Abacavir once or twice daily combined with once-daily lamivudine and efavirenz for the treatment of antiretroviral-naive HIV-infected adults: results of the Ziagen Once Daily in Antiretroviral Combination Study

The long intracellular half-life of abacavir (ABC) supports its once-daily use, and this would be expected to simplify treatment if ABC could be given as part of a complete once-daily regimen. A randomized double-blind clinical trial compared the efficacy and safety of 600 mg of ABC administered once daily (n = 384) versus 300 mg of ABC administered twice daily (n = 386) in combination with 300 mg of lamivudine (3TC) and 600 mg of efavirenz (EFV) administered once daily in antiretroviral-naive patients over 48 weeks. The baseline median plasma HIV-1 RNA level was 4.89 log10 copies/mL (44% with viral load >100,000 copies/mL), and the median CD4 cell count was 262 cells/mm. ABC administered once daily was non-inferior to the twice-daily regimen, with 66% and 68% of patients in these respective treatment arms achieving a confirmed plasma HIV-1 RNA level <50 copies/mL (95% confidence interval: -8.4%, 4.9%). The ABC once-daily and twice-daily regimens were similar with respect to infrequency of virologic failure (10% vs. 8%), emergence of resistance mutations, CD4 cell increases from baseline (median, 188 vs. 200 cells/mm), safety profile, and incidence of ABC-related hypersensitivity reactions (9% vs. 7%). ABC administered once daily in combination with 3TC and EFV administered once daily was non-inferior to the ABC twice-daily dosing schedule when combined with 3TC and EFV over 48 weeks.     

Rapid Screening Tests for Determining In Vitro Susceptibility of Herpes Simplex Virus Clinical Isolates

The susceptibility of human herpes simplex virus (HSV) to acyclovir (ACV) was determined with the use of a single dose of the drug (1 and 2 μg of ACV per ml for HSV-1 and HSV-2, respectively) in two rapid assays: a rapid cytopathic effect inhibitory assay (Rapid CIA) and a rapid dye uptake assay (Rapid DUA). These tests allow the simultaneous determination of virus titer and susceptibility to ACV at a determined viral concentration (100 50% tissue culture infective doses and 100 50% dye uptake units). These tests were compared with a conventional susceptibility assay (dye uptake assay) and showed similar results. Indeterminate results with the Rapid CIA appeared in 3 of 30 samples. With the use of both Rapid CIA and Rapid DUA, we were able to determine the susceptibility of 100% of the isolates. The rapid tests, unlike conventional assays, are able to provide susceptibility results within 3 days after the virus has been isolated from a clinical specimen and could thus play a direct role in therapeutic decisions.     

Population structure and admixture in Cerro Largo, Uruguay, based on blood markers and mitochondrial DNA polymorphisms.

Recent studies of the Uruguayan population revealed different amounts of Amerindian and African genetic contributions. Our previous analysis of Afro-Uruguayans from the capital city of the Department of Cerro Largo showed a high proportion of African genes, and the effects of directional mating involving Amerindian women. In this paper, we extended the analysis to a sample of more than 100 individuals representing a random sample of the population of the whole Department. Based on 18 autosomal markers and one X-linked marker, we estimated 82% European, 8% Amerindian, and 10% African contributions to their ancestry, while from seven mitochondrial DNA site-specific polymorphic markers and sequences of hypervariable segment I, we determined 49% European, 30% Amerindian, and 21% African maternal contributions. Directional matings between Amerindian women and European men were detected, but differences involving Africans were not significant. Data about the specific origins of maternal lineages were also provided, and placed in a historical context.     

Electrophysiological analysis of a sensorimotor integration task

The present experiment aimed at investigating electrophysiologic changes observed as beta band asymmetry, by Quantitative Electroencephalography (qEEG), when individuals performed a reaching motor task (catching a ball in free fall). The sample was composed of 23 healthy individuals, of both sexes, with ages varying between 25 and 40 years old. All the subjects were right handed. A two-way ANOVA was applied for the statistical analysis, to verify the interaction between task moment (i.e., 2 s before and 2 s after ball's fall) and electrode (i.e., frontal, central and temporal regions). The first analysis compared electrodes placed over the somatosensory cortex. Central sites (C3–C4) were compared with temporal regions (T3–T4). The results showed a main effect for moment and position. The second analysis was focused over the premotor cortex, which was represented by the electrodes placed on the frontal sites (F3–F4 versus F7–F8), and a main effect was observed for position. Taken together, these results show a pattern of asymmetry in the somatosensory cortex, associated with a preparatory mechanism when individuals have to catch an object during free fall. With respect to task moment, after the ball's fall, the asymmetry was reduced. Moreover, the difference in asymmetry between the observed regions were related to a supposed specialization of areas (i.e., temporal and central). The temporal region was associated with cognitive processes involved in the motor action (i.e., explicit knowledge). On the other hand, the central sites were related to the motor control mechanisms per se (i.e., implicit knowledge). The premotor cortex, represented by two frontal regions (i.e., F3–F4 versus F7–F8), showed a decrease on neural activity in the contralateral hemisphere (i.e., to the right hand). This result is in agreement with other experiments suggesting a participation of the frontal cortex in the planning of the apprehension task. This sensorimotor paradigm may contribute to the repertoire of tasks used to study clinical conditions such as depression, alzheimer and Parkinson diseases.     

