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La polypathologie touche 70 % des personnes âgées de 65 ans et plus, augmentant considérablement le risque de complications graves. Associée à la polypathologie, la polypharmacie accroît le risque d’interactions médicamenteuses, d’effets indésirables, d’hospitalisations, de chutes, de détérioration de la qualité de vie et de décès. Face à ces enjeux, notre centre hospitalier a répondu à l’appel du projet « OPTIMEDOC » de l’OMEDIT et de l’ARS Normandie. Ce projet se concentre sur l’optimisation des prescriptions médicamenteuses chez les personnes âgées et vise à renforcer les pratiques professionnelles communes entre la ville et l’hôpital.

ABSTRACTObserving system experiments have been carried out with two operational ocean data assimilation systems to assess the impact of assimilating satellite sea surface salinity (SSS) data. The SSS data reduces the errors in tropical Pacific salinity by 4% and 8% in the Met Office and Mercator Ocean systems respectively with an impact down to about 50 m depth on average. Salinity errors were reduced by up to 30% in the tropical Atlantic in both systems. There were significant reductions in near-surface temperature and sea level anomaly errors in both the central tropical Pacific and Amazon outflow regions in the Met Office system. The experiment results and characteristics of the operational ocean forecasting systems lead to a new set of requirements for satellite salinity data. The product accuracy required to significantly improve real-time ocean analysis and forecasts should be less than 0.2 pss at a resolution of at least 50 km for daily products. Improvements to spatial resolution down to the order of 10 km would represent an even more significant breakthrough. To be assimilated in near-real time, products should be available within 24 h and estimates of the systematic and random components of the uncertainty should be provided with each measurement.

Assessing the exposure of adults to magnetic field is a central point in the context of epidemiological studies. The EXPERS study is the first study at national scale in Europe with measurements of personal exposure to extremely low frequency magnetic fields, involving 1046 French adults with 24 h personal measurements. The proportion of adults with a 24 h AM of ≥ 1 µT was 2.1% for all adults and 0.3% for adults for which no alarm clock was identified, as this requirement of the measurement protocol was sometimes not respected. The alarm clocks were the main variable linked to the adults’ exposure measurements. The vicinity of the home to a high voltage power line increased the magnetic field exposure. However, only 1.7% of the adults were living close to a 63 to 400 kV overhead line, and only one of them had a personal exposure ≥ 1 μT with an AM of 1.1 μT. The exposure of adults was also correlated with some characteristics of the home and its environment, and some durations of activities, such as the duration of work and the duration in rail transport. The distribution of adults’ personal exposure was significantly different from the distribution of exposure during sleep, and from the distribution of exposure assessed from measurements during sleep and work. This highlights the complexity of the exposure assessment in epidemiological studies.

HPLC-MS analysis revealed the presence of an unreported peptide in the extract of the marine sponge Neopetrosiasp. Its structure was determined as a tripeptide, named neopetromin (1), composed of two tyrosine and one tryptophan residues with a heteroaromatic C–N cross-link between side chains. The absolute configuration of amino acids was determined using Marfey’s method after ozonolysis and hydrolysis of 1. Compound 1promoted vacuole fragmentation in an actin-independent manner in tobacco BY-2 cells.

Les chimiothérapies administrées en hôpital de jour (HDJ) sont consécutives à une planification anticipée et bihebdomadaire des patients par les IDE. Cette planification est toujours discordante avec les durées des protocoles paramétrés.

•Pour la rétrocession, 6 never eventsont été définis.•La rétrocession est une activité généralement rentable.•Certaines situations mises en lumière rendent cette activité fortement déficitaire.

This study is devoted to the synthesis and the characterization of porous metal oxide microsphere from metal loaded ion exchange resin. Their application concerns the fabrication of uranium-americium oxide pellets using the powder-free process called Calcined Resin Microsphere Pelletization (CRMP). Those mixed oxide ceramics are one of the materials envisaged for americium transmutation in sodium fast neutron reactors. The advantage of such microsphere precursor compared to classical oxide powder is the diminution of the risk of fine dissemination which can be critical for the handling of highly radioactive powders such as americium based oxides and the improvement of flowability for the filling of compaction chamber. Those millimetric oxide microspheres incorporating uranium and americium were synthesized and characterizations showed a very porous microstructure very brittle in nature which occurred to be adapted to shaping by compaction. Studies allowed to determine an optimal heat treatment with calcination temperature comprised between 700–800 ∘C and temperature rate lower than 2 ∘C/min. Oxide Precursors were die-pressed into pellets and then sintered under air to form regular ceramic pellets of 95% of theoretical density (TD) and of homogeneous microstructure. This study validated thus the scientific feasibility of the CRMP process to prepare bearing americium target in a powder free manner.

