Safety and availability of dapivirine (TMC120) delivered from an intravaginal ring.

Vaginal delivery of 200 mg or 25 mg dapivirine from intravaginal rings (IVRs) was evaluated over a 7-day period in two phase 1 safety trials (IPM001 and IPM008, respectively) in a total of 25 healthy women 19 to 46 years of age. The IVR was generally safe and well tolerated with similar adverse events observed in the placebo and dapivirine groups. Across both studies, dapivirine concentrations in vaginal fluids measured at the introitus, cervix, and ring area were within the mean range of 0.

The future of HIV microbicides: challenges and opportunities.

HIV microbicides are topical, self-administered products aimed at preventing or reducing HIV infection in women and may represent the most promising strategy for combating the HIV/AIDS epidemic at the present time. Although a safe and effective microbicide has yet to be identified, all products tested in Phase III trials to date have been vaginal gels containing non-specific compounds with modest potency that had to be applied close to the time of sexual intercourse. Issues regarding these early generation products were further complicated by widely publicized cases of halted efficacy trials.

Microbicide delivery: formulation technologies and strategies.

Purpose Of Review: The aim of this article is to summarize the latest information on microbicide formulations for prevention of sexual transmission of HIV infection in women.

Recent Findings: Although early microbicide formulations were conventionally coitally dependent gel products, new technologies are being developed for vaginal delivery of anti-HIV agents. Intravaginal rings for delivery of microbicides, for example, are being developed and evaluated clinically.

Progress in rehabilitation of hemianopic visual field defects.

Visual field defects (VFDs) are common after stroke, affecting between 8 and 25% of all stroke survivors. The impact of VFDs on daily activities is significant, with poor mobility, collisions, impaired reading and driving. Up to recently, visual rehabilitation was neglected by rehabilitation specialists.

A comparison of self-hypnosis versus progressive muscle relaxation in patients with multiple sclerosis and chronic pain.

Twenty-two patients with multiple sclerosis (MS) and chronic pain we recruited into a quasi-experimental trial comparing the effects of self-hypnosis training (HYP) with progressive muscle relaxation (PMR) on pain intensity and pain interference; 8 received HYP and the remaining 14 participants were randomly assigned to receive either HYP or PMR. HYP-condition participants reported significantly greater pre- to postsession as well as pre- to posttreatment decreases in pain and pain interference than PMR-condition participants, and gains were maintained at 3-month follow-up. Most of the participants in both conditions reported that they continued to use the skills they learned in treatment and experienced pain relief when they did so.

Characterization of vaginal transmission of a simian human immunodeficiency virus (SHIV) encoding the reverse transcriptase gene from HIV-1 in Chinese rhesus macaques.

Replication competent recombinant simian-human immunodeficiency virus encoding the reverse transcriptase gene (RT SHIV) from HIV-1 was characterized for vaginal transmission in rhesus macaques. RT SHIV was shown to transmit efficiently via the vaginal route in macaques with detectable plasma viremia persisting for a year in some animals. Analyses of virus load in tissues of infected animals revealed accumulation of viral RNA in lymph nodes and spleen with levels correlating with plasma viremia.

Characterization of a human immunodeficiency virus type 1 V3 deletion mutation that confers resistance to CCR5 inhibitors and the ability to use aplaviroc-bound receptor.

The human immunodeficiency virus type 1 (HIV-1) V3 loop is essential for coreceptor binding and principally determines tropism for the CCR5 and CXCR4 coreceptors. Using the dual-tropic virus HIV-1(R3A), we previously made an extensive panel of V3 deletions and identified subdomains within V3 that could differentially mediate R5 and X4 tropism. A deletion of residues 9 to 12 on the N-terminal side of the V3 stem ablated X4 tropism while leaving R5 tropism intact.

Search for gravitational-wave bursts from soft gamma repeaters.

We present a LIGO search for short-duration gravitational waves (GWs) associated with soft gamma ray repeater (SGR) bursts. This is the first search sensitive to neutron star f modes, usually considered the most efficient GW emitting modes. We find no evidence of GWs associated with any SGR burst in a sample consisting of the 27 Dec.

Failure of antithrombotic therapy and risk of stroke in patients with symptomatic intracranial stenosis.

Background And Purpose: We sought to determine if patients with intracranial stenosis who have a transient ischemic attack or stroke on antithrombotic therapy are at particularly high risk for recurrent stroke.

Methods: We compared baseline features and the rates of stroke or vascular death and stroke in the territory of the symptomatic artery between patients ON (n=299) versus OFF (n=269) antithrombotics at the time of their qualifying event for the Warfarin-Aspirin Symptomatic Intracranial Disease (WASID) trial.

Results: In univariate analyses, there was no difference in the rates of stroke or vascular death (21% versus 23%; hazard ratio [ON/OFF], 0.

