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PubMed2026

Comparative effects of 12-week resistance training on unstable and stable surfaces on muscle stiffness, muscle co-activation, and balance in older patients with knee osteoarthritis.

OBJECTIVE: This randomized trial compared the effects of unstable resistance training (URT), involving resistance exercises on unstable surfaces, and stable resistance training (SRT), performed on stable surfaces, on muscle stiffness, co-activation, and balance in older adults with knee osteoarthritis (KOA). We hypothesized that URT would yield greater improvements by enhancing neuromuscular adaptability. METHODS: Fifty patients with KOA were randomly assigned to the URT group (n = 25) or the SRT group (n = 25). After attrition, 46 participants (URT: n = 23; SRT: n = 23) completed the intervention and were included in the final analysis. Both groups completed a 12-week supervised lower-limb resistance training program (3 sessions/week) consisting of 10 exercises performed under either unstable or stable support conditions. RESULTS: After 12 weeks of intervention, both groups showed significant reductions in pain intensity (p < 0.001). However, compared with the SRT group, the URT group demonstrated significantly greater reductions in quadriceps stiffness (p < 0.05), selected hamstring stiffness outcomes (p < 0.05), and quadriceps-hamstring co-activation (p < 0.001), alongside superior improvements in both dynamic balance and static balance (all p < 0.05). CONCLUSION: While both training modalities are effective for pain relief, URT elicited greater improvements in balance-related performance and neuromuscular-mechanical outcomes than SRT in older adults with KOA. These findings suggest that incorporating unstable support conditions into resistance training may provide additional rehabilitation benefits for this population.

Humans↗

PubMed2026

Digital healthcare solutions in preoperative care: A systematic review.

OBJECTIVE: Active participation in preoperative anesthesia preparation is crucial to ensure safe and efficient care. Compliance with preoperative instructions improves clinical outcomes, enhances patient satisfaction and optimizes use of healthcare resources. As digital communication becomes increasingly integrated into healthcare, interactive digital tools such as smartphone applications and Short Message Service (SMS) reminders may offer a valuable means of engaging patients in their own care. In this review, we evaluated the role of digital tools in guiding patients during their preoperative care pathway for anesthesia. METHODS: Following registration (CRD420250655119), we conducted a systematic review of studies evaluating the use of smartphone applications or SMS reminders designed to support preoperative preparation for anesthesia or procedural sedation in adult patients undergoing elective procedures. The primary outcome was compliance with preoperative instructions. Secondary outcomes included rate of late cancellations, patient satisfaction and cost-effectiveness. Studies were eligible if they reported at least one of these outcomes. RESULTS: Ten studies (1 RCT and 9 observational studies), including 11501 participants, were identified. Compliance with preoperative instructions was assessed in 8 studies, most of which reported higher compliance in patients receiving digital interventions across multiple instruction domains, although statistical significance was not consistently observed. Evidence suggested a beneficial effect on reducing late cancellations and improving patient satisfaction. However, results varied across study designs, and data on cost-effectiveness were limited. CONCLUSIONS: Digital tools for preoperative anesthesia guidance were associated with higher compliance and showed potential reduction of late cancellations and increase of patient satisfaction. However, the current evidence is predominantly observational and heterogeneous, limiting the strength of conclusions. PRACTICAL IMPLICATIONS: With healthcare systems under pressure, digital technologies may offer a scalable and patient-centered care solution to support preoperative anesthesia preparation. Nonetheless, further high-quality research is needed to evaluate their long-term clinical, economic and equity implications.

Humans↗

PubMed2026

Investigation of ACE gene polymorphism and serum ACE activity in relation to alopecia areata among Iraqi patients.

