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PubMed2026

Proteomic insights into the immunomodulatory effects of Ca/Sr co-doped sol-gel coatings for titanium implants.

Ionic functionalization of biomaterial coatings has emerged as a powerful strategy to regulate early host responses at the implant interface. However, how combined Ca/Sr incorporation governs the adsorbed proteome and downstream immune signaling remains poorly understood. This study analyses, employing in vitro tests and proteomics, the effect of adding Sr and Ca to Si-based coatings designed to bioactivate Ti implants. Hybrid Si-based coatings were synthesized by the sol-gel route with a fixed Ca content (0.5 wt%) and increasing Sr contents (0.5, 1.0, 1.5 wt%), and their physicochemical properties, ion release kinetics, and hydrolytic stability were characterized. The coatings remained highly crosslinked despite Ca/Sr incorporation, whereas the highest Sr content increased hydrolytic degradation to around 70% after 56 days. Proteomic analysis identified 183 adsorbed proteins, of which 56 were differentially adsorbed on Ca/Sr-coatings, mainly associated with immune and coagulation pathways. In vitro, RAW 264.7 showed increased gene expression of TNF-α and TGF-β; with an enhanced TNF-α secretion by the addition of Ca and Sr. In parallel, MC3T3-E1 indicated that Ca/Sr-coatings were not cytotoxic and did not impair cell proliferation. However, ALP activity was reduced in the co-doped groups, indicating that the immunomodulatory effects induced by Ca/Sr incorporation were not accompanied by enhanced early osteogenic differentiation. The Ca/Sr combination induced alterations in the adsorption of immune-related proteins, which correlated with the in vitro findings. The deeper insight into how Ca/Sr mixtures modulate protein adsorption on biomaterial surfaces may be key to understanding the immunomodulatory capacity of these bioactive cations.

Animals↗

PubMed2026

Clinical pharmacokinetics of afatinib: A systematic review.

BACKGROUND: Afatinib is commonly used in the treatment of non-small cell lung cancer (NSCLC). This systematic review summarizes clinical pharmacokinetics (PK) evidence focusing on the effect of disease state and drug interactions on afatinib exposure. METHODS: Google Scholar, Science Direct, PubMed, and the Cochrane library were searched for human studies reporting the clinical PK of afatinib. The search yielded 24 articles that met the predefined inclusion criteria. RESULTS: Afatinib exposure increased slightly more than dose proportionally, with higher doses producing greater AUC0-24 and Cmax values. The apparent oral clearance reported after administration of the oral solution was lower than that observed following tablet administration. The Cmax of afatinib increases by 38.5% after coadministration with ritonavir and exposure decreases 34.3% with rifampicin. The Cmax decreases 31.45% when given with pemetrexed. Both the AUC0-24 and Cmax increase in NSCLC and tumor state. The AUC0-24 of afatinib is 2.61 folds higher following multiple oral doses among patients with solid tumors. Afatinib exposure is 22.1 % higher in renal impaired patients than in healthy controls. In grade 2 diarrhea, the AUC0-24 of afatinib is 83.93% higher as than in grade 0-1 diarrhea in solid tumor patients. CONCLUSION: This systematic review provides an updated synthesis of clinical PK evidence on afatinib. Afatinib exposure is influenced by dose, repeated administration, renal impairment, diarrhea associated toxicity, and P-glycoprotein mediated drug interactions. These findings may support individualized dosing, toxicity-guided dose adjustment, and future development of PK models for afatinib.

Humans↗

PubMed2026

Hyper-oncotic albumin administration reduces mortality in acute Respiratory Distress Syndrome compared to crystalloid: a systematic review and meta-analysis.

