Durable immunity to SARS-CoV-2 in both lower and upper airways achieved with a gorilla adenovirus (GRAd) S-2P vaccine in non-human primates.

SARS-CoV-2 continues to pose a global threat, and current vaccines, while effective against severe illness, fall short in preventing transmission. To address this challenge, there's a need for vaccines that induce mucosal immunity and can rapidly control the virus. In this study, we demonstrate that a single immunization with a novel gorilla adenovirus-based vaccine (GRAd) carrying the pre-fusion stabilized Spike protein (S-2P) in non-human primates provided protective immunity for over one year against the BA.5 variant of SARS-CoV-2. A prime-boost regimen using GRAd followed by adjuvanted S-2P (GRAd+S-2P) accelerated viral clearance in both the lower and upper airways. GRAd delivered via aerosol (GRAd(AE)+S-2P) modestly improved protection compared to its matched intramuscular regimen, but showed dramatically superior boosting by mRNA and, importantly, total virus clearance in the upper airway by day 4 post infection. GrAd vaccination regimens elicited robust and durable systemic and mucosal antibody responses to multiple SARS-CoV-2 variants, but only GRAd(AE)+S-2P generated long-lasting T cell responses in the lung. This research underscores the flexibility of the GRAd vaccine platform to provide durable immunity against SARS-CoV-2 in both the lower and upper airways.

Youth Ending the HIV Epidemic (YEHE): Protocol for a pilot of an automated directly observed therapy intervention with conditional economic incentives among young adults with HIV.

BACKGROUND: Young adults have a disproportionately high rate of HIV infection, high rates of attrition at all stages of the HIV care continuum, and an elevated probability of disease progression and transmission. Tracking and monitoring objective measures of antiretroviral therapy (ART) adherence in real time is critical to bolster the accuracy of research data, support adherence, and improve clinical outcomes. However, adherence monitoring often relies on self-reported and retrospective data or requires additional effort from providers to understand individual adherence patterns. In this study, we will monitor medication-taking using a real-time objective measure of adherence that does not rely on self-report or healthcare providers for measurement. METHODS: The Youth Ending the HIV Epidemic (YEHE) study will pilot a novel automated directly observed therapy-conditional economic incentive (aDOT-CEI) intervention to improve ART adherence among youth with HIV (YWH) in California and Florida who have an unsuppressed HIV viral load. The aDOT app uses facial recognition to record adherence each day, and then economic incentives are given based on a participant's confirmed adherence. We will enroll participants in a 3-month pilot study to assess the feasibility and acceptability of the aDOT-CEI intervention using predefined metrics. During and after the trial, a subsample of the pilot participants and staff/providers from participating AIDS Healthcare Foundation (AHF) clinics will participate in individual in-depth interviews to explore intervention and implementation facilitators and barriers. DISCUSSION: YEHE will provide data on the use of an aDOT-CEI intervention to improve adherence among YWH who are not virologically suppressed. The YEHE study will document the feasibility and acceptability and will explore preliminary data to inform a trial to test the efficacy of aDOT-CEI. This intervention has the potential to effectively improve ART adherence and virologic suppression among a key population experiencing health disparities. TRIAL REGISTRATION: The trial registration number is NCT05789875.

Examining Associations Between Mental Health, IPV Exposure, HIV Risk Behaviors, and PrEP Use in South African Women: An Analysis of Data from the Charisma Study.

Intimate partner violence (IPV) has been associated with poorer mental health outcomes and increased human immunodeficiency virus (HIV) risk behaviors. We examine the relations between IPV, mental health symptomology (defined as psychological distress and alcohol misuse), and engagement in HIV risk behaviors among a sample of South African women who participated in a randomized controlled trial of CHARISMA, an intervention to increase women's agency to use oral pre-exposure prophylaxis (PrEP) safely and consistently as well as mitigate relationship challenges. We also examined the impact of trial participation on women's mental health, as well as the impact of psychological distress on the effectiveness of the CHARISMA intervention. Mental health symptomology and IPV exposure were prevalent and associated with some HIV risk and protective behaviors. Trial participation reduced psychological distress. There was no evidence for mental health symptomology impacting the effectiveness of the CHARISMA intervention.

High time-resolution measurements of ultrafine and fine woodsmoke aerosol number and surface area concentrations in biomass burning kitchens: A case study in Western Kenya.

Indoor air pollution associated with biomass combustion for cooking remains a significant environmental health challenge in rural regions of sub-Saharan Africa; however, routine monitoring of woodsmoke aerosol concentrations continues to remain sparse. There is a paucity of field data on concentrations of combustion-generated ultrafine particles, which efficiently deposit in the human respiratory system, in such environments. Field measurements of ultrafine and fine woodsmoke aerosol (diameter range: 10-2500 nm) with field-portable diffusion chargers were conducted across nine wood-burning kitchens in Nandi County, Kenya. High time-resolution measurements (1 Hz) revealed that indoor particle number (PN) and particle surface area (PSA) concentrations of ultrafine and fine woodsmoke aerosol are strongly temporally variant, reach exceedingly high levels (PN > 106 /cm3 ; PSA > 104 µm2 /cm3 ) that are seldom observed in non-biomass burning environments, are influenced by kitchen architectural features, and are moderately to poorly correlated with carbon monoxide concentrations. In five kitchens, PN concentrations remained above 105 /cm3 for more than half of the day due to frequent cooking episodes. Indoor/outdoor ratios of PN and PSA concentrations were greater than 10 in most kitchens and exceeded 100 in several kitchens. Notably, the use of metal chimneys significantly reduced indoor PN and PSA concentrations.

Real-Time Measurements of Gas-Phase Trichloramine (NCl3) in an Indoor Aquatic Center.