BACKGROUND: Alopecia areata (AA) is a multifactorial disorder with immune dysregulation and genetic susceptibility, affecting 0.5-2% globally. OBJECTIVE: This study investigated angiotensin converting enzyme (ACE) gene insertion /deletion (I/D) polymorphism and serum ACE activity in Iraqi AA patients and their association with inflammatory cytokines (interleukin [IL]-17) and nutritional markers to understand disease progression. METHODS: This case-control study included 50 AA patients (Male and Female) and 35 healthy controls. ACE gene polymorphism (rs1799752) was analyzed using real-time polymerase chain reaction (qPCR) with high-resolution melting (HRM) analysis. Serum IL-17 levels were determined by enzyme-linked immunosorbent assay (ELISA), and biochemical markers were measured using an automated analyzer. RESULTS: ACE gene polymorphism (rs1799752) showed non-significant genotype distribution between patient and control groups (p > 0.05), though a trend toward DD genotype enrichment was observed in patients. Serum ACE levels were significantly higher in patients versus controls (p < 0.0001) with high diagnostic performance. ACE correlated positively with IL-17 (P < 0.0001) and negatively with vitamin D3 and zinc (P < 0.0001). Female patients had significantly higher ACE levels than males (P < 0.01). CONCLUSIONS: ACE emerges as an immunometabolic hub in AA pathogenesis, integrating inflammation with nutritional deficits, suggesting its potential as a biomarker and therapeutic target.

Humans↗

PubMed2026

Histidine Supplementation Stabilizes Hearing and Vision and Improves Growth in HARS1-Related Autosomal Recessive Disorder Associated With Usher-Like Symptoms.

Autosomal recessive HARS1-related disorder (originally described as Usher syndrome type 3B) caused by a homozygous Y454S variant in the histidyl-tRNA synthetase gene (HARS1) is characterized by progressive sensorineural hearing and vision loss and respiratory deterioration with risk for sudden death following febrile illnesses. In-vitro studies have previously shown that histidine can rescue a humanized yeast model for pathogenic HARS alleles. Fourteen children homozygous for HARS Y454S were treated with supplemental oral histidine (50 mg/kg BID) and monitored with bloodwork and physical, visual, and audiometry assessments during a 3-year clinical trial, then followed for more than 4 years on histidine in the post-trial period. Patient fibroblasts were assessed for response to histidine. Hearing and vision remained stable, and growth improved significantly. Children remained healthy, with no severe deteriorations despite exposure to bacterial and viral infections, including COVID-19. Gains in growth were maintained in the post-trial period on varying levels of histidine supplementation. Daily oral histidine supplementation in children with autosomal recessive HARS1-related disorder can ameliorate or slow the progression of disease and is safe, inexpensive, and well tolerated. This study adds to the growing list of autosomal recessive ARSopathies (aminoacyl-tRNA synthetase disorders) that are amenable to amino acid supplementation.

Humans↗

PubMed2026

Hyperbaric oxygen for the treatment of traumatic incomplete spinal cord injury: a systematic review and meta-analysis of randomized controlled trials.

The therapeutic efficacy of hyperbaric oxygen therapy for traumatic incomplete spinal cord injury remains a subject of debate. To comprehensively evaluate the impact of hyperbaric oxygen on motor function, sensory function, and activities of daily living in patients with traumatic incomplete spinal cord injury, we conducted a systematic review and meta-analysis. We performed a comprehensive search across PubMed, Embase, the Cochrane Library, Web of Science, and major Chinese databases for randomized controlled trials published through June 2025. A total of 15 randomized controlled trials were included. The pooled results indicated that hyperbaric oxygen therapy significantly improved the American Spinal Injury Association motor score (mean difference = 10.30, 95% confidence interval: 7.70-12.90), the total American Spinal Injury Association sensory score (mean difference = 29.29, 95% confidence interval: 18.82-39.75), the American Spinal Injury Association light touch score (mean difference = 9.84, 95% confidence interval: 6.15-13.53), and the American Spinal Injury Association pinprick score (mean difference = 8.75, 95% confidence interval: 4.40-13.11). Furthermore, hyperbaric oxygen therapy was associated with significant enhancements in the Barthel Index (mean difference = 16.60, 95% confidence interval: 10.51-22.68) and the Functional Independence Measure (mean difference = 17.41, 95% confidence interval: 10.83-23.98). In conclusion, adjunctive hyperbaric oxygen therapy appears to improve motor function, sensory function, and activities of daily living in patients with traumatic incomplete spinal cord injury compared to conventional treatments alone. However, due to methodological limitations and potential publication bias in the included studies, these findings should be interpreted with caution, and further high-quality, multi-center randomized controlled trials are warranted.