BACKGROUND: To evaluate the association between albumin administration as volume replacement and mortality in adult ARDS patients, we performed this meta-analysis and trial sequential analysis (TSA). METHODS: We searched databases including PubMed, Science Direct, Scopus, Web of Science databases and Cochrane Central Register of Controlled Trials up to 12 December 2024. We screened trials that included adult ARDS patients and compared albumin with crystalloid. The 28-day mortality served as the primary endpoint, while the oxygenation change, the length of ICU stay and the length of hospital stay were designated as secondary outcomes. To clarify the differing concentrations of albumin, we formed two distinct subgroups: the hyper-oncotic albumin subgroup (≥20%) and the iso-oncotic albumin subgroup (4%∼5%). Statistical synthesis was performed with Cochrane Review Manager 5.4.1, employing random-effects models. To mitigate random errors, TSA was implemented with α = 0.05 and β = 0.20 parameters. RESULTS: The analysis incorporated 5 publications: 3 randomized controlled trials (RCTs) and 2 non-randomized studies (NRSs). Overall mortality was lower in the albumin group (33.2%, 97/292) than in the crystalloid group (44.9%, 133/296) (OR = 0.61, 95%CI 0.43-0.85, p = 0.004). RCTs (n = 204) showed no benefit (OR = 0.83, p = 0.54), but NRSs (n = 384) demonstrated reduced mortality (OR = 0.52, p = 0.002). Hyper-oncotic albumin was associated with lower mortality in NRSs (OR = 0.40, p = 0.02) but not in RCTs (OR = 0.74, p = 0.57). Iso-oncotic albumin showed no benefit (OR = 0.88, p = 0.72). Regarding the impact of albumin on oxygenation, significant improvements in oxygenation were observed only on the first (p = 0.05) and second days (p < 0.0001). The TSA indicated a continued need for high-quality RCTs. CONCLUSIONS: Our analysis suggests that hyper-oncotic albumin may reduce mortality and improve early oxygenation in ARDS patients compared to crystalloids. Larger RCTs are urgently needed to validate these findings and define their potential role in clinical management.

Humans↗

PubMed2026

A multi-center, open-labelled, randomized controlled extended phase III non-inferiority clinical trial to evaluate the immunogenicity and tolerability of poliomyelitis vaccine (Vero cells), inactivated, Sabin strains administered with or without routine infant vaccines.

BACKGROUND: Oral poliovirus vaccine (OPV) has been reported to cause vaccine-derived poliovirus and vaccine-associated paralytic poliomyelitis, and the limited global supply of conventional IPV has led many countries to rely on fractional-dose IPV regimens alongside OPV. The current study aims to assess the sIPV safety and immunogenicity when given concurrently with or in a staggered manner with routine immunization. METHODS: A multi-country, multi-center, open-label, randomized controlled, extended phase III non-inferiority clinical trial was conducted with 1442 healthy infants aged 6-8 weeks from Bangladesh and Pakistan enrolled and randomized into four groups, i.e., co-administration group 1 (group C1), co-administration group 2 (group C2), staggered administration group 1 (group S1) and staggered administration group 2 (group S2). Antibody levels were determined using the collected sera for immunogenicity evaluation. The difference in seroconversion rates between the coadministration group and the staggered administration group is compared using the Cochran-Mantel-Haenszel χ2 (CMH-χ2) test, stratified by study site. Non-inferiority is concluded if the lower bound of the 95% confidence interval (CI) for the rate difference (coadministration group minus staggered administration group) is greater than -10%. The trial was registered prior to patient enrollment at clinicaltrials.gov (NCT05850364), and the protocol and statistical analysis plan are available at https://clinicaltrials.gov/study/NCT05850364. The trial is closed to new participants. FINDINGS: The post-vaccination seroconversion rates for PV I were 90.3% (306/339) in group C1 and 87.0% (261/300) in group S1, for PV II, 91.7% (311/339) in group C1 and 91.3% (274/300) in group S1 and for PV III, 86.4% (293/339) in group C1 and 92.3% (277/300) in group S1. Among adverse reactions (ARs) reported within 7 days of vaccination, the incidence was similarly high in both the co-administration and staggered vaccination groups (92.8% vs. 95.5%). INTERPRETATION: Our results demonstrated favorable safety and immunogenicity of co-administration of sIPV with other routine infant vaccines according to a 3-dose primary immunization schedule.

