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PubMed2026

Herbicolin A, an antifungal lipopeptide produced by Pantoea agglomerans APC 4211 is a promising biocontrol agent against food spoilage fungi.

Fungal contamination of food with yeast and molds is associated with major economic losses due to spoilage and also poses health risks in the form of mycotoxin production. The strain Pantoea agglomerans APC 4211 isolated from leaves of Ilex aquifolium (holly tree) has broad spectrum antifungal activity against a variety of food spoilage fungi. Genomic analysis of the strain confirmed the presence of biosynthetic gene clusters potentially encoding for the enzymatic machinery required for the production of the antifungal lipopeptide herbicolin A. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis of the cell-free supernatant (CFS) confirmed the presence of molecular masses corresponding to herbicolin A (1300.8 Da), and herbicolin B (1138 Da). Purified herbicolin A has desirable properties for biotechnological applications, including potent antifungal activity against a range of spoilage fungi, thermal stability and resistance to proteases. The lipopeptide has low cytotoxicity against epithelial cell lines and has minimum inhibitory concentrations (MICs) lower than those of some commercial antifungal drugs (0.2-2.5 mg/L). In a model dairy system (10% skim milk), herbicolin A demonstrated excellent solubility and stability, effectively eliminating Aspergillus niger and Penicillium notatum at a concentration of 5 mg/L. Overall, the study determines herbicolin's A spectrum against food spoilage organisms and examines potential applications in food. In conclusion, herbicolin A is a potent, naturally occurring antifungal agent with the potential to be applied as a biopreservative in food systems, providing a safe, clean-label, and efficient compound for synthetic preservatives replacement.

Pantoea↗

PubMed2026

Yoga MAT: A factorial randomized study using the Multiphase Optimization Strategy to develop a multicomponent yoga intervention for people with chronic pain taking medications for opioid use disorder.

BACKGROUND: People taking medications for opioid use disorder (MOUD) commonly experience chronic pain. Yoga interventions show promise for decreasing pain-related disability in other populations. More time spent in yoga practice may improve pain-related outcomes. METHODS: The Multiphase Optimization Strategy (MOST) provided the framework for developing an optimized yoga intervention package. In a 2x2x2x2 factorial experiment, we evaluated four candidate intervention components which, when added to a weekly yoga class, might increase yoga engagement. The primary outcome was minutes per week of yoga practice (classes and other yoga practice) over the 12-week intervention period. We sought to determine which combination of intervention components was associated with the most yoga practice for people with chronic pain taking buprenorphine or methadone as MOUD. RESULTS: We enrolled 192 adults. There was a significant main effect for Component "B" (having two private sessions with a yoga teachers; IRR = 1.10, 90%CI 1.02; 1.18), and a synergistic interaction between Components "B" and "D" (D was financial incentives for attending class; IRR = 1.11, 90%CI 1.02; 1.19). This combination of these two components (without other potential components) was associated with the second highest model-predicted mean minutes of yoga per week (157.1min; 90% CI = 120.1-194.0) which was only 4min less than the combination including all four components. CONCLUSIONS: We identified a combination of intervention components as the optimized intervention. A next step will be to test the effect of this optimized intervention on pain and substance use outcomes in a randomized controlled clinical trial.

Humans↗

PubMed2026

Sleep stage-dependent distribution of interictal epileptiform discharges in epilepsy: A systematic review.

BACKGROUND: Sleep and epilepsy interact through complex bidirectional mechanisms. Although NREM sleep facilitates interictal epileptiform discharges (IED), the diagnostic contribution of individual sleep stages remains uncertain. In particular, it is unclear whether deeper sleep stages such as N3 provide an advantage over N2 for spike detection or localization in clinical (electroencephalography) EEG practice. METHODS: This systematic review followed PRISMA 2020 guidelines. PubMed and Web of Science were searched for studies reporting quantitative IED measures across sleep stages in patients with epilepsy. Eligible studies included scalp EEG, video-EEG, polysomnography, or intracranial recordings. Mean IED rates per minute were derived when possible. Comparisons between NREM and REM sleep and between N2 and N3 stages were performed using study level non-parametric tests. Risk of bias was assessed with the ROBINS-I tool. RESULTS: Ten observational studies including 266 patients (mean age 30.1 years) were analyzed. IED rates were significantly higher during NREM than REM sleep (Wilcoxon signed-rank test, W = 0, p = 0.0019, r = 0.87). No significant difference was observed between N2 and N3 sleep, although median spike rates were slightly higher during N3 than N2 (0.99 vs 0.86 IED/min). REM showed the lowest activity. CONCLUSIONS: NREM sleep consistently exhibited higher IED rates than REM sleep, reinforcing the neurophysiological association between sleep stage and epileptiform activity without establishing diagnostic superiority.

