Functional connectivity in prenatally stressed rats with and without maternal treatment with ladostigil, a brain-selective monoamine oxidase inhibitor.

Stress during pregnancy in humans is known to be a risk factor for neuropsychiatric disorders in the offspring. Prenatal stress in rats caused depressive-like behavior that was restored to that of controls by maternal treatment with ladostigil (8.5 mg/kg per day), a brain-selective monoamine oxidase (MAO) inhibitor that prevented increased anxiety-like behavior in stressed mothers. Ladostigil inhibited maternal striatal MAO-A and -B by 45-50% at the time the pups were weaned. Using resting state-functional connectivity magnetic resonance imaging on rat male offspring of control mothers, and mothers stressed during gestation with and without ladostigil treatment, we identified neuronal connections that differed between these groups. The percentage of significant connections within a predefined predominantly limbic network in control rats was 23.3 within the right and 22.0 within the left hemisphere. Prenatal stress disturbed hemispheric symmetry, resulting in 30.2 and 21.6%, significant connections in the right and left hemispheres, respectively, but this was fully restored in the maternal ladostigil group to 24.6% in both hemispheres. All connections that were modified in prenatally stressed rats and restored by maternal drug treatment were associated with the dopaminergic system. Specifically, we observed that restoration of the connections of the right nucleus accumbens shell with frontal areas, the cingulate, septum and motor and sensory cortices, and those of the right globus pallidus with the infra-limbic and the dentate gyrus, were most important for prevention of depressive-like behavior.

Distinct resistance patterns to etravirine and rilpivirine in viruses containing nonnucleoside reverse transcriptase inhibitor mutations at baseline.

OBJECTIVE: The current in-vitro study examined HIV-1 drug resistance patterns following etravirine (ETR) and rilpivirine (RPV) drug pressure in viruses containing baseline nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance mutations. DESIGN AND METHOD: Several baseline mutations were introduced into NL-4.3 (subtype B clone) by site-directed mutagenesis. This virus, together with two subtype C clinical isolates containing baseline mutations, was passaged in increasing drug pressure of NNRTIs in cord blood mononuclear cells. Genotypic analysis was performed at different weeks. Phenotypic resistance for ETR, RPV, and efavirenz (EFV) and the replication capacity of several mutations and combinations were tested. RESULTS: In wild-type viruses and viruses containing K103N alone at baseline, E138K or E138G mutations were observed following pressure with either ETR or RPV prior to the appearance of other NNRTI resistance mutations. These changes were observed regardless of viral subtype. However, subtype B viruses containing Y181C generated V179I/F or A62V/A but not E138K following exposure to ETR or RPV, respectively, whereas subtype C viruses containing Y181C developed E138V together with Y188H and V179I under ETR pressure. The addition of mutations at position 138 to Y181C did not significantly enhance levels of resistance to ETR or RPV. The replicative capacity of viruses containing Y181C and either E138K or E138A was similar to that of viruses containing either E138K or E138A alone. CONCLUSION: These results demonstrate that ETR and RPV are likely to select for E138K as a major resistance mutation if no or very few other resistance mutations are present and that Y181C may be antagonistic to E138K.

Heidelberg Retina Tomography analysis in optic disks with anatomic particularities.

Due to its objectivity, reproducibility and predictive value confirmed by many large-scale statistical clinical studies, Heidelberg Retina Tomography has become one of the most used computerized image analysis of the optic disc in glaucoma. It has been signaled, though, that the diagnostic value of Moorfieds Regression Analyses and Glaucoma Probability Score decreases when analyzing optic discs with extreme sizes. The number of false positive results increases in cases of megalopapillae and the number of false negative results increases in cases of small size optic discs. The present paper is a review of the aspects one should take into account when analyzing a HRT result of an optic disc with anatomic particularities.