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PubMed2026

Genomic insights into an optrA-carrying plasmid associated with linezolid resistance in clinical Enterococcus faecalis isolates, Argentina.

The spread of the transferable optrA gene poses an increasing threat to the clinical efficacy of oxazolidinones. Here, we characterized a novel optrA-carrying plasmid, pEfa-optrA-Arg, from a linezolid-resistant Enterococcus faecalis clinical isolate from Argentina. The 68,653-bp conjugative plasmid harbored optrA together with multiple antimicrobial resistance genes and showed high similarity to a plasmid previously identified in a bovine isolate from Switzerland. pEfa-optrA-Arg, or a closely related variant, was also detected in E. faecalis isolates from several Argentinian hospitals, highlighting the role of horizontal gene transfer in the spread of antimicrobial resistance across human and animal reservoirs within the One Health continuum.

Enterococcus faecalis↗

PubMed2026

Ageing effects on chemical, physical, mechanical, and morphological properties of clear aligners - a systematic review.

BACKGROUND: Clear aligner (CA) therapy has experienced rapid use over the past two decades to treat orthodontic malocclusions. However, evidence on CA material degradation in the oral environment remains limited and often focuses on single brands or isolated material properties. OBJECTIVES: To investigate CA ageing characteristics across different materials and brands and evaluate the chemical, physical, mechanical, and morphological changes following simulated or intraoral ageing. SEARCH METHODS: Five databases (PubMed, Web of Science, MEDLINE [Ovid], ProQuest, and Scopus) were searched to 18 March 2026, with no restrictions. ELIGIBILITY CRITERIA: Studies assessing CA properties after intraoral use or simulated ageing (thermocycling, cyclic loading, or liquid immersion) were included. DATA COLLECTION AND ANALYSIS: Study selection followed PRISMA 2020. RoB was assessed using QUIN for purely in vitro studies, JBI for cohort in vivo studies, and Cochrane RoB 2 for RCTs. Results were synthesised narratively and organised by property domain, as substantial methodological heterogeneity precluded formal meta-analysis. Where protocols were comparable, a simple pooled weighted mean was calculated and presented graphically. RESULTS: Ninety-five studies were included. RoB was low in eight studies, moderate in sixty-two, and high in twenty-five. Chemical composition remained largely stable during ageing, though some brands showed trace elemental release. Physical, mechanical, and morphological properties showed material-dependent deterioration. Pooled discolouration was greatest with coffee (weighted mean ΔE = 70.9), versus tea (ΔE = 18.4) and red wine (ΔE = 11.5), with Invisalign® consistently exceeding the clinically perceptible threshold. Force decay of 40-90% typically occurred within 48 h. Thermoplastic polyurethane (TPU)-based and directly printed aligners (DPAs) generally showed greater susceptibility than polyethylene terephthalate glycol-modified (PETG)-based aligners, though findings on hardness, roughness, and stiffness were inconsistent. CONCLUSIONS: CA materials undergo clinically relevant degradation during use, particularly in TPU-based and DPAs aligners. Clinicians may need to prioritise material-specific protocols, reinforce dietary and cleaning instructions, and consider force decay when determining aligner replacement intervals. PROSPERO number: CRD420251110248.

Humans↗

PubMed2026

Unravelling Ovarian Cancer: an analysis of the Influence of LRP1 and PAI1 Genetic Variations.

To assess the potential association between LRP1 (rs715948) and PAI1 (rs2227631, rs1799889) gene variation and ovarian cancer (OC) susceptibility. This study evaluated the genotypic and allelic distributions of LRP1 gene and PAI1 gene variants using Restriction Fragment Length Polymorphism (RFLP) analysis in 134 °C patients and 134 healthy controls. LRP1 (rs715948) showed a significant association with OC risk. The TC genotype was (OR = 3.7823, 95% CI: 2.1732-6.5825, p < 0.0001), and the CC genotype has (OR = 2.1613, 95% CI: 1.0054-4.6459, p = 0.0484). The C allele was significantly more frequent in cases (46%) than controls (32%) (OR = 1.7684, 95% CI: 1.2443-2.5133, p = 0.0015). For PAI1 (rs2227631), AG and GG genotypes showed no significant association (p = 0.3519 and p = 0.1165, respectively). PAI1 (rs1799889) AG genotype was (OR = 5.855, 95% CI: 2.4663-13.9027, p < 0.0001), while GG genotype showed no significance (p = 0.1025). The dominant model of LRP1, (TC + CC) and C alleles, were significantly more frequent in OC cases, indicating a potential risk factor. In contrast, the dominant models (AG + GG) and G alleles of PAI1 (rs2227631, rs1799889) showed no significance with OC susceptibility. Genetic variation in LRP1 (rs715948) significantly associated with increased OC risk, particularly the TC and CC genotypes and C allele. The C allele of this gene is key markers linked to higher OC susceptibility. Whereas in PAI1 (rs2227631, rs1799889), dominant models (AG + GG) show no significance, association suggesting a less prominent role in OC susceptibility. These findings highlight LRP1 as a potential genetic biomarker for OC risk assessment, while the role of PAI1 variants warrants further investigation in larger sample size.