Humans↗

PubMed2026

Multi-omic biomarkers in cardiovascular disease: Discovery to clinical translation.

Cardiovascular disease (CVD) remains the leading cause of mortality worldwide, necessitating improved risk stratification and early detection strategies. Multiomics approaches that integrate genomics, transcriptomics, proteomics, metabolomics, and epigenomics offer unprecedented opportunities for biomarker discovery and precision medicine in cardiovascular care. This narrative review examines the current landscape of multiomics biomarkers for CVD, tracing their evolution from discovery to clinical translation. We synthesize evidence from recent studies evaluating the clinical utility of integrated omics approaches across diverse cardiovascular conditions, including atherosclerotic cardiovascular disease, heart failure, and atrial fibrillation. High-throughput proteomics has identified novel protein signatures that enhance cardiovascular risk prediction beyond traditional risk factors. Metabolomics has revealed pathway-specific biomarkers, including trimethylamine N-oxide and lipid species, associated with atherogenesis. Polygenic risk scores derived from genomic data demonstrate incremental value when combined with clinical risk scores. Multiomics biomarkers represent a transformative approach to cardiovascular risk assessment and disease management.

Humans↗

PubMed2026

Cognitive-metabolic relationship in temporal lobe epilepsy: A systematic review.

OBJECTIVE: To summarize the current literature on neurometabolic dysfunction identified through brain imaging and its cognitive correlates in temporal lobe epilepsy (TLE). BACKGROUND: Cognitive decline contributes to chronic disability in TLE. The pathophysiology of cognitive decline in TLE is poorly understood, limiting therapeutic advances. Characterizing metabolic changes in patients with TLE and cognitive impairment may identify biomarkers and inform new treatment strategies. DESIGN/METHODS: We conducted a systematic review of five major databases, gathering studies published through December 2024, in accordance with PRISMA guidelines. We included all observational studies describing associations between metabolic imaging findings and cognitive measures in TLE. RESULTS: Of 1449 reports, 38 met the inclusion criteria, encompassing 1161 patients with TLE aged 5-66 years. Twenty-two studies applied fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) to assess interictal brain glucose metabolism. Two studies utilized PET with other tracers to assess more specific metabolic aspects. Fourteen studies used proton magnetic resonance spectroscopy (1H-MRS) to quantify local concentrations of brain metabolites. Impairment of verbal memory was consistently associated with left temporal lobe metabolite changes. Non-memory cognitive impairments correlated with changes in glucose metabolism, N-acetylaspartate, and gamma-aminobutyrate in both temporal and extratemporal areas. CONCLUSION: 18F-FDG PET remains the most widely used imaging modality to assess cognitive-metabolic correlates in TLE, while other PET tracers and 1H-MRS are potentially underexplored. Verbal memory impairment correlates robustly with left temporal dysmetabolism. Cognitive impairment in TLE is multifaceted and correlates with measurable changes in metabolism in both temporal and extratemporal regions. While our synthesis was restricted by some methodological limitations, these neurometabolic signatures may hold promise as potential biomarkers for identifying risk of cognitive decline and highlight avenues for future research.

Humans↗

PubMed2026

Evaluation of Physical and Mental Workload and Transfusion Time in Trauma Resuscitation.

BACKGROUND: Trauma resuscitation is time sensitive and complex. Whole blood (WB) and blood components are standard treatments for trauma related hemorrhage, yet their nursing workload and transfusion time have not been well evaluated. PURPOSE: To assess feasibility of a simulation-based crossover trial and obtain preliminary estimates comparing nursing workload and transfusion completion time between WB and blood component administration. METHODS: A randomized crossover pilot study using in situ simulation was conducted with experienced trauma nurses. Time-motion analysis measured transfusion completion time, and the National Aeronautical and Space Administration Task Load Index assessed workload domains. RESULTS: Strong feasibility was demonstrated across recruitment, retention, adherence, and completion. WB was associated with significantly shorter transfusion time, lower overall workload and mental demand, less effort, and better perceived performance. CONCLUSIONS: These findings support the feasibility and justify a fully powered trial. WB may improve resuscitation efficiency and reduce cognitive burden, with potential implications for patient outcomes and nursing workflow.

