Sex Differences in the Neurobiology of Stress.

This review highlights the existing knowledge and data that explain the physiologic impacts of stress, especially pertaining to neurobiology, and how these impacts differ by sex. Furthermore, this review explains the benefits of interventions aimed at preventing or mitigating the adverse effects of stress, because of both the significant toll of stress on the body and the disproportionate impact of these changes experienced by women.

Mini-review: Elucidating the psychological, physical, and sex-based interactions between HIV infection and stress.

Stress is generally classified as any mental or emotional strain resulting from difficult circumstances, and can manifest in the form of depression, anxiety, post-traumatic stress disorder (PTSD), or other neurocognitive disorders. Neurocognitive disorders such as depression, anxiety, and PTSD are large contributors to disability worldwide, and continue to affect individuals and communities. Although these disorders affect men and women, women are disproportionately represented among those diagnosed with affective disorders, a result of both societal gender roles and physical differences. Furthermore, the incidence of these neurocognitive disorders is augmented among People Living with HIV (PLWH); the physical ramifications of stress increase the likelihood of HIV acquisition, pathogenesis, and treatment, as both stress and HIV infection are characterized by chronic inflammation, which creates a more opportunistic environment for HIV. Although the stress response is facilitated by the autonomic nervous system (ANS) and the hypothalamic pituitary adrenal (HPA) axis, when the response involves a psychological component, additional brain regions are engaged. The impact of chronic stress exposure and the origin of individual variation in stress responses and resilience are at least in part attributable to regions outside the primary stress circuity, including the amygdala, prefrontal cortex, and hippocampus. This review aims to elucidate the relationship between stress and HIV, how these interact with sex, and to understand the physical ramifications of these interactions.

HIV-1 infection of the kidney: mechanisms and implications.

People living with HIV are at higher risk for acute and chronic kidney disease compared with uninfected individuals. Kidney disease in this population is multifactorial, with several contributors including HIV infection of kidney cells, chronic inflammation, genetic predisposition, aging, comorbidities, and coinfections. In this review, we provide a summary of recent advancements in the understanding of the mechanisms and implications of HIV infection and kidney disease, with particular focus on the role of direct HIV infection of renal cells.

Immunogenicity, safety, and efficacy of sequential immunizations with an SIV-based IDLV expressing CH505 Envs.

A preventative HIV-1 vaccine is an essential intervention needed to halt the HIV-1 pandemic. Neutralizing antibodies protect against HIV-1 infection in animal models, and thus an approach toward a protective HIV-1 vaccine is to induce broadly cross-reactive neutralizing antibodies (bnAbs). One strategy to achieve this goal is to define envelope (Env) evolution that drives bnAb development in infection and to recreate those events by vaccination. In this study, we report the immunogenicity, safety, and efficacy in rhesus macaques of an SIV-based integrase defective lentiviral vector (IDLV) expressing sequential gp140 Env immunogens derived from the CH505 HIV-1-infected individual who made the CH103 and CH235 bnAb lineages. Immunization with IDLV expressing sequential CH505 Envs induced higher magnitude and more durable binding and neutralizing antibody responses compared to protein or DNA +/- protein immunizations using the same sequential envelopes. Compared to monkeys immunized with a vector expressing Envs alone, those immunized with the combination of IDLV expressing Env and CH505 Env protein demonstrated improved durability of antibody responses at six months after the last immunization as well as lower peak viremia and better virus control following autologous SHIV-CH505 challenge. There was no evidence of vector mobilization or recombination in the immunized and challenged monkeys. Although the tested vaccines failed to induce bnAbs and to mediate significant protection following SHIV-challenge, our results show that IDLV proved safe and successful at inducing higher titer and more durable immune responses compared to other vaccine platforms.

HIV-1 diversity and compartmentalization in urine, semen, and blood.

