Gender differences in the use of cardiovascular interventions in HIV-positive persons; the D:A:D Study

Peer reviewe

RT distributional analysis of cognitive-control-related brain activity in first-episode schizophrenia

Impairments in cognitive control are a defining feature of schizophrenia. Aspects of cognitive control include proactive control, the maintenance of task rules or goals to bias attention and maintain preparedness, and reactive control, the engagement of attention in reaction to changing cognitive demands. Proactive control is thought to be particularly impaired in schizophrenia. We sought to examine proactive and reactive control in schizophrenia, as measured by reaction time (RT) variability and especially long RTs, thought to represent lapses in proactive control, during the Stroop paradigm. Furthermore we sought to examine the neural underpinnings of lapses in proactive control and the subsequent engagement of reactive control in those with schizophrenia compared to healthy controls, using fMRI. We found that patients with schizophrenia displayed greater RT variability and more especially long RTs than controls, suggesting that proactive control is weaker in the schizophrenia compared with the control group. All participants engaged regions of the cognitive control network during long RTs, consistent with an engagement of reactive control following a failure in proactive control on these trials. The schizophrenia group, however, displayed significantly diminished activity in these regions compared to controls. Our results suggest increased failures in proactive but also impaired reactive control in schizophrenia compared to healthy subjects

CNS-specific regulatory elements in brain-derived HIV-1 strains affect responses to latency-reversing agents with implications for cure strategies

Latency-reversing agents (LRAs), including histone deacetylase inhibitors (HDACi), are being investigated as a strategy to eliminate latency in HIV-infected patients on suppressive antiretroviral therapy. The effectiveness of LRAs in activating latent infection in HIV strains derived from the central nervous system (CNS) is unknown. Here we show that CNS-derived HIV-1 strains possess polymorphisms within and surrounding the Sp transcription factor motifs in the long terminal repeat (LTR). These polymorphisms result in decreased ability of the transcription factor specificity protein 1 to bind CNS-derived LTRs, reducing the transcriptional activity of CNS-derived viruses. These mutations result in CNS-derived viruses being less responsive to activation by the HDACi panobinostat and romidepsin compared with lymphoid-derived viruses from the same subjects. Our findings suggest that HIV-1 strains residing in the CNS have unique transcriptional regulatory mechanisms, which impact the regulation of latency, the consideration of which is essential for the development of HIV-1 eradication strategies