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Neurocognitive impairment (NCI) associated with HIV infection of the brain impacts a large proportion of people with HIV (PWH) regardless of antiretroviral therapy (ART). While the number of PWH and severe NCI has dropped considerably with the introduction of ART, the sole use of ART is not sufficient to prevent or arrest NCI in many PWH. As the HIV field continues to investigate cure strategies, adjunctive therapies are greatly needed. HIV imaging, cerebrospinal fluid, and pathological studies point to the presence of continual inflammation, and the presence of HIV RNA, DNA, and proteins in the brain despite ART. Clinical trials exploring potential adjunctive therapeutics for the treatment of HIV NCI over the last few decades have had limited success. Ideally, future research and development of novel compounds need to address both the HIV replication and neuroinflammation associated with HIV infection in the brain. Brain mononuclear phagocytes (MPs) are the primary instigators of inflammation and HIV protein expression; therefore, adjunctive treatments that act on MPs, such as immunomodulating agents, look promising. In this review, we will highlight recent developments of innovative therapies and discuss future approaches for HIV NCI treatment.

This study examined the impact of congestion-related controls on runner density, flow rate, perceived safety, and satisfaction during an Australian running event. Runner congestion was compared between races organized at the Sunshine Coast Marathon and Running Festival in 2019 without controls and in 2021 with added controls, including modifications to the start corral design and use of wave starts. Following a mixed-method design, runner congestion was quantitatively measured via determining runner density and flow rate in the start corrals with video analyses, while post-event surveys were used to gather qualitative evidence regarding the prevalence of congestion and its impact on runner safety and satisfaction. Descriptive analyses for quantitative data showed runner density (1.48–3.01 vs. 0.52–1.20 runners per m2) and flow rate (102–152 vs. 36–59 runners per min per m) were reduced across races with controls. Regarding qualitative data, Wilcoxon–Mann–Whitney rank-sum tests demonstrated a significantly (p < 0.01) lower prevalence of congestion was perceived on course while running, alongside a reduced (p = 0.08) perceived impact of congestion on event satisfaction across races with controls. Furthermore, descriptive analyses for qualitative data showed a reduced proportion of runners indicated the start corrals were “somewhat” to “extremely” (rating of at least 3 on a 5-point scale) congested upon race commencement with controls (64% vs. 75%), and perceived safety (10% vs. 17%) and satisfaction (17% vs. 30%) were “somewhat” to “extremely” impacted by congestion across races with controls. Adopting suitable start corral designs with wave starts may enable race directors to reduce runner congestion to enhance continued participation among the public and viability of their running events.

Basketball games are currently played across 48 and 40 minutes; however, little is known about the influence of game duration on team statistics. Therefore, we examined (i) differences in game-rela...

Following HIV infection, most people make antibodies to gp120 and gp41, yet only a few make broadly neutralizing antibodies that target key antigenic sites on the envelope glycoproteins. The induction of broadly neutralizing antibodies by immunization remains a major challenge of HIV vaccine research. Difficulties include: variable protein sequence, epitopes that depend on the native conformation, glycosylation that conceals key antigenic determinants, and the assembly of Env trimers that mimic viral spikes. In addition, more potent immunogens may be needed to initiate the response of germline antibody precursors and drive B cell maturation toward antibodies with broad neutralizing activity. We have expressed HIV Env glycoproteins by incorporation into live attenuated rubella viral vectors. The rubella vaccine strain RA27/3 has demonstrated its safety and potency in millions of children. As a vector, it has elicited potent and durable immune responses in macaques to SIV Gag vaccine inserts. We now find that rubella/env vectors can stably express Env core derived glycoproteins ranging in size up to 363 amino acids from HIV clade C strain 426c. The expressed Env glycoproteins bind broadly neutralizing antibodies that target the native CD4 binding site. The vectors grew well in rhesus macaques, and they elicited a vaccine "take" in all animals, as measured by anti-rubella antibodies. By themselves, the vectors elicited modest antibody titers to the Env insert. But the combination of rubella/env prime followed by a homologous protein boost gave a strong response. Neutralizing antibodies appeared gradually after multiple vaccine doses. The vectors will be useful for testing new vaccine inserts and immunization strategies under optimized conditions of vector growth and protein expression.

