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Clinical trials investigating drugs for the acute treatment of hereditary angioedema attacks have assessed many different outcomes. This heterogeneity limits the comparability of trial results and may lead to selective outcome reporting bias and a high burden on trial participants.

The trapeziometacarpal prosthesis is mostly used in Europe to treat osteoarthritis of the basal joint of the thumb. Its supposed benefits are that it restores the length of the thumb, improves strength, function and mobility while reducing recovery time compared to other surgical treatments. However, previous reviews of the literature could not confirm these assumptions. This article provides an updated systematic review to help answer to these questions through a methodical statistical analysis and to quantify the two main complications, namely failure and deep infection. To achieve these aims, a selection of articles including implant case series was done in the Medline database based on specific criteria. Data about pain, function, strength, infection, and failure were compiled and a statistical analysis was performed. Results show a fast recovery in terms of pain and function but the positive effect on strength seems limited. The failure rate represented by the revision rate is high and the deep infection rate is fairly low. Randomized controlled studies are needed to obtain reliable data to compare the prosthesis to other surgical treatments.

Psychological and neurobiological markers in individuals with gambling disorder (GD) could reflect transdiagnostic vulnerability to addiction or neuroadaptive consequences of long-term gambling. Using an endophenotypic approach to identify vulnerability markers, we tested the biological relatives of cases with GD. Male participants seeking treatment for GD (n= 20) were compared with a male control group (n= 18). Biological siblings of cases with GD (n= 17, unrelated to the current GD group) were compared with a separate control group (n= 19) that overlapped partially with the GD control group. Participants completed a comprehensive assessment of clinical scales, neurocognitive functioning, and fMRI of unexpected financial reward. The GD group displayed elevated levels of self-report impulsivity and delay discounting, and increased risk-taking on the Cambridge Gamble Task. We did not observe impaired motor impulsivity on the stop-signal task. Siblings of GD showed some overlapping effects; namely, elevated impulsivity (negative urgency) and increased risk-taking on the Cambridge Gamble Task. We did not observe any differences in the neural response to win outcomes, either in the GD or sibling analysis compared with their control group. Within the GD group, activity in the thalamus and caudate correlated negatively with gambling severity. Increased impulsivity and risk-taking in GD are present in biological relatives of cases with GD, suggesting these markers may represent pre-existing vulnerability to GD.

Depuis 2019, un programme wallon de biomonitoring humain (BMH-Wal), financé par le Gouvernement wallon, a pour objectif d’établir les niveaux de contamination de la population générale à diverses substances chimiques. L’objectif ici est de présenter les résultats des dosages de perfluorés, pesticides organochlorés et PCB sur une population d’adultes, adolescents et nouveau-nés.

The mobility of mercury (Hg), particularly organic Hg, has been studied in the Thur river basin using an ultra-sensitive and specific analytical equipment (High Performance Liquid Chromatography (HPLC) with on-line CVAFS detection). The Thur river, sub-tributary of the Rhine river is polluted by mercury since the beginning of the 20th century because of industrial effluents from chlorine and soda industry. This study allows to determine in different environmental compartments (soils and river sediments) the total mercury contents (THg) and, for the first time in such an industrialized catchment, the methyl mercury concentrations (MeHg). The ratio between MeHg and THg concentrations is higher in the grassland soils than in the industrial and alluvial soils even if MeHg and THg contents are higher in these latters. The highest MeHg/THg ratios can be observed for lowest C/N ratios and slightly acidic soils. MeHg/THg ratio is very low in the industrial channel despite high MeHg and THg concentrations. For river sediments, MeHg/THg ratios are higher in the suspended matters than in the bottom sediments. These first results are very helpful to better understand the transformation of Hg species in the different compartments and the processes of Hg transfer from one compartment to another.

