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The Long Road to Long-Acting: What Oral PrEP and CAB-LA Teach Us About Scaling Lenacapavir.

Despite significant biomedical advances, human immunodeficiency virus (HIV) remains a persistent global health crisis, with over 40 million people affected as of 2023, two-thirds of whom live in the World Health Organization (WHO) African Region. However, from an HIV prevention perspective, the more urgent concern is the continued occurrence of approximately 1.3 million new infections annually, particularly in sub-Saharan Africa and in settings where incidence is stable or increasing. This commentary explores the evolving landscape of HIV prevention, focusing on the trajectory of oral pre-exposure prophylaxis (PrEP), long-acting injectable cabotegravir (CAB-LA), and the newly emerging lenacapavir. While oral PrEP opened new possibilities, adherence challenges have limited its impact. CAB-LA demonstrated superior efficacy but encountered access, cost, and delivery barriers that restricted uptake. Lenacapavir, offering 6-monthly subcutaneous dosing with ≥ 99.9% efficacy in trials, holds the potential to overcome these hurdles. As of May 2026, lenacapavir had received regulatory approval in 17 countries, including several African nations, while regulatory reviews remained ongoing in multiple additional countries, reflecting the rapid global expansion of access to this long-acting HIV prevention option. However, its success depends on clinical promise, timely licensing, affordability, and integration into health systems. Drawing from real-world lessons of oral PrEP and CAB-LA, this paper argues that a proactive, coordinated rollout of lenacapavir could dramatically expand prevention reach. With global stakeholders aiming for 3 million users by 2028 and strategic licensing in 120 countries, the groundwork is in place. The recent release of WHO guidance recommending lenacapavir as an additional PrEP option further strengthens this momentum. Yet, equitable delivery, user-centred models, and strong policy backing will be critical. Ultimately, long-acting PrEP is not just a clinical breakthrough; it is a test of health systems' ability to deliver innovation at scale.

Humans

Simultaneous Administration of Human Papillomavirus (HPV) Vaccine With Other Recommended Vaccines Among Adolescents Aged 13-17 years, National Immunization Survey-Teen (NIS-Teen), United States, 2023.

PURPOSE: To investigate the percent of adolescents who receive human papillomavirus (HPV) vaccine with one or more other vaccines recommended for adolescents in a single medical visit. METHODS: Data from the 2023 National Immunization Survey-Teen were analyzed. Timing of receipt of HPV vaccine, tetanus, diphtheria, and acellular pertussis vaccine (Tdap), quadrivalent meningococcal conjugate vaccine (MenACWY), and influenza vaccine was assessed using provider-reported vaccination histories. RESULTS: In 2023, among adolescents aged 13-17 years, 69.5% received HPV vaccine with one or more other vaccines recommended for adolescents in a single medical visit. In addition, 47.8% received specifically HPV vaccine, Tdap, and MenACWY together in a single medical visit. DISCUSSION: The HPV vaccine is commonly given with other vaccines recommended for adolescents in a single medical visit. These findings demonstrate variation in simultaneous vaccination patterns, suggesting that flexibility in the recommended adolescent vaccination schedule allows for different approaches to vaccination across clinical settings and family preferences while maintaining adherence to the recommended schedule.

Humans

Postoperative complications and outcomes after surgical treatment for tophaceous gout: A systematic review and meta-analysis.

