Recent studies show that emotional stimuli impair the identification of
subsequently presented, briefly flashed stimuli. In the present study, we
investigated whether emotional distractors (primes) ...impaired target processing
when presentation of the target stimulus was not impoverished. In lexical
decision, animacy decision, rhyme decision, and nonword naming, targets were
presented in such a manner that they were clearly visible (i.e., targets were
not masked and presented until participants responded). In all tasks
taboo-sexual distractors caused a slowdown in responding to the subsequent
neutral target. Our results indicate that the detrimental effects of emotional
distractors are not confined to paradigms in which visibility of the target is
limited. Moreover, impairments were obtained even when semantic processing of
stimuli was not required.
Watching motivationally relevant pictures modulates two types of event-related brain potentials (ERPs), the early posterior negativity (EPN) and the P3. Several studies show that the EPN and P3 to ...emotional stimuli are enhanced as compared to neutral stimuli. The goal of the present study was to investigate whether experimentally conditioned abstract stimuli (Gabor patches) that predict the occurrence of a subsequent emotional event are able to elicit an enhanced EPN and P3. This would confirm that these ERP components indeed reflect the motivational relevance of a stimulus, rather than other stimulus properties such as complexity. In a conditioning paradigm, abstract patches (conditioned stimuli; CS) were contingently paired with emotional or neutral pictures (unconditioned stimuli; UCS). Both EPN and P3 to these CS were measured in 80 healthy participants. The results demonstrate an enhanced P3 to CS predicting emotional stimuli as compared to CS predicting neutral stimuli. The EPN was not modulated by the CS. These results show that the P3 is a suitable index of acquired motivational relevance and is not, at least not completely, dependent on task-irrelevant stimulus properties such as complexity and contrast. The EPN seems less suitable as an index of recently acquired motivational relevance because, although the CS acquired emotional significance, this did not result in the typical EPN modulation.
Mice were immunosuppressed using corticosteroids and infected with conidia of Aspergillus fumigatus. Beginning 1 day after infection, mice were treated orally either with Noble agar or with SCH56592 ...suspended in Noble agar, or intraperitoneally with amphotericin B. SCH56592 prolonged survival and reduced lung tissue counts of A. fumigatus, while amphotericin B had marginal benefit. SCH56592 merits further development for treatment of aspergillosis.
Meningoencephalitis caused by Cryptococcus gattii is associated with significant morbidity and the need for aggressive therapy, and often necessitates neurosurgical intervention. We adapted a ...previously described murine model of cryptococcal meningoencephalitis due to Cryptococcus neoformans to that caused by C. gattii.
Mice were inoculated intracranially with either C. gattii (genotype VGIIa) or C. neoformans. In virulence studies, different C. gattii infecting inocula were compared with a fixed inoculum of C. neoformans, and differences were assessed by survival, brain tissue fungal burden, serum antigen titres and histopathological changes within brain tissue. For treatment, fluconazole or posaconazole (10 mg/kg orally twice daily) was initiated 24 h post-inoculation.
C. gattii was more virulent than C. neoformans, as evident by shorter median survival, earlier histopathological changes and higher serum antigen titres. However, no differences in fungal burden or dissemination to other organs were observed among the various groups. In treatment studies, both fluconazole and posaconazole improved the median survival of mice infected with either species. However, neither regimen improved the percentage of animals surviving to the predetermined study endpoint.
These results demonstrate the virulence of C. gattii meningoencephalitis and the potential of this model for the assessment of new treatment strategies.
The Management and Uncertainties of Severe Accidents (MUSA) project was funded in HORIZON 2020 and is coordinated by CIEMAT (Spain). The project aims at consolidating a harmonized approach for the ...analysis of uncertainties and sensitivities associated with Severe Accidents (SAs) analysis, focusing on source term figures of merit. The Application of Uncertainty Quantification (UQ) Methods against Integral Experiments (AUQMIE – Work Package 4 (WP4)), led by ENEA (Italy), was devoted to apply and test UQ methodologies adopting the internationally recognized PHEBUS FPT1 test. FPT1 was chosen to test UQ methodologies because, even though it is a simplified SA scenario, it was representative of the in-vessel phase of a severe accident initiated by a break in the cold leg of a PWR primary circuit. WP4 served as a platform to identify and discuss the issues encountered in the application of UQ methodologies to SA analyses (e.g. discuss the UQ methodology, perform the coupling between the SA codes and the UQ tools, define the results post-processing methods, etc.). The purpose of this paper is to describe the MUSA PHEBUS FPT1 uncertainty application exercise with the related specifications and the methodologies used by the partners to perform the UQ exercise. The main outcomes and lessons learned of the analysis are: scripting was in general needed for the SA code and uncertainty tool coupling and to have more flexibility; particular attentions hould be devoted to the proper choice of the input uncertain parameters; outlier values of figures of merit should be carefully analyzed; the computational time is a key element to perform UQ in SA; the large number of uncertain input parameters may complicate the interpretation of correlation or sensitivity analysis; there is the need for a statistically solid handling of failed calculations.
The efficacy of 5-chloro-2-methylthio-6-(1-naphthyloxy)- 1H-benzimidazole, called "alpha", was tested against Fasciola hepatica. Fluke-free calves ( n=32) were divided into 8 groups and infected with ...150 metacercariae per animal. All animals subsequently received a second infection with another 150 metacercariae, given at different time intervals aimed to produce flukes of differing ages within the experimental animals. When the flukes reached the required age in the animals, four groups were treated with a single oral dose of 12 mg/kg of compound alpha and the remaining ones served as non-treated controls. Two weeks after treatment the animals of all groups were sacrificed and the livers were removed to determine the numbers of parasites present in the treated and untreated controls. In the treated groups the fluke reduction for the 3 day/2 week group was 100%, for the 3 week/4 week group it was 96.4%, for the 6 week/8 week group it was 99.2% and for the 10 week/12 week group it was 100%.
Objectives
Amphotericin B inhalation powder (ABIP) is a novel dry-powder amphotericin B formulation that is directly delivered to the lung, resulting in elevated lung tissue drug concentrations of ...this polyene. We evaluated the prophylactic efficacy of single dose administration of ABIP in a guinea pig model of invasive pulmonary aspergillosis.
Methods
Guinea pigs were immunosuppressed with cyclophosphamide and cortisone acetate and challenged with Aspergillus fumigatus conidia in an aerosol chamber. Guinea pigs received prophylaxis with a single inhaled dose of ABIP at 0.05, 0.5, 4 or 10 mg/kg administered 24 h prior to infection. Treatment with oral voriconazole at doses of 5 or 10 mg/kg twice daily beginning 24 h post-challenge served as the positive control.
Results
Improvements in survival were observed with ABIP prophylaxis. A single inhaled dose of 4 mg/kg ABIP and treatment with 5 mg/kg voriconazole both improved median and percentage survival compared with untreated controls. In addition, pulmonary fungal burden, as assessed by cfu, quantitative PCR and galactomannan, was also reduced in a dose-dependent fashion with ABIP prophylaxis as well as with both doses of voriconazole treatment.
Conclusions
Single-dose prophylaxis with inhaled ABIP as prophylaxis demonstrated a significant survival advantage and reductions in pulmonary fungal burden in this model of invasive pulmonary aspergillosis. Optimization of the dose and dosing frequency of ABIP dose may help to further enhance the anti-Aspergillus activity of this novel amphotericin B formulation.
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