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PubMed2026

LINE-1 repeats are a defining feature of the Xce.

During early development, female mammals inactivate one X chromosome to balance their X-linked gene dosage with males. While allelic choice is random in inbred mouse populations, choice can be significantly skewed in interstrain hybrids. The genetic basis of skewing has long been attributed to the mysterious "X chromosome controlling element(s)" (Xce) with different strengths among species, subspecies, and strains. When two X-chromosomes with different Xce strengths are inherited by offspring, the X chromosome with the stronger Xce will have a higher probability of remaining active. Here, we provide evidence that L1Tf repeats-a subfamily of long interspersed nuclear elements 1-plays a role in determining Xce strength. L1Tf elements form a condensed core within the inactive X (Xi) territory. Mouse strains with varying Xce strengths differ in the L1Tf copy number on the X chromosome, with the strength of the Xce allele being inversely related to L1Tf copy number. L1Tf expression mediates the Xce effect. However, in contrast to a prior report, L1Tf RNA does not coat the Xi. Rather, L1Tf promotes condensation of the Xi core. Intriguingly, L1Tfs recruit and sequester YY1 from active genes, accelerating XCI in cis. Thus, L1Tf copy number, expression, and binding of YY1 are key defining features of the Xce. We propose a model in which the Xce influences the choice of Xist alleles by promoting YY1 binding to the nucleation site for the initiation of Xist spreading.

Animals↗

PubMed2026

Evaluating the utility of melatonin in spine surgery: a systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Spine surgery is increasingly performed worldwide, and acute postoperative stressors such as pain and anxiety remain highly prevalent despite historical management with opioids and other pharmacological agents. Recently, interest has emerged in melatonin administration given its endogenous physiological roles, low cost, favorable adverse event profile, and documented benefits throughout surgical literature. PURPOSE: This study aims to consolidate the existing evidence on melatonin's utility specifically in spine surgery, an area not yet comprehensively evaluated, to inform clinical practice and enhance spine surgeon comprehension. STUDY DESIGN/SETTING: Preregistered on PROSPERO, this systematic review queried PubMed/MEDLINE, CINAHL, SPORTDiscus, and Web of Science on November 21st, 2025, for studies reporting outcomes following melatonin administration in patients undergoing spine surgery. METHODS: Study quality was assessed using the Cochrane Risk-of-Bias 2 tool. Extracted variables included demographics, comparator medications, dosages, and other relevant details. Statistical analyses included frequency-weighted means (FWMs), associated standard deviations, narrative syntheses, and limited meta-analyses, where appropriate. RESULTS: A total of 6 moderate-quality randomized trials were included from 749 screened. Melatonin (3-10 mg) was administered to 227 patients (FWM age=43.3±8.6 years; 46.2% male; BMI=26.6±3.2 kg/m2), placebo to 125 patients (age=43.2±10.1 years; 60% male; BMI=28.5±4.3 kg/m2), and active pharmacologic comparators (fentanyl, gabapentin, dexmedetomidine, zolpidem) to 151 patients (age=46.6±8.9 years; 40.5% male; BMI=26.3±3.5 kg/m2). Procedures primarily involved uncomplicated lumbar laminectomies (1-4 levels), with outcomes assessed up to 24 hours postoperatively. Melatonin was associated with significant improvements in early postoperative VAS-pain scores, blood-pressure-related, analgesic-related, and anxiety-related outcomes versus placebo across most reporting studies. Compared with active pharmacologic agents, significant benefits were observed only in select nausea- and anxiety-related instances. Limited meta-analysis (n=2) demonstrated higher 24-hour VAS-pain for melatonin versus gabapentin, though mean difference was near-negligible and harbored extensive statistical constraints. CONCLUSION: Melatonin demonstrates variable utility following spine surgery, with generally consistent anxiolysis and frequent benefit versus placebo but less consistent and comparatively weaker efficacy relative to active pharmacologic comparators. Future outcome-homogenous studies incorporating more granular, expansive comparator arms and more robust quantitative analyses are needed to further elucidate melatonin's role in advancing spine care. LEVEL OF EVIDENCE: Level II.

Humans↗

PubMed2026

Sexual selection purges mutation load, but not overall genetic diversity, decreasing vulnerability to extinction.