BACKGROUND: Surgical treatment remains necessary for selected patients with tophaceous gout, particularly when mechanical limitation, nerve compression, ulceration, infection, deformity, or failure of conservative treatment is present. However, postoperative outcomes after surgery for tophaceous gout have not been comprehensively quantified. This systematic review and meta-analysis evaluated postoperative complication profiles and recurrence burden after surgical treatment for tophaceous gout. METHODS: A systematic search of PubMed, Embase, Web of Science, and the Cochrane Library was conducted from database inception to March 25, 2026. Original studies reporting postoperative outcomes after surgical treatment for tophaceous gout were included. Pooled event rates with 95% confidence intervals (CIs) were calculated using a random-effects single-arm meta-analytic approach. Primary outcomes were postoperative infection, delayed wound healing, and recurrence. Secondary outcomes were reoperation, amputation, and overall complications. Functional outcomes were summarized descriptively. RESULTS: 18 retrospective studies were included. The pooled postoperative infection rate was 11.3% (95% CI 8.0%-15.7%), delayed wound healing 9.9% (95% CI 5.1%-18.2%), and recurrence 8.5% (95% CI 4.7%-14.9%). Secondary pooled rates were 9.7% (95% CI 5.5%-16.7%) for reoperation, 3.7% (95% CI 2.0%-6.8%) for amputation, and 24.0% (95% CI 14.0%-38.1%) for overall complications. Significant subgroup differences were identified only for infection according to anatomic site and intervention type. Sensitivity analyses showed that pooled estimates were robust. The certainty of evidence was very low for all outcomes. CONCLUSIONS: Surgical treatment for tophaceous gout is associated with measurable postoperative risks, particularly infection and overall complications. These findings support careful perioperative counseling, structured postoperative surveillance, integrated long-term urate-lowering management, and more standardized reporting of perioperative risk factors and postoperative outcomes in future surgical studies of tophaceous gout.

Humans

Viscoelastic-Assisted Patient Interface Docking: A Technical Optimization in LenSx Femtosecond Laser-Assisted Cataract Surgery.

PURPOSE: To evaluate the efficacy of viscoelastic-assisted patient interface docking in LenSx (Alcon Laboratories, Inc) femtosecond laser-assisted cataract surgery (FLACS). METHODS: This was a randomized controlled trial. Patients undergoing FLACS from January to August 2025 at Aier Eye Hospital of Wuhan University were randomized via a random number table to receive balanced salt solution (BSS) or visoeleastic as the patient interface docking medium. The primary outcome was docking efficiency, measured by one-time docking success rate, the number of docking attempts, and mean docking time. Secondary outcomes included surgical safety (subconjunctival hemorrhage, capsulotomy completeness/tear rate), laser treatment duration (anterior capsulotomy time, nucleus pretreatment time, total laser emission time), and patient comfort (post-laser pain sensation). RESULTS: A total of 100 patients were enrolled, 50 in each group. Suction loss occurred in 7 patients (14%) in the BSS group and 1 patient (2%) in the viscoelastic group; the one-time docking success rate was significantly higher in the viscoelastic group (98%) than in the BSS group (86%) (chi-square = 3.93, P < .05). The viscoelastic group also had fewer mean docking attempts (1.02 &#xb1; 0.14) than the BSS group (1.16 &#xb1; 0.42), showing a significant difference (t = 2.23, P < .05). The viscoelastic group exhibited significantly shorter mean docking time (44.66 &#xb1; 4.47 seconds) compared to the BSS group (48.62 &#xb1; 3.11 seconds) (t = 2.17, P < .05). No significant differences were observed between the groups in subconjunctival hemorrhage, capsulotomy completeness/tear rate, anterior capsulotomy time, nucleus pretreatment time, total femtosecond laser emission time, or patient-reported pain sensation (all P > .05). CONCLUSIONS: Viscoelastic-assisted patient interface docking in FLACS effectively elevates one-time docking success rate, reduces docking attempts, and shortens docking time.

Humans

Flexible ureteroscopy with a flexible and negative suction ureteral access sheath versus traditional sheath for treatment of infectious upper urinary tract stones: A prospective, randomized controlled study.

