12 resultados para Benzodiazepine usage in Ireland

em BORIS: Bern Open Repository and Information System - Berna - Suiça


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A lacustrine sediment core from Fiddaun, western Ireland was studied to reconstruct summer temperature changes during the Weichselian Lateglacial. This site is located close to the Atlantic Ocean; and so is potentially sensitive to climatic changes associated with changes in ocean circulation. The record, comprising the end of the Weichselian Pleniglacial to the early Holocene, was analysed for fossil chironomids, lithology, and oxygen and carbon isotopes in the sedimentary carbonates. These proxies clearly show rapid warming at the onset of the Lateglacial Interstadial, relatively high summer temperatures during the Interstadial, pronounced cooling during the Younger Dryas, and subsequent warming at the transition to the Holocene. Chironomid-inferred mean July air temperatures for the Interstadial are ~12.5–14.5 °C, ~7.5 °C for the Younger Dryas, and ~15.0 °C for the early Holocene. Furthermore, this research provides evidence for at least two cold events during the Interstadial. These more moderate temperature oscillations can be correlated to Greenland Interstadial events 1b and 1d, on the basis of the age-depth model for the Fiddaun sequence. Based on multiple proxies, the first cold oscillation (GI-1d) was the more severe of the two in Ireland.

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Range expansions are extremely common, but have only recently begun to attract attention in terms of their genetic consequences. As populations expand, demes at the wave front experience strong genetic drift, which is expected to reduce genetic diversity and potentially cause ‘allele surfing’, where alleles may become fixed over a wide geographical area even if their effects are deleterious. Previous simulation models show that range expansions can generate very strong selective gradients on dispersal, reproduction, competition and immunity. To investigate the effects of range expansion on genetic diversity and adaptation, we studied the population genomics of the bank vole (Myodes glareolus) in Ireland. The bank vole was likely introduced in the late 1920s and is expanding its range at a rate of ~2.5 km/year. Using genotyping-by-sequencing, we genotyped 281 bank voles at 5979 SNP loci. Fourteen sample sites were arranged in three transects running from the introduction site to the wave front of the expansion. We found significant declines in genetic diversity along all three transects. However, there was no evidence that sites at the wave front had accumulated more deleterious mutations. We looked for outlier loci with strong correlations between allele frequency and distance from the introduction site, where the direction of correlation was the same in all three transects. Amongst these outliers, we found significant enrichment for genic SNPs, suggesting the action of selection. Candidates for selection included several genes with immunological functions and several genes that could influence behaviour.

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During the last decade, medical education in the German-speaking world has been striving to become more practice-oriented. This is currently being achieved in many schools through the implementation of simulation-based instruction in Skills Labs. Simulators are thus an essential part of this type of medical training, and their acquisition and operation by a Skills Lab require a large outlay of resources. Therefore, the Practical Skills Committee of the Medical Education Society (GMA) introduced a new project, which aims to improve the flow of information between the Skills Labs and enable a transparent assessment of the simulators via an online database (the Simulator Network).

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A total of 474 serum samples from client owned Irish dogs were tested for the presence of antibodies to serovars Canicola, Icterohaemorrhagiae, Bratislava, Autumnalis, Pomona, Altodouro, Grippotyphosa, Mozdok, Hardjobovis and Ballum. Six per cent of dogs presented to veterinary practitioners for problems unrelated to leptospirosis showed evidence of prior exposure to leptospiral serovars belonging to the serogropus Ballum, Australis, Pomona and Sejroe. One unvaccinated dog suspected to have leptospirosis showed seroconversion to serogroup Icterohaemorrhagiae. Based on these results the authors conclude that canine exposure to serogroup Ballum should be monitored because dogs may serve as sentinels for this serovar in the environment. Vaccination with multivalent vaccines containing serovar Bratislava in addition to serogroups Icterohaemorrhagiae and Canicola is advisable.