HIV-1 persists indefinitely in multiple cellular reservoirs despite antiretroviral therapy. We previously demonstrated HIV-1 compartmentalization in kidney and urine. Here, we further characterized viruses in urine and when available, compared them to those present in semen from HIV-1 positive participants with detectable plasma viremia to further understand the viral dynamics in the upper and lower genitourinary tract.Blood and urine samples were obtained from 19 HIV-1 positive participants. Simultaneous semen samples were obtained from 16 of the 19 participants. HIV-1 envelope (env) gene sequences were obtained by single-genome amplification (SGA) and neighbor-joining trees were constructed using the Kimura 2-parameter model.HIV-1 env gene sequences were amplified from blood in 19/19 (100%) participants, urine in 18/19 (95%) participants, and semen in 12/16 (75%). In individuals from which both urine and semen samples were obtained, differences in viral shedding between the 2 sources were observed, where HIV-1 env sequences could only be amplified from either urine or semen. Longitudinal phylogenetic analysis of urine-derived env sequences from 1 participant demonstrated that urine clusters distinct from blood are maintained over time (20 weeks), consistent with viral compartmentalization and local replication. Comparison of urine and semen derived sequences demonstrated either virus compartmentalization or equilibration.Our results demonstrate that when present, viral compartmentalization in urine persists over time. Comparison of timing of viral shedding in urine and semen samples from our cohort suggest different viral kinetics between the upper and lower genitourinary tract and sequence analysis suggests that HIV-1 populations in urine and semen can either be imported from blood or produced locally.

Waterpipe tobacco smoke toxicity: the impact of waterpipe size.

INTRODUCTION: Waterpipe tobacco smoking continues to show increasing popularity, especially among individuals between 18 and 22 years old. Waterpipe tobacco smoke (WTS) is a mixture of particulates and gases formed from the combustion of the charcoal and volatilisation and humidification of the tobacco+humectant+flavouring substrate known as shisha or mu'assel. As such, variation in the configuration of the waterpipe may affect the particles produced. Our study focuses on the effects of waterpipe size on the physical properties and cytotoxicity of the smoke produced. METHODS: Shisha type and headspace volume were held constant and a modified Beirut puff protocol was followed while the size of the waterpipe was varied. Particle concentrations and size distributions were measured using a TSI Engine Exhaust Particle Sizer. Type II alveolar cells were exposed to smoke at the air-liquid interface and two metrics of cell health analysed. RESULTS: In a 30 min session, we observed a decrease in total particle concentration (1014-1013) and mass (10 000-2800 mg/m3) and an increase in particle size (125-170 nm) as pipe height increases from 22 to 55 cm and bowl size from 300 to 1250 mL. Smoke from all pipe sizes caused decreases in lysosomal function (>40%) and membrane integrity (>60%) 24 hours post 57 min exposure, and meet the National Institutes of Health definition of a cytotoxic agent (≥30% decrease in cell viability). CONCLUSION: Smoke from waterpipes of all sizes causes significant alveolar cellular harm, indicating that this device needs regulation as a hazard to human health.

Contributions of charcoal, tobacco, and syrup to the toxicity and particle distribution of waterpipe tobacco smoke.

The use of waterpipes in the United States is increasing in a largely unregulated market. The shisha smoked in a waterpipe is a complex matrix of tobacco, flavorings, and humectant with smoke generated by an external heat source. This study explored the relationship between shisha components and the particulate matter size distributions and toxicity of smoke generated with heating. Standard waterpipe puff topography of charcoal- or electronic- heated whole shisha and shisha components generated smoke particulate matter that was characterized using a TSI Engine Exhaust Particle Sizer. Relative toxicity of the whole smoke was determined via measurement of lysosomal integrity and measures of membrane integrity following acute exposure of type II alveolar cells at the air-liquid interface. All waterpipe aerosols exhibited a unimodal particle size distribution, the peak and concentration of which varied depending upon the shisha components present. Acute exposure to charcoal-heated whole shisha, flavoring syrup, or humectant smoke, or electronic-heated whole shisha smoke caused significant alveolar cell damage and death, indicating neither tobacco nor charcoal are needed for these cytotoxic effects to occur.