Humans↗

PubMed2026

Glucocorticoid receptor antagonism in major depressive disorder with childhood trauma: a randomized controlled trial.

Childhood trauma (CT) is a key risk factor for major depressive disorder (MDD) onset and persistence. Hypothalamic-pituitary-adrenal (HPA) axis dysregulation may underlie this link, and preclinical studies suggest glucocorticoid receptor (GR) antagonism can reverse early life stress effects. This study tested whether the GR antagonist mifepristone reduces depressive symptoms in adults with MDD and CT. The RESET-medication study was a randomized, double-blind, placebo-controlled trial evaluating a 7-day course of mifepristone (1200 mg/day) or placebo in 158 adults with MDD and CT, assessed at baseline, 1 week, 6 weeks (primary endpoint), 3 months, and 6 months. The primary outcome was depressive symptom severity (IDS-SR) at week 6; secondary outcomes included symptom severity at other timepoints, clinical response, remission, anxiety, sleep, stress, disability, and salivary cortisol. At week 6, depressive symptoms declined in both groups, with no significant difference between mifepristone and placebo (b=-0.25, d=-0.03, 95% CI [-0.42, 0.36], pnom=0.887), and no group differences were found for secondary outcomes. Morning and evening cortisol were significantly higher with mifepristone at week 1, consistent with GR antagonism, but not at week 6. Adverse events were more frequent with mifepristone; mild and severe events occurred significantly more often, while the proportion reporting at least one adverse event was numerically higher but not statistically significant (93.6%vs. 82.5%, χ²(1)=3.60, p=0.058). Mifepristone produced the expected endocrine response but did not lead to clinical improvements in individuals with MDD and CT compared to placebo.

Humans↗

PubMed2026

Coordinated use of three homocysteine methyltransferases supports l-methionine biosynthesis and environmental adaptation among plant-associated bacteria.

Plant pathogens colonize multiple plant-associated habitats throughout their life cycle, encountering distinct nutrient conditions and microbial communities. l-methionine is required for bacterial growth and environmental adaptation. However, how plant pathogens coordinate l-methionine biosynthetic pathways to adapt to different plant-associated environments remains poorly understood. Here, using the plant pathogen Xanthomonas campestris pv. campestris strain XC1 as a model, we show that three homocysteine methyltransferase pathways allow XC1 to catalyze the final step of l-methionine biosynthesis using different methyl donors and cofactors under different environmental conditions. Bioinformatic and transcriptional analyses identified three homocysteine methyltransferase-associated operons in XC1, mesMXD, mmuPM, and metHRHaHb, corresponding to the MesD-, MmuM-, and MetHaHb-dependent pathways, respectively. MesD uses an endogenously synthesized methyl donor and functions as the dominant homocysteine methyltransferase under l-methionine-limiting conditions, supporting bacterial growth, intracellular l-methionine accumulation, and full virulence. Furthermore, MmuM enables XC1 to use plant-derived S-methylmethionine for l-methionine biosynthesis, whereas MetHaHb enables XC1 to use vitamin B12 supplied by a neighboring bacterium for l-methionine biosynthesis in co-culture. Expression analyses showed that mesMXD was the only homocysteine methyltransferase-associated operon that responded to l-methionine availability, and its expression also decreased when S-methylmethionine- or vitamin B12-dependent pathways supported l-methionine biosynthesis. Comparative genomic analysis further showed that the three-homocysteine methyltransferase configuration is conserved in Xanthomonas and is also present in other plant-associated bacteria. Together, these findings show that a plant pathogen can coordinate endogenous, plant-derived, and microbially supported homocysteine methyltransferase pathways to maintain l-methionine biosynthesis, providing a metabolic strategy for adaptation to plant-associated environments.

Methionine↗

PubMed2026

Safety, tolerability, and efficacy of RIPK1 inhibitor, SAR443820, in amyotrophic lateral sclerosis (HIMALAYA): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial.