Humans↗

PubMed2026

Pain outcomes of pediatric circumcision patients following administration of pre-operative ketorolac: A randomized clinical trial.

INTRODUCTION: Circumcision is a common surgical intervention, and pain is the most common complaint. Poorly managed pain can increase morbidity and reduce patient and parent satisfaction. Ketorolac, a non-steroidal anti-inflammatory drug (NSAID), provides analgesia and may be effective in reducing pain after circumcision in pediatric patients. STUDY OBJECTIVES: The primary objective was to determine the effect of pre-operative intravenous ketorolac versus normal saline placebo on parental perception of postoperative pain at 24 h. We also explored the effect of ketorolac on postoperative pain scores, incidence of bleeding, incidence of vomiting, and analgesic use. MATERIALS AND METHODS: A prospective, randomized, single-blinded trial was conducted at a single tertiary children's hospital. Patients aged 1-17 presenting for circumcision were included and randomized to either normal saline injectate or ketorolac (0.5 mg/kg, maximum 30 mg). Postoperative delirium and pain scores were recorded in the post-anesthetic care unit. Parents completed the parents' postoperative pain measure (PPPM) at 24 h. The CONSORT criteria and checklist were used to guide reporting of this randomized controlled trial. RESULTS: A total of 100 participants were included. 50 participants were in each group. Mean (SD) PPPM score 24 h after normal saline and ketorolac was 6.1 (3.4) and 5.5 (3.3), respectively for a mean difference of -0.55 points [95% CI: -1.9 to 0.83; p = 0.427]. The mean (95% CI) fixed effect size of ketorolac on post anesthetic care unit reported Face, Leg, Activity, Cry, Consolability score was -0.17 (-0.77 to 0.43, p = 0.585) points, while the mean (95% CI) effect size of ketorolac on numerical rating scale was -1.2 (-2.2 to -0.18, p = 0.026) points. DISCUSSION: Pre-operative intravenous ketorolac, compared to normal saline placebo, did not result in a difference in parental perception of postoperative pain at 24 h after circumcision surgery. As part of exploratory analyses, those receiving ketorolac had modestly lower mean immediate postoperative pain scores, likely not of clinical importance. Ketorolac has often been avoided due to concerns of increased bleeding risk, however it is important to consider that there is no substantial evidence to support this. This is the first study to our knowledge evaluating the effect of ketorolac in pediatric circumcision patients. While the PPPM score is a family centered outcome, it is an indirect measurement of pediatric pain. CONCLUSIONS: Pre-operative intravenous ketorolac was not associated with lower parental reported pain scores at 24 h compared to normal saline placebo after pediatric circumcision surgery. CLINICAL TRIAL REGISTRATION: NCT02973958.

Humans↗

PubMed2026

Phase 1 Study Evaluating Gefurulimab Pharmacokinetics and Safety Following Delivery Via Autoinjector or Prefilled Syringe With Needle Safety Device in Healthy Adults.

PURPOSE: Gefurulimab, a novel dual-binding nanobody targeting complement component 5 (C5), is in clinical development for anti-acetylcholine receptor antibody-positive generalized myasthenia gravis. Gefurulimab has a low molecular weight, enabling subcutaneous (SC) self-administration by autoinjector (AI) or prefilled syringe with needle safety device (PFS-SD). We compared gefurulimab pharmacokinetic (PK) exposure and safety in healthy adults following a single SC dose administered by AI versus PFS-SD. METHODS: In this phase 1, open-label, randomized, parallel-group study (NCT06208488), healthy participants aged 18 to 65 years were stratified by weight and randomized equally to 1 of 6 combination groups of device and injection site (abdomen/thigh/upper arm). Participants received a single SC dose of gefurulimab on day 1 and were assessed throughout the 92-day evaluation period. Primary endpoints were PK parameters for each device: maximum observed concentration (Cmax) and area under the serum concentration-time curve (AUCinf, AUClast). PK across injection sites, pharmacodynamics, safety, immunogenicity, and device performance were also assessed. FINDINGS: Overall, 175 participants were randomized: AI (n = 87), PFS-SD (n = 88). Geometric least squares mean ratios (90% CI) comparing AI/PFS-SD for Cmax, AUCinf, and AUClast were 97.6% (94.5-100.8), 99.6% (96.1-103.3), and 98.8% (95.2‒102.6), respectively. Secondary analyses found no meaningful differences in PK parameters across injection sites. Serum-free C5 concentrations over time, treatment-emergent adverse event (TEAE) profiles, and antidrug antibody responses were similar between cohorts. Most TEAEs were mild; none led to study discontinuation. IMPLICATIONS: SC administration of gefurulimab by AI and PFS-SD was well tolerated with comparable exposure, meeting bioequivalence criteria.