Humans↗

PubMed2026

Efficacy, Safety, and Pharmacokinetics of Upadacitinib Among Patients in East Asia With Moderately to Severely Active Ulcerative Colitis: A Post Hoc Subanalysis of Randomized Phase 3 Studies.

BACKGROUND AND AIM: Upadacitinib, a selective Janus kinase 1 inhibitor, is approved to treat moderately to severely active ulcerative colitis (UC). This post hoc subanalysis evaluated the efficacy, safety, and pharmacokinetics of upadacitinib in patients in East Asia. METHODS: U-ACHIEVE (UC1; NCT02819635) and U-ACCOMPLISH (UC2; NCT03653026) were Phase 3, multicenter, randomized, double-blind, induction studies evaluating upadacitinib 45 mg or placebo daily in adults with moderately to severely active UC. Clinical responders to 8 weeks of upadacitinib induction were eligible to receive upadacitinib 15 mg, upadacitinib 30 mg, or placebo daily in the 52-week U-ACHIEVE maintenance study (UC3; NCT02819635). Efficacy outcomes, safety, and pharmacokinetics were evaluated among East Asian patients. RESULTS: A higher proportion of East Asian patients achieved clinical remission with upadacitinib than placebo at induction Week 8 (UC1: n = 127, 31.4% vs. 7.3%; UC2: n = 114, 31.2% vs. 2.7%) and maintenance Week 52 (UC3: n = 184, upadacitinib 15 mg, 52.4%; upadacitinib 30 mg, 53.8%; placebo, 10.7%). Rates of endoscopic outcomes were higher with upadacitinib than with placebo across studies. No new safety signals were identified. Herpes zoster occurrences were low (UC1 and UC2: upadacitinib 45 mg, two events [in one patient]; placebo, zero events; UC3: upadacitinib 15 mg, five events; upadacitinib 30 mg, eight events; placebo, zero events). Pharmacokinetics and trends in the relationship between upadacitinib exposure and efficacy were consistent in the East Asian and global populations. CONCLUSION: Upadacitinib was generally well tolerated and effective for treating moderately to severely active UC in patients in East Asia, with a favorable benefit-risk profile consistent with the global population. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02819635, NCT03653026.

Humans↗

PubMed2026

Integrated phytochemical and bioactivity profiling of Xanthium strumarium fruits from Korea and China: Implications for origin-specific quality specification.

BACKGROUND: Geographic origin influences the phytochemical composition and biological activities of medicinal plant resources. Xanthium strumarium L. (XS) fruit is widely used in East Asian traditional medicine. However, current pharmacopeial standards primarily recognize Chinese-derived material, despite the availability and traditional use of XS in Korea. To address this gap and support origin-informed quality specification, we compared fruits from Korea (XS-K) and China (XS-C) using chloroplast genome sequencing, targeted phytochemical profiling (high-performance liquid chromatography (HPLC) for selected phenolics and gas chromatography-flame ionization detection (GC-FID) for fatty acids and phytosterols, and multivariate chemometric analysis. RESULTS: Chloroplast genome analysis revealed high overall similarity but localized divergence around the rpoC2 locus and a greater mutation burden in XS-C, supporting origin-associated genomic differentiation. Phytochemical profiling revealed distinct origin-dependent metabolic signatures. XS-K showed higher levels of phytosterols, chlorogenic acid, 4,5-dicaffeoylquinic acid (4,5-DCQ), and xanthatin was detected only in XS-K, whereas XS-C exhibited greater abundance of total fatty acids, particularly oleic acid. Unsupervised clustering and log2 fold-change ranking confirmed clear compositional separation, and variable importance in projection (VIP) analysis identified chlorogenic acid, β-sitosterol, oleic acid, 4,5-DCQ, and xanthatin as major discriminators between origins. Bioactivity assays demonstrated that XS-K exerted stronger antioxidant effects in ABTS, DPPH and FRAP assays, stronger skin-related enzyme inhibition, and greater antibacterial activity against Staphylococcus aureus, consistent with its enriched phenolic and sterol profile. CONCLUSION: Together, chloroplast sequence variation, targeted metabolite quantification, and screening bioassays consistently distinguished XS-K from XS-C. These findings support the use of candidate markers for the origin-based authentication and quality control of XS fruit-derived ingredients. © 2026 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Fruit↗

