The impact of the PAI-1 4G/5G polymorphism on the outcome of patients with ALI/ARDS

Intoduction

Increased levels of plasminogen activator inhibitor-1 (PAI-1) have been associated with worse outcome in ALI/ARDS. A single guanosine insertion/deletion (4G/5G) polymorphism in the promoter region of the PAI-1 gene, may play an important role in the regulation of PAI-1 expression. The objective of the study was to evaluate the effect of this polymorphism on the outcome of critically ill patients with ALI/ARDS.

Materials and Methods

52 consecutive ventilated patients with ALI/ARDS were studied. Bronchoalveolar lavage was performed within 48 hours from diagnosis. Measurement of plasma and BALF PAI-1 activity and D-dimers levels, and 4G/5G genotyping of PAI-1 were carried out. The primary outcome was 28-day mortality, and secondary outcomes included organ dysfunction and ventilator-free days.

Results

17 patients were homozygotes for the 4G allele. Severity scores were not different between subgroups upon study enrollment. 28-day mortality was 70.6% and 42.9% for the 4G-4G and the non-4G-4G patients, respectively (p = 0.06). PAI-1 activity levels and D-dimer in plasma and BALF were not significantly different between the 4G-4G and the non-4G-4G subgroups. In the multivariate analysis, genotype 4G/4G was the only variable independently associated with 28-day mortality (Odds Ratio = 9.95, 95% CI: 1.79-55.28, p = 0.009). Furthermore, genotype 4G/4G and plasma PAI-1 activity levels were independently negatively associated with ventilator free days (p = 0.033 and p = 0.008, respectively).

Conclusions

ALI/ARDS patients, homozygous for the 4G allele of the PAI-1 gene, experienced higher 28-day mortality. This genotype was associated with a reduction in the number of days of unassisted ventilation and was inversely associated with the number of days without organ failure.     

Combined effects of motor response,sensory modality,and stimulus intensity on temporal reproduction

The ability to estimate a filled interval of time is affected by numerous non-temporal factors, such as the sensory modality, duration, and the intensity of the stimulus. Here we explore the role of modality (auditory or visual), stimulus intensity (low vs. high), and motor response speed on the ability to reproduce the duration of short (<1 s) filled intervals. In accordance with the literature, the reproduced duration was affected by both the modality and the intensity of the stimulus; longer reproduction times were generally observed for visual as compared to auditory stimuli, and for low as compared to high-intensity stimuli. We used general estimating equations in order to determine whether these factors independently affected participants’ ability to reproduce a given duration, after eliminating the variability associated with reaction time, since it covaried with the reproduced durations. This analysis revealed that stimulus duration, modality, and intensity were all significant independent predictors of the reproduced durations. Additionally, duration interacted with intensity when reproducing auditory intervals. That is, after taking into account the general speeding-up effect that high-intensity stimuli have on responses, they seem to have an additional effect on the rate of the internal clock. These results support previous evidence suggesting that auditory and visual clocks run at different speeds.     

Improved technique that allows the performance of large-scale SNP genotyping on DNA immobilized by FTA technology.

FTA technology is a novel method designed to simplify the collection, shipment, archiving and purification of nucleic acids from a wide variety of biological sources. The number of punches that can normally be obtained from a single specimen card are often however, insufficient for the testing of the large numbers of loci required to identify genetic factors that control human susceptibility or resistance to multifactorial diseases. In this study, we propose an improved technique to perform large-scale SNP genotyping. We applied a whole genome amplification method to amplify DNA from buccal cell samples stabilized using FTA technology. The results show that using the improved technique it is possible to perform up to 15,000 genotypes from one buccal cell sample. Furthermore, the procedure is simple. We consider this improved technique to be a promising methods for performing large-scale SNP genotyping because the FTA technology simplifies the collection, shipment, archiving and purification of DNA, while whole genome amplification of FTA card bound DNA produces sufficient material for the determination of thousands of SNP genotypes.     

1-Deprenyl test in migraine: neuroendocrinological aspects

We evaluated the effect of 1-deprenyl, a drug that increases the availability of endogenous dopamine, on the plasma levels of prolactin and growth hormone in 10 female patients with migraine and in 10 control subjects matched for age and menstrual phase. The patients showed a significant decrease in prolactin levels at 30, 60 and 120 min after the oral administration of 5 mg of 1-deprenyl when compared with the values obtained in controls ( p < 0.001). The effects of 1-deprenyl on growth hormone plasma levels were not significantly different between patients and controls. These data suggest that 1-deprenyl inhibits prolactin release in migraine patients, but not in control subjects. This differential sensitivity could be explained by dopamine receptor supersensitivity in migraine patients.     