In an area where human activities (mainly chlorine and soda industry) have been releasing Hg in the environment, natural and anthropogenic contributions to mercury contents in soils and stream sediments could be assessed using mercury concentrations in the deepest soil horizons and in the stream bottom sediments located upstream from the industrial effluents. Hg concentrations have been measured by Cold Vapor Atomic Fluorescence Spectrometry. The regional natural background level could be estimated to $0.079\pm0.005$Fg.g--1from, he Hg contents in the deepest soil horizons (Hg deriving ftom rock weathering) which appear to be proportional to the organic matter percentage. Hg concentrations in stream sediments vary between $0.108\pm0.001$and $8.42\pm0.44$gg.g-1. The mercury enrichment factor (EF(Hg)) that could be calculated show that the anthropogenic contribution is not negligible, even in the upper part of the basin. The relationship between organic matter percentage and Hg content in the deepest soil horizons allows us to estimate by difference the anthropogenic contribution (18 to 86% of the total Hg content) in the upper stream sediments. This contribution could probably be attributed to regional atmospheric deposition of Hg.

Résumé: Introduction: L’analyse des plaintes est un élément essentiel de la démarche qualité dans un service d’urgence. Notre étude a pour objectif de recenser les lettres de plaintes, d’analyser leur contenu et les réponses. Méthodologie: Il s’agit d’une étude rétrospective monocentrique des lettres de plaintes reçues entre 2002 et 2007. Les données concernant l’épidémiologie, la typologie des doléances, les buts recherchés, les réponses apportées et les suites ont été analysées. Résultats: Cent lettres de plaintes ont été étudiées entre 2002 et 2007, correspondant à une incidence globale de 5,6/10 000 passages, avec des variations selon les années entre 3,5 et 8,6/10 000. Les plaignants étaient le plus souvent un parent (47 %) ou le patient (38 %). Dans ces 100 lettres, 153 doléances étaient recensées. Elles étaient d’ordre médical (50 %), organisationnel ou relationnel (44 %), ou divers (6 %). Les plus fréquentes concernaient les erreurs diagnostiques (32), les prises en charge non appropriées (23), le comportement du personnel (21) et les atteintes à la dignité (14). Le signalement (71 %) était le but le plus recherché. Une lettre de réponse était adressée à 78 % des plaignants. Un tiers environ des erreurs diagnostiques ont été reconnues. Quatre-vingt-neuf plaintes n’ont pas eu de suite. Neuf conciliations, une indemnisation, une procédure au tribunal administratif ont eu lieu. Conclusion: L’incidence des plaintes aux urgences est faible. Elles sont autant médicales qu’organisationnelles ou relationnelles. Elles sont un indicateur de dysfonctionnement qui doit être utilisé pour améliorer la prise en charge des patients.

The photocatalytic inactivation of two E. coli strains, a wild strain and a hyper-adherent strain, was examined using two industrial TiO2photocatalysts, Degussa P25 and Millennium PC-500, either suspended or supported. The cultivability of both strains and the formation of ammonium ions and of organic acid during their inactivation were determined. The inactivation of E. coli using different initial concentrations of bacteriae follows an apparent first order kinetics at concentrations below 107CFU/mL, whereas an initial lag period was observed above this value, suggesting that the first attack of photo-generated active species on microorganisms does not lead to inactivation. The inactivation of both E. coli strains is strongly influenced by the presence of curli on bacteria membrane. Whereas titania Degussa P-25 is slightly more efficient than TiO2Millennium PC-500 to inactivate wild E. coli, the opposite was observed in the inactivation of a hyper-adherent E. coli strain containing curli at its surface. Ammonium and three organic acids (oxalic acid, oxamic acid and fumaric acid) were identified in solution. The different behaviours of both TiO2photocatalysts with respect to both E. coli strains were discussed in term of interactions between the bacteriae and the solid, surface taking into account the IEP (IsoElectricPoint), the particle size, the agglomeration of TiO2particles and the nature of the surface of bacteriae. The efficiency of supported PC-500 is smaller than that of suspended. PC-500 SEM micrographs clearly indicated smaller interactions between bacteriae and the supported photocatalyst particles.