To evaluate the efficacy and safety of the flexible ureteroscopy (fURS) with a flexible and negative suction ureteral access sheath (FANS) versus traditional sheath for patients with infectious upper urinary tract stones (IUUTS). A total of 185 patients were enrolled, with 93 assigned to the FANS group and 92 to the traditional UAS group. The primary outcome was the stone-free rate (SFR) at the first postoperative day. Secondary outcomes included the SFR at 30 days postoperatively, operative time, hemoglobin reduction, length of hospital stay, quality of life (QoL) improvement, incidence of ureteral stricture at 3 months, and surgery-related complications. No significant differences were observed between the two groups in baseline demographics or preoperative clinical characteristics (P&#x2009;>&#x2009;0.05). The FANS group had significantly lower white blood cell count, C-reactive protein, and procalcitonin levels at 6 and 24&#xa0;h postoperatively (all P&#x2009;<&#x2009;0.05). Mean operative time was significantly shorter (P&#x2009;<&#x2009;0.001), QoL improvement was obviously greater (P&#x2009;<&#x2009;0.001), and average hospital stay was shorter in the FANS group (P&#x2009;<&#x2009;0.001). The SFRs on postoperative day 1 and at 30 days were both significantly higher in the FANS group (both P&#x2009;<&#x2009;0.05). At 3 months, ureteral strictures occurred in three patients in the traditional UAS group and one in the FANS group, a difference that was not statistically significant (P&#x2009;>&#x2009;0.05). The overall complication rate was significantly lower in the FANS group (P&#x2009;<&#x2009;0.05). For patients with IUUTS, fURS combined with FANS effectively improves stone clearance efficiency and reduces the risk of postoperative infection.

Humans

Acetazolamide to prevent ventilatory drive withdrawal in REM sleep apnoea: a randomised controlled trial.

BACKGROUND: Obstructive sleep apnoea (OSA) pathogenesis during rapid-eye movement (REM) sleep has been linked to dips in ventilatory drive and downstream genioglossus hypotonia. The carbonic anhydrase inhibitor acetazolamide is known to increase ventilatory drive and improve OSA severity. Therefore, we tested the effect of acetazolamide on REM-predominant OSA severity (apnoea hypopnoea index (AHI) and hypoxic burden, co-primary outcomes) and underlying physiological mechanisms (ventilatory drive, ventilation and pharyngeal muscle activity). METHODS: 11 participants with REM-predominant OSA per baseline polysomnography (REM AHI/non-REM AHI&#x2265;2) were allocated to receiving acetazolamide 500&#x2009;mg for three nights (first night at half dose) or placebo according to a randomised, crossover, double-blind design. Detailed physiological polysomnography with recording of diaphragm and genioglossus electromyography was conducted after each intervention, with a 1-week washout in between. RESULTS: As hypothesised, acetazolamide reduced AHI by 35.5% (95% CI 23.1% to 46.3%) and hypoxic burden by 35.9% (95% CI 21.1% to 48.4%) vs placebo (p<0.001), meeting the primary endpoint. Mechanistic analysis in REM revealed that, unexpectedly, acetazolamide did not mitigate dips in ventilatory drive versus placebo (first decile (+0.1 (-1.0 to 1.3) L/min, p=0.8). Rather, acetazolamide reduced collapsibility (increased ventilation at eupneic drive: +1.4 (1.2 to 1.8) L/min) and raised muscle responsiveness (ventilation vs drive slope: +32 (25 to 41) %ventilation/drive, p<0.001; genioglossus versus drive slope: +0.33 (0.13 to 0.54) %max/(L/min), p=0.001). CONCLUSIONS: Acetazolamide modestly improved REM OSA, with meaningful improvements in upper airway physiology, but failed to mitigate the dips in ventilatory drive responsible for REM OSA. TRIAL REGISTRATION NUMBER: NCT05589792.

Humans

List randomization for prevalence estimation of sensitive behavioral data among women with HIV of reproductive age in Lilongwe, Malawi.