BACKGROUND: RIPK1, a protein regulating inflammatory signalling and cell death, is implicated in amyotrophic lateral sclerosis (ALS) pathophysiology. SAR443820 is a selective, oral, CNS-penetrant, reversible RIPK1 inhibitor. We aimed to evaluate the safety, tolerability, and efficacy of SAR443820 in participants with ALS. METHODS: This multicentre, randomised, double-blind, placebo-controlled, phase 2 trial was conducted at 63 clinical sites in 13 countries (Belgium, Canada, China, France, Germany, Italy, Japan, the Netherlands, Poland, Spain, Sweden, the UK, and the USA). Adults (aged 18-80 years) with a diagnosis of possible ALS, clinically probable ALS, clinically probable laboratory-supported ALS, or clinically definite ALS, in accordance with the revised El Escorial World Federation of Neurology criteria, were randomly assigned (2:1) by use of a stratified block design (blocks of three) to receive either 20 mg SAR443820 orally twice per day or matching placebo in the 24-week double-blind period. Randomisation was done centrally using interactive response technology and stratified by geographical region of trial site, region of ALS onset, use of riluzole, use of edaravone, and use of the combination of sodium phenylbutyrate and taurursodiol. Participants, care providers, investigators, and outcomes assessors were masked to trial intervention. The primary outcome was a change in ALS Functional Rating Scale Revised (ALSFRS-R) total score from baseline to week 24 and was calculated for all participants who had an ALSFRS-R total score available at baseline and at week 24. Safety analyses included all randomly assigned participants receiving one dose or more of trial intervention. This trial is registered with ClinicalTrials.gov (NCT05237284) and was terminated early. FINDINGS: Between April 13, 2022, and July 17, 2023, 397 participants were screened and 305 randomly assigned to SAR443820 (n=203) or placebo (n=102); six were excluded from the primary analysis due to missing baseline ALSFRS-R values. Mean age was 56·9 years (SD 11·5); 183 (60%) participants were male and 122 (40%) were female. Least squares mean change in ALSFRS-R from baseline to week 24 was -6·73 (95% CI -7·48 to -5·98) for SAR443820 group (n=169) and -6·32 (-7·36 to -5·27) for placebo group (n=87). There was no statistically significant difference between the study groups (least squares mean difference -0·41 [95% CI -1·71 to 0·88]). Participants in the SAR443820 group had higher incidence of adverse events (171 [85%] of 202 vs placebo 80 [78%] of 102) and treatment discontinuations (28 [14%] of 202 vs placebo five [5%] of 102), with elevated hepatic enzymes being the most common cause. Nine deaths occurred in the double-blind period (seven [3%] of 202 in the SAR443820 group and two [2%] of 102 in the placebo group); none was attributed to SAR443820. INTERPRETATION: SAR443820 did not show clinical benefit and was associated with higher hepatic enzyme increase, indicating that further clinical development of SAR443820 in ALS is not warranted. FUNDING: Sanofi.

Humans↗

PubMed2026

Electroencephalographic evidence of cortical network disruption preceding overt cardioinhibition during tilt-induced reflex syncope.

OBJECTIVE: Reflex syncope is a common cause of transient loss of consciousness. However, the early cerebral mechanisms underlying cardiovascular changes remain poorly understood. Our objective was to investigate early cerebral changes by quantitatively analyzing EEG activity preceding overt cardioinhibition during tilt-induced reflex syncope. METHODS: EEG recordings from patients undergoing tilt testing were retrospectively analyzed. Patients who experienced reflex syncope were compared to those who did not. Spectral and functional connectivity analyses were performed across baseline, pre-cardioinhibition, and syncopal phases. RESULTS: Prior to the onset of cardioinhibitory pathological reflex, a significant increase in theta-band spectral power was observed in the right temporal region, accompanied by a widespread increase in functional connectivity within the same frequency band. These findings suggest the involvement of brain networks before cardioinhibition. CONCLUSIONS: EEG changes in the theta band (power and functional connectivity) were observed before overt cardioinhibition during tilt-induced reflex syncope. SIGNIFICANCE: Our findings support the hypothesis of cortical processing preceding cardioinhibition in reflex syncope. EEG may represent a valuable complementary tool for improving the understanding and diagnosis of these events.

Humans↗

PubMed2026

Molecular Landscape and Advanced Diagnostic Technologies for BRAF Mutations in Cancer: From Quantitative PCR and ddPCR to CRISPR-Based Platforms.

BRAF mutations are key oncogenic alterations across multiple malignancies, including melanoma, thyroid carcinoma, colorectal cancer, non-small cell lung cancer, glioma, and hairy cell leukemia. The most prevalent variant, BRAF-V600E, induces constitutive activation of the MAPK signaling pathway, promoting tumor progression and influencing therapeutic responsiveness. Accurate detection of BRAF alterations is therefore essential for molecular classification, prognostic assessment, treatment selection, and resistance surveillance. This review summarizes the molecular heterogeneity of BRAF mutations and critically evaluates current diagnostic methodologies. Conventional approaches such as allele-specific PCR and Sanger sequencing are compared with advanced quantitative platforms, including high-resolution melting analysis, droplet digital PCR, and next-generation sequencing, with emphasis on analytical sensitivity, mutation coverage, and clinical applicability. Emerging technologies such as CRISPR-based assays, rolling circle amplification systems, and nanoparticle-based biosensors and point-of-care diagnostic platforms are also discussed for their potential to enhance ultra-sensitive detection, particularly in liquid biopsy settings. These emerging tools are highlighted for their potential to enable ultra-sensitive, rapid, and decentralized mutation detection, particularly in liquid biopsy settings. Key challenges, including intratumoral heterogeneity, low allele-frequency variants, FFPE-associated artifacts, and clonal evolution under therapeutic pressure, are examined within a translational framework. In addition, we examine critical barriers to clinical implementation, including standardization, cost, and global accessibility of molecular diagnostics, and outline potential solutions through scalable technologies and decentralized testing strategies. We propose that optimal BRAF testing requires a mutation subclass-informed and clinically integrated strategy combining comprehensive baseline profiling with longitudinal molecular monitoring. Future diagnostic paradigms will likely integrate multi-omics data and artificial intelligence (AI)-assisted interpretation to refine precision oncology implementation. Looking forward, we propose that optimal BRAF testing will require integration of multi-omics profiling with AI-assisted interpretation, enabling automated variant classification, real-time clinical decision support, and improved prediction of therapeutic response and resistance.

Humans↗

PubMed2026

Development of a new recombineering system for Edwardsiella species.

Edwardsiella species are important aquaculture pathogens that also cause opportunistic infections in humans, necessitating efficient genome editing tools to study their pathogenesis and develop control strategies. In this study, we identified and characterized six endogenous recombinases pairs from Edwardsiella and its phages. Among these, the BAS_MS17 system exhibited the highest recombination efficiency in E. piscicida EIB202Δp. Extending homology arms from 150 bp to 200 bp improved editing efficiency by 2-fold, while the addition of Redg or Plug further enhanced recombination by 3-fold and 2.5-fold, respectively, without compromising accuracy (100%). More importantly, when applied to E. piscicida sdu12S, Redg or Plug improved the editing efficiency by 8-fold and 7-fold, respectively. Deletion of the phage-derived single-strand binding protein (SSB) reduced efficiency to 25% of the BAS_MS17 level, whereas expression of the endogenous RecA-family SSB (rSSB) increased recombinant yield by 5-fold, highlighting functional conservation. Furthermore, SSB proteins from heterologous hosts failed to enhance recombination efficiency. Using the optimized system, we successfully knocked out ten distinct genes, including virulence-associated loci, with editing accuracy exceeding 85%. Phenotypic analysis revealed that luxR, but not the other tested genes, contributes to biofilm formation. Virulence evaluation results showed that aroA, fur, and hfq are critical virulence-associated factors. Collectively, this streamlined recombineering system provides a simple, rapid, and efficient genetic tool for Edwardsiella, supporting mechanistic studies of virulence and the development of live attenuated vaccine candidates.

Edwardsiella piscicida↗

PubMed2026

Peripheral inflammation and executive function among community samples across the lifespan: A systematic review and meta-analysis.

Higher levels of peripheral inflammatory markers are proposed to disrupt cognitive processes; however, the extent to which this relationship applies to executive functions, specifically, has yet to be systematically evaluated. The current meta-analysis synthesizes all available literature measuring the association between peripheral inflammation and executive functions among community individuals across the lifespan. This systematic review searched Web of Science, PubMed, and PsycINFO for published and unpublished studies, in the English language, that assessed the association between markers of peripheral inflammation and self-report and behavioral measures of executive function. In addition to methodological and demographic information, correlation/beta coefficients were extracted from included studies to quantify the association between inflammation and executive functions. This review included 58 studies, 41 of which were included in the random-effects meta-analysis (N = 255,539). Among community individuals, higher levels of CRP and IL-6 were associated with poorer executive functioning. These results did not differ when models accounted for potential confounding variables. Meta-regressions revealed that the relationship between inflammatory biomarkers and executive function did not differ as a function of age, adiposity, or percentage of the sample who identified as female. Results of the present review indicate that higher levels of specific inflammatory markers are associated with lower performance on executive function measures; however, we observed significant heterogeneity in the study design and measurement of both inflammation and executive functioning, suggesting important considerations for future research.

Humans↗

PubMed2026

Perinatal depression, maternal thyroid status and fetus/infant health and development: A systematic review.

BACKGROUND: Thyroid hormones are known to influence both maternal depression and child developmental outcomes, while maternal depression independently affects child outcomes. The potential interaction between thyroid dysfunction and depression in shaping child development remains insufficiently explored. The present study addresses such interplay. METHODS: Following PRISMA 2020 and JBI guidelines, three databases were searched through December 2025 for primary studies on maternal thyroid status, perinatal depression, and child development. Risk of bias (RoB) was assessed using validated tools. Due to clinical and methodological heterogeneity, data were synthesized narratively following SWiM guidelines. RESULTS: Eleven studies were included. Beyond independent risks for preterm birth and behavioral problems, limited evidence supports a synergistic model, while most studies likely reflect the simple co-occurrence of risks. Maternal thyroid peroxidase antibodies (TPO-Ab) were associated with child externalizing problems exclusively in the presence of clinical depression. High depressive symptoms also attenuated the cognitive benefits of prenatal iodine supplementation. Thyroid status appears to function as a risk moderator rather than a mediator. However, 50% of observational studies presented high RoB, primarily due to participant attrition. CONCLUSION: Findings are still scarce to support a synergistic risk model where specific maternal thyroid parameters (i.e. thyroid autoimmunity and iodine status) may moderate the impact of depressive symptoms on child development. Despite the high RoB in half of the studies, results highlight the need for integrated screening protocols. Simultaneously assessing mental health and thyroid status may optimize risk stratification for high-risk mother-infant dyads.

Female↗

PubMed2026

Complementary feeding patterns in preterm and term infants.

Complementary feeding is essential for infants' nutritional status and development, marking the transition to solid foods when breast milk or formula alone is insufficient. Despite its importance, clear recommendations on which foods to introduce when initiating complementary feeding in preterm infants are lacking. By using data from our previously published randomized controlled trial on the timing of complementary feeding in preterm infants, the current study explores the complementary feeding patterns of preterm infants and compares them with those of term-born infants, providing insights into parental decision-making and potential long-term health impacts. Complementary feeding practices differed significantly between preterm (n = 255) and term (n = 159) infants, with preterm infants more often receiving vegetables as their first solid food (85.4% versus 68.8%, difference 17.6% with 95% CI 12-35%). The group with early introduction of vegetables had a lower BMI-for-age z-scores (β -0.28 [95% CI -0.55 - 0.02]) and weight-for-height z-scores (β -0.27 [95% CI -0.53 to -0.01]) at two years of age. Additionally, preterm infants showed a greater variety in the numbers of different fruits and vegetables consumed by six months (corrected) age than term-born counterparts (8.29 (SD 3.65) versus 6.26 (SD 3.47), p < 0.001). These results indicate that complementary feeding patterns in preterm infants differ from term-born infants, with potential positive implications on growth. These data contribute to the development of accurate feeding protocols for preterm infants. Given that feeding practices are culturally influenced, further multinational research is essential to refine complementary feeding guidelines for preterm infants and support caregivers in informed decision-making.

Humans↗

PubMed2026

Opposite metabolic and gut responses to oral glutamine in male and female mice with diet-induced obesity.

Obesity is often associated with sex-dependent metabolic complications, to which altered intestinal barrier function and gut microbiota contribute. Glutamine supplementation has previously shown beneficial effects on gut barrier function and glycemic control. We thus aimed to characterize, in male and female mice, the effects of oral glutamine supplementation during high-fat-diet-induced obesity. Male and female C57BL/6 mice received a standard (SD) or high-fat diet (HFD; 60 % kcal from fat) for 14 weeks (W14). From W12 onward, mice received glutamine in drinking water (2 g/kg/day) or no supplementation. Body composition, glucose tolerance, insulin sensitivity, intestinal permeability, colonic inflammatory response, cecal microbiota and inflammatory/endocrine adipose response were assessed. In both male and female mice, glutamine supplementation failed to improve body weight and body composition. However, glutamine reduced glucose intolerance in HFD-fed males (AUC reduced by 14.57 %) that was associated with a partial restoration of plasma resistin and insulin and a trend toward limiting adipose inflammatory response. In males, glutamine did not affect gut microbiota composition and colonic response. Conversely, in HFD-fed females, glutamine supplementation led to gut microbiota changes (increase in Bacteroidota and Pseudomonadota phyla; increase in Muribaculaceae and Tannerellaceae families), increased colonic inflammatory markers (Il1b, Tlr4, Myd88, Irf3), increased inflammatory response in subcutaneous adipose tissue and increased HOMA-IR. Finally, HFD-fed mice exhibited sex-specific responses to glutamine supplementation with protective effects in males and harmful effects in females that need to be further deeply explored.

Animals↗

PubMed2026

Artificial intelligence-derived myocardial fibrosis on cardiac magnetic resonance for prognosis in cardiomyopathy: A systematic review of a sparse evidence base.

BACKGROUND: Myocardial fibrosis on cardiovascular magnetic resonance (CMR), assessed by late gadolinium enhancement (LGE) and parametric mapping, is an established predictor of adverse events in cardiomyopathy. We assessed whether artificial intelligence (AI) quantification of fibrosis adds independent prognostic value. METHODS: We searched six databases, a clinical-trials register, and a preprint server from inception to 13 June 2026. Eligible studies used AI to generate a fibrosis marker in adults with ischemic or nonischemic cardiomyopathy, with covariate-adjusted outcomes over ≥12 months. Risk of bias was assessed using PROBAST, PROBAST+AI, and QUIPS. Fewer than three comparable studies precluded meta-analysis; certainty was rated using GRADE. RESULTS: Of 448 records (381 after de-duplication), 18 full texts were reviewed and two included, one peer-reviewed and one preprint. In an ischemic-cardiomyopathy registry (Ghanbari et al.; n = 216 analytic, 26 events), AI-derived dense LGE scar predicted arrhythmic events (univariable hazard ratio [HR] 2.35, 95% CI 1.33-4.15), and AI-derived but not manual scar improved discrimination beyond guideline criteria (area under the curve 0.63 to 0.68; p = 0.02). In a nonischemic dilated-cardiomyopathy preprint (Kim et al.; n = 347, 119 events), automated extracellular volume ≥30% predicted cardiovascular death or heart-failure hospitalization (adjusted HR 2.00, 95% CI 1.32-3.03). Both were at high risk of bias, with data-derived thresholds and no external validation. CONCLUSIONS: Across only two studies, AI-derived fibrosis was independently associated with adverse cardiovascular events, but its added value over manual quantification remains unproven. Certainty was very low. The evidence base is sparse and not yet ready for clinical use.

Humans↗

PubMed2026

Recurrent myocardial infarction identified by centralized troponin review: Insights from the MINT trial.

BACKGROUND: The utility of routine troponin testing to identify recurrent myocardial infarction (MI) after an incident MI is unclear. We assessed the incidence and prognosis of recurrent MIs identified from centralized troponin review in patients from the Myocardial Ischemia and Transfusion (MINT) trial. METHODS: The MINT trial randomized patients with acute MI and anemia to a liberal vs restrictive red blood cell transfusion strategy. Suspected recurrent MIs were identified through both site-report and centralized review of troponin levels collected for 3 days following randomization. Differences in cardiac, noncardiac, and all-cause death at 30 and 180 days were compared across patients with any site-reported MI, only centrally identified MI, and no recurrent MI. RESULTS: Among 3,504 patients, 275 (7.8%) had a recurrent MI within 30 days; 119 (43.3%) by site-report, and 156 (56.7%) by central troponin review only. Rates of cardiac and all-cause death at 30 and 180 days were highest for patients with site-reported MI, intermediate for centrally identified MI, and lowest for no recurrent MI; rates of noncardiac death did not vary. Patients with only centrally identified recurrent MI had an increased risk of cardiac death at 30 days (RR 1.9, 95% CI 1.0-3.4) and 180 days (RR 1.7, 95% CI 1.1-2.7) compared to those without recurrent MI. CONCLUSIONS: In patients with acute MI and anemia, centralized troponin review identified more than half of all recurrent MI events. Patients with centrally identified MI had a higher risk of cardiac death than those with no recurrent MI. TRIAL REGISTRATION: ClinicalTrials.gov NCT02981407 https://clinicaltrials.gov/study/NCT02619136.

Humans↗