PubMed2026

Novelty seeking and rapid symptom improvement across active and sham accelerated iTBS conditions: A pooled individual-patient data analysis.

INTRODUCTION: Major depressive disorder (MDD) is highly prevalent and often treatment-resistant. Accelerated intermittent theta burst stimulation (aiTBS) is a promising intervention for treatment-resistant depression (TRD), though outcomes vary. Personality traits have been examined in relation to rTMS outcomes, yet their role in aiTBS remains underexplored. This pooled individual-patient-data analysis of two randomized, sham-controlled trials examined associations between baseline Temperament and Character Inventory (TCI) traits and one-week symptom change, and whether they differed by condition. METHODS: The left dorsolateral prefrontal cortex was targeted for 20 sessions over 4 days. Personality was assessed with the TCI, depression severity with the 17-item Hamilton Depression Rating Scale (HDRS-17). TCI-symptom-change associations were examined with a robust linear mixed-effects model, adjusting for age, gender, repeated measurements, and study membership. RESULTS: 104 participants were included (M/F 45/59; mean age 40.9 ± 12.7; active/sham 50/54). The model yielded a Time × Novelty Seeking interaction (β = -1.70, p = 0.021): higher baseline Novelty Seeking was associated with faster symptom reduction, without a between-arm difference. However, the interaction did not survive Holm correction across 14 trait-interaction tests (adjusted p = 0.294) and is therefore exploratory. No other interaction reached the uncorrected threshold. CONCLUSIONS: Higher baseline Novelty Seeking showed a nominal association with faster symptom reduction, without a difference between active and sham conditions. Because it did not survive multiplicity correction and was not reproduced in within-arm analyses, it is preliminary and may reflect contextual or nonspecific processes. Independent replication is required before temperament assessment can be clinically informative.

Humans↗

PubMed2026

Craniotomy versus Endoscopic Membranectomy in the Treatment of Non-Homogeneous Chronic Subdural Hematoma: A Pilot Randomized Parallel-Group Active-Controlled Trial (EMiT CSDH 2).

BACKGROUND: Chronic subdural hematoma (CSDH) is a prevalent neurosurgical condition with persistent challenges related to recurrence. Endoscopic membranectomy (EM) has shown promising results in managing symptomatic non-homogenous (SNH)-CSDH, but comparative evidence against craniotomy with membranectomy (CM) is lacking. OBJECTIVES: To compare the safety and efficacy of EM versus CM in managing SNH-CSDH. MATERIALS AND METHODS: A pilot randomized parallel-group active-controlled open- labeled superiority trial from September 2023 to November 2024 at Government Kilpauk Medical College, Chennai, India. Sixty patients with SNH-CSDH were randomized into EM and CM groups. Recurrence was the primary outcome. Secondary outcomes included operative time, complications, radiological indices, pain, hospital stay, and functional recovery. All patients were followed for six months. RESULTS: No recurrence was observed in either group at six months. Two CM patients required reoperation on postoperative day one ( P = 0.15). EM was associated with shorter operative time ( P = 0.02), lower incidence of post-operative subdural residual fluid ( P = 0.015), better early hematoma reduction/subdural space reduction index ( P = 0.008), midline shift/symmetry improvement index ( P = 0.001), and lesser surgical site swelling ( P < 0.001). All patients were ambulant and had a Glasgow coma scale (GCS) 15 at discharge and at six months (including reoperated patients). Pain scores and functional recovery were comparable. EM patients had shorter hospital stays ( P = 0.004) and no significant complications. CONCLUSION: EM demonstrated favorable early radiological outcomes, fewer complications, and comparable functional recovery and recurrence versus CM in SNH-CSDH. Independent reproduction and larger multicentric trials are needed for validity and generalizability.