Theory suggests sexual selection will enhance population viability by purging deleterious alleles. However, direct genomic evidence for this fundamental idea is scarce and contradictory. We combined long-term experimental evolution with whole-genome resequencing to directly test how sexual selection affects mutation load, genomic divergence, and extinction risk in small populations (maximum Ne = 40) of Tribolium castaneum. After 156 generations, populations evolving under strong sexual selection carried substantially fewer deleterious alleles than populations under weak sexual selection, based on both individual-level estimates of missense and nonsense variants and population-level Rxy analyses, indicating more efficient purging of deleterious alleles. In contrast, nucleotide diversity and runs of homozygosity were similar across treatments, indicating that purging acted most strongly on deleterious variation, and that reduced mutation load in these small populations under strong sexual selection was not explained by demographic effects. Importantly, population-level mutation load estimates best explained extinction risk under inbreeding, directly linking sexual selection to purging and population viability. Genome scans of high and low sexual selection populations revealed peaks of divergence, which included genes involved in courtship, sex discrimination, and seminal fluid proteins. Our results provide direct genomic evidence that sexual selection can reduce mutation load without eroding standing genetic diversity and thus adaptive potential, while driving adaptive divergence in reproductive traits. This beneficial purging may help explain the widespread prevalence of sexual reproduction in nature despite inherent costs and have important ramifications as to how we manage populations of conservation concern.

Animals↗

PubMed2026

Integrative modeling of the genome structure and dynamics in fission yeast.

Genome organization in the nucleus is highly structured and dynamic. Recent advances in genomic technology have enabled the measurement of genome-wide architecture and locus-specific motion, yielding contact maps and live-cell trajectories. However, these outcomes are derived from different modalities and are not directly comparable, with their quantitative integration being a key challenge. Here we establish a genome-wide live-cell imaging platform in fission yeast Schizosaccharomyces pombe, tracking 131 chromosomal loci, along with the spindle pole body (SPB) and nucleolus, to construct a quantitative map of locus dynamics. By integrating these dynamics with contact data through polymer modeling of Hi-C data, we build a physics-based "digital twin" of the S. pombe genome consistent with the spatiotemporal dynamics of interphase chromatin. We validate it against genome-wide mobility patterns and known architectural features, including centromere and telomere clustering. The model also identifies distinct dynamical regimes: centromere- and telomere-proximal loci relax within [Formula: see text]150 s, whereas the remaining loci relax within [Formula: see text]70 s. We measure semiperiodic dynamics of SPB motion, including a characteristic peak near 225 s and [Formula: see text] fluctuations. We use the model with SPB-directed forcing to show how these low-frequency components propagate through the genome to drive genome-wide chromatin displacements. Together, this predictive physics-based modeling framework integrates genome structure and dynamics to reveal how nuclear mechanical driving forces shape chromosome motion, linking mechanically driven chromatin responses to genome maintenance and regulation.

Schizosaccharomyces↗

PubMed2026

The genomic origins and evolutionary path to a key innovation in the world's most venomous snakes.

Evolutionary innovation is a catalyst for the colonization of new environments and the adaptive radiations of major groups. Novel traits typically evolve through the modification of preexisting characters, but the genetic paths underlying their origin have been challenging to trace, and the general requirements for and relative order of different kinds of gene mutations have been difficult to assess. Here, we trace the genomic origins of four procoagulant venom toxins (factor X, factor V, group I phospholipase A2, and Kunitz-type toxins) that collectively underlie a novel, especially potent blood-clotting venom type in the recently evolved Australian brown snake and taipan clade. We find evidence for a previously unknown fifth toxin, coagulation factor VII, and show that the toxins evolved through two distinct genetic paths. The factor X and factor V toxins evolved through the sequential de novo co-option of ancestral clotting factor proteins that entailed their heterotopic expression in the venom gland, the fixation of segmental duplications containing each locus, and subsequent gain-of-function mutations that rendered factor X and factor V constitutively active. In contrast, the phospholipase A2 and Kunitz-type toxins evolved by modifying the functions of neurotoxins that were part of the venom arsenal. Our findings support models in which innovative mutations in single-copy genes precede gene duplication in the evolution of novel proteins and offer a rare view into the genesis of a complex trait that has played a central role in a major adaptive radiation.

Animals↗

PubMed2026

Ribosome stalling position, spacing, and A-site occupancy impact translation and cotranslational mRNA decay in plants.

