Effect of β-lactamase inhibitors on in vitro activity of β-lactam antibiotics against Burkholderia cepacia complex species

Background: Bacteria belonging to the Burkholderia cepacia complex (Bcc) are an important cause of chronic respiratory tract infections in cystic fibrosis patients. Intrinsic resistance to a wide range of antimicrobial agents, including a variety of beta-lactam antibiotics, is frequently observed in Bcc strains. Resistance to beta-lactams is most commonly mediated by efflux pumps, alterations in penicillin-binding proteins or the expression of beta-lactamases. beta-lactamase inhibitors are able to restore the in vitro activity of beta-lactam molecules against a variety of Gram-negative species, but the effect of these inhibitors on the activity of beta-lactam treatment against Bcc species is still poorly investigated. Methods: In the present study, the susceptibility of a panel of Bcc strains was determined towards the beta-lactam antibiotics ceftazidime, meropenem, amoxicillin, cefoxitin, cefepime and aztreonam; alone or in combination with a beta-lactamase inhibitor (clavulanic acid, sulbactam, tazobactam and avibactam). Consequently, beta-lactamase activity was determined for active beta-lactam/beta-lactamase inhibitor combinations. Results: Clavulanic acid had no effect on minimum inhibitory concentrations, but addition of sulbactam, tazobactam or avibactam to ceftazidime, amoxicillin, cefoxitin, cefepime or aztreonam leads to increased susceptibility (at least 4-fold MIC-decrease) in some Bcc strains. The effect of beta-lactamase inhibitors on beta-lactamase activity is both strain-and/or antibiotic-dependent, and other mechanisms of beta-lactam resistance (besides production of beta-lactamases) appear to be important. Conclusions: Considerable differences in susceptibility of Bcc strains to beta-lactam antibiotics were observed. Results obtained in the present study suggest that resistance of Bcc strains against beta-lactam antibiotics is mediated by both beta-lactamases and non-beta-lactamase-mediated resistance mechanisms

On the (un)conditionality of automatic attitude activation: the valence proportion effect

Affective priming studies have shown that participants are faster to pronounce affectively polarized target words that are preceded by affectively congruent prime words than affectively polarized target words that are preceded by affectively incongruent prime words. We examined whether affective priming of naming responses depends on the valence proportion (i.e., the proportion of stimuli that are affectively polarized). In one group of participants, experimental trials were embedded in a context of filler trials that consisted of affectively polarized stimulus materials (i.e., high valence proportion condition). In a second group, the same set of experimental trials was embedded in a context of filler trials consisting of neutral stimuli (i.e., low valence proportion condition). Results showed that affective priming of naming responses was significantly stronger in the high valence proportion condition than in the low valence proportion condition. We conclude that (a) subtle aspects of the procedure can influence affective priming of naming responses, (b) finding affective priming of naming responses does not allow for the conclusion that affective stimulus processing is unconditional, and (c) affective stimulus processing depends on selective attention for affective stimulus information

Effects in the affect misattribution procedure are modulated by feature-specific attention allocation

We examined whether automatic stimulus evaluation as measured by the Affect Misattribution Procedure (AMP) is moderated by the degree to which attention is assigned to the evaluative stimulus dimension (i.e., feature-specific attention allocation, FSAA). In two experiments, one group of participants completed a standard AMP while attending to evaluative stimulus information. A second group of participants completed the AMP while attending to non-evaluative stimulus information. In line with earlier work, larger AMP effects were observed when participants were encouraged to attend to evaluative stimulus information than when they were not. These observations support the idea that the impact of FSAA on measures of automatic stimulus evaluation results from a genuine change in the degree of automatic stimulus evaluation rather than a change in the degree to which automatic stimulus evaluation is picked up by these measures

Extinction of likes and dislikes : effects of feature-specific attention allocation

The evaluative conditioning (EC) effect refers to the change in the liking of a neutral stimulus (conditioned stimulus, CS) due to its pairing with another stimulus (unconditioned stimulus, US). We examined whether the extinction rate of the EC effect is moderated by feature-specific attention allocation. In two experiments, CSs were abstract Gabor patches varying along two orthogonal, perceptual dimensions (i.e. spatial frequency and orientation). During the acquisition phase, one of these dimensions was predictive of the valence of the USs. During the extinction phase, CSs were presented alone and participants were asked to categorise the CSs either according to their valence, the perceptual dimension that was task-relevant during the acquisition phase, or a perceptual dimension that was task-irrelevant during the acquisition phase. As predicted, explicit valence measures revealed a linear increase in the extinction rate of the EC effect as participants were encouraged to assign attention to non-evaluative stimulus information during the extinction phase. In Experiment 1, Affect Misattribution Paradigm (AMP) data mimicked this pattern of results, although the effect just missed conventional levels of significance. In Experiment 2, the AMP data revealed an increase of the EC effect if attention was focused on evaluative stimulus information. Potential mechanisms to explain these findings are discussed

To IMPRES or to EXPRES? Exploiting comparative judgments to measure and visualize implicit and explicit preferences