Humans↗

PubMed2026

Identifying stakeholder behaviors for competency-based pharmacy education: A stage 1 behavior change wheel analysis.

INTRODUCTION/OBJECTIVES: Competency-Based Pharmacy Education (CBPE) is a strategic priority for preparing graduates to meet evolving healthcare needs. However, efforts to implement CBPE can stall due to behavioral challenges among faculty, administrators, preceptors, and learners. This study aimed to apply Stage 1 of the Behavior Change Wheel (BCW) to identify stakeholder-specific behaviors and associated determinants needed to implement the five core components of CBPE. METHODS: A multi-method approach grounded in the BCW, the Capability, Opportunity, Motivation - Behavior (COM-B) model, and the Theoretical Domains Framework (TDF) was used. Data were gathered through (1) targeted literature review; (2) structured focus groups with competency-based education experts and pharmacy education stakeholders; and (3) an iterative consensus process. Behaviors were mapped to the five CBPE components: (1) defined competencies, (2) developmental progression, (3) tailored instruction, (4) authentic experiential learning, and (5) programmatic assessment, and then mapped to COM-B and TDF constructs. RESULTS: Over fifty stakeholder-specific behaviors were identified and specified across the CBPE framework. This revealed shared barriers such as limited instructional design knowledge (psychological capability), insufficient assessment of infrastructure (physical opportunity), and misaligned professional identity (reflective motivation). Key TDF domains included knowledge, environmental context, beliefs about capabilities, and professional roles. The behavioral problem statements, specifications, and determinants were identified to support future intervention planning. CONCLUSION: This Stage 1 analysis provides a behaviorally grounded foundation for CBPE implementation by identifying stakeholder behaviors and conditions that enable change. These findings will inform the development of readiness-to-change assessments and targeted interventions (BCW Stages 2 and 3), supporting scalable and sustainable CBPE transformation in pharmacy education.

Education, Pharmacy↗

PubMed2026

Understanding FDA's reasons for nonapproval: A systematic review of complete response letters in cell and gene therapy.

BACKGROUND AIMS: Cell and gene therapy products face unique regulatory challenges due to their biological complexity and the stringent expectations for manufacturing control, analytical testing, and clinical assessment. As the pipeline grows, understanding the drivers of FDA non‑approval is increasingly important for improving first‑cycle success and reducing development delays. In this study, we aimed to characterize the frequency and impact of refuse‑to‑file actions, major amendments, and complete response letters issued for biologics licensing applications; and to identify recurring patterns of deficiencies contributing to delayed approval. METHODS: Publicly available documents were extracted from the FDA website. Data from each approved cell and gene therapy product's regulatory history-including complete responses, major amendments, inspection timing, and cited deficiencies-were compiled and categorized across clinical, quality, and labeling domains. RESULTS: Analysis showed that informational deficiencies were common across modalities. Major amendments occurred in roughly half of applications, and complete responses had the most significant impact. Quality deficiencies appeared in all complete responses and were the predominant barrier, while clinical and labeling issues were less frequent but meaningful when present. CONCLUSION: Overall, these findings highlight the need for proactive FDA engagement, comprehensive readiness, and early inspection preparation to reduce regulatory risk and improve first cycle approval outcomes.

Humans↗

PubMed2026

Safety, pharmacokinetics and pharmacodynamics of TQC3721, an innovative, dual PDE3 and PDE4 inhibitor, in healthy subjects and patients with chronic obstructive pulmonary disease: Randomised, double-blind, placebo-controlled phase I and IIa clinical trials.