Ribosomes can pause during mRNA translation, but what causes pausing, how pauses affect protein production, and whether they trigger cotranslational mRNA decay are poorly understood in plants. Here, we investigate the causes and consequences of ribosome pausing in Arabidopsis and maize. This is accomplished by sizing, mapping, and quantifying footprints of individual ribosomes (monosomes) and closely spaced ribosome pairs (disomes) at single-codon resolution on open reading frames (ORFs). Ribosome footprinting was combined with 5'P-degradome-seq to examine the coincidence of pausing with cotranslational decay under control conditions and brief hypoxia in Arabidopsis. The data resolve two monosome conformations and three disome configurations. These include monosomes with a vacant or occupied A-site and disomes that have collided or are separated by one or two codons. Pausing is prevalent at initiation, termination, and di-Proline codons. Di-Proline pauses do not trigger cotranslational decay but appear important in cotranslational protein processing. Brief hypoxia induces stalling of A-site vacant ribosomes at Aspartate codons, often coinciding with 5'P peaks, indicating that rate-limiting decoding can trigger cotranslational mRNA decay. Notably, actively transcribed and translated hypoxia-response mRNAs accumulate 1- to 2-codon-separated disomes and are actively degraded. Comparative analysis of footprints in the two species reveals ribosome conformations and codon-specific pausing can be conserved or lineage-specific, as exemplified by pausing at di-Prolines and on Conserved Peptide upstream ORFs. In sum, the stalling of ribosomes at specific codons, coupled with ribosome A-site occupancy and disome spacing, modulates protein production and cotranslational mRNA decay in plants.

Ribosomes↗

PubMed2026

Neighborhood Hostility is Associated With the Relationship Between Park Proximity and Physical Activity Among Youth: National Evidence From Chile.

PURPOSE: Physical inactivity among youth is highly prevalent worldwide. Although proximity to parks and recreational facilities is generally associated with higher physical activity (PA), unsafe or hostile neighborhood environments may limit their use. This study examined whether neighborhood hostility moderates the association between access to recreational facilities and adherence to World Health Organization PA guidelines among Chilean youth. METHODS: This cross-sectional study analyzed data from the 2024 National Physical Activity and Sport Survey of Chile, including 3,477 urban participants stratified into childhood (5-10 years), early adolescence (11-13 years), and late adolescence (14-17 years). Built environment exposures included perceived access to recreational facilities, a cumulative neighborhood hostility score (0-5). Logistic regression models were stratified by age group and adjusted for covariates. Interaction terms assessed moderation by neighborhood hostility, and causal mediation analyses were performed. RESULTS: Adherence to World Health Organization guidelines was low (41.9% in childhood, 43.8% in early adolescence, and 43.9% in late adolescence). Greater distance to recreational facilities was associated with lower odds of meeting activity guidelines. Higher neighborhood hostility was independently associated with lower PA levels. Among adolescents, neighborhood hostility substantially attenuated the association between proximity and activity. Mediation analyses indicated partial mediation, with effective park utilization emerging as the strongest mechanism, accounting for 21.8% of the association (p < .001), followed by psychological motivation (11.9%). DISCUSSION: Proximity to recreational infrastructure alone is insufficient to promote PA in hostile neighborhoods. Policy approaches should integrate infrastructure provision with strategies addressing neighborhood safety and promoting active engagement.

Humans↗

PubMed2026

A Randomized Clinical Trial to Compare Moxifloxacin Versus Azithromycin for the Treatment of Mycoplasma genitalium: The FARTHEST Study.

BACKGROUND: Mycoplasma genitalium (MG) is increasingly characterized by high rates of macrolide and fluoroquinolone resistance. International guidelines recommend resistance-guided therapy; however, access to genotypic testing is limited, and randomized trial evidence is lacking. We assessed the efficacy of moxifloxacin and azithromycin without resistance assays. METHODS: This monocentric, open-label, superiority, randomized controlled trial enrolled adults with MG infection detected by multiplex PCR, randomized 1:1 to receive moxifloxacin 400 mg daily for 10 days or azithromycin 500 mg daily for 6 days. A test of cure was performed ≥28 days after treatment completion. The primary endpoint was microbiological cure in the intention-to-treat (ITT) and per-protocol (PP) populations. Subgroup analyses assessed symptomatic versus asymptomatic infections, doxycycline exposure, re-treatment, and sexual behavior. RESULTS: Among 358 randomized participants, 87.0% of those treated with moxifloxacin and 61.2% of those treated with azithromycin achieved microbiological cure in the ITT analysis (absolute risk difference 25.8%, 95% CI 16.5, 35.2). The superiority of moxifloxacin was confirmed in the ITT and PP populations. Moxifloxacin remained superior across most subgroups, whereas azithromycin showed comparable efficacy only among heterosexual individuals. Doxycycline coadministration did not improve outcomes. Both regimens were well tolerated, with only one case of discontinuation. CONCLUSIONS: Moxifloxacin demonstrated superior efficacy compared to azithromycin for treating MG infection in the absence of resistance testing. These randomized data support the use of moxifloxacin as a first-line option when resistance assays are unavailable and may inform treatment strategies.