Self-reported data are subject to reporting biases, including social desirability bias. List randomization is one method that can help mitigate the impact of such biases. Here, we examined the utility of list randomization among women of reproductive age living with HIV in sub-Saharan Africa. In the Family Planning and Antiretroviral Therapy study, participants were randomized to answer 5 blocks of true/false statements via either direct or list response. Each block contained 3 nonsensitive statements and 1 sensitive statement related to either condom use or HIV disclosure. For each sensitive statement, we calculated the prevalence difference (PD) comparing list response to direct response overall and stratified by socioeconomic status. The PD for 4 of the sensitive statements was negligible. However, we found that self-report of always using a condom was reported by 53.1% at list response visits vs 34.7% at direct response visits (PD, 18.5%; 95% CI, 6.2%-30.7%), a difference that was attenuated among those with higher socioeconomic status. In this setting, list randomization did not meaningfully change the estimated prevalence for most questions, except for one question, which unexpectedly produced a higher estimate for a positive behavior. Examining this method in other settings and populations is warranted.

Humans

Exploring precision risk in pediatric vesicoureteral reflux: Innate immune gene variations and reflux outcomes in the RIVUR cohort.

INTRODUCTION: Children with vesicoureteral reflux (VUR) are at increased risk for morbidity from recurrent urinary tract infections (UTIs), yet the factors influencing spontaneous VUR resolution remain poorly defined. This study evaluates whether genetic variations in key urinary innate immune effectors (DEFA1A3, DMBT1, and RNASE7) influences VUR resolution and interacts with prophylaxis to alter clinical response. METHODS: We conducted a secondary analysis of 303 RIVUR participants with available DEFA1A3 and DMBT1 copy number variation (CNV) data and RNASE7 rs1263872 genotype. Primary outcomes were (1) VUR improvement (decrease in grade) and (2) VUR resolution at study exit. Multivariable logistic regression models included genotype, treatment, and their interactions, adjusting for age, sex, baseline grade (high vs low), laterality, bowel/bladder dysfunction, and any UTI. Internal validation used 2000-sample bootstrap with bias-corrected and accelerated confidence intervals and influence diagnostics. RESULTS: Clinical covariates did not significantly predict VUR improvement. Children with DEFA1A3 CNV >5 had higher odds of improvement (OR 2.36, 95% CI 1.12-4.96, p = 0.023), an effect that remained significant in bootstrap analyses. High-grade VUR was associated with lower odds of resolution (OR 0.34, 95% CI 0.12-0.94, p = 0.038). A significant interaction was observed between prophylaxis and high DMBT1 copy number for VUR resolution (interaction OR 2.99, 95% CI 1.11-8.04, p = 0.031); no interaction was seen for improvement. RNASE7 rs1263872 was not associated with either outcome. CONCLUSION: Innate immune gene variation may contribute to heterogeneity in VUR outcomes. High DEFA1A3 copy number was associated with reflux improvement and a DMBT1-prophylaxis interaction was associated with reflux resolution. The results of this study is hypothesis-generating and prompt further evaluation to assess whether a subset of children may experience structural benefit from prophylaxis or have a more favorable natural history based on their innate immune genotype.

Humans

Waterborne norovirus outbreaks in China, 2000-2022: a systematic review.

In China, waterborne transmission is a relatively rare route for norovirus outbreaks; however, once it occurs, the outbreaks tend to be large in scale, prolonged in duration, and difficult to control. This systematic review characterizes the epidemiological features of such outbreaks in China. We searched the WANFANG, CNKI, PubMed, and Web of Science databases for literature on waterborne norovirus outbreaks published up to November 2023. From 2000 to 2022, a total of 112 outbreaks were reported in China among the 97 articles included. These outbreaks involved approximately 19,796 cases and 565,485 exposures, median of 98 cases per outbreak, with a median attack rate of 6.09&#x202f;%. Most outbreaks occurred in southern regions, particularly in coastal provinces, with schools (59, 52.68&#x202f;%) and towns or villages (25, 22.52&#x202f;%) being the most common settings. The highest number of outbreaks was reported in February and the lowest in July, with an average of 8.25 outbreaks per month. Higher attack rates were associated with outbreaks occurring in winter, in primary schools, and in southern regions of the Qinling-Huaihe line. Contamination of barreled water and self-provided wells was the primary risk factor for waterborne norovirus outbreaks. Although waterborne transmission is a relatively rare route for norovirus outbreaks in China, it can cause large-scale outbreaks in a short period. Consequently, it is still necessary to enhance protection of water sources, rigorous water quality monitoring, and public health education on water sanitation.