Four new sesquiterpenes, lamellodysidines A and B, O,O-dimethyllingshuiolide A, and 11-epi-O,O-dimethyllingshuiolide A (1–4), were obtained from the marine sponge, Lamellodysidea herbacea, collected in Indonesia. Their planar structures were elucidated by analysis of spectroscopic data. The absolute configurations of the new compounds were determined by the calculated ECD spectra. Compound 1has a unique carbon framework, and 2is a new nitrogenous sesquiterpene.

Three new furanosesterterpene tetronic acids, sulawesins A–C (1–3), were isolated from a Psammociniasp. marine sponge, along with the known compounds ircinins-1 (4) and -2 (5). Although ircinins-1 and -2 were previously isolated as (+)- or (−)-enantiomers from marine sponges, we isolated them as enantiomeric mixtures. Sulawesins A and B possess a new carbon skeleton with a 5-(furan-3-yl)-4-hydroxycyclopent-2-enone moiety and were also found to be diastereomeric mixtures of four isomers by an HPLC analysis with a chiral-phase column. Sulawesin C has a dimeric structure of ircinin-1 and is the first dimer in this family. USP7, a deubiquitinating enzyme, is an emergent target of cancer therapy, and the isolated compounds inhibited USP7 with IC50values in the range of 2.7–4.6 μM.

Six new spongian diterpene derivatives, ceylonins A–F (1–6), were isolated from the Indonesian marine sponge Spongia ceylonensisalong with spongia-13(16),14-dien-19-oic acid (7). They contained three additional carbons in ring D to supply an ether-bridged bicyclic ring system. Their structures were elucidated by analyzing NMR spectroscopic data and calculated ECD spectra in comparison to experimental ECD spectra. The bicyclic ring system may be derived from the major metabolite 7and a C3unit (an acrylic acid equivalent) through an intermolecular Diels–Alder reaction, which was experimentally supported by the formation of 1–6from 7and acrylic acid. The inhibitory effects of the isolated compounds on the RANKL-induced formation of multinuclear osteoclasts in RAW264 macrophages were examined.

La gemcitabine est désormais commercialisée en préparation prête à l’emploi. À l’unité centrale des préparations (UPC), 5500 fabrications par an sont réalisées dont près de 120 poches de gemcitabine.

Seven new spongian diterpenes, ceylonamides A–F (1–6) and 15α,16-dimethoxyspongi-13-en-19-oic acid (7), were isolated from the Indonesian marine sponge Spongia ceylonensisalong with eight known spongian diterpenes, 8–15. Compounds 1–6were determined to be nitrogenous spongian diterpenes. The isolated compounds were examined for the inhibition of RANKL-induced osteoclastogenesis in RAW264 macrophages. Ceylonamide A (1) exhibited the most potent inhibitory activity with an IC50value of 13 μM, followed by ceylonamide B (2) (IC50, 18 μM). An examination of the structure–activity relationships of the isolated compounds revealed that the position of the carbonyl group of the γ-lactam ring and bulkiness of the substituent at its nitrogen atom were important for inhibitory activity.

This study is devoted to the synthesis and the characterization of porous metal oxide microsphere from metal loaded ion exchange resin. Their application concerns the fabrication of uranium-americium oxide pellets using the powder-free process called Calcined Resin Microsphere Pelletization (CRMP). Those mixed oxide ceramics are one of the materials envisaged for americium transmutation in sodium fast neutron reactors. The advantage of such microsphere precursor compared to classical oxide powder is the diminution of the risk of fine dissemination which can be critical for the handling of highly radioactive powders such as americium based oxides and the improvement of flowability for the filling of compaction chamber. Those millimetric oxide microspheres incorporating uranium and americium were synthesized and characterizations showed a very porous microstructure very brittle in nature which occurred to be adapted to shaping by compaction. Studies allowed to determine an optimal heat treatment with calcination temperature comprised between 700–800 °C and temperature rate lower than 2 °C/min. Oxide Precursors were die-pressed into pellets and then sintered under air to form regular ceramic pellets of 95% of theoretical density (TD) and of homogeneous microstructure. This study validated thus the scientific feasibility of the CRMP process to prepare bearing americium target in a powder free manner.

