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PubMed2026

Advanced mitigation strategies for acrylamide formation in foods: Mechanistic insights, emerging innovations, and future perspectives.

Acrylamide is a heat-induced contaminant formed predominantly in carbohydrate-rich foods during high-temperature processing, posing significant concerns due to its potential carcinogenic, neurotoxic, and genotoxic effects. This review critically examines the mechanisms of acrylamide formation, emphasizing the role of the Maillard reaction and key precursors such as asparagine and reducing sugars, along with the influence of processing conditions including temperature, time, pH, and moisture. Various mitigation strategies are comprehensively discussed, ranging from raw material selection and genetic approaches to enzymatic treatments such as asparaginase and the application of natural and chemical inhibitors. Advances in processing technologies, including optimization of conventional thermal methods and emerging non-thermal techniques such as cold plasma and ultrasound, are evaluated for their effectiveness. The review also highlights the role of food additives, functional ingredients, and fermentation in reducing acrylamide formation. Furthermore, recent developments in analytical techniques, including chromatographic methods, biosensors, and artificial intelligence-based predictive models, are explored for improved detection and control. Risk assessment, toxicological implications, and global regulatory frameworks are also examined. Finally, future perspectives focusing on genetic engineering, personalized nutrition, and digital technologies such as AI and blockchain are discussed to support sustainable and industry-applicable mitigation strategies.

Acrylamide↗

PubMed2026

Efficacy and safety of ferric citrate tablets in Chinese patients with hyperphosphatemia undergoing maintenance hemodialysis: a multicenter, randomized, open-label, active-controlled, phase III trial.

BACKGROUND: This study aimed to evaluate the efficacy and safety of ferric citrate tablets in Chinese patients with hyperphosphatemia undergoing maintenance hemodialysis (MHD). METHODS: In this phase III, multicenter, randomized, open-label, non-inferiority trial, patients with hyperphosphatemia on maintenance hemodialysis were randomly assigned to receive either ferric citrate or sevelamer carbonate tablets for 12 weeks. The primary endpoint was the change in serum phosphorus levels from baseline to week 12, with a non-inferiority margin of 0.32 mmol/L. Secondary endpoints included changes in serum calcium, intact parathyroid hormone, and safety assessments. RESULTS: A total of 239 patients were randomized to the ferric citrate group (n = 119) or the sevelamer carbonate group (n = 120). The mean change in serum phosphorus levels was -0.70 ± 0.50 mmol/L in the ferric citrate group and -0.61 ± 0.59 mmol/L in the sevelamer carbonate group (least squares mean difference, -0.09 mmol/L; 95% CI, -0.24 to 0.05 mmol/L; non-inferiority margin, 0.32 mmol/L). No significant inter-group differences were found in the percentage of patients achieving target phosphorus levels (49.09% vs. 48.28%, p = 0.902). Ferric citrate significantly improved iron-related parameters and hemoglobin levels. Most treatment-emergent adverse events were mild, with gastrointestinal disorders being the most common. CONCLUSIONS: Ferric citrate tablets were non-inferior to sevelamer carbonate in reducing serum phosphorus levels in hyperphosphatemia patients on maintenance hemodialysis, with the added benefit of improving iron-related anemia and a favorable safety profile.

Adult↗

PubMed2026

Emergence of an optrA-positive Enterococcus faecalis ST699 lineage in animal-derived foods in Beijing, China.

Enterococci from animal-derived foods are key reservoirs for antimicrobial resistance (AMR) in the food chain. However, comparative genomic studies investigating the distribution of the oxazolidinone resistance gene optrA among food- and human-derived Enterococci remain limited. This study assessed linezolid-resistant Enterococci from retail meat and healthy humans in Beijing, China (2023-2024). Among 87 isolates, E. faecalis and E. faecium predominated. Food-derived isolates showed broader resistance profiles than human isolates. Fourteen optrA-positive strains were identified, accounting for 92.9% of food isolates. optrA frequently co-localized with erm(A), ant(9)-Ia, and fexA on Tn554-family transposons, suggesting a potentially transferable multidrug resistance module. Notably, an optrA-positive E. faecalis ST699 clone was identified for the first time in Chinese retail meat. This clone formed a distinct lineage and carried a complete Tn554-optrA island. A representative ST699 isolate exhibited enhanced fitness and virulence potential in the Galleria mellonella model. These findings highlight animal-derived foods as important reservoirs of linezolid-resistant Enterococci and provide genomic evidence consistent with their role as potential sources of optrA-mediated resistance. The emergence of a multidrug-resistant E. faecalis ST699 clone with enhanced fitness characteristics underscores the need for continued surveillance of foodborne antimicrobial resistance within the One Health framework.