Humans

A multi-model genome-wide association study identifies genetic variants underlying resistance to Largemouth Bass Ranavirus (LMBV) in Micropterus salmoides.

Largemouth bass (Micropterus salmoides) is an economically important freshwater aquaculture species, yet recurrent outbreaks of Largemouth Bass Ranavirus (LMBV) continue to impair production and cause substantial losses. The genetic basis of host variation in LMBV resistance remains insufficiently characterized. Here, we applied a multi-model genome-wide association study (GWAS) to identify loci associated with resistance following a controlled challenge with the LMBV-23PY strain. Whole-genome resequencing was performed for 146 phenotyped fish, including 72 susceptible and 74 resistant individuals. After stringent quality control, 877,262 high-quality variants were retained and tested using six GWAS models. Across binary survival status and survival time phenotypes, 32 shared suggestive variants were consistently detected across models, representing suggestive loci for LMBV-23PY resistance. Genes within &#xb1;50&#xa0;kb of these loci were annotated, and functional enrichment highlighted immune- and redox-related biological processes. Three prioritized candidates-GSTT3L (glutathione S-transferase theta-3-like), CGRP2 (calcitonin gene-related peptide 2), and NPPC (natriuretic peptide C)-were associated with pathways involved in oxidative stress responses and immune regulation. Collectively, these results provide insight into the genetic architecture of LMBV-23PY resistance in largemouth bass and identify suggestive variants and associated candidate genes for downstream validation, functional interrogation, and the development of marker-assisted and genome-enabled breeding strategies.

Animals

The effect of combining visuo-vestibular exercises with manual therapy and exercise on sensorimotor function in chronic neck pain: A randomized controlled trial.

OBJECTIVE: To investigate whether adding visuo-vestibular exercises to standard manual therapy and exercise produces superior improvements in sensorimotor function, pain, balance, and functional disability in adults with chronic neck pain. METHODS: This prospective, randomized controlled trial enrolled 58 adults with chronic neck pain (&#x2265;3 months) allocated to a manual therapy and exercise group (MtE; n&#x202f;=&#x202f;29) or MtE plus visuo-vestibular exercises (MtE-VVE; n&#x202f;=&#x202f;29). Both groups completed 12 supervised sessions over six weeks with a daily home exercise programme. Outcomes were assessed at baseline, 6 weeks, and 12 weeks, and included pain intensity (Visual Analog Scale [VAS]), upper extremity reaction time, computerized posturography, the Neck Disability Index (NDI), and cervical muscle endurance. RESULTS: Fifty-four participants (27 per group) completed the study. Both groups improved significantly across all outcomes (p&#x202f;<&#x202f;0.001). At 12-week follow-up, the MtE-VVE group demonstrated superior outcomes: activity-related pain was reduced by an additional 2.00&#x202f;cm (95% CI: 0.75-3.25; p&#x202f;=&#x202f;0.005), bilateral reaction time improved by 1.70&#x202f;s (p&#x202f;=&#x202f;0.001), eyes-open mediolateral sway decreased by 0.50&#x202f;mm (p&#x202f;<&#x202f;0.001), NDI score was 6.30 points lower (95% CI: 3.42-9.18; p&#x202f;<&#x202f;0.001), and cervical flexion and extension endurance improved by 12.00&#x202f;s and 27.70&#x202f;s, respectively (p&#x202f;&#x2264;&#x202f;0.020). CONCLUSION: Adding visuo-vestibular exercises to standard manual therapy and exercise produces clinically meaningful and sustained improvements in activity-related pain, sensorimotor function, postural control, and functional disability in adults with chronic neck pain, and may be recommended as an effective adjunctive intervention.

Humans

A systematic review of qualitative research on HIV and food insecurity in high-income countries.