BACKGROUND AND PURPOSE: TQC3721 is a novel inhaled dual phosphodiesterase (PDE3/4) inhibitor designed to provide bronchodilation and anti-inflammatory effects for chronic obstructive pulmonary disease (COPD). EXPERIMENTAL APPROACH: First-in-human randomised, double-blind, placebo-controlled phase I (SAD: 0.2 to 24 mg single dose; MAD: 12 mg once daily (QD) for 7 days in healthy subjects) and phase IIa studies (0.75 to 6 mg once or twice daily for 4 weeks in moderate-to-severe patients with COPD) were conducted. Primary outcomes included safety, pharmacokinetics (PKs) and pharmacodynamics (PDs), change from baseline of forced expiratory volume in the first second [FEV1], and FEV1 at 12 and 24 h post-dose on days 1 and 28. KEY RESULTS: TQC3721 was rapidly absorbed (median Tmax of 0.25 to 0.5 h), mainly by pulmonary absorption rather than gastrointestinal absorption, along with low systemic exposure and lack of significant accumulation. TQC3721 demonstrated favourable safety profiles in healthy subjects and patients with COPD. In patients with COPD, TQC3721 produced rapid and outstanding bronchodilation effect sustained over 12 h post-administration, with FEV1 peaking at approximately 2 h post-dose and returning to baseline levels by 12 h, which supports a twice-daily dosing regimen for the future, and peak FEV₁ improvements ranging from 186 to 272 ml across dose groups after 4 weeks of treatment. Moreover, twice-daily 3 and 6 mg regimens were recommended for further clinical study. CONCLUSIONS AND IMPLICATIONS: Pharmacokinetic features, significant bronchodilation effects and overall favourable safety characteristics support further clinical development of TQC3721 as a potential dual-mechanism therapy for COPD.

Adult↗

PubMed2026

Randomised, Multicentre Clinical Trial Found That Hypertonic Saline Did Not Reduce the Length of Stay of Hospitalised Patients With Acute Bronchiolitis.

AIM: Bronchiolitis is a major cause of hospitalisation in young children, but the effectiveness of inhaled hypertonic saline remains unclear. We compared treating hospitalised infants with nebulised hypertonic saline or normal saline. METHOD: This multisite, double-blind RCT was conducted from 1 October 2023 to 1 April 2025 in four Polish paediatric units. Children from 5 weeks to 24 months, who had been hospitalised with mild-to-moderate bronchiolitis, were randomly assigned to receive nebulised 3% hypertonic saline or 0.9% normal saline until discharge. They were followed for 7 days. RESULTS: The study comprised 181 children (55% male) with a mean age of 8.3 ± 6.3 months: 90 were randomised to hypertonic saline and 91 to normal saline. The median hospital stay was 2.68 (1.92-4.03) days in the hypertonic saline group and 2.79 (1.8-3.96) days in the normal saline group. The mean difference was -0.11 days (95% confidence interval -0.73 to 0.12, p = 0.3). No differences were observed in clinical severity scores between the groups. Readmissions only occurred in the normal saline group (5.9%). CONCLUSION: Hypertonic saline inhalation did not reduce the length of hospital stay or improve clinical severity scores in hospitalised children with bronchiolitis, but it was associated with a lower risk of rehospitalisation.

Humans↗

PubMed2026

Integrated assessment of biocontrol potential and genome analysis of endophytic Bacillus velezensis MGL-B1 against mango stem-end rot.