Enterococcus faecalis↗

PubMed2026

Hepatotoxicity of OBS: A review of the emerging PFOS substitute.

As an alternative to perfluorooctanesulfonic acid (PFOS), sodium perfluorononenyl oxobenzene sulfonate (OBS) is widely used due to its cost-effectiveness. Multiple studies have shown that the liver is a classic target organ for OBS. However, there is currently no systematic review on the hepatotoxic effects of OBS. This review systematically summarizes the exposure characteristics of OBS in the environment and human populations, as well as its mechanisms of liver toxicity. In vivo studies consistently demonstrate that OBS induces hepatotoxic effects, such as hepatomegaly, vacuolization, elevated serum transaminases, and lipid dysregulation, though the manifestation of these phenotypes varies across species and exposure routes. In vitro evidence further shows that OBS reduces cell viability and survival, and triggers necrosis accompanied by inflammation. Mechanistically, oxidative stress, inflammatory signaling, and metabolism disorder are implicated. Critically, most existing work addresses subacute or subchronic exposure, leaving a gap in chronic risk assessment for long-term, low-dose OBS exposure. Moreover, mechanistic studies have focused predominantly on downstream transcriptional and signaling changes, with limited exploration of upstream epigenetic controls. Overall, this study aims to provide a comprehensive reference for future toxicological investigations and liver injury risk assessments related to OBS exposure.

Humans↗

PubMed2026

Stage-specific ROMO1 in rheumatoid arthritis: predictive immune insights into the MIF pathway and HLA-DR/IL2RA axis via integrated GWAS, transcriptomic, single-cell, and spatial profiling.

Emerging evidence links reactive oxygen species modulator 1 (ROMO1), a key mitochondrial ROS regulator, to rheumatoid arthritis (RA) pathogenesis. However, its exact mechanism remains elusive given the conflicting evidence about its specific function. We used a four-level integrative framework combining multi-omics data and literature‑supported mechanistic inference. At the genetic level, Mendelian randomization (MR) was performed to explore potential causal relationships between ROMO1, IL2RA, HLA-DR, MIF, and RA risk, followed by differential expression analysis and machine learning-based feature selection to identify key mROS genes. The temporal expression dynamics of ROMO1 were assessed in RA progression. At the cellular and tissue levels, we integrated single-cell RNA sequencing and spatial transcriptomics to map cell-type-specific expression and synovial localization of ROMO1-related immune cells and pathways. Finally, our multi-omics findings were contextualized with literature-supported mechanistic inference. (1) MR results were consistent with a potential protective effect of ROMO1 on RA (OR = 0.52) and its potential regulation of risk factors IL2RA (OR = 0.46) and HLA-DR (OR = 0.40). Conversely, IL2RA (OR = 1.42), HLA-DR (OR = 1.88), and MIF (OR = 1.17) were positively associated with RA risk. Additionally, ROMO1 was identified as a top candidate diagnostic predictor with stage-specific dynamics: downregulated in the early but upregulated in the late/remission stages. (2) Single-cell RNA sequencing showed ROMO1's cell-specific expression in CD14+ HLA-DR+ CD74+ monocytes and CD4+ IL2RA+ T cells. Cell communication analysis further suggested that these cells may participate in MIF pathway regulation. Spatial transcriptomics subsequently identified that ROMO1-related cells localized to synovial pathological regions, with MIF pathway changes correlated with RA progression. (3) Finally, literature-supported mechanistic inference suggests that ROMO1 may modulate mROS levels to promote anti-inflammatory M2 macrophage polarization, which could theoretically contribute to reduced systemic inflammation and the alleviation of multi-organ decline in RA. This integrated multi-omics investigation, supported by literature-based mechanistic inference, suggests ROMO1 as a stage-dependent biomarker candidate and potential immune regulator in RA.

Humans↗

PubMed2026

Efficacy and safety of Ruxolitinib-based combination therapy in the patients with Myelofibrosis (MF): a systematic review and meta-analysis.

