Functional characterization of Vif proteins from HIV-1 infected patients with different APOBEC3G haplotypes.

Objective: The human cytidine deaminase APOBEC3G (A3G) potently restricts HIV-1 but the virus, in turn, expresses a Vif protein which degrades A3G. A natural A3G-H186R variant, common in African populations, has been associated with a more rapid AIDS disease progression, but the underlying mechanism remains unknown. We hypothesized that differences in HIV-1 Vif activity towards A3G wild type and A3G-H186R contribute to the distinct clinical AIDS manifestation.

The Effects of Pop-up Harm Minimisation Messages on Electronic Gaming Machine Gambling Behaviour in New Zealand.

In New Zealand a simple pop-up message feature that provides gambling session information and forces a break in play is mandatory on all electronic gaming machines in all venues (EGMs). Previous research has demonstrated small effects of more sophisticated pop-up messages tested predominantly in laboratory environments. The present research examined gambler engagement with and views on the New Zealand pop-up messages and on the relationship between pop-up messages and EGM expenditure.

Meaningful correlation between asymptomatic retinal arteriole emboli and calcified carotid plaque found on panoramic dental imaging of males with diabetes.

Objective: There is ongoing controversy with regard to the stability of calcified carotid artery plaques (CCAPs) seen in the bifurcation area on panoramic images (PIs). Therefore, we sought to evaluate the possibility of these plaques shedding emboli by observing their relationship with ipsilateral retinal emboli.

Study Design: The study group included 50 neurologically and visually asymptomatic males with diabetes, with PIs that incidentally demonstrated CCAPs (CCAP+) and contemporaneous digital retinal images that had been obtained for evaluation of diabetic retinopathy.

Lomustine Nanoparticles Enable Both Bone Marrow Sparing and High Brain Drug Levels - A Strategy for Brain Cancer Treatments.

Purpose: The blood brain barrier compromises glioblastoma chemotherapy. However high blood concentrations of lipophilic, alkylating drugs result in brain uptake, but cause myelosuppression. We hypothesised that nanoparticles could achieve therapeutic brain concentrations without dose-limiting myelosuppression.

Effect of prosthetic restoration on masticatory function in patients with shortened dental arches: a multicentre study.

The aim of this multicentre study was to investigate the effect of prosthetic restoration for missing posterior teeth on mastication in patients with shortened dental arches (SDAs). Partially dentate patients who had an intact teeth in anterior region and missed distal molar(s) (2-12 missing occlusal units) classified as Kennedy Class I or Class II were recruited from seven university-based dental hospitals in Japan. Of the 125 subjects who underwent baseline (pre-treatment) and follow-up/post-treatment evaluation, 53 chose no replacement of missing teeth and 72 chose treatment with removable partial dentures (n = 53) or implant-supported fixed partial dentures (n = 19).

Innate Lymphoid Cells Are Depleted Irreversibly during Acute HIV-1 Infection in the Absence of Viral Suppression.

Innate lymphoid cells (ILCs) play a central role in the response to infection by secreting cytokines crucial for immune regulation, tissue homeostasis, and repair. Although dysregulation of these systems is central to pathology, the impact of HIV-1 on ILCs remains unknown. We found that human blood ILCs were severely depleted during acute viremic HIV-1 infection and that ILC numbers did not recover after resolution of peak viremia.

Broadly neutralizing antibody specificities detected in the genital tract of HIV-1 infected women.

Background: Broadly neutralizing antibodies (bNAbs) targeting conserved epitopes on the HIV envelope glycoprotein have been identified in blood from HIV-1 infected women. We investigated whether antibodies in the genital tract from these women share similar epitope specificities and functional profiles as those in blood.

Methods: Immunoglobulin (Ig)G and IgA antibodies were isolated from cervicovaginal lavages or Softcups from 13 HIV-infected women in the CAPRISA cohort using Protein G and Peptide M, respectively.

Distinct genital tract HIV-specific antibody profiles associated with tenofovir gel.

The impact of topical antiretrovirals for pre-exposure prophylaxis on humoral responses following HIV infection is unknown. Using a binding antibody multiplex assay, we investigated HIV-specific IgG and IgA responses to envelope glycoproteins, p24 Gag and p66, in the genital tract (GT) and plasma following HIV acquisition in women assigned to tenofovir gel (n=24) and placebo gel (n=24) in the CAPRISA 004 microbicide trial to assess if this topical antiretroviral had an impact on mucosal and systemic antibody responses. Linear mixed effect modeling and partial least squares discriminant analysis was used to identify multivariate antibody signatures associated with tenofovir use.

Killer-cell Immunoglobulin-like Receptor (KIR) gene profiles modify HIV disease course, not HIV acquisition in South African women.

Background: Killer-cell Immunoglobulin-like Receptors (KIR) interact with Human Leukocyte Antigen (HLA) to modify natural killer- and T-cell function. KIR are implicated in HIV acquisition by small studies that have not been widely replicated. A role for KIR in HIV disease progression is more widely replicated and supported by functional studies.

Forming Beliefs: Why Valence Matters.

One of the most salient attributes of information is valence: whether a piece of news is good or bad. Contrary to classic learning theories, which implicitly assume beliefs are adjusted similarly regardless of valence, we review evidence suggesting that different rules and mechanisms underlie learning from desirable and undesirable information. For self-relevant beliefs this asymmetry generates a positive bias, with significant implications for individuals and society.

Intraosseous hydroxocobalamin versus intravenous hydroxocobalamin compared to intraosseous whole blood or no treatment for hemorrhagic shock in a swine model.

Objective: To determine if intraosseous (IO) hydroxocobalamin can improve systolic blood pressure (SBP) in a swine model after severe hemorrhagic shock.