Humans↗

PubMed2026

Natural products alleviate exercise-induced fatigue by modulating gut microbiota: a systematic review.

BACKGROUND: Exercise-induced fatigue critically impairs athletic performance and training quality. The gut microbiota, as a key regulator of the "gut-muscle axis," has emerged as a promising anti-fatigue target. Natural products - owing to their diverse sources, structural complexity, and favorable safety profiles - have attracted growing research interest. However, a systematic synthesis comparing their anti-fatigue effects via gut microbiota modulation across different sources is lacking. SCOPE AND APPROACH: We systematically searched PubMed, Web of Science, the Cochrane Library, and CNKI for original studies that administered natural products and concurrently assessed gut microbiota changes and anti-fatigue outcomes. Twenty-six studies (25 animal experiments and 1 human trial) were included and categorized into seven groups by source and chemical characteristics. A descriptive systematic review was conducted to identify common mechanisms and source-specific differentiations. KEY FINDINGS AND CONCLUSIONS: The enrichment of short-chain fatty acid (SCFA)-producing bacteria and the activation of the SCFA-AMPK/PGC-1α axis were shared core events across all product categories. However, source-dependent mechanistic divergences emerged: polysaccharides acted primarily as fermentable substrates with an optimal dose window; polyphenols and saponins exerted dual modulation on both microbiota and host signaling pathways; compound extracts achieved systemic synergy through functional complementation; marine- and animal-derived products exhibited unique targeting profiles and rapid action. Intestinal barrier maintenance and brain-gut axis regulation further extended the anti-fatigue repertoire. Collectively, natural products possess a solid mechanistic basis for alleviating exercise-induced fatigue via gut microbiota remodeling. The differentiated characteristics of these methods in targeting precision and pathway engagement provide a theoretical foundation for designing precision intervention strategies tailored to specific fatigue contexts.

Humans↗

PubMed2026

Does co-administration of cannabidiol (CBD) influence the plasma availability of delta-9-tetrahydrocannabinol (THC) and its active metabolite in humans? A systematic review and meta-analysis.

BACKGROUND: Research on the pharmacokinetic influence of cannabidiol (CBD) on delta-9-tetrahydrocannabinol (THC) has produced equivocal results. METHODS: We conducted a systematic search following PRISMA guidelines (last search: 24th November 2025, PROSPERO: CRD42023480695). Included studies were acute dosing trials that administered a) a single, fixed dose of THC and b) a matched dose of THC co-administered with CBD. Our objective was to investigate between-group differences in the Cmax, AUCt and AUCinf of circulating THC and its active metabolite, 11-hydroxy-THC (11-OH-THC). Hedges' g and ratio of means (RoM) were pooled from random-effects meta-analyses. The dose-effects of CBD and THC on Hedges' g were explored using meta-regression. Risk of bias was assessed using the Cochrane Collaboration tool RoB 2. RESULTS: 14 studies were included (12 crossover, two parallel group; seven oral administration, five inhalation, one IV, one mixed IV and oral; total participants: 341). In meta-analyses, average AUCt of THC was significantly higher in CBD co-administration study arms versus THC-only (Hedges' g= 0.526, 95%CI= 0.222-0.830), with very low certainty evidence. Both Cmax and AUCt of 11-OH-THC were significantly higher in CBD co-administration study arms (Cmax: g= 0.428, 0.115-0.741; AUCt: g= 0.692, 0.284-1.099), both with medium certainty evidence. In meta-regression analyses, CBD demonstrated dose effects on the Hedges' g of the Cmax and AUCt of 11-OH-THC (P < 0.05), but not THC levels. CONCLUSIONS: Cannabis users and prescribers of cannabinoid-based products should be made aware of the potential for drug-drug pharmacokinetic interactions between CBD and THC.