BACKGROUND: Myelofibrosis (MF) is a chronic myeloproliferative neoplasm. Although Ruxolitinib, a JAK1/2 inhibitor, remains the cornerstone of MF treatment, it does not reverse disease progression, and resistance frequently emerges. These limitations have prompted investigation into combination therapies targeting pathways beyond the JAK-STAT axis. This meta-analysis aims to evaluate the efficacy and safety of Ruxolitinib-based combination therapies in patients with MF. METHODS: We conducted a systematic search of databases for studies published through August 1, 2025. Thirteen distinct Ruxolitinib-based combination regimens were included. Primary efficacy endpoints were ≥35% spleen volume reduction at 24 weeks (SVR35) and ≥50% reduction in total symptom score (TSS50). Safety endpoints focused on the incidence of grade 3/4 thrombocytopenia and anemia. Subgroup analyses were performed based on prior JAK inhibitor exposure and therapeutic mechanism of action. RESULTS: A total of 19 studies comprising 1,088 patients were included in the meta-analysis. Among JAK inhibitor-naïve patients, the combination of Ruxolitinib with Selinexor demonstrated the highest efficacy (SVR35: 92%; TSS50: 78%), followed by Ruxolitinib plus BMS-986158 (SVR35: 90%). For patients with prior JAK inhibitor exposure, Ruxolitinib plus Siremadlin (SVR35: 45%) showed notable activity. CONCLUSION: For JAK inhibitor-naïve patients, Ruxolitinib-based combination regimens demonstrated satisfactory clinical responses and the potential for meaningful disease control. For patients with prior JAK inhibitor exposure, the addition of combination therapy drugs may further enhance the efficacy. Personalized treatment selection remains essential, as therapeutic efficacy is significantly influenced by prior JAK inhibitor exposure.

Humans↗

PubMed2026

Cardiovascular risks in psychiatric disorders and psychiatric risks in cardiovascular disorders: implications for prevention and clinical management - a large-scale umbrella review encompassing 76 meta-analyses.

OBJECTIVE: Psychiatric and cardiovascular disorders often co-occur, complicating their assessment and management. No umbrella review(UR) has summarized the meta-analytic evidence on the co-occurrence of psychiatric and cardiovascular disorders and assessed its credibility. METHODS: Meta-analytic systematic reviews of observational studies documenting the prevalence, risk factors, and outcomes associated with the co-occurrence of cardiovascular and psychiatric disorders, indexed from inception through March.16.2026, and meeting established diagnostic criteria, were included. Meta-analytic association and prevalence estimates were recalculated and graded based on established or adapted criteria. The AMSTAR-2 assessed the quality of the meta-analyses, while several subgroup analyses and meta-regressions aimed to explain the heterogeneity. RESULTS: We included 76 meta-analyses yielding 131 meta-analytic estimates. Based on pre-existing meta-analytic evidence, 22/24 prevalence estimates (91.7%) met moderate/strong credibility criteria. Strong credibility emerged for: orthostatic hypotension in Lewy body(58%;95%C.I. = 50-66%) and Alzheimer's dementias(28.0% = 95%C.I. = 17.0-40.0%); pericardial effusion in anorexia nervosa(25.0%;95%C.I. = 17.0-34.0%); in heart failure(HF): major depressive disorder(MDD)(41.9%;95%C.I. = 36.7-47.1%), mild cognitive impairment(MCI)(41.4%;95%C.I. = 38.3-45.6%), anxiety(32.0%;95%C.I. = 26.5-37.6%), MDD + anxiety(24.7%;95%C.I. = 17.9-34.3%), and dementia(19.8%;95%C.I. = 12.9-27.8%); in atrial fibrillation(AF): MCI(26.0%;95%C.I. = 21.0-30.0%), anxiety in patients undergoing pulmonary vein isolation(PVI)(25.0%;95%C.I. = 12.0-46.0%), MDD in PVI patients (20.0%;95%C.I. = 13.0-29.0%); in coronary artery disease: MDD + anxiety(19.8%;95%C.I. = 16.0-24.6%): in schizophrenia spectrum disorders: clozapine-associated-cardiomyopathy(0.6%;95%C.I. = 0.2-2.3%); clozapine-associated-cardiomyopathy absolute death rates (0.0003;95%C.I. = 0.0001-0.0012); clozapine-associated-cardiomyopathy case fatality rate (0.078;95%C.I. = 0.018-0.285). Several additional disorders were multimorbid in>5% of people, yet with a lower credibility rating. No re-pooled risk factors/outcomes reached strong credibility criteria. CONCLUSIONS: The present study provides an atlas of cardiovascular and psychiatric multimorbidity across varying levels of credibility, reinforcing the need for an integrated, multidisciplinary approach to patient care and for more research on actionable risk/protective factors and outcomes.