A simple synthetic strategy is described to incorporate a protected diaminedithiol (N2S2) chelator during Fmoc solid-phase synthesis of short peptides. The resulting constructs could be efficiently labeled with technetium-99m (^99mTc). The chelator was assembled at the N-terminus of peptides in a two-step procedure where the deprotected terminal amino group was first reacted with di-Fmoc-diaminopropionic acid (Fmoc-DAP-[Fmoc]-OH). The two protected amino groups were then simultaneously deprotected and subsequently reacted with S-benzoylthiolglycolic acid (TGA) to generate a protected N2S2 chelator. This metal binding site was introduced into di- and tripeptides. Each peptide construct was composed of a C-terminal lysine residue and an N-terminal diaminopropionic moiety modified to create the chelator site. The ε-amino group at the C-terminal lysine was further derivatized with a nitroimidazole group to facilitate cellular retention. The resulting constructs were then cleaved from the resin support, purified, and labeled with [^99mTc]pertechnetate. Six constructs were prepared differing by a single amino acid inserted between the diaminopropionic acid and lysine residues. Optimal labeling yields of >70% were achieved around neutral pH and heating at 75 °C for 10 min. Purified ^99mTc-labeled constructs were found to accumulate in Chinese hamster ovary (CHO) cells in vitro as a function of charge and hydrophobicity.

A saturated solution of tetrazepam in Krebs-Ringer did not affect the contraction force of the isolated diaphragm in vitro significantly during indirect stimulation at frequencies from 10 to 50 Hz. An overdose of crystalline tetrazepam, added to the bath (Krebs-Ringer solution) induced an increase of contraction force of the tetanus at various frequencies, with a maximum at 30 Hz, up to 400% ± 30 (n=4) of the control value. It is suggested that the solubility of tetrazepam in Krebs-Ringer solution is increased by substances released from the muscle. At a concentration of 10^–4 M tetrazepam in Tween 80 (final concentration 0.25%), a comparable increase in contraction force occurred at indirect stimulation with 30 Hz. The maxima occurred at about one hour after exposure and were followed by a gradual decrease. At a stimulation frequency of 70 Hz, a gradual decrease in contraction force of 68% (± 3) (n=4) occurred after 2.5 hours, while the control force (in Tween 80, 0.25% - in order to enhance the solubility of tetrazepam) decreased with 18% (± 6). At a concentration of 10^–5 M, tetrazepam caused an increase in contraction force to about 150% (± 6) at 30 Hz (first stimulation of each cycle), and significant decrease in contraction force of about 20% at 70 Hz. At direct stimulation with 30 Hz the tetanic contraction force was increased as well by 10^–4 M tetrazepam, whereas at 10^–3 M of the benzodiazepine the force was depressed. These in vitro results fit with the muscle relaxation mentioned in a case report (two times 100 mg dose) in relation to 50 mg doses resulting in plasma level with a peak of about 2×10^–6 M reported earlier (1). The results of the study tentatively suggest that the use of tetrazepam in the appropriate dose is more favourable than using diazepam in treating spasms associated with lumbago.

We investigated whether polyphenolic extracts from black tea, green tea or red wine affect azoxymethane (AOM)-induced intestinal carcinogenesis. Male F344 rats were treated 10 times (1 week apart) with AOM (7.4 mg/kg, s.c.) and then allocated into groups receiving black tea, green tea or red wine extracts mixed in the diet at a dose of 50 mg/kg body weight for 16 weeks. In the rats treated with black tea or wine extracts, there were significantly fewer colorectal tumours than in controls (the mean +/- SE number of tumours/rat was 2.54 +/- 1.6 in controls, 1.54 +/- 1.4 in the black tea group, 3.2 +/- 1.9 in the green tea group and 1.63 +/- 1.6 in the wine extract group). Significantly fewer rats in the black tea and wine extract groups had adenomas than in controls (86%, 59%, 90% and 50% of rats in the control, black tea, green tea and wine extract groups, respectively, had adenomas). The tumours from the black tea group and, to a lesser extent, those from the wine group, had a significantly greater apoptotic index than tumours in controls (mean +/- SE apoptotic index: 2.92 +/- 0.25, 4.13 +/- 0.46, 2.88 +/- 0.30 and 3.72 +/- 0.46 in controls, black tea, green tea or wine extract groups, respectively). In contrast, the apoptotic index of the normal mucosa did not vary among groups. These data indicate that black tea and wine extracts, but not green tea extracts, can protect against AOM-induced colon carcinogenesis by a mechanism probably involving increased apoptosis in tumours.