Humans↗

PubMed2026

Genomic and Phenotypic Characterization of Two Novel Enterobacter Phages With EDTA-Enhanced Antibiofilm Activity.

Multidrug-resistant members of the Enterobacter cloacae complex (ECC) are increasingly linked to difficult-to-treat infections and biofilm-mediated antimicrobial tolerance. Here, two lytic phages, vB_EhoIP_HHH and vB_EluM_RZH, displaying podovirus-like and myovirus-like morphology, respectively, were isolated from the River Chelt. HHH has a 39,582 bp genome (51.2% GC, 63 ORFs), while RZH has a 174,197 bp genome (39.4% GC, 314 ORFs), with neither genome carrying antimicrobial resistance, virulence or lysogeny-associated genes. VIRIDIC and VICTOR analyses placed HHH within Kayfunavirus and RZH within Karamvirus, supporting their classification as distinct species. Both phages demonstrated rapid adsorption, short latent periods and stability across physiological pH and temperature ranges. A phage cocktail targeting MDR ECC strain was evaluated with EDTA against established biofilms. Crystal violet assays showed the greatest biomass reduction at MOI 10 with 0.5-0.75 mM EDTA. Bliss independence analysis revealed localized synergy within this window but significant overall antagonism at higher EDTA concentrations. CFU enumeration confirmed greater activity against 24 h than 48 h biofilms. The optimized combination also reduced recoverable bacteria in a fibroblast infection model while maintaining low LDH release. These findings identify two novel lytic Enterobacter phages and support a narrow EDTA concentration window for enhanced phage-mediated antibiofilm activity.

Biofilms↗

PubMed2026

Pre-clinical evaluation of the anticaries effect of an experimental Malva sylvestris extract mouthwash using a cariogenic model in situ.

OBJECTIVE: The aim of this study was to evaluate the antimicrobial and anticariogenic potential of Malva sylvestris extract on enamel and dentin in situ. METHODS: A double-blind crossover in situ study was conducted with 12 participants wearing palatal appliances containing two bovine enamel and two dentin specimens per 3 phases, a total of 72 enamel and dentin specimens. Biofilm formation and daily sucrose exposure were allowed. Treatments were applied twice daily in three phases: Malva sylvestris (2.5%, MS); fluoride (225 ppm, F); and placebo (P). After seven days, biofilm was collected from the bovine specimens for analysis of Lactobacillus spp. and mutans streptococci by Colony Forming Unit counts (CFU log₁₀/mL). Dental demineralization of the bovine specimens was assessed by transverse microradiography (TMR). RESULTS: MS did not reduce Lactobacillus spp. counts (CFU log₁₀/mL: enamel 6.63±0.81; dentin 6.68±0.92) compared to P (6.63±0.70; 6.62±0.51). F also did not differ (6.29±0.75; 6.32±0.41; ANOVA/Tukey, p>0.38). Mutans streptococci data were inconclusive. In enamel, both MS (2320.8±768.2 %vol·µm; 101.6±27.0 µm) and F (1777.3±733.3 %vol·µm; 95.8±23.5 µm) significantly reduced integrated mineral loss and lesion depth compared to P (3517.2±1119.9 %vol·µm; 138.6±19.5 µm; ANOVA/Tukey, p≤0.0003). In dentin, MS significantly reduced integrated mineral loss (322.5 [250-580] %vol·µm) and lesion depth (30.1 [15-42.2] µm) compared to P (880 [580-1705]; 58.3 [32.2-88.6] µm; Kruskal-Wallis/Dunn, p≤0.001), while F (587.5 [305-720]; 25.2 [16.5-38.8] µm) did not differ significantly (p>0.05). CONCLUSIONS: Malva sylvestris extract had no antimicrobial effect on Lactobacillus spp. counts, but significantly reduced enamel and dentin demineralization, showing anticaries effect comparable to fluoride. CLINICAL RELEVANCE: Malva sylvestris has demonstrated promising biological activity. This study investigates the antimicrobial efficacy of Malva sylvestris against cariogenic microorganisms in situ. Our findings provide relevant evidence that M. sylvestris exert significant anticaries effects using an in situ model.