Molecular peculiarities of the lytA gene isolated from clinical pneumococcal strains that are bile insoluble

The autolytic LytA amidase from 12 bile (deoxycholate)-insoluble streptococcal isolates (formerly classified as atypical Streptococcus pneumoniae) showing different antibiotic resistance patterns was studied. These atypical strains, which autolyze at the end of the stationary phase of growth, contain highly divergent lytA alleles (pairwise evolutionary distances of about 20%) compared to the lytA alleles of typical pneumococci. The atypical LytA amidases exhibit a peculiar deletion of two amino acids responsible for cell wall anchoring in the carboxy-terminal domain and have a reduced specific activity. These enzymes were inhibited by 1% deoxycholate but were activated by 1% Triton X-100, a detergent that could be used as an alternative diagnostic test for this kind of strain. Preparation of functional chimeric enzymes, PCR mutagenesis, and gene replacements demonstrated that the characteristic bile insolubility of these atypical strains was due to their peculiar carboxy-terminal domain and that the 2-amino-acid deletion was responsible for the inhibitory effect of deoxycholate. However, the deletion alone did not affect the specific activity of LytA. A detailed characterization of the genes encoding the 16S rRNA and SodA together with multilocus sequence typing indicated that the strains studied here are not a single clone and, although they cannot be strictly classified as typical pneumococci, they represent a quite diverse pool of organisms closely related to S. pneumoniae. The clinical importance of these findings is underlined by the role of the lytA gene in shaping the course of pneumococcal diseases. This study can also contribute to solving diagnostic problems and to understanding the evolution and pathogenic potential of species of the Streptococcus mitis group.     

Profilin-mediated food-induced allergic reactions are associated with oral epithelial remodeling

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The CARD15 2936insC mutation and TLR4 896 A>G polymorphism in African Americans and risk of preterm premature rupture of membranes (PPROM)

Infection is believed to be a leading cause of preterm premature rupture of membranes (PPROM). The bacterial cell wall component, lipopolysaccharide (LPS), is thought to initiate tissue responses leading to PPROM in the setting of Gram negative infection. LPS is recognized by the innate immune system, including the proteins encoded by the CARD15 and TLR4 genes. A recently described mutation (2936insC) in CARD15 and a polymorphism in TLR4 896 A>G impair responses to LPS. The objective of this study was to determine if African Americans, who have a higher incidence of PPROM than Caucasians, have different frequencies of the mutant CARD15 allele and the TLR4 hyporesponsive variant, and if risk of PPROM is influenced by fetal carriage of these alleles. The allele frequencies for the CARD15 mutation and the TLR4 896G variant in African Americans were similar to those reported for Caucasians. There was no association between the TLR4 alleles examined and PPROM. However, the CARD15 mutation was only detected in controls and not in PPROM cases. We conclude that the CARD15 mutation and hyporesponsive TLR4 allele do not contribute to ethnic variation in the incidence of PPROM.     

Histopathological and ultrastructural changes associated with herpesvirus infection in waterfowl

Duck virus enteritis is an acute contagious viral disease affecting birds of the order Anseriformes (ducks, geese and swans). The disease agent is a member of the Herpesviridae family (Anatidae herpes virus 1). A group of Anseriformes waterfowl from a Nature Reserve and Centre for the Recovery of Endangered Species in Spain suffered an outbreak of the disease, affecting adults, young and newborns. Other non-Anseriformes waterfowl such as coots, from the family Rallidae, order Gruiformes, were also affected. Histopathological and ultrastructural findings confirmed the viral infection. The present study provides evidence that birds different from the order Anseriformes can be affected, suggesting that the virus has the ability to infest other non-Anseriformes waterfows.