Humans↗

PubMed2026

Integrated bioinformatics analysis reveals cross-talking hub genes and therapeutic agents between sepsis and acute myocardial infarction.

BACKGROUND: Sepsis and acute myocardial infarction (AMI) are two significant diseases that may share overlapping etiological mechanisms. This study aims to systematically identify core genes common to both conditions and to explore their potential as therapeutic targets and drug candidates through an integrative analysis of clinical data and bioinformatics. METHODS: The AMI dataset was obtained from the GEO database, and RNA sequencing data were collected from blood samples of patients with sepsis at our hospital. Common genes were identified using differential expression gene analysis (DEG) and weighted gene co-expression network analysis (WGCNA). Functional enrichment analyses, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, were performed. A protein-protein interaction (PPI) network was constructed, and hub genes were identified using the MCC/Degree algorithm. Diagnostic value was assessed via receiver operating characteristic curve analysis. Immune infiltration patterns, single-cell sequencing data, and molecular docking simulations were employed to evaluate immune relevance and identify potential therapeutic compounds. RESULTS: A total of 417 genes were identified between sepsis and AMI, with enrichment analysis revealing significant involvement in inflammatory responses. Three hub genes-JAK2, MYD88, and TIMP1-were selected for further investigation. ROC curves confirmed their strong diagnostic performance for both diseases. Immune infiltration analysis showed that these core genes were significantly correlated with the infiltration levels of various immune cell types. Molecular docking indicated that quercetin exhibited stable binding affinity with the proteins encoded by these genes. qPCR validation further confirmed the upregulation of these three genes, supporting the anti-inflammatory effects of quercetin as a potential targeted therapy. CONCLUSION: JAK2, MYD88, and TIMP1 were identified as shared core genes in sepsis and AMI. These genes not only serve as potential diagnostic biomarkers but also offer novel targets for developing common therapeutic strategies for both conditions. Furthermore, quercetin emerges as a promising candidate for targeted treatment.

Humans↗

PubMed2026

Transformation of antibiotics mediated by iron-bearing minerals: A review.

Iron-bearing minerals are ubiquitous in water, sediments and soil, where their surface chemical properties and redox activity can play an important role in degradation of trace antibiotics. This review systematically summarizes the roles of various iron-bearing minerals in chemical transformation and microbial degradation of antibiotics and reaction mechanisms involved, and refines the critical idea for iron-driven control of antibiotics with trace level in natural environment. Overall, antibiotics removal in the presence of iron-bearing minerals involves combination of adsorption, surface oxidative degradation, photo-induced degradation, Fenton-like reaction and microbial degradation. Adsorption of antibiotics by Fe(III)-minerals involves electrostatic interaction, complexation, H-bonding, π-π interaction and hydrophobic interaction. Adsorbed antibiotics form complexes with Fe(III)-minerals, undergoing electron transfer to generate radical intermediates, subsequently generating final products through hydroxylation, dealkylation, and deamination. Additionally, Fe(III)-minerals can be excited to produce electrons and holes under sunlight and to produce antibiotics-degrading hydroxyl radical through O2 reduction, H2O oxidation and ligand-to-metal charge transfer. Reduced iron minerals can activate oxygen to participate in Fenton-like degradation reactions. Finally, antibiotics are mainly removed by bio-driven Fenton reaction and direct enzyme biodegradation. The presence of iron-bearing minerals can promote antibiotics microbial degradation by providing nutrients for microorganisms or by changing microbial activity and microbial community structure. Existing problems and future research directions are identified. New insights for application of iron-bearing minerals in transformation of antibiotics are proposed. The work aims to suggest new methods and insights for pollution control and remediation of emerging contaminants including trace antibiotics in the natural environment.

Anti-Bacterial Agents↗

PubMed2026

Microplastic contamination in South Asian commercially important seafood: A comprehensive assessment of occurrence, source, and human health risk.