Humans↗

PubMed2026

Direct Initiation of Long-Acting Cabotegravir Plus Rilpivirine in People with HIV and Suboptimal Virologic Suppression: A Randomized Trial.

BACKGROUND: Long-acting injectable cabotegravir plus rilpivirine (LA CAB+RPV) is approved for virally suppressed people with human immunodeficiency virus (HIV), but evidence for its use in those with persistent viremia and adherence challenges remains limited. METHODS: We conducted a multicenter, open-label, randomized study involving oral antiretroviral therapy (ART)-experienced people with HIV who had been diagnosed with HIV for at least 12 months and a most recent HIV-1 RNA level of at least 200 copies per milliliter. Participants with resistance-associated mutations to CAB or RPV were excluded. Eligible participants were randomly assigned in a 1:1 ratio to receive immediate LA CAB+RPV or to continue standard oral therapy until Week 24 (delayed switch group). The primary endpoint was the proportion of participants with an HIV-1 RNA level of less than 200 copies per milliliter at Week 24. RESULTS: Of 61 randomized participants, 45 met eligibility criteria and were included in the analysis; 91% were male, and the median baseline HIV-1 RNA was 35,000 copies/mL. At Week 24, viral suppression was achieved in 88.0% (22/25) in the immediate LA group versus 55.0% (11/20) in the delayed switch group (relative risk for failure to achieve viral suppression, 0.27; 95% CI, 0.08-0.86; p = 0.026). The effect of LA CAB+RPV was sustained through Week 52. CONCLUSIONS: Among people with HIV and viremia associated with adherence challenges, immediate initiation of LA CAB+RPV resulted in higher rates of viral suppression than continued oral ART, supporting its use beyond populations with stable suppression.

HIV↗

PubMed2026

High-Dose Intravenous Vitamin C and Mortality and Organ Dysfunction in Severe Burn Injury: The VICTORY Randomized Clinical Trial.

IMPORTANCE: Severe burn injury triggers systemic inflammation that can lead to multiple organ dysfunctions and death. High-dose intravenous vitamin C has been proposed to mitigate these effects, but strong evidence in patients with burn injury is lacking. OBJECTIVE: To evaluate the efficacy of high-dose intravenous vitamin C in patients with severe burn injury. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled phase 3 trial conducted across 24 burn centers in North, Central, and South America; Europe; and Asia. Adults (≥18 years) with deep second- and/or third-degree burns covering 20% or more of total body surface area and requiring skin grafting were enrolled between August 18, 2020, and September 12, 2025. Final follow-up was completed in March 2026. The trial was stopped early after the first prespecified interim analysis for futility/harm. INTERVENTIONS: Patients were randomly assigned (1:1) to receive intravenous vitamin C (50 mg/kg every 6 hours for 96 hours) or matched placebo. MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of 28-day mortality and persistent organ dysfunction (defined as dependence on mechanical ventilation, kidney replacement therapy, or vasopressor/inotrope support at day 28). The main secondary outcome was time to discharge alive from hospital within 90 days. RESULTS: Among 238 patients enrolled (mean age, 48.9 [SD, 19.1] years; 79% male; mean total body surface area, 37.0% [SD, 14.6%]), 120 were assigned to vitamin C and 118 to placebo. The primary composite outcome occurred in 49 patients (40.8%) in the vitamin C group and 35 patients (29.7%) in the placebo group (adjusted risk ratio [RR], 1.28 [95% CI, 0.99-1.65]; P = .06), crossing the prespecified futility/harm threshold and prompting early trial termination. Time to discharge alive from hospital within 90 days was not improved (adjusted subdistribution hazard ratio, 0.85 [95% CI, 0.62-1.16]; P = .31). Twenty-eight-day mortality was higher in the vitamin C group (15.0% vs 7.6%; adjusted RR, 1.96 [95% CI, 1.32-2.90]; P = .001), as was hospital mortality (23.3% vs 16.1%; adjusted RR, 1.44 [95% CI, 1.03-2.00]; P = .03). CONCLUSIONS AND RELEVANCE: Among patients with severe burn injury, high-dose intravenous vitamin C did not reduce 28-day mortality and persistent organ dysfunction and is possibly harmful. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04138394.