Two forms of implicit learning in young adults with dyslexia.

Implicit learning is thought to underlie the acquisition of many skills including reading. Previous research has shown that some forms of implicit learning are reduced in individuals with dyslexia (e.g.

Inhibition of human immunodeficiency virus type 1 infection by the candidate microbicide dapivirine, a nonnucleoside reverse transcriptase inhibitor.

Heterosexual transmission of human immunodeficiency virus (HIV) remains the major route of infection worldwide; thus, there is an urgent need for additional prevention strategies, particularly strategies that could be controlled by women, such as topical microbicides. Potential microbicide candidates must be both safe and effective. Using cellular and tissue explant models, we have evaluated the activity of the nonnucleoside reverse transcriptase inhibitor (NNRTI) dapivirine as a vaginal microbicide.

Galaxies appear simpler than expected.

Galaxies are complex systems the evolution of which apparently results from the interplay of dynamics, star formation, chemical enrichment and feedback from supernova explosions and supermassive black holes. The hierarchical theory of galaxy formation holds that galaxies are assembled from smaller pieces, through numerous mergers of cold dark matter. The properties of an individual galaxy should be controlled by six independent parameters including mass, angular momentum, baryon fraction, age and size, as well as by the accidents of its recent haphazard merger history.

Two key strategies for teaching prevention: specialized course and infusion.

Prevention is taught only rarely in counseling and counseling psychology curricula. Failure to teach it suggests that graduates may be less likely to conduct prevention. In this article, we describe two key strategies for addressing this problem, where prevention is being taught through (a) required courses, and (b) infusion within existing courses.

Examination of perceived spouse responses to patient well and pain behavior in patients with headache.

Objectives: Primary: to examine the association between perceived spouse responses to patient well behaviors and important patient variables (pain behavior, pain intensity, pain interference, and depressive symptoms). Secondary: to examine whether perceived spouse responses to patient pain behaviors are associated with important pain-related variables.

Methods: Sixty-four patients with headache and their spouses completed self-report questionnaire packets that included measures of pain intensity, pain behaviors, depression, marital satisfaction, and perceived spouse responses to pain and well behaviors.

Ultrasound velocity criteria for vertebral origin stenosis.

Background: Despite remaining an important cause of posterior circulation stroke, the non-invasive diagnosis of vertebral artery origin (VAo) stenosis is problematic. We here examine peak systolic velocity (PSV) criteria for the diagnosis of VAo stenosis and assess if the PSV ratio at the origin to the distal segments improves diagnostic accuracy.

Methods: We performed a retrospective analysis of patients studied by catheter cerebral angiography and extracranial Duplex ultrasonography.

Visual field changes after a rehabilitation intervention: vision restoration therapy.

Background: The objective of this study was to determine the effect of a visual rehabilitation intervention on visual field defects in a US cohort. Vision Restoration Therapy (VRT) consists of a specific pattern of stimulation that is directed at the border of the blind field.

Methods: This retrospective study evaluated individuals with homonymous visual field defect from retrochiasmatic lesions treated with 6 modules of VRT.

Microemboli in aneurysmal subarachnoid hemorrhage.

Background And Purpose: The determinants of ischemic complications in subarachnoid hemorrhage (SAH) are not well defined. The objective of this study is to evaluate the role of microemboli in SAH-related cerebral ischemia.

Methods: Forty patients with aneurysmal SAH were monitored with transcranial Doppler (TCD) for the presence of embolic signals (ES) and vasospasm, and followed clinically for the development of cerebral ischemic symptoms, from the time the aneurysm was secured until day 14 posthemorrhage or discharge.

Progress in secondary stroke prevention.

Objectives: There are about 200,000 recurrent strokes each year in the United States. In addition, a large proportion of strokes are preceded by a transient ischemic attack. Therefore, secondary stroke prevention strategies are of great importance.

Increased prevalence of significant recurrent headache in preclinical familial Alzheimer's disease mutation carriers.

Background/aims: A previous study found a high prevalence of headaches in persons with familial Alzheimer's disease (FAD) due to a PSEN1 mutation. In our study we compared the prevalence of headaches between nondemented FAD mutation carriers (MCs) and non-mutation-carrying controls (NCs).

Methods: A headache questionnaire that assessed the prevalence of significant headaches and diagnosis of migraine and aura by ICHD-2 criteria was administered to 27 individuals at risk for FAD.

Rapid blood pressure reduction in acute intracerebral hemorrhage: feasibility and safety.

Background: The optimal blood pressure (BP) for treating acute intracerebral hemorrhage remains (ICH) uncertain. High BP may contribute to hematoma growth while excessive BP reduction might precipitate peri-hemorrhage ischemia. We examine here the feasibility and safety of reducing BP to lower than presently recommended levels in patients with acute ICH.