Under GODAE OceanView the operational ocean modelling community has developed a suite of global ocean forecast, reanalysis and analysis systems. Each system has a critical dependence on ocean observations – routinely assimilating observations of in-situtemperature and salinity, and satellite sea-level anomaly and sea surface temperature. This paper demonstrates the value and impact of ocean observations to three global eddy-permitting forecast systems, one global eddy-permitting model-independent analysis system, one eddy-resolving reanalysis system, and two seasonal prediction systems. All systems have been used to assess the impact of Argo profiles, including scenarios with no Argo data, and a degraded Argo array – unanimously concluding that Argo is a critical data set – the most critical for seasonal prediction, and as critical as satellite altimetry for eddy-permitting applications. Most systems show that TAO data are as important as Argo in the tropical Pacific, and that XBT data have an impact that is comparable to other data types in the vicinity of XBT transects. It is clear that no currently available data type is redundant. On the contrary, the components of the global ocean observing system complement each other remarkably well, providing sufficient information to monitor and forecast the global ocean.

Two new manzamine alkaloids, acantholactam (3) and pre-neo-kauluamine (4), were isolated from the marine sponge Acanthostrongylophora ingensalong with manzamine A (1) and neo-kauluamine (2). Acantholactam contains a γ-lactam ring N-substituted with a (Z)-2-hexenoic acid moiety and is proposed to be biosynthetically derived from manzamine A by oxidative cleavage of the eight-membered ring. Compound 4was converted to the dimer 2during storage, suggesting nonenzymatic dimer formation. Among the four isolated compounds, 1, 2, and 4showed proteasome inhibitory activity.

Two new dimeric sterols, manadosterols A (1) and B (2), were isolated from the marine sponge Lissodendryx fibrosacollected in Indonesia. The two compounds are comprised of two sulfonated sterol cores connected through the respective side chains. Manadosterols A (1) and B (2) inhibited the Ubc13-Uev1A interaction with IC50values of 0.09 and 0.13 μM, respectively. They are the second and third natural compounds showing inhibitory activities against the Ubc13–Uev1A interaction and are more potent than leucettamol A (IC50, 106 μM), the first such inhibitor, isolated from another marine sponge.

This Microreview covers some general strategies for the preparation of uronic acid residues and their incorporation into anionically charged oligosaccharides. Two distinct strategies can be recognized: (1) glycosylation followed by oxidation, and (2) oxidation of the monosaccharide building blocks followed by glycosylation. Examples of both strategies are discussed, with a focus on the advantages and disadvantages of the respective strategies. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Motivation:The integrated dynamical modelling of mixed metabolic/genetic networks constitutes one of the challenges of systems biology. Furthermore, as most of available data about genetic and metabolic regulations are qualitative, there is a pressing need for rigorous qualitative mathematical approaches.Results:On the basis of two established formalisms, the logical modelling of genetic regulatory networks and the Petri net modelling of metabolic networks, we propose a systematic approach for the modelling of regulated metabolic networks. This approach leans on previous work defining a systematic procedure to translate logical regulatory graphs into standard (discrete) Petri nets (PNs). This approach is illustrated by the qualitative modelling of the biosynthesis of tryptophan (Trp) in Escherichia coli, taking into account two types of regulatory feedbacks: the direct inhibition of the first enzyme of the pathway by the final product of the pathway, and the transcriptional inhibition of the Trp operon by the Trp–repressor complex. On the basis of this integrated PN model, we further indicate how available dynamical analysis tools can be applied to obtain significant insights in the behaviour of the system.Availability:The software GINsim for the logical modelling of genetic regulatory networks together with the PN model of the regulated Trp biosynthesis pathway are available at: http://gin.univ-mrs.fr/GINsim.Contact:chaouiya@ibdm.univ-mrs.fr