OBJECTIVES: Food insecurity leads to adverse health outcomes in people living with HIV, including obesity, poor mental health and viral non-suppression. Qualitative studies in low- and middle-income countries have described the impact of food insecurity on medication adherence. However, limited qualitative research exists on the lived experiences of food insecurity among people living with HIV in high-income countries (HICs). We aimed to synthesize qualitative literature on food insecurity among people living with HIV in HICs. DESIGN: Systematic review and textual narrative synthesis. METHODS: We searched MEDLINE, CINAHL, Scopus, Embase, and PsycINFO, extracting data from included articles on a standardized form in Covidence. We synthesized literature using a textual narrative approach. We conducted quality appraisal (Critical Appraisal Skills Programme Qualitative Studies Checklist) and graded certainty of findings (GRADE-CERQual). RESULTS: We reviewed 2772 articles, reduced to 940 after deduplication, with 12 articles included after full text screening. Included articles reported on studies conducted in the United States ( n &#x200a;=&#x200a;7), and Canada ( n &#x200a;=&#x200a;5). We identified three key themes, each with their own sub-themes: the role of structural inequalities in shaping and navigating food insecurity; the impacts of food insecurity on health and wellbeing; and the labour of acquiring of food. CONCLUSIONS: Our review highlights the syndemic nature of food insecurity and HIV; intersecting experiences of multiple structural hardships constellate and interact synergistically to amplify poor health outcomes. Interventions should address the multiple and reinforcing social and structural conditions that shape food insecurity among people living with HIV.

Humans

Repeated low-level red-light therapy for improving asthenopic symptoms and accommodation in presbyopia.

BACKGROUND: To assess the short-term effectiveness of repeated low-level red light (RLRL) therapy in relieving asthenopia and enhancing accommodation in presbyopia. METHODS: This randomized, parallel-group, double-masked clinical trial enrolled adults with presbyopia and self-reported asthenopia. Participants were allocated using computer-generated randomization and randomly assigned at a 1:1 ratio to RLRL or sham groups. Blinding included participants, examiners, assessors, and statisticians. The primary outcome was the change from baseline in the Computer Vision Syndrome Questionnaire (CVS-Q) score at day 31. Secondary outcomes were the change in accommodative amplitude (AA), Near Activity Visual Questionnaire (NAVQ) score, habitual near visual acuity, near-addition power, accommodative facility, positive and negative relative accommodation, binocular cross-cylinder response, and accommodative convergence-to-accommodation ratio. Continuous outcomes were analyzed using linear mixed-effects models. RESULTS: Sixty-four of 66 randomized participants (aged 41-62&#x2009;years) completed the 1-month trial. At day 31, RLRL showed greater improvement than sham in CVS-Q score (adjusted mean difference, -1.75 points; 95% CI, -3.10 to -0.39), binocular AA (1.09 D; 95% CI, 0.37 to 1.82), and NAVQ score (-8.07 points; 95% CI, -14.17 to -1.97). The effect on AA was most pronounced in a subgroup of eyes with baseline amplitude >2.0&#x2009;D (adjusted mean difference 1.33&#x2009;D; 95% CI 0.32-2.34). Other measures did not differ between groups at each visit. No treatment-related adverse events were reported. Adherence was similar between groups (mean compliance: 98.2% vs 97.5%). CONCLUSIONS: Short-term treatment with RLRL significantly reduced asthenopic symptoms and improved accommodative amplitude in individuals with presbyopia.Trial registration: NCT06745661 (registered December 8, 2024).

Humans

Pathways of onward HIV disclosure in relationships among young people living with vertically acquired HIV receiving antiretroviral therapy: A qualitative analysis from the BREATHER Plus trial, South Africa.