Periodical Density Functional (DFT) calculations were done on a hypothetical 1T-TaTe"2 phase in order to understand why this compound has not yet been synthetized. The combined analysis of the density of states and of the crystal orbital overlap populations have disclosed bands interaction that could be at the origin of the non existence of the 1T-TaTe"2 phase.

In this study, we examined the influence of the actions of the halogenated phenylpiperazine LY 165,163 at dopamine D1, D2 and D3 receptors on its 5-HT1A agonist properties in vivo. LY 165,163 displayed marked affinity at striatal rat (r)D2 (pKi = 7.0), cloned rD2 (pKi = 7.3), cloned rD3 (pKi = 8.0), cloned human (h)D2 (pKi = 7.2) and cloned hD3 (pKi = 7.8) receptors, whereas its affinity at striatal rD1 receptors was weak (pKi = 5.7). In contrast, the prototypical 5-HT1A agonist 8-OH-DPAT displayed low affinity at each of these sites (pKi < 5.5). In vivo, LY 165,163 behaved as an antagonist at D2 autoreceptors in enhancing the synthesis of dopamine throughout the brain. Consistently with antagonist properties at postsynaptic D2 receptors, in unilateral substantia nigra-lesioned rats, the rotation elicited by the D2 agonist quinpirole was potently blocked by LY 165,163, whereas that elicited by the D1 agonist SKF 38393 was only weakly inhibited. In addition, LY 165,163 potently evoked prolactin secretion in rats and abolished apomorphine-induced climbing in mice. At native rat 5-HT1A receptors and cloned human 5-HT1A receptors, LY 165,163 (pKi values of 8.7 and 8.9, respectively) mimicked the high affinity of 8-OH-DPAT (pKi values of 9.0 and 9.2). Further, like 8-OH-DPAT, LY 165,163 acted as an agonist in inhibiting the firing of dorsal raphé nucleus neurons, in reducing striatal turnover of 5-HT and in eliciting both hypothermia and corticosterone secretion. However, in contrast to 8-OH-DPAT, LY 165,163 failed to evoke spontaneous tail-flicks (STFs). This difference probably reflects its D2 antagonist properties because the induction of STFs by 8-OH-DPAT was, in contrast to its induction of hypothermia and corticosterone secretion, blocked by the preferential D2 antagonist haloperidol. Moreover, in the presence of quinpirole and in the presence of a further dopaminergic agonist, apomorphine, LY 165,163 did elicit STFs. Further, STFs evoked by LY 165,163 in the presence of apomorphine were abolished by the 5-HT1A antagonists (-)-alprenolol, BMY 7378 and NAN-190. We conclude that LY 165,163 exhibits marked activity at both pre- and postsynaptic dopaminergic D2 (D3 and D1) receptors.(ABSTRACT TRUNCATED AT 400 WORDS)

Chemokines are chemotactic proteins which play a central role in immune and inflammatory responses. Chemokine receptors are members of the seven transmembrane G-protein coupled family and have recently been shown to be involved in the entry of human immunodeficiency virus (HIV) into target cells. To study chemokine endocytosis in detail we have used novel site-specific chemistry to make a fluorescently labeled CC-chemokine agonist (rhodamine-MIP-1alpha) and antagonist (NBD-RANTES). We have also generated a CHO cell line stably expressing a hemagglutinin-tagged version of the CC-chemokine receptor 1 (CCR1), and using these reagents we have examined the receptor-mediated endocytosis of CC-chemokines by confocal microscopy. Our studies reveal that the agonist was internalized and accumulated in transferrin receptor-positive endosomes whereas the antagonist failed to internalize. However, receptor-bound antagonist could be induced to internalize by co-administration of agonist. Analysis of receptor redistribution following chemokine addition confirmed that sequestration was induced by agonists but not by antagonists.