The effectiveness in terms of yield and stereoselectivity of (phenylsulfinyl)piperidine (BSP) 1b/ trifluoromethanesulfonic anhydride (Tf2O) and diphenyl sulfoxide (DPS) 1c/Tf2O-mediated glycosidations of 2-azido-3-O-benzyl-4,6-O-benzylidene-2-deoxy-D-thiomannosides 2a/b is described. Application of the BSP/Tf2O activator led to productive condensations using p-methoxyphenyl 2-azido-3-O-benzyl-4,6-O-benzylidene-2-deoxy-D-thiomannoside (2b) as a donor, while the more powerful DPS/Tf2O combination gave similar results using both p-methoxyphenyl and phenyl 2-azido-3-O-benzyl-4,6-O-benzylidene-2-deoxy-D-thiomannosides 2a/b. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

The first synthesis of the trisaccharide repeating unit of the acidic polysaccharide of the bacteriolytic complex of lysoamidase is presented. The construction is based on a linear glycosylation strategy that starts from the reducing end and employs thio‐ and selenoglycosides in a highly stereoselective manner by a single set of activation conditions. The thus‐formed trisaccharide is selectively deprotected and oxidised, after which a final deprotection step furnishes the desired repeating unit.

This tutorial reviewsurveys the use of thioglycosides in the development of sequential glycosylation methodologies, with a focus on chemoselective, orthogonal and iterative glycosylation strategies reported since the beginning of this century. Both fundamental aspects of glycosidic bond formation and ingenious state-of-the-art methodologies are presented.

The biological and dynamical importance of feedback circuits in regulatory graphs has often been emphasized. The work presented here aims at completly describing the dynamics of isolated elementary regulatory circuits. Our analytical approach is based on a discrete formal framework, built upon the logical approach of R. Thomas.
Given a regulatory circuit, we show that the structure of synchronous and asynchronous dynamical graphs depends only on the length of the circuit (number of genes) and on its sign (which depends on the parity of the number of negative interactions). This work constitutes a first step towards the analytical characterisation of discrete dynamical graphs for more complex regulatory networks in terms of contributions corresponding to their embedded elementary circuits.
Contact: remy@iml.univ-mrs.fr

A general, modular strategy for the first completely stereoselective synthesis of defined heparin oligosaccharides is described. Six monosaccharide building blocks (four differentially protected glucosamines, one glucuronic and one iduronic acid) were utilized to prepare di- and trisaccharide modules in a fully selective fashion. Installation of the α-glucosamine linkage was controlled by placing a conformational constraint on the uronic acid glycosyl acceptors thereby establishing a new concept for stereochemical control. Combination of disaccharide modules to form trans-uronic acid linkages was completely selective by virtue of C2 participating groups. Coupling reactions between disaccharide modules exhibited sequence dependence. While the union of many glucosamine uronic acid disaccharide modules did not meet any problems, certain sequences proved not accessible. Elaboration of glucosamine uronic acid disaccharide building blocks to trisaccharide modules by addition of either one additional glucosamine or uronic acid allowed for stereoselective access to oligosaccharides as demonstrated on the example of a hexasaccharide resembling the ATIII-binding sequence. Final deprotection and sulfation yielded the fully synthetic heparin oligosaccharides.

A general, modular strategy for the first completely stereoselective synthesis of defined heparin oligosaccharides is described. Six monosaccharide building blocks (four differentially protected glucosamines, one glucuronic and one iduronic acid) were utilized to prepare di‐ and trisaccharide modules in a fully selective fashion. Installation of the α‐glucosamine linkage was controlled by placing a conformational constraint on the uronic acid glycosyl acceptors thereby establishing a new concept for stereochemical control. Combination of disaccharide modules to form trans‐uronic acid linkages was completely selective by virtue of C2 participating groups. Coupling reactions between disaccharide modules exhibited sequence dependence. While the union of many glucosamine uronic acid disaccharide modules did not meet any problems, certain sequences proved not accessible. Elaboration of glucosamine uronic acid disaccharide building blocks to trisaccharide modules by addition of either one additional glucosamine or uronic acid allowed for stereoselective access to oligosaccharides as demonstrated on the example of a hexasaccharide resembling the ATIII‐binding sequence. Final deprotection and sulfation yielded the fully synthetic heparin oligosaccharides.