Mango stem-end rot is a globally significant postharvest disease that severely threatens the mango industry, primarily caused by Botryosphaeria dothidea. However, information on biocontrol agents targeting this pathogen in mango remains limited. In this study, we isolated and identified a strain of Bacillus velezensis MGL-B1 from mango leaf tissues for the first time, which exhibited broad-spectrum antifungal activity. Both in vitro and in vivo assays demonstrated that MGL-B1 effectively inhibited the growth of B. dothidea, with an in vivo biocontrol efficacy reaching 83.72 ± 5.10%, comparable to that of the commonly used chemical fungicide thiabendazole. Further mechanistic analysis revealed that MGL-B1 acts by directly disrupting the integrity of the pathogen's mycelial cell membrane. In addition, its released volatile organic compounds (VOCs) also displayed significant antifungal activity, with components such as 2-nonanone, 2-nonanol, and phenylethyl alcohol being confirmed to exert antifungal effects in in vitro fumigation assays. qPCR analysis showed that MGL-B1 treatment significantly upregulated the transcriptional levels of genes involved in plant-pathogen interaction, phenylpropanoid biosynthesis, and antioxidant defense pathways in mango fruits, with upregulation folds of 16.32, 37.19, and 75.93, respectively; meanwhile, the expression of browning-related genes such as polyphenol oxidase (PPO) was markedly suppressed. Whole-genome sequencing further revealed 14 biosynthetic gene clusters for antimicrobial compounds, including five unknown gene clusters. Collectively, B. velezensis MGL-B1 represents a promising biocandidate strain with multiple antifungal mechanisms and excellent control efficacy, providing a valuable resource for green and sustainable management of mango diseases.

Mangifera↗

PubMed2026

Efficacy of Oral Baicalin in Canine Atopic Dermatitis: A Randomised Placebo Controlled Trial.

BACKGROUND: Baicalin has shown efficacy in various dermatitis models in animals. However, its therapeutic effects on naturally occurring canine atopic dermatitis (cAD) have not been evaluated. OBJECTIVE: To evaluate the efficacy and safety of baicalin in dogs with cAD. ANIMALS: 56 client-owned dogs were enrolled. MATERIALS AND METHODS: All dogs were randomly divided to receive oral baicalin or placebo over a 90day period. All subjects had veterinary evaluations using the Canine Atopic Dermatitis Extent and Severity Index, 4th iteration (CADESI-04) during the trial and owners were requested to evaluate itching using the pruritus Visual Analog Scale (PVAS) and to complete a quality-of-life (QoL) questionnaire at Day (D)0 and D90. Additionally, the transepidermal water loss (TEWL), total serum IgE levels (IgE), complete blood count and serum biochemical results were measured at D0 and D90. RESULTS: The significant decreases in CADESI-04 (p < 0.001), PVAS (p < 0.001), TEWL (p = 0.014), IgE (p < 0.001) and QoL scores (p < 0.001) were observed in the baicalin group D90 compared to baseline. When compared to placebo, the baicalin group had significantly lower scores in CADESI-4 and PVAS (p < 0.001). A significantly higher proportion of subjects in the baicalin group showed a good-to-excellent treatment response (82.1%) compared to those in the placebo group (35.7%). The treatment was well tolerated. CONCLUSIONS AND RELEVANCE: Baicalin had a significant benefit in alleviating pruritus and reducing clinical signs in dogs with mild-to-moderate cAD and was well tolerated.

Animals↗

PubMed2026

The influence of organizational culture on medication safety practices and associated risk factors in the community setting: A systematic review.

BACKGROUND: Increasing attention has been given to the role of organizational culture in influencing medication safety practices across healthcare settings. The lack of widely accepted standardized instrumentation makes operational measurement of organizational culture and medication safety challenging. The purpose of this systematic review was to examine the impact of organizational culture on medication safety within community healthcare settings. METHODS: MEDLINE, CINAHL, Scopus, and Nursing & Allied Health were searched in August 2025 using keywords, subject terms, field codes, and Boolean operators to identify papers relevant to the review question; bibliographies of included studies were also reviewed. Screening and full-text review were completed independently by two reviewers with a third to adjudicate conflicts. The Critical Appraisal Skills Programme was used for quality assessment. The PRISMA statement guided the development and implementation of the review. RESULTS: Thirteen articles were included representing various community settings. Most studies reported on untoward medication events, but few measured systematically collected safety data before and after an intervention. Organizational culture was seldom defined or operationalized. Most studies were methodologically sound, but the overall level of evidence was weak to moderate. CONCLUSION: Organizational culture influences medication safety through aspects such as communication channels, teamwork, training, and an environment that allows error and near-miss reporting. Few studies explicitly evaluate the causal impact of culture interventions on measurable medication safety outcomes in community healthcare settings. Further research should incorporate standardized measurement tools and intervention-based, pre-post designs to better understand how organizational culture influences medication safety in community healthcare settings.

