois cas d’hemolyse post-transfusionnelle retardee. La chromatographie haute performance evaluant le pourcentage d’HbA1 est l’examen permettant d’etablir le diagnostic. La physiopathologie de cet evenement est encore mal connue. Plusieurs traitements ont ete utilises, cependant, la prise en charge therapeutique reste discutee a l’heure actuelle. Conclusion La transfusion de tout patient susceptible d’avoir une hemolyse post-transfusionnelle retardee est fortement deconseillee car elle risque d’aggraver l’hemolyse. La prevention d’une recidive est primordiale.

Parcours 5. Métier, métiers, proposé par Dominique Lahary Bertrand Calenge est un formateur. Pas seulement parce qu’il a dirigé l’Institut de formation des bibliothécaires (INFB) et exercé à l’Enssib. Plus profondément, parce qu’au-delà des différentes responsabilités qu’il a exercées, il n’a eu de cesse de rechercher, se documenter, documenter, produire,...

Nous sommes tous redevables à Bertrand Calenge, bibliothécaire de renom, théoricien et praticien des bibliothèques, disparu en 2016. Un collectif de bibliothécaires fait revivre cet auteur, en proposant un parcours de lecture à travers son blog Carnet de notes. Ces parcours thématiques et transversaux recontextualisent les billets selon les principaux sujets traités par l’auteur – collections, médiation, évaluation, métier, numérique, etc. – autant dire toutes les questions vives des bibliothèques. Ce livre expérimente une mise en book du blog d’un professionnel, pour nous inviter, comme l'écrit Martine Poulain dans sa préface, « à penser, échanger, proposer ».

Parcours 8. De Biblio-fr à l’info-blogosphère : chaîne unique et multicanaux, proposé par Dominique Lahary Il faut s’imaginer le monde d’avant ou se le remémorer si on l’a connu. Une communauté professionnelle, prenons les bibliothécaires, n’avait pour s’informer, capitaliser, faire doctrine et débat, que le papier sous forme de livres et périodiques. Ainsi que les rencontres bi...

Disulfonic stilbene (DS) derivatives are a member of the large family of compounds widely employed in medicine and biology as modulators for membrane transporters or inhibitors of a protein involved in DNA repair. They constitute interesting compounds that have not yet been investigated within the bioavailability framework. No crystallographic structures exist involving such compounds embedded in the most common drug carrier, human serum albumin (HSA). The present work studies, for the first time, the physico-chemical features driving the inclusion of three DS derivatives (amino, nitro and acetamido, named DADS, DNDS and DATDS, respectively) within the four common HSA binding sites using combined molecular docking and molecular dynamics simulations. A careful analysis of each ligand within each of the studied binding sites is carried out, highlighting specific interactions and key residues playing a role in stabilizing the ligand within each pocket. The comparison between DADS, DNDS and DATDS reveals that depending on the binding site, the conclusions are rather different. For instance, the IB binding site shows a specificity to DADS compounds while IIIA is the most favorable site for DNDS and DATDS.

INTRODUCTION Development of additional parameters for complete blood count has emerged in recent hematology analyzers, leading to many publications. However, few studies have been conducted on advanced RBC parameters and hemolytic anemias. We investigated the interest of Sysmex unique parameters, MicroR and HypoHe, as well as the immature fraction of reticulocytes (IRF) in combination with complete blood and reticulocyte count, for screening hereditary spherocytosis (HS) and pyruvate kinase deficiency. METHODS We analyzed 182 samples using Sysmex XE-5000 analyzers from a cohort of red cell disorder patients from the Rouen University Hospital. These included 47 HS, 17 pyruvate kinase deficiencies, sickle cell diseases and trait, β-thalassemia minor, iron deficiencies, and 489 samples from a routine group. RESULTS Combining five parameters (hemoglobin level, reticulocyte count, IRF, MicroR, and %HypoHe), we developed a specific screening tool for HS allowing a sensitivity of 100% and a specificity of 92.1% and a specific screening tool for pyruvate kinase deficiencies allowing a sensitivity of 100% and a specificity of 96.5%. These parameters were also found accurate in infants and in HS without anemia. CONCLUSION We propose a costless, easy-to-use, and efficient approach to detect HS and pyruvate kinase deficiencies using Sysmex analyzers. These screening tools may help diagnosis of these disorders, help prevent complications, and result in a better management of these patients.