A mutant glgC gene contained in a 10.9-kb PstI fragment was cloned from the Escherichia coli B strain SG5 via colony hybridization by using a wild-type glgC probe. The altered allosteric properties of the expressed ADPglucose synthetase were found to result from the conversion of proline to serine at amino acid residue 295.

Assessments of oedema and decrease in hand strength are useful for patients with a hand lesion. This study examined the asymmetry of the arms and determined the estimates of the unknown prior to lesion values for hand volume, grip strengths assessed with a Jamar dynamometer (GSJ) and a Collins dynamometer (GSC), and pinch strength with a Jamar pinch gauge (PS) in 100 healthy working people. Hand volume, GSJ, GSC, and PS of the dominant hand were respectively 3.6 ± 4.1%, 6.6 ± 9.2%, 11.7 ± 11.2%, and 8.0 ± 13.2% higher than those of the non-dominant hand (p < 0.001). Very good estimates were obtained with the values of the contralateral arm for all the indices studied. The correlation coefficient equalled 0.95 for hand volume, 0.91 for GSJ, 0.83 for GSC, and 0.72 for PS. These estimates allow us to evaluate the evolution of oedema and hand strengths in patients with hand injury, especially to determine whether they could return to work as they are mostly manual workers with demanding jobs.

Edema and hand strength measurements are useful for the recovery assessment of patients with a hand lesion. This work determined and compared estimates of hand volume, grip strengths (measured with a Jamar and a Collins dynamometer), and pinch strength (with a Jamar pinch gauge) in terms of sex and age with or without anthropometric indices in healthy working people. The sample included 100 subjects from within the staffs of two rehabilitation centres. For both grip strengths, multiple linear regression models including body height, weight, and arm muscle area were very good (multiple correlation coefficient R of about 0.84) and clearly better than those obtained with sex and age only. For pinch strength, the best estimate was obtained with sex and arm muscle area (R of 0.76); for hand volume, the model with sex, body height, and weight provided the best result (R of 0.93). These findings suggested that anthropometric indices easy to measure must be taken into account to estimate hand volume and hand strengths.

The nucleocapsid protein NCp7 of the human immunodeficiency virus type 1 contains two zinc fingers of the CX2CX4HX4C type, flanked by several basic residues, and plays a major role in viral infectivity. Thus, NCp7 was shown to promote annealing of the tRNA3Lys to the primer binding site, a key step in reverse transcription. However, previous in vitro experiments were unable to clarify the role of the zinc fingers in this process, due to nucleic acid aggregation induced by the basic N- and C-terminal domains of NCp7. We show here that deletion of these sequences in (12-53)NCp7 strongly reduces the formation of aggregates and allows a direct visualization of the binary or ternary complexes between NCp7 and nucleic acids by gel electrophoresis. (12-53)NCp7 is able to induce hybridization of the 33P tRNA3Lys and the human immunodeficiency virus type 1 viral RNA-(77-257), which contains the primer binding site. Modification of the proximal zinc finger conformation in Cys23(12-53)NCp7 led to a large reduction in this hybridization process, while replacement of Trp37 by Leu in the distal zinc fingers resulted in a complete absence of annealing activity. These data account for the in vivo loss of viral infectivity following these mutations and emphasize the critical role of the structure of the zinc finger domain of NCp7. This could facilitate a rational approach to new antiviral agents directed toward NCp7.

A new technique for tissue microdissection is described. This procedure, using an u.v.-laser micropreparation instrument, overcomes the extremely timeconsuming manual preparation. The u.v.-laser micropreparation design allows fast, precise, reproducible and smear-contamination-free tissue microdissection. The preparation of the tissue sample can be programmed by tracing out the area to be sampled with a non-destructive 0.5 m W He-Ne-laser aiming-beam. The trace is stored in a small electronic unit, which then guides the motor-driven stepping stage on the microscope in the actual dissection run with the u.v.-laser. The laser power is adjustable in the range 4 to 40 kW and controlled by a photo diode displayed on an oscilloscope screen. In the tissue slice, prepared according to Lowry, an unlimited number of cells or tissue compartments can be dissected and afterwards weighed. The procedure described offers a broader use of the quantitative microhistochemical techniques of Lowry and of Neuhoff.