Biofilms↗

PubMed2026

Systematic review of the mutations in the active antigenic site Ø of the prefusion F protein of the Respiratory Syncytial Virus (RSV) following the implementation of monoclonal antibody prophylaxis.

BACKGROUND: Monoclonal antibody (mAb) nirsevimab, which targets the antigenic site Ø of the prefusion F protein (pre-F) of RSV, was introduced for RSV prophylaxis in several countries. METHODS: A systematic search was conducted between January 1, 2022, and July 31, 2026 for studies analyzing substitutions within the epitope of pre-F RSV protein, which is the target of nirsevimab, after the implementation of the mAb. We searched across PubMed, Scopus, Web of Science and ClinicalTrial.gov for studies involving children with confirmed RSV infection, that conducted genomic analysis. RESULTS: Seven studies (five observational and two randomized controlled trials) including 2156 RSV-positive samples (RSV-A: 1347, RSV-B: 809) were analyzed. RSV-A strains showed limited variability within antigenic site Ø, with K65R being the most common substitution and K209E being the only intermediate-resistance RSV-A substitution. RSV-B strains demonstrated substantially higher substitution frequencies, particularly involving I206M, Q209R, and S211N. Most identified substitutions appeared to represent naturally occurring polymorphisms and retained susceptibility to nirsevimab, while multiple RSV-B substitutions and combinations involving residues 64-68 and 204-208 demonstrated reduced susceptibility or high-level resistance. Resistance-associated variants were detected in 28 of 2156 (1.3%) RSV-positive samples and exclusively among nirsevimab breakthrough infections. In a sub-analysis restricted to nirsevimab-treated individuals, resistance-associated variants were significantly more frequent among RSV-B than RSV-A (9.8% vs 0.5%; p < 0.001). CONCLUSION: Most substitutions that were detected within the nirsevimab antigenic site reflect ongoing natural RSV evolution and do not significantly affect nirsevimab susceptibility. However, detection of resistance-associated variants highlights the importance of continuous genomic and phenotypic surveillance.

Humans↗

PubMed2026

E-cigarette product characteristics and packaging features and interest in e-cigarette use: Results from a randomized within-person trial nested in three prospective cohorts.

BACKGROUND: Product characteristics and packaging may be key targets for regulation to reduce e-cigarette use among youth, but existing data are limited. METHODS: Data are from an experimental study (2018-2020) nested within three prospective cohorts (age 14-26) in southern California (N = 3565). Participants were shown five e-cigarette (e-liquid) packages in a random order that varied in flavor (sweet vs. tobacco), flavor name (descriptive ["blueberry cheesecake"] vs. concept ["smurf cake"] vs. none [number only]), and cartoon image on package (yes/no). For each stimuli, survey items assessed the following outcomes: product appeal (self-enjoyment, others' enjoyment; Likert scale [1-5]), susceptibility to use (use if friends offered, curiosity; 4 ordered responses [definitely not-definitely yes]), peer acceptability (definitely not-definitely yes), and perceived harm (definitely not-definitely yes). Mixed effects proportional odds models evaluated within-person effects of each factor (flavor, flavor name, cartoon) with each outcome. RESULTS: Participants reported greater appeal, susceptibility, and peer acceptability (OR range=3.7-16.9; ps<0.05), and lower perceived harm (OR=0.61; 95%CI=0.53, 0.70) for sweet (vs. tobacco-flavored) e-cigarettes; effects were progressively stronger for younger cohorts. The descriptive flavor name rated higher than the concept flavor (OR range=1.13-2.02; ps<0.05) or number only (OR range=1.18-1.69; ps<0.05) for appeal and susceptibility measures; no differences for concept vs. number were found. The cartoon image rated higher for appeal, curiosity, and peer acceptability (OR range=1.24-1.51; ps<0.05). CONCLUSIONS: Sweet flavors, descriptive flavor names, and cartoon images may increase the appeal of e-cigarettes among youth and young adults with no history of e-cigarette use, and are key targets for regulation.