Zip folder containing (a) the raw data files, (b) the R-script for data analysis reproduction, (c) and documentation (README.txt)<div><br></div

The role of stimulus-driven versus goal-directed processes in fight and flight tendencies measured with motor evoked potentials induced by Transcranial Magnetic Stimulation

This study examines two contrasting explanations for early tendencies to fight and flee. According to a stimulus-driven explanation, goal-incompatible stimuli that are easy/difficult to control lead to the tendency to fight/flee. According to a goal-directed explanation, on the other hand, the tendency to fight/flee occurs when the expected utility of fighting/fleeing is the highest. Participants did a computer task in which they were confronted with goal-incompatible stimuli that were (a) easy to control and fighting had the highest expected utility, (b) easy to control and fleeing had the highest expected utility, and (c) difficult to control and fleeing and fighting had zero expected utility. After participants were trained to use one hand to fight and another hand to flee, they either had to choose a response or merely observe the stimuli. During the observation trials, single-pulse Transcranial Magnetic Stimulation (TMS) was applied to the primary motor cortex 450 ms post-stimulus onset and motor evoked potentials (MEPs) were measured from the hand muscles. Results showed that participants chose to fight/flee when the expected utility of fighting/fleeing was the highest, and that they responded late when the expected utility of both responses was low. They also showed larger MEPs for the right/left hand when the expected utility of fighting/fleeing was the highest. This result can be interpreted as support for the goal-directed account, but only if it is assumed that we were unable to override the presumed natural mapping between hand (right/left) and response (fight/flight)

Automatic motor activation by mere instruction

Previous behavioral studies have shown that instructions about stimulus-response (S-R) mappings can influence task performance even when these instructions are irrelevant for the current task. In the present study, we tested whether automatic effects of S-R instructions occur because the instructed stimuli automatically activate their corresponding responses. We registered the lateralized readiness potentials (LRPs) that were evoked by the instructed stimuli while participants were performing a task for which those mappings were irrelevant. Instructed S-R mappings clearly affected task performance in electrophysiological and behavioral measures. The LRP was found to deflect in the direction of the response tendency that corresponded with the instructed S-R mapping. Early activation of the instructed response was observed but occurred predominantly on slow trials. In contrast, response conflict evoked by instructed S-R mappings did not modulate the N2 amplitude. The results strongly suggest that, like experienced S-R mappings, instructed S-R mappings can lead to automatic response activation, but possibly via a different route

Targeting the nonmevalonate pathway in Burkholderia cenocepacia increases susceptibility to certain β-lactam antibiotics

The nonmevalonate pathway is the sole pathway for isoprenoid biosynthesis in Burkholderia cenocepacia and is possibly a novel target for the development of antibacterial chemotherapy. The goals of the present study were to evaluate the essentiality of dxr, the second gene of the nonmevalonate pathway, in B. cenocepacia and to determine whether interfering with the nonmevalonate pathway increases susceptibility toward antibiotics. To this end, a rhamnose-inducible conditional dxr knockdown mutant of B. cenocepacia strain K56-2 (B. cenocepacia K56-2dxr) was constructed, using a plasmid which enables the delivery of a rhamnose-inducible promoter in the chromosome. Expression of dxr is essential for bacterial growth; the growth defect observed in the dxr mutant could be complemented by expressing dxr in trans under the control of a constitutive promoter, but not by providing 2C-methyl-D-erythritol-4-phosphate, the reaction product of DXR (1-deoxy-D-xylulose 5-phosphate reductoisomerase). B. cenocepacia K56-2dxr showed markedly increased susceptibility to the beta-lactam antibiotics aztreonam, ceftazidime, and cefotaxime, while susceptibility to other antibiotics was not (or was much less) affected; this increased susceptibility could also be complemented by in trans expression of dxr. A similarly increased susceptibility was observed when antibiotics were combined with FR900098, a known DXR inhibitor. Our data confirm that the nonmevalonate pathway is essential in B. cenocepacia and suggest that combining potent DXR inhibitors with selected beta-lactam antibiotics is a useful strategy to combat B. cenocepacia infections

Specificity and overlap of attention and memory biases in depression

Attentional and memory biases are viewed as crucial cognitive processes underlying symptoms of depression. However, it is still unclear whether these two biases are uniquely related to depression or whether they show substantial overlap. We investigated the degree of specificity and overlap of attentional and memory biases for depressotypic stimuli in relation to depression and anxiety by means of meta-analytic commonality analysis. By including four published studies, we considered a pool of 463 healthy and subclinically depressed individuals, different experimental paradigms, and different psychological measures. Memory bias is reliably and strongly related to depression and, specifically, to symptoms of negative mood, worthlessness, feelings of failure, and pessimism. Memory bias for negative information was minimally related to anxiety. Moreover, neither attentional bias nor the overlap between attentional and memory biases were significantly related to depression. Limitations include cross-sectional nature of the study. Our study showed that, across different paradigms and psychological measures, memory bias (and not attentional bias) represents a primary mechanism in depression