Seafood is a cornerstone of global food security and human nutrition, serving as the primary source of animal protein for more than one-fourth of the global population, with South Asia representing one of the world's fastest-growing seafood-consuming regions. However, escalating microplastic (MP) pollution in marine ecosystems poses an emerging threat to seafood safety and human health, yet a comprehensive regional assessment of MP contamination in South Asian seafood remains lacking. This study presents the first region-wide systematic synthesis of the literature on MP contamination in commercially important seafood across South Asia, integrating occurrence patterns, human exposure assessment, polymer-specific hazard evaluation, and bibliometric analysis to address this critical knowledge gap. The meta-analysis estimated an average microplastic exposure of 145 particles/person/day through seafood consumption in South Asia, with fish contributing the highest intake (121 particles/person/day). The detected polymers were classified into PHI hazard levels I-IV, with polyvinyl chloride (PVC), polyurethane (PU), and polyacrylamide (PAM) representing the highest hazard categories. The mean pollution load index (PLI) was 7.71 (Category I), with crustaceans exhibiting the highest contamination (PLI = 10.07). Polypropylene was the predominant polymer, whereas fragments and blue particles were the most frequently reported microplastic characteristics. These findings provide the first regional baseline for assessing microplastic contamination, polymer-associated hazards, and human exposure through seafood consumption in South Asia, underscoring the need for standardized monitoring and targeted mitigation strategies to safeguard seafood safety and public health.

Animals↗

PubMed2026

Patient and hospital factors associated with disparities in acute stroke treatment in community and academic hospitals.

BACKGROUND: Systemic barriers may affect identification, emergency transportation (EMS), and care coordination for people with stroke. We assessed patient- and hospital-level factors for associations with pre-hospital and emergency department care. We compared trends for patients presenting to an academic medical center (AMC) versus community hospitals (CHs). METHODS: We conducted a retrospective cohort study at an AMC (Tufts Medical Center) with 542 patients aged ≥18 years hospitalized with acute ischemic stroke or transient ischemic attack between 1/1/2018-12/31/2020 who presented directly to AMC or presented to AMC as a transfer from initial contact CHs. Primary outcomes were EMS use, stroke code activation, door-to-CT time, and door-to-needle time. RESULTS: AMC patients identifying as non-Hispanic Asian (odds ratio (OR) = 0.25; 95% confidence interval (CI) = 0.13-0.47) and Hispanic (OR = 0.19; 95% CI = 0.05-0.72) and CH non-Hispanic Black/African-American patients (OR = 0.17; 95% CI = 0.05-0.62) were less likely to use EMS compared to non-Hispanic white patients. Patients with non-English primary language were less likely to use EMS (OR = 0.38; 95% CI = 0.23-0.63) compared to English-speaking patients in both hospital settings. CH Hispanic patients were less likely to have stroke code activation (OR = 0.24; 95% CI = 0.05-0.86) compared to non-Hispanic white patients. CH patients were less likely to have stroke code activation (OR = 0.12; 95% CI = 0.07-0.19), had 31% shorter door-to-CT time (95% CI = 15-43% shorter), and had 29% longer door-to-needle time (95% CI = 5-58% longer). CONCLUSION: Patient-level factors and hospital setting were associated with differences in acute care suggesting opportunities for community outreach on EMS use, interventions to alleviate language barriers, and a need to address systemic biases.

Humans↗

PubMed2026

Rotavirus vaccine effectiveness against rotavirus and acute gastroenteritis mortality: an analysis of pooled case-control studies from the MNSSTER-V dataset.