We report two members of a French family who are carriers of a rare hemoglobin (Hb) variant leading to erythrocytosis: Hb Saint Nazaire [β103(G5)Phe→Ile; HBB: c.310T>A]. The proband is a 38-year-old woman referred to our institution for a moderate but persistent polycythemia without any clinical consequence. As her mother had a similar blood count, a diagnosis of a Hb variant with high oxygen affinity was proposed. The variant was difficult to detect by capillary electrophoresis (CE) and not distinguishable by high performance liquid chromatography (HPLC) and isoelectric focusing. Finally, a heterozygous mutation on the HBB gene corresponding to Hb Saint Nazaire was identified. This case report illustrates that this rare cause of erythrocytosis can be easily under or misdiagnosed unless several Hb separation techniques are used.

Glycated haemoglobin (HbA(1c)) is considered the gold standard for assessing diabetes compensation and treatment. In addition, fortuitous detection of haemoglobin variants during HbA1c measurement is not rare. Recently, two publications reported different conclusions on accuracy of HbA(1c) value using capillary electrophoresis method in presence of haemoglobin J-Baltimore (HbJ). Here we describe the fortuitous detection of unknown HbJ using capillary electrophoresis for measurement of HbA(1c). A patient followed for gestational diabetes in our laboratory presented unknown haemoglobin on Capillarys 2 Flex Piercing analyser which was identified as HbJ. HbJ is not associated with haematological abnormalities. High Performance Liquid Chromatography methods are known to possibly underestimate HbA(1c) value in the presence of this variant. This variant and its glycated form are clearly distinguished on electropherogram but HbJ was responsible for underestimating the true area of HbA(1c). Capillary electrophoresis is a good method for detecting HbJ but does not seem suitable for evaluation of HbA(1C) value in patients in presence of HbJ variant.

Progressivement, à partir de 2003, s’est formé en France un regroupement d’associations professionnelles qui a conquis sa légitimité auprès des pouvoirs publics et des autres professions du livre et a à son actif des résultats législatifs incontestables. Cela mérite une narration, mais aussi et surtout une tentative d’analyse. LE RÉCIT Le 12 novembre 2003, sur proposition du ministre de la Culture Jean-Jacques Aillagon, le gouvernement de Jean-Pierre Raffarin adopta le projet de loi Dadvsi (D...

Enquêter sur la fréquentation, les usages ou l'image des bibliothèques requiert des collectes de données variées, fiables, concertées. Pour ce faire, les professionnels des bibliothèques doivent connaître les spécificités du domaine et les processus généraux de la méthodologie des enquêtes. Qu’elle soit confiée à un prestataire extérieur ou réalisée en interne avec les moyens du bord, l'enquête de publics ne s'improvise pas. Elle suppose en effet, en plus d’une phase de préparation minutieuse, le respect d'une démarche rigoureuse. C’est ce dont rend compte ce guide en présentant de façon détaillée et pratique les étapes qui jalonnent le déroulement des études de publics, selon les trois temps de l’enquête : sa préparation, sa réalisation et l’exploitation-communication de ses résultats. Conçu tel un recueil de bonnes pratiques, l’ouvrage s’attache à fournir des éléments méthodologiques précis complétés par des comptes rendus critiques de travaux pilotés ou réalisés par des bibliothécaires aussi bien en bibliothèques universitaires qu’au sein de médiathèques de lecture publique. Coordonné par Christophe Evans, chargé d'études en sociologie au service Études et Recherche de la Bibliothèque publique d’information, et écrit par des experts rodés à l’exercice de l’enquête de publics, l’ouvrage traite aussi des aspects financiers, juridiques et des conséquences des enquêtes sur la politique générale des établissements.