Humans↗

PubMed2026

Probiotic supplementation increases fecal TLR4 agonists without improving disease activity in juvenile idiopathic arthritis: a randomized placebo-controlled trial.

Gut dysbiosis has been implicated in the pathogenesis of juvenile idiopathic arthritis (JIA), suggesting that microbiota-targeted interventions may influence immune signalling during early immune development. We conducted the PERMAJI multicentre randomized, double-blind, placebo-controlled trial to evaluate the effects of probiotic supplementation (VSL#3) on host-microbiota immune interactions and disease activity in children with oligoarticular or RF-negative polyarticular JIA. Participants were randomly assigned (1:1) to receive VSL#3 or placebo for 3 months in addition to standard therapy. Stool and serum samples collected at baseline and month 3 were used to assess gut microbiota composition, fecal innate immune agonists, intestinal permeability, and systemic cytokines. The primary clinical endpoint was the proportion achieving an ACR Pedi 30 response at 3 months. Forty-four children were enrolled between September 2017 and July 2022. Clinical responses did not differ between groups (ACR Pedi 30: 47% with VSL#3 vs 63% with placebo; p = 0.33), and conservative worst-case assumptions for missing data suggested lower response rates with VSL#3 (36% vs 68%; p = 0.03). Probiotic supplementation significantly increased fecal Toll-like receptor 4 (TLR4) agonist activity, whereas gut microbiota diversity, intestinal permeability, and systemic cytokine levels remained unchanged. These findings indicate that probiotic supplementation can modify microbial innate immune signalling without detectable changes in microbial community diversity and may increase exposure to pro-inflammatory microbial stimuli in early-life autoimmune disease. The results highlight the complexity of host-microbiota immune interactions and underscore the need for careful evaluation of microbiome-targeted therapies in paediatric autoimmune disorders.

Humans↗

PubMed2026

Evolutionary diversification of invertase paralogs couples carbon metabolism and sexual reproduction in fission yeasts.

Dynamic patterns of gene gain and loss play a major role in the diversification of eukaryotes, reflecting adaptation to a broad range of ecological contexts. Reconstructing the evolutionary history of genes provides a powerful framework for understanding how functional innovation shapes life-history traits. Here we report a comprehensive analysis of gene gain and loss across the fission yeast clade, whose evolutionary trajectory remains elusive. Reductive evolution of metabolic genes is a major contributor to species diversification, as observed in other fungal taxa. Notably, we uncovered an evolutionary scenario in which an ancestral gene duplication was followed by lineage-specific loss of one or the other paralog, except in S. pombe, which retained both. We demonstrate that these paralogs encode catalytically-active invertases, named Inv1 and Inv2, with distinct enzymatic properties, localization, regulation, and physiological roles. Inv1 is a secreted enzyme subject to glucose catabolite repression and is the sole invertase required for sucrose assimilation, resembling canonical yeast invertases. In contrast, Inv2 is intracellular, constitutively expressed, and required for inducing sexual differentiation in response to nutrient availability. Overall, these findings reveal an unexpected role for carbon metabolism in modulating the haploid-diploid cycle of fission yeasts, suggesting that diversification of core metabolic functions may contribute to adaptation to environments with distinct sugar compositions.

Evolution↗

PubMed2026

The Role of Artificial Intelligence for Intimate Partner Violence Prevention: A Systematic Review.

