Plos One
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Cystic fibrosis (CF) airways disease represents an example of polymicrobial infection whereby different bacterial species can interact and influence each other. In CF patients Staphylococcus aureus is often the initial pathogen colonizing the lungs during childhood, while Pseudomonas aeruginosa is the predominant pathogen isolated in adolescents and adults. During chronic infection, P. aeruginosa undergoes adaptation to cope with antimicrobial therapy, host response and co-infecting pathogens. ⋯ P. aeruginosa reference and early strains, isolated at the onset of chronic infection, outcompeted S. aureus in vitro and in vivo models of co-infection. On the contrary, our results indicated a reduced capacity to outcompete S. aureus of P. aeruginosa patho-adaptive strains, isolated after several years of chronic infection and carrying several phenotypic changes temporally associated with CF lung adaptation. Our findings provide relevant information with respect to interspecies interaction and disease progression in CF.
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Morphine and structurally related derivatives are highly effective analgesics, and the mainstay in the medical management of moderate to severe pain. Pharmacological actions of opioid analgesics are primarily mediated through agonism at the µ opioid peptide (MOP) receptor, a G protein-coupled receptor. Position 17 in morphine has been one of the most manipulated sites on the scaffold and intensive research has focused on replacements of the 17-methyl group with other substituents. ⋯ In vivo, they were highly effective against acute thermal nociception in mice with marked increased antinociceptive potency compared to the lead molecules. It was also demonstrated that a carbonyl group at position 6 is preferable to a hydroxyl function in these N-phenethyl derivatives, enhancing MOP receptor affinity and agonist potency in vitro and in vivo. These results expand the understanding of the impact of different moieties at the morphinan nitrogen on ligand-receptor interaction, molecular mode of action and signaling, and may be instrumental to the development of new opioid therapeutics.
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When faced with sensory stimuli, an organism may be required to detect very small differences in a physical parameter (discrimination), while in other situations it may have to generalize over many possible values of the same physical parameter. This decision may be based both on learned information and on sensory aspects of perception. In the present study we describe frequency processing in the behaving mouse using both discrimination and generalization as two key aspects of behaviour. ⋯ In contrast, pre-exposure frequencies that were half an octave or less below the conditioned tone elicited latent inhibition, showing a generalization bandwidth of at least half an octave. Thus, in the same apparatus and using the same general memory paradigm, mice showed generalization gradients that were considerably wider than their discrimination threshold, indicating that environmental requirements and previous experience can determine whether the same two frequencies will be considered same or different. Remarkably, generalization gradients paralleled the typical bandwidths established in the auditory periphery and midbrain, suggesting that frequencies may be considered similar when falling within the same critical band.
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Multicenter Study
Association between different indexations of extravascular lung water (EVLW) and PaO2/FiO2: a two-center study in 231 patients.
Variability of body weight (BW) and height calls for indexation of volumetric hemodynamic parameters. Extravascular lung water (EVLW) has formerly been indexed to actual BW (BW(act)) termed EVLW-index (EVLWI). In overweight patients indexation to BW(act) might inappropriately lower indexed EVLWI(act). Several studies suggest indexation of EVLWI to predicted BW (EVLWI(pred)). However, data regarding association of EVLWI(act) and EVLW(pred) to mortality and PaO2/FiO2 are inconsistent. Two recent studies based on biometric database-analyses suggest indexation of EVLWI to height (EVLWI(height)). Therefore, our study compared the association of un-indexed EVLW, EVLWI(height), EVLW(pred) and EVLWI(act) to PaO2/FiO2 and Oxygenation index (OI = mean airway pressure*FiO2*/PaO2). ⋯ Indexation of EVLW to height (EVLWI(height)) improves the association of EVLW(I) to PaO2/FiO2 and OI compared to all other indexations including EVLWI(pred) and EVLWI(act). Also considering two recent biometric database analyses, EVLWI should be indexed to height.
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Review Meta Analysis
The influence of the patient-clinician relationship on healthcare outcomes: a systematic review and meta-analysis of randomized controlled trials.
To determine whether the patient-clinician relationship has a beneficial effect on either objective or validated subjective healthcare outcomes. ⋯ This systematic review and meta-analysis of RCTs suggests that the patient-clinician relationship has a small, but statistically significant effect on healthcare outcomes. Given that relatively few RCTs met our eligibility criteria, and that the majority of these trials were not specifically designed to test the effect of the patient-clinician relationship on healthcare outcomes, we conclude with a call for more research on this important topic.