SUMMARY Pemphigus vulgaris (PV) is an autoimmune disease characterized by blistering sores on skin and mucosal membranes, caused by autoantibodies primarily targeting the cellular adhesion protein, desmoglein-3 (Dsg3). To better understand how Dsg3-specific autoantibodies develop and cause disease in humans, we performed a cross-sectional study of PV patients before and after treatment to track relevant cellular responses underlying disease pathogenesis, and we provide an in-depth analysis of two patients by generating a panel of mAbs from single Dsg3-specific memory B cells (MBCs). Additionally, we analyzed a paired sample from one patient collected 15-months prior to disease diagnosis. We find that Dsg3-specific MBCs have an activated phenotype and show signs of ongoing affinity maturation and clonal selection. Monoclonal antibodies (mAbs) with pathogenic activity primarily target epitopes in the extracellular domains EC1 and EC2 of Dsg3, though they can also bind to the EC4 domain. Combining antibodies targeting different epitopes synergistically enhances in vitro pathogenicity., Graphical Abstract, In Brief Cho et al. use single-cell sorting methods to detect and characterize autoantigen-specific memory B cells before and during the development of pemphigus vulgaris disease. They find that memory B cells undergo ongoing affinity maturation to generate a limited repertoire or pathogenic antibodies, which work synergistically to enhance overall pathogenic activity.

The purpose of the study was to describe the differences in the activity demands of sub-elite and elite Australian men's basketball competition. Ten elite (age 28.3 ± 4.9 years, mass 97.0 ± 13.9 kg, height 197.4 ± 8.3 cm) and 12 sub-elite (age 26.1 ± 5.3 years, mass 85.9 ± 13.2 kg, height 191.4 ± 7.6 cm) Australian basketball players participated in the study. Player activity was analysed using video-based time-motion analysis across multiple in-season matches. Customized analytical software was used to calculate player activity into frequencies, mean and total durations (s), and mean and total distances (m) for standing/walking, jogging, running, sprinting, low shuffling, high shuffling, and dribbling movements. Only movement frequency was calculated for jumping and upper body activity. Multivariate analysis of variance revealed that elite players performed significantly more total movement changes (P0.001), and experienced greater activity workloads while jogging (P0.01) and running (P0.002). In contrast, sub-elite players performed significantly more standing/walking (P0.023) and sprinting (P0.003) activities. These data suggest that elite basketball competition requires a greater intermittent workload and more sustained activity demands, whereas sub-elite competition may involve greater bursts of activity and longer recovery periods. These differences are likely to reflect variations in player skill and fitness, as well as playing structure between playing standards.

Open-skill agility qualities have yet to be described in adult male basketball players. Further, the importance of open- and closed-skill agility for team selection remains unknown. Thus, this study aimed to: 1) describe the open- and closed-skill agility of adult male basketball players; and 2) compare these properties between starting and non-starting players.A cross-sectional between-group design was used. Six starting (playing time: 30.1 ± 8.8 min; age: 30.5 ± 4.8 years; height: 192.1 ± 7.7 cm; body mass: 100.5 ± 15.0 kg; VO(2max): 48.4 ± 6.6 mL∙kg⁻¹∙min⁻¹) and six non-starting (4.3 ± 3.6 min; 21.3 ± 5 years; 185.7 ± 7.4 cm; 94.4 ± 17.9 kg; 50.6 ± 3.9 mL∙kg⁻¹∙min⁻¹) state-level basketball players completed multiple trials for the Change of Direction Speed Test (CODST) and Reactive Agility Test (RAT).No statistically significant between-group differences were evident for CODST movement time (starters: 1.652 ± 0.047 s; non-starters: 1.626 ± 0.040 s, P=0.68), RAT response time (starters: 307.5 ± 100.5 ms; non-starters: 426.5 ± 140.7 ms, P=0.12), and RAT decision-making time (starters: 110.7 ± 11.0 ms; non-starters: 147.3 ± 14.2 ms, P=0.08). However, starters (2.001 ± 0.051 s) possessed significantly (P=0.02) faster RAT total movement times than non-starters (2.182 ± 0.040 s).These data support the utility of perceptual and cognitive components of agility performance in distinguishing starting from non-starting players in basketball. Consequently, basketball coaching and conditioning staff should incorporate sport-specific reactive training drills for all players during the annual conditioning plan.