Humans↗

PubMed2026

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 ±50 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↗

PubMed2026

A host-encoded prophage targets a Candidate Phyla Radiation bacterium and shapes episymbiotic interactions.

The Patescibacteriota, also known as the Candidate Phyla Radiation (CPR), represent a large lineage of ultrasmall bacteria with highly reduced genomes and obligate dependence on bacterial hosts. Although genomic analyses have revealed CRISPR-Cas and restriction-modification systems in many CPR genomes, no cognate bacteriophages (phages) have been isolated, leaving CPR-phage interactions unexplored. Nanosynbacter lyticus TM7x, the first cultivated CPR bacterium, grows episymbiotically on its host, Schaalia odontolytica XH001, in the human oral microbiome. Here, we identify Xhp1, an inducible prophage of XH001 that is preferentially activated during episymbiosis with TM7x. Released Xhp1 particles infect prophage-free XH001 via distinct strategies determined by host growth mode, establishing lysogeny under planktonic conditions but driving lytic infection during surface-associated growth. Xhp1 also binds efficiently to TM7x and exhibits limited infection under the conditions tested, indicating direct phage-CPR interactions. Importantly, TM7x modulates Xhp1 availability in a spatially dependent manner. In planktonic culture, free-floating TM7x reduces lysogenic conversion of XH001ΔXhp1, consistent with TM7x acting as a phage sink that lowers effective phage concentration. In contrast, during surface-associated growth, TM7x increases XH001ΔXhp1 susceptibility to lytic infection, likely by locally concentrating phage particles within a constrained niche. These results demonstrate that CPR bacteria can regulate viral encounter rates through spatial organization. In spatially structured environments such as oral biofilms, such modulation may shape infection dynamics and community structure. Together, this work characterizes the first CPR-targeting phage and reveals a an important role for phages in CPR-host bacteria interactions.

Prophages↗

PubMed2026

Draft genome sequence of Enterococcus casseliflavus strain MBBL_MP4 isolated from healthy bovine milk.

We report the draft genome sequence of Enterococcus casseliflavus MBBL_MP4, recovered from healthy bovine milk. The 3.45-Mbp genome assembly comprises 27 contigs and indicates low pathogenic potential, with no acquired antimicrobial resistance or known virulence genes. This genome provides a valuable resource for the genomic characterization of bovine-associated E. casseliflavus.

Enterococcus casseliflavus↗

PubMed2026

Endocrine-disrupting chemical-induced gene networks confer coronary heart disease risk revealed by causal inference and single-cell analyses.

BACKGROUND: Endocrine-disrupting chemicals (EDCs) are linked to coronary heart disease (CHD), but underlying mechanisms remain unclear. We aimed to identify EDC-related genes and evaluate their causal roles in CHD. METHODS: We curated EDC-related genes from a compound-gene interaction database and integrated them with CHD genome-wide association study (GWAS) summary statistics and tissue-specific expression quantitative trait loci (eQTL) data. Two-sample Mendelian randomization (MR) and Bayesian colocalization were applied to infer causality. Functional enrichment, single-cell RNA sequencing of human coronary arteries, and EDC-gene networks were further analyzed. RESULTS: After FDR correction, 39 genes were significantly associated with CHD risk via MR. Four genes-ZNF827, FCHO1, IPO9 (protective), and RPL13 (risk-increasing)-showed strong colocalization (PPH4 > 0.9). Pathway and single-cell analyses of coronary artery tissue indicated that vascular and immune pathways mediate these effects. An interaction network highlighted associations between specific EDCs and candidate genes implicated in CHD susceptibility. CONCLUSION: This integrative genomic study provides evidence that EDCs influence CHD susceptibility through distinct gene networks, revealing potential mechanisms and molecular targets for prevention and therapy.

