IntroductionMethicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia is a frequent condition, with high mortality rates. There is a growing interest in identifying new therapeutic regimens ...able to reduce therapeutic failure and mortality observed with the standard of care of beta-lactam monotherapy. In vitro and small-scale studies have found synergy between cloxacillin and fosfomycin against S. aureus. Our aim is to test the hypothesis that cloxacillin plus fosfomycin achieves higher treatment success than cloxacillin alone in patients with MSSA bacteraemia.MethodsWe will perform a superiority, randomised, open-label, phase IV–III, two-armed parallel group (1:1) clinical trial at 20 Spanish tertiary hospitals. Adults (≥18 years) with isolation of MSSA from at least one blood culture ≤72 hours before inclusion with evidence of infection, will be randomly allocated to receive either cloxacillin 2 g/4-hour intravenous plus fosfomycin 3 g/6-hour intravenous or cloxacillin 2 g/4-hour intravenous alone for 7 days. After the first week, sequential treatment and total duration of antibiotic therapy will be determined according to clinical criteria by the attending physician.Primary endpoints: (1) Treatment success at day 7, a composite endpoint comprising all the following criteria: patient alive, stable or with improved quick-Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA at day 7. (2) Treatment success at test of cure (TOC) visit: patient alive and no isolation of MSSA in blood culture or at another sterile site from day 8 until TOC (12 weeks after randomisation).We assume a rate of treatment success of 74% in the cloxacillin group. Accepting alpha risk of 0.05 and beta risk of 0.2 in a two-sided test, 183 subjects will be required in each of the control and experimental groups to obtain statistically significant difference of 12% (considered clinically significant).Ethics and disseminationEthical approval has been obtained from the Ethics Committee of Bellvitge University Hospital (AC069/18) and from the Spanish Medicines and Healthcare Product Regulatory Agency (AEMPS, AC069/18), and is valid for all participating centres under existing Spanish legislation. The results will be presented at international meetings and will be made available to patients and funders.Trial registration numberThe protocol has been approved by AEMPS with the Trial Registration Number EudraCT 2018-001207-37. ClinicalTrials.gov Identifier: NCT03959345; Pre-results.
To determine whether levels of HDL are associated with viral load response in HIV-treated patients, and to seek an explanation based on amino acid sequence similarity between the key apolipoprotein ...A1 and HIV proteins concerned in viral replication.
The major HDL lipoprotein is apolipoprotein A1, which is able to inhibit HIV-induced syncytium formation. This retrospective clinical study assessed the relationship between the response to antiretroviral treatment (time of undetectable viral load/duration of viral suppression below the limit of detection) and HDL-cholesterol levels on commencing antiretroviral treatment.
HIV-treated patients with undetectable HIV viral loads were followed every 3 months for 36 months. We measured total cholesterol, HDL-cholesterol, triglycerides, previous responses to antiretroviral treatment, opportunistic infections, sex and age. These variables were assessed in relation to the time of undetectable viral load until viral rebound. Amino acid sequence alignment was performed with HIV proteins and apolipoprotein A1 to detect shared similarity.
The Cox proportional hazards model showed a significant association between HDL-cholesterol and the time of undetectable viral load. The other variables studied were not associated. There was 30% sequence similarity in an area of 50 amino acids shared between apolipoprotein A1 and p17 Gag-HIV protein.
High levels of HDL-cholesterol are associated with a better viral response in treated HIV patients. This association could be related to the sequence similarity and structure homology between apolipoprotein A1 and p17 Gag-HIV protein, which raises the intriguing clinical possibility that inducing an increase in HDL could assist HIV therapy.
A tripodal tris-amidopyridine receptor forms a 1:1 complex with trans-1,3,5-cyclohexane tricarboxylic acid that is 1 order of magnitude less stable than the one formed with the corresponding ...cis-triacid epimer. The X-ray crystal structures of the complexes have been determined, confirming the binding geometry derived from NMR data in solution and force-field calculations, and its geometrical features are used to explain the observed selectivity.
Parler des mots Arrivé, Michel; Attié Figueira, Rosa; Authier-Revuz, Jacqueline ...
2004
Book
Odprti dostop
Le fait autonymique est ce qui inscrit, dans les langues naturelles et sous diverses formes, la possibilité de « parler des mots ». Il est ainsi forcément présent dans les discours dont l’objet porte ...sur le langage ou qui s’interrogent sur la langue : dans les grammaires, les dictionnaires, ou les interactions dans les cours de langue, par exemple. Mais il surgit également dans les situations les plus diverses dès que les discours ne se contentent pas de parler des « choses » avec des mots, échangeant alors des mots à propos des mots : je ne comprends pas ce mot, comme vous dites, etc. Les études rassemblées dans ce volume analysent des pratiques langagières variées, des conversations familières, des dialogues de théâtre, des débats idéologiques, des journaux télévisés, des écrits psychanalytiques, des récits romanesques, etc., saisissant, au-delà de la variété des formes, les différents enjeux (didactiques, esthétiques, subjectifs, idéologiques, etc.) du fait autonymique. Il apparaît ainsi une « rhétorique de l’autonymie », qui se décline différemment selon les époques, les genres, les situations, les styles, et qui constitue désormais une « entrée » opératoire dans la description des discours.
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