Time-dependent modulation of AMPA receptor phosphorylation and mRNA expression of NMDA receptors and glial glutamate transporters in the rat hippocampus and cerebral cortex in a pilocarpine model of epilepsy

The pilocarpine model in rodents reproduces the main features of mesial temporal lobe epilepsy related to hippocampus sclerosis (MTLE-HS) in humans. It has been demonstrated in this model that the phosphorylation of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor GluR1 subunit is increased 1 h after pilocarpine treatment. Moreover, alterations in the levels of glutamate transporters have been associated with chronic epilepsy in humans. Despite these studies, the profile of these changes has not yet been addressed. We analyzed the protein content and phosphorylation profile of the AMPA receptor GluR1 subunit by western blotting. We also used quantitative real-time polymerase chain reaction to analyze the expression of glial glutamate transporters and the N-methyl-d-aspartate receptor NR1 subunit in the hippocampus (Hip) and cerebral cortex (Ctx) at different time points after pilocarpine-induced status epilepticus (Pilo-SE) in male adult Wistar rats. Biochemical analysis was performed in the Hip and Ctx at 1, 3, 12 h (acute period), 5 days (latent period), and 50 days (chronic period) after Pilo-SE. Key findings include an increase in the phosphorylation of GluR1-Ser⁸⁴⁵ in the Ctx and GluR1-Ser⁸³¹ in the Hip at different times during the acute period, and a decrease in the total content of the GluR1 subunit in the Ctx in the latent period. There was a down-regulation of the mRNA expression and protein levels of EAAT1 and EAAT2, and a decrease of the NR1 mRNA expression, in the Ctx during the latent period. Notably, during the chronic period, the EAAT2 mRNA expression and protein levels decreased while the NR1 mRNA levels increased in the Hip. Taken together, our findings suggest a time- and structure-dependent imbalance of glutamatergic transmission in response to Pilo-SE, which might be associated with either epileptogenesis or the seizure threshold in MTLE-HS.     

Effect of pitch–space correspondence on sound-induced visual motion perception

The brain tends to associate specific features of stimuli across sensory modalities. The pitch of a sound is for example associated with spatial elevation such that higher-pitched sounds are felt as being “up” in space and lower-pitched sounds as being “down.” Here we investigated whether changes in the pitch of sounds could be effective for visual motion perception similar to those in the location of sounds. We demonstrated that only sounds that alternate in up/down location induced illusory vertical motion of a static visual stimulus, while sounds that alternate in higher/lower pitch did not induce this illusion. The pitch of a sound did not even modulate the visual motion perception induced by sounds alternating in up/down location. Interestingly, though, sounds alternating in higher/lower pitch could become a driver for visual motion if they were paired in a previous exposure phase with vertical visual apparent motion. Thus, only after prolonged exposure, the pitch of a sound became an inducer for upper/lower visual motion. This occurred even if during exposure the pitch and location of the sounds were paired in an incongruent fashion. These findings indicate that pitch–space correspondence is not so strong to drive or modulate visual motion perception. However, associative exposure could increase the saliency of pitch–space relationships and then the pitch could induce visual motion perception by itself.     

Helicobacter pylori Infection in Infants and Toddlers in South America: Concordance between [13C]Urea Breath Test and Monoclonal H. pylori Stool Antigen Test

Accurate noninvasive tests for diagnosing Helicobacter pylori infection in very young children are strongly required. We investigated the agreement between the [¹³C]urea breath test ([¹³C]UBT) and a monoclonal ELISA (HpSA) for detection of H. pylori antigen in stool. From October 2007 to July 2011, we enrolled 414 infants (123 from Brazil and 291 from Peru) of ages 6 to 30 months. Breath and stool samples were obtained at intervals of at least 3 months from Brazilian (n = 415) and Peruvian (n = 908) infants. [¹³C]UBT and stool test results concurred with each other in 1,255 (94.86%) cases (kappa coefficient = 0.90; 95% confidence interval [CI] = 0.87 to 0.92). In the H. pylori-positive group, delta-over-baseline (DOB) and optical density (OD) values were positively correlated (r = 0.62; P < 0.001). The positivity of the tests was higher (P < 0.001; odds ratio [OR] = 6.01; 95% CI = 4.50 to 8.04) in Peru (546/878; 62.2%) than in Brazil (81/377; 21.5%) and increased with increasing age in Brazil (P = 0.02), whereas in Peru it decreased with increasing age (P < 0.001). The disagreement between the test results was associated with birth in Brazil and female gender but not with age and diarrhea. Our results suggest that both [¹³C]UBT and the stool monoclonal test are reliable for diagnosing H. pylori infection in very young children, which will facilitate robust epidemiological studies in infants and toddlers.     