L'enjeu de la communication en direction des élus, des décideurs, mais aussi des journalistes, est devenu vital pour les bibliothèques : il s'agit de donner à voir aux tutelles leurs activités, de rendre intelligible leur stratégie de développement, de construire une image institutionnelle forte. De quels moyens dispose la bibliothèque pour faire la preuve du bienfondé de son existence ? Comment communiquer en direction d'un élu municipal ou régional, d'un responsable politique de la bibliothèque ? Que peut apporter une bonne collaboration avec des journalistes, avec les partenaires naturels ou hiérarchiques au sein de l'université ou de la collectivité territoriale ? Comment utiliser à bon escient les méthodes du lobbying et du marketing, ou l'emploi des réseaux sociaux ? Voilà quelques-unes des questions abordées ici. Une quinzaine d'auteurs d'horizons divers (des sociologues, des enseignants, des journalistes, des bibliothécaires, des responsables de communication…) nous font part de leurs propres expériences, donnent des conseils méthodologiques et des outils fort utiles, en proposant de nombreux exemples et des mises en situation. Auteur de plusieurs ouvrages dans le domaine de la documentation et des sciences de l'information, Jean-Philippe Accart est actuellement directeur des bibliothèques de la Faculté des sciences de l'Université de Genève.

The risk and clinical significance of cardiac iron overload due to chronic transfusion varies with the underlying disease. Cardiac iron overload shortens the life expectancy of patients with thalassemia, whereas its effect is unclear in those with myelodysplastic syndromes (MDS). In patients with sickle cell anemia (SCA), iron does not seem to deposit quickly in the heart. Our primary objective was to assess through a multicentric study the prevalence of cardiac iron overload, defined as a cardiovascular magnetic resonance T2*8 ECs in the past year, and age older than 6 years. We included from 9 centers 20 patients with thalassemia, 41 with SCA, and 25 with MDS in 2012-2014. Erythrocytapharesis did not consistently prevent iron overload in patients with SCA. Cardiac iron overload was found in 3 (15%) patients with thalassemia, none with SCA, and 4 (16%) with MDS. The liver iron content (LIC) ranged from 10.4 to 15.2 mg/g dry weight, with no significant differences across groups (P = 0.29). Abnormal T2* was not significantly associated with any of the measures of transfusion or chelation. Ferritin levels showed a strong association with LIC. Non-transferrin-bound iron was high in the thalassemia and MDS groups but low in the SCA group (P

22nd Congress of the European-Hematology-Association, Madrid, SPAIN, JUN 22-25, 2017; International audience

The paper presents an overview of the various types of libraries in France, including public libraries, academic and research libraries, other types of libraries, documentation, France’s library policy and the library staff and professional association environment The paper is based on a chapter from Les bibliothèques en Europe, projets, perspectives, (Libraries in Europe, Projects and Prospects) by Frederic Blin and Thierry Claerr, Paris, Editions du Cercle de la Librairie, 2013, with kind permission of the publisher and authors.

In situ NMR spectroelectrochemistry is presented in this study as a useful hybrid technique for the chemical structure elucidation of unstable intermediate species. An experimental setting was designed to follow the reaction in real time during the experimental electrochemical process. The analysis of (1)H NMR spectra recorded in situ permitted us (1) to elucidate the reaction pathway of the electrochemical oxidation of phenacetin and (2) to reveal the quinone imine as a reactive intermediate species without using any trapping reaction. Phenacetin has been considered as hepatotoxic at high therapeutic amounts, which is why it was chosen as a model to prove the applicability of the analytical method. The use of 1D and 2D NMR experiments led to the elucidation of the major species produced from the oxidation process. We demonstrated that in situ NMR spectroelectrochemistry constitutes a fast way for monitoring unstable quinone imines and elucidating their chemical structures.