BACKGROUND: Rotavirus accounts for an estimated 25% of diarrhoea deaths in children under 5 years globally, and more than 140 countries have included rotavirus vaccines in their routine national infant vaccination programmes. We aimed to calculate rotavirus vaccine effectiveness against rotavirus-positive and all-cause acute gastroenteritis deaths. METHODS: The Multi-National Subpopulations Study to Evaluate Rotavirus Vaccines (MNSSTER-V) dataset combines child-level data from test-negative case-control studies of rotavirus vaccine effectiveness that enrolled children under 5 years of age seeking care for acute gastroenteritis at hospitals or emergency departments in 24 countries between July 1, 2007, and Aug 24, 2023. Children were included in this study if they were: younger than 5 years, met the acute gastroenteritis case definition (had at least three episodes of diarrhoea in a 24-h period, had non-bloody and non-chronic diarrhoea, and were enrolled within 7 days of diarrhoea onset), met vaccine card quality metrics, had vaccine delivery dates if the child was reported to have received a rotavirus vaccine, and had a reported outcome of death or discharge. In-hospital acute gastroenteritis deaths were characterised, and rotavirus vaccine effectiveness against all-cause and rotavirus-positive acute gastroenteritis mortality was calculated using an unconditional logistic regression model with adjustment for national under-5 mortality strata and child's age. Vaccine effectiveness analyses against all-cause and rotavirus-positive acute gastroenteritis mortality were restricted to children aged at least 3 months who received any routine vaccines from countries reporting at least one acute gastroenteritis death. FINDINGS: From the MNSSTER-V dataset, we included 27 252 children younger than 5 years enrolled from 22 countries; outcomes of patients were not available for two countries. At least one in-hospital acute gastroenteritis death was reported from 16 countries including 21 522 children; in total, 183 all-cause acute gastroenteritis deaths and 25 rotavirus-positive deaths were reported. Among children aged at least 3 months who had received any routine vaccines, receiving at least one dose of a rotavirus vaccine had an adjusted vaccine effectiveness of 75·8% (95% CI 28·4 to 91·8; n=13 630) against rotavirus-positive acute gastroenteritis mortality and 20·8% (-47·0 to 57·3; n=20 005) against all-cause acute gastroenteritis mortality. INTERPRETATION: Rotavirus vaccines are effective in preventing rotavirus-positive acute gastroenteritis mortality. Continued efforts to improve vaccine delivery could help to reduce acute gastroenteritis mortality due to rotavirus worldwide. FUNDING: None.

Humans↗

PubMed2026

Dissemination of blaKPC-3-harbouring Klebsiella pneumoniae across ST48 and ST628 in multiple healthcare facilities in the Republic of Korea.

Klebsiella pneumoniae carbapenemase-3 (KPC-3) remains rare in South Korea, where KPC-2 is the dominant carbapenemase, making the repeated detection of a concentrated blaKPC-3 signal over five years notable. We performed genomic analyses of blaKPC-3-harbouring K. pneumoniae from a regional healthcare network. Two chromosomally distinct lineages with concordant capsule loci (ST628/KL15 and ST48/KL62) presented multidrug-resistant phenotypes, and the virulence-associated loci were confined to ST48. Single-nucleotide polymorphism (SNP) analyses revealed near-clonal relatedness within lineages, with 0-38 pairwise SNPs among ST628 isolates and 8 SNPs between the two ST48 isolates. Core-genome multilocus sequence typing (cgMLST) supported this structure, as ST628 isolates were assigned to complex type 19149 with 0-7 allelic differences, and ST48 isolates were assigned to complex type 19150 with 5 allelic differences. These patterns support vertical spread via clonal expansion across multiple facilities. Despite substantial chromosomal separation, most isolates carried the same IncFII(K) plasmid backbone and blaKPC-3, and they were nearly indistinguishable from a plasmid previously reported in South Korea. One isolate carried blaKPC-3 on a distinct multireplicon IncFIB(K)/IncFII(K) plasmid, indicating that the signal was not confined to a single plasmid backbone. In both plasmids, blaKPC-3 was embedded within Tn4401b. These findings indicate that a rare blaKPC-3 genotype can persist regionally through sustained clonal dissemination and that cross-lineage linkage is compatible with past horizontal transfer involving a conserved plasmid. These findings underscore the need for subtype-resolved, regionally coordinated genomic surveillance in connected healthcare networks to detect uncommon carbapenemase variants early.

Klebsiella pneumoniae↗

PubMed2026

Effect of intraoperative 40-hz gamma-frequency auditory stimulation on postoperative delirium in older adults undergoing major surgery: a randomized clinical trial protocol.