NCl3 is formed as a disinfection byproduct in chlorinated swimming pools and can partition between the liquid and gas phases. Exposure to gas-phase NCl3 has been linked to asthma and can irritate the eyes and respiratory airways, thereby affecting the health and athletic performance of swimmers. This study involved an investigation of the spatiotemporal dynamics of gas-phase NCl3 in an aquatic center during a collegiate swim meet. Real-time (up to 1 Hz) measurements of gas-phase NCl3 were made via a novel on-line derivatization cavity ring-down spectrometer and a proton transfer reaction time-of-flight mass spectrometer. Significant temporal variations in gas-phase NCl3 and CO2 concentrations were observed across varying time scales, from seconds to hours. Gas-phase NCl3 concentrations increased with the number of active swimmers due to swimming-enhanced liquid-to-gas transfer of NCl3, with peak concentrations between 116 and 226 ppb. Strong correlations between concentrations of gas-phase NCl3 with concentrations of CO2 and water (relative humidity) were found and attributed to similar features in their physical transport processes in pool air. A vertical gradient in gas-phase NCl3 concentrations was periodically observed above the water surface, demonstrating that swimmers can be exposed to elevated levels of NCl3 beyond those measured in the bulk air.

The relationship between vaginal ring use and intimate partner violence and social harms: formative research outcomes from the CHARISMA study in Johannesburg, South Africa.

Despite being designed for autonomous use, research suggests partner approval is often in women's microbicide use. Microbicide study participants have described many ways product use affects relationships, from improving sexual pleasure to increasing harm, including exacerbating intimate partner violence (IPV). As the dapivirine ring proceeds closer to licensure, supporting women's agency to use microbicides safely is a priority. We conducted 42 in-depth interviews with former participants of the Microbicide Trials Network (MTN)-020 trial of the dapivirine vaginal ring and their male partners in Johannesburg, South Africa, to explore how ring use and partnership dynamics interacted. We sampled women who reported harms or partner non-support and women with supportive partners. Male and female narratives revealed high background levels of IPV. Women described how study participation/ring use exacerbated violence, and for a few couples served as a rationale for additional abuse. In response, women described feeling powerless and fearful of conflict, resulting in product nonuse. For one participant violence was reduced, and for several others, empowerment was sparked. These findings suggest future providers have the opportunity to shift more women from a place of fear/violence to one of safety/empowerment through the integration of IPV screening and relationship counselling.

Short-term neurocognitive outcomes following anterior temporal lobectomy.

Changes in cognitive function are a well established risk of anterior temporal lobectomy (ATL). Deficits in verbal memory are a common postoperative finding, though a small proportion of patients may improve. Postoperative evaluation typically occurs after six to 12months. Patients may benefit from earlier evaluation to identify potential needs; however, the results of a formal neuropsychological assessment at an early postoperative stage are not described in the literature. We compared pre- and postoperative cognitive function for 28 right ATL and 23 left ATL patients using repeated measures ANOVA. Changes in cognitive function were compared to ILAE seizure outcome. The mean time to postoperative neuropsychological testing was 11.1weeks (SD=6.7weeks). There was a side×surgery interaction for the verbal tasks: immediate memory recall (F(1,33)=20.68, p<0.001), short delay recall (F(1,29)=4.99, p=0.03), long delay recall (F(1,33)=10.36, p=0.003), recognition (F(1,33)=5.69, p=0.02), and naming (F(1,37)=15.86, p<0.001). This indicated that the left ATL group had a significant decrement in verbal memory following surgery, while the right ATL group experienced a small but significant improvement. For the right ATL group, there was a positive correlation between ILAE outcome and improvement in immediate recall (r=-0.62, p=0.02) and long delay recall (r=-0.57, p=0.03). There was no similar finding for the left ATL group. This study demonstrates that short-interval follow-up is effective in elucidating postoperative cognitive changes. Right ATL was associated with improvement in verbal memory, while left ATL resulted in a decrement in performance. Improvement in the right ATL group was related to improved seizure outcome. Short-interval follow-up may lend itself to the identification of patients who could benefit from early intervention.

Glycocalyx restricts adenoviral vector access to apical receptors expressed on respiratory epithelium in vitro and in vivo: role for tethered mucins as barriers to lumenal infection.

Inefficient adenoviral vector (AdV)-mediated gene transfer to the ciliated respiratory epithelium has hindered gene transfer strategies for the treatment of cystic fibrosis lung disease. In part, the inefficiency is due to an absence of the coxsackie B and adenovirus type 2 and 5 receptor (CAR) from the apical membranes of polarized epithelia. In this study, using an in vitro model of human ciliated airway epithelium, we show that providing a glycosylphosphatidylinositol (GPI)-linked AdV receptor (GPI-CAR) at the apical surface did not significantly improve AdV gene transfer efficiency because the lumenal surface glycocalyx limited the access of AdV to apical GPI-CAR. The highly glycosylated tethered mucins were considered to be significant glycocalyx components that restricted AdV access because proteolytic digestion and inhibitors of O-linked glycosylation enhanced AdV gene transfer. To determine whether these in vitro observations are relevant to the in vivo situation, we generated transgenic mice expressing GPI-CAR at the surface of the airway epithelium, crossbred these mice with mice that were genetically devoid of tethered mucin type 1 (Muc1), and tested the efficiency of gene transfer to murine airways expressing apical GPI-human CAR (GPI-hCAR) in the presence and absence of Muc1. We determined that AdV gene transfer to the murine airway epithelium was inefficient even in GPI-hCAR transgenic mice but that the gene transfer efficiency improved in the absence of Muc1. However, the inability to achieve a high gene transfer efficiency, even in mice with a deletion of Muc1, suggested that other glycocalyx components, possibly other tethered mucin types, also provide a significant barrier to AdV interacting with the airway lumenal surface.