Betaine 30 is known for the extraordinary solvatochromism of its visible absorption band that goes from λ=882 nm in tetrachloromethane to λ=453 nm in water (Δλ=-429 nm). This large blueshift partly originates from a dramatic decrease of the dipole moment upon excitation. Despite several decades of research, experimental works still disagree on the exact value of the excess dipole moment, the orientation of the dipole moment of the excited-state, the role and amplitude of the change of the polarisability upon excitation as well as on the gas-phase excitation energy. In this work, we present an in-depth theoretical investigation. First, we carefully tested several levels of theory on the model system and next calculated the electric properties of betaine 30 at the CC2 level. Our best estimates are Δμ=-7 D for the excess dipole moment, that is, a significant decrease but no change of direction, a Δα value of -120 a.u. and a gas-phase vertical excitation energy of 1.127 eV. The implicit solvation models are able to reproduce the experimental trends, with large correlation coefficients for non-hydrogen-bond-donating solvents, the smallest root-mean-square deviation error being reached with the vertical excitation model (VEM). The explicit effective fragment potential method combined with time-dependent density functional theory (TD-DFT) in a QM/MM framework provides accurate estimates for hydrogen-bond-donating solvents, whereas the addition of a dispersion correction is needed to restore the correct solvatochromic direction in tetrachloromethane.

International audience; The synthesis of two unprecedented series of dissymmetric molecular tweezers, with usnic acid, phenanthrene, or substituted naphthalimide arms as pincers, is described. Their association ability with the 2,4,7-trinitrofluorenone guest molecule has been quantified through NMR experiments in CD2Cl2 solution. Density Functional Theory calculations, including dispersion terms, have been carried out and rationalize both the conformational and the complexation mode behaviors of these new tweezers. With a naphthalimide and an usnic acid arms, the U-tweezer series indeed appears to behave as molecular tweezers. Conversely, in the P-tweezer series, involving a naphthalimide and a phenanthrene arm, the selected theoretical approach indicates that external complexes are more stabilized than the internal tweezed structures, corroborating experimental evidence of qualitatively different behaviors of the two series of tweezers.

International audience; The present contribution constitutes an extensive density functional theory (DFT) investigation of the nonlinear optical (NLO) properties of a large number of molecules belonging to the azobenzene and azothiophene families of photochromic compounds which can act as NLO switches. Toward the design of systems simultaneously presenting both large total nonlinear response values, beta(tot), and large contrast, beta(ratio), between the cis and trans isomers, we have focused not only on the monomers but also on azobenzene dimers, the latter containing two N=N bonds along the molecular backbone. After it was established that the inclusion of implicit solvation is not important in drawing qualitative conclusions on the NLO switching ability for the investigated systems, gas-phase calculations have shown that for the asymmetric pushpull azobenzene and azothiophene candidates, the combination of strong donating groups such as NPh2, N(Ph-OMe)(2), and N(Ph-NMe2)(2) with the dicyanoethene group CH=C(C=N)(2) as an acceptor delivers large ?trans (150-217 x 10(-30) esu) and non-negligible beta(cis) (18-55 x 10(-30) esu) values as well as substantial contrast, beta(ratio) (3.9-8.7). For the investigated double azobenzenes, it is found that, with a careful choice of donor and acceptor groups, the contrast, beta(ratio), can be significantly increased compared to that of the monomers while maintaining large beta values that facilitate their detection with standard experimental techniques (e.g., electric-field-induced second-harmonic generation). Our results set the stage on which further theoretical and experimental studies can be based in the search for efficient and versatile NLO switches.

Although dehydroepiandrosterone (DHEA) is widely used in the elderly to prevent some adverse effects of ageing, possible deleterious side effects have not been fully assessed. We evaluated the direct actions of DHEA and DHEA sulphate on angiogenesis, a critical event in pathologies that are common in the elderly (cancer, atherosclerosis, inflammation… etc.). At physiological concentrations found in human plasma following DHEA therapy (1–50 nM), DHEA had no action on angiogenesis in vitro. In contrast, higher concentrations of DHEA (10–100 μM), which can be found in tissues after local administration or storage, inhibited in vitro endothelial cell proliferation (blockage in G2/M), migration and capillary tube formation and in vivo angiogenesis in the Matrigel plug assay. This inhibition might be due to a decreased glucose-6-phosphate dehydrogenase activity and to a modification of the tubulin network involved in cell proliferation and migration. The sulphate ester form of DHEA had no effect on angiogenesis.