For young people living with HIV (YPLHIV) navigating their status since birth, managing onward disclosure of a potentially stigmatising condition in relationships is challenging, and may or may not lead to social support, with implications for wellbeing. In a clinical trial setting in KwaZulu-Natal, South Africa, we investigate how young people living with vertically acquired HIV navigate onward disclosure. Data were from the qualitative component of the BREATHER Plus randomised controlled trial evaluating the efficacy, safety and acceptability of short-cycle dolutegravir/tenofovir-based triple antiretroviral therapy (ART) in young people aged 12-19 years. We analyse data on 35 participants receiving ART engaged in clinical trials at the research site: 29 in longitudinal in-depth interviews (IDIs) and 12 across three focus group discussions (FGDs), including 6 in IDIs and FGDs. The Disclosure Processes Model was applied in the thematic analysis. Pre-disclosure was characterised by social assessments of potential confidants. During disclosure, reciprocal vulnerability and partial information-sharing were employed. Post-disclosure processes entailed linear and non-linear feedback trajectories, impacting future disclosures. The findings show that the study cohort of young people receiving ART navigated many bidirectional disclosure pathways to maintain social connections in relationships, and counselling guidelines need to be responsive to this.

Humans

Brief Report: Beyond Testing: Exploring the Psychosocial Impact of HIV Self-Testing Among Ugandan Gender-Diverse Sex Workers.

BACKGROUND: The psychosocial effect of HIV self-testing (HIVST) on sex workers' self-esteem, depression, alcohol misuse, perceived sex work stigma, and empowerment remains poorly characterized. We hypothesized that HIVST would reduce sex work stigma and improve these psychosocial outcomes by enabling private, autonomous testing and reducing exposure to stigmatizing healthcare encounters. SETTING: Kampala, Uganda. METHODS: We conducted a secondary analysis of the Empower study (NCT03426670), an open-label randomized trial in which 117 cisgender female, transgender female, and cisgender male sex workers were assigned 1:1 to monthly HIVST plus quarterly clinic-based testing, or to quarterly clinic-based testing alone, and followed for 12 months. Self-esteem (Rosenberg Self-Esteem Scale), depressive symptoms (PHQ-2), alcohol misuse (RAPS4), perceived sex work stigma (adapted Female Sex Worker Stigma Scale), and empowerment were assessed quarterly. Mixed-effects regression models, adjusted for baseline values, evaluated intervention effects. RESULTS: Data from 117 participants were analyzed, including 7 early disenrollments. Over 12 months, HIVST participants reported significantly lower perceived sex work stigma than standard of care participants (&#x3b2; = -0.38, P = 0.04; monthly reduction P = 0.003), although the rate of decline did not differ significantly between arms (interaction P = 0.08). Self-esteem and depressive symptoms improved in both arms, with no between-arm differences (interaction P = 0.41 and 0.32). Alcohol misuse and empowerment showed no significant arm differences. CONCLUSION: HIVST may reduce sex work stigma without adverse psychosocial effects, supporting its integration into combination HIV prevention for gender-diverse sex workers in sub-Saharan Africa.

Humans

Development and protective efficacy of a live attenuated vaccine candidate against goose astrovirus.

Goose astrovirus (GAstV) is a significant pathogen affecting goslings by inducing visceral gout, yet no commercial vaccine is currently available. This study involved the serial passaging of the GAstV-GXNN strain in LMH cells to investigate alterations in viral replication, genomic stability, and pathogenicity, as well as to assess the potential of a vaccine candidate. The findings indicated that the viral titer increased progressively with each passage, reaching 107.35 TCID50/mL by the 120th passage (GAstV-GXNNP120). Whole-genome sequencing revealed the presence of 6, 19, 26, and 28 nucleotide mutations at the 30th, 60th, 90th, and 120th passages, respectively. Pathogenicity assays demonstrated a reduction in virulence with successive passages, culminating in the complete attenuation of GAstV-GXNNP120, which did not induce clinical signs or lesions in one-day-old goslings. Following five successive passages in goslings, the attenuated strain exhibited stable genetic characteristics without any reversion to virulence. Goslings aged one day, inoculated with GAstV-GXNNP120 at dosages ranging from 102.0 to 105.0 TCID50, developed neutralizing antibodies by the third day post-vaccination. Antibody levels increased in a dose-dependent manner, peaking at day 21 and remaining elevated through day 42. Challenge experiments utilizing the virulent GAstV-GXNN strain revealed that groups vaccinated with doses of 103.0 TCID50 and above achieved complete protection. These groups exhibited no clinical symptoms or pathological damage post-challenge, and both tissue viral loads and virus shedding levels were significantly reduced compared to the control group. Consequently, the minimum effective vaccination dose was established at 103.0 TCID50. These results provide a crucial foundation for the development of a live attenuated GAstV vaccine.