Humans↗

PubMed2026

ARR1 and ARR12 negatively regulate arsenic stress tolerance by controlling flavonoid metabolism in Arabidopsis.

ARR1/12-mediated cytokinin signaling negatively regulates the accumulation of glycosylated flavonoids, thereby increasing plant susceptibility to As(III) stress. Cytokinins negatively regulate arsenic stress tolerance in plants through cytokinin-signaling type-B Arabidopsis response regulators (B-ARRs), specifically ARR1 and ARR12. However, the mechanism by which cytokinin signaling regulates plant metabolite dynamics, particularly antioxidant flavonoids, in response to arsenic toxicity remains largely unknown. Here, we hypothesized that ARR1/12-mediated cytokinin signaling modulates flavonoid metabolism to regulate arsenite [As(III)] tolerance. By comparing the global metabolic changes in roots of the arr1 12 double mutant (rD) and wild-type (WT) plants, we found that As(III) stress globally reduced metabolite abundance in WT roots. Importantly, the rD mutant accumulated significantly more flavonoids, most in glycosylated forms, than WT under As(III) exposure, which was supported by the specific upregulation of UDP-glycosyltransferase genes involved in flavonoid glycosylation. Accordingly, exogenous application of the glycosylated quercitrin-enhanced As(III) tolerance in WT roots, strengthening that the increase of glycosylated flavonoids in rD roots was beneficial for plant survival under As(III) exposure. Our data collectively strongly support that the increased glycosylation of flavonoids in the rD mutant improves their antioxidant functionality, thereby enhancing the As(III) stress tolerance. This study provides a new insight into the negative role of cytokinin signaling in repressing glycosylated flavonoid accumulation, causing increased susceptibility of plants to As(III) stress. Manipulation of cytokinin signaling or flavonoid glycosylation is, therefore, a promising approach for heavy metal stress mitigation in crops.

Arabidopsis↗

PubMed2026

Evolution of Candidaemia and azole resistance in Italy: A multicentre retrospective study.

PURPOSE: Candidaemia is the most common healthcare-associated invasive fungal infection. The evolution of the epidemiology of candidaemia in Italy has not been assessed, except at the local level. The primary objective of this study is monitoring changes in the epidemiology of candidaemia and in the susceptibility profiles of Candida isolates between 2015 and 2023. METHODS: This retrospective multicentre study (2015-2023), involved 11 tertiary-care hospital microbiology laboratories across the Italian country. The confirmed candidaemia episodes were included and demographic data, hospital ward, species identification, and antifungal susceptibility profiles (Sensititre Yeast One) were collected. RESULTS: 6,927 candidaemia cases were identified; incidence increased from 1.1/1000 hospitalisations in 2017 to 2.3/1000 in 2020-2021, peaking during the COVID-19 pandemic, and declined in 2023 while remaining above prepandemic levels. Patients older than 65 years accounted for most infections. Medical wards represented the main setting of occurrence, followed by intensive care units, especially during pandemic years. C. albicans remained the most common species (45.4%), followed by C. parapsilosis (24.7%), C. glabrata (11.8%), and C. tropicalis (11.4%). Echinocandin resistance remained low (< 2% for C. albicans and C. glabrata), whereas azole resistance increased markedly, particularly in C. parapsilosis, reaching fluconazole resistance rates of 25.6% in 2022. CONCLUSIONS: Candidaemia increased during the 9-year study period in Italy, particularly in the COVID-19 pandemic, in medical wards and ICU. Emerged a growing azole resistance, underscoring the need for enhanced surveillance and informed empirical treatment strategies.

Candida species etiology↗

PubMed2026

Ribosomal protein S3: a critical regulator of human disease mechanisms.

Ribosomal protein S3 (RPS3) is an essential structural component of the 40S ribosomal subunit, yet growing evidence highlights crucial extraribosomal roles in genome maintenance, cell-cycle control, and immune signaling. Dysregulation of RPS3 contributes to diverse human disorders, including cancer, inflammatory diseases, neurodegeneration, and resistance to antimicrobial and anticancer therapies. As a cofactor of NF-κB and a participant in DNA damage responses, RPS3 occupies a node that integrates stress signaling with transcriptional reprogramming, enabling both protective and pathological outcomes. The present review critically evaluates mechanistic insights into RPS3 biology, emphasizing recent findings that delineate its context-dependent effects, discrepancies across models, and remaining gaps that restrict translational applications. Understanding these complexities is essential to assess RPS3's potential as a biomarker and therapeutic target.