Organizational Culture↗

PubMed2026

Characterization of the Immune Response after Oral Cholera Vaccination (OCV) and Effects of Mycophenolate Mofetil on Priming of this Immune Response-A Randomized, Placebo-Controlled Trial.

Mycophenolate mofetil (MMF) is an immunosuppressive drug widely used by solid organ transplant recipients. Although it is known that MMF suppresses immune responses, its exact effects on specific vaccinations have not been investigated yet. Mucosal vaccinations are increasingly used, such as a cholera vaccination consisting of two oral immunizations (oral cholera vaccination; OCV). This study aimed to investigate the specific immunosuppressive effects of MMF use during the first dose of OCV in a randomized, placebo-controlled trial in healthy volunteers. Moreover, the study aimed to characterize the immune response provoked by OCV in detail. This randomized, placebo-controlled, single-blind trial included 16 healthy volunteers, each receiving two doses of Dukoral® and an intranasal rechallenge. Outcome measures were serum antibody responses (IgA and IgG) and IgA levels in saliva. Additionally, peripheral blood mononuclear cells (PBMCs) of participants were investigated for ex vivo cytokine production and expression of tissue-specific homing markers after OCV. There were considerable serum IgA and IgG responses after vaccination. MMF-treated volunteers still showed a significant cholera antibody response, though data suggest a potential suppression by MMF without reaching statistical significance. There was no substantial IgA response in saliva. Investigation of PBMCs from OCV-treated participants showed a Th2 skewing with increased ex vivo production of TNF, IL-2, IL-5, IL-13, and IL-22 compared to the placebo group. Taken together, this study provides a framework for future clinical pharmacology studies building on OCV as a challenge model and for further investigation of specific effects of MMF on mucosal vaccination responses.

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

Comparative Efficacy and Safety of Adjunctive 0.015% Triamcinolone Acetonide Topical Spray With Lokivetmab Versus Lokivetmab Monotherapy as 'Reactive Therapy' for Canine Atopic Dermatitis: A Randomised, Single-Blinded, Controlled Preliminary Trial.

BACKGROUND: Lokivetmab is considered an effective systemic therapy for dogs with atopic dermatitis (AD); however, utilisation of lokivetmab with adjunctive topical anti-inflammatory glucocorticoids has not been investigated in canine AD. OBJECTIVES: To evaluate the efficacy and safety of the combination therapy of lokivetmab and 0.015% triamcinolone acetonide (TCA) spray in dogs with AD. ANIMALS: Twenty dogs with nonseasonal AD. MATERIALS AND METHODS: This study was a randomised, single-blinded (investigators only) 4-week controlled trial. Dogs were randomised to receive lokivetmab monotherapy or lokivetmab-TCA spray per manufacturer instructions. Clinical assessments included the Canine Atopic Dermatitis Extent and Severity Index, 4th iteration (CADESI-04), CADESI-04E (i.e., extracted erythema grade alone) and the 10-grade pruritus Visual Analog Scale (PVAS10) at Day (D)0, D14 and D28. Complete blood count and serum biochemical analysis were performed on D0 and D28. RESULTS: The median CADESI-04 and CADESI-04E scores in the lokivetmab-TCA group were significantly reduced on D14 (p < 0.05 for both) and D28 (p < 0.01 for both) compared to baseline; there were no significant differences in lesional scores at any time point for the lokivetmab monotherapy group. Lokivetmab-TCA significantly reduced CADESI-04E values compared to the lokivetmab monotherapy group on D28 (p = 0.04). Both interventions significantly reduced PVAS10 scores on D14 and D28 compared to D0 (p < 0.05 for both groups). CONCLUSIONS AND CLINICAL RELEVANCE: Topical application of TCA spray may be a useful and safe adjunctive therapy for systemic lokivetmab to alleviate pruritus and clinical lesions in the initial management of canine AD patients.