Animals

Searching for New Genes That Cause Usher Syndrome.

PURPOSE: The purpose of this project was to identify novel Usher syndrome (USH) candidate genes from phenotyping data of 9139 knockout (KO) mouse lines. METHODS: We evaluated phenotype data for concurrent retinopathy and hearing abnormalities in single-gene KO mice generated by the International Mouse Phenotyping Consortium (IMPC). A search was performed to determine whether each gene had been previously associated with retinopathy and/or deafness in humans. Bioinformatic tools were used to predict protein interactions, molecular functions, signaling pathways, and the expression of human orthologues of candidate genes in the retina and inner ear. RESULTS: We identified 18 single-gene KO lines exhibiting hearing abnormality and retinopathy after ear and eye examinations, respectively, and/or by histopathology. The molecular functions and signaling pathways of the human orthologues of the 18 candidate genes partially overlapped with those of USH genes. Particularly, FER and DYRK1B proteins were predicted to interact with proteins encoded by known ciliopathy genes. ADIPOR1, ATP8B1, and MPDZ were associated with retinal degeneration in humans. CHSY1 and IDUA may be pathogenic causes of hearing impairment in people. Furthermore, CHSY1, CSTB, and SPRED1 were located adjacent to unsolved genetic loci related to USH. CONCLUSIONS: A screen of 9139 KO mouse lines revealed 18 candidate genes exhibiting both retinal and inner ear abnormalities consistent with the principal clinical features associated with USH. As the observed phenotypes are attributed to gene deletion in mice, these genes warrant further study to determine the causation of retinal degeneration and hearing loss in patients.

Animals

Exposure to size-specific particulate matter accelerates DNA methylation aging in people with HIV.

BACKGROUND: People with HIV (PWH) face accelerated aging and increased health risks, with DNA methylation age (DNAmAge) as a critical senescence biomarker. Particulate matter is linked to DNAmAge acceleration (DNAmAA) in general population, but its impact in PWH remains unstudied. METHODS: Thirty-two PWH from Wuhan, China, were enrolled in a prospective panel study with follow-up, and each participant underwent at least two repeated measurements during the study period. Portable air quality monitor measured PM 1 , PM 2.5 , and PM 10 exposures 72&#x200a;h preblood sampling. We analyzed genome-wide DNA methylation in peripheral blood and calculated six AA metrics. Linear mixed-effects and weighted quantile sum regression models evaluated associations between particulate matter exposure and DNAmAA. RESULTS: Significant associations between particulate matter exposure and DNAmAA were observed at various lag windows. For every 10&#x200a;&#x3bc;g/m 3 increase in 24-h average PM 2.5 , Hannum DNAmAA, Pheno DNAmAA, Grim DNAmAA, SkinBlood DNAmAA, and Elastic DNAmAA increased by 0.266&#x200a;years [95% confidence interval (CI): 0.035-0.480], 0.421&#x200a;years (95% CI: 0.032-0.701), 0.336&#x200a;years (95% CI: 0.073-0.546), 0.295&#x200a;years (95% CI: 0.021-0.495), and 0.254&#x200a;years (95% CI: 0.034-0.445), respectively. PM 10 contributed most substantially to the cumulative PM effect on epigenetic AA in the lag0-24&#x200a;h window. CONCLUSION: Short-term particulate matter exposure, particularly PM 10 , significantly accelerates epigenetic aging in PWH, highlighting the need to integrate air quality management into healthy aging strategies for this vulnerable population.

China