Humans↗

PubMed2026

Comparison of posterior cellular bonegraft options for single-level lumbar spinal fusion: a randomized trial.

BACKGROUND: Iliac bone autograft (IBG) is osteoinductive/osteogenic/osteoconductive but requires an additional harvesting procedure with known morbidities. Bone morphogenic protein (BMP) is osteoinductive and effective in obtaining fusion but is used off label for posterior fusion, has multiple side effects, and is expensive. Stem cell bone products, both auto- and allograft are attractive osteoinductive alternatives that avoid morbidity related to the graft donor site and may have a better safety profile than BMP. Morcelized allograft bone is osteoconductive but not osteoinductive or osteogenic. PURPOSE: Evaluate and compare the effectiveness of 6 types of viable or osteoinductive bone graft material in obtaining a solid posterior spinal fusion (PSF) for single level anterior/posterior lumbar spinal fusion. The bone grafts were IBG, BMP, autogenous stem cells (MSC) from concentrated bone marrow aspirate (BMA), allograft MSC from bone marrow, adipose tissue, or amniotic fluid, combined with inert cancellous allograft (Allo). STUDY DESIGN/SETTING: Prospective, single-blinded randomized study of 6 cohorts and inert historical control. PATIENT SAMPLE: Elective anterior-posterior lumbar spinal fusion of 175 patients. OUTCOME MEASURES: Assessments included pre and postoperative back and leg pain (VAS) scores, pain drawing, disability (ODI) scores, pain medication usage, and 1-year postoperative thin-cut CT scans (read by blinded radiologists). METHODS: Patients who were surgical candidates for a 1-level anterior/posterior lumbar fusion were randomized to 1 of 6 types of posterior bone graft alternatives: IBG, BMP, BMA, allograft MSC derived from bone marrow combined with morcelized Allo (cAlloBone), adipose derived MSC combined with morcelized Allo (cAlloFat), or amnion derived MSC combined with morcelized Allo (cAlloAm). Historical Allo patients served as a negative control group. Each group (n 27) had prospective outcomes and were followed for a minimum of 2 years. Fusion rate and outcomes were compared and referenced to Allo group. RESULTS: All but 5 patients had a solid ASF. The posterior fusion rates were 98% for IBG, 94% for BMP, 85% for BMA, 67% for cAlloBone, 64% for cAlloFat, 62% for cAlloAm, and 50% for Allo. Outcomes were significantly improved for all measures for all groups and there was no difference between groups except cAlloFat had slightly greater improvement in back pain in the 7-12 month follow-up period. BMP was the most expensive graft material; cellular allografts had a high-cost relative to fusion rate. CONCLUSIONS: For single level ASF/PSF, the PSF fusion rate was significantly greater for IBG and BMP followed by BMA. Various allograft MSC bone graft options resulted in lower fusion rates but may be greater than Allo. Outcomes were uniformly improved regardless of the type of graft used or the fusion status of the posterior fusion as long as the interbody fusion was solid. If bone graft cost savings is a consideration for PSF, then IBG has the greatest radiographic value, and Allo the greatest clinical value as long as the anterior interbody fusion is solid.

Humans↗

PubMed2026

Pregnancy diet based on ancestral patterns increases growth in subcortical fetal brain regions.