Humans↗

PubMed2026

Adherence and efficacy of the 0 - 7 - 21-day versus the 0 - 1 - 6-month hepatitis B vaccination schedules among people who use drugs: a two-year randomized controlled trial.

BACKGROUND: To compare the adherence and efficacy between the 0 - 7 - 21-day and the 0 - 1 - 6-month hepatitis B virus (HBV) vaccination schedules among people who use drugs (PWUD) in China. RESEARCH DESIGN AND METHODS: A randomized controlled trial was conducted in 1261 HBV-susceptible PWUD from compulsory isolated detoxification centers (CIDCs) and methadone maintenance treatment (MMT) clinics in Xi'an. A 20 µg per-dose vaccine was used. HBV surface antibody (anti-HBs), surface antigen, and core antibody were tested at months 7, 15, and 22 after the first dose. RESULTS: Third-dose coverage was significantly higher in the 0 - 7 - 21-day group (74.40%) than in the 0 - 1 - 6-month group (51.58%, p < 0.001), mainly driven by participants from CIDCs (77.75% vs. 45.69%). Anti-HBs positive rates at months 7, 15, and 22 among participants who completed all three doses were significantly higher for the 0 - 1 - 6-month schedule (90.71%, 76.82%, and 67.35%) than for the 0 - 7 - 21-day schedule (74.23%, 49.40%, and 40.95%; all p < 0.001). HBV infection incidence was similar between schedules, but significantly different between vaccinees and non-vaccinees (p = 0.018). CONCLUSIONS: The 0 - 7 - 21-day schedule substantially enhances three-dose completion in PWUD, but induces a notably weaker anti-HBs response and persistence. Schedules should be selected based on the management models for PWUD and their individual characteristics. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR1900022403).

Humans↗

PubMed2026

Comparing Clinical and Cytokine Profiling of Genital Inflammation as Predictors of HIV Acquisition in Women.

BACKGROUND: Inflammation in the female genital tract is a key risk factor for HIV acquisition, but it remains unclear whether clinical or immunological measures best predict risk. We aimed to compare HIV acquisition among women with clinically and/or immunologically defined inflammation. SETTING: HIV-uninfected women enrolled in the CAPRISA 004 tenofovir gel randomized controlled trial in South Africa were followed for up to 34 months. METHODS: We analyzed data from 889 women, with cytokine measurements available for 774 participants. Clinical genital abnormalities were assessed at scheduled visits, and 9 cytokines were measured in cervicovaginal lavage samples. HIV incidence was compared across categories of clinical and immunological inflammation using time varying Cox proportional hazards models, adjusting for relevant covariates. RESULTS: Immunological inflammation, defined as ≥9 elevated cytokines, was present in 18% (140/774) of women. Among specific clinical signs, abnormal genital discharge (adjusted hazard ratio: 2.67, 95% confidence interval [CI]: 1.14 to 6.23, P = 0.024) and cervicitis (adjusted hazard ratio: 10.34, 95% CI: 2.46 to 43.65, P = 0.001) were significantly associated with increased HIV acquisition. Women with both clinical and immunological inflammation had the highest risk of HIV acquisition, with adjusted hazard ratios of 2.08 (95% CI: 1.10 to 3.91, P = 0.022) and 2.46 (95% CI: 1.21 to 5.03, P = 0.013), respectively. CONCLUSIONS: Clinical and immunological definitions of inflammation were each independently associated with increased HIV acquisition risk and combined, they reflected greater susceptibility. These findings highlight the important role of genital inflammation in women's HIV susceptibility, suggesting that clinical signs may provide practical early indicators of risk even as cytokine profiles provide more sensitive measures of underlying inflammation.

Humans↗

PubMed2026

Whole cell inactivated poly-bacterial preparation MV130 effect on nasal mucosal immunity and experimental human pneumococcal carriage: double-blind randomised controlled trial with controlled human infection model.