INTRODUCTION: Intimate partner violence (IPV), encompassing physical, sexual, emotional and economic abuse, remains a pervasive global health concern. Traditional prevention efforts face obstacles such as underreporting, delayed detection and limited personalised support. Emerging artificial intelligence (AI) approaches offer new opportunities to enhance IPV prevention. AIM: This systematic review maps and synthesises evidence on AI-driven tools in IPV prevention based on studies published between 2004 and 2024. METHODS: Following PRISMA 2020 guidelines and PROSPERO registration, we searched PubMed, Embase, CINAHL, PsycINFO, IEEE Xplore and Web of Science. Eligible studies explicitly evaluated AI technologies targeting IPV prediction, screening, intervention or support delivery. Study quality was appraised using the Mixed Methods Appraisal Tool (MMAT). RESULTS: Of 1304 records initially identified, 41 studies met eligibility criteria. AI applications ranged from machine learning (ML) for risk prediction and natural language processing (NLP) for IPV detection in clinical and social media data, to image analysis for forensic evaluation and chatbot-based support. Predictive modelling demonstrated strong discriminative performance, while NLP-based screening detected IPV with notable sensitivity. Chatbots showed feasibility and user acceptability, but evidence of their direct impact on reducing IPV incidence was limited, with one randomised controlled trial showing a modest reduction. Key challenges identified included algorithmic bias, data privacy risks and barriers to integration across health and social care systems. DISCUSSION: AI-informed interventions show promise for improving IPV detection, risk assessment, and scalable support, but questions remain about long-term effectiveness, ethical fairness, transparency and equitable implementation. Future interdisciplinary research should address these concerns to responsibly deploy AI in IPV prevention. RELEVANCE TO CLINICAL PRACTICE: The findings highlight the importance of trauma-informed, culturally responsive care and provider training in AI applications. Nurse-led innovation and policy advocacy will be crucial for safe, equitable integration of AI in IPV prevention.

Artificial Intelligence↗

PubMed2026

Symptom Burden After Dialysis Initiation and Its Association With Hospitalization.

RATIONALE & OBJECTIVE: Symptom burden is distressing for patients living with kidney failure, but there is limited information about the combination of symptoms and individual symptoms that most strongly predict health care use in this group. We classified and summarized patients' symptom burden levels and changes over time and estimated associations with hospitalizations among patients receiving incident hemodialysis. STUDY DESIGN: Longitudinal, observational. SETTING & PARTICIPANTS: Individuals initiating dialysis in the United States. EXPOSURE: Kidney Disease Quality of Life-36 (KDQOL-36) measure. OUTCOME: First hospitalization after dialysis initiation. ANALYTICAL APPROACH: Latent transition analysis was used to identify symptom burden classes using the KDQOL-36. Cox regression models were used to assess whether individual KDQOL-36 symptoms and symptom burden groups were associated with hospitalization risk after dialysis initiation, independent of demographics and comorbid conditions. RESULTS: 1,818 participants were Black (29%), were aged >65 years (59%), were women (42%), had diabetes (49%), and had hypertension (74%). Latent transition analysis identified the following 3 symptom burden groups: (1) low (low severity of all symptoms and kidney disease impacts), (2) moderate (high physical health impact and overall burden of kidney disease), and (3) high (high levels of all symptoms and kidney disease impact). After adjusting for patient characteristics, all KDQOL-36 scales except the Effects of Kidney Disease scale were associated with a higher hazard of hospitalization. Using the symptom burden groups, a high symptom burden was associated with a 20% increase in the hazard of hospitalization. A 1-category worsening in pain interference and in fatigue was associated with a 12% and an 8% increased hazard of hospitalization, respectively. LIMITATIONS: Findings may not generalize outside the United States. CONCLUSIONS: Pain interference and fatigue, as well as an overall symptom burden, are useful prognostic indicators in patients receiving in-center hemodialysis. Symptom burden should remain a treatment target in hemodialysis.

Hemodialysis↗

PubMed2026

ATF4-histone 2-hydroxyisobutyrylation feedback loop drives sepsis-induced inflammation.