Evidence on the biological basis for maternal nutrition effects on fetal and newborn neurodevelopment remains limited. This randomized controlled trial in Ecuador tested a maternal dietary pattern-derived from empirical studies of nutrition in human evolution and adapted locally-on offspring growth and brain development. Pregnant women (n = 215) in their first trimester were randomized to: 1) control (n = 104); or 2) Mikhuna ("nourish" in Kichwa) intervention (n = 111). The intervention, from 12 wk gestation to birth, consisted of a weekly food delivery (8 eggs, 500 g fish, and a variety of sustainably sourced fruits and vegetables) and a behavior change communication strategy encouraging diet diversity and limiting highly processed foods. Longitudinal data collection occurred at 12 wk, 21 wk, 35 wk gestation, and 2 wk postpartum, and included ultrasound imaging of fetal bone and brain parameters, maternal dietary intakes, anthropometry, socioeconomic and demographic variables, and other biomarkers. At close of intervention, a significantly higher percentage of women met the minimum dietary diversity threshold in Mikhuna (74.5%) vs. control groups (55.8%) (P = 0.004). Generalized linear regression models showed significant differences in Mikhuna compared to control for: corpus callosum length 0.19 cm (95% CI [0.02, 0.35]), gangliothalamic ovoid height 0.15 cm (95% CI [0.03 to 0.26]), and femur length -0.10 cm (95% CI [-0.19, -0.02]) from 21 wk to 35 wk; and corpus callosum Z 0.56 (95% CI [0.03, 1.09]) and femur length Z -0.21 (95% CI [-0.42, 0.00]) at 35 wk. The Mikhuna intervention increased the growth of subcortical fetal brain structures, which have established roles in motor control, cognition, and signal transmission.

Female↗

PubMed2026

Swab Testing to Optimize Pneumonia Treatment With Empiric Vancomycin: A Randomized Controlled Trial.

BACKGROUND: Fear of methicillin-resistant Staphylococcus aureus (MRSA) as a cause of community-acquired pneumonia (CAP) frequently leads to empiric vancomycin coverage. Data evaluating the use of MRSA polymerase chain reaction (PCR) nasal swab testing to guide vancomycin de-escalation is limited for patients in the intensive care unit (ICU). METHODS: Swab Testing to Optimize Pneumonia Treatment With Empiric Vancomycin (STOP-Vanc) is a pragmatic, prospective, single-center, non-blinded randomized trial in which adult ICU patients with suspicion of CAP were randomized 1:1 to receive usual care either with (intervention) or without (control) the addition of MRSA nares PCR testing following ICU admission. The primary outcome was vancomycin-free hours alive, defined as the expected number of hours alive and free of vancomycin use within the first 7 days of trial enrollment as estimated using a longitudinal proportional odds state transition model adjusted for baseline covariates. RESULTS: A total of 277 adult ICU patients were randomized. Methicillin-resistant Staphylococcus aureus PCR nasal swab testing had a negative predictive value (NPV) of 98.9% in the intervention arm. The primary endpoint, vancomycin-free hours alive, was 105.7 in the control arm and 109.7 in the intervention arm (adjusted difference, 4 hours; 95% CI, -9.5-18.2; P = .458). CONCLUSIONS: Despite MRSA PCR nasal swab testing demonstrating a high NPV in this critically ill population, MRSA PCR nasal swab testing did not decrease the duration of vancomycin use or 30-day mortality among ICU patients with suspected CAP. Additional clinician education and antimicrobial stewardship interventions might be needed to reduce vancomycin use in this patient population. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov NCT06272994 (STOP-Vanc).

Humans↗

PubMed2026

Recombinant vs Standard Influenza Vaccine in Adults With Severe Obesity: A Randomized Clinical Trial.

BACKGROUND: Individuals with severe obesity are at increased risk of severe influenza and may have impaired immune responses to vaccination. Recombinant influenza vaccine (RIV) may provide enhanced protection compared with egg-based standard-dose influenza vaccine (SD), but data in this high-risk population are limited. METHODS: The AP-HP FLUO trial (NCT05409612) was an open-label, randomized clinical trial conducted in 15 centers in France (November 2022-March 2023) with 6 months of follow-up. Adults with BMI ≥35 kg/m2 were randomized 1:1 to receive RIV or SD, using minimization by center, age (<50 vs ≥50 years), and BMI (<40 vs ≥40 kg/m2). The primary outcome was the ratio (RIV/SD) of geometric mean hemagglutinin-inhibition (HAI) titers (GMTs) for 4 influenza strains 28 days after vaccination. Safety and reactogenicity were also assessed. RESULTS: A total of 206 participants were included (104 RIV, 102 SD). Median age was 50 years, 60.2% were women, and median BMI was 41.0 kg/m2. At Day 28, GMT ratios favored RIV for A/H1N1 (1.6; 95% CI, 1.1-2.3), A/H3N2 (2.0; 95% CI, 1.3-3.2), and B/Yamagata (1.3; 95% CI, 1.0-1.8), but not for B/Victoria (0.9; 95% CI, 0.6-1.3). The effect did not vary significantly across the different age and BMI groups. By Day 180, titers did not differ significantly. Reactogenicity and safety profiles were similar between groups. CONCLUSIONS: In adults with severe obesity, RIV elicited stronger short-term humoral immune responses than an egg-based standard-dose vaccine, suggesting potential additional benefit for influenza prevention in this vulnerable population.