INTRODUCTION: Postoperative delirium (POD) is a common and clinically significant complication among older adults undergoing major surgery under general anesthesia. Gamma-frequency (40-Hz) auditory stimulation has demonstrated potential neuroprotective and cognition-enhancing effects, suggesting a plausible role in perioperative delirium prevention. However, direct clinical evidence supporting intraoperative 40-Hz auditory stimulation in reducing POD remains limited, warranting rigorous evaluation in a randomized trial. PATIENTS AND METHODS: This prospective, parallel-group, randomized controlled trial will enroll 550 older adults scheduled for major noncardiac, nonneurosurgical surgery under general anesthesia. Participants will be randomized in a 1:1 ratio to either the active stimulation group, receiving intraoperative 40-Hz gamma-frequency auditory stimulation delivered via headphones for 2 h following successful anesthesia induction, or the sham stimulation group, wearing headphones without active auditory output. The primary outcome is the incidence of POD on postoperative day 1 though 3, assessed using the Confusion Assessment Method (CAM) or the CAM for the ICU (CAM-ICU). Secondary outcomes include POD severity, sleep quality, pain scores, analgesic consumption, the incidence of postoperative nausea and vomiting (PONV), rescue antiemetic use, duration of post-anesthesia care unit (PACU) stay, length of hospital stay, quality of postoperative recovery, incidence of perioperative adverse events; postoperative morbidity, health-related quality of life, and all-cause 30-day mortality. DISCUSSION: This trial will determine whether intraoperative 40-Hz gamma-frequency auditory stimulation reduces the incidence of POD among older adults undergoing major surgery under general anesthesia. If efficacious, this noninvasive intervention could constitute a feasible perioperative strategy to mitigate delirium risk and enhance postoperative recovery. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2500115156).

Humans↗

PubMed2026

Leading with Innovation: Maternal Health Transformation in New York City Health + Hospitals.

New York City's (NYC) maternal health crisis drew close attention in the late 2010s, driven by alarming data: Approximately 30 women died annually during childbirth in NYC, Black non-Hispanic women were 12 times more likely to die than white women, and more than 3,000 women experienced life-threatening birth complications each year. In response, NYC committed $12.8 million in July 2018 to reduce maternal mortality and eliminate racial disparities.NYC Health + Hospitals (H+H)-the nation's largest public health system, serving 1.1 million patients annually with roughly 15,000 births per year-became the primary vehicle for this initiative. With 80 percent of the system's deliveries covered by Medicaid and a patient population that is 51.2 percent Hispanic and 27.1 percent Black, H+H is uniquely positioned to lead the fight against maternal health inequity.Three flagship programs anchor H+H's response to the city's maternal mortality rate. The OB Simulation Program, launched in 2012 and expanded in 2018, was the first in the nation to use mannequins of color to train thousands of providers in obstetric emergencies. The Maternal Home Program, piloted at H+H's Kings County Hospital in 2019 and scaled system-wide by 2021, has served more than 10,341 patients, generating more than 33,000 referrals for social, behavioral health, and community resources. The Cardio-Obstetrics Program located at Kings County Hospital targets cardiovascular disease-the leading cause of maternal death among Black women-through screening, education, and community outreach. These programs are a health equity imperative, made more urgent by impending federal Medicaid cuts resulting from the H.R.1 One Big Beautiful Bill Act (passed on July 4, 2025).

Humans↗

PubMed2026

Simultaneous determination of imiquimod and terbinafine in skin permeation studies: Validation of a liquid chromatography method with fluorescence detection.

Chromoblastomycosis is a chronic, neglected subcutaneous mycosis posing significant therapeutic challenges. A topical strategy combining terbinafine (TBF), an antifungal, with imiquimod (IMQ), a TLR-7/8 agonist immunomodulator, has emerged a promising alternative. However, no validated analytical method is currently available to simultaneously quantify both drugs in skin, which is crucial for novel formulation development. This study reports the development and validation of a simple HPLC method with fluorescence detection (excitation 236 nm, emission 340 nm) for the simultaneous determination of TBF and IMQ extracted from porcine skin. Separation was achieved on a C8 reversed-phase column (125 × 4.0 mm, 5 μm) using a mobile phase of methanol and water (60,40, v/v), both containing 0.1% formic acid at a flow rate of 0.8 mL/min. The method showed excellent linearity (r > 0.999) over 0.01-1.0 μg/mL for IMQ and 0.1-2.0 μg/mL for TBF. Intra- and inter-day precision demonstrated coefficients of variation below 5%, and recovery rates from skin (79-105%) confirmed accuracy. Limits of detection were 0.001 μg/mL for IMQ and 0.004 μg/mL for TBF, with quantification limits of 0.02 μg/mL and 0.16 μg/mL, respectively. This selective, sensitive, and reproducible method represents a valuable analytical tool for supporting the development and quality control of topical formulations for chromoblastomycosis and other fungal skin diseases.

Animals↗

PubMed2026

Metabolic ketosis attenuates NLRP3 inflammasome activation and is associated with improvements in hepatic steatosis and liver stiffness in MASLD: a pilot randomized controlled trial.