BACKGROUND AND PURPOSE: The role and mechanisms of lysine 2-hydroxyisobutyrylation (Khib) in the acute inflammatory phase of sepsis remain unclear. We investigated the function and underlying mechanisms of histone H4 lysine 5 2-hydroxyisobutyrylation (H4K5-hib) in sepsis-induced inflammation in vivo and in vitro. EXPERIMENTAL APPROACH: Acute sepsis was induced by caecal ligation and puncture (CLP) in mice, and inflammatory responses were modelled in lipopolysaccharide (LPS)-stimulated macrophages. CUT&Tag-seq was used to identify genomic targets associated with H4K5-hib and activating transcription factor 4 (ATF4). Immunofluorescence, Western blotting, qPCR, dual-luciferase assays, and ELISA were performed to investigate the underlying mechanisms. KEY RESULTS: H4K5-hib levels were increased in macrophages during the acute inflammatory phase of sepsis. LPS stimulation enhanced H4K5-hib enrichment at the ATF4 promoter, thereby promoting ATF4 transcription. Inhibition of EP300-mediated 2-hydroxyisobutyrylation or mutation of H4K5 abolished ATF4 activation. Increased H4K5-hib activated the ATF4/NLRP3 signalling axis, promoting inflammasome assembly and amplifying inflammatory responses. ATF4 directly bound to the EP300 promoter and enhanced its transcription, forming a positive feedback loop that further increased H4K5-hib levels. In CLP-induced sepsis, pharmacological inhibition of EP300 or ATF4 reduced H4K5-hib levels and suppressed NLRP3 inflammasome activation. CONCLUSION AND IMPLICATIONS: These findings reveal a previously unrecognized epigenetic mechanism underlying sepsis-induced inflammation and identify the EP300/ATF4/H4K5-hib positive feedback loop as a potential therapeutic target for sepsis.

Animals↗

PubMed2026

Understanding specificity in immune-brain pathways: A systematic review of differential associations between individual cytokines and brain structure and function measured through magnetic resonance imaging in humans.

Research shows that cytokines are associated with psychiatric disorders, including major depression, and multiple aspects of brain structure and function. Accumulating data suggest that different cytokines may have unique profiles of biological activity, particularly in their neuromodulatory roles, but it is currently unclear whether they have unique associations with specific neural circuits in humans. In this paper, we systematically review magnetic resonance imaging studies conducted with depressed or healthy control human participants under age 65 that examine associations between peripheral cytokines and brain structure and function, with the goal of evaluating evidence for the specificity of these cytokine-brain associations. We find that across multiple measures of brain structure and function, the majority of studies reviewed reported unique associations between individual cytokines and brain outcomes. A synthesis of findings across studies also suggests a preliminary hypothesis of specific associations of interleukin-6 levels in circulation with the default mode network and tumor necrosis factor-alpha with the salience network, which could be tested in future research. We conclude the review with future directions for research that can strengthen understanding of these associations.

Humans↗

PubMed2026

LitCTL1: A novel C-type lectin involved in the mucosal and cellular immunity of the common periwinkle Littorinalittorea.

C-type lectins (CTLs) are vital pattern-recognition receptors (PRRs) that mediate innate immune responses in mollusks, yet their characterization in Caenogastropoda, the largest gastropod group, remains limited. This study characterizes LitCTL1, a novel secreted single-domain C-type lectin from the common periwinkle, Littorina littorea. The 199-amino acid polypeptide contains a conserved carbohydrate recognition domain with canonical QPD and WND motifs and is predicted to form a homodimer. Uniquely, LitCTL1 was localized in both circulating hemocytes and mucus-secreting epithelial cells of the foot, mantle, and hypobranchial gland - the first report of such dual localization for a molluscan lectin, linking systemic and mucosal defense. Expression analysis revealed that LitCTL1 is constitutively expressed in hemocytes. Functional assays with recombinant LitCTL1 demonstrated its role as a potent opsonin with hemagglutinating activity, significantly enhancing hemocyte spreading and the phagocytosis of zymosan. Genomic analysis reveals that LitCTL1 belongs to a rapidly diversifying, genus-specific expansion distinct from conserved perlucin-like lineages. These results identify LitCTL1 as a key effector molecule in both systemic and mucosal innate immunity, likely reflecting an evolutionary adaptation to the microbial challenges of the intertidal environment.

Animals↗