Humans↗

PubMed2026

Hypertension in a Randomized Trial of Dolutegravir- Versus Efavirenz-Based Antiretroviral Therapy in Pregnant and Postpartum Women with HIV.

INTRODUCTION: We performed an analysis of incident hypertension in a randomized trial comparing dolutegravir (DTG) + emtricitabine (F)/tenofovir alafenamide (TAF) versus DTG + F/tenofovir disoproxil fumarate (TDF) versus efavirenz (EFV)/F/TDF in pregnant and postpartum women with HIV. METHODS: Women were randomized at 14-28 weeks gestational age (GA) to start DTG + F/TAF, DTG + F/TDF, or EFV/F/TDF and followed through 50 weeks postpartum. The composite incident hypertension outcome was defined as initiation of antihypertensive medication or ≥2 elevated blood pressures categorized as elevated (130-139 and/or 80-89 mmHg), mild (140-159 and/or 90-99 mmHg), moderate (≥160-179 and/or ≥100-109 mmHg), and severe (≥180 and/or ≥110 mmHg). Incident gestational hypertension was defined by initiation of antihypertensive medication or ≥2 blood pressures ≥ 140 and/or ≥90 mmHg at ≥20 weeks GA with resolution by 12 weeks postpartum. Cox proportional hazard models were used for by-arm comparisons of the composite outcome and to look for the effect of weight change within arm. RESULTS: Of 626 women without baseline hypertension (median age 26.6 years), the composite incident outcome occurred in 49% (n = 308), predominantly due to the incident elevated category of elevated blood pressure, with no significant differences by arm, although hypertension was numerically more likely in the DTG arms. Each additional 5 kg of weight was associated with an 8%-17% higher hazard of the composite hypertension outcome. Twenty-seven participants (4.3%) had gestational hypertension with no apparent differences between arms. CONCLUSIONS: Our data contribute information regarding the safety of DTG-based ART and TAF in pregnant and postpartum women and highlight the importance of monitoring weight and performing hypertension screening as part of maternal health care for young women with HIV.

Humans↗

PubMed2026

Safety and Tolerability of Oral Islatravir Once Monthly as Pre-exposure Prophylaxis in Cisgender Men and Transgender Women Who Have an Elevated Likelihood of HIV-1 Exposure: Results From the IMPOWER-24 Randomized Phase 3 Study.

BACKGROUND: Islatravir once monthly (qm), a nucleoside reverse transcriptase translocation inhibitor with a long half-life, was evaluated for safety and tolerability in cisgender men and transgender women who have sex with men and are at increased likelihood of HIV-1 (HIV) exposure. METHODS: IMPOWER-24 (NCT04652700) was a double-blind, Phase 3 study. Participants were randomized 2:1 to islatravir 60 mg oral qm or emtricitabine (FTC; 200 mg) coformulated with either tenofovir disoproxil (245 mg) or tenofovir alafenamide (TAF; 25 mg) once daily (qd). After ∼9 months, blinded islatravir was discontinued due to lymphocyte reductions; participants were offered open-label comparator for 20 months. RESULTS: In total, 494 participants were enrolled (328 islatravir; 166 comparator): 91.5% were cisgender men, 41.7% were White, and median age was 27 years. Mean blinded dosing duration was 4.7 months (islatravir) versus 4.3 months (comparator). Overall, 211 participants (64.3%) in the islatravir group and 128 (77.1%) in the comparator group had ≥1 adverse event (AE). Most AEs were mild or moderate, with 1 AE leading to product discontinuation (islatravir; gastroesophageal reflux). Serious AEs occurred in <2%; none were related to study product. Change in total lymphocytes in the islatravir group at Month 3 was -7.4%; a trend toward recovery was observed after islatravir was stopped. Mean total lymphocytes remained within normal range. No HIV infections occurred in either group during the double-blind phase. CONCLUSIONS: Islatravir qm was generally well tolerated; decreases in total lymphocytes were observed with islatravir. Original primary efficacy objectives were not assessed due to early study stoppage.