BACKGROUND: Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized as a systemic metabolic-inflammatory disorder in which metabolic stress and innate immune activation, particularly through the NLRP3 inflammasome, contribute to disease progression. Metabolic ketosis, characterized by increased levels of circulating ketone bodies, especially β-hydroxybutyrate, has emerged as a promising strategy to modulate substrate utilization, inflammatory signaling, and hepatic injury. However, clinical evidence integrating molecular, metabolic, and hepatic outcomes remains limited. METHODS: In this pilot randomized controlled trial, 20 participants with newly diagnosed MASLD were randomly assigned to either a 3-month intervention with a daily C8-enriched medium-chain fatty acid formulation (m-CAP; meta-Capridin, providing approximately 20 g/day of C8) or a standardized low-carbohydrate dietary protocol. Metabolic indices, inflammatory mediators, adipokines, and hepatic enzymes were assessed. The expression of key inflammasome components (NLRP3, caspase-1, and ASC) was evaluated in peripheral blood mononuclear cells, and hepatic steatosis and liver stiffness were measured via transient elastography. RESULTS: The C8-enriched intervention was associated with increased circulating β-hydroxybutyrate levels, indicating the achievement of nutritional ketosis. Changes over time were observed in metabolic parameters, including fasting serum glucose (p < 0.05), HOMA-IR (p < 0.05), body fat percentage (p < 0.05), and BMI (p < 0.05). Alterations in inflammatory mediators and adipokine-related outcomes were also observed following the intervention. At the molecular level, changes in inflammasome-related markers were detected, including caspase-1 mRNA expression (p < 0.05) and NLRP3 expression at the transcriptional (p < 0.05) and protein levels (p < 0.01), whereas ASC expression remained unchanged. Changes in hepatic steatosis (p < 0.01) and liver stiffness measurements were observed following the intervention. Given the absence of significant Group × Time interactions for several secondary outcomes, these findings should be interpreted as exploratory and hypothesis-generating. CONCLUSIONS: Induction of metabolic ketosis was associated with changes in metabolic, inflammatory, and hepatic parameters in patients with MASLD. The observed associations between ketosis, inflammasome-related markers, and noninvasive liver outcomes warrant further investigation of ketosis-based interventions as adjunctive approaches in MASLD. Larger and longer-term clinical trials are needed to confirm these findings and to determine whether short-term changes in liver stiffness reflect sustained alterations in hepatic status rather than structural fibrosis regression. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT); Unique identifier: IRCT20170315033086N12; Registration date: 19 September 2024; Registry URL: https://www.irct.ir. IRCT is a primary registry in the WHO Registry Network (https://www.who.int/tools/clinical-trials-registry-platform/network/primary-registries).

Humans↗

PubMed2026

Safety of early discharge and abbreviated nimodipine course in patients with good-grade aneurysmal subarachnoid hemorrhage.

Aneurysmal subarachnoid hemorrhage (aSAH) remains a devastating cerebrovascular emergency associated with substantial morbidity and mortality. Current guidelines recommend 14-21 days of inpatient monitoring and a 21-day course of nimodipine following aSAH. This retrospective study evaluates early outcomes early discharge (≤14 days post-ictus) and an abbreviated nimodipine course in highly selected patients with good-grade aSAH managed under a standardized institutional protocol. Consecutive patients enrolled in the Vancouver Ruptured Aneurysm Database (VRAD) at Vancouver General Hospital between 2022 and 2025 were included. Inclusion criteria were good-grade aSAH (WFNS Grade I-III) and discharge home within 14 days of ictus. The primary outcome was re-presentation to emergency care within 30 days of discharge; secondary outcomes included hospital readmission and need for additional treatment. Of 333 total patients in VRAD, 49 patients met inclusion criteria. All patients received ≤ 14 days of nimodipine therapy. Forty-two patients (85.7%) were WFNS Grade I on presentation, 3 (6.1%) were WFNS Grade II, and 4 (8.2%) were WFNS Grade III. Radiographic vasospasm was reported in 18 cases (36.7%). No patients developed DCI or clinical vasospasm. Four patients (8.2%) re-presented to emergency care within 30 days of discharge, and only one patient (2%) required hospital re-admission within 30 days. While radiographic vasospasm was seen in over one third of patients, none developed clinical sequelae, supporting the premise that radiographic vasospasm alone may be insufficient to preclude early discharge in select good-grade patients.

Humans↗