Development of Doxycycline MIC and Disk Diffusion Interpretive Breakpoints and Revision of Tetracycline Breakpoints for Streptococcus pneumoniae

A study was performed to derive susceptibility testing interpretive breakpoints for doxycycline with Streptococcus pneumoniae and to reassess breakpoints for tetracycline using the requirements defined in Clinical and Laboratory Standards Institute (CLSI) document M23-A3. Tetracycline and doxycycline MICs and disk diffusion zone sizes were determined on 189 isolates selected from the 2009-2010 CDC Active Bacterial Core surveillance strain collection according to the testing methods described in CLSI documents M07-A8 and M02-A10. Tetracycline and doxycycline MICs and zones were compared to each other directly, and the reproducibility of MICs and zone diameters for both drugs was determined. Scattergrams of tetracycline MICs versus corresponding zone diameters and doxycycline MICs versus zones were prepared, and analysis indicated that the present CLSI tetracycline MIC and disk breakpoints did not fit the susceptibility data for doxycycline. Doxycycline was 1 to 3 dilutions more potent than tetracycline, especially in strains harboring the tetM resistance determinant. tetM was detected in ≥90% of isolates having tetracycline MICs of ≥4 μg/ml and in ≥90% with doxycycline MICs of ≥1. Limited pharmacokinetic/pharmacodynamic (PK/PD) data coupled with application of the error-rate bounded method of analysis suggested doxycycline-susceptible breakpoints of either ≤0.25 μg/ml or ≤0.5 μg/ml, with intermediate and resistant breakpoints 1 and 2 dilutions higher, respectively. The disk diffusion zone diameter correlates were susceptible at ≥28 mm, intermediate at 25 to 27 mm, and resistant at ≤24 mm. Revised lower tetracycline MIC breakpoints were suggested as susceptible at ≤1 μg/ml, intermediate at 2 μg/ml, and resistant at ≥4 μg/ml. Suggested tetracycline disk diffusion zones were identical to those of doxycycline.     

Comparison of careHPV and Hybrid Capture 2 Assays for Detection of High-Risk Human Papillomavirus DNA in Cervical Samples from HIV-1-Infected African Women

The careHPV and HC2 assays were compared for high-risk human papillomavirus (HR-HPV) DNA detection in cervical samples from 149 HIV-1-infected African women. The HR-HPV DNA detection rates were 37.6% and 34.9% for careHPV and HC2, respectively. Agreement between the two tests was 94.6% (95% confidence interval [CI], 89.7% to 97.7%) with a kappa value of 0.88 (95% CI, 0.81 to 0.96), indicating an excellent agreement. careHPV may be considered as suitable as HC2 for cervical cancer screening among HIV-infected African women.     

Interspecies differences with in vitro and in vivo models of vascular tissue engineering

In arterial replacement there is a clear clinical need for a functional substitute possessing appropriate haemocompatible properties to be implanted as small diameter artery. Endothelial cell seeding constitutes an appreciated method to improve blood compatibility on the condition that cells firmly adhere to the support. Along this way, an innovative technique based on multilayered polyelectrolyte films (PEM) as cell adhesive substrate was previously validated in vitro and in vivo in a small-animal model. In this study, we extended the work on a larger animal (sheep) to validate furthermore the paradigm of PEM functionalization for vascular substitutes. We tested in vitro: the efficiency of PEM to induce endothelial progenitor differentiation in sheep endothelial cells; the ability of PEM to sustain cell proliferation and allow resistance to shear stress; the fate of PEM-coated de-endothelialized human saphenous veins under flow conditions, a prerequisite step before in vivo experiments. Despite in vitro differences we were encouraged by testing in vivo PEM-coated prosthesis as carotid replacement in sheep, but without success. In order to explain the implantation failure, an in vitro haemocompatibility evaluation was performed that highlighted interspecies differences able to explain, at least in part, the graft failure obtained.     

Effects of physiological aging on mismatch negativity: A meta-analysis

Mismatch negativity (MMN) is a promising window on how the functional integrity of auditory sensory memory and change discrimination is modulated by age and relevant clinical conditions. However, the effects of aging on MMN have remained somewhat elusive, particularly at short interstimulus intervals (ISIs). We performed a meta-analysis of peer-reviewed MMN studies that had targeted both young and elderly adults to estimate the mean effect size. Nine studies, consisting of 29 individual investigations, were included and the final total study population consisted of 182 young and 165 elderly subjects. The effects of different deviant types and duration of ISIs on the effect size were assessed. The overall mean effect size was 0.63 (95% CI at 0.43–0.82). The effect sizes for long ISI (> 2 s, effect size 0.68, 95% CI at 0.31–1.06) and short ISI (< 2 s, effect size 0.61, 95% CI at 0.39–0.84) were both considered moderate. A further analysis showed a prominent aging-related decrease in MMN responses to duration and frequency changes at short ISIs. It was also interesting to note that the effect size was about 25% larger for duration deviant condition compared to the frequency deviant condition. In conclusion, a reduced MMN response to duration and frequency deviants is a robust feature among the aged adults, which suggests that there has been a decline in the functional integrity of central auditory processing in this population.