Humans↗

PubMed2026

Predictors of Treatment Failure in Children With HIV Starting First-line Antiretroviral Therapy in the ODYSSEY Trial.

BACKGROUND: Data on predictors of treatment failure in children starting antiretroviral therapy (ART) are limited, particularly on dolutegravir-based regimens (DTG). METHODS: ODYSSEY demonstrated superior efficacy of DTG versus standard-of-care (SOC). We assessed predictors at ART initiation of treatment failure by 96 weeks. RESULTS: Three hundred and eighty-one children started first-line ART (82% African). At ART-initiation, median age was 10.5 years (IQR: 6.5, 14.0, 67 < 3 years), CD4% 20% (IQR: 12, 28), BMI-for-age Z-score -.58 (IQR:-1.48, +.25). One hundred and eighty-nine children started DTG, 192 started SOC (91% ≥3 years started efavirenz; 79% <3 years started lopinavir). Seventy-five children experienced treatment failure (24 DTG, 51 SOC). Failure risk was lower on DTG than SOC (hazard ratio [HR] = 0.47, 95% CI: 0.29-0.77, P = .002). Lower BMI-for-age Z-score (HR = 0.82 for each unit gain, 95% CI: 0.70-0.96, P = .01) and being at an African site (HR = 2.09, 95% CI: 0.82-5.31, P = .09) were associated with higher failure risk. Risk was also higher at younger ages with the steepest increase in the youngest children and increased at lower CD4%, with a stronger CD4% effect at younger ages. At CD4% = 20, HRs relative to age 10 years were 2.40 (95% CI: 1.58-3.65) at age 1 year, 1.30 (95% CI: 1.15-1.48) at age 5 years, and 0.80 (95% CI: 0.72-0.89) at age 18 years. At age 1 year, HRs relative to CD4% = 20 were 1.39 (95% CI: 1.16-1.66) at CD4% = 15, and 0.52 (95% CI: 0.36-0.75) at CD4% = 30; at age 10, corresponding estimates were 1.07 (95% CI: 0.94-1.20) at CD4% = 15, and 0.88 (95% CI: 0.69-1.13) at CD4% = 30. CONCLUSIONS: Young age, low BMI-for-age, and low CD4% at ART initiation predicted higher risk of treatment failure and can guide targeted support.

Humans↗

PubMed2025

The impact of the COVID-19 pandemic on osteoporotic fractures: a systematic review and meta-analysis.

BACKGROUND: Recent reports suggest that the COVID-19 pandemic and associated lockdowns may have influenced the epidemiology of osteoporotic fractures, but results vary across regions and fracture types. The aim of this study was to provide evidence-based insights into the impact of the pandemic on osteoporotic fracture incidence. METHODS: We searched four databases (PubMed, Embase, Cochrane Library, and Web of Science) up to August 2025 for observational or retrospective studies comparing osteoporotic fracture incidence during the COVID-19 pandemic (2020) with the pre-pandemic period (2019). The primary outcome of interest was the change in fracture incidence, analysed using risk ratios (RR) with 95% confidence intervals (CI) in Review Manager 5.4. Subgroup analyses were performed by sex, geographic region, and fracture type. RESULTS: Nine studies meeting the inclusion criteria were analysed. Overall, "all types" of osteoporotic fractures showed a significant decrease during the pandemic (RR = 0.85, 95% CI 0.80-0.91, p < 0.0001). Specifically, forearm fractures decreased significantly (RR = 0.87, 95% CI 0.79-0.96, p = 0.002). However, for the most clinically significant fractures, no statistically significant global change was found for hip fractures (RR = 0.93, 95% CI 0.76-1.15, p = 0.14) or vertebral fractures (RR = 1.35, 95% CI 0.85-2.15, p = 0.20). In regional subgroup analysis, hip fracture incidence decreased significantly in South America (RR = 0.79, p = 0.0004) and in both males and females, but no significant change was observed in Europe (RR = 0.92, 95% CI 0.81-1.04, p = 0.17). CONCLUSION: During the COVID-19 pandemic, there was a decrease in the incidence of minor fractures, such as those of the forearm, likely due to reduced outdoor activity. However, the incidence of major osteoporotic fractures (hip and vertebral) remained stable globally, with significant reductions observed only in specific regions like South America.

Humans↗