After i.p. injection of ketamine (75 mg/kg) or pentobarbital-Na (40 mg/kg) to rats, there was a rapid, then a steady decrease of the sodium-dependent high affinity choline (HAC) accumulation rate to a minimum. This minimum was followed by a rapid increase (ketamine) or a gradual rise (pentobarbital-Na). Immediately after the rats came out of anaesthesia, the accumulation rate had not yet completely recovered. We suggest the ketamine or pentobarbital-Na induce alterations in central cholinergic systems, i.e. changes in choline uptake and incorporation into acetylcholine. It is conceivable that interactions of cholinesterase inhibitors or corticosteroids with the anaesthetics are based upon some modification of these changes.

Diazepam, midazolam and clonazepam were examined at concentrations varying from 3.10^–5 to 3.10^–4 M. In the isolated rat sciatic nerve preparation all compounds produced significant time- and concentration-dependent inhibition of evoked action potentials. With increasing time intervals the response became increasingly concentration-dependent. Concentrations of 3.10^–5 M of midazolam or clonazepam - and diazepam, at the time intervals up to 24 min, to a lesser extent - produced a slight increase of the amplitude. The time-response curves of diazepam tended to flatten between 24 and 60 min. Clonazepam, after eliciting intitial increase at 6.10^–5 M, reduced the action potentials only in the range of l.l0^–4 to 3.10^–4 M. The latter reduction was time-dependent in a significant way at concentrations of 3.10^–4 M. The Emax values of the benzodiazepines were increased progressively with the exposure time, i.e. that of diazepam > midazolam > clonazepam. It is concluded that, in the concentrations studied, benzodiazepines have direct time-dependent blocking actions on nerve conduction in isolated motor nerves - involving ion channel currents - those of diazepam being the most potent.

We studied the effect of intraperitoneally administered corticosteroids on the neuromuscular transmission in the sciatic nerve-tibialis anterior muscle preparation of the anesthetized rat stimulated at a rate of 10 Hz. Administered simultaneously with hemicholinium-3 (HC-3), 80 pg per kilogram (that is, half the lethal dose for 50 percent survival), prednisolone and dexamethasone cause a marked reversal of the block of the neuromuscular transmission caused by HC-3. The effect of aldosterone is very small. The blocking action of d-tubocurarine is not antagonized by either prednisolone or dexamethasone. Choline provides total protection against the HC-3 blockade, whereas physostigmine, in a just sublethal dose, is ineffective. We tentatively conclude that in myasthenia gravis the carrier-mediated transport of choline into the nerve endings may be deficient and that the beneficial effect of corticosteroids in this condition is based on their ability to ameliorate the deficient choline transoort.

In the rat shock-induced ultrasonic vocalization test, the anxiolytic effects of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) obtained after systemic (IP) and intracerebral injection into the dorsal raphe nucleus (DRN) were selectively abolished by pretreatment with the 5-HT1A receptor antagonist WAY-100635 [N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclo-hexanecarboxamide trihydrochloride]. This blockade was demonstrated both after systemic and DRN application of WAY-100635. Therefore, it is concluded that the anxiolytic effects of 8-OH-DPAT are mediated by activation of somatodendritic 5-HT1A receptors.

Les intégrines sont des récepteurs cellulaires capables de se lier au cytosquelette d’actine et permettant à la cellule d’interagir avec son environnement. En oncologie, elles jouent un rôle clé dans l’angiogenèse tumorale, participant ainsi à la croissance et à la dissémination des cancers. En cardiologie, elles participent au recrutement des globules blancs lors des phénomènes inflammatoires et sont essentielles lors du remodelage ventriculaire suivant l’infarctus du myocarde. Le ciblage de l’expression des intégrines constitue donc une piste prometteuse en imagerie nucléaire. L’objectif de ce travail est de déterminer les conditions de marquage optimales du NODAGA-RGD par le gallium-68, sans prépurification, à l’aide de l’automate miniAIO.