Methods: Thirty six swine (45-55 kg) were anesthetized, intubated, and instrumented with continuous femoral and pulmonary artery pressure monitoring and then hemorrhaged such that 30 percent of their blood volume was extracted over 20 minutes. Five minutes later, animals were randomly assigned to receive 500 mL IO whole blood, 150 mg/kg IO or intravenous (IV) hydroxocobalamin in 180 mL of saline, or no treatment and then monitored for 60 minutes.

Targeted screening of at-risk adults for acute HIV-1 infection in sub-Saharan Africa.

Background: Patients with acute HIV-1 infection (AHI) have elevated infectivity, but cannot be diagnosed using antibody-based testing. Approaches to screen patients for AHI are urgently needed to enable counselling and treatment to reduce onward transmission.

Methods: We pooled data from four African studies of high-risk adults that evaluated symptoms and signs compatible with acute retroviral syndrome and tested for HIV-1 at each visit.

Cognitive neuropsychological functioning in New Zealand Māori diagnosed with schizophrenia.

Objective: Previous research suggests that New Zealand Māori may have an elevated rate of schizophrenia. However, there is limited evidence on important clinical features of the illness in this population. This study examined cognitive neuropsychological functioning in 54 adult Māori diagnosed with schizophrenia and 56 Māori controls.

Human Frontal-Subcortical Circuit and Asymmetric Belief Updating.

Unlabelled: How humans integrate information to form beliefs about reality is a question that has engaged scientists for centuries, yet the biological system supporting this process is not well understood. One of the most salient attributes of information is valence. Whether a piece of news is good or bad is critical in determining whether it will alter our beliefs.

Drug delivery into microneedle-porated nails from nanoparticle reservoirs.

This study demonstrates the potential of polymeric nanoparticles as drug reservoirs for sustained topical drug delivery into microneedle-treated human nail. Laser scanning confocal microscopy was used to image the delivery of a fluorescent model compound from nanoparticles into the nail. A label-free imaging technique, stimulated Raman scattering microscopy, was applied, in conjunction with two-photon fluorescence imaging, to probe the disposition of nanoparticles and an associated lipophilic 'active' in a microneedle-porated nail.

New Member of the V1V2-Directed CAP256-VRC26 Lineage That Shows Increased Breadth and Exceptional Potency.

Unlabelled: The epitopes defined by HIV-1 broadly neutralizing antibodies (bNAbs) are valuable templates for vaccine design, and studies of the immunological development of these antibodies are providing insights for vaccination strategies. In addition, the most potent and broadly reactive of these bNAbs have potential for clinical use. We previously described a family of 12 V1V2-directed neutralizing antibodies, CAP256-VRC26, isolated from an HIV-1 clade C-infected donor at years 1, 2, and 4 of infection (N.

Viral variants that initiate and drive maturation of V1V2-directed HIV-1 broadly neutralizing antibodies.

The elicitation of broadly neutralizing antibodies (bNAbs) is likely to be essential for a preventative HIV-1 vaccine, but this has not yet been achieved by immunization. In contrast, some HIV-1-infected individuals naturally mount bNAb responses during chronic infection, suggesting that years of maturation may be required for neutralization breadth. Recent studies have shown that viral diversification precedes the emergence of bNAbs, but the significance of this observation is unknown.

Increased Likelihood of Missed Appointments ("No Shows") for Racial/Ethnic Minorities in a Safety Net Health System.

Missed appointments have been linked to adverse outcomes known to affect racial/ethnic minorities. However, the association of missed appointments with race/ethnicity has not been determined. We sought to determine the relationships between race/ethnicity and missed appointments by performing a cross-sectional study of 161 350 patients in a safety net health system.

Restoration of CD4+ Responses to Copathogens in HIV-Infected Individuals on Antiretroviral Therapy Is Dependent on T Cell Memory Phenotype.

Antiretroviral therapy (ART) induces rapid suppression of viral replication and a progressive replenishment of CD4(+) T cells in HIV-infected individuals. However, the effect of ART on restoring pre-existing memory CD4(+) T cells specific for common copathogens is still unclear. To better understand the dynamics of Ag-specific CD4(+) T cells during ART, we assessed the frequency, functional capacity, and memory profile of CD4(+) T cells specific for Mycobacterium tuberculosis and CMV in 15 HIV-infected individuals before and 1 y after ART initiation.

Randomized Cross-Sectional Study to Compare HIV-1 Specific Antibody and Cytokine Concentrations in Female Genital Secretions Obtained by Menstrual Cup and Cervicovaginal Lavage.

Introduction: Optimizing methods for genital specimen collection to accurately characterize mucosal immune responses is a priority for the HIV prevention field. The menstrual cup (MC) has been proposed as an alternative to other methods including cervicovaginal lavage (CVL), but no study has yet formally compared these two methods.

Methods: Forty HIV-infected, antiretroviral therapy-naïve women from the CAPRISA 002 acute HIV infection cohort study were randomized to have genital fluid collected using the MC with subsequent CVL, or by CVL alone.

South African HIV-1 subtype C transmitted variants with a specific V2 motif show higher dependence on α4β7 for replication.

Background: The integrin α4β7 mediates the trafficking of immune cells to the gut associated lymphoid tissue (GALT) and is an attachment factor for the HIV gp120 envelope glycoprotein. We developed a viral replication inhibition assay to more clearly evaluate the role of α4β7 in HIV infection and the contribution of viral and host factors.

Results: Replication of 60 HIV-1 subtype C viruses collected over time from 11 individuals in the CAPRISA cohort were partially inhibited by antibodies targeting α4β7.