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Benzodiazepines are widely used drugs. They exert sedative/hypnotic, anxiolytic, muscle relaxant, and anticonvulsant effects and act through a specific high affinity binding site on the major inhibitory neurotransmitter receptor, the gamma-aminobutyric acid type A (GABA(A)) receptor. Ligands of the benzodiazepine-binding site are classified into three groups depending on their mode of action: positive and negative allosteric modulators and antagonists. To rationally design ligands of the benzodiazepine site in different isoforms of the GABA(A) receptor, we need to understand the relative positioning and overlap of modulators of different allosteric properties. To solve these questions, we used a proximity-accelerated irreversible chemical coupling reaction. GABA(A) receptor residues thought to reside in the benzodiazepine-binding site were individually mutated to cysteine and combined with a cysteine-reactive benzodiazepine site ligand. Direct apposition of reaction partners is expected to lead to a covalent reaction. We describe here such a reaction of predominantly alpha(1)H101C and also three other mutants (alpha(1)G157C, alpha(1)V202C, and alpha(1)V211C) with an Imid-NCS derivative in which a reactive isothiocyanate group (-NCS) replaces the azide group (-N(3)) in the partial negative allosteric modulator Ro15-4513. Our results show four contact points of imidazobenzodiazepines with the receptor, alpha(1)H101C being shared by classical benzodiazepines. Taken together with previous data, a similar orientation of these ligands within the benzodiazepine-binding pocket may be proposed.

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Benzodiazepines are widely used drugs exerting sedative, anxiolytic, muscle relaxant, and anticonvulsant effects by acting through specific high affinity binding sites on some GABA(A) receptors. It is important to understand how these ligands are positioned in this binding site. We are especially interested here in the conformation of loop A of the alpha(1)beta(2)gamma(2) GABA(A) receptor containing a key residue for the interaction of benzodiazepines: alpha(1)H101. We describe a direct interaction of alpha(1)N102 with a diazepam- and an imidazobenzodiazepine-derivative. Our observations help to better understand the conformation of this region of the benzodiazepine pocket in GABA(A) receptor.

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The blaESBL and blaAmpC genes in Enterobacteriaceae are spread by plasmid-mediated integrons, insertion sequences, and transposons, some of which are homologous in bacteria from food animals, foods, and humans. These genes have been frequently identified in Escherichia coli and Salmonella from food animals, the most common being blaCTX-M-1, blaCTX-M-14, and blaCMY-2. Identification of risk factors for their occurrence in food animals is complex. In addition to generic antimicrobial use, cephalosporin usage is an important risk factor for selection and spread of these genes. Extensive international trade of animals is a further risk factor. There are no data on the effectiveness of individual control options in reducing public health risks. A highly effective option would be to stop or restrict cephalosporin usage in food animals. Decreasing total antimicrobial use is also of high priority. Implementation of measures to limit strain dissemination (increasing farm biosecurity, controls in animal trade, and other general postharvest controls) are also important.

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The question of how Constantinople got enough water to support its vast population has been an important area of research. A great deal of valuable work has been done in recent years on the water supply and its technology. Something that has been less thoroughly investigated is the water usage in Constantinople. Once the water was collected in the city, how was it dispersed? How was it used? This paper attempts to trace water distribution, use, and disposal in the city. I will use a combination of literary and material sources to understand the technology of the Constantinopolitan water supply.

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In many surgical disciplines the ultrasound examination is performed by the surgeon himself. With the development of high-resolution ultrasound, hand surgeons use this diagnostic tool more and more to visualize the patient's hand anatomy noninvasively. This article gives an introduction to performing the ultrasound examination in the hand and how to interpret the findings correctly. Additionally, the top ten indications for ultrasound usage in the hand are illustrated.

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Gender-fair language consists of the symmetric linguistic treatment of women and men instead of using masculine forms as generics. In this study, we examine how the use of gender-fair language affects readers' support for social initiatives in Poland and Austria. While gender-fair language is relatively novel in Poland, it is well established in Austria. This difference may lead to different perceptions of gender-fair usage in these speech communities. Two studies conducted in Poland investigate whether the evaluation of social initiatives (Study 1: quotas for women on election lists; Study 2: support for women students or students from countries troubled by war) is affected by how female proponents (lawyers, psychologists, sociologists, and academics) are referred to, with masculine forms (traditional) or with feminine forms (modern, gender-fair). Study 3 replicates Study 2 in Austria. Our results indicate that in Poland, gender-fair language has negative connotations and therefore, detrimental effects particularly when used in gender-related contexts. Conversely, in Austria, where gender-fair language has been implemented and used for some time, there are no such negative effects. This pattern of results may inform the discussion about formal policies regulating the use of gender-fair language.