Zusammenfassung Nachdem durch Versuche festgestellt war, daß Kreatinin durch reines Aluminium-hydroxyd nicht, dagegen der größte Teil der die Fleischextraktlösungen und die Fleischauszüge färbenden Substanzen adsorbiert wird, wurden unter Verwendung von Aluminiumhydroxyd reinst, Merck, Filterkerzen hergestellt, die teils farblose, teils nur schwach gelb gefärbte Filtrate der genannten Lösungen bzw. Auszüge gaben. Mit diesen Lösungen bzw. Auszügen ließ sich die colorimetrische Kreatininbestimmung leicht und ohne Schwierigkeiten in verhältnismäßig kurzer Zeit ausführen. Durchweg wurden hierbei etwas höhere Werte als nach der Methode des Schweizer Lebensmittelbuches erhalten.

Zusammenfassung 1.Die Bestimmung der Größe der relativen und absoluten Oberflächenspannung bei den von uns untersuchten Weißweinen ergab, daß die entsprechenden Werte des Weines selbst und des alkoholischen Destillates nur wenig voneinander abweichen, sowie daß die gefundenen Unterschiede nur unerheblichen Schwankungen unterliegen. Mit Hilfe der oben näher erläuterten Formel war es möglich, den Alkoholgehalt der Weine in guter Übereinstimmung mit den durch Destillation ermittelten und nach der Tabelle von K. Windisch errechneten Werten aus der Größe der absoluten Oberflächenspannung der Weine zu bestimmen.2.Der mittlere Arsengehalt der Weine wurde zu 0,49mg As.., der an Kupfer zu 1,01mg Cu.. im Liter gefunden.3.Sowohl die Weine selbst als auch die alkoholischen Destillate besitzen gegenüber dem von Tillmans und seinen Mitarbeitern als Reduktionsindicator bei der Untersuchung von Lebensmitteln angewandten 2,6-Dichlorphenolindophenol ein nur sehr geringes Reduktionsvermögen, woraus man für die Weine selbst auf einen nur sehr geringen Gehalt an Vitamin C schließen kann, dem praktisch keine Bedeutung beizumessen ist.

Zusammenfassung 1.In den von uns untersuchten handelsüblichen Glykogenen konnte in allen Fällen das Vorhandensein stickstoffhaltiger Verbindungen von zum Teil proteinartiger Natur nachgewiesen werden, wenn auch ihre Mengen nur gering sind. Diese Mengen besitzen aber, wie die Versuche von Uhlenhuth und Remy gezeigt haben, antigene Eigenschaften.2.Der Gehalt an Mineralstoffen zeigte bei den einzelnen Glykogenen recht erhebliche Schwankungen, von 0,238% bis 3,553%, absolut reine Präparate der Zusammensetzung (C6H10O5)n lagen in keinem Falle vor. Bei den Präparaten H und Sd fand ich die gleiche spezifische Drehung wie sie Gutin Gruzewska bei seinen zahlreichen Untersuchungen von Glykogenpräparaten feststellte, nämlich+196,57° im Mittel. Bei den beiden übrigen Präparaten waren die Werte ein wenig abweichend, mit einer Differenz von -1,07° bzw. -3,25°.3.Die Werte der nephelometrischen Messungen von Lösungen gleichen Konzentrationsgrades lassen erkennen, daß die Teilchengröße bei den einzelnen Glykogenen eine recht verschiedene war.

Zusammenfassung

Zusammenfassung

For certain toroidal closed surfaces (M-and-S surfaces) of a ?= 1 plasma without resultant azimuthal currents, theory predicts equilibrium. We have produced a toroidal plasma by means of a toroidal theta pinch discharge (Bmax= 10 kG, frequency of main discharge, 30 kHz). By adding periodic, additional windings we corrugate the azimuthal field and thus approach M-and-S surfaces. Smear-camera and image-converter investigations of discharges in helium and hydrogen show that in approaching the theoretical surface we approximate equilibrium. This could be observed over time intervals more than three times as long as the drift time in a purely azimuthal field under otherwise identical conditions. The electron densities are in the range of 1015to 1017cm?3, the temperature 5 to 10 eV and beta (?) between 0.1 and 1.