Animals↗

PubMed2026

Descemet Stripping Only in Fuchs Endothelial Corneal Dystrophy: Results of a Randomized Clinical Trial of Topical Ripasudil and Directions for Future Innovation.

PURPOSE: To review history of Descemet stripping only (DSO) in Fuchs endothelial corneal dystrophy, describe the results of a clinical trial of topical ripasudil after DSO (K-321-201 study), and discuss future directions. METHODS: A 1-year, phase 2, randomized, placebo-controlled multicenter clinical trial of two doses of K-321 (ripasudil) administered for 12 weeks after DSO surgery in Fuchs endothelial corneal dystrophy was performed. The primary endpoint, central corneal endothelial cell density (ECD) at 12 weeks after surgery, was determined by an independent reading center that was masked to study group assignment. Duration of corneal edema, need for medical or surgical rescue therapy, corneal thickness, and central ECD throughout the entire study period were also examined. Adverse events and exploratory endpoints were collected. RESULTS: Sixty-five subjects were enrolled (21 in the QID group, 22 in the BID, and in the placebo group). Over 95% of subjects completed the trial. The QID group had a higher central ECD 12 weeks after DSO than the placebo group (531 ± 312 cells/mm2 vs 228 ± 298 cells/mm2, P = .0065). Corneal edema cleared in 17/21 (81.0%) of the QID group at 12 weeks, compared with 2/22 (9.1%) of the placebo group (P < .0001). Rescue was required in 2/21 (9.5%) subjects in the QID group and 6/22 (27.3%) subjects in the placebo group (P = .0092). Adverse events were mild and did not lead to discontinuation of treatment. CONCLUSIONS: Topical K-321 given QID improves DSO outcomes, as demonstrated by a higher ECD, more rapid resolution of corneal edema, and reduced failure rate. The medication was well-tolerated.

Humans↗

PubMed2026

Reassessment of the effect of oral l-arginine on blood pressure: A systematic review and meta-analysis based on ambulatory blood pressure monitoring.

OBJECTIVE: This meta-analysis aimed to evaluate the effect of oral l-arginine supplementation on ambulatory blood pressure (ABP). METHODS: A systematic search of PubMed, Cochrane Library, Embase, and Web of Science databases was conducted from their inception through March 1, 2026. Randomized controlled trials (RCTs) assessing the effects of oral l-arginine intervention were included. Outcome measures included 24-h systolic blood pressure (24h SBP), 24-h diastolic blood pressure (24h DBP), daytime systolic blood pressure (dSBP), daytime diastolic blood pressure (dDBP), nighttime systolic blood pressure (nSBP), and nighttime diastolic blood pressure (nDBP). Meta-analysis was performed using Stata 17.0. The weighted mean difference (WMD) was used as the effect size, and the results were pooled with 95% confidence intervals (CIs). RESULTS: A total of 5 RCTs comprising 202 participants were included. Meta-analysis results demonstrated that oral l-arginine significantly reduced 24h SBP (WMD = -4.23 mmHg, 95% CI [-5.87, -2.58]; P < 0.01) and 24h DBP (WMD = -3.04 mmHg, 95% CI [-4.48, -1.59]; P < 0.01). Significant reductions were also observed for dSBP (WMD = -4.16 mmHg, 95% CI [-5.90, -2.41]; P < 0.01) and dDBP (WMD = -4.25 mmHg, 95% CI [-5.85, -2.66]; P < 0.01). Furthermore, oral l-arginine significantly lowered nSBP (WMD = -5.70 mmHg, 95% CI [-7.81, -3.58]; P < 0.01) and nDBP (WMD = -4.18 mmHg, 95% CI [-6.27, -2.09]; P < 0.01). CONCLUSION: Oral l-arginine supplementation significantly reduces ABP. However, the number of included studies was limited, and further validation through additional relevant research is warranted.

Arginine↗