BACKGROUND: Bacterial mucosal immunotherapy has shown protection of children and adults from both viral and bacterial respiratory infections, offering the potential to reduce antimicrobial use, and hence also control antimicrobial resistance (AMR). Pneumococcal carriage of vaccine type Streptococcus pneumoniae remains high in Malawi despite infant conjugate vaccination and AMR is increasing. We compared nasal inflammation following sublingual bacterial immunotherapy including S. pneumoniae (MV130, Inmunotek, Spain) or placebo and determined the effect in an experimental human pneumococcal carriage model. METHODS: A double-blind, randomised, placebo-controlled trial in healthy adult volunteers was conducted at Queen Elizabeth Central Hospital in Blantyre, Malawi. Participants were randomly allocated to receive MV130 or placebo sublingually once daily for 42 days. Mucosal inflammation (neutrophil to T cell ratio, NTR) was measured in nasal micro-biopsies. Post-treatment, participants were challenged with 160,000 CFU/naris S. pneumoniae 6B (Spn6b). Experimental pneumococcal carriage rates post inoculation were compared between the two arms. All participants completing the study were included in the analysis. Prospective trial registration: PACTR202403820001276. FINDINGS: 107 participants were enrolled and randomised to MV130/placebo between May and December 2024. There were no serious adverse events, complete compliance was good (72%) and all adverse events were mild. 96 participants (53 male, 43 female) completed the study with 52 participants randomised to MV130 and 44 to placebo. There was no difference in mucosal inflammation (neutrophil to T cell ratio) at day 14 of the intervention MV130 NTR median = 0.737 (IQR 0.294, 2.059) and placebo NTR = 0.831 (IQR 0.450, 2.073), p = 0.64. Secondary analyses showed a rise in mucosal neutrophils after MV130 treatment and after experimental pneumococcal inoculation. There was no difference in nasal or serum anti-pneumococcal immunoglobulin or in experimental pneumococcal carriage proportion between MV130 (12/52, 23%) and placebo (10/44, 23%) groups (unadjusted risk ratio 1.02 (CI 0.49-2.12) p = 1.0). INTERPRETATION: MV130 induced non-specific mild neutrophil inflammation of the nasal mucosa but had no protective effect against experimental human pneumococcal carriage. FUNDING: Wellcome Trust.

Humans↗

PubMed2026

Timing of aneurysm repair and clinical outcomes after aneurysmal subarachnoid hemorrhage: a systematic review.

BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) causes substantial morbidity and mortality, and guidelines recommend aneurysm repair as early as feasible. However, the association between onset-to-treatment time and outcomes remains uncertain. This review synthesized evidence across multiple clinical outcomes and examined whether treatment modality modifies this association. METHODS: Searches were conducted in PubMed/MEDLINE, Scopus, and LILACS for studies comparing clinical outcomes across different onset-to-treatment windows in adults with confirmed aSAH. Findings were synthesized narratively according to the Synthesis Without Meta-analysis (SWiM) guideline. The review was prospectively registered in PROSPERO (CRD420261415084). RESULTS: Twenty reports comprising 11,096 participant records were included, with likely overlap between two reports. Treatment categories ranged from <6 h to ≥15 days. Earlier securement likely reduced pretreatment rebleeding, particularly when untreated or markedly delayed patients were included, although treated-cohort comparisons were inconsistent. More methodologically informative adjusted analyses showed no reproducible independent association between treatment timing and functional outcome or mortality. No consistent association emerged for vasospasm or related cerebral ischemia, hydrocephalus, or length of stay. Two observational studies modeled time continuously: one found a significant U-shaped mortality association with an estimated nadir at 32.6 h, whereas the other showed a similar but non-significant adjusted pattern with an estimated nadir near 12.16 h. These findings are highly susceptible to confounding by indication and survivor bias and do not establish benefit from treatment delay. Three studies formally tested modality-timing interaction; one found a significant mortality interaction and two did not. Additional stratified analyses showed no consistent modality-specific pattern. Certainty of evidence for the timing-mortality association was very low because of serious risk of bias, inconsistency, and imprecision. CONCLUSION: Earlier aneurysm securement remains supported for preventing pretreatment rebleeding. The independent association of treatment timing with mortality or functional outcome remains uncertain. The observed mortality patterns are hypothesis-generating and do not define a validated therapeutic window, support intentional treatment delay, or justify changing current guideline recommendations. Prospective multicenter studies using continuous-time modeling and rigorous methods to address confounding and survivor bias are needed.

Humans↗