Facilitation of multisensory integration by the "unity effect" reveals that speech is special

Whenever two or more sensory inputs are highly consistent in one or more dimension(s), observers will be more likely to perceive them as a single multisensory event rather than as separate unimodal events. For audiovisual speech, but not for other noncommunicative events, participants exhibit a "unity effect," whereby they are less sensitive to temporal asynchrony (i.e., that are more likely to bind the multisensory signals together) for matched (than for mismatched) speech events. This finding suggests that the modulation of multisensory integration by the unity effect in humans may be specific to speech. To test this hypothesis directly, we investigated whether the unity effect would also influence the multisensory integration of vocalizations from another primate species, the rhesus monkey. Human participants made temporal order judgments for both matched and mismatched audiovisual stimuli presented at a range of stimulus-onset asynchronies. The unity effect was examined with (1) a single call-type across two different monkeys, (2) two different call-types from the same monkey, (3) human versus monkey "cooing," and (4) speech sounds produced by a male and a female human. The results show that the unity effect only influenced participants' performance for the speech stimuli; no effect was observed for monkey vocalizations or for the human imitations of monkey calls. These findings suggest that the facilitation of multisensory integration by the unity effect is specific to human speech signals.     

Principal component analysis of the P600 waveform: RF and gender effects

The aim of the present study was to examine the patterns of activation of the P600 waveform of the event-related potentials (ERP), applying principal component analysis (PCA) and repeated measures ANOVA, and whether these patterns are RF and gender dependent. The ERPs of thirty-nine healthy subjects (20 male and 19 female) were recorded during an auditory memory task in the presence and absence of RF, similar to that emitted by mobile phones. Both PCA and ANOVA produced congruent results, showing that activation of the P600 component occurs early and more intensely in the region of the posterior electrodes and in a less intense manner in the central electrodes. Conversely, the activation at the anterior electrodes arises later with a considerably reduced intensity. In the absence of RF female subjects exhibited significantly lower amplitudes at anterior electrodes and earlier latencies at central electrodes than male subjects. These differences disappear in the presence of RF. Consequently, the P600 component follows distinct patterns of activation in the anterior, central and posterior brain areas and gender differences are observed simultaneously at several electrodes within these areas. Finally, the gender-related functional architecture with regard the P600 component appears to be RF sensitive. In conclusion, the application of the PCA procedure provides an adequate model of the spatially distributed event-related dynamics that correspond to the P600 waveform.     

Audiovisual temporal adaptation of speech: temporal order versus simultaneity judgments

The temporal perception of simple auditory and visual stimuli can be modulated by exposure to asynchronous audiovisual speech. For instance, research using the temporal order judgment (TOJ) task has shown that exposure to temporally misaligned audiovisual speech signals can induce temporal adaptation that will influence the TOJs of other (simpler) audiovisual events (Navarra et al. (2005) Cognit Brain Res 25:499–507). Given that TOJ and simultaneity judgment (SJ) tasks appear to reflect different underlying mechanisms, we investigated whether adaptation to asynchronous speech inputs would also influence SJ task performance. Participants judged whether a light flash and a noise burst, presented at varying stimulus onset asynchronies, were simultaneous or not, or else they discriminated which of the two sensory events appeared to have occurred first. While performing these tasks, participants monitored a continuous speech stream for target words that were either presented in synchrony, or with the audio channel lagging 300 ms behind the video channel. We found that the sensitivity of participant’s TOJ and SJ responses was reduced when the background speech stream was desynchronized. A significant modulation of the point of subjective simultaneity (PSS) was also observed in the SJ task but, interestingly, not in the TOJ task, thus supporting previous claims that TOJ and SJ tasks may tap somewhat different aspects of temporal perception.

Identification of a candidate vaccine peptide on the 37 kDa Schistosoma mansoni GAPDH

A previous study performed in adolescents living in an area endemic for Schistosoma mansoni in Brazil has shown that a 37 kDa schistosome surface antigen is a selective target for antibodies in sera from those who were resistant to reinfection. This antigen was shown by molecular cloning to be the schistosome GAPDH. The aim of the present work was to assess whether peptides corresponding to GAPDH antigenic determinants could be used in a subunit vaccine. Five B cell and two T cell epitopic regions were identified on Sm37-GAPDH. One of the B cell determinants (Sm37-5, aa 268-289) is highly antigenic in human infections and antibody reactivity toward this determinant is associated with resistance to reinfection. Mice and rats immunized with Sm37-5 were partially protected against a challenge infection, indicating that this peptide can induce protective immunity. Analysis of Sm37-5 amino acid sequence indicated that this antigenic determinant is likely conserved among other pathogenic strains of schistosome (S. haematobium, S. intercalatum and S. japonicum), although it shows major amino acid differences with the corresponding human GAPDH sequence. All together these results indicate that Sm37-5 should be considered as a candidate component for an anti-schistosome subunit vaccine.