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PubMed2026

Adjuvant apatinib therapy following concurrent chemoradiotherapy in patients with high-risk nasopharyngeal carcinoma: A multicenter, prospective phase 2 study.

PURPOSE: To assess the efficacy and safety of concurrent chemoradiotherapy (CCRT) combined with apatinib in locoregionally advanced nasopharyngeal carcinoma (LA-NPC). METHODS: This multicenter, prospective, phase II study enrolled patients with newly histologically confirmed LA-NPC, who were randomly assigned to receive CCRT followed by adjuvant apatinib (investigational arm) or CCRT alone (control arm). The investigational arm received 250 mg/day of oral apatinib administered every 28 days for up to six cycles after CCRT. The primary endpoint was 3-year progression-free survival (PFS) and secondary endpoints of overall survival (OS), distant metastasis-free survival (DMFS) and local recurrence-free survival (LRFS) of 3-year, and safety. RESULTS: From July 2018 to September 2020, 44 and 44 patients were randomized into the CCRT-alone and CCRT and apatinib groups, respectively. The median follow-up duration 56 (range: 40.0-58.6) months. The survival outcomes were the 3-year PFS, OS, and DMFS rates in the adjuvant apatinib following CCRT group were significantly higher than those observed in the CCRT-alone group((PFS, 78.6%vs. 54.5%, p = 0.027; OS, 88.1% vs. 75.0%, p = 0.029; DMFS, 85.4%vs. 59.1%, p = 0.009). The 3-year LRFS was similar between the groups. The grade 3-4 treatment-related adverse events(TRAEs) were higher in the former group than in the latter. The most common grade 3-4 non-hematology-related adverse events were hypertension (14.3%), hand-foot syndrome (9.5%), increased transaminase levels (7.1%), and headache (7.1%). CONCLUSION: Apatinib significantly improved the treatment effects of CCRT for high-risk LA-NPC patients. Therefore, CCRT and adjuvant apatinib may represent a promising option for this patient population.

Adjuvant therapy↗

PubMed2026

Ossicle occurrence characteristics and related molecular mechanisms in the sea cucumber Apostichopus japonicus.

To investigate the morphogenetic pattern and molecular mechanism of ossicle formation in the sea cucumber Apostichopus japonicus, this study systematically examined the morphological development and temporal sequence of spicules using the NaClO maceration method, in-situ squash preparation and microscopic observation. Comparative transcriptome sequencing was performed between doliolaria and pentactula larvae to screen differentially expressed genes (DEGs) related to ossicles formation, followed by pathway enrichment analysis. The function of the candidate key gene papilin-like was verified using siRNA-mediated gene silencing. The results were as follows: 1) Ossicles of A. japonicus first appeared at the late auricularia stage, initiating as X-shaped ossicles at the base of the oral tentacles. The number of X-shaped ossicles increased dramatically during the doliolaria stage. X-shaped ossicles were gradually replaced by table-shaped and rosette-shaped ossicles at the pentactula stage, suggesting that X-shaped ossicles may differentiate into these two ossicle types. The morphology of table-shaped ossicles showed a "simple-complex-simple" pattern with development. 2) Key genes related to ossicles formation, including CA1, COL1A2, and papilin-like, were identified by transcriptome analysis. After papilin-like knockdown, abnormal morphologies were observed in table-shaped ossicles of 1-year-old A. japonicus, such as spine-like protrusions on the outer margin of the disc and loss of table legs, confirming its crucial roles in maintaining ossicle morphology. This study clarified the morphological development pattern of ossicles in A. japonicus and identified a key regulatory gene (papilin-like) involved in ossicle morphogenesis, providing preliminary insights into the underlying molecular regulatory mechanism. These findings enrich our understanding on ossicles formation in echinoderms, and provide important morphological and molecular biological information for further studies on the developmental mechanism of ossicles in A. japonicus.

Animals↗

PubMed2026

Insights from changes in NDEV biomarkers of metabolism: effects of PPARγ and GLP1 receptor agonists on brain metabolism.

BACKGROUND: Insulin resistance (IR) is implicated in central nervous system disorders, including depression and Alzheimer's disease (AD). METHODS: We analyzed biological samples from two cohorts of clinical trial participants: (1) participants with unremitted depression after six months of treatment as usual who received pioglitazone (PPARγ agonist, N = 12) or placebo and (2) middle-aged participants at genetic risk for AD who received liraglutide (glucagon-like peptide 1 [GLP1] receptor agonist, N = 15) or placebo. These cohorts, which previously showed treatment-related improvements in peripheral IR, were used to assess the effects of pioglitazone and liraglutide on CNS insulin signaling using neuron-derived extracellular vesicles (NDEVs) as biomarkers. We utilized biological samples to measure biomarkers of IR in NDEVs. Eleven Akt-mTOR pathway proteins were measured before and after 12 weeks of treatment in both groups. RESULTS: Participants who received pioglitazone experienced broader changes, with significant increases in GSK3β (Ser9), mTOR (Ser2448), and RPS6 (Ser235/Ser236; all P ≤ .02) compared with placebo, and 77% of participants showed mTOR (Ser2448) response. Participants who received liraglutide demonstrated significantly increased NDEV-associated phosphorylated Akt (Ser473) and mTOR (Ser2448; P = .04 and P = .025, respectively) compared with placebo, with 40% and 30% of participants in the liraglutide group showing biomarker response in both Akt (Ser473) and mTOR (Ser2448), respectively. These effects appeared relatively independent from changes in fasting plasma insulin and glucose concentration at 120-minutes during the oral glucose tolerance test. DISCUSSION: Our findings demonstrate CNS-specific biomarker responses to both PPARγ agonists and GLP1 receptor agonists.

Humans↗

PubMed2026

Perspectives of participating neurologists and study nurses - Mixed-methods process evaluation of a web-based program for relapse management in multiple sclerosis (POWER@M2).

BACKGROUND: Relapsing-remitting multiple sclerosis is a chronic inflammatory disease of the central nervous system and the leading cause of disability in young adults. In Germany, 90% of relapses are treated with high-dose intravenous glucocorticoids, despite limited evidence for long-term benefit and international preference for oral administration. Time constraints often hinder informed decision-making. The multicentre Randomized Controlled Trial (RCT) POWER@MS2 (N = 160, 2020-2023), conducted at 18 German MS-centres, aimed to promote self-determined relapse management through a complex intervention (dialogue-based decision aid, nurse-led webinar, online-chat). OBJECTIVE: While RCTs demonstrate effectiveness, process evaluations are essential to understand implementation, mechanisms of impact and contextual factors. This study explored healthcare professionals' experiences and attitudes toward implementing relapse self-management and self-medication in clinical practice. METHODS: A mixed-methods process evaluation followed the UK Medical Research Council- framework. Quantitative data were collected via validated questionnaires at up to three time points and analysed descriptively. Interview guides were developed based on these results. Qualitative data from neurologist and study nurse interviews were thematically analysed. Results were triangulated using a joint display. RESULTS: Data were collected from 55 neurologists and 17 study nurses (quantitative) and from 7 neurologists and 4 nurses (qualitative) (2020-2024). Most neurologists opposed routine steroid use, reserving it for severe relapses. Some voiced concerns about self-management, but informed patients were generally viewed as capable of safe self-medication. Study nurses gave mixed feedback on the intervention, citing overload and improved guidance. CONCLUSION: Clinicians showed openness toward implementing the intervention. Enhancing accessibility and addressing specific concerns may support broader adoption.

Humans↗

PubMed2026

Indications, Techniques and Complications Associated With Pterygoid Implants: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Pterygoid implants represent a graftless option for rehabilitation of patients with posterior maxillary atrophy, engaging the dense cortical bone of the pterygomaxillary complex. Despite clinical growth, a comprehensive synthesis of indications, surgical techniques, and complications is lacking. This review evaluated the prevalence of complications, implant survival rates, and marginal bone loss (MBL) associated with pterygoid implant placement. METHODS: The reporting of this review follows PRISMA 2020 guidelines. Six electronic databases (PubMed, Ovid, Scopus, WoS, CENTRAL, and Dentistry & Oral Sciences Source) were searched from 1 January 2020 to 31 December 2025. Included criteria comprised randomized and non-randomized clinical studies reporting outcomes of pterygoid implants (≥ 13 mm) in adult patients with posterior maxillary atrophy (minimum 10 implants). Risk of bias was assessed using JBI critical appraisal checklists. Proportions were pooled using the Freeman-Tukey double arcsine transformation under a random-effects model. Certainty of evidence was assessed using GRADE. RESULTS: Seventeen studies reporting 846 patients and 1915 pterygoid implants were included. The pooled survival rate was 97.9% (95% CI: 97.1%-98.6%; I2 = 0%; 14 studies) and the overall failure rate was 2.1% (95% CI: 1.4%-3.0%). Early failure rate was 0.9% (95% CI: 0.0%-3.0%; I2 = 59.5%). Late failure and MBL were summarized narratively. Certainty of evidence was low to very low. CONCLUSIONS: Pterygoid implants demonstrate excellent survival (97.9%) and low failure rates (2.1%), primarily early, supporting their reliability as a graftless solution for posterior maxillary atrophy. Complications appear infrequent though heterogeneously reported. Low evidence certainty necessitates prospective studies with standardized outcome reporting.

Humans↗

PubMed2026

Tissue origins of the plasma proteomic response to glucose ingestion in humans.

AIMS/HYPOTHESIS: Circulating proteins act as important hormonal signals of nutrient intake. We aimed to systematically characterise the time-resolved proteomic response to glucose ingestion in humans, and to assess its robustness following prolonged complete caloric restriction. METHODS: We conducted oral glucose tolerance tests (OGTTs) in 11 healthy volunteers before and after 7 days of complete caloric restriction and measured the response of >2900 targets through high-resolution plasma protein profiling. RESULTS: We identified a signature of 44 proteins that changed significantly following glucose ingestion, which was reproducible after 7 days without food, and was strongly (20-fold) enriched for 'stomach-specific' proteins. We report that annexin A10 (ANXA10) shows the most significant post-glucose change observed, similar to the trajectories of secreted hormones. We present observational human evidence from multiple sources suggesting that ANXA10 is secreted upon sensing an increase in gastric pH, with the stomach as the major contributing tissue. Despite a profound metabolic shift after 7 days of complete caloric restriction, characterised by delayed insulin secretion and postprandial hyperglycaemia, only four proteins showed robust evidence for a differential trajectory during both OGTTs. This included plasma levels of tryptophanyl-tRNA synthetase 1 (WARS), for which we found a genetic association with glucose homeostasis and coronary artery disease. CONCLUSIONS/INTERPRETATION: Our exploratory study identifies the proteomic response to glucose ingestion and demonstrates its reproducibility despite major shifts in glucose homeostasis. We characterise the gastrointestinal origin of these changes, and hypothesise a hitherto under-recognised role for sensing of changes in gastric pH on the plasma proteome.

Humans↗

PubMed2026

Phytolacca acinosa Roxb. induces intestinal toxicity through the histamine-MLCK-tight junction axis: Integrated evidence from proteomics, metabolomics, intestinal organoids and epithelial barrier validation.

Phytolacca acinosa Roxb. (PR) is a saponin-rich medicinal plant associated with gastrointestinal toxicity, but the mechanisms underlying PR-induced intestinal barrier injury remain unclear. In this study, raw PR extract was analytically characterized by UPLC-ZenoTOF-MS/MS, confirming triterpenoid saponins as the predominant constituents. C57BL/6 J mice were orally exposed to characterized PR extract (1.20 or 12.0 g/kg for 5 h), and Caco-2 cells and mouse intestinal organoids were used to assess epithelial toxicity and barrier disruption. Histopathology, ELISA, FITC-dextran permeability assays, immunofluorescence, CCK-8, LDH release, western blotting, DIA-based proteomics and untargeted metabolomics were integrated to define toxicological mechanisms. PR induced dose-dependent intestinal inflammation and barrier dysfunction, with the ileum as the most sensitive target. PR increased serum DAO and D-lactate and intestinal TNF-α and IL-1β, disrupted organoid morphology, enhanced epithelial permeability, and reduced ZO-1 expression. Proteomics revealed changes in inflammatory, lipid-metabolic, cytoskeletal and tight-junction pathways, including upregulation of MLCK3 and phospholipase-related proteins and downregulation of ZO-1 and ZO-2. Metabolomics identified histidine metabolism disturbance and histamine accumulation. Integrated multi-omics and pharmacological validation indicated that histamine activated the PLC/IP₃/Ca²⁺/CaM/MLCK cascade, promoting MLC phosphorylation, tight-junction disassembly and epithelial leakiness. MLCK inhibition partially restored ZO-1/ZO-2 expression and attenuated PR-induced epithelial injury. These findings identify the histamine-MLCK-tight junction axis as a key mechanism of PR-induced intestinal toxicity and support hazard identification of saponin-rich PR exposure.

Animals↗

PubMed2026

Bacterial Lysates Add-On Therapy to Reduce Postoperative Recurrence in Nasal Polyps.

OBJECTIVE: This study aimed to investigate the potential role of OM-85 in reducing polyp recurrence (PR). METHODS: A single-center randomized, prospective study was performed to compare the inter-group PR rate, patient-reported outcome measures (PROMs), CT and endoscopic scores. Hundred patients were randomized to receive either add-on OM-85 (34/50) or control group (43/50); 77 participants completed the 12-month follow-up. The OM-85 group received oral treatment for 10 days, followed by a 20-day washout (Months 1-3 and 7-9). Primary outcome was the PR rate. Secondary outcomes included PROMs, Lund-Kennedy (L-K) scores, Lund-Mackay (L-M) scores, and complete blood count (CBC) parameters. RESULTS: The PR rate was significantly lower in the OM-85 group (8.82%) than in the control group (27.91%, χ 2 = 4.408, p = 0.036). Univariable analysis identified pre-operative Lund-Mackay (L-M) score (p = 0.008) and hyposmia VAS score (p = 0.031) as significant predictors of PR. In multivariable analysis, the L-M score remained an independent predictor (OR = 1.15, p = 0.012), with an optimal cutoff of 10. The OM-85 group showed significant improvements in nasal obstruction, olfactory dysfunction, and mucopurulent discharge at 6 and 12 months (p < 0.05). Lund-Kennedy (L-K) score and 22-item Sinonasal Outcome Test (SNOT-22) score were also significantly improved (p < 0.05). Furthermore, the OM-85 group exhibited elevated white blood cell counts and lymphocyte percentages from 6 months onward (p < 0.05). CONCLUSION: Adjuvant OM-85 may reduce postoperative PR, with improved endoscopic and symptom scores, potentially mediated by enhanced systemic immune function.

Humans↗

PubMed2026

Integrated genomic and biochemical diagnosis of a novel homozygous start-loss variant in AKR1D1 associated with neonatal cholestasis.

INTRODUCTION: Congenital bile acid synthesis defects are rare autosomal recessive disorders that typically present in early infancy with cholestasis, progressive liver dysfunction, and, in severe cases, acute liver failure. These conditions may mimic other metabolic diseases detected in newborn screening, complicating early diagnosis. The AKR1D1 gene encodes Δ4-3-oxosteroid 5β-reductase, a key enzyme in primary bile acid synthesis, and pathogenic variants cause bile acid synthesis defect type 2 (OMIM #235555). CASE DESCRIPTION: We report a 3-month-old male infant with severe neonatal cholestasis and a history of elevated tyrosine levels in newborn screening. Pregnancy was high risk and unmonitored, with birth outside a hospital. Parental consanguinity was first-degree. Early metabolic evaluation showed transient normalization of tyrosine levels, but subsequent analyses revealed recurrent hyper-tyrosinemia. Urinary organic acids showed increased 4-hydroxyphenyl metabolites, with absent succinylacetone, excluding tyrosinemia type I. Progressive cholestasis developed, accompanied by coagulopathy, hyperbilirubinemia, hyperammonemia, and markedly elevated alpha-fetoprotein. Imaging revealed no structural liver abnormalities. Clinical exome sequencing identified a novel homozygous start-loss variant in AKR1D1, likely abolishing functional enzyme production. Metabolic studies confirmed increased urinary excretion of 3-oxocholenoic acids consistent with abnormal bile acid synthesis and supporting a diagnosis of bile acid synthesis defect type 2. Oral cholic acid therapy led to stabilization and improvement in clinical and biochemical parameters. DISCUSSION/CONCLUSION: This case illustrates the diagnostic complexity of neonatal cholestasis, particularly when initial metabolic findings suggest alternative etiologies. It highlights the importance of newborn screening as a tool for broader diagnostic suspicion and the critical role of early molecular diagnosis and multidisciplinary care. Timely recognition and targeted therapy can improve outcomes, prevent liver transplantation, and enable accurate genetic counseling, especially in consanguineous families.

Humans↗

PubMed2025

Respiratory-swallow coordination training using bimodal signal biofeedback for patients with post-stroke dysphagia: a randomized controlled trial.

OBJECTIVE: The purpose was to investigate the effects of respiratory-swallow coordination training with bimodal signal biofeedback on swallowing function in patients with post-stroke dysphagia. METHODS: Post-stroke dysphagia Patients were randomly assigned to either the control group or the experimental group. The control group received conventional rehabilitation, while the experimental group underwent additional respiratory-swallow coordination training based on biofeedback. The training protocol consisted of three phases, conducted at an intensity of 30 min/day, 6 days/week, for two consecutive weeks. Outcome measures included the Functional Oral Intake Scale (FOIS) score, the Rosenbek Penetration-Aspiration Scale (PAS) score, respiratory-swallow coordination, and videofluoroscopic swallowing study temporal and kinematic parameter. Assessments were conducted at baseline, post-treatment, and at a one-month follow-up. RESULTS: Thirty patients were enrolled. Both groups showed significant improvement in FOIS scores from baseline to both two-week post-treatment and one-month follow-up (p < 0.001). Compared to the controls, the experimental group demonstrated significantly greater FOIS scoreimprovement at both post-treatment and follow-up (p < 0.001). The proportion of patients with a ≥ 2-point increase in FOIS scores was significantly higher in the experimental group than in the control group at both post-treatment (p < 0.01) and one-month follow-up (p < 0.01). After two weeks of treatment, the percentage of PAS scores ≥6 was significantly lower in the experimental group than in the control group (p < 0.001). Additionally, the percentage of optimal respiratory-swallow pattern was significantly higher in the experimental group than in the control group (p < 0.001). CONCLUSION: Bimodal signal biofeedback-based respiratory-swallow coordination training can effectively improve respiratory-swallow coordination and swallowing function in patients with post-stroke dysphagia.

Humans↗

PubMed2026

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

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

Humans↗

PubMed2026

Same-day initiation of tenofovir alafenamide-based pre-exposure prophylaxis with drug-level feedback for transgender women in Uganda.

OBJECTIVE: To evaluate the feasibility and acceptability of same-day initiation of emtricitabine/tenofovir alafenamide (F/TAF) pre-exposure prophylaxis (PrEP) and test the impact of drug-level feedback on PrEP adherence among transgender women (TGW) in Uganda. DESIGN: Randomized controlled trial. METHODS: HIV-negative TGW were randomly assigned 1 : 1 to intervention (drug-level feedback with tailored adherence counseling) or standard-of-care (SOC), and followed quarterly for 12 months (November 2021-July 2023; NCT04491422). Quarterly clinic visits included demographic and socio-behavioral data collection, PrEP refills, STI testing, and quarterly PrEP adherence assessment using tenofovir levels in dried blood spots (DBS; long-term) and urine (short-term). RESULTS: We enrolled 200 TGW (100 per arm), median age 21 years. Same-day F/TAF PrEP initiation was 100%. Tenofovir detection in urine (intervention arm) was 79, 80, 85, and 70% at the 3, 6, 9, and 12-month visits, respectively. Tenofovir detection in DBS was 46, 40, 35, and 31% at 3, 6, 9, and 12 months, respectively. Median tenofovir DBS concentrations were 40.6 and 47.0 fmol/punch in intervention and SOC arms, respectively. There was no intervention effect on PrEP adherence (DBS tenofovir levels) [adjusted incidence rate ratio (aIRR) 1.06; 95% CI: 0.82-1.37]. Never being harassed by police for being transgender (aIRR 1.66; 95% CI: 1.24-2.23), history of taking daily medication for more than 7 days (aIRR 1.51; 95% CI: 1.18-1.93) and higher monthly income (aIRR 1.44; 95% CI: 1.10-2.04) were associated with PrEP adherence. CONCLUSION: Oral F/TAF PrEP adherence among TGW in Uganda was low and not affected by drug-level feedback or tailored adherence counseling. Long-acting injectable PrEP formulations should be considered for this population.

Humans↗

PubMed2026

Social support and cognitive function in postmenopausal women.

OBJECTIVE: An active social lifestyle may protect against cognitive decline in older adults, but few studies have examined specific social support dimensions in relation to specific cognitive domains. This study examines associations between social support dimensions and cognitive function in older women. METHODS: The Early versus Late Intervention Trial with Estradiol (ELITE) was a randomized, double-blinded, placebo-controlled trial of oral 17β-estradiol versus placebo in postmenopausal women, designed primarily to evaluate the timing hypothesis on atherosclerosis progression and cognitive decline; the present analysis is a secondary, hypothesis-generating examination of the psychosocial substudy data (2009-2012). A total of 448 women completed psychosocial assessments every 6 months. Cognitive function was assessed at baseline, 2.5, and 5 years using composite scores for executive function, verbal memory, visual memory, and global cognition derived from 14 standardized tests. Perceived social support was assessed using the Medical Outcomes Study-Social Support Survey (MOS-SSS; 0-100 scale). Paired cognitive-psychosocial assessments were analyzed using linear mixed-effects models adjusted for age, marital status, blood pressure medication, BMI, education, income, race, and randomized treatment (hormone therapy or placebo). RESULTS: A total of 298 women (mean age 60.3 y) provided 322 paired visits. Positive associations were observed between instrumental social support and visual memory (β(SE)=0.0044(0.0022), 95% CI: -0.00002 to 0.0088, P=0.051) and between positive social interaction and global cognition (β(SE)=0.0092(0.0046), 95% CI: 0.0001-0.0182, P=0.047). In age-stratified analyses, the positive social interaction-global cognition association was significant among women <65 years (P=0.042) but not women ≥65 years (P=0.34). No association survived false discovery rate (FDR) correction for multiple comparisons. CONCLUSIONS: In this sample of healthy middle- to older-aged women, no association between specific dimensions of social support and cognitive domains was statistically significant after correction for multiple comparisons. These hypothesis-generating findings suggest any association is modest at best and warrant confirmation in studies designed specifically for this question.

Cognitive function↗

PubMed2026

Faecal Microbiota Transplantation Reduces Lesion Severity and Medication Use in Canine Atopic Dermatitis: A Randomised, Placebo-Controlled, Double-Blinded Clinical Trial.

BACKGROUND: Faecal microbiota transplantation (FMT) is an established therapy for gastrointestinal disease, yet its role in canine atopic dermatitis (cAD) remains unclear. HYPOTHESIS/OBJECTIVES: We hypothesised that adjunctive FMT improves clinical severity and reduces symptomatic medication use in dogs with cAD. The objective was to evaluate efficacy and safety versus placebo. ANIMALS: Forty-six client-owned dogs with naturally occurring cAD were enrolled from a referral hospital population; 40 completed the study (FMT n = 20, placebo n = 20). MATERIALS AND METHODS: Prospective, randomised, placebo-controlled, double-blinded clinical trial. Dogs received daily oral lyophilised FMT capsules for 90 days plus three monthly rectal FMT administrations (Day [D]0, D30, D60) or placebo capsules with sham handling. Concomitant symptomatic therapies were permitted. Outcomes included Canine Atopic Dermatitis Extent and Severity Index, fourth iteration (CADESI-04), pruritus Visual Analog Scale (PVAS), Medication Score (D0-90) and Owner Global Assessment of Treatment Efficacy (OGATE, D90). RESULTS: CADESI-04 scores were lower with FMT at month (M) 2 (7 ± 6 vs. 16 ± 12; p = 0.006) and month 3 (8 ± 6 vs. 15 ± 12; p = 0.020). Sustained responders (≥ 50% CADESI-04 improvement at M2 and M3) were more frequent with FMT (35% vs. 5%; p = 0.044). In the FMT group, the medication scores were lower at M2 (16 ± 10 vs. 23 ± 11; p = 0.033) and M3 (13 ± 10 vs. 24 ± 15; p = 0.007) compared to placebo. PVAS decreased in both groups without between-group differences. OGATE favoured FMT (p = 0.028). FMT was well tolerated. CONCLUSIONS AND CLINICAL RELEVANCE: Adjunctive FMT reduced lesion severity and medication requirements, supporting its use as a safe microbiome-based add-on therapy in cAD.

Animals↗

PubMed2026

Effect of Food on Balcinrenone/Dapagliflozin Pharmacokinetics and the Pharmacokinetics of Balcinrenone When Dosed with a P-gp Inhibitor.

Balcinrenone (AZD9977) is a novel selective non-steroidal mineralocorticoid receptor antagonist with a distinct mode of action being developed as a fixed-dose combination with the sodium-glucose cotransporter-2 inhibitor dapagliflozin for the treatment of heart failure with impaired kidney function, and chronic kidney disease. In this Phase 1 randomized open-label three-way crossover study we investigated the effect of food on balcinrenone/dapagliflozin pharmacokinetics, and the pharmacokinetics of balcinrenone when dosed with a P-glycoprotein (P-gp) inhibitor. Fourteen healthy participants were administered an oral capsule of balcinrenone/dapagliflozin 40 mg/10 mg in three dosing periods: fasted (reference), fed (high-fat, high-calorie meal) and with a P-gp inhibitor (quinidine 300 mg × 2). Balcinrenone exposure was comparable in the fed and fasted states (geometric mean ratios [GMRs] [90% CI]: maximum plasma concentration [Cmax] 1.05 [0.88, 1.25]; area under the plasma concentration-time curve from time 0 to infinity [AUCinf] 1.12 [1.06, 1.19]). In the fed state, dapagliflozin AUCinf was comparable to the fasted state (GMR [90% CI] 1.05 [1.01, 1.09]), whereas Cmax was decreased (GMR [90% CI] 0.59 [0.51, 0.69]), in line with previous dapagliflozin food interaction studies. Co-administration with quinidine increased balcinrenone exposure: GMRs (90% CI) 1.48 (1.24, 1.76) and 1.24 (1.17, 1.31) for Cmax and AUCinf, respectively, but AUC fold increase was <2, the level used for classification of sensitive P-gp substrates. All interventions were well tolerated. In conclusion, this study supports dosing of balcinrenone/dapagliflozin without regard to food. Balcinrenone is not considered a sensitive P-gp substrate. No P-gp based dosing precautions are warranted based on this study.

Adult↗

PubMed2026

Transcriptomic responses of gill and intestinal tissues in Nile tilapia (Oreochromis niloticus) to bacterial infection following sequential nanoimmersion and hydrogel-based multivalent vaccination.

Bacterial pathogens, including Flavobacterium oreochromis, Aeromonas veronii, Streptococcus agalactiae, and Edwardsiella tarda, represent major infectious threats to Nile tilapia (Oreochromis niloticus). A multivalent vaccination strategy integrating cationic nanoemulsion immersion with oral hydrogel boosters was developed to investigate tissue-specific immune responses at the transcriptomic level. Gill tissues were collected following immersion challenge and intestinal tissues following intraperitoneal injection challenge, reflecting the physiologically relevant infection biology of each pathogen and the mechanistic rationale of each delivery platform. RNA sequencing (RNA-seq) generated high-quality datasets (mapping rate > 81.64%) with strong concordance to quantitative real-time PCR (qRT-PCR) validation (r = 0.83). Comparative transcriptomic analysis revealed distinct yet complementary immune signatures between tissues. Gill transcriptomes were enriched in phagosome, focal adhesion, extracellular matrix-receptor interaction (ECM-receptor interaction), and cytokine-cytokine receptor interaction pathways, accompanied by increased expression of major histocompatibility complex class I/II (MHC class I/II), mannose receptor, αVβ3 integrin, and calnexin, indicating innate activation, enhanced phagocytic capacity, epithelial barrier reinforcement, and adaptive immune coordination. Intestinal transcriptomes showed predominant enrichment of adaptive immune pathways, including the intestinal immune network for immunoglobulin (Ig) production, Forkhead box O (FoxO) signaling, and mitogen-activated protein kinase (MAPK) signaling, with increased expression of T-cell receptor (TCR), inducible T-cell co-stimulator ligand (ICOS-L), C-X-C chemokine receptor type 4 (CXCR4), and polymeric immunoglobulin receptor (pIgR), reflecting T and B cell coordination, lymphocyte trafficking, and mucosal immunoglobulin transport, alongside innate engagement through phagosome pathway enrichment. Shared upregulation of MHC class II, B-cell receptor (BCR) signaling, integrin alpha M (ITGAM), and immunoglobulin-associated components across both tissues suggests coordinated mucosal immune activation through a conserved immune module, warranting direct experimental validation. Collectively, these findings provide transcriptomic evidence that this vaccination strategy elicits an integrated, tissue-specialized immune response, advancing mechanistic understanding of gill and intestinal immunity in vaccine-induced protection of teleost fish.

Animals↗

PubMed2026

Evaluation of pilocarpine effects on sweat proteome.

BACKGROUND: Sweat is increasingly recognized as a valuable, non-invasive biofluid for biomarker discovery, yet its composition depends on the stimulation method. This study aimed to determine how pharmacological induction with pilocarpine compares to physiologically induced sweat through exercise in shaping the sweat proteome. RESULTS: We analyzed thermoregulatory sweat from exercise, pilocarpine-induced sweat, and combined pilocarpine plus exercise sweat. Total protein concentrations were similar across conditions, but pilocarpine markedly increased proteomic diversity, with combined pilocarpine plus exercise sweat showing the highest number of identifications. The core sweat proteome remained stable, while pilocarpine selectively enriched low-abundance proteins involved in vesicular trafficking, cytoskeletal remodelling, and metabolism. Proteins linked to the canonical M3-Gq-PLC-Ca2+ pathway, including AQP5, CALML5, and CLIC1, were consistently enriched, confirming cholinergic activation. Pilocarpine-induced sweat also contained plasma-derived and immune-related proteins, reflecting enhanced secretion and reduced ductal reabsorption. CONCLUSIONS: Exercise yields a physiologically relevant but less complex proteome, pilocarpine-induced sweat produces a pharmacologically enriched yet biased profile, and combined pilocarpine plus exercise sweat maximizes protein detection at the expense of interpretability. These findings highlight the critical impact of stimulation paradigm on sweat proteomics and provide a reference framework for biomarker research. SIGNIFICANCE: This study employed LC-MS/MS to systematically characterize eccrine sweat and delineate how stimulation paradigms-exercise, pilocarpine, and their combination-shape its proteomic landscape. By demonstrating that pharmacological induction profoundly alters protein diversity and composition compared to physiologically induced sweat, these findings establish a critical benchmark for sweat-based biomarker research and highlight the need for paradigm-aware sampling strategies in clinical and translational contexts. Nonetheless, several methodological constraints warrant consideration: the limited sample size (five individuals per group), the exclusive inclusion of women under combined oral contraceptive treatment (21 active pills followed by 7 pill-free days), which restricts extrapolation to naturally cycling women, and the focus on healthy young adults (18-25 years), limiting generalizability to older or clinically heterogeneous populations. Despite these limitations, this work provides a foundational framework for optimizing sweat collection protocols and advancing precision approaches in non-invasive diagnostics.

Pilocarpine↗

PubMed2026

Preoperative Carbohydrate Supplementation Reduces Thirst and Improves Patient Satisfaction Before Elective Cesarean Delivery: A Randomized Controlled Trial.

BACKGROUND & AIMS: Prolonged preoperative fasting is a major source of patient discomfort, particularly thirst, before elective cesarean delivery. This study aimed to evaluate whether preoperative carbohydrate (CHO) supplementation could alleviate these discomforts and improve patient satisfaction without compromising safety. METHODS: In this single-center randomized controlled trial, 262 women scheduled for elective cesarean delivery under neuraxial anesthesia were randomly allocated to either the CHO group (Group CHO, n = 131), which received 355 mL of an oral carbohydrate solution on the night before and the morning of surgery, or the control group (Group C, n = 131), which followed conventional fasting. The primary outcome was the thirst Numeric Rating Scale (NRS, 0-10) score measured immediately before surgery. Secondary outcomes included hunger NRS, satisfaction NRS, and maternal and neonatal safety parameters. RESULTS: Baseline characteristics were comparable between groups. Despite a longer preoperative fasting duration in Group CHO (9.25 ± 1.05 vs. 8.74 ± 0.97 h, P < 0.001), this group exhibited significantly lower thirst NRS scores (1.69 ± 0.90 vs. 4.02 ± 0.99, P < 0.001) and hunger NRS scores (1.25 ± 0.94 vs. 2.09 ± 0.82, P < 0.001), as well as higher satisfaction NRS scores (7.70 ± 0.69 vs. 5.69 ± 1.17, P < 0.001). Subgroup analyses confirmed consistent benefits of CHO supplementation across most patient characteristics. Further analyses suggested that the maximum effect on thirst reduction occurred at approximately 9.2 h of solid fasting; however, the interaction between fasting duration and treatment group was not statistically significant (P = 0.187). CONCLUSION: Preoperative carbohydrate supplementation effectively reduces thirst and hunger and improves patient satisfaction before elective cesarean delivery without increasing maternal or neonatal risk. The beneficial effects were consistent across varying fasting durations, with exploratory spline analyses suggested a potential peak effect around 9.2 h, though this was not statistically significant and should be interpreted cautiously. These findings support the incorporation of carbohydrate loading into enhanced recovery protocols. TRIAL REGISTRATION: China Clinical Trial